US20080249503A1 - Methods and devices for lung treatment - Google Patents

Methods and devices for lung treatment Download PDF

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US20080249503A1
US20080249503A1 US12/133,326 US13332608A US2008249503A1 US 20080249503 A1 US20080249503 A1 US 20080249503A1 US 13332608 A US13332608 A US 13332608A US 2008249503 A1 US2008249503 A1 US 2008249503A1
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lung
lung region
targeted
flow
bronchial
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US12/133,326
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Antony J. Fields
Ronald Hundertmark
John McCutcheon
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Pulmonx Corp
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Assigned to EMPHASYS MEDICAL, INC. reassignment EMPHASYS MEDICAL, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: FIELDS, ANTONY J., HUNDERTMARK, RONALD, MCCUTCHEON, JOHN
Publication of US20080249503A1 publication Critical patent/US20080249503A1/en
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    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16KVALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K15/00Check valves
    • F16K15/14Check valves with flexible valve members
    • F16K15/144Check valves with flexible valve members the closure elements being fixed along all or a part of their periphery
    • F16K15/147Check valves with flexible valve members the closure elements being fixed along all or a part of their periphery the closure elements having specially formed slits or being of an elongated easily collapsible form
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/04Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/00491Surgical glue applicators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/04Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2/06Blood vessels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/24Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body
    • A61F2/2412Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body with soft flexible valve members, e.g. tissue valves shaped like natural valves
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/24Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body
    • A61F2/2412Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body with soft flexible valve members, e.g. tissue valves shaped like natural valves
    • A61F2/2418Scaffolds therefor, e.g. support stents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/24Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body
    • A61F2/2427Devices for manipulating or deploying heart valves during implantation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A61F2/91Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/04Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2002/043Bronchi

Definitions

  • This invention relates generally to methods and devices for use in performing pulmonary procedures and, more particularly, to procedures for treating various diseases of the lung.
  • COPD chronic obstructive pulmonary disease
  • COPD can include such disorders as chronic bronchitis, bronchiectasis, asthma, and emphysema. While each has distinct anatomic and clinical considerations, many patients may have overlapping characteristics of damage at both the acinar (as seen in emphysema) and the bronchial (as seen in bronchitis) levels, almost certainly because one pathogenic mechanism—cigarette smoking is common to both. (Robbins, Pathological Basis of Disease, 5 th edition, pg 683)
  • Emphysema is a condition of the lung characterized by the abnormal permanent enlargement of the airspaces distal to the terminal bronchiole, accompanied by the destruction of their walls, and without obvious fibrosis. It is known that emphysema and other pulmonary diseases reduce the ability of one or both lungs to fully expel air during the exhalation phase of the breathing cycle. One of the effects of such diseases is that the diseased lung tissue is less elastic than healthy lung tissue, which is one factor that prevents full exhalation of air. During breathing, the diseased portion of the lung does not fully recoil due to the diseased (e.g., emphysematic) lung tissue being less elastic than healthy tissue.
  • the diseased lung tissue exerts a relatively low driving force, which results in the diseased lung expelling less air volume than a healthy lung.
  • the reduced air volume exerts less force on the airway, which allows the airway to close before all air has been expelled, another factor that prevents full exhalation.
  • the problem is further compounded by the diseased, less elastic tissue that surrounds the very narrow airways that lead to the alveoli (the air sacs where oxygen-carbon dioxide exchange occurs).
  • This tissue has less tone than healthy tissue and is typically unable to maintain the narrow airways open until the end of the exhalation cycle.
  • the trapped air causes the tissue to become hyper-expanded and no longer able to effect efficient oxygen-carbon dioxide exchange.
  • One way of deflating the diseased portion of the lung is to applying suction to these narrow airways. However, such suction may undesirably collapse the airways, especially the more proximal airways, due to the surrounding diseased tissue, thereby preventing successful fluid removal.
  • hyper-expanded lung tissue occupies more of the pleural space than healthy lung tissue. In most cases, a portion of the lung is diseased while the remaining part is relatively healthy and therefore still able to efficiently carry out oxygen exchange. By taking up more of the pleural space, the hyper-expanded lung tissue reduces the amount of space available to accommodate the healthy, functioning lung tissue. As a result, the hyper-expanded lung tissue causes inefficient breathing due to its own reduced functionality and because it adversely affects the functionality of adjacent, healthier tissue.
  • Lung volume reduction surgery is a conventional method of treating lung diseases such as emphysema.
  • a diseased portion of the lung is surgically removed, which makes more of the pleural space available to accommodate the functioning, healthier portions of the lung.
  • the lung is typically accessed through a median sternotomy or lateral thoracotomy.
  • a portion of the lung, typically the upper lobe of each lung, is freed from the chest wall and then resected, e.g., by a stapler lined with bovine pericardium to reinforce the lung tissue adjacent the cut line and also to prevent air or blood leakage.
  • the chest is then closed and tubes are inserted to remove fluid from the pleural cavity.
  • the conventional surgical approach is relatively traumatic and invasive, and, like most surgical procedures, is not a viable option for all patients.
  • Some recently proposed treatments include the use of devices that isolate a diseased region of the lung in order to reduce the volume of the diseased region, such as by collapsing the diseased lung region.
  • isolation devices are implanted in airways feeding the targeted region of the lung to isolate the region of the lung targeted for volume reduction or collapse.
  • These implanted isolation devices can be, for example, one-way valves that allow flow in the exhalation direction only, occluders or plugs that prevent flow in either direction, or two-way valves that control flow in both directions.
  • air can flow into the isolated lung region via a collateral pathway.
  • Collateral flow can be, for example, air flow that flows between segments of a lung, or it can be, for example, air flow that flows between lobes of a lung, as described in more detail below.
  • Collateral flow into an isolated lung region can make it difficult to achieve a desired flow dynamic for the lung region.
  • the collateral flow throughout the lung can increase, which makes it even more difficult to properly isolate a diseased lung region by simply implanting flow control valves in the bronchial passageways that directly feed air to the diseased lung region.
  • a method of regulating fluid flow for a targeted lung region comprising identifying at least one collateral pathway that provides collateral fluid flow into the targeted lung region and performing an intervention within the lung to reduce the amount of collateral fluid flow provided to the targeted lung region through the collateral pathway.
  • the method can also include identifying at least one direct pathway that provides direct fluid flow into the targeted lung region and deploying a bronchial isolation device in the direct pathway to regulate fluid flow to the targeted lung region through the direct pathway.
  • Also disclosed is a method of regulating fluid flow for a targeted lung region comprising reducing direct fluid flow in a direct pathway that provides direct fluid flow to the targeted lung region; and reducing collateral fluid flow that flows through a collateral pathway to the targeted lung region.
  • Also disclosed is a method of treating a patient's lung region comprising deploying a catheter into a lung; and using the catheter to apply heat to a targeted lung region wherein the heat affects fluid flow within the targeted lung region.
  • Also disclosed is a method of diagnosing collateral ventilation between regions of a lung comprising positioning a catheter transtracheally into a bronchial passageway that provides direct fluid flow into a target region of the lung; and detecting the presence of collateral fluid flow into or out of the target region of the lung based on the presence of the catheter in the bronchial passageway.
  • Also disclosed is a method of diagnosing collateral ventilation between regions of a lung comprising modifying direct fluid flow into a target lung region; and detecting the presence of collateral fluid flow into the target lung region.
  • Also disclosed is a method of diagnosing collateral ventilation between regions of a lung comprising measuring at least one parameter associated with a target lung region while a catheter is positioned in the target lung region; and calculating a level of collateral fluid flow into the target lung region based on the at least one parameter.
  • Also disclosed is a method of diagnosing collateral ventilation between regions of a lung comprising: positioning a catheter transtracheally into a bronchial passageway that provides direct fluid flow into a target region of the lung; generating at least one measurement associated with the target region of the lung; and calculating a level of collateral fluid flow into the target lung region based on the at least one measurement.
  • Also disclosed is a method of treating the lung comprising inserting a balloon catheter into a bronchial passageway that provides direct fluid flow to a first lung region; inflating a balloon on the balloon catheter to seal the catheter in the bronchial passageway; inserting a marker gas into the lung; measuring a lung parameter through the catheter based on the presence of the marker gas within the lung; detecting the presence of a collateral pathway to the first lung region based on the measured lung parameter; and treating the lung.
  • Also disclosed is a method of treating a lung comprising: deploying a delivery catheter through a bronchial tree into a targeted lung region such that a distal end of the delivery catheter is positioned at or near the targeted lung region; delivering a fibrinogen suspension through the delivery catheter so that the fibrinogen suspension exits the distal end of the delivery catheter into the targeted lung region, wherein the fibrinogen suspension comprises fibrinogen and poly-L-lysine; delivering thrombin through the delivery catheter so that the thrombin exits the distal end of the delivery catheter into the targeted lung region; causing the fibrinogen suspension and the thrombin to mix; and promoting the lung to collapse.
  • the fibrinogen suspension is delivered prior to delivering the thrombin.
  • the thrombin is delivered prior to delivering the fibrinogen suspension.
  • the fibrinogen suspension and the thrombin are mixed prior to delivering the fibrinogen suspension and the thrombin through the delivery catheter.
  • FIG. 1 illustrates an anterior view of a pair of human lungs and a bronchial tree.
  • FIG. 2 illustrates a lateral view of the right lung.
  • FIG. 3 illustrates a lateral view of the left lung.
  • FIG. 4 illustrates an anterior view of the trachea and a portion of the bronchial tree.
  • FIG. 5 illustrates an anterior view of a lung having a lung lobe that is receiving collateral air flow through a collateral pathway comprised of an incomplete interlobar fissure.
  • FIG. 6 illustrates an anterior view of a lung having a lung segment that is receiving collateral air flow.
  • FIG. 7 illustrates the delivery of a flowable therapeutic agent to a targeted lung region using a balloon-tipped delivery catheter.
  • FIG. 8 illustrates the delivery of a flowable therapeutic agent to a targeted lung region using a delivery catheter.
  • FIG. 9 illustrates the percutaneous injection of a flowable therapeutic agent to a targeted lung region.
  • FIG. 10 illustrates the injection of a flowable therapeutic agent into a targeted lung region through a catheter that has a sharpened tip.
  • FIG. 11 illustrates the deployment of a delivery catheter in a patient using a bronchoscope.
  • FIG. 12 illustrates a lateral view of the right lung, showing a targeted lung region and an adjacent healthy lung region.
  • FIG. 13 illustrates the injection of a therapeutic agent into a targeted lung region, controlled by applied pressure in an adjacent lung region.
  • FIG. 14 illustrates the treatment of collateral flow paths using a beta-emitting radiation source.
  • FIG. 15 illustrates the treatment of collateral flow paths using flow-limiting isolation devices.
  • FIG. 16 illustrates the percutaneous suction of a targeted lung region using a suction catheter.
  • FIG. 17 illustrates the sealing of collateral flow paths between the right upper lobe and the right middle lobe through the use of a two-part adhesive.
  • FIG. 18 illustrates the use of shunt tubes that are mounted in bronchial passageway to provide free air pathways to a targeted lung region.
  • FIG. 19 is a cross-sectional view of a flow control element that allows fluid flow in a first direction but blocks fluid flow in a second direction.
  • FIG. 20 shows a perspective view of another embodiment of a flow control element.
  • FIG. 21 shows a cross-sectional, perspective view of the flow control element of FIG. 21 .
  • FIG. 22 shows a valve element
  • FIG. 23 shows a side view of the valve element of FIG. 22 .
  • FIG. 24 shows a cross-sectional view of the valve element of FIG. 22 along the line 24 - 24 of FIG. 23 .
  • FIG. 25 shows an enlarged, sectional view of the portion of the flow control element contained within line 25 of FIG. 22 .
  • An identified region of the lung (referred to herein as the “targeted lung region”) is targeted for flow regulation, such as to achieve volume reduction or collapse.
  • the targeted lung region is then bronchially isolated to regulate fluid flow to the targeted lung region through bronchial pathways that directly feed fluid to the targeted lung region.
  • a collateral pathway is feeding air to the targeted lung region.
  • the collateral flow can prevent the targeted lung region from collapsing.
  • the collateral pathway is identified and an intervention is performed within the lung to modify or inhibit fluid flow into the targeted lung region via the collateral pathway, such as according to the methods described herein. While the invention can involve such treatment of collateral flow pathways in combination with bronchial isolation, it should be understood that the invention may also be practiced without bronchial isolation in some circumstances. Further, the invention also encompasses temporary bronchial isolation while treating lung regions fed by collateral pathways.
  • lung region refers to a defined division or portion of a lung.
  • lung regions are described herein with reference to human lungs, wherein some exemplary lung regions include lung lobes and lung segments.
  • lung region can refer, for example, to a lung lobe or a lung segment.
  • Such nomenclature conform to nomenclature for portions of the lungs that are known to those skilled in the art.
  • lung region does not necessarily refer to a lung lobe or a lung segment, but can refer to some other defined division or portion of a human or non-human lung.
  • FIG. 1 shows an anterior view of a pair of human lungs 110 , 115 and a bronchial tree 120 that provides a fluid pathway into and out of the lungs 110 , 115 from a trachea 125 , as will be known to those skilled in the art.
  • the term “fluid” can refer to a gas, a liquid, or a combination of gas(es) and liquid(s).
  • FIG. 1 shows only a portion of the bronchial tree 120 , which is described in more detail below with reference to FIG. 4 .
  • FIG. 1 shows a path 102 that travels through the trachea 125 and through a bronchial passageway into a location in the right lung 110 .
  • proximal direction refers to the direction along such a path 102 that points toward the patient's mouth or nose and away from the patient's lungs.
  • the proximal direction is generally the same as the expiration direction when the patient breathes.
  • the arrow 104 in FIG. 1 points in the proximal or expiratory direction.
  • the term “distal direction” refers to the direction along such a path 102 that points toward the patient's lung and away from the mouth or nose.
  • the distal direction is generally the same as the inhalation or inspiratory direction when the patient breathes.
  • the arrow 106 in FIG. 1 points in the distal or inhalation direction.
  • the lungs include a right lung 110 and a left lung 115 .
  • the right lung 110 includes lung regions comprised of three lobes, including a right upper lobe 130 , a right middle lobe 135 , and a right lower lobe 140 .
  • the lobes 130 , 135 , 140 are separated by two interlobar fissures, including a right oblique fissure 126 and a right transverse fissure 128 .
  • the right oblique fissure 126 separates the right lower lobe 140 from the right upper lobe 130 and from the right middle lobe 135 .
  • the right transverse fissure 128 separates the right upper lobe 130 from the right middle lobe 135 .
  • the left lung 115 includes lung regions comprised of two lobes, including the left upper lobe 150 and the left lower lobe 155 .
  • An interlobar fissure comprised of a left oblique fissure 145 of the left lung 115 separates the left upper lobe 150 from the left lower lobe 155 .
  • the lobes 130 , 135 , 140 , 150 , 155 are directly supplied air via respective lobar bronchi, as described in detail below.
  • FIG. 2 is a lateral view of the right lung 110 .
  • the right lung 110 is subdivided into lung regions comprised of a plurality of bronchopulmonary segments. Each bronchopulmonary segment is directly supplied air by a corresponding segmental tertiary bronchus, as described below.
  • the bronchopulmonary segments of the right lung 110 include a right apical segment 210 , a right posterior segment 220 , and a right anterior segment 230 , all of which are disposed in the right upper lobe 130 .
  • the right lung bronchopulmonary segments further include a right lateral segment 240 and a right medial segment 250 , which are disposed in the right middle lobe 135 .
  • the right lower lobe 140 includes bronchopulmonary segments comprised of a right superior segment 260 , a right medial basal segment (which cannot be seen from the lateral view and is not shown in FIG. 2 ), a right anterior basal segment 280 , a right lateral basal segment 290 , and a right posterior basal segment 295 .
  • FIG. 3 shows a lateral view of the left lung 115 , which is subdivided into lung regions comprised of a plurality of bronchopulmonary segments.
  • the bronchopulmonary segments include a left apical segment 310 , a left posterior segment 320 , a left anterior segment 330 , a left superior segment 340 , and a left inferior segment 350 , which are disposed in the left lung upper lobe 150 .
  • the lower lobe 155 of the left lung 115 includes bronchopulmonary segments comprised of a left superior segment 360 , a left medial basal segment (which cannot be seen from the lateral view and is not shown in FIG. 3 ), a left anterior basal segment 380 , a left lateral basal segment 390 , and a left posterior basal segment 395 .
  • FIG. 4 shows an anterior view of the trachea 125 and a portion of the bronchial tree 120 , which includes a network of bronchial passageways, as described below.
  • the trachea 125 divides at a lower end into two bronchial passageways comprised of primary bronchi, including a right primary bronchus 410 that provides direct air flow to the right lung 110 , and a left primary bronchus 415 that provides direct air flow to the left lung 115 .
  • Each primary bronchus 410 , 415 divides into a next generation of bronchial passageways comprised of a plurality of lobar bronchi.
  • the right primary bronchus 410 divides into a right upper lobar bronchus 417 , a right middle lobar bronchus 420 , and a right lower lobar bronchus 422 .
  • the left primary bronchus 415 divides into a left upper lobar bronchus 425 and a left lower lobar bronchus 430 .
  • Each lobar bronchus, 417 , 420 , 422 , 425 , 430 directly feeds fluid to a respective lung lobe, as indicated by the respective names of the lobar bronchi.
  • the lobar bronchi each divide into yet another generation of bronchial passageways comprised of segmental bronchi, which provide air flow to the bronchopulmonary segments discussed above.
  • a bronchial passageway defines an internal lumen through which fluid can flow to and from a lung.
  • the diameter of the internal lumen for a specific bronchial passageway can vary based on the bronchial passageway's location in the bronchial tree (such as whether the bronchial passageway is a lobar bronchus or a segmental bronchus) and can also vary from patient to patient.
  • the internal diameter of a bronchial passageway is generally in the range of 3 millimeters (mm) to 10 mm, although the internal diameter of a bronchial passageway can be outside of this range.
  • a bronchial passageway can have an internal diameter of well below 1 mm at locations deep within the lung.
  • direct pathway refers to a bronchial passageway that branches directly or indirectly from the trachea and either (1) terminates in the targeted lung region to thereby directly provide air to the targeted lung region; or (2) branches into at least one other bronchial passageway that terminates in the targeted lung region to thereby directly provide air to the targeted lung region.
  • collateral pathway refers to any pathway that provides air to the targeted lung region and that is not a direct pathway.
  • direct is used to refer to air flow that flows into or out of a targeted lung region via a direct pathway.
  • the term “collateral” is used to refer to fluid flow (such as air flow) that flows into or out of a targeted lung region via a collateral pathway.
  • fluid flow such as air flow
  • direct is fluid flow (such as air flow) that enters or exits the targeted lung region via a direct pathway
  • longitudinal is fluid flow (such as air flow) that enters or exits the targeted lung region via a collateral pathway.
  • a collateral flow can be, for example, air flow that flows between segments of a lung, which is referred to as intralobar flow, or it can be, for example, air flow that flows between lobes of a lung, which is referred to as interlobar flow.
  • intralobar flow or it can be, for example, air flow that flows between lobes of a lung, which is referred to as interlobar flow.
  • a targeted region of the lung is identified, wherein the targeted lung region can comprise, for example, a single one of the lung regions described above with reference to FIGS. 1-3 , or the targeted lung region can comprise a collection of the regions described above. Alternately, the targeted lung region can be some other portion of the lung.
  • the targeted lung region can be, for example, a diseased lung region for which it is desired to bronchially isolate the region for the purposes of inhibiting fluid flow into the region.
  • to “bronchially isolate” a lung region means to modify the flow to the targeted lung region, such as to regulate, prevent, or inhibit direct air flow to the lung region.
  • an attempt is made to bronchially isolate the targeted lung region, such as by occluding the bronchial pathway(s) that directly feed air to the targeted lung region. This may be accomplished, for example, by advancing and implanting a bronchial isolation device into the one or more bronchial pathways that directly feed air to the targeted lung region to thereby regulate direct flow into the lung region.
  • the bronchial isolation device can be, for example, a device that regulates the flow of air into a lung region through a bronchial passageway.
  • Some exemplary bronchial isolation devices comprised of flow control elements are described in detail below with reference to FIG. 19-25 .
  • the following references describe exemplary flow control elements: U.S. Pat. No. 5,954,766 entitled “Body Fluid Flow Control Device; U.S. patent application Ser. No. 09/797,910, entitled “Methods and Devices for Use in Performing Pulmonary Procedures”; and U.S. patent application Ser. No. 10/270,792, entitled “Bronchial Flow Control Devices and Methods of Use”.
  • the foregoing references are all incorporated herein by reference in their entirety and are all assigned to Emphasys Medical, Inc., the assignee of the instant application.
  • the targeted lung region does not collapse, then it can be assumed that the targeted lung region is not collapsing because of collateral air flow into the lung.
  • the collateral flow into the targeted lung region can be completely prevented so that there is no collateral flow into the targeted lung region.
  • the collateral flow into the targeted lung region can simply be reduced, such as to minimize the effect of the collateral flow on the targeted lung region.
  • One way of impeding collateral fluid flow into the targeted lung region is by injecting one or more flowable therapeutic agents into the targeted lung region in order to partially or completely seal the collateral pathway(s) that are providing collateral flow into the targeted lung region.
  • the agent is “flowable” in that the agent is at least initially in a fluid state, which can be, for example, a liquid, gas, aerosol, etc.
  • the agent is “therapeutic” in that, when the agent contacts lung tissue, the agent generates a reaction in the tissue of the targeted lung region that serves to reduce, inhibit, or prevent collateral fluid flow into the targeted lung region.
  • the reaction can result in, for example (1) gluing or sealing portions of the targeted lung region together to thereby seal collateral pathways; (2) sclerosing or scarring target lung tissue to thereby occlude the collateral pathway(s) and seal off collateral flow into the targeted lung region; (3) promoting fibrosis in or around the targeted lung region to thereby seal off collateral flow into the region; (4) creating of an inflammatory response that would seal or fuse collateral pathway(s) that lead into the targeted lung region; (5) or creation of a bulking agent that fills space (such as space within the targeted lung region and/or the collateral pathway) and thereby partially or entirely seal off collateral flow into the targeted lung region.
  • a variety of flowable therapeutic agents have been identified that achieve one or more of the above reactions in lung tissue.
  • the agents include, for example, the following:
  • the foam expands in volume from an initial injected volume to an expanded volume by a predetermined volume amount.
  • the foam may double in volume from an injected volume to expanded volume.
  • Such volume expansion would cause the foam to fill-up and seal the volume of the targeted lung region or the volume of a collateral pathway.
  • the foam can be resorbable or degradable in the tissue of a patient's body, such that, when the foam is injected into the targeted lung region, the targeted lung region would absorb the foam and shrink in volume.
  • the foam could comprise a biodegradable polymer, such as polyethylene glycol (PEG) or polyglycolic acid (PGA).
  • the foam could be a biodegradable polymer that is foamed with hydrogen or some other gas and that is permeable through the cellular structure of the foam.
  • the foam has balanced properties of flow and viscosity in order to increase the likelihood that the foam will adequately fill the targeted lung region. Such balanced properties would also reduce the likelihood of the foam running or leaking into regions of the lung adjacent to the targeted lung region through the collateral pathway(s).
  • the foam can retain a foamy consistency until it is absorbed into the lung tissue, or it can cure and harden and then dissolve over time.
  • a sealant or glue such as, for example, fibrin, fibrinogen and thrombin epoxy, various cyanoacrylate adhesives and sealants, such as n-butyl-2-cyanoacrylate, synthetic biocompatible sealants made from polyethylene polymers, etc.
  • Sclerosing agents such as, for example, doxycycline, minocycline, tetracycline, bleomycin, cisplatin, doxorubicin, fluorouracil, interferon-beta, mitomycin-c, Corynebacterium parvum, methylprednisolone, and talc.
  • Antibiotics such as, for example, doxycycline, minocycline or bleomycin, tetracycline, etc.
  • Bulking agents such as, for example, collagen, gelatin, Gelfoam, or Surgicel solutions, polyvinyl acetate (PVA), ethylene vinyl alcohol copolymer (EVAL) or ethylene vinyl alcohol copolymer solutions.
  • PVA polyvinyl acetate
  • EVAL ethylene vinyl alcohol copolymer
  • ethylene vinyl alcohol copolymer solutions ethylene vinyl alcohol copolymer solutions.
  • PVA polyvinyl acetate
  • EVAL ethylene vinyl alcohol copolymer
  • ethylene vinyl alcohol copolymer solutions ethylene vinyl alcohol copolymer solutions.
  • DMSO dimethyl sulfoxide
  • Agents for inducing a localized infection and scar such as, for example, a weak strain of Pneumococcus.
  • Fibrosis promoting agents such as a polypeptide growth factor (fibroblast growth factor (FGF), basic fibroblast growth factor (bFGF), transforming growth factor-beta (TGF- ⁇ ))
  • FGF fibroblast growth factor
  • bFGF basic fibroblast growth factor
  • TGF- ⁇ transforming growth factor-beta
  • Pro-apoptopic agents such as sphingomyelin, Bax, Bid, Bik, Bad, caspase-3, caspase-8, caspase-9, or annexin V.
  • ECM extracellular matrix
  • HA hyaluronic acid
  • CS chondroitin sulfate
  • Fn fibronectin
  • ECM-like substances such as poly-L-lysine or peptides consisting of praline and hydroxyproline.
  • any well-known radiopaque contrast agent could be added to the therapeutic agent in order to facilitate viewing of the agent as it is dispersed in the targeted lung region.
  • a sufficient quantity of agent is dispersed to seal collateral pathways, but not so much that adjacent tissue is affected.
  • the flowable therapeutic agents that can be used to limit collateral flow into a targeted lung region are not limited to those described above.
  • the targeted lung region can be an entire lobe of one of the lungs 110 , 115 , or the targeted lung region can be one or more lung segments, such as, for example, the lung segments described above with reference to FIGS. 2 and 3 .
  • the targeted lung region being a lung lobe
  • an attempt is made to bronchially isolate the target lobe by sealing the direct pathways(s) into the target lobe, such as by implanting a bronchial isolation device into the lobar bronchus that supplies air to the targeted lobe. If the targeted lobe still does not collapse, then it can be assumed that a collateral pathway is supplying air to the targeted lobe, wherein the collateral pathway is through an incomplete interlobar fissure.
  • the outer surface of the lung is covered with a serous membrane called the visceral pleura.
  • the visceral pleura When the fissure between lobes is complete, the two adjacent lobes are separated and are completely covered with visceral pleura of all surfaces, and there is no collateral air flow possible between lobes.
  • the fissure is incomplete, the adjacent lobes are not completely separated, the visceral pleura does not completely surround the lobes, and parenchyma from the adjacent lobes in the incomplete portion of the fissure touch and are not separated. This incomplete formation of the fissure occurs naturally in about 50% of fissures in human lungs, and collateral air flow can occur between the lobes through these regions. See, Raasch B N, et al.
  • Radiographic Anatomy of the Interlobar Fissure A Study of 100 Specimens. AJR 1982; 138:1043-1049.
  • the lung can be treated to cause the fissure to seal (either partially or entirely) and thereby reduce or prevent collateral flow into the targeted lung lobe via the interlobar fissure.
  • FIG. 5 shows an example of a lung lobe that has been bronchially isolated using a bronchial isolation device comprised of a flow control element, which regulates fluid flow through a bronchial passageway that supplies fluid to the lobe.
  • the lobe receives collateral air flow through a collateral pathway comprised of an incomplete interlobar fissure.
  • a bronchial isolation device 510 such a flow control element, is implanted in the right middle lobar bronchus 420 in order to prevent direct flow into the targeted lung region comprised of the right middle lobe 135 .
  • the right middle lobe 135 is still receiving collateral flow (as exhibited by a series of arrows 512 in FIG.
  • the collateral flow comes from the right upper lobar bronchus 417 and passes into the right middle lobe 135 through the incomplete right transverse fissure 128 .
  • the right upper lobar bronchus 417 can also be considered to be a portion of the collateral pathway into the right middle lobe 135 .
  • the collateral flow into the right middle lobe 135 could be prevented or reduced by sealing the air pathways through the incomplete right transverse fissure 128 where the middle lobe 135 contacts the inferior surface of the right upper lobe 130 .
  • the targeted lung region can be a specific lung segment or some other portion of the lung that is within a lobe.
  • an attempt is made to bronchially isolate the targeted lung segment (or other portion of the lung), such as by inserting a flow control element into the direct pathway(s) to the targeted lung segment. If the targeted lung segment still does not collapse, it can be assumed that the flow is originating from other lung segments or other regions within the same lobe as the targeted segment, or from an incomplete interlobar fissure that is adjacent to the targeted lung segment.
  • FIG. 6 shows an example of this scenario. As shown in FIG. 6 , a targeted lung segment 610 is located within the right upper lobe 130 . The targeted lung segment 610 can receive direct flow via segmental bronchus 615 . The targeted lung segment 610 also receives collateral flow from an adjacent segment 620 that is also located within the right upper lobe 130 .
  • a targeted lung segment 630 is located in the right upper lobe 130 adjacent to the right transverse fissure 128 .
  • the targeted lung segment 630 can receive collateral flow from an adjacent lung segment in the right upper lobe 130 .
  • the targeted lung segment 130 can also receive collateral flow from the right middle lobe 135 via an incomplete right transverse fissure 128 , in which case a bronchial passageway of the right middle lobe 135 is the source of the collateral flow.
  • collateral flow to a targeted lung segment is originating from other segments or regions within the same lobe as the targeted lung region, or is originating from a separate, adjacent lobe via an incomplete fissure, it might be necessary to determine the bronchial passageway that is supplying collateral flow to the targeted lung region.
  • One method of determining the magnitude of collateral flow using selective bronchial balloon catheterization combined with ventilation on a helium-based marker gas and a helium detector, is disclosed in the literature. See, Morrell N W, et al. Collateral Ventilation and Gas Exchange in Emphysema, Am J Respir Crit Care Med 1994; 150:635-41.
  • the bronchial sub-branches such as segmental bronchi, feeding parenchyma adjacent to the interlobar fissure of an isolated lobe are determined fluoroscopically utilizing a standard guide wire.
  • the following example illustrates the technique as applied in the right upper lobe, although the same principles could be used in any of the human lung's five lobes or any segments within those lobes.
  • the lung is 3-dimensional and the airways are not sequentially related to linear lung regions (e.g., the most inferior segmental bronchus may partially feed the mid-section of a lung lobe or may preferentially feed the anterior or posterior aspect of that lobe), the goal is to determine the lowest (most inferior) sub-branch of the target upper lobe, as this sub-branch provides airflow to the lung parenchyma that borders the fissure between the upper lobe and the middle and lower lobes.
  • a bronchoscope is passed through the most inferior bronchus as seen from a bronchoscopic perspective. This is performed according to well-known methods using a standard bronchoscope. A guidewire is then passed through the working channel of the bronchoscope and visually fed into the subsequent, most inferior sub-branches to the visual limits of the bronchoscope. The guidewire is then advanced further with the aid of fluoroscopic visualization. For inferior/superior determination, the fluoroscope will generally be in an anterior-posterior orientation (90 degrees to the patient's chest). The position of the guidewire relative to fluoroscopic landmarks (e.g.: relative to a rib or to the diaphragm) is then noted. The aforementioned steps are repeated in multiple sub-branches until it can be determined which bronchial sub-branch feeds the most inferior lung tissue (and thus adjacent to the interlobar fissure), and this sub-branch is selected for treatment.
  • fluoroscopic landmarks e.g.: relative to a rib or to the dia
  • these steps can be repeated in other views (e.g. the camera in a 90 degree lateral view for anterior/posterior position) to map the sub-branches in 3-dimensions.
  • a physician can determine which bronchial sub-branch or branches feed the most inferior lung tissue, tissue that borders the right middle and right lower lobes. This technique could be applied to any lobe in the lung, and to either the inferior or superior surfaces.
  • the flowable therapeutic agent can be delivered to the targeted lung region according to a variety of methods. Some exemplary methods of delivering a flowable therapeutic agent to the targeted lung region are described below. Regardless of the method used, the therapeutic agent can be delivered to the targeted lung region either before or after an attempt is made to bronchially isolate the targeted lung region using a bronchial isolation device, or without bronchial isolation.
  • FIG. 7 illustrates an example of a method wherein a flowable therapeutic agent 705 is delivered to a targeted lung region using a delivery catheter 710 .
  • the targeted lung region is located in the right middle lobe 135 of the right lung 110 .
  • the delivery catheter 710 can be a conventional delivery catheter of the type known to those of skill in the art.
  • the delivery catheter 710 is deployed in a bronchial passageway, such as in the segmental bronchi 715 , that leads to the targeted lung region.
  • the delivery catheter 710 is deployed such that a distal end of the catheter 710 is positioned distal of a bronchial isolation device 510 that has also been deployed in the bronchial passageway 710 .
  • the bronchial isolation device 510 can be deployed either before or after deployment of the delivery catheter 710 .
  • the flowable therapeutic agent 705 can be delivered into the targeted lung region using the delivery catheter 710 . This can be accomplished by passing the flowable therapeutic agent through an internal lumen in the delivery catheter so that the agent exits a hole in the distal end of the delivery catheter 710 into the targeted lung region. As shown in FIG. 7 , the distal end of the delivery catheter 710 can be sealed within the targeted lung region by inflating a balloon 720 that is disposed near the distal end of the catheter according to well-known methods. In another embodiment, shown in FIG. 8 , the bronchial isolation device 510 provides the sealing so that a balloon is not needed when delivering the flowable therapeutic agent 705 using the delivery catheter 710 .
  • FIG. 9 illustrates another method of delivering the flowable therapeutic agent to the targeted lung region.
  • a delivery device such as a delivery catheter or a hypodermic needle 910 , is used to percutaneously inject the flowable therapeutic agent 705 directly into the lung tissue of the targeted lung region.
  • the hypodermic needle 910 is used to puncture the chest wall according to well-known methods so that a sharpened delivery tip 915 of the needle 910 locates within the targeted lung region.
  • the targeted lung region could comprise a portion of the right middle lobe 135 located near the fissure 128 , as shown in FIG. 9 .
  • the hypodermic needle 910 is then used to puncture the chest wall and the needle 910 is positioned so that the delivery tip 915 locates within the right middle lobe 135 .
  • the flowable therapeutic agent 705 is then injected directly into the targeted lung region via the hypodermic needle 910 according to well-known methods.
  • FIG. 10 shows yet another method of delivering the flowable therapeutic agent to the targeted lung region.
  • a delivery catheter 710 has a distal tip 1005 that can be used to puncture the wall of a bronchial passageway 1010 at a location that is at or near the targeted lung region.
  • the distal tip 1005 is configured to facilitate puncturing of the bronchial wall, as described more fully below.
  • the distal tip of the delivery catheter 710 is passed through the bronchial wall and the flowable therapeutic agent can be injected into the targeted lung region through the delivery catheter 710 .
  • the method shown in FIG. 10 differs from the method described above with reference to FIGS.
  • FIG. 10 actually punctures the bronchial wall so that the flowable therapeutic agent can be injected directly into the lung tissue.
  • the method shown in FIGS. 7 and 8 does not include puncturing of the bronchial wall, and the flowable therapeutic agent is injected into the bronchial lumen leading to the targeted lung region rather than directly into the lung tissue.
  • the puncturing of the bronchial wall can be accomplished using any of a variety of methods and devices.
  • the distal tip 1010 of the delivery catheter is configured to facilitate puncturing of the bronchial wall.
  • the distal tip 1005 can be sharpened to an appropriate sharpness that will facilitate puncturing of a bronchial wall. It has been determined that a delivery catheter with a diameter of up to 3 millimeters (mm) will be sufficient.
  • a hypodermic needle can be mounted on the distal tip 1005 to facilitate puncturing of the bronchial wall.
  • a stiff guidewire is delivered to the targeted lung region via the inner lumen of a flexible bronchoscope. The guidewire is then used to puncture the bronchial wall.
  • a delivery catheter is delivered over the stiff guidewire to the targeted lung region.
  • radio frequency (RF) energy is applied to a catheter that comprises an RF cutting tip, and the cutting tip is applied to the bronchial wall at a location at or near the targeted lung region, thereby causing the bronchial wall to puncture.
  • RF radio frequency
  • a device approved for this purpose is the Exhale RF Probe, Broncus Technologies, Inc. Mountain View, Calif., FDA 510(k) #K011267.
  • a flexible biopsy forceps is delivered through a working channel of the bronchoscope and used to cut a hole through the bronchial wall in a well-known manner.
  • the delivery catheter 710 can be deployed at the targeted lung region according to a variety of methods.
  • the delivery catheter 710 can be deployed using a bronchoscope 1111 , which in an exemplary embodiment has a steering mechanism 1115 , a delivery shaft 1120 , a working channel entry port 1125 , and a visualization eyepiece 1130 .
  • the bronchoscope 1111 has been passed into a patient's trachea 125 and guided into the right primary bronchus 410 according to well-known methods.
  • the delivery catheter 710 is then deployed into the working channel entry port 1125 and down a working channel (not shown) of the bronchoscope shaft 1120 , and the distal end 1135 of the catheter 710 is guided to a desired location within the bronchial tree, such as to a lobar bronchi 417 located within the upper lobe 130 of the right lung 110 .
  • the steering mechanism 1115 can be used to deliver the shaft 1120 to a desired location.
  • the delivery catheter 710 can have a central guidewire lumen and can be deployed using a guide wire that guides the catheter to the delivery site.
  • the delivery catheter 710 could have a well-known steering function, which would allow the catheter 710 to be delivered with or without use of a guidewire.
  • one or more nasal cannulae are deployed through a patient's nasal cavity, through the trachea, and to a desired location in the bronchial tree 120 at the targeted lung region.
  • One or more bronchial isolation devices such as a flow control element, can also be deployed to bronchially isolate the targeted lung region, with a distal end(s) of the cannula(e) being passed through the bronchial isolation device(s).
  • a catheter with multiple divided lumens or cannulae could be deployed.
  • the cannula can be left in place for a desired amount of time and an infusion of one or more flowable therapeutic agents is deployed to the targeted lung region via the cannula.
  • the delivery catheter 710 can be used to bronchially isolate the targeted lung region without the use of, or in combination with the use of, a flow control element.
  • the distal end of the delivery catheter 710 is equipped with a balloon (such as the balloon 720 shown in FIG. 7 ), which is inflated to occlude or partially occlude the bronchial passageway that provides fluid flow to the targeted lung region. In this manner, fluid flow through the bronchial passageway can be reduced or eliminated.
  • the therapeutic agent in the course of delivering the therapeutic agent to the targeted lung region, it can be desirable to control the dispersion of the therapeutic agent in the lung so that the agent does not flow through any collateral pathways into areas of healthy lung tissue. It can also be desirable to move the therapeutic agent preferentially toward the collateral pathway(s) (rather than toward some other area of the lung) in order to increase the likelihood that sealing of collateral pathway(s) is successful.
  • One way of controlling the movement of the therapeutic agent within the lung is to provide pressure differentials in different regions of the lung, wherein the pressure differentials encourage the therapeutic agent to flow in a desired manner.
  • a targeted lung region 1210 is located in the right lower lobe 140 of the right lung 110 .
  • a healthy lung region 1220 is located adjacent to the targeted lung region 1210 .
  • the pressure within the targeted lung region is P 1 and the pressure within the adjacent lung region 1220 is P 2 . If P 1 is greater than P 2 , then a therapeutic agent located in the targeted lung region 1210 will be inclined to flow toward the adjacent lung region 1220 due to the pressure differential. Likewise, if P 2 is greater P 1 , then a therapeutic agent located in the targeted lung region 1210 will be inclined to flow away from the adjacent lung region 1220 .
  • One way to accomplish such a pressure differential is to control the injection pressure that is used to inject the therapeutic agent into the targeted lung region, and to also control a back pressure in an adjacent lung region where collateral pathways to the targeted lung region originate. If the therapeutic agent is radiopaque, a physician can view the extent of the therapeutic agent dispersion while also varying the injection pressure and the back pressure to control the dispersion.
  • FIG. 13 shows a cross-sectional view of the right lung 110 , wherein the targeted lung region comprises the right middle lobe 135 , which is adjacent to a healthier lung region comprised of the right upper lobe 130 .
  • the incomplete right transverse fissure 128 provides a collateral pathway through which collateral flow originating in the right upper lobe 130 passes into the right middle lobe 135 .
  • a first delivery catheter 710 which can have a balloon 720 , is passed through a bronchial isolation device 510 so that the distal end of the catheter 710 is disposed in the targeted lung region.
  • a second catheter 1305 is deployed in a bronchial passageway that provides flow to a lung region adjacent to the target region, wherein some collateral flow originates at the adjacent lung region.
  • FIG. 13 shows the second catheter 1305 deployed through the right lobar bronchus 417 , which provides flow to the right upper lobe 130 where the collateral flow into the right middle lobe originates.
  • the second catheter can have a balloon 1310 that is inflated.
  • the delivery catheter 710 is then used to inject the flowable therapeutic agent 705 into the targeted lung region at a desired injection pressure. This will cause the targeted lung region to achieve a pressure P 1 .
  • a suction can be applied to the distal end of the second catheter 1305 to thereby achieve a pressure P 2 in the adjacent lung region comprised of the right upper lobe 130 .
  • a desired pressure differential between P 1 and P 2 can be achieved to thereby control the dispersion of the therapeutic agent.
  • the pressure differential can be manipulated to encourage the therapeutic agent to flow toward the collateral pathway and even enter the collateral pathway.
  • the dispersion can be visually monitored if the therapeutic agent includes a radiopaque.
  • the desired dispersion level has been achieved, such as when the therapeutic agent has filled the targeted lung region or has filled the collateral pathways, it might then be desirable to further control the dispersion to reduce the likelihood that the therapeutic agent will flow into the healthy lung region.
  • This can be accomplished by again varying the pressure differential so that the therapeutic agent no longer flows towards the healthy lung region.
  • the injection pressure can be reduced or eliminated, while also changing the suction pressure at the second catheter 1305 .
  • Suction can then be applied to the delivery catheter 710 to remove any excess therapeutic agent from the targeted lung region.
  • the catheters 710 , 1305 are then removed. In this manner, the therapeutic agent is preferentially moved toward the collateral pathway(s).
  • the aforementioned technique for sealing the collateral flow pathway could also be performed prior to the implantation of the bronchial isolation device(s) 510 .
  • a follow-on therapy procedure can be followed.
  • the treated portion of the lung (the portion of the lung to which the therapeutic agent was applied) is left alone, with the therapeutic agent in place.
  • the treated lung portion is allowed to collapse by either absorption of the therapeutic agent by the body, absorption of the trapped gas in the isolated lung region, exhalation of trapped gas out through a flow control device (such as an implanted one-way or two-way valve device) or any combination of these events.
  • the therapeutic agent is removed from the lung following the passage of a predetermined treatment period.
  • the therapeutic agent could be removed after a short period of time such as one or two minutes, or a longer period of 30 or 60 minutes.
  • the therapeutic agent could be removed in a separate procedure hours or days later. The necessary time period would depend on the particular therapeutic agent used. This could be done with the implanted bronchial isolation devices in place, or could be done before implantation of the bronchial isolation devices if the therapeutic agent was deployed prior to implantation of the bronchial isolation devices.
  • the therapeutic agent can be removed from the lung in any number of ways, which include the following:
  • the catheter could either be sealed by the valve in the implanted device, or it could be a balloon catheter where the balloon is inflated in the bronchial passageway distal to the implanted device.
  • Implant one or more bronchial isolation devices to isolate targeted lung region; inject a flowable therapeutic agent into the targeted lung region distal to the bronchial isolation devices; allow the lung region to collapse, such as, for example, by absorption of the therapeutic agent by the body, absorption of the trapped gas in the isolated lung portion, exhalation of trapped gas out through the implanted one-way or two-way valve devices, or any combination of these events.
  • Implant one or more bronchial isolation devices inject a flowable therapeutic agent into the targeted lung region distal to devices; wait a pre-determined treatment time period; remove the therapeutic agent, such as, for example, by using suction, needle aspiration, etc.; and allow the lung region to collapse, such as, for example, by absorption of the trapped gas in the isolated lung portion, exhalation of trapped gas out through the implanted one-way or two-way valve devices, or both.
  • (c) Inject a flowable therapeutic agent into the targeted lung region; implant bronchial isolation devices; allow the targeted lung region to collapse, such as, for example, by absorption of the therapeutic agent by the body, absorption of the trapped gas in the isolated lung portion, exhalation of trapped gas out through the implanted one-way or two-way valve devices, or any combination of these events.
  • (d) Inject a flowable a therapeutic agent into parenchyma of the targeted lung region; implant one or more bronchial isolation devices; wait a pre-determined treatment time period; remove the therapeutic agent, such as, for example, using suction, needle aspiration, etc.; and allow lung region to collapse, such as, for example, by absorption of the trapped gas in the isolated lung portion, exhalation of trapped gas out through the implanted one-way or two-way valve devices, or both.
  • An alternate way of reducing or preventing collateral fluid flow into the targeted lung region is to apply energy to the targeted lung region, wherein the application of energy generates a reaction in the tissue of the targeted lung region that serves to reduce or prevent collateral fluid flow into the targeted lung region.
  • the reaction can result in, for example: (1) gluing or sealing portions of the lung together to thereby partially or entirely seal collateral pathways; (2) sclerosing or scarring target lung tissue to thereby partially or entirely occlude the collateral pathway(s) and partially or entirely seal off collateral flow into the targeted lung region; (3) promoting fibrosis in or around the targeted lung region to thereby partially or entirely seal off collateral flow into the region; (4) creating of an inflammatory response that would partially or entirely seal or fuse collateral pathway(s) that lead into the targeted lung region.
  • a variety of energy sources have been identified that can be used to apply energy to lung tissue to achieve any of the aforementioned reactions.
  • the types of energy include Beta-emitting radiation, radio frequency energy, heat, ultrasound, cryo-ablation, laser energy, and electrical energy.
  • the process of identifying the lung region for treatment can be the same as that described above with reference to the use of the flowable therapeutic agent.
  • the therapeutic agent can be delivered to the targeted lung region either without bronchial isolation, or before or after an attempt is made to bronchially isolate the targeted lung region using a bronchial isolation device.
  • FIG. 14 illustrates a method wherein an energy source is delivered to a targeted lung region using a delivery catheter 710 .
  • the targeted lung region is located in the right middle lobe 135 of the right lung 110 .
  • the delivery catheter 710 can be a conventional delivery catheter of the type known to those of skill in the art.
  • the delivery catheter 710 is deployed in a bronchial passageway, such as in the sub-segmental bronchi 715 , that leads to the targeted lung region.
  • a distal end of the catheter 710 is inserted into the bronchial passageway and is positioned distal of a bronchial isolation device 510 that has been deployed in a bronchial passageway that provides direct flow to the targeted lung region.
  • the bronchial isolation device 510 can be deployed either before or after deployment of the delivery catheter 710 .
  • an energy source 1410 can be delivered into the targeted lung region using the delivery catheter 710 . This can be accomplished, for example, by passing a push wire 1415 having a distally-mounted energy source 1410 through an internal lumen in the delivery catheter 710 so that the energy source 1410 exits a hole in the distal end of the delivery catheter 710 into the targeted lung region.
  • the energy source 1410 can be mounted on the distal end of the delivery catheter 710 .
  • the distal end of the delivery catheter 710 can be sealed within the targeted lung region by inflating a balloon that is disposed near the distal end of the catheter according to well-known methods.
  • the bronchial isolation device 510 can provide the sealing so that a balloon is not needed.
  • a delivery device such as delivery catheter or a hypodermic needle, is used to percutaneously reach the targeted lung region by puncturing the chest wall and outer surface of the lung.
  • the energy source is then advanced directly into the lung tissue. This would be similar to the method shown in FIG. 9 , although an energy source would be used in place of the flowable therapeutic agent.
  • a delivery catheter has a distal tip that can be used to puncture the wall of a bronchial passageway that is located at or near the targeted lung region.
  • the distal tip is configured to facilitate puncturing of the bronchial wall.
  • the energy source is advanced into the targeted lung region through the delivery catheter. This would be similar to the process shown in FIG. 10 .
  • the puncturing of the bronchial wall can be accomplished using any of a variety of methods and devices, such as was described above with reference to FIG. 10 .
  • the delivery catheter for delivering the energy source to the targeted lung region could be deployed in the same manner described above with reference to the flowable therapeutic agents, such as by using a bronchoscope.
  • beta-emitting radiation could be accomplished with a brachytherapy delivery system that includes a beta-emitting radiation source mounted to the end of a delivery catheter, such as was described above. As mentioned previously, this could be done either before or after the implantation of bronchial isolation devices.
  • a beta radiation-emitting source is passed through one or more target bronchial passageways, either sequentially or concurrently, that lead to the targeted lung region.
  • the source can also be passed through one or more of the bronchial isolation devices that were previously implanted.
  • the radiation source is left in place for a period of time so as to elicit a scarring/healing response in the treated lung tissue. For example, it may be discovered through animal and/or human clinical trials that an exposure time period of 30 minutes to one hour will achieve satisfactory results. A maximum time may be identified wherein the risk of radiation to the surrounding tissue is greater than the benefits of scarring the target tissue. For example, it may be discovered that the radiation source can remain in up to an hour, but that exposure for greater than 90 minutes increases risk to the patient.
  • the application procedure is performed over a predetermined time period and/or over bronchial sub-branches.
  • a patient can first be admitted for a procedure to deploy bronchial isolation devices, such as flow limiting valves, and then discharged with periodic reassessment of anatomical or clinical results.
  • the physician and patient could decide when the next step of transvalvular brachytherapy should take place (e.g.: 15-30 days after the primary procedure).
  • Brachytherapy could also be staged over time in such a way as to minimize risk while continually assessing benefit (e.g.: valves placed day one, first brachytherapy procedure of 30 minutes exposure day 30, second brachytherapy procedure of 30 minutes at day 60, etc.).
  • the first brachytherapy session could be targeted at the RUL, inferior sub-segment of the anterior, segmental bronchus; the second session would target the RUL superior sub-segment of the anterior, segmental bronchus; etc.
  • beta-emitting radiation could be followed for other radiation sources such as RF energy, heat, ultrasound, or cryo-ablation. These energy sources might require different treatment times, a different number of treatment sites, etc., but the general application method would be the same.
  • the lung region targeted for isolation and collapse is identified, and bronchial isolation devices are implanted in all airways that provide direct flow to the targeted lung region.
  • the implanted isolation devices can be, for example, one-way valves that allow flow in the exhalation direction only, one-way valves that allow flow in the inhalation direction only, occluders or plugs that prevent flow in either direction, or two-way valves that control flow in both directions according to well-known methods. If the lung region does not collapse, such as due to either absorption atelectasis, or through exhalation of trapped gas through the implanted devices, then the lung region is likely being kept inflated through collateral in-flow through collateral pathways from adjacent lung regions. If the collateral flow from the adjacent lung regions could be reduced substantially or eliminated, the targeted lung region will likely collapse.
  • One way to reduce or substantially eliminate the collateral flow from adjacent lung regions is to implant inhalation flow limiting two-way valve devices in the bronchial passageways leading to adjacent lung regions not targeted for collapse, wherein the adjacent lung regions act as a source for collateral flow into the targeted lung region.
  • Such devices would allow free fluid flow in the exhalation direction for the adjacent lung regions, but would limit the flow to a predetermined level in the inhalation direction.
  • flow into the adjacent lung region would be limited, thereby limiting the flow of gas into the targeted lung region through the collateral pathways from the adjacent lung regions.
  • the flow limitation is desirably sufficient to allow the isolated lung region to collapse, but would not collapse the adjacent lung regions. Once sufficient time had passed to allow the targeted lung region to become chronically atelectatic, the flow limiting two-way valve devices could be removed from the adjacent lung regions in order to restore normal ventilation to the lung portion not targeted for collapse.
  • FIG. 15 shows a targeted lung region comprised of the right upper lobe 130 that is isolated by one-way bronchial isolation devices 510 that are implanted in all bronchial passageways leading to the lobe 130 .
  • the devices 510 are one-way valve devices that stop all flow in the inhalation direction to thereby prevent direct flow into the lobe 130 .
  • a flow limiting two-way valve bronchial isolation device 1510 is implanted in the bronchial passageway in the right middle lobe 135 in the segment that lies just below the interlobar fissure 128 adjacent to the lobe 130 .
  • the device 1510 allows free flow in the exhalation direction and a limited flow in the inhalation direction.
  • the collateral flow into the targeted upper lobe 130 that originates in the middle lobe 130 is also limited.
  • the flow limitation into the middle lobe 135 is sufficient to allow the right upper lobe 130 to collapse, as the collateral flow into the upper lobe 135 via the fissure 128 is insufficient to inflate the upper lobe 130 .
  • FIGS. 22-25 One exemplary embodiment of a flow limiting two-way valve 2500 is shown in FIGS. 22-25 .
  • the valve would behave as a one-way valve in the forward or exhalation direction in that it would allow free flow of fluid through the valve.
  • the valve would also allow a controlled rate of flow in the reverse or inhalation direction. This could be achieved in a duckbill style valve by adding a small flow channel 2510 through the lips 2512 of the valve, as shown in FIG. 25 .
  • the reverse flow channel shown would allow fluid to flow in the inhalation direction, and the rate of flow would be controlled by diameter and length of the flow channel.
  • bronchial isolation devices may be implanted in any bronchial passageways that provide direct flow to the targeted lung region.
  • Percutaneous suction is then applied to the targeted lung region for a time period sufficient to adhere or fuse the lung tissue in the targeted lung region in a collapsed state such that the targeted lung region will not re-inflate through collateral pathways after the suction is stopped.
  • the percutaneous suction method is described in more detail with reference to FIG. 16 , which shows the targeted lung region being located in the right upper lobe 130 .
  • An attempt is made to bronchially isolate the targeted lung region by implanting one or more bronchial isolation devices 705 in bronchial passageway that provide direct flow into the targeted lung region.
  • a suction catheter 1610 is percutaneously inserted into the targeted lung region, such as by inserting the catheter 705 through the rib space in a well-known manner.
  • the suction catheter 1610 includes an internal lumen and has a distal end 1615 on which are located one or more suction holes 1620 that communicate with the internal lumen.
  • a suction force can be applied to a proximal end 1625 of the catheter 1610 to suck fluid into the internal lumen through the suction holes 1620 on the distal end 1615 of the catheter 1610 .
  • a fixation balloon 1630 is mounted on the catheter 1610 a short distance from the distal end 1615 of the catheter 1610 . In one embodiment, the fixation balloon 1630 is mounted approximately 2 centimeters from the distal end 1615 .
  • An exemplary suction catheter that can be used is the 8-French Venography Catheter, manufactured by The Cook Group, Inc., Bloomington, Ind.
  • the suction catheter 1610 is percutaneously inserted into the targeted lung region so that the suction holes 1620 in the distal end 1615 are positioned within the targeted lung region.
  • the fixation balloon 1630 is positioned in the pleural space of the lung and is then inflated to thereby fix the suction catheter 1610 in a fixed position and to also seal the incision that was used to percutaneously insert the catheter 1610 .
  • the suction catheter 1610 can be maneuvered into the correct location using guidance assistance, such as computer tomography (CT) or fluoroscopic guidance.
  • CT computer tomography
  • fluoroscopic guidance such as computer tomography (CT) or fluoroscopic guidance.
  • a suction force can be applied to the internal lumen of the catheter to thereby cause a sucking force that draws fluid into the internal lumen through the suction holes 1620 .
  • the suction force will draw air or other fluid in the targeted lung region into the internal lumen through the suction holes 1620 , which will aspirate the targeted lung region into a collapsed state. It has been determined that a suction force of approximately 100-160 mmHg is sufficient to aspirate the targeted lung region into a collapsed state.
  • the suction force can be continuously maintained for a time period sufficient to permanently collapse the lung and reduce the likelihood of inflation through collateral pathways. In one embodiment, the suction is continuously maintained for a minimum time period of eight hours. In another embodiment, the suction is maintained for a time period of one to eight days.
  • the suction can be performed while the patient is on bed rest, using a stationary vacuum source, or it could be performed using a portable vacuum source in order to permit the patient to ambulate.
  • a flowable therapeutic agent (such as any of the agents described above) can optionally be infused into the targeted lung region. This could be performed using the suction catheter 1610 , such as by infusing the agent through a separate internal lumen located in the catheter 1610 or through the same lumen that was used for suction.
  • the therapeutic agent could be used to increase the likelihood that the targeted lung region is properly sealed.
  • the fixation balloon 1630 is then deflated and the suction catheter 1610 is removed.
  • a two-part adhesive or glue is used to occlude a collateral pathway to the targeted lung region.
  • the adhesive can comprise a two-part mixture that includes a first part and a second part, wherein the first part and the second part collectively solidify when brought into contact with each other.
  • the two parts do not necessarily require complete mixing in order for the solidification to occur.
  • the solidification can be triggered, for example, by a catalytic reaction that occurs when the two parts contact one another.
  • the two-part glue is a fibrin glue and the two parts of the glue are thrombin and fibrinogen.
  • the collateral pathway is located in a lung region between two or more bronchial passageway, such as a first bronchial passageway and a second bronchial passageway.
  • the collateral pathway can be an incomplete interlobar 128 fissure that is located between a first bronchial passageway 1710 and a second bronchial passageway 1715 .
  • the bronchial passageway are not necessarily in the same lobe.
  • the bronchial passageway 1710 is in the right upper lobe 130 and the bronchial passageway 1715 is in the right middle lobe 135 , where the targeted lung region is also located.
  • the first part of the two-part adhesive is injected into the first bronchial passageway and the second part of the two-part adhesive is injected into the second bronchial passageway.
  • the injection pressure and flow rates of the first and second parts can be controlled to encourage the first and second parts to flow to a common location, wherein the common location coincides with the location of the collateral flow path. That is, the first and second parts will contact one another within the collateral flow path. As mentioned, the first and second parts solidify when they contact one another. In this manner, the first and second parts solidify within the collateral flow path and thereby partially or entirely seal the collateral flow path.
  • FIG. 17 shows a balloon-tipped catheter 1712 that has been deployed in the second bronchial passageway 1715 , which supplies direct flow to the targeted lung region.
  • a bronchial isolation device 510 is deployed in a segmental bronchus 1735 that is proximal to the second bronchial passageway 1715 in order to bronchially isolate the targeted lung region.
  • the catheter 1712 is sealed within the bronchial passageway 1715 by inflating a balloon 1720 mounted on the catheter 1712 .
  • a second balloon-tipped catheter 1725 is deployed in the first bronchial passageway 1710 and sealed by inflating a balloon 1730 .
  • the first part 1728 of the two-part adhesive is then injected into the bronchial passageway 1715 via the catheter 1712 and the second part 1732 of the two-part adhesive is injected into the bronchial passageway 1710 via the catheter 1725 .
  • the first and second parts are injected in such a manner that they flow into the lung and meet at the collateral pathway comprised of the incomplete interlobar fissure 128 . As a result of the contact between the first and second parts, they solidify within the interlobar fissure and thereby partially or entirely seal the interlobar fissure.
  • any remaining quantity of the first and second parts can be suctioned out of the lung.
  • the first and second parts could be absorbable by the body so that excess material need not be removed.
  • the aforementioned technique for sealing the collateral flow pathway could also be performed prior to the implantation of the bronchial isolation device(s) 510 .
  • bronchial passageways collapse during exhalation thus leading to reduced flow through these lumens.
  • This often results in trapped gas in certain regions of the lung that exhale air through the collapsed lumen.
  • This in turn can lead to hyperinflation of the lung region, as well as compression of the healthy lung tissue that is adjacent to the lung region.
  • One way of treating the hyperinflated lung region is to implant bronchial isolation devices, such as one-way or two-way valves, in the bronchial passageway that lead to the lung region in order to promote lung region collapse.
  • bronchial isolation devices can be limited due to the reduced air flow during exhalation through the native bronchial passageways, especially if collateral flow is present.
  • One method of counteracting this effect is to implant one or more shunt tubes that are inserted through the bronchial passageways and into the targeted lung region comprised of a damaged lung region.
  • the shunt tubes provide a clear flow path for exhaled air that is not be occluded by the collapsed bronchial passageway.
  • one-way valves may be either mounted to a proximal end of the shunt tubes, or implanted in the bronchial passageways at some distance proximal to the proximal end of the tubes. These valves allow exhaled air to escape in the exhalation direction through the valve or valves, but do not allow inhaled air to return to the isolated targeted lung region.
  • a self expanding braided tube can be used to prop the collapsed airway open. This allows side branches to continue to exhale air into the braided tube while keeping the bronchi open.
  • FIG. 18 shows an example of how shunt tubes can be utilized.
  • a bronchial isolation device 510 is implanted in a bronchial passageway of the right upper lobe 130 .
  • Two implanted shunt tubes 1810 and 1820 are shown deployed in two lumens.
  • the shunt tubes 1810 , 1820 are located distal to the implanted isolation device 510 .
  • the shunt tubes 1810 , 1820 keep the airways open and provide a flow path through which exhaled air can pass.
  • the implanted shunt tubes 1810 and 1820 are shown in FIG. 18 as being implanted just distally to the implanted bronchial isolation device 510 .
  • the shunt tubes may be implanted more distally, and a greater quantity may be implanted.
  • the shunt tubes may be anchored in the bronchial lumen in a number of ways.
  • the shunt tube have spring resilience and expand when released from a smaller constrained diameter to a larger diameter, thus gripping the bronchial lumen wall.
  • the shunt tubes may comprise a deformable retainer that is expanded to grip the bronchial lumen wall by inflating a balloon placed inside the collapsed shunt tube.
  • the shunt tubes may also comprise a cylindrical structure that increases in diameter when its temperature is raised to body temperature.
  • the shunt tubes may also have barbs, prongs or other features on the outside that assist in gripping the bronchial lumen wall for retention.
  • a target lung region can be bronchially isolated by advancing a bronchial isolation device into the one or more bronchial pathways that directly feed air to the targeted lung region.
  • the bronchial isolation device can be a device that regulates the flow of fluid into or out of a lung region through a bronchial passageway.
  • FIG. 19 shows a cross-sectional view of an exemplary bronchial isolation device comprised of a flow control element 1910 .
  • the flow control element 1910 is merely an exemplary bronchial isolation device and that other types of bronchial isolation devices for regulating air flow can also be used.
  • the following references describe exemplary bronchial isolation devices: U.S. Pat. No.
  • the flow control element 1910 is in the form of a valve with a valve member 1915 supported by a ring 1920 .
  • the valve member 1915 is a duckbill-type valve and has two flaps defining an opening 1925 .
  • the valve member 1915 is shown in a flow-preventing orientation in FIG. 19 with the opening 1925 closed.
  • the valve member 1915 is configured to allow free fluid flow in a first direction (along arrow A) while controlling fluid flow in a second direction (along arrow B). In the illustrated embodiment, fluid flow in the direction of arrow B is controlled by being completely blocked by valve member 1915 .
  • the first and second directions in which fluid flow is allowed and controlled, respectively, can be opposite or substantially opposite each other, such as is shown in FIG. 19 .
  • the valve member 1915 functions as a one-way valve by completely blocking fluid flow in a certain direction. It should be appreciated that the flow control element could be configured to block or regulate flow along two-directions.
  • FIGS. 20 and 21 show another embodiment of an exemplary flow control element, comprising flow control element 2000 .
  • the flow control element 2000 includes a main body that defines an interior lumen 2010 through which fluid can flow along a flow path.
  • the flow of fluid through the interior lumen 2010 is controlled by a valve member 2012 .
  • the valve member 2012 in FIGS. 20-21 is a one-way valve, although two-way valves can also be used, depending on the type of flow regulation desired.
  • FIGS. 22-25 show an exemplary two-way valve member 2500 .
  • the flow control element 2010 has a general outer shape and contour that permits the flow control device 2010 to fit entirely within a body passageway, such as within a bronchial passageway.
  • the flow control member 2000 includes an outer seal member 2015 that provides a seal with the internal walls of a body passageway when the flow control device is implanted into the body passageway.
  • the seal member 2015 includes a series of radially-extending, circular flanges 2020 that surround the outer circumference of the flow control device 2000 .
  • the flow control device 2000 also includes an anchor member 2018 that functions to anchor the flow control device 2000 within a body passageway. It should be appreciated that other types of flow control devices can also be used to bronchially isolate the targeted lung region.
  • the flow control element can be implanted in the bronchial passageway using a delivery catheter.
  • the flow control element is mounted on a distal end of the delivery catheter.
  • the distal end of the delivery catheter is then deployed to the bronchial passageway, such as by inserting the delivery catheter through the patient's mouth or nose, through the trachea, and through the bronchial tree to the desired location in the bronchial passageway.
  • the delivery catheter can be deployed, for example, using a guide wire or without a guide wire.
  • a bronchoscope is deployed to the location in the bronchial passageway where the flow control device will be deployed.
  • the delivery catheter with the flow control element is then deployed to the bronchial passageway by inserting the delivery catheter through a working channel of the bronchoscope such that the distal end of the delivery catheter and the attached flow control element protrude from the distal end of the working channel into the bronchial passageway.
  • the flow control element is then removed from the delivery catheter so that the flow control elements is positioned within and retained in the bronchial passageway.
  • U.S. patent application Ser. No. 10/270,792 entitled “Bronchial Flow Control Devices and Methods of Use” (which is assigned to Emphasys Medical, Inc., the assignee of the instant application) describes various methods and devices for implanting a flow control element into a bronchial passageway.

Abstract

A method of treating a lung comprises deploying a delivery catheter through a bronchial tree into a targeted lung region and delivering a fibrinogen suspension through the delivery catheter so that the fibrinogen suspension exits the distal end of the delivery catheter into the targeted lung region. Thrombin is also delivered through the delivery catheter so that the thrombin exits the distal end of the delivery catheter into the targeted lung region. The lung is promoted to collapse.

Description

    REFERENCE TO PRIORITY DOCUMENTS
  • This application is a continuation and claims the benefit of priority under 35 USC 120 of co-pending U.S. patent application Ser. No. 11/696,627 entitled “Methods and Devices for Lung Treatment”, filed Apr. 4, 2007, which claims priority of U.S. patent application Ser. No. 10/384,899 entitled “Methods and Devices for Inducing Collapse in Lung Regions Fed by Collateral Pathways”, filed Mar. 6, 2003, which claims priority of U.S. Provisional Patent Application Ser. No. 60/363,328 entitled “Methods and Devices for Inducing Collapse in Lung Regions Fed by Collateral Pathways”, filed Mar. 8, 2002. Priority of the aforementioned filing dates is hereby claimed, and the disclosures of the aforementioned patent application are hereby incorporated by reference.
  • BACKGROUND
  • This invention relates generally to methods and devices for use in performing pulmonary procedures and, more particularly, to procedures for treating various diseases of the lung.
  • Pulmonary diseases such as chronic obstructive pulmonary disease (COPD) reduce the ability of one or both lungs to fully expel air during the exhalation phase of the breathing cycle. The term “Chronic Obstructive Pulmonary Disease” (COPD) refers to a group of diseases that share a major symptom, dyspnea. Such diseases are accompanied by chronic or recurrent obstruction to air flow within the lung. Because of the increase in environmental pollutants, cigarette smoking, and other noxious exposures, the incidence of COPD has increased dramatically in the last few decades and now ranks as a major cause of activity-restricting or bed-confining disability in the United States. COPD can include such disorders as chronic bronchitis, bronchiectasis, asthma, and emphysema. While each has distinct anatomic and clinical considerations, many patients may have overlapping characteristics of damage at both the acinar (as seen in emphysema) and the bronchial (as seen in bronchitis) levels, almost certainly because one pathogenic mechanism—cigarette smoking is common to both. (Robbins, Pathological Basis of Disease, 5th edition, pg 683)
  • Emphysema is a condition of the lung characterized by the abnormal permanent enlargement of the airspaces distal to the terminal bronchiole, accompanied by the destruction of their walls, and without obvious fibrosis. It is known that emphysema and other pulmonary diseases reduce the ability of one or both lungs to fully expel air during the exhalation phase of the breathing cycle. One of the effects of such diseases is that the diseased lung tissue is less elastic than healthy lung tissue, which is one factor that prevents full exhalation of air. During breathing, the diseased portion of the lung does not fully recoil due to the diseased (e.g., emphysematic) lung tissue being less elastic than healthy tissue. Consequently, the diseased lung tissue exerts a relatively low driving force, which results in the diseased lung expelling less air volume than a healthy lung. The reduced air volume exerts less force on the airway, which allows the airway to close before all air has been expelled, another factor that prevents full exhalation.
  • The problem is further compounded by the diseased, less elastic tissue that surrounds the very narrow airways that lead to the alveoli (the air sacs where oxygen-carbon dioxide exchange occurs). This tissue has less tone than healthy tissue and is typically unable to maintain the narrow airways open until the end of the exhalation cycle. This traps air in the lungs and exacerbates the already-inefficient breathing cycle. The trapped air causes the tissue to become hyper-expanded and no longer able to effect efficient oxygen-carbon dioxide exchange. One way of deflating the diseased portion of the lung is to applying suction to these narrow airways. However, such suction may undesirably collapse the airways, especially the more proximal airways, due to the surrounding diseased tissue, thereby preventing successful fluid removal.
  • In addition, hyper-expanded lung tissue occupies more of the pleural space than healthy lung tissue. In most cases, a portion of the lung is diseased while the remaining part is relatively healthy and therefore still able to efficiently carry out oxygen exchange. By taking up more of the pleural space, the hyper-expanded lung tissue reduces the amount of space available to accommodate the healthy, functioning lung tissue. As a result, the hyper-expanded lung tissue causes inefficient breathing due to its own reduced functionality and because it adversely affects the functionality of adjacent, healthier tissue.
  • Lung volume reduction surgery is a conventional method of treating lung diseases such as emphysema. According to the lung reduction procedure, a diseased portion of the lung is surgically removed, which makes more of the pleural space available to accommodate the functioning, healthier portions of the lung. The lung is typically accessed through a median sternotomy or lateral thoracotomy. A portion of the lung, typically the upper lobe of each lung, is freed from the chest wall and then resected, e.g., by a stapler lined with bovine pericardium to reinforce the lung tissue adjacent the cut line and also to prevent air or blood leakage. The chest is then closed and tubes are inserted to remove fluid from the pleural cavity. The conventional surgical approach is relatively traumatic and invasive, and, like most surgical procedures, is not a viable option for all patients.
  • Some recently proposed treatments include the use of devices that isolate a diseased region of the lung in order to reduce the volume of the diseased region, such as by collapsing the diseased lung region. According to such treatments, isolation devices are implanted in airways feeding the targeted region of the lung to isolate the region of the lung targeted for volume reduction or collapse. These implanted isolation devices can be, for example, one-way valves that allow flow in the exhalation direction only, occluders or plugs that prevent flow in either direction, or two-way valves that control flow in both directions. However, even with the implanted isolation devices properly deployed, air can flow into the isolated lung region via a collateral pathway. This can result in the diseased region of the lung still receiving air even though the isolation devices were implanted into the direct pathways to the lung. Collateral flow can be, for example, air flow that flows between segments of a lung, or it can be, for example, air flow that flows between lobes of a lung, as described in more detail below.
  • Collateral flow into an isolated lung region can make it difficult to achieve a desired flow dynamic for the lung region. Moreover, it has been shown that as the disease progresses, the collateral flow throughout the lung can increase, which makes it even more difficult to properly isolate a diseased lung region by simply implanting flow control valves in the bronchial passageways that directly feed air to the diseased lung region.
  • In view of the foregoing, there is a need for a method and device for regulating fluid flow to and from a region of a lung that is supplied air through a collateral pathway, such as to achieve a desired flow dynamic or to induce collapse in the lung region.
  • SUMMARY
  • Disclosed are methods and devices for regulating fluid flow to and from a lung region that is supplied air through one or more collateral pathways, such as to induce collapse in the lung region or to achieve a desired flow dynamic. In accordance with one aspect of the invention, there is disclosed a method of regulating fluid flow for a targeted lung region, comprising identifying at least one collateral pathway that provides collateral fluid flow into the targeted lung region and performing an intervention within the lung to reduce the amount of collateral fluid flow provided to the targeted lung region through the collateral pathway. The method can also include identifying at least one direct pathway that provides direct fluid flow into the targeted lung region and deploying a bronchial isolation device in the direct pathway to regulate fluid flow to the targeted lung region through the direct pathway.
  • Also disclosed is a method of regulating fluid flow for a targeted lung region, comprising reducing direct fluid flow in a direct pathway that provides direct fluid flow to the targeted lung region; and reducing collateral fluid flow that flows through a collateral pathway to the targeted lung region.
  • Also disclosed is a method of treating a patient's lung region, comprising deploying a catheter into a lung; and using the catheter to apply heat to a targeted lung region wherein the heat affects fluid flow within the targeted lung region.
  • Also disclosed is a method of diagnosing collateral ventilation between regions of a lung, comprising positioning a catheter transtracheally into a bronchial passageway that provides direct fluid flow into a target region of the lung; and detecting the presence of collateral fluid flow into or out of the target region of the lung based on the presence of the catheter in the bronchial passageway.
  • Also disclosed is a method of diagnosing collateral ventilation between regions of a lung, comprising modifying direct fluid flow into a target lung region; and detecting the presence of collateral fluid flow into the target lung region.
  • Also disclosed is a method of diagnosing collateral ventilation between regions of a lung, comprising measuring at least one parameter associated with a target lung region while a catheter is positioned in the target lung region; and calculating a level of collateral fluid flow into the target lung region based on the at least one parameter.
  • Also disclosed is a method of diagnosing collateral ventilation between regions of a lung, comprising: positioning a catheter transtracheally into a bronchial passageway that provides direct fluid flow into a target region of the lung; generating at least one measurement associated with the target region of the lung; and calculating a level of collateral fluid flow into the target lung region based on the at least one measurement.
  • Also disclosed is a method of treating the lung, comprising inserting a balloon catheter into a bronchial passageway that provides direct fluid flow to a first lung region; inflating a balloon on the balloon catheter to seal the catheter in the bronchial passageway; inserting a marker gas into the lung; measuring a lung parameter through the catheter based on the presence of the marker gas within the lung; detecting the presence of a collateral pathway to the first lung region based on the measured lung parameter; and treating the lung.
  • Also disclosed is a method of treating a lung, comprising: deploying a delivery catheter through a bronchial tree into a targeted lung region such that a distal end of the delivery catheter is positioned at or near the targeted lung region; delivering a fibrinogen suspension through the delivery catheter so that the fibrinogen suspension exits the distal end of the delivery catheter into the targeted lung region, wherein the fibrinogen suspension comprises fibrinogen and poly-L-lysine; delivering thrombin through the delivery catheter so that the thrombin exits the distal end of the delivery catheter into the targeted lung region; causing the fibrinogen suspension and the thrombin to mix; and promoting the lung to collapse. In an embodiment, the fibrinogen suspension is delivered prior to delivering the thrombin. In another embodiment, the thrombin is delivered prior to delivering the fibrinogen suspension. In another embodiment, the fibrinogen suspension and the thrombin are mixed prior to delivering the fibrinogen suspension and the thrombin through the delivery catheter.
  • Other features and advantages of the present invention should be apparent from the following description of various embodiments, which illustrate, by way of example, the principles of the invention.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • FIG. 1 illustrates an anterior view of a pair of human lungs and a bronchial tree.
  • FIG. 2 illustrates a lateral view of the right lung.
  • FIG. 3 illustrates a lateral view of the left lung.
  • FIG. 4 illustrates an anterior view of the trachea and a portion of the bronchial tree.
  • FIG. 5 illustrates an anterior view of a lung having a lung lobe that is receiving collateral air flow through a collateral pathway comprised of an incomplete interlobar fissure.
  • FIG. 6 illustrates an anterior view of a lung having a lung segment that is receiving collateral air flow.
  • FIG. 7 illustrates the delivery of a flowable therapeutic agent to a targeted lung region using a balloon-tipped delivery catheter.
  • FIG. 8 illustrates the delivery of a flowable therapeutic agent to a targeted lung region using a delivery catheter.
  • FIG. 9 illustrates the percutaneous injection of a flowable therapeutic agent to a targeted lung region.
  • FIG. 10 illustrates the injection of a flowable therapeutic agent into a targeted lung region through a catheter that has a sharpened tip.
  • FIG. 11 illustrates the deployment of a delivery catheter in a patient using a bronchoscope.
  • FIG. 12 illustrates a lateral view of the right lung, showing a targeted lung region and an adjacent healthy lung region.
  • FIG. 13 illustrates the injection of a therapeutic agent into a targeted lung region, controlled by applied pressure in an adjacent lung region.
  • FIG. 14 illustrates the treatment of collateral flow paths using a beta-emitting radiation source.
  • FIG. 15 illustrates the treatment of collateral flow paths using flow-limiting isolation devices.
  • FIG. 16 illustrates the percutaneous suction of a targeted lung region using a suction catheter.
  • FIG. 17 illustrates the sealing of collateral flow paths between the right upper lobe and the right middle lobe through the use of a two-part adhesive.
  • FIG. 18 illustrates the use of shunt tubes that are mounted in bronchial passageway to provide free air pathways to a targeted lung region.
  • FIG. 19 is a cross-sectional view of a flow control element that allows fluid flow in a first direction but blocks fluid flow in a second direction.
  • FIG. 20 shows a perspective view of another embodiment of a flow control element.
  • FIG. 21 shows a cross-sectional, perspective view of the flow control element of FIG. 21.
  • FIG. 22 shows a valve element.
  • FIG. 23 shows a side view of the valve element of FIG. 22.
  • FIG. 24 shows a cross-sectional view of the valve element of FIG. 22 along the line 24-24 of FIG. 23.
  • FIG. 25 shows an enlarged, sectional view of the portion of the flow control element contained within line 25 of FIG. 22.
  • DETAILED DESCRIPTION
  • Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which the invention(s) belong.
  • Disclosed are methods and devices for regulating fluid flow to and from a region of a patient's lung, such as to achieve a desired fluid flow dynamic to a lung region during respiration and/or to induce collapse in one or more lung regions that are supplied air through one or more collateral pathways. An identified region of the lung (referred to herein as the “targeted lung region”) is targeted for flow regulation, such as to achieve volume reduction or collapse. The targeted lung region is then bronchially isolated to regulate fluid flow to the targeted lung region through bronchial pathways that directly feed fluid to the targeted lung region. If a desired flow characteristic to the targeted region is not achieved, or if the targeted lung region does not collapse after bronchially isolating the targeted lung region, then it is possible that a collateral pathway is feeding air to the targeted lung region. The collateral flow can prevent the targeted lung region from collapsing. In such a case, the collateral pathway is identified and an intervention is performed within the lung to modify or inhibit fluid flow into the targeted lung region via the collateral pathway, such as according to the methods described herein. While the invention can involve such treatment of collateral flow pathways in combination with bronchial isolation, it should be understood that the invention may also be practiced without bronchial isolation in some circumstances. Further, the invention also encompasses temporary bronchial isolation while treating lung regions fed by collateral pathways.
  • Exemplary Lung Regions
  • Throughout this disclosure, reference is made to the term “lung region”. As used herein, the term “lung region” refers to a defined division or portion of a lung. For purposes of example, lung regions are described herein with reference to human lungs, wherein some exemplary lung regions include lung lobes and lung segments. Thus, the term “lung region” as used herein can refer, for example, to a lung lobe or a lung segment. Such nomenclature conform to nomenclature for portions of the lungs that are known to those skilled in the art. However, it should be appreciated that the term lung region does not necessarily refer to a lung lobe or a lung segment, but can refer to some other defined division or portion of a human or non-human lung.
  • FIG. 1 shows an anterior view of a pair of human lungs 110, 115 and a bronchial tree 120 that provides a fluid pathway into and out of the lungs 110, 115 from a trachea 125, as will be known to those skilled in the art. As used herein, the term “fluid” can refer to a gas, a liquid, or a combination of gas(es) and liquid(s). For clarity of illustration, FIG. 1 shows only a portion of the bronchial tree 120, which is described in more detail below with reference to FIG. 4.
  • Throughout this description, certain terms are used that refer to relative directions or locations along a path defined from an entryway into the patient's body (e.g., the mouth or nose) to the patient's lungs. The path of airflow into the lungs generally begins at the patient's mouth or nose, travels through the trachea into one or more bronchial passageways, and terminates at some point in the patient's lungs. For example, FIG. 1 shows a path 102 that travels through the trachea 125 and through a bronchial passageway into a location in the right lung 110. The term “proximal direction” refers to the direction along such a path 102 that points toward the patient's mouth or nose and away from the patient's lungs. In other words, the proximal direction is generally the same as the expiration direction when the patient breathes. The arrow 104 in FIG. 1 points in the proximal or expiratory direction. The term “distal direction” refers to the direction along such a path 102 that points toward the patient's lung and away from the mouth or nose. The distal direction is generally the same as the inhalation or inspiratory direction when the patient breathes. The arrow 106 in FIG. 1 points in the distal or inhalation direction.
  • The lungs include a right lung 110 and a left lung 115. The right lung 110 includes lung regions comprised of three lobes, including a right upper lobe 130, a right middle lobe 135, and a right lower lobe 140. The lobes 130, 135, 140 are separated by two interlobar fissures, including a right oblique fissure 126 and a right transverse fissure 128. The right oblique fissure 126 separates the right lower lobe 140 from the right upper lobe 130 and from the right middle lobe 135. The right transverse fissure 128 separates the right upper lobe 130 from the right middle lobe 135.
  • As shown in FIG. 1, the left lung 115 includes lung regions comprised of two lobes, including the left upper lobe 150 and the left lower lobe 155. An interlobar fissure comprised of a left oblique fissure 145 of the left lung 115 separates the left upper lobe 150 from the left lower lobe 155. The lobes 130, 135, 140, 150, 155 are directly supplied air via respective lobar bronchi, as described in detail below.
  • FIG. 2 is a lateral view of the right lung 110. The right lung 110 is subdivided into lung regions comprised of a plurality of bronchopulmonary segments. Each bronchopulmonary segment is directly supplied air by a corresponding segmental tertiary bronchus, as described below. The bronchopulmonary segments of the right lung 110 include a right apical segment 210, a right posterior segment 220, and a right anterior segment 230, all of which are disposed in the right upper lobe 130. The right lung bronchopulmonary segments further include a right lateral segment 240 and a right medial segment 250, which are disposed in the right middle lobe 135. The right lower lobe 140 includes bronchopulmonary segments comprised of a right superior segment 260, a right medial basal segment (which cannot be seen from the lateral view and is not shown in FIG. 2), a right anterior basal segment 280, a right lateral basal segment 290, and a right posterior basal segment 295.
  • FIG. 3 shows a lateral view of the left lung 115, which is subdivided into lung regions comprised of a plurality of bronchopulmonary segments. The bronchopulmonary segments include a left apical segment 310, a left posterior segment 320, a left anterior segment 330, a left superior segment 340, and a left inferior segment 350, which are disposed in the left lung upper lobe 150. The lower lobe 155 of the left lung 115 includes bronchopulmonary segments comprised of a left superior segment 360, a left medial basal segment (which cannot be seen from the lateral view and is not shown in FIG. 3), a left anterior basal segment 380, a left lateral basal segment 390, and a left posterior basal segment 395.
  • FIG. 4 shows an anterior view of the trachea 125 and a portion of the bronchial tree 120, which includes a network of bronchial passageways, as described below. In the context of describing the lung, the terms “pathway” and “lumen” are used interchangeably herein. The trachea 125 divides at a lower end into two bronchial passageways comprised of primary bronchi, including a right primary bronchus 410 that provides direct air flow to the right lung 110, and a left primary bronchus 415 that provides direct air flow to the left lung 115. Each primary bronchus 410, 415 divides into a next generation of bronchial passageways comprised of a plurality of lobar bronchi. The right primary bronchus 410 divides into a right upper lobar bronchus 417, a right middle lobar bronchus 420, and a right lower lobar bronchus 422. The left primary bronchus 415 divides into a left upper lobar bronchus 425 and a left lower lobar bronchus 430. Each lobar bronchus, 417, 420, 422, 425, 430 directly feeds fluid to a respective lung lobe, as indicated by the respective names of the lobar bronchi. The lobar bronchi each divide into yet another generation of bronchial passageways comprised of segmental bronchi, which provide air flow to the bronchopulmonary segments discussed above.
  • As is known to those skilled in the art, a bronchial passageway defines an internal lumen through which fluid can flow to and from a lung. The diameter of the internal lumen for a specific bronchial passageway can vary based on the bronchial passageway's location in the bronchial tree (such as whether the bronchial passageway is a lobar bronchus or a segmental bronchus) and can also vary from patient to patient. However, the internal diameter of a bronchial passageway is generally in the range of 3 millimeters (mm) to 10 mm, although the internal diameter of a bronchial passageway can be outside of this range. For example, a bronchial passageway can have an internal diameter of well below 1 mm at locations deep within the lung.
  • Direct and Collateral Flow
  • Throughout this disclosure, reference is made to a “direct pathway” to a targeted lung region and to a “collateral pathway” to a targeted lung region. The term “direct pathway” refers to a bronchial passageway that branches directly or indirectly from the trachea and either (1) terminates in the targeted lung region to thereby directly provide air to the targeted lung region; or (2) branches into at least one other bronchial passageway that terminates in the targeted lung region to thereby directly provide air to the targeted lung region. The term “collateral pathway” refers to any pathway that provides air to the targeted lung region and that is not a direct pathway. The term “direct’ is used to refer to air flow that flows into or out of a targeted lung region via a direct pathway. Likewise, the term “collateral” is used to refer to fluid flow (such as air flow) that flows into or out of a targeted lung region via a collateral pathway. Thus, for example, “direct” flow is fluid flow (such as air flow) that enters or exits the targeted lung region via a direct pathway, and “collateral” flow is fluid flow (such as air flow) that enters or exits the targeted lung region via a collateral pathway.
  • A collateral flow can be, for example, air flow that flows between segments of a lung, which is referred to as intralobar flow, or it can be, for example, air flow that flows between lobes of a lung, which is referred to as interlobar flow. One exemplary process of identifying a collateral pathway that provides collateral air flow into a targeted lung region is described below.
  • In accordance with one aspect of the disclosed methods, a targeted region of the lung is identified, wherein the targeted lung region can comprise, for example, a single one of the lung regions described above with reference to FIGS. 1-3, or the targeted lung region can comprise a collection of the regions described above. Alternately, the targeted lung region can be some other portion of the lung. The targeted lung region can be, for example, a diseased lung region for which it is desired to bronchially isolate the region for the purposes of inhibiting fluid flow into the region. As used herein, to “bronchially isolate” a lung region means to modify the flow to the targeted lung region, such as to regulate, prevent, or inhibit direct air flow to the lung region. In one embodiment, after the targeted lung region is identified, an attempt is made to bronchially isolate the targeted lung region, such as by occluding the bronchial pathway(s) that directly feed air to the targeted lung region. This may be accomplished, for example, by advancing and implanting a bronchial isolation device into the one or more bronchial pathways that directly feed air to the targeted lung region to thereby regulate direct flow into the lung region.
  • The bronchial isolation device can be, for example, a device that regulates the flow of air into a lung region through a bronchial passageway. Some exemplary bronchial isolation devices comprised of flow control elements are described in detail below with reference to FIG. 19-25. In addition, the following references describe exemplary flow control elements: U.S. Pat. No. 5,954,766 entitled “Body Fluid Flow Control Device; U.S. patent application Ser. No. 09/797,910, entitled “Methods and Devices for Use in Performing Pulmonary Procedures”; and U.S. patent application Ser. No. 10/270,792, entitled “Bronchial Flow Control Devices and Methods of Use”. The foregoing references are all incorporated herein by reference in their entirety and are all assigned to Emphasys Medical, Inc., the assignee of the instant application.
  • If the targeted lung region does not collapse, then it can be assumed that the targeted lung region is not collapsing because of collateral air flow into the lung. In such a case, it is desirable to modify collateral flow into the targeted lung region in order to encourage collapse or to achieve a desired flow dynamic for the lung region. For example, the collateral flow into the targeted lung region can be completely prevented so that there is no collateral flow into the targeted lung region. Alternately, the collateral flow into the targeted lung region can simply be reduced, such as to minimize the effect of the collateral flow on the targeted lung region.
  • Use of Flowable Therapeutic Agents to Reduce or Prevent Collateral Flow
  • One way of impeding collateral fluid flow into the targeted lung region is by injecting one or more flowable therapeutic agents into the targeted lung region in order to partially or completely seal the collateral pathway(s) that are providing collateral flow into the targeted lung region. The agent is “flowable” in that the agent is at least initially in a fluid state, which can be, for example, a liquid, gas, aerosol, etc. The agent is “therapeutic” in that, when the agent contacts lung tissue, the agent generates a reaction in the tissue of the targeted lung region that serves to reduce, inhibit, or prevent collateral fluid flow into the targeted lung region. The reaction can result in, for example (1) gluing or sealing portions of the targeted lung region together to thereby seal collateral pathways; (2) sclerosing or scarring target lung tissue to thereby occlude the collateral pathway(s) and seal off collateral flow into the targeted lung region; (3) promoting fibrosis in or around the targeted lung region to thereby seal off collateral flow into the region; (4) creating of an inflammatory response that would seal or fuse collateral pathway(s) that lead into the targeted lung region; (5) or creation of a bulking agent that fills space (such as space within the targeted lung region and/or the collateral pathway) and thereby partially or entirely seal off collateral flow into the targeted lung region.
  • A variety of flowable therapeutic agents have been identified that achieve one or more of the above reactions in lung tissue. The agents include, for example, the following:
  • (1) a foam created from either synthetic materials or natural biological materials that has one or more of the following-described properties. According to one property, the foam expands in volume from an initial injected volume to an expanded volume by a predetermined volume amount. For example, the foam may double in volume from an injected volume to expanded volume. Such volume expansion would cause the foam to fill-up and seal the volume of the targeted lung region or the volume of a collateral pathway. According to another property, the foam can be resorbable or degradable in the tissue of a patient's body, such that, when the foam is injected into the targeted lung region, the targeted lung region would absorb the foam and shrink in volume. For example, the foam could comprise a biodegradable polymer, such as polyethylene glycol (PEG) or polyglycolic acid (PGA). In another example, the foam could be a biodegradable polymer that is foamed with hydrogen or some other gas and that is permeable through the cellular structure of the foam.
  • When a foam as described above is injected into the targeted lung region, gas would begin to diffuse out of the foam matrix, which would cause cells within the foam to collapse. As the foam collapses, the adjacent tissue will be drawn to a smaller volume simultaneously due to adhesion between the foam and the surrounding tissue. In one embodiment, the foam has balanced properties of flow and viscosity in order to increase the likelihood that the foam will adequately fill the targeted lung region. Such balanced properties would also reduce the likelihood of the foam running or leaking into regions of the lung adjacent to the targeted lung region through the collateral pathway(s). The foam can retain a foamy consistency until it is absorbed into the lung tissue, or it can cure and harden and then dissolve over time.
  • (2) A sealant or glue, such as, for example, fibrin, fibrinogen and thrombin epoxy, various cyanoacrylate adhesives and sealants, such as n-butyl-2-cyanoacrylate, synthetic biocompatible sealants made from polyethylene polymers, etc.
  • (3) Sclerosing agents such as, for example, doxycycline, minocycline, tetracycline, bleomycin, cisplatin, doxorubicin, fluorouracil, interferon-beta, mitomycin-c, Corynebacterium parvum, methylprednisolone, and talc.
  • (4) Antibiotics such as, for example, doxycycline, minocycline or bleomycin, tetracycline, etc.
  • (5) Bulking agents such as, for example, collagen, gelatin, Gelfoam, or Surgicel solutions, polyvinyl acetate (PVA), ethylene vinyl alcohol copolymer (EVAL) or ethylene vinyl alcohol copolymer solutions. One example of an appropriate bulking material is the Onyx Liquid Embolic System manufactured by Micro Therapeutics, Irvine, Calif. This material is ethylene vinyl alcohol copolymer combined with micronized tantalum powder for fluoroscopy contrast dissolved in dimethyl sulfoxide (DMSO) solvent. It solidifies through precipitation upon contact with an aqueous solution, such as saline, and forms a spongy mass.
  • (6) Agents for inducing a localized infection and scar such as, for example, a weak strain of Pneumococcus.
  • (7) Other agents such as mucolytics (to reduce or eliminate mucus), steroids, factor XIIIa transglutaminase.
  • (8) Fibrosis promoting agents such as a polypeptide growth factor (fibroblast growth factor (FGF), basic fibroblast growth factor (bFGF), transforming growth factor-beta (TGF-β))
  • (9) Pro-apoptopic agents such as sphingomyelin, Bax, Bid, Bik, Bad, caspase-3, caspase-8, caspase-9, or annexin V.
  • (10) Components of the extracellular matrix (ECM) such as hyaluronic acid (HA), chondroitin sulfate (CS), fibronectin (Fn), or ECM-like substances such as poly-L-lysine or peptides consisting of praline and hydroxyproline.
  • Any well-known radiopaque contrast agent could be added to the therapeutic agent in order to facilitate viewing of the agent as it is dispersed in the targeted lung region. A sufficient quantity of agent is dispersed to seal collateral pathways, but not so much that adjacent tissue is affected. The flowable therapeutic agents that can be used to limit collateral flow into a targeted lung region are not limited to those described above.
  • Identification of Regions for Treatment
  • As discussed above, the targeted lung region can be an entire lobe of one of the lungs 110, 115, or the targeted lung region can be one or more lung segments, such as, for example, the lung segments described above with reference to FIGS. 2 and 3. In the case of the targeted lung region being a lung lobe, an attempt is made to bronchially isolate the target lobe by sealing the direct pathways(s) into the target lobe, such as by implanting a bronchial isolation device into the lobar bronchus that supplies air to the targeted lobe. If the targeted lobe still does not collapse, then it can be assumed that a collateral pathway is supplying air to the targeted lobe, wherein the collateral pathway is through an incomplete interlobar fissure. The outer surface of the lung is covered with a serous membrane called the visceral pleura. When the fissure between lobes is complete, the two adjacent lobes are separated and are completely covered with visceral pleura of all surfaces, and there is no collateral air flow possible between lobes. When the fissure is incomplete, the adjacent lobes are not completely separated, the visceral pleura does not completely surround the lobes, and parenchyma from the adjacent lobes in the incomplete portion of the fissure touch and are not separated. This incomplete formation of the fissure occurs naturally in about 50% of fissures in human lungs, and collateral air flow can occur between the lobes through these regions. See, Raasch B N, et al. Radiographic Anatomy of the Interlobar Fissure: A Study of 100 Specimens. AJR 1982; 138:1043-1049. When there is collateral airflow through an incomplete interlobar fissure thereby preventing collapse of the treated lobe, the lung can be treated to cause the fissure to seal (either partially or entirely) and thereby reduce or prevent collateral flow into the targeted lung lobe via the interlobar fissure.
  • FIG. 5 shows an example of a lung lobe that has been bronchially isolated using a bronchial isolation device comprised of a flow control element, which regulates fluid flow through a bronchial passageway that supplies fluid to the lobe. The lobe receives collateral air flow through a collateral pathway comprised of an incomplete interlobar fissure. As shown in FIG. 5, a bronchial isolation device 510, such a flow control element, is implanted in the right middle lobar bronchus 420 in order to prevent direct flow into the targeted lung region comprised of the right middle lobe 135. However, the right middle lobe 135 is still receiving collateral flow (as exhibited by a series of arrows 512 in FIG. 5) through a collateral pathway comprised of an incomplete right transverse fissure 128. The collateral flow comes from the right upper lobar bronchus 417 and passes into the right middle lobe 135 through the incomplete right transverse fissure 128. Thus, the right upper lobar bronchus 417 can also be considered to be a portion of the collateral pathway into the right middle lobe 135. The collateral flow into the right middle lobe 135 could be prevented or reduced by sealing the air pathways through the incomplete right transverse fissure 128 where the middle lobe 135 contacts the inferior surface of the right upper lobe 130.
  • In another exemplary scenario, the targeted lung region can be a specific lung segment or some other portion of the lung that is within a lobe. In this case, an attempt is made to bronchially isolate the targeted lung segment (or other portion of the lung), such as by inserting a flow control element into the direct pathway(s) to the targeted lung segment. If the targeted lung segment still does not collapse, it can be assumed that the flow is originating from other lung segments or other regions within the same lobe as the targeted segment, or from an incomplete interlobar fissure that is adjacent to the targeted lung segment. FIG. 6 shows an example of this scenario. As shown in FIG. 6, a targeted lung segment 610 is located within the right upper lobe 130. The targeted lung segment 610 can receive direct flow via segmental bronchus 615. The targeted lung segment 610 also receives collateral flow from an adjacent segment 620 that is also located within the right upper lobe 130.
  • In another example with reference to FIG. 6, a targeted lung segment 630 is located in the right upper lobe 130 adjacent to the right transverse fissure 128. The targeted lung segment 630 can receive collateral flow from an adjacent lung segment in the right upper lobe 130. The targeted lung segment 130 can also receive collateral flow from the right middle lobe 135 via an incomplete right transverse fissure 128, in which case a bronchial passageway of the right middle lobe 135 is the source of the collateral flow.
  • If collateral flow to a targeted lung segment is originating from other segments or regions within the same lobe as the targeted lung region, or is originating from a separate, adjacent lobe via an incomplete fissure, it might be necessary to determine the bronchial passageway that is supplying collateral flow to the targeted lung region. One method of determining the magnitude of collateral flow, using selective bronchial balloon catheterization combined with ventilation on a helium-based marker gas and a helium detector, is disclosed in the literature. See, Morrell N W, et al. Collateral Ventilation and Gas Exchange in Emphysema, Am J Respir Crit Care Med 1994; 150:635-41.
  • One technique of identifying the bronchial passageway(s) that feed the parenchyma that communicates through the incomplete interlobar fissure with the targeted lung portion is now described. According to this technique, the bronchial sub-branches, such as segmental bronchi, feeding parenchyma adjacent to the interlobar fissure of an isolated lobe are determined fluoroscopically utilizing a standard guide wire. The following example illustrates the technique as applied in the right upper lobe, although the same principles could be used in any of the human lung's five lobes or any segments within those lobes. Although the lung is 3-dimensional and the airways are not sequentially related to linear lung regions (e.g., the most inferior segmental bronchus may partially feed the mid-section of a lung lobe or may preferentially feed the anterior or posterior aspect of that lobe), the goal is to determine the lowest (most inferior) sub-branch of the target upper lobe, as this sub-branch provides airflow to the lung parenchyma that borders the fissure between the upper lobe and the middle and lower lobes.
  • In a first step of the technique, a bronchoscope is passed through the most inferior bronchus as seen from a bronchoscopic perspective. This is performed according to well-known methods using a standard bronchoscope. A guidewire is then passed through the working channel of the bronchoscope and visually fed into the subsequent, most inferior sub-branches to the visual limits of the bronchoscope. The guidewire is then advanced further with the aid of fluoroscopic visualization. For inferior/superior determination, the fluoroscope will generally be in an anterior-posterior orientation (90 degrees to the patient's chest). The position of the guidewire relative to fluoroscopic landmarks (e.g.: relative to a rib or to the diaphragm) is then noted. The aforementioned steps are repeated in multiple sub-branches until it can be determined which bronchial sub-branch feeds the most inferior lung tissue (and thus adjacent to the interlobar fissure), and this sub-branch is selected for treatment.
  • Utilizing a fully articulating C-arm (fluoroscope), these steps can be repeated in other views (e.g. the camera in a 90 degree lateral view for anterior/posterior position) to map the sub-branches in 3-dimensions. In this way, a physician can determine which bronchial sub-branch or branches feed the most inferior lung tissue, tissue that borders the right middle and right lower lobes. This technique could be applied to any lobe in the lung, and to either the inferior or superior surfaces.
  • Delivery of Flowable Therapeutic Agent to Targeted Lung Region
  • The flowable therapeutic agent can be delivered to the targeted lung region according to a variety of methods. Some exemplary methods of delivering a flowable therapeutic agent to the targeted lung region are described below. Regardless of the method used, the therapeutic agent can be delivered to the targeted lung region either before or after an attempt is made to bronchially isolate the targeted lung region using a bronchial isolation device, or without bronchial isolation.
  • FIG. 7 illustrates an example of a method wherein a flowable therapeutic agent 705 is delivered to a targeted lung region using a delivery catheter 710. The targeted lung region is located in the right middle lobe 135 of the right lung 110. The delivery catheter 710 can be a conventional delivery catheter of the type known to those of skill in the art. The delivery catheter 710 is deployed in a bronchial passageway, such as in the segmental bronchi 715, that leads to the targeted lung region. The delivery catheter 710 is deployed such that a distal end of the catheter 710 is positioned distal of a bronchial isolation device 510 that has also been deployed in the bronchial passageway 710. As mentioned, the bronchial isolation device 510 can be deployed either before or after deployment of the delivery catheter 710.
  • Once the delivery catheter 710 is deployed in the targeted lung region, the flowable therapeutic agent 705 can be delivered into the targeted lung region using the delivery catheter 710. This can be accomplished by passing the flowable therapeutic agent through an internal lumen in the delivery catheter so that the agent exits a hole in the distal end of the delivery catheter 710 into the targeted lung region. As shown in FIG. 7, the distal end of the delivery catheter 710 can be sealed within the targeted lung region by inflating a balloon 720 that is disposed near the distal end of the catheter according to well-known methods. In another embodiment, shown in FIG. 8, the bronchial isolation device 510 provides the sealing so that a balloon is not needed when delivering the flowable therapeutic agent 705 using the delivery catheter 710.
  • FIG. 9 illustrates another method of delivering the flowable therapeutic agent to the targeted lung region. According to the method shown in FIG. 9, a delivery device, such as a delivery catheter or a hypodermic needle 910, is used to percutaneously inject the flowable therapeutic agent 705 directly into the lung tissue of the targeted lung region. The hypodermic needle 910 is used to puncture the chest wall according to well-known methods so that a sharpened delivery tip 915 of the needle 910 locates within the targeted lung region. For example, the targeted lung region could comprise a portion of the right middle lobe 135 located near the fissure 128, as shown in FIG. 9. The hypodermic needle 910 is then used to puncture the chest wall and the needle 910 is positioned so that the delivery tip 915 locates within the right middle lobe 135. The flowable therapeutic agent 705 is then injected directly into the targeted lung region via the hypodermic needle 910 according to well-known methods.
  • FIG. 10 shows yet another method of delivering the flowable therapeutic agent to the targeted lung region. According to this method, a delivery catheter 710 has a distal tip 1005 that can be used to puncture the wall of a bronchial passageway 1010 at a location that is at or near the targeted lung region. The distal tip 1005 is configured to facilitate puncturing of the bronchial wall, as described more fully below. Once the distal tip 1005 has been used to puncture the bronchial wall, the distal tip of the delivery catheter 710 is passed through the bronchial wall and the flowable therapeutic agent can be injected into the targeted lung region through the delivery catheter 710. The method shown in FIG. 10 differs from the method described above with reference to FIGS. 7 and 8 in that the method shown in FIG. 10 actually punctures the bronchial wall so that the flowable therapeutic agent can be injected directly into the lung tissue. The method shown in FIGS. 7 and 8 does not include puncturing of the bronchial wall, and the flowable therapeutic agent is injected into the bronchial lumen leading to the targeted lung region rather than directly into the lung tissue.
  • The puncturing of the bronchial wall can be accomplished using any of a variety of methods and devices. According to one embodiment, the distal tip 1010 of the delivery catheter is configured to facilitate puncturing of the bronchial wall. For example, the distal tip 1005 can be sharpened to an appropriate sharpness that will facilitate puncturing of a bronchial wall. It has been determined that a delivery catheter with a diameter of up to 3 millimeters (mm) will be sufficient. Alternately, a hypodermic needle can be mounted on the distal tip 1005 to facilitate puncturing of the bronchial wall. In another configuration, a stiff guidewire is delivered to the targeted lung region via the inner lumen of a flexible bronchoscope. The guidewire is then used to puncture the bronchial wall. After puncturing, a delivery catheter is delivered over the stiff guidewire to the targeted lung region. In another configuration radio frequency (RF) energy is applied to a catheter that comprises an RF cutting tip, and the cutting tip is applied to the bronchial wall at a location at or near the targeted lung region, thereby causing the bronchial wall to puncture. A device approved for this purpose is the Exhale RF Probe, Broncus Technologies, Inc. Mountain View, Calif., FDA 510(k) #K011267. In yet another configuration, a flexible biopsy forceps is delivered through a working channel of the bronchoscope and used to cut a hole through the bronchial wall in a well-known manner.
  • The delivery catheter 710 can be deployed at the targeted lung region according to a variety of methods. For example, with reference to FIG. 11, the delivery catheter 710 can be deployed using a bronchoscope 1111, which in an exemplary embodiment has a steering mechanism 1115, a delivery shaft 1120, a working channel entry port 1125, and a visualization eyepiece 1130. The bronchoscope 1111 has been passed into a patient's trachea 125 and guided into the right primary bronchus 410 according to well-known methods. The delivery catheter 710 is then deployed into the working channel entry port 1125 and down a working channel (not shown) of the bronchoscope shaft 1120, and the distal end 1135 of the catheter 710 is guided to a desired location within the bronchial tree, such as to a lobar bronchi 417 located within the upper lobe 130 of the right lung 110. The steering mechanism 1115 can be used to deliver the shaft 1120 to a desired location.
  • Alternately, the delivery catheter 710 can have a central guidewire lumen and can be deployed using a guide wire that guides the catheter to the delivery site. The delivery catheter 710 could have a well-known steering function, which would allow the catheter 710 to be delivered with or without use of a guidewire.
  • In yet another method of delivering the flowable therapeutic agent, one or more nasal cannulae are deployed through a patient's nasal cavity, through the trachea, and to a desired location in the bronchial tree 120 at the targeted lung region. One or more bronchial isolation devices, such as a flow control element, can also be deployed to bronchially isolate the targeted lung region, with a distal end(s) of the cannula(e) being passed through the bronchial isolation device(s). Alternately, a catheter with multiple divided lumens or cannulae could be deployed. The cannula can be left in place for a desired amount of time and an infusion of one or more flowable therapeutic agents is deployed to the targeted lung region via the cannula. The flowable therapeutic agents could be continuously or intermittently administered at a desired flow rate until the desired level of therapeutic effect has been obtained. In another embodiment, the delivery catheter 710 can be used to bronchially isolate the targeted lung region without the use of, or in combination with the use of, a flow control element. In such a case, the distal end of the delivery catheter 710 is equipped with a balloon (such as the balloon 720 shown in FIG. 7), which is inflated to occlude or partially occlude the bronchial passageway that provides fluid flow to the targeted lung region. In this manner, fluid flow through the bronchial passageway can be reduced or eliminated.
  • Controlling Dispersion of the Therapeutic Agent in the Lung
  • In the course of delivering the therapeutic agent to the targeted lung region, it can be desirable to control the dispersion of the therapeutic agent in the lung so that the agent does not flow through any collateral pathways into areas of healthy lung tissue. It can also be desirable to move the therapeutic agent preferentially toward the collateral pathway(s) (rather than toward some other area of the lung) in order to increase the likelihood that sealing of collateral pathway(s) is successful.
  • One way of controlling the movement of the therapeutic agent within the lung is to provide pressure differentials in different regions of the lung, wherein the pressure differentials encourage the therapeutic agent to flow in a desired manner. For example, as shown in FIG. 12, a targeted lung region 1210 is located in the right lower lobe 140 of the right lung 110. A healthy lung region 1220 is located adjacent to the targeted lung region 1210. The pressure within the targeted lung region is P1 and the pressure within the adjacent lung region 1220 is P2. If P1 is greater than P2, then a therapeutic agent located in the targeted lung region 1210 will be inclined to flow toward the adjacent lung region 1220 due to the pressure differential. Likewise, if P2 is greater P1, then a therapeutic agent located in the targeted lung region 1210 will be inclined to flow away from the adjacent lung region 1220.
  • One way to accomplish such a pressure differential is to control the injection pressure that is used to inject the therapeutic agent into the targeted lung region, and to also control a back pressure in an adjacent lung region where collateral pathways to the targeted lung region originate. If the therapeutic agent is radiopaque, a physician can view the extent of the therapeutic agent dispersion while also varying the injection pressure and the back pressure to control the dispersion.
  • This is described in more detail with reference to FIG. 13, which shows a cross-sectional view of the right lung 110, wherein the targeted lung region comprises the right middle lobe 135, which is adjacent to a healthier lung region comprised of the right upper lobe 130. The incomplete right transverse fissure 128 provides a collateral pathway through which collateral flow originating in the right upper lobe 130 passes into the right middle lobe 135. A first delivery catheter 710, which can have a balloon 720, is passed through a bronchial isolation device 510 so that the distal end of the catheter 710 is disposed in the targeted lung region. A second catheter 1305 is deployed in a bronchial passageway that provides flow to a lung region adjacent to the target region, wherein some collateral flow originates at the adjacent lung region. For example, FIG. 13 shows the second catheter 1305 deployed through the right lobar bronchus 417, which provides flow to the right upper lobe 130 where the collateral flow into the right middle lobe originates. The second catheter can have a balloon 1310 that is inflated.
  • The delivery catheter 710 is then used to inject the flowable therapeutic agent 705 into the targeted lung region at a desired injection pressure. This will cause the targeted lung region to achieve a pressure P1. While the therapeutic agent is being injected, a suction can be applied to the distal end of the second catheter 1305 to thereby achieve a pressure P2 in the adjacent lung region comprised of the right upper lobe 130. By controlling the injection pressure and suction, a desired pressure differential between P1 and P2 can be achieved to thereby control the dispersion of the therapeutic agent. The pressure differential can be manipulated to encourage the therapeutic agent to flow toward the collateral pathway and even enter the collateral pathway. As discussed, the dispersion can be visually monitored if the therapeutic agent includes a radiopaque.
  • When the desired dispersion level has been achieved, such as when the therapeutic agent has filled the targeted lung region or has filled the collateral pathways, it might then be desirable to further control the dispersion to reduce the likelihood that the therapeutic agent will flow into the healthy lung region. This can be accomplished by again varying the pressure differential so that the therapeutic agent no longer flows towards the healthy lung region. For example, the injection pressure can be reduced or eliminated, while also changing the suction pressure at the second catheter 1305. Suction can then be applied to the delivery catheter 710 to remove any excess therapeutic agent from the targeted lung region. The catheters 710, 1305 are then removed. In this manner, the therapeutic agent is preferentially moved toward the collateral pathway(s).
  • The aforementioned technique for sealing the collateral flow pathway could also be performed prior to the implantation of the bronchial isolation device(s) 510.
  • Follow-On Therapy After Treatment with Flowable Therapeutic Agent
  • After the infusion of the flowable therapeutic agents into the targeted lung region, a follow-on therapy procedure can be followed. According to one procedure, the treated portion of the lung (the portion of the lung to which the therapeutic agent was applied) is left alone, with the therapeutic agent in place. The treated lung portion is allowed to collapse by either absorption of the therapeutic agent by the body, absorption of the trapped gas in the isolated lung region, exhalation of trapped gas out through a flow control device (such as an implanted one-way or two-way valve device) or any combination of these events.
  • According to another follow-on therapy procedure, the therapeutic agent is removed from the lung following the passage of a predetermined treatment period. The therapeutic agent could be removed after a short period of time such as one or two minutes, or a longer period of 30 or 60 minutes. Alternatively, if required, the therapeutic agent could be removed in a separate procedure hours or days later. The necessary time period would depend on the particular therapeutic agent used. This could be done with the implanted bronchial isolation devices in place, or could be done before implantation of the bronchial isolation devices if the therapeutic agent was deployed prior to implantation of the bronchial isolation devices. The therapeutic agent can be removed from the lung in any number of ways, which include the following:
  • (a) Inflating a balloon catheter in the bronchial passageway leading to the targeted lung region and aspirating through the catheter central lumen. If bronchial isolation devices had been implanted already, the suction in the catheter would pull the excess therapeutic agent through the one-way or two-way valves of the isolation devices. This method is likely not used where the implanted devices are plugs or occluders.
  • (b) Crossing the implanted one-way or two-way valves with a catheter and applying suction through the central lumen of the catheter. The catheter could either be sealed by the valve in the implanted device, or it could be a balloon catheter where the balloon is inflated in the bronchial passageway distal to the implanted device.
  • (c) Percutaneously suctioning the therapeutic agent directly out of the lung tissue, such as by using a hypodermic needle.
  • (d) Suctioning the therapeutic agent out of the targeted lung region through the a hole created in the bronchial wall. This can be done using a new catheter or using the same catheter as was used to inject the agent.
  • Thus, there have been disclosed several basic approaches to injecting a flowable therapeutic agent for preventing or reducing collateral flow into a targeted lung region. Some examples of the basic approaches are summarized as follows:
  • (a) Implant one or more bronchial isolation devices to isolate targeted lung region; inject a flowable therapeutic agent into the targeted lung region distal to the bronchial isolation devices; allow the lung region to collapse, such as, for example, by absorption of the therapeutic agent by the body, absorption of the trapped gas in the isolated lung portion, exhalation of trapped gas out through the implanted one-way or two-way valve devices, or any combination of these events.
  • (b) Implant one or more bronchial isolation devices; inject a flowable therapeutic agent into the targeted lung region distal to devices; wait a pre-determined treatment time period; remove the therapeutic agent, such as, for example, by using suction, needle aspiration, etc.; and allow the lung region to collapse, such as, for example, by absorption of the trapped gas in the isolated lung portion, exhalation of trapped gas out through the implanted one-way or two-way valve devices, or both.
  • (c) Inject a flowable therapeutic agent into the targeted lung region; implant bronchial isolation devices; allow the targeted lung region to collapse, such as, for example, by absorption of the therapeutic agent by the body, absorption of the trapped gas in the isolated lung portion, exhalation of trapped gas out through the implanted one-way or two-way valve devices, or any combination of these events.
  • (d) Inject a flowable a therapeutic agent into parenchyma of the targeted lung region; implant one or more bronchial isolation devices; wait a pre-determined treatment time period; remove the therapeutic agent, such as, for example, using suction, needle aspiration, etc.; and allow lung region to collapse, such as, for example, by absorption of the trapped gas in the isolated lung portion, exhalation of trapped gas out through the implanted one-way or two-way valve devices, or both.
  • (e) Inject a flowable therapeutic agent into the targeted lung region; wait a pre-determined treatment time period; remove therapeutic agent; implant bronchial isolation devices; and allow the lung region to collapse.
  • (f) Temporarily isolate the targeted lung region; inject a flowable therapeutic agent into the targeted lung region; wait a pre-determined treatment time period; and remove therapeutic agent.
  • (g) Temporarily isolate the targeted lung region; and inject a flowable therapeutic agent into the targeted lung region.
  • Application of Energy to Reduce or Prevent Collateral Flow
  • An alternate way of reducing or preventing collateral fluid flow into the targeted lung region is to apply energy to the targeted lung region, wherein the application of energy generates a reaction in the tissue of the targeted lung region that serves to reduce or prevent collateral fluid flow into the targeted lung region. The reaction can result in, for example: (1) gluing or sealing portions of the lung together to thereby partially or entirely seal collateral pathways; (2) sclerosing or scarring target lung tissue to thereby partially or entirely occlude the collateral pathway(s) and partially or entirely seal off collateral flow into the targeted lung region; (3) promoting fibrosis in or around the targeted lung region to thereby partially or entirely seal off collateral flow into the region; (4) creating of an inflammatory response that would partially or entirely seal or fuse collateral pathway(s) that lead into the targeted lung region. A variety of energy sources have been identified that can be used to apply energy to lung tissue to achieve any of the aforementioned reactions. The types of energy include Beta-emitting radiation, radio frequency energy, heat, ultrasound, cryo-ablation, laser energy, and electrical energy. The process of identifying the lung region for treatment can be the same as that described above with reference to the use of the flowable therapeutic agent.
  • A variety of different methods can be used to deliver energy to a desired location in the targeted lung region. Regardless of the method used, the therapeutic agent can be delivered to the targeted lung region either without bronchial isolation, or before or after an attempt is made to bronchially isolate the targeted lung region using a bronchial isolation device.
  • FIG. 14 illustrates a method wherein an energy source is delivered to a targeted lung region using a delivery catheter 710. The targeted lung region is located in the right middle lobe 135 of the right lung 110. The delivery catheter 710 can be a conventional delivery catheter of the type known to those of skill in the art. The delivery catheter 710 is deployed in a bronchial passageway, such as in the sub-segmental bronchi 715, that leads to the targeted lung region. A distal end of the catheter 710 is inserted into the bronchial passageway and is positioned distal of a bronchial isolation device 510 that has been deployed in a bronchial passageway that provides direct flow to the targeted lung region. As discussed above, the bronchial isolation device 510 can be deployed either before or after deployment of the delivery catheter 710.
  • Once the delivery catheter 710 is deployed in the targeted lung region, an energy source 1410 can be delivered into the targeted lung region using the delivery catheter 710. This can be accomplished, for example, by passing a push wire 1415 having a distally-mounted energy source 1410 through an internal lumen in the delivery catheter 710 so that the energy source 1410 exits a hole in the distal end of the delivery catheter 710 into the targeted lung region. Alternately, the energy source 1410 can be mounted on the distal end of the delivery catheter 710. The distal end of the delivery catheter 710 can be sealed within the targeted lung region by inflating a balloon that is disposed near the distal end of the catheter according to well-known methods. Alternately, the bronchial isolation device 510 can provide the sealing so that a balloon is not needed.
  • According to another method of delivering the energy, a delivery device, such as delivery catheter or a hypodermic needle, is used to percutaneously reach the targeted lung region by puncturing the chest wall and outer surface of the lung. The energy source is then advanced directly into the lung tissue. This would be similar to the method shown in FIG. 9, although an energy source would be used in place of the flowable therapeutic agent.
  • In yet another method of delivering the energy to the targeted lung region, a delivery catheter has a distal tip that can be used to puncture the wall of a bronchial passageway that is located at or near the targeted lung region. The distal tip is configured to facilitate puncturing of the bronchial wall. Once the distal tip has been used to puncture the bronchial wall, the energy source is advanced into the targeted lung region through the delivery catheter. This would be similar to the process shown in FIG. 10. The puncturing of the bronchial wall can be accomplished using any of a variety of methods and devices, such as was described above with reference to FIG. 10.
  • The delivery catheter for delivering the energy source to the targeted lung region could be deployed in the same manner described above with reference to the flowable therapeutic agents, such as by using a bronchoscope.
  • Exemplary Method for Applying Energy to Targeted Lung Region
  • The delivery of beta-emitting radiation could be accomplished with a brachytherapy delivery system that includes a beta-emitting radiation source mounted to the end of a delivery catheter, such as was described above. As mentioned previously, this could be done either before or after the implantation of bronchial isolation devices.
  • According to one method of applying the energy, a beta radiation-emitting source is passed through one or more target bronchial passageways, either sequentially or concurrently, that lead to the targeted lung region. The source can also be passed through one or more of the bronchial isolation devices that were previously implanted. The radiation source is left in place for a period of time so as to elicit a scarring/healing response in the treated lung tissue. For example, it may be discovered through animal and/or human clinical trials that an exposure time period of 30 minutes to one hour will achieve satisfactory results. A maximum time may be identified wherein the risk of radiation to the surrounding tissue is greater than the benefits of scarring the target tissue. For example, it may be discovered that the radiation source can remain in up to an hour, but that exposure for greater than 90 minutes increases risk to the patient.
  • In another application method, the application procedure is performed over a predetermined time period and/or over bronchial sub-branches. For example, a patient can first be admitted for a procedure to deploy bronchial isolation devices, such as flow limiting valves, and then discharged with periodic reassessment of anatomical or clinical results. The physician and patient could decide when the next step of transvalvular brachytherapy should take place (e.g.: 15-30 days after the primary procedure). Brachytherapy could also be staged over time in such a way as to minimize risk while continually assessing benefit (e.g.: valves placed day one, first brachytherapy procedure of 30 minutes exposure day 30, second brachytherapy procedure of 30 minutes at day 60, etc.). The first brachytherapy session could be targeted at the RUL, inferior sub-segment of the anterior, segmental bronchus; the second session would target the RUL superior sub-segment of the anterior, segmental bronchus; etc.
  • The same procedures described above for beta-emitting radiation could be followed for other radiation sources such as RF energy, heat, ultrasound, or cryo-ablation. These energy sources might require different treatment times, a different number of treatment sites, etc., but the general application method would be the same.
  • Use of Flow-Limiting Isolation Devices to Limit Collateral Flow
  • Another way of impeding collateral fluid flow into the targeted lung region is now described, wherein flow-limiting devices are implanted in the bronchial passageway leading to lung regions adjacent to the target region, wherein the adjacent lung region that is not targeted for collapse.
  • As with the previously described methods, the lung region targeted for isolation and collapse is identified, and bronchial isolation devices are implanted in all airways that provide direct flow to the targeted lung region. The implanted isolation devices can be, for example, one-way valves that allow flow in the exhalation direction only, one-way valves that allow flow in the inhalation direction only, occluders or plugs that prevent flow in either direction, or two-way valves that control flow in both directions according to well-known methods. If the lung region does not collapse, such as due to either absorption atelectasis, or through exhalation of trapped gas through the implanted devices, then the lung region is likely being kept inflated through collateral in-flow through collateral pathways from adjacent lung regions. If the collateral flow from the adjacent lung regions could be reduced substantially or eliminated, the targeted lung region will likely collapse.
  • One way to reduce or substantially eliminate the collateral flow from adjacent lung regions is to implant inhalation flow limiting two-way valve devices in the bronchial passageways leading to adjacent lung regions not targeted for collapse, wherein the adjacent lung regions act as a source for collateral flow into the targeted lung region. Such devices would allow free fluid flow in the exhalation direction for the adjacent lung regions, but would limit the flow to a predetermined level in the inhalation direction. As a result, flow into the adjacent lung region would be limited, thereby limiting the flow of gas into the targeted lung region through the collateral pathways from the adjacent lung regions. The flow limitation is desirably sufficient to allow the isolated lung region to collapse, but would not collapse the adjacent lung regions. Once sufficient time had passed to allow the targeted lung region to become chronically atelectatic, the flow limiting two-way valve devices could be removed from the adjacent lung regions in order to restore normal ventilation to the lung portion not targeted for collapse.
  • An example of this method is shown in FIG. 15, which shows a targeted lung region comprised of the right upper lobe 130 that is isolated by one-way bronchial isolation devices 510 that are implanted in all bronchial passageways leading to the lobe 130. The devices 510 are one-way valve devices that stop all flow in the inhalation direction to thereby prevent direct flow into the lobe 130. A flow limiting two-way valve bronchial isolation device 1510 is implanted in the bronchial passageway in the right middle lobe 135 in the segment that lies just below the interlobar fissure 128 adjacent to the lobe 130. The device 1510 allows free flow in the exhalation direction and a limited flow in the inhalation direction. This limits the flow into the middle lobe 135, in a manner determined by the back flow restriction of the two-way valve. By limiting the flow into the middle lobe 135, the collateral flow into the targeted upper lobe 130 that originates in the middle lobe 130 is also limited. The flow limitation into the middle lobe 135 is sufficient to allow the right upper lobe 130 to collapse, as the collateral flow into the upper lobe 135 via the fissure 128 is insufficient to inflate the upper lobe 130.
  • One exemplary embodiment of a flow limiting two-way valve 2500 is shown in FIGS. 22-25. In this embodiment, the valve would behave as a one-way valve in the forward or exhalation direction in that it would allow free flow of fluid through the valve. However, the valve would also allow a controlled rate of flow in the reverse or inhalation direction. This could be achieved in a duckbill style valve by adding a small flow channel 2510 through the lips 2512 of the valve, as shown in FIG. 25. The reverse flow channel shown would allow fluid to flow in the inhalation direction, and the rate of flow would be controlled by diameter and length of the flow channel.
  • Use of Percutaneous Suction to Limit Collateral Flow
  • Another method for limiting collateral flow into a targeted lung region is through the use of percutaneous suction. As discussed, bronchial isolation devices may be implanted in any bronchial passageways that provide direct flow to the targeted lung region. Percutaneous suction is then applied to the targeted lung region for a time period sufficient to adhere or fuse the lung tissue in the targeted lung region in a collapsed state such that the targeted lung region will not re-inflate through collateral pathways after the suction is stopped.
  • The percutaneous suction method is described in more detail with reference to FIG. 16, which shows the targeted lung region being located in the right upper lobe 130. An attempt is made to bronchially isolate the targeted lung region by implanting one or more bronchial isolation devices 705 in bronchial passageway that provide direct flow into the targeted lung region. A suction catheter 1610 is percutaneously inserted into the targeted lung region, such as by inserting the catheter 705 through the rib space in a well-known manner. The suction catheter 1610 includes an internal lumen and has a distal end 1615 on which are located one or more suction holes 1620 that communicate with the internal lumen. A suction force can be applied to a proximal end 1625 of the catheter 1610 to suck fluid into the internal lumen through the suction holes 1620 on the distal end 1615 of the catheter 1610. A fixation balloon 1630 is mounted on the catheter 1610 a short distance from the distal end 1615 of the catheter 1610. In one embodiment, the fixation balloon 1630 is mounted approximately 2 centimeters from the distal end 1615. An exemplary suction catheter that can be used is the 8-French Venography Catheter, manufactured by The Cook Group, Inc., Bloomington, Ind.
  • As shown in FIG. 16, the suction catheter 1610 is percutaneously inserted into the targeted lung region so that the suction holes 1620 in the distal end 1615 are positioned within the targeted lung region. The fixation balloon 1630 is positioned in the pleural space of the lung and is then inflated to thereby fix the suction catheter 1610 in a fixed position and to also seal the incision that was used to percutaneously insert the catheter 1610. The suction catheter 1610 can be maneuvered into the correct location using guidance assistance, such as computer tomography (CT) or fluoroscopic guidance.
  • After the suction catheter 1610 has been properly positioned, a suction force can be applied to the internal lumen of the catheter to thereby cause a sucking force that draws fluid into the internal lumen through the suction holes 1620. The suction force will draw air or other fluid in the targeted lung region into the internal lumen through the suction holes 1620, which will aspirate the targeted lung region into a collapsed state. It has been determined that a suction force of approximately 100-160 mmHg is sufficient to aspirate the targeted lung region into a collapsed state. The suction force can be continuously maintained for a time period sufficient to permanently collapse the lung and reduce the likelihood of inflation through collateral pathways. In one embodiment, the suction is continuously maintained for a minimum time period of eight hours. In another embodiment, the suction is maintained for a time period of one to eight days. The suction can be performed while the patient is on bed rest, using a stationary vacuum source, or it could be performed using a portable vacuum source in order to permit the patient to ambulate.
  • After the suction time period has elapsed, a flowable therapeutic agent (such as any of the agents described above) can optionally be infused into the targeted lung region. This could be performed using the suction catheter 1610, such as by infusing the agent through a separate internal lumen located in the catheter 1610 or through the same lumen that was used for suction. The therapeutic agent could be used to increase the likelihood that the targeted lung region is properly sealed. The fixation balloon 1630 is then deflated and the suction catheter 1610 is removed.
  • Use of Two-Part Adhesive to Limit Collateral Flow
  • According to another method of inhibiting collateral flow into a targeted lung region, a two-part adhesive or glue is used to occlude a collateral pathway to the targeted lung region. The adhesive can comprise a two-part mixture that includes a first part and a second part, wherein the first part and the second part collectively solidify when brought into contact with each other. The two parts do not necessarily require complete mixing in order for the solidification to occur. The solidification can be triggered, for example, by a catalytic reaction that occurs when the two parts contact one another. In one embodiment, the two-part glue is a fibrin glue and the two parts of the glue are thrombin and fibrinogen.
  • A method for deploying a two-part adhesive in order to seal a collateral pathway is now described. The collateral pathway is located in a lung region between two or more bronchial passageway, such as a first bronchial passageway and a second bronchial passageway. For example, as shown in FIG. 17, the collateral pathway can be an incomplete interlobar 128 fissure that is located between a first bronchial passageway 1710 and a second bronchial passageway 1715. The bronchial passageway are not necessarily in the same lobe. For example, in FIG. 17 the bronchial passageway 1710 is in the right upper lobe 130 and the bronchial passageway 1715 is in the right middle lobe 135, where the targeted lung region is also located.
  • According to the method, the first part of the two-part adhesive is injected into the first bronchial passageway and the second part of the two-part adhesive is injected into the second bronchial passageway. The injection pressure and flow rates of the first and second parts can be controlled to encourage the first and second parts to flow to a common location, wherein the common location coincides with the location of the collateral flow path. That is, the first and second parts will contact one another within the collateral flow path. As mentioned, the first and second parts solidify when they contact one another. In this manner, the first and second parts solidify within the collateral flow path and thereby partially or entirely seal the collateral flow path.
  • An example of this is shown in FIG. 17, which shows a balloon-tipped catheter 1712 that has been deployed in the second bronchial passageway 1715, which supplies direct flow to the targeted lung region. A bronchial isolation device 510 is deployed in a segmental bronchus 1735 that is proximal to the second bronchial passageway 1715 in order to bronchially isolate the targeted lung region. The catheter 1712 is sealed within the bronchial passageway 1715 by inflating a balloon 1720 mounted on the catheter 1712. A second balloon-tipped catheter 1725 is deployed in the first bronchial passageway 1710 and sealed by inflating a balloon 1730. The first part 1728 of the two-part adhesive is then injected into the bronchial passageway 1715 via the catheter 1712 and the second part 1732 of the two-part adhesive is injected into the bronchial passageway 1710 via the catheter 1725. The first and second parts are injected in such a manner that they flow into the lung and meet at the collateral pathway comprised of the incomplete interlobar fissure 128. As a result of the contact between the first and second parts, they solidify within the interlobar fissure and thereby partially or entirely seal the interlobar fissure.
  • Once the adhesive has solidified, any remaining quantity of the first and second parts can be suctioned out of the lung. Alternately, the first and second parts could be absorbable by the body so that excess material need not be removed. The aforementioned technique for sealing the collateral flow pathway could also be performed prior to the implantation of the bronchial isolation device(s) 510.
  • Implanted Shunt Tubes
  • One of the major challenges with emphysematic patients is that certain bronchial passageways collapse during exhalation, thus leading to reduced flow through these lumens. This often results in trapped gas in certain regions of the lung that exhale air through the collapsed lumen. This in turn can lead to hyperinflation of the lung region, as well as compression of the healthy lung tissue that is adjacent to the lung region. One way of treating the hyperinflated lung region is to implant bronchial isolation devices, such as one-way or two-way valves, in the bronchial passageway that lead to the lung region in order to promote lung region collapse. However, the effectiveness of the bronchial isolation devices can be limited due to the reduced air flow during exhalation through the native bronchial passageways, especially if collateral flow is present.
  • One method of counteracting this effect is to implant one or more shunt tubes that are inserted through the bronchial passageways and into the targeted lung region comprised of a damaged lung region. The shunt tubes provide a clear flow path for exhaled air that is not be occluded by the collapsed bronchial passageway. In order to collapse the targeted lung region, one-way valves may be either mounted to a proximal end of the shunt tubes, or implanted in the bronchial passageways at some distance proximal to the proximal end of the tubes. These valves allow exhaled air to escape in the exhalation direction through the valve or valves, but do not allow inhaled air to return to the isolated targeted lung region. In this way, the targeted lung region eventually collapses after sufficient air had been exhaled. Alternatively, a self expanding braided tube can be used to prop the collapsed airway open. This allows side branches to continue to exhale air into the braided tube while keeping the bronchi open.
  • FIG. 18 shows an example of how shunt tubes can be utilized. A bronchial isolation device 510 is implanted in a bronchial passageway of the right upper lobe 130. Two implanted shunt tubes 1810 and 1820 are shown deployed in two lumens. The shunt tubes 1810, 1820 are located distal to the implanted isolation device 510. The shunt tubes 1810, 1820 keep the airways open and provide a flow path through which exhaled air can pass. The implanted shunt tubes 1810 and 1820 are shown in FIG. 18 as being implanted just distally to the implanted bronchial isolation device 510. Alternatively, the shunt tubes may be implanted more distally, and a greater quantity may be implanted. The shunt tubes may be anchored in the bronchial lumen in a number of ways. In a first embodiment, the shunt tube have spring resilience and expand when released from a smaller constrained diameter to a larger diameter, thus gripping the bronchial lumen wall. Alternately, the shunt tubes may comprise a deformable retainer that is expanded to grip the bronchial lumen wall by inflating a balloon placed inside the collapsed shunt tube. The shunt tubes may also comprise a cylindrical structure that increases in diameter when its temperature is raised to body temperature. The shunt tubes may also have barbs, prongs or other features on the outside that assist in gripping the bronchial lumen wall for retention.
  • Exemplary Bronchial Isolation Devices
  • As discussed above, a target lung region can be bronchially isolated by advancing a bronchial isolation device into the one or more bronchial pathways that directly feed air to the targeted lung region. The bronchial isolation device can be a device that regulates the flow of fluid into or out of a lung region through a bronchial passageway. FIG. 19 shows a cross-sectional view of an exemplary bronchial isolation device comprised of a flow control element 1910. It should be appreciated that the flow control element 1910 is merely an exemplary bronchial isolation device and that other types of bronchial isolation devices for regulating air flow can also be used. For example, the following references describe exemplary bronchial isolation devices: U.S. Pat. No. 5,954,766 entitled “Body Fluid Flow Control Device; U.S. patent application Ser. No. 09/797,910, entitled “Methods and Devices for Use in Performing Pulmonary Procedures”; and U.S. patent application Ser. No. 10/270,792, entitled “Bronchial Flow Control Devices and Methods of Use”. The foregoing references are all incorporated by reference in their entirety and are all assigned to Emphasys Medical, Inc., the assignee of the instant application.
  • With reference to FIG. 19, the flow control element 1910 is in the form of a valve with a valve member 1915 supported by a ring 1920. The valve member 1915 is a duckbill-type valve and has two flaps defining an opening 1925. The valve member 1915 is shown in a flow-preventing orientation in FIG. 19 with the opening 1925 closed. The valve member 1915 is configured to allow free fluid flow in a first direction (along arrow A) while controlling fluid flow in a second direction (along arrow B). In the illustrated embodiment, fluid flow in the direction of arrow B is controlled by being completely blocked by valve member 1915. The first and second directions in which fluid flow is allowed and controlled, respectively, can be opposite or substantially opposite each other, such as is shown in FIG. 19. The valve member 1915 functions as a one-way valve by completely blocking fluid flow in a certain direction. It should be appreciated that the flow control element could be configured to block or regulate flow along two-directions.
  • FIGS. 20 and 21 show another embodiment of an exemplary flow control element, comprising flow control element 2000. The flow control element 2000 includes a main body that defines an interior lumen 2010 through which fluid can flow along a flow path. The flow of fluid through the interior lumen 2010 is controlled by a valve member 2012. The valve member 2012 in FIGS. 20-21 is a one-way valve, although two-way valves can also be used, depending on the type of flow regulation desired. FIGS. 22-25 show an exemplary two-way valve member 2500.
  • With reference again to FIGS. 20-21, the flow control element 2010 has a general outer shape and contour that permits the flow control device 2010 to fit entirely within a body passageway, such as within a bronchial passageway. The flow control member 2000 includes an outer seal member 2015 that provides a seal with the internal walls of a body passageway when the flow control device is implanted into the body passageway. The seal member 2015 includes a series of radially-extending, circular flanges 2020 that surround the outer circumference of the flow control device 2000. The flow control device 2000 also includes an anchor member 2018 that functions to anchor the flow control device 2000 within a body passageway. It should be appreciated that other types of flow control devices can also be used to bronchially isolate the targeted lung region.
  • The flow control element can be implanted in the bronchial passageway using a delivery catheter. According to this process, the flow control element is mounted on a distal end of the delivery catheter. The distal end of the delivery catheter is then deployed to the bronchial passageway, such as by inserting the delivery catheter through the patient's mouth or nose, through the trachea, and through the bronchial tree to the desired location in the bronchial passageway. The delivery catheter can be deployed, for example, using a guide wire or without a guide wire. In one embodiment, a bronchoscope is deployed to the location in the bronchial passageway where the flow control device will be deployed. The delivery catheter with the flow control element is then deployed to the bronchial passageway by inserting the delivery catheter through a working channel of the bronchoscope such that the distal end of the delivery catheter and the attached flow control element protrude from the distal end of the working channel into the bronchial passageway. The flow control element is then removed from the delivery catheter so that the flow control elements is positioned within and retained in the bronchial passageway. U.S. patent application Ser. No. 10/270,792, entitled “Bronchial Flow Control Devices and Methods of Use” (which is assigned to Emphasys Medical, Inc., the assignee of the instant application) describes various methods and devices for implanting a flow control element into a bronchial passageway.
  • Although embodiments of various methods and devices are described herein in detail with reference to certain versions, it should be appreciated that other versions, embodiments, methods of use, and combinations thereof are also possible. Therefore the spirit and scope of the appended claims should not be limited to the description of the embodiments contained herein.

Claims (10)

1. A method of treating a lung, comprising:
deploying a delivery catheter through a bronchial tree into a targeted lung region such that a distal end of the delivery catheter is positioned at or near the targeted lung region;
delivering a fibrinogen suspension through the delivery catheter so that the fibrinogen suspension exits the distal end of the delivery catheter into the targeted lung region, wherein the fibrinogen suspension comprises fibrinogen and poly-L-lysine;
delivering thrombin through the delivery catheter so that the thrombin exits the distal end of the delivery catheter into the targeted lung region;
causing the fibrinogen suspension and the thrombin to mix; and
promoting the lung to collapse.
2. A method as in claim 1, wherein the fibrinogen suspension is delivered prior to delivering the thrombin.
3. A method as in claim 1, wherein the thrombin is delivered prior to delivering the fibrinogen suspension.
4. A method as in claim 1, further comprising mixing the fibrinogen suspension and the thrombin prior to delivering the fibrinogen suspension and the thrombin through the delivery catheter.
5. A method as in claim 1, wherein the fibrinogen suspension further comprises chondroitin sulfate.
6. A method as in claim 1, wherein the fibrinogen suspension further comprises tetracycline.
7. A method as in claim 1, further comprising:
puncturing a bronchial wall of a bronchial passageway located near the targeted lung region;
passing the distal end of the delivery catheter through the bronchial wall into the target lung region; and
causing the fibrinogen suspension or the thrombin to exit the distal end of the delivery catheter into the targeted lung region.
8. A method as in claim 1, wherein the delivery catheter is a bronchoscope.
9. A method as in claim 1, wherein the delivery catheter has at least two lumens.
10. A method as in claim 1, wherein the fibrinogen suspension and the thrombin are delivered simultaneously through the delivery catheter.
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Cited By (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080228130A1 (en) * 2007-03-12 2008-09-18 Pulmonx Methods and systems for occluding collateral flow channels in the lung
US20100125271A1 (en) * 2008-11-19 2010-05-20 Samuel Victor Lichtenstein System for treating undesired body tissue
US20100229863A1 (en) * 2007-03-16 2010-09-16 Dolphys Technologies, B.V. Jet ventilation catheter, in particular for ventilating a patient
US20110245665A1 (en) * 2010-03-30 2011-10-06 Angiodynamics, Inc. Bronchial catheter and method of use
US20120053566A1 (en) * 2010-08-25 2012-03-01 Terumo Kabushiki Kaisha Method for treatment of emphysema
US8579785B2 (en) 2011-05-10 2013-11-12 Nazly Makoui Shariati Source/seed delivery surgical staple device for delivering local source/seed direclty to a staple margin
JP2016534787A (en) * 2013-10-25 2016-11-10 マーケイター メドシステムズ, インコーポレイテッド Maintaining bronchial patency by cytotoxicity, cytostatics, or local delivery of antineoplastic agents
US9598691B2 (en) 2008-04-29 2017-03-21 Virginia Tech Intellectual Properties, Inc. Irreversible electroporation to create tissue scaffolds
US9757196B2 (en) 2011-09-28 2017-09-12 Angiodynamics, Inc. Multiple treatment zone ablation probe
US9867652B2 (en) 2008-04-29 2018-01-16 Virginia Tech Intellectual Properties, Inc. Irreversible electroporation using tissue vasculature to treat aberrant cell masses or create tissue scaffolds
US9895189B2 (en) 2009-06-19 2018-02-20 Angiodynamics, Inc. Methods of sterilization and treating infection using irreversible electroporation
US10117707B2 (en) 2008-04-29 2018-11-06 Virginia Tech Intellectual Properties, Inc. System and method for estimating tissue heating of a target ablation zone for electrical-energy based therapies
CN108837283A (en) * 2018-04-12 2018-11-20 上海市东方医院 Stem bronchi cell precise positioning slow-released system
US10154874B2 (en) 2008-04-29 2018-12-18 Virginia Tech Intellectual Properties, Inc. Immunotherapeutic methods using irreversible electroporation
US10238447B2 (en) 2008-04-29 2019-03-26 Virginia Tech Intellectual Properties, Inc. System and method for ablating a tissue site by electroporation with real-time monitoring of treatment progress
US10245105B2 (en) 2008-04-29 2019-04-02 Virginia Tech Intellectual Properties, Inc. Electroporation with cooling to treat tissue
US10272178B2 (en) 2008-04-29 2019-04-30 Virginia Tech Intellectual Properties Inc. Methods for blood-brain barrier disruption using electrical energy
US10292755B2 (en) 2009-04-09 2019-05-21 Virginia Tech Intellectual Properties, Inc. High frequency electroporation for cancer therapy
US10363290B2 (en) 2014-10-17 2019-07-30 Kodiak Sciences Inc. Butyrylcholinesterase zwitterionic polymer conjugates
US10470822B2 (en) 2008-04-29 2019-11-12 Virginia Tech Intellectual Properties, Inc. System and method for estimating a treatment volume for administering electrical-energy based therapies
US10471254B2 (en) 2014-05-12 2019-11-12 Virginia Tech Intellectual Properties, Inc. Selective modulation of intracellular effects of cells using pulsed electric fields
US10694972B2 (en) 2014-12-15 2020-06-30 Virginia Tech Intellectual Properties, Inc. Devices, systems, and methods for real-time monitoring of electrophysical effects during tissue treatment
US10702326B2 (en) 2011-07-15 2020-07-07 Virginia Tech Intellectual Properties, Inc. Device and method for electroporation based treatment of stenosis of a tubular body part
US10842969B2 (en) 2013-10-25 2020-11-24 Mercator Medsystems, Inc. Systems and methods of treating malacia by local delivery of hydrogel to augment tissue
US10980737B1 (en) 2016-03-08 2021-04-20 Samuel Victor Lichtenstein System for treating unwanted tissue using heat and heat activated drugs
US11254926B2 (en) 2008-04-29 2022-02-22 Virginia Tech Intellectual Properties, Inc. Devices and methods for high frequency electroporation
US11272979B2 (en) 2008-04-29 2022-03-15 Virginia Tech Intellectual Properties, Inc. System and method for estimating tissue heating of a target ablation zone for electrical-energy based therapies
US11311329B2 (en) 2018-03-13 2022-04-26 Virginia Tech Intellectual Properties, Inc. Treatment planning for immunotherapy based treatments using non-thermal ablation techniques
US11382681B2 (en) 2009-04-09 2022-07-12 Virginia Tech Intellectual Properties, Inc. Device and methods for delivery of high frequency electrical pulses for non-thermal ablation
US11453873B2 (en) 2008-04-29 2022-09-27 Virginia Tech Intellectual Properties, Inc. Methods for delivery of biphasic electrical pulses for non-thermal ablation
US11607537B2 (en) 2017-12-05 2023-03-21 Virginia Tech Intellectual Properties, Inc. Method for treating neurological disorders, including tumors, with electroporation
US11638603B2 (en) 2009-04-09 2023-05-02 Virginia Tech Intellectual Properties, Inc. Selective modulation of intracellular effects of cells using pulsed electric fields
US11707629B2 (en) 2009-05-28 2023-07-25 Angiodynamics, Inc. System and method for synchronizing energy delivery to the cardiac rhythm
US11723710B2 (en) 2016-11-17 2023-08-15 Angiodynamics, Inc. Techniques for irreversible electroporation using a single-pole tine-style internal device communicating with an external surface electrode
US11925405B2 (en) 2018-03-13 2024-03-12 Virginia Tech Intellectual Properties, Inc. Treatment planning system for immunotherapy enhancement via non-thermal ablation
US11931096B2 (en) 2021-06-14 2024-03-19 Angiodynamics, Inc. System and method for electrically ablating tissue of a patient

Families Citing this family (167)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6997189B2 (en) * 1998-06-05 2006-02-14 Broncus Technologies, Inc. Method for lung volume reduction
US6679264B1 (en) * 2000-03-04 2004-01-20 Emphasys Medical, Inc. Methods and devices for use in performing pulmonary procedures
US8474460B2 (en) 2000-03-04 2013-07-02 Pulmonx Corporation Implanted bronchial isolation devices and methods
JP5190169B2 (en) 2000-10-19 2013-04-24 アプライド メディカル リソーシーズ コーポレイション Surgical access instruments and methods
US6527761B1 (en) * 2000-10-27 2003-03-04 Pulmonx, Inc. Methods and devices for obstructing and aspirating lung tissue segments
WO2003015848A1 (en) 2001-08-14 2003-02-27 Applied Medical Resources Corporation Access sealing apparatus and method
US7883471B2 (en) * 2001-09-10 2011-02-08 Pulmonx Corporation Minimally invasive determination of collateral ventilation in lungs
US20030050648A1 (en) 2001-09-11 2003-03-13 Spiration, Inc. Removable lung reduction devices, systems, and methods
EP1434615B1 (en) 2001-10-11 2007-07-11 Emphasys Medical, Inc. Bronchial flow control device
US6958037B2 (en) 2001-10-20 2005-10-25 Applied Medical Resources Corporation Wound retraction apparatus and method
US6592594B2 (en) 2001-10-25 2003-07-15 Spiration, Inc. Bronchial obstruction device deployment system and method
US6929637B2 (en) 2002-02-21 2005-08-16 Spiration, Inc. Device and method for intra-bronchial provision of a therapeutic agent
US20030181922A1 (en) 2002-03-20 2003-09-25 Spiration, Inc. Removable anchored lung volume reduction devices and methods
US20030216769A1 (en) 2002-05-17 2003-11-20 Dillard David H. Removable anchored lung volume reduction devices and methods
EP2343032B1 (en) 2002-06-05 2012-05-09 Applied Medical Resources Corporation Wound retractor
EP1524942B1 (en) 2002-07-26 2008-09-10 Emphasys Medical, Inc. Bronchial flow control devices with membrane seal
US20140107396A1 (en) * 2002-09-10 2014-04-17 Pulmonx Corporation Systems and methods for delivering a therapeutic agent
US7814912B2 (en) 2002-11-27 2010-10-19 Pulmonx Corporation Delivery methods and devices for implantable bronchial isolation devices
US20050020884A1 (en) 2003-02-25 2005-01-27 Hart Charles C. Surgical access system
US7100616B2 (en) 2003-04-08 2006-09-05 Spiration, Inc. Bronchoscopic lung volume reduction method
US7811274B2 (en) 2003-05-07 2010-10-12 Portaero, Inc. Method for treating chronic obstructive pulmonary disease
US7426929B2 (en) 2003-05-20 2008-09-23 Portaero, Inc. Intra/extra-thoracic collateral ventilation bypass system and method
US7252086B2 (en) 2003-06-03 2007-08-07 Cordis Corporation Lung reduction system
US7377278B2 (en) 2003-06-05 2008-05-27 Portaero, Inc. Intra-thoracic collateral ventilation bypass system and method
US20050016530A1 (en) * 2003-07-09 2005-01-27 Mccutcheon John Treatment planning with implantable bronchial isolation devices
US7682332B2 (en) 2003-07-15 2010-03-23 Portaero, Inc. Methods to accelerate wound healing in thoracic anastomosis applications
EP1651094A4 (en) 2003-08-06 2008-07-30 Applied Med Resources Surgical device with tack-free gel and method of manufacture
US7533671B2 (en) 2003-08-08 2009-05-19 Spiration, Inc. Bronchoscopic repair of air leaks in a lung
US7163510B2 (en) 2003-09-17 2007-01-16 Applied Medical Resources Corporation Surgical instrument access device
US7036509B2 (en) 2003-12-04 2006-05-02 Emphasys Medical, Inc. Multiple seal port anesthesia adapter
US8206684B2 (en) 2004-02-27 2012-06-26 Pulmonx Corporation Methods and devices for blocking flow through collateral pathways in the lung
US20050288702A1 (en) * 2004-06-16 2005-12-29 Mcgurk Erin Intra-bronchial lung volume reduction system
ES2645340T3 (en) * 2004-11-16 2017-12-05 Uptake Medical Technology Inc. Lung treatment device
US7771472B2 (en) 2004-11-19 2010-08-10 Pulmonx Corporation Bronchial flow control devices and methods of use
US8220460B2 (en) 2004-11-19 2012-07-17 Portaero, Inc. Evacuation device and method for creating a localized pleurodesis
US7824366B2 (en) 2004-12-10 2010-11-02 Portaero, Inc. Collateral ventilation device with chest tube/evacuation features and method
US11883029B2 (en) 2005-01-20 2024-01-30 Pulmonx Corporation Methods and devices for passive residual lung volume reduction and functional lung volume expansion
US8496006B2 (en) 2005-01-20 2013-07-30 Pulmonx Corporation Methods and devices for passive residual lung volume reduction and functional lung volume expansion
US20080228137A1 (en) 2007-03-12 2008-09-18 Pulmonx Methods and devices for passive residual lung volume reduction and functional lung volume expansion
EP2614853B1 (en) 2005-01-20 2016-12-28 Pulmonx Minimally invasive determination of collateral ventilation in lungs
US20070186932A1 (en) * 2006-01-06 2007-08-16 Pulmonx Collateral pathway treatment using agent entrained by aspiration flow current
US8876791B2 (en) * 2005-02-25 2014-11-04 Pulmonx Corporation Collateral pathway treatment using agent entrained by aspiration flow current
US20070142742A1 (en) * 2005-07-13 2007-06-21 Pulmonx Methods and systems for segmental lung diagnostics
US8104474B2 (en) 2005-08-23 2012-01-31 Portaero, Inc. Collateral ventilation bypass system with retention features
WO2007044850A1 (en) 2005-10-14 2007-04-19 Applied Medical Resources Corporation Wound retractor with gel cap
CN101466408A (en) * 2005-11-02 2009-06-24 艾里斯治疗公司 Polycation-polyanion complexes, compositions and methods of use thereof
US20140142455A1 (en) * 2005-12-07 2014-05-22 Pulmonx Corporation Minimally invasive determination of collateral ventilation in lungs
US8523782B2 (en) 2005-12-07 2013-09-03 Pulmonx Corporation Minimally invasive determination of collateral ventilation in lungs
US7406963B2 (en) 2006-01-17 2008-08-05 Portaero, Inc. Variable resistance pulmonary ventilation bypass valve and method
US8136526B2 (en) * 2006-03-08 2012-03-20 Pulmonx Corporation Methods and devices to induce controlled atelectasis and hypoxic pulmonary vasoconstriction
US8721734B2 (en) * 2009-05-18 2014-05-13 Pneumrx, Inc. Cross-sectional modification during deployment of an elongate lung volume reduction device
US9402633B2 (en) 2006-03-13 2016-08-02 Pneumrx, Inc. Torque alleviating intra-airway lung volume reduction compressive implant structures
US8157837B2 (en) 2006-03-13 2012-04-17 Pneumrx, Inc. Minimally invasive lung volume reduction device and method
US8888800B2 (en) 2006-03-13 2014-11-18 Pneumrx, Inc. Lung volume reduction devices, methods, and systems
US7691151B2 (en) 2006-03-31 2010-04-06 Spiration, Inc. Articulable Anchor
WO2008027293A2 (en) * 2006-08-25 2008-03-06 Emphasys Medical, Inc. Bronchial isolation devices for placement in short lumens
US7993323B2 (en) 2006-11-13 2011-08-09 Uptake Medical Corp. High pressure and high temperature vapor catheters and systems
WO2008111070A2 (en) * 2007-03-12 2008-09-18 David Tolkowsky Devices and methods for performing medical procedures in tree-like luminal structures
DE102007021717A1 (en) * 2007-05-09 2008-10-02 Siemens Ag Broncho-pulmonal diagnose and therapy system for treating diseases in vascular and lymphatic system, has X-ray imaging arrangement arranged for three-dimensional movement within diagnostic-and therapy areas at multi-axial support system
US7931641B2 (en) 2007-05-11 2011-04-26 Portaero, Inc. Visceral pleura ring connector
ES2623049T3 (en) 2007-05-11 2017-07-10 Applied Medical Resources Corporation Surgical retractor
AU2008251303B2 (en) 2007-05-11 2013-09-19 Applied Medical Resources Corporation Surgical access device
US8163034B2 (en) 2007-05-11 2012-04-24 Portaero, Inc. Methods and devices to create a chemically and/or mechanically localized pleurodesis
US8062315B2 (en) 2007-05-17 2011-11-22 Portaero, Inc. Variable parietal/visceral pleural coupling
NZ569226A (en) 2007-06-22 2010-02-26 Resmed Ltd Flexible forehead support
BRPI0817421A2 (en) 2007-10-05 2015-06-16 Tyco Healthcare Sealing fastener for use in surgical procedures
US8043301B2 (en) 2007-10-12 2011-10-25 Spiration, Inc. Valve loader method, system, and apparatus
US8136230B2 (en) 2007-10-12 2012-03-20 Spiration, Inc. Valve loader method, system, and apparatus
US8322335B2 (en) * 2007-10-22 2012-12-04 Uptake Medical Corp. Determining patient-specific vapor treatment and delivery parameters
EP2237815B1 (en) 2008-01-22 2020-08-19 Applied Medical Resources Corporation Surgical instrument access device
US8475389B2 (en) 2008-02-19 2013-07-02 Portaero, Inc. Methods and devices for assessment of pneumostoma function
WO2009105432A2 (en) 2008-02-19 2009-08-27 Portaero, Inc. Devices and methods for delivery of a therapeutic agent through a pneumostoma
US8336540B2 (en) 2008-02-19 2012-12-25 Portaero, Inc. Pneumostoma management device and method for treatment of chronic obstructive pulmonary disease
EP2259726B1 (en) * 2008-04-03 2018-10-31 Koninklijke Philips N.V. Respiration determination apparatus
US20090306544A1 (en) * 2008-06-09 2009-12-10 Ho-Kin Ng Instillation/aspiration device
US20100036361A1 (en) * 2008-06-20 2010-02-11 Pulmonx System and method for delivering multiple implants into lung passageways
US8632605B2 (en) 2008-09-12 2014-01-21 Pneumrx, Inc. Elongated lung volume reduction devices, methods, and systems
USD738500S1 (en) 2008-10-02 2015-09-08 Covidien Lp Seal anchor for use in surgical procedures
AU2009303470B2 (en) 2008-10-13 2015-04-23 Applied Medical Resources Corporation Single port access system
US8347881B2 (en) 2009-01-08 2013-01-08 Portaero, Inc. Pneumostoma management device with integrated patency sensor and method
US8518053B2 (en) 2009-02-11 2013-08-27 Portaero, Inc. Surgical instruments for creating a pneumostoma and treating chronic obstructive pulmonary disease
US8317690B2 (en) 2009-03-31 2012-11-27 Covidien Lp Foam port and introducer assembly
US8323184B2 (en) 2009-03-31 2012-12-04 Covidien Lp Surgical access port and associated introducer mechanism
US8932212B2 (en) 2009-10-01 2015-01-13 Covidien Lp Seal anchor with non-parallel lumens
US8740904B2 (en) 2009-11-24 2014-06-03 Covidien Lp Seal anchor introducer including biasing member
US8480683B2 (en) 2009-11-24 2013-07-09 Covidien Lp Foam introduction system including modified port geometry
US20110301483A1 (en) * 2009-12-23 2011-12-08 Pulmonx Corporation Local lung measurement and treatment
US20110184258A1 (en) * 2010-01-28 2011-07-28 Abbott Diabetes Care Inc. Balloon Catheter Analyte Measurement Sensors and Methods for Using the Same
US8808194B2 (en) 2010-07-01 2014-08-19 Pulmonx Corporation Methods and systems for endobronchial diagnostics
US9592008B2 (en) * 2010-07-01 2017-03-14 Pulmonx Corporation Devices and systems for lung treatment
US20120150027A1 (en) * 2010-07-01 2012-06-14 Pulmonx Corporation Methods and systems for endobronchial diagnosis and treatment
US9364168B2 (en) 2010-07-01 2016-06-14 Pulmonx Corporation Methods and systems for endobronchial diagnosis
EP2621348B1 (en) 2010-10-01 2019-06-12 Applied Medical Resources Corporation Natural orifice surgery system
US9289115B2 (en) 2010-10-01 2016-03-22 Applied Medical Resources Corporation Natural orifice surgery system
US9023040B2 (en) 2010-10-26 2015-05-05 Medtronic Advanced Energy Llc Electrosurgical cutting devices
US8753267B2 (en) 2011-01-24 2014-06-17 Covidien Lp Access assembly insertion device
US9427281B2 (en) 2011-03-11 2016-08-30 Medtronic Advanced Energy Llc Bronchoscope-compatible catheter provided with electrosurgical device
KR102423785B1 (en) 2011-05-10 2022-07-21 어플라이드 메디컬 리소시스 코포레이션 Wound retractor
US8795241B2 (en) 2011-05-13 2014-08-05 Spiration, Inc. Deployment catheter
EP2758010B1 (en) 2011-09-23 2017-02-08 Pulmonx, Inc Implant loading system
US9271639B2 (en) 2012-02-29 2016-03-01 Covidien Lp Surgical introducer and access port assembly
US10058332B2 (en) * 2012-08-01 2018-08-28 Terumo Kabushiki Kaisha Method for treatment of chronic obstructive pulmonary disease
AU2014228334B2 (en) 2013-03-15 2018-11-29 Applied Medical Resources Corporation Mechanical gel surgical access device
JP6151129B2 (en) 2013-08-19 2017-06-21 テルモ株式会社 Fibrotic agent
JP2015037505A (en) * 2013-08-19 2015-02-26 テルモ株式会社 Method for reducing lung capacity
JP6210794B2 (en) * 2013-08-19 2017-10-11 テルモ株式会社 Fibrotic agent
US9782211B2 (en) 2013-10-01 2017-10-10 Uptake Medical Technology Inc. Preferential volume reduction of diseased segments of a heterogeneous lobe
WO2015061790A2 (en) 2013-10-25 2015-04-30 Pneumrx, Inc. Genetically-associated chronic obstructive pulmonary disease treatment
US10064649B2 (en) 2014-07-07 2018-09-04 Covidien Lp Pleated seal for surgical hand or instrument access
US9642608B2 (en) 2014-07-18 2017-05-09 Applied Medical Resources Corporation Gels having permanent tack free coatings and method of manufacture
KR102509415B1 (en) 2014-08-15 2023-03-10 어플라이드 메디컬 리소시스 코포레이션 Natural orifice surgery system
US10390838B1 (en) 2014-08-20 2019-08-27 Pneumrx, Inc. Tuned strength chronic obstructive pulmonary disease treatment
US9707011B2 (en) 2014-11-12 2017-07-18 Covidien Lp Attachments for use with a surgical access device
US9949730B2 (en) 2014-11-25 2018-04-24 Applied Medical Resources Corporation Circumferential wound retraction with support and guidance structures
US10485604B2 (en) 2014-12-02 2019-11-26 Uptake Medical Technology Inc. Vapor treatment of lung nodules and tumors
WO2016118663A1 (en) * 2015-01-20 2016-07-28 Pulmonx Corporation Bronchial sealant delivery methods and systems
US10531906B2 (en) 2015-02-02 2020-01-14 Uptake Medical Technology Inc. Medical vapor generator
GB2550099B (en) 2015-03-24 2020-09-02 Gyrus Acmi Inc Airway stent
US10413300B2 (en) * 2015-06-22 2019-09-17 Pulmonx Corporation Collateral flow channel sealant delivery methods and systems
EP4151165A1 (en) 2015-09-15 2023-03-22 Applied Medical Resources Corporation Surgical robotic access system
ES2951168T3 (en) 2015-10-07 2023-10-18 Applied Med Resources Multi-segment outer ring wound retractor
EP3383266B1 (en) * 2015-11-30 2021-08-11 Materialise N.V. Computer-implemented method of providing a device for placement in an airway passage
JP7021200B2 (en) 2016-09-12 2022-02-16 アプライド メディカル リソーシーズ コーポレイション Surgical robot access system
CN108272538B (en) * 2016-12-30 2020-06-12 先健科技(深圳)有限公司 Elastic implant for lung volume reduction and lung volume reduction instrument
US11129673B2 (en) 2017-05-05 2021-09-28 Uptake Medical Technology Inc. Extra-airway vapor ablation for treating airway constriction in patients with asthma and COPD
US11160682B2 (en) 2017-06-19 2021-11-02 Covidien Lp Method and apparatus for accessing matter disposed within an internal body vessel
US10828065B2 (en) 2017-08-28 2020-11-10 Covidien Lp Surgical access system
US11344364B2 (en) 2017-09-07 2022-05-31 Uptake Medical Technology Inc. Screening method for a target nerve to ablate for the treatment of inflammatory lung disease
US10675056B2 (en) 2017-09-07 2020-06-09 Covidien Lp Access apparatus with integrated fluid connector and control valve
CN109464186B (en) 2017-09-08 2023-12-22 泽丹医疗股份有限公司 Device and method for treating lung tumors
WO2019051274A2 (en) 2017-09-08 2019-03-14 Zidan Medical, Inc. Devices for treating lung tumors
WO2019051251A1 (en) * 2017-09-08 2019-03-14 Zidan Medical, Inc. Devices and methods for treating lung tumors
US11350988B2 (en) 2017-09-11 2022-06-07 Uptake Medical Technology Inc. Bronchoscopic multimodality lung tumor treatment
USD845467S1 (en) 2017-09-17 2019-04-09 Uptake Medical Technology Inc. Hand-piece for medical ablation catheter
US11419658B2 (en) 2017-11-06 2022-08-23 Uptake Medical Technology Inc. Method for treating emphysema with condensable thermal vapor
US11490946B2 (en) 2017-12-13 2022-11-08 Uptake Medical Technology Inc. Vapor ablation handpiece
US11344356B2 (en) 2018-02-28 2022-05-31 Medtronic Cryocath Lp Apparatus and method for targeted bronchial denervation by cryo-ablation
US11389193B2 (en) 2018-10-02 2022-07-19 Covidien Lp Surgical access device with fascial closure system
US11457949B2 (en) 2018-10-12 2022-10-04 Covidien Lp Surgical access device and seal guard for use therewith
US11166748B2 (en) 2019-02-11 2021-11-09 Covidien Lp Seal assemblies for surgical access assemblies
US10792071B2 (en) 2019-02-11 2020-10-06 Covidien Lp Seals for surgical access assemblies
US11653927B2 (en) 2019-02-18 2023-05-23 Uptake Medical Technology Inc. Vapor ablation treatment of obstructive lung disease
WO2020185399A2 (en) 2019-03-08 2020-09-17 Zidan Medical, Inc. Systems, devices and methods for treating lung tumors
US20210007796A1 (en) 2019-07-10 2021-01-14 Zidan Medical, Inc. Systems, devices and methods for treating lung tumors
US11000313B2 (en) 2019-04-25 2021-05-11 Covidien Lp Seals for surgical access devices
US11413068B2 (en) 2019-05-09 2022-08-16 Covidien Lp Seal assemblies for surgical access assemblies
US11259841B2 (en) 2019-06-21 2022-03-01 Covidien Lp Seal assemblies for surgical access assemblies
US11357542B2 (en) 2019-06-21 2022-06-14 Covidien Lp Valve assembly and retainer for surgical access assembly
US11259840B2 (en) 2019-06-21 2022-03-01 Covidien Lp Valve assemblies for surgical access assemblies
US11413065B2 (en) 2019-06-28 2022-08-16 Covidien Lp Seal assemblies for surgical access assemblies
US11399865B2 (en) 2019-08-02 2022-08-02 Covidien Lp Seal assemblies for surgical access assemblies
US11432843B2 (en) 2019-09-09 2022-09-06 Covidien Lp Centering mechanisms for a surgical access assembly
US11523842B2 (en) 2019-09-09 2022-12-13 Covidien Lp Reusable surgical port with disposable seal assembly
US11812991B2 (en) 2019-10-18 2023-11-14 Covidien Lp Seal assemblies for surgical access assemblies
US11464540B2 (en) 2020-01-17 2022-10-11 Covidien Lp Surgical access device with fixation mechanism
US11576701B2 (en) 2020-03-05 2023-02-14 Covidien Lp Surgical access assembly having a pump
US11642153B2 (en) 2020-03-19 2023-05-09 Covidien Lp Instrument seal for surgical access assembly
US11541218B2 (en) 2020-03-20 2023-01-03 Covidien Lp Seal assembly for a surgical access assembly and method of manufacturing the same
US11446058B2 (en) 2020-03-27 2022-09-20 Covidien Lp Fixture device for folding a seal member
US11717321B2 (en) 2020-04-24 2023-08-08 Covidien Lp Access assembly with retention mechanism
US11529170B2 (en) 2020-04-29 2022-12-20 Covidien Lp Expandable surgical access port
US11622790B2 (en) 2020-05-21 2023-04-11 Covidien Lp Obturators for surgical access assemblies and methods of assembly thereof
US11751908B2 (en) 2020-06-19 2023-09-12 Covidien Lp Seal assembly for surgical access assemblies
EP4178434A1 (en) 2020-07-10 2023-05-17 Pulmonx Corporation Methods and systems for determining collateral ventilation
US11666370B2 (en) 2020-07-27 2023-06-06 Medtronic, Inc. Apparatus and method for targeted temporary bronchial nerve modulation by cryo-ablation for prevention and treatment of acute respiratory distress syndromes
JP2023542052A (en) 2020-08-28 2023-10-04 ジダン メディカル インコーポレイテッド Systems and devices for treating lung tumors
WO2022067146A2 (en) 2020-09-28 2022-03-31 Zidan Medical, Inc. Systems, devices and methods for treating lung tumors with a robotically delivered catheter

Citations (94)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US981254A (en) * 1909-10-27 1911-01-10 Murphy Iron Works Refuse-burner.
US3657744A (en) * 1970-05-08 1972-04-25 Univ Minnesota Method for fixing prosthetic implants in a living body
US3788327A (en) * 1971-03-30 1974-01-29 H Donowitz Surgical implant device
US3874388A (en) * 1973-02-12 1975-04-01 Ochsner Med Found Alton Shunt defect closure system
US4014318A (en) * 1973-08-20 1977-03-29 Dockum James M Circulatory assist device and system
US4086665A (en) * 1976-12-16 1978-05-02 Thermo Electron Corporation Artificial blood conduit
US4212463A (en) * 1978-02-17 1980-07-15 Pratt Enoch B Humane bleeder arrow
US4250873A (en) * 1977-04-26 1981-02-17 Richard Wolf Gmbh Endoscopes
US4732152A (en) * 1984-12-05 1988-03-22 Medinvent S.A. Device for implantation and a method of implantation in a vessel using such device
US4759758A (en) * 1984-12-07 1988-07-26 Shlomo Gabbay Prosthetic heart valve
US4795449A (en) * 1986-08-04 1989-01-03 Hollister Incorporated Female urinary incontinence device
US4808183A (en) * 1980-06-03 1989-02-28 University Of Iowa Research Foundation Voice button prosthesis and method for installing same
US4819664A (en) * 1984-11-15 1989-04-11 Stefano Nazari Device for selective bronchial intubation and separate lung ventilation, particularly during anesthesia, intensive therapy and reanimation
US4830003A (en) * 1988-06-17 1989-05-16 Wolff Rodney G Compressive stent and delivery system
US4832680A (en) * 1986-07-03 1989-05-23 C.R. Bard, Inc. Apparatus for hypodermically implanting a genitourinary prosthesis
US4846836A (en) * 1988-10-03 1989-07-11 Reich Jonathan D Artificial lower gastrointestinal valve
US4850999A (en) * 1980-05-24 1989-07-25 Institute Fur Textil-Und Faserforschung Of Stuttgart Flexible hollow organ
US4852568A (en) * 1987-02-17 1989-08-01 Kensey Nash Corporation Method and apparatus for sealing an opening in tissue of a living being
US4934999A (en) * 1987-07-28 1990-06-19 Paul Bader Closure for a male urethra
US5116360A (en) * 1990-12-27 1992-05-26 Corvita Corporation Mesh composite graft
US5116564A (en) * 1988-10-11 1992-05-26 Josef Jansen Method of producing a closing member having flexible closing elements, especially a heart valve
US5123919A (en) * 1991-11-21 1992-06-23 Carbomedics, Inc. Combined prosthetic aortic heart valve and vascular graft
US5151105A (en) * 1991-10-07 1992-09-29 Kwan Gett Clifford Collapsible vessel sleeve implant
US5306234A (en) * 1993-03-23 1994-04-26 Johnson W Dudley Method for closing an atrial appendage
US5382261A (en) * 1992-09-01 1995-01-17 Expandable Grafts Partnership Method and apparatus for occluding vessels
US5392775A (en) * 1994-03-22 1995-02-28 Adkins, Jr.; Claude N. Duckbill valve for a tracheostomy tube that permits speech
US5409019A (en) * 1992-10-30 1995-04-25 Wilk; Peter J. Coronary artery by-pass method
US5411507A (en) * 1993-01-08 1995-05-02 Richard Wolf Gmbh Instrument for implanting and extracting stents
US5411552A (en) * 1990-05-18 1995-05-02 Andersen; Henning R. Valve prothesis for implantation in the body and a catheter for implanting such valve prothesis
US5413599A (en) * 1988-09-20 1995-05-09 Nippon Zeon Co., Ltd. Medical valve apparatus
US5417226A (en) * 1994-06-09 1995-05-23 Juma; Saad Female anti-incontinence device
US5445626A (en) * 1991-12-05 1995-08-29 Gigante; Luigi Valve operated catheter for urinary incontinence and retention
US5486154A (en) * 1993-06-08 1996-01-23 Kelleher; Brian S. Endoscope
US5499995A (en) * 1994-05-25 1996-03-19 Teirstein; Paul S. Body passageway closure apparatus and method of use
US5500014A (en) * 1989-05-31 1996-03-19 Baxter International Inc. Biological valvular prothesis
US5614204A (en) * 1995-01-23 1997-03-25 The Regents Of The University Of California Angiographic vascular occlusion agents and a method for hemostatic occlusion
US5645565A (en) * 1995-06-13 1997-07-08 Ethicon Endo-Surgery, Inc. Surgical plug
US5660175A (en) * 1995-08-21 1997-08-26 Dayal; Bimal Endotracheal device
US5662713A (en) * 1991-10-09 1997-09-02 Boston Scientific Corporation Medical stents for body lumens exhibiting peristaltic motion
US5727593A (en) * 1996-06-26 1998-03-17 Red Valve Company, Inc. Tide gate valve with curvilinear bill
US5755770A (en) * 1995-01-31 1998-05-26 Boston Scientific Corporatiion Endovascular aortic graft
US5800339A (en) * 1989-02-09 1998-09-01 Opticon Medical Inc. Urinary control valve
US5855601A (en) * 1996-06-21 1999-01-05 The Trustees Of Columbia University In The City Of New York Artificial heart valve and method and device for implanting the same
US5855597A (en) * 1997-05-07 1999-01-05 Iowa-India Investments Co. Limited Stent valve and stent graft for percutaneous surgery
US5855587A (en) * 1996-06-13 1999-01-05 Chon-Ik Hyon Hole forming device for pierced earrings
US5944738A (en) * 1998-02-06 1999-08-31 Aga Medical Corporation Percutaneous catheter directed constricting occlusion device
US5947997A (en) * 1992-11-25 1999-09-07 William Cook Europe A/S Closure prothesis for transcatheter placement
US5954766A (en) * 1997-09-16 1999-09-21 Zadno-Azizi; Gholam-Reza Body fluid flow control device
US5957949A (en) * 1997-05-01 1999-09-28 World Medical Manufacturing Corp. Percutaneous placement valve stent
US6009614A (en) * 1998-04-21 2000-01-04 Advanced Cardiovascular Systems, Inc. Stent crimping tool and method of use
US6016839A (en) * 1997-06-24 2000-01-25 Red Valve Co., Inc. Air diffuser valve
US6020380A (en) * 1998-11-25 2000-02-01 Tap Holdings Inc. Method of treating chronic obstructive pulmonary disease
US6022312A (en) * 1995-05-05 2000-02-08 Chaussy; Christian Endosphincter, set for releasable closure of the urethra and method for introduction of an endosphincter into the urethra
US6027525A (en) * 1996-05-23 2000-02-22 Samsung Electronics., Ltd. Flexible self-expandable stent and method for making the same
US6051022A (en) * 1998-12-30 2000-04-18 St. Jude Medical, Inc. Bileaflet valve having non-parallel pivot axes
US6068635A (en) * 1998-03-04 2000-05-30 Schneider (Usa) Inc Device for introducing an endoprosthesis into a catheter shaft
US6068638A (en) * 1995-10-13 2000-05-30 Transvascular, Inc. Device, system and method for interstitial transvascular intervention
US6077291A (en) * 1992-01-21 2000-06-20 Regents Of The University Of Minnesota Septal defect closure device
US6083255A (en) * 1997-04-07 2000-07-04 Broncus Technologies, Inc. Bronchial stenter
US6117425A (en) * 1990-11-27 2000-09-12 The American National Red Cross Supplemented and unsupplemented tissue sealants, method of their production and use
US6123663A (en) * 1996-07-04 2000-09-26 Rebuffat; Carlo Surgical appliance for the treatment of pulmonary emphysema
US6168614B1 (en) * 1990-05-18 2001-01-02 Heartport, Inc. Valve prosthesis for implantation in the body
US6174323B1 (en) * 1998-06-05 2001-01-16 Broncus Technologies, Inc. Method and assembly for lung volume reduction
US6183520B1 (en) * 1996-08-13 2001-02-06 Galt Laboratories, Inc. Method of maintaining urinary continence
US6200333B1 (en) * 1997-04-07 2001-03-13 Broncus Technologies, Inc. Bronchial stenter
US6206918B1 (en) * 1999-05-12 2001-03-27 Sulzer Carbomedics Inc. Heart valve prosthesis having a pivot design for improving flow characteristics
US6234996B1 (en) * 1999-06-23 2001-05-22 Percusurge, Inc. Integrated inflation/deflation device and method
US6240615B1 (en) * 1998-05-05 2001-06-05 Advanced Cardiovascular Systems, Inc. Method and apparatus for uniformly crimping a stent onto a catheter
US6245102B1 (en) * 1997-05-07 2001-06-12 Iowa-India Investments Company Ltd. Stent, stent graft and stent valve
US6258100B1 (en) * 1999-08-24 2001-07-10 Spiration, Inc. Method of reducing lung size
US6270527B1 (en) * 1998-10-16 2001-08-07 Sulzer Carbomedics Inc. Elastic valve with partially exposed stent
US20020007831A1 (en) * 2000-07-19 2002-01-24 Davenport Paul W. Method for treating chronic obstructive pulmonary disorder
US20020026233A1 (en) * 2000-08-29 2002-02-28 Alexander Shaknovich Method and devices for decreasing elevated pulmonary venous pressure
US6355014B1 (en) * 1996-05-20 2002-03-12 Medtronic Percusurge, Inc. Low profile catheter valve
US20020062120A1 (en) * 1999-07-02 2002-05-23 Pulmonx Methods, systems, and kits for lung volume reduction
US6398775B1 (en) * 1999-10-21 2002-06-04 Pulmonx Apparatus and method for isolated lung access
US6402754B1 (en) * 1999-10-20 2002-06-11 Spiration, Inc. Apparatus for expanding the thorax
US20020087153A1 (en) * 1999-08-05 2002-07-04 Broncus Technologies, Inc. Devices for creating collateral channels
US6416554B1 (en) * 1999-08-24 2002-07-09 Spiration, Inc. Lung reduction apparatus and method
US20020111619A1 (en) * 1999-08-05 2002-08-15 Broncus Technologies, Inc. Devices for creating collateral channels
US20020111620A1 (en) * 2001-02-14 2002-08-15 Broncus Technologies, Inc. Devices and methods for maintaining collateral channels in tissue
US20020112729A1 (en) * 2001-02-21 2002-08-22 Spiration, Inc. Intra-bronchial obstructing device that controls biological interaction with the patient
US20030018327A1 (en) * 2001-07-20 2003-01-23 Csaba Truckai Systems and techniques for lung volume reduction
US20030018344A1 (en) * 2001-07-19 2003-01-23 Olympus Optical Co., Ltd. Medical device and method of embolizing bronchus or bronchiole
US6510846B1 (en) * 1999-12-23 2003-01-28 O'rourke Sam Sealed back pressure breathing device
US6527761B1 (en) * 2000-10-27 2003-03-04 Pulmonx, Inc. Methods and devices for obstructing and aspirating lung tissue segments
US20030050648A1 (en) * 2001-09-11 2003-03-13 Spiration, Inc. Removable lung reduction devices, systems, and methods
US20030083671A1 (en) * 2001-10-25 2003-05-01 Spiration, Inc. Bronchial obstruction device deployment system and method
US6599311B1 (en) * 1998-06-05 2003-07-29 Broncus Technologies, Inc. Method and assembly for lung volume reduction
US6610043B1 (en) * 1999-08-23 2003-08-26 Bistech, Inc. Tissue volume reduction
US6679264B1 (en) * 2000-03-04 2004-01-20 Emphasys Medical, Inc. Methods and devices for use in performing pulmonary procedures
US20040073201A1 (en) * 1999-08-05 2004-04-15 Broncus Technologies, Inc. Methods for treating chronic obstructive pulmonary disease
US20040073155A1 (en) * 2000-01-14 2004-04-15 Broncus Technologies, Inc. Methods and devices for maintaining patency of surgically created channels in tissue
US6743259B2 (en) * 2001-08-03 2004-06-01 Core Medical, Inc. Lung assist apparatus and methods for use

Family Cites Families (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US73201A (en) * 1868-01-07 Improved beige-machine
US111619A (en) * 1871-02-07 Improvement in saws
US112729A (en) * 1871-03-14 Improvement in dress-swords
US73155A (en) * 1868-01-07 baylet and john mccluskey
US111620A (en) * 1871-02-07 Improvement in devices for enlarging wells
US138135A (en) * 1873-04-22 Improvement in fire-place backs
US2981254A (en) * 1957-11-12 1961-04-25 Edwin G Vanderbilt Apparatus for the gas deflation of an animal's stomach
FR1309901A (en) * 1961-10-09 1962-11-23 Safety valve for liquefied gas tank
US4302854A (en) 1980-06-04 1981-12-01 Runge Thomas M Electrically activated ferromagnetic/diamagnetic vascular shunt for left ventricular assist
US4477930A (en) 1982-09-28 1984-10-23 Mitral Medical International, Inc. Natural tissue heat valve and method of making same
US4710192A (en) 1985-12-30 1987-12-01 Liotta Domingo S Diaphragm and method for occlusion of the descending thoracic aorta
US4877025A (en) * 1988-10-06 1989-10-31 Hanson Donald W Tracheostomy tube valve apparatus
US4968294A (en) * 1989-02-09 1990-11-06 Salama Fouad A Urinary control valve and method of using same
US5352240A (en) * 1989-05-31 1994-10-04 Promedica International, Inc. Human heart valve replacement with porcine pulmonary valve
US5562608A (en) 1989-08-28 1996-10-08 Biopulmonics, Inc. Apparatus for pulmonary delivery of drugs with simultaneous liquid lavage and ventilation
US5061274A (en) * 1989-12-04 1991-10-29 Kensey Nash Corporation Plug device for sealing openings and method of use
IT1247037B (en) * 1991-06-25 1994-12-12 Sante Camilli ARTIFICIAL VENOUS VALVE
US5161524A (en) * 1991-08-02 1992-11-10 Glaxo Inc. Dosage inhalator with air flow velocity regulating means
US5366478A (en) 1993-07-27 1994-11-22 Ethicon, Inc. Endoscopic surgical sealing device
US5957672A (en) 1993-11-10 1999-09-28 The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration Blood pump bearing system
US5683451A (en) 1994-06-08 1997-11-04 Cardiovascular Concepts, Inc. Apparatus and methods for deployment release of intraluminal prostheses
WO1996036967A2 (en) 1995-05-17 1996-11-21 Philips Electronics N.V. Magnetic-tape cassette with a tape-pressure device, tape pressure device with a pressure pad for such a cassette, and pressure pad for such a tape-pressure device
US6312407B1 (en) 1995-06-05 2001-11-06 Medtronic Percusurge, Inc. Occlusion of a vessel
US5697968A (en) 1995-08-10 1997-12-16 Aeroquip Corporation Check valve for intraluminal graft
EP1011889B1 (en) 1996-01-30 2002-10-30 Medtronic, Inc. Articles for and methods of making stents
US6325777B1 (en) 1996-05-20 2001-12-04 Medtronic Percusurge, Inc. Low profile catheter valve and inflation adaptor
US6050972A (en) 1996-05-20 2000-04-18 Percusurge, Inc. Guidewire inflation system
US6077295A (en) * 1996-07-15 2000-06-20 Advanced Cardiovascular Systems, Inc. Self-expanding stent delivery system
AU6688398A (en) * 1997-03-06 1998-09-22 Percusurge, Inc. Intravascular aspiration system
US5851232A (en) 1997-03-15 1998-12-22 Lois; William A. Venous stent
US6162245A (en) 1997-05-07 2000-12-19 Iowa-India Investments Company Limited Stent valve and stent graft
US6007575A (en) 1997-06-06 1999-12-28 Samuels; Shaun Laurence Wilkie Inflatable intraluminal stent and method for affixing same within the human body
US5957919A (en) * 1997-07-02 1999-09-28 Laufer; Michael D. Bleb reducer
US5984965A (en) 1997-08-28 1999-11-16 Urosurge, Inc. Anti-reflux reinforced stent
US5976174A (en) 1997-12-15 1999-11-02 Ruiz; Carlos E. Medical hole closure device and methods of use
US6141855A (en) 1998-04-28 2000-11-07 Advanced Cardiovascular Systems, Inc. Stent crimping tool and method of use
US6328689B1 (en) 2000-03-23 2001-12-11 Spiration, Inc., Lung constriction apparatus and method
US6722360B2 (en) * 2000-06-16 2004-04-20 Rajiv Doshi Methods and devices for improving breathing in patients with pulmonary disease
US6929637B2 (en) * 2002-02-21 2005-08-16 Spiration, Inc. Device and method for intra-bronchial provision of a therapeutic agent
US7100616B2 (en) * 2003-04-08 2006-09-05 Spiration, Inc. Bronchoscopic lung volume reduction method

Patent Citations (100)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US981254A (en) * 1909-10-27 1911-01-10 Murphy Iron Works Refuse-burner.
US3657744A (en) * 1970-05-08 1972-04-25 Univ Minnesota Method for fixing prosthetic implants in a living body
US3788327A (en) * 1971-03-30 1974-01-29 H Donowitz Surgical implant device
US3874388A (en) * 1973-02-12 1975-04-01 Ochsner Med Found Alton Shunt defect closure system
US4014318A (en) * 1973-08-20 1977-03-29 Dockum James M Circulatory assist device and system
US4086665A (en) * 1976-12-16 1978-05-02 Thermo Electron Corporation Artificial blood conduit
US4250873A (en) * 1977-04-26 1981-02-17 Richard Wolf Gmbh Endoscopes
US4212463A (en) * 1978-02-17 1980-07-15 Pratt Enoch B Humane bleeder arrow
US4850999A (en) * 1980-05-24 1989-07-25 Institute Fur Textil-Und Faserforschung Of Stuttgart Flexible hollow organ
US4808183A (en) * 1980-06-03 1989-02-28 University Of Iowa Research Foundation Voice button prosthesis and method for installing same
US4819664A (en) * 1984-11-15 1989-04-11 Stefano Nazari Device for selective bronchial intubation and separate lung ventilation, particularly during anesthesia, intensive therapy and reanimation
US4732152A (en) * 1984-12-05 1988-03-22 Medinvent S.A. Device for implantation and a method of implantation in a vessel using such device
US4759758A (en) * 1984-12-07 1988-07-26 Shlomo Gabbay Prosthetic heart valve
US4832680A (en) * 1986-07-03 1989-05-23 C.R. Bard, Inc. Apparatus for hypodermically implanting a genitourinary prosthesis
US4795449A (en) * 1986-08-04 1989-01-03 Hollister Incorporated Female urinary incontinence device
US4852568A (en) * 1987-02-17 1989-08-01 Kensey Nash Corporation Method and apparatus for sealing an opening in tissue of a living being
US4934999A (en) * 1987-07-28 1990-06-19 Paul Bader Closure for a male urethra
US4830003A (en) * 1988-06-17 1989-05-16 Wolff Rodney G Compressive stent and delivery system
US5413599A (en) * 1988-09-20 1995-05-09 Nippon Zeon Co., Ltd. Medical valve apparatus
US4846836A (en) * 1988-10-03 1989-07-11 Reich Jonathan D Artificial lower gastrointestinal valve
US5116564A (en) * 1988-10-11 1992-05-26 Josef Jansen Method of producing a closing member having flexible closing elements, especially a heart valve
US5800339A (en) * 1989-02-09 1998-09-01 Opticon Medical Inc. Urinary control valve
US5500014A (en) * 1989-05-31 1996-03-19 Baxter International Inc. Biological valvular prothesis
US6168614B1 (en) * 1990-05-18 2001-01-02 Heartport, Inc. Valve prosthesis for implantation in the body
US5411552A (en) * 1990-05-18 1995-05-02 Andersen; Henning R. Valve prothesis for implantation in the body and a catheter for implanting such valve prothesis
US6117425A (en) * 1990-11-27 2000-09-12 The American National Red Cross Supplemented and unsupplemented tissue sealants, method of their production and use
US5116360A (en) * 1990-12-27 1992-05-26 Corvita Corporation Mesh composite graft
US5151105A (en) * 1991-10-07 1992-09-29 Kwan Gett Clifford Collapsible vessel sleeve implant
US5662713A (en) * 1991-10-09 1997-09-02 Boston Scientific Corporation Medical stents for body lumens exhibiting peristaltic motion
US5123919A (en) * 1991-11-21 1992-06-23 Carbomedics, Inc. Combined prosthetic aortic heart valve and vascular graft
US5445626A (en) * 1991-12-05 1995-08-29 Gigante; Luigi Valve operated catheter for urinary incontinence and retention
US6077291A (en) * 1992-01-21 2000-06-20 Regents Of The University Of Minnesota Septal defect closure device
US5382261A (en) * 1992-09-01 1995-01-17 Expandable Grafts Partnership Method and apparatus for occluding vessels
US5409019A (en) * 1992-10-30 1995-04-25 Wilk; Peter J. Coronary artery by-pass method
US5947997A (en) * 1992-11-25 1999-09-07 William Cook Europe A/S Closure prothesis for transcatheter placement
US5411507A (en) * 1993-01-08 1995-05-02 Richard Wolf Gmbh Instrument for implanting and extracting stents
US5306234A (en) * 1993-03-23 1994-04-26 Johnson W Dudley Method for closing an atrial appendage
US5486154A (en) * 1993-06-08 1996-01-23 Kelleher; Brian S. Endoscope
US5392775A (en) * 1994-03-22 1995-02-28 Adkins, Jr.; Claude N. Duckbill valve for a tracheostomy tube that permits speech
US5499995C1 (en) * 1994-05-25 2002-03-12 Paul S Teirstein Body passageway closure apparatus and method of use
US5499995A (en) * 1994-05-25 1996-03-19 Teirstein; Paul S. Body passageway closure apparatus and method of use
US5417226A (en) * 1994-06-09 1995-05-23 Juma; Saad Female anti-incontinence device
US5614204A (en) * 1995-01-23 1997-03-25 The Regents Of The University Of California Angiographic vascular occlusion agents and a method for hemostatic occlusion
US5755770A (en) * 1995-01-31 1998-05-26 Boston Scientific Corporatiion Endovascular aortic graft
US6022312A (en) * 1995-05-05 2000-02-08 Chaussy; Christian Endosphincter, set for releasable closure of the urethra and method for introduction of an endosphincter into the urethra
US5645565A (en) * 1995-06-13 1997-07-08 Ethicon Endo-Surgery, Inc. Surgical plug
US5660175A (en) * 1995-08-21 1997-08-26 Dayal; Bimal Endotracheal device
US6068638A (en) * 1995-10-13 2000-05-30 Transvascular, Inc. Device, system and method for interstitial transvascular intervention
US6355014B1 (en) * 1996-05-20 2002-03-12 Medtronic Percusurge, Inc. Low profile catheter valve
US6027525A (en) * 1996-05-23 2000-02-22 Samsung Electronics., Ltd. Flexible self-expandable stent and method for making the same
US5855587A (en) * 1996-06-13 1999-01-05 Chon-Ik Hyon Hole forming device for pierced earrings
US5855601A (en) * 1996-06-21 1999-01-05 The Trustees Of Columbia University In The City Of New York Artificial heart valve and method and device for implanting the same
US5727593A (en) * 1996-06-26 1998-03-17 Red Valve Company, Inc. Tide gate valve with curvilinear bill
US6123663A (en) * 1996-07-04 2000-09-26 Rebuffat; Carlo Surgical appliance for the treatment of pulmonary emphysema
US6183520B1 (en) * 1996-08-13 2001-02-06 Galt Laboratories, Inc. Method of maintaining urinary continence
US6200333B1 (en) * 1997-04-07 2001-03-13 Broncus Technologies, Inc. Bronchial stenter
US6083255A (en) * 1997-04-07 2000-07-04 Broncus Technologies, Inc. Bronchial stenter
US5957949A (en) * 1997-05-01 1999-09-28 World Medical Manufacturing Corp. Percutaneous placement valve stent
US5855597A (en) * 1997-05-07 1999-01-05 Iowa-India Investments Co. Limited Stent valve and stent graft for percutaneous surgery
US6245102B1 (en) * 1997-05-07 2001-06-12 Iowa-India Investments Company Ltd. Stent, stent graft and stent valve
US6016839A (en) * 1997-06-24 2000-01-25 Red Valve Co., Inc. Air diffuser valve
US20020077696A1 (en) * 1997-09-16 2002-06-20 Gholam-Reza Zadno-Azizi Body fluid flow control device
US20020095209A1 (en) * 1997-09-16 2002-07-18 Gholam-Reza Zadno-Azizi Body fluid flow control device
US5954766A (en) * 1997-09-16 1999-09-21 Zadno-Azizi; Gholam-Reza Body fluid flow control device
US5944738A (en) * 1998-02-06 1999-08-31 Aga Medical Corporation Percutaneous catheter directed constricting occlusion device
US6068635A (en) * 1998-03-04 2000-05-30 Schneider (Usa) Inc Device for introducing an endoprosthesis into a catheter shaft
US6009614A (en) * 1998-04-21 2000-01-04 Advanced Cardiovascular Systems, Inc. Stent crimping tool and method of use
US6240615B1 (en) * 1998-05-05 2001-06-05 Advanced Cardiovascular Systems, Inc. Method and apparatus for uniformly crimping a stent onto a catheter
US6599311B1 (en) * 1998-06-05 2003-07-29 Broncus Technologies, Inc. Method and assembly for lung volume reduction
US6174323B1 (en) * 1998-06-05 2001-01-16 Broncus Technologies, Inc. Method and assembly for lung volume reduction
US6270527B1 (en) * 1998-10-16 2001-08-07 Sulzer Carbomedics Inc. Elastic valve with partially exposed stent
US6020380A (en) * 1998-11-25 2000-02-01 Tap Holdings Inc. Method of treating chronic obstructive pulmonary disease
US6051022A (en) * 1998-12-30 2000-04-18 St. Jude Medical, Inc. Bileaflet valve having non-parallel pivot axes
US6206918B1 (en) * 1999-05-12 2001-03-27 Sulzer Carbomedics Inc. Heart valve prosthesis having a pivot design for improving flow characteristics
US6234996B1 (en) * 1999-06-23 2001-05-22 Percusurge, Inc. Integrated inflation/deflation device and method
US20020062120A1 (en) * 1999-07-02 2002-05-23 Pulmonx Methods, systems, and kits for lung volume reduction
US20020111619A1 (en) * 1999-08-05 2002-08-15 Broncus Technologies, Inc. Devices for creating collateral channels
US6712812B2 (en) * 1999-08-05 2004-03-30 Broncus Technologies, Inc. Devices for creating collateral channels
US20040073201A1 (en) * 1999-08-05 2004-04-15 Broncus Technologies, Inc. Methods for treating chronic obstructive pulmonary disease
US20020087153A1 (en) * 1999-08-05 2002-07-04 Broncus Technologies, Inc. Devices for creating collateral channels
US6610043B1 (en) * 1999-08-23 2003-08-26 Bistech, Inc. Tissue volume reduction
US6416554B1 (en) * 1999-08-24 2002-07-09 Spiration, Inc. Lung reduction apparatus and method
US6258100B1 (en) * 1999-08-24 2001-07-10 Spiration, Inc. Method of reducing lung size
US6402754B1 (en) * 1999-10-20 2002-06-11 Spiration, Inc. Apparatus for expanding the thorax
US6398775B1 (en) * 1999-10-21 2002-06-04 Pulmonx Apparatus and method for isolated lung access
US20020077593A1 (en) * 1999-10-21 2002-06-20 Pulmonx Apparatus and method for isolated lung access
US6510846B1 (en) * 1999-12-23 2003-01-28 O'rourke Sam Sealed back pressure breathing device
US20040073155A1 (en) * 2000-01-14 2004-04-15 Broncus Technologies, Inc. Methods and devices for maintaining patency of surgically created channels in tissue
US6694979B2 (en) * 2000-03-04 2004-02-24 Emphasys Medical, Inc. Methods and devices for use in performing pulmonary procedures
US6679264B1 (en) * 2000-03-04 2004-01-20 Emphasys Medical, Inc. Methods and devices for use in performing pulmonary procedures
US20020007831A1 (en) * 2000-07-19 2002-01-24 Davenport Paul W. Method for treating chronic obstructive pulmonary disorder
US20020026233A1 (en) * 2000-08-29 2002-02-28 Alexander Shaknovich Method and devices for decreasing elevated pulmonary venous pressure
US6527761B1 (en) * 2000-10-27 2003-03-04 Pulmonx, Inc. Methods and devices for obstructing and aspirating lung tissue segments
US20020111620A1 (en) * 2001-02-14 2002-08-15 Broncus Technologies, Inc. Devices and methods for maintaining collateral channels in tissue
US20020112729A1 (en) * 2001-02-21 2002-08-22 Spiration, Inc. Intra-bronchial obstructing device that controls biological interaction with the patient
US20030018344A1 (en) * 2001-07-19 2003-01-23 Olympus Optical Co., Ltd. Medical device and method of embolizing bronchus or bronchiole
US20030018327A1 (en) * 2001-07-20 2003-01-23 Csaba Truckai Systems and techniques for lung volume reduction
US6743259B2 (en) * 2001-08-03 2004-06-01 Core Medical, Inc. Lung assist apparatus and methods for use
US20030050648A1 (en) * 2001-09-11 2003-03-13 Spiration, Inc. Removable lung reduction devices, systems, and methods
US20030083671A1 (en) * 2001-10-25 2003-05-01 Spiration, Inc. Bronchial obstruction device deployment system and method

Cited By (55)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8137302B2 (en) * 2007-03-12 2012-03-20 Pulmonx Corporation Methods and systems for occluding collateral flow channels in the lung
US20080228130A1 (en) * 2007-03-12 2008-09-18 Pulmonx Methods and systems for occluding collateral flow channels in the lung
US20100229863A1 (en) * 2007-03-16 2010-09-16 Dolphys Technologies, B.V. Jet ventilation catheter, in particular for ventilating a patient
US10406308B2 (en) * 2007-03-16 2019-09-10 Ventinova Technologies B.V. Jet ventilation catheter, in particular for ventilating a patient
US10118007B2 (en) 2007-03-16 2018-11-06 Ventinova Technologies B.V. Jet ventilation catheter, in particular for ventilating a patient
US10470822B2 (en) 2008-04-29 2019-11-12 Virginia Tech Intellectual Properties, Inc. System and method for estimating a treatment volume for administering electrical-energy based therapies
US11453873B2 (en) 2008-04-29 2022-09-27 Virginia Tech Intellectual Properties, Inc. Methods for delivery of biphasic electrical pulses for non-thermal ablation
US10537379B2 (en) 2008-04-29 2020-01-21 Virginia Tech Intellectual Properties, Inc. Irreversible electroporation using tissue vasculature to treat aberrant cell masses or create tissue scaffolds
US11890046B2 (en) 2008-04-29 2024-02-06 Virginia Tech Intellectual Properties, Inc. System and method for ablating a tissue site by electroporation with real-time monitoring of treatment progress
US11737810B2 (en) 2008-04-29 2023-08-29 Virginia Tech Intellectual Properties, Inc. Immunotherapeutic methods using electroporation
US9598691B2 (en) 2008-04-29 2017-03-21 Virginia Tech Intellectual Properties, Inc. Irreversible electroporation to create tissue scaffolds
US11655466B2 (en) 2008-04-29 2023-05-23 Virginia Tech Intellectual Properties, Inc. Methods of reducing adverse effects of non-thermal ablation
US9867652B2 (en) 2008-04-29 2018-01-16 Virginia Tech Intellectual Properties, Inc. Irreversible electroporation using tissue vasculature to treat aberrant cell masses or create tissue scaffolds
US11607271B2 (en) 2008-04-29 2023-03-21 Virginia Tech Intellectual Properties, Inc. System and method for estimating a treatment volume for administering electrical-energy based therapies
US10117707B2 (en) 2008-04-29 2018-11-06 Virginia Tech Intellectual Properties, Inc. System and method for estimating tissue heating of a target ablation zone for electrical-energy based therapies
US11272979B2 (en) 2008-04-29 2022-03-15 Virginia Tech Intellectual Properties, Inc. System and method for estimating tissue heating of a target ablation zone for electrical-energy based therapies
US11254926B2 (en) 2008-04-29 2022-02-22 Virginia Tech Intellectual Properties, Inc. Devices and methods for high frequency electroporation
US10154874B2 (en) 2008-04-29 2018-12-18 Virginia Tech Intellectual Properties, Inc. Immunotherapeutic methods using irreversible electroporation
US10238447B2 (en) 2008-04-29 2019-03-26 Virginia Tech Intellectual Properties, Inc. System and method for ablating a tissue site by electroporation with real-time monitoring of treatment progress
US10245105B2 (en) 2008-04-29 2019-04-02 Virginia Tech Intellectual Properties, Inc. Electroporation with cooling to treat tissue
US10959772B2 (en) 2008-04-29 2021-03-30 Virginia Tech Intellectual Properties, Inc. Blood-brain barrier disruption using electrical energy
US10272178B2 (en) 2008-04-29 2019-04-30 Virginia Tech Intellectual Properties Inc. Methods for blood-brain barrier disruption using electrical energy
US10286108B2 (en) 2008-04-29 2019-05-14 Virginia Tech Intellectual Properties, Inc. Irreversible electroporation to create tissue scaffolds
US10828085B2 (en) 2008-04-29 2020-11-10 Virginia Tech Intellectual Properties, Inc. Immunotherapeutic methods using irreversible electroporation
US10828086B2 (en) 2008-04-29 2020-11-10 Virginia Tech Intellectual Properties, Inc. Immunotherapeutic methods using irreversible electroporation
US10245098B2 (en) 2008-04-29 2019-04-02 Virginia Tech Intellectual Properties, Inc. Acute blood-brain barrier disruption using electrical energy based therapy
US8444635B2 (en) * 2008-11-19 2013-05-21 Samuel Victor Lichtenstein Methods for selectively heating tissue
US20100125271A1 (en) * 2008-11-19 2010-05-20 Samuel Victor Lichtenstein System for treating undesired body tissue
US10292755B2 (en) 2009-04-09 2019-05-21 Virginia Tech Intellectual Properties, Inc. High frequency electroporation for cancer therapy
US11382681B2 (en) 2009-04-09 2022-07-12 Virginia Tech Intellectual Properties, Inc. Device and methods for delivery of high frequency electrical pulses for non-thermal ablation
US10448989B2 (en) 2009-04-09 2019-10-22 Virginia Tech Intellectual Properties, Inc. High-frequency electroporation for cancer therapy
US11638603B2 (en) 2009-04-09 2023-05-02 Virginia Tech Intellectual Properties, Inc. Selective modulation of intracellular effects of cells using pulsed electric fields
US11707629B2 (en) 2009-05-28 2023-07-25 Angiodynamics, Inc. System and method for synchronizing energy delivery to the cardiac rhythm
US9895189B2 (en) 2009-06-19 2018-02-20 Angiodynamics, Inc. Methods of sterilization and treating infection using irreversible electroporation
US20110245665A1 (en) * 2010-03-30 2011-10-06 Angiodynamics, Inc. Bronchial catheter and method of use
US8425455B2 (en) * 2010-03-30 2013-04-23 Angiodynamics, Inc. Bronchial catheter and method of use
US20120053566A1 (en) * 2010-08-25 2012-03-01 Terumo Kabushiki Kaisha Method for treatment of emphysema
US8579785B2 (en) 2011-05-10 2013-11-12 Nazly Makoui Shariati Source/seed delivery surgical staple device for delivering local source/seed direclty to a staple margin
US10702326B2 (en) 2011-07-15 2020-07-07 Virginia Tech Intellectual Properties, Inc. Device and method for electroporation based treatment of stenosis of a tubular body part
US9757196B2 (en) 2011-09-28 2017-09-12 Angiodynamics, Inc. Multiple treatment zone ablation probe
US11779395B2 (en) 2011-09-28 2023-10-10 Angiodynamics, Inc. Multiple treatment zone ablation probe
JP2016534787A (en) * 2013-10-25 2016-11-10 マーケイター メドシステムズ, インコーポレイテッド Maintaining bronchial patency by cytotoxicity, cytostatics, or local delivery of antineoplastic agents
US10842969B2 (en) 2013-10-25 2020-11-24 Mercator Medsystems, Inc. Systems and methods of treating malacia by local delivery of hydrogel to augment tissue
US11406820B2 (en) 2014-05-12 2022-08-09 Virginia Tech Intellectual Properties, Inc. Selective modulation of intracellular effects of cells using pulsed electric fields
US10471254B2 (en) 2014-05-12 2019-11-12 Virginia Tech Intellectual Properties, Inc. Selective modulation of intracellular effects of cells using pulsed electric fields
US10363290B2 (en) 2014-10-17 2019-07-30 Kodiak Sciences Inc. Butyrylcholinesterase zwitterionic polymer conjugates
US10694972B2 (en) 2014-12-15 2020-06-30 Virginia Tech Intellectual Properties, Inc. Devices, systems, and methods for real-time monitoring of electrophysical effects during tissue treatment
US11903690B2 (en) 2014-12-15 2024-02-20 Virginia Tech Intellectual Properties, Inc. Devices, systems, and methods for real-time monitoring of electrophysical effects during tissue treatment
US10980737B1 (en) 2016-03-08 2021-04-20 Samuel Victor Lichtenstein System for treating unwanted tissue using heat and heat activated drugs
US11723710B2 (en) 2016-11-17 2023-08-15 Angiodynamics, Inc. Techniques for irreversible electroporation using a single-pole tine-style internal device communicating with an external surface electrode
US11607537B2 (en) 2017-12-05 2023-03-21 Virginia Tech Intellectual Properties, Inc. Method for treating neurological disorders, including tumors, with electroporation
US11925405B2 (en) 2018-03-13 2024-03-12 Virginia Tech Intellectual Properties, Inc. Treatment planning system for immunotherapy enhancement via non-thermal ablation
US11311329B2 (en) 2018-03-13 2022-04-26 Virginia Tech Intellectual Properties, Inc. Treatment planning for immunotherapy based treatments using non-thermal ablation techniques
CN108837283A (en) * 2018-04-12 2018-11-20 上海市东方医院 Stem bronchi cell precise positioning slow-released system
US11931096B2 (en) 2021-06-14 2024-03-19 Angiodynamics, Inc. System and method for electrically ablating tissue of a patient

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EP1482863A1 (en) 2004-12-08
US20030228344A1 (en) 2003-12-11
AU2003220124A1 (en) 2003-09-22
US7412977B2 (en) 2008-08-19
WO2003075796A2 (en) 2003-09-18
US20060283462A1 (en) 2006-12-21

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