US20060004400A1 - Method of treating a lung - Google Patents

Abstract

This invention provides methods for treating a lung, such as to treat a patient suffering from COPD. One aspect of the invention provides a method of treating a lung including the steps of: endotracheally delivering an expandable member (such as an inflatable member) to an air passageway of the lung with a delivery system; expanding the expandable member to make contact with a wall of the air passageway; and providing an open lumen through the expandable member to provide access to a portion of the lung distal to the expandable member. Some embodiments add the step of plugging the lumen, such as by contacting a plug with the expandable member or closing a port in the lumen. Some embodiments of the invention also include the step of reducing collateral flow around the expandable member and/or reducing collateral flow to lung regions distal to the expandable member, such as by delivering a collateral flow blocking agent, through the lumen. In some embodiments, the method includes the step of causing the portion of the lung distal to the expandable member to reduce volume, such as by compressing the lung portion.

Description

CROSS-REFERENCE
• This application claims the benefit of U.S. Provisional Application No. 60/580,565, filed Jun. 16, 2004, which is incorporated herein by reference in its entirety.
BACKGROUND OF THE INVENTION
• The primary role of the lung is to perform the function of breathing which assists in the intake of oxygen and removal of carbon dioxide from the body. The oxygen in air is inhaled through the mouth and trachea to the main bronchi. The bronchi divide at the end of the trachea into the left and right main bronchi and these respectively divide into bronchial branches, which “feed” the three lobes of the lung on the right and two on the left. These bronchi continue to subdivide into bronchioles (smaller bronchi), over twenty three times in total. The over 100,000 bronchioles get smaller in diameter and ultimately terminate in over 300 million air sacs, called alveoli. The alveoli, which are clustered like grapes, are approximately 0.3 mm in diameter and provide a huge surface area for gas exchange to take place. There are capillaries surrounding the alveoli and this is where the inspired oxygen is diffused into the vascular system of the body. Likewise, toxic CO₂is diffused into the alveoli from the capillaries and is removed from the body during expiration.
• With no external loads, the lung structure is approximately the size of a grapefruit. It is expanded larger in the chest cavity with a physiologic level of vacuum that stretches it to the chest wall. As we inhale, we are forcing the lung cavity to a larger condition by flexing the ribs and lowering the diaphragm. The vacuum around the lungs pull the lung volume larger as the chest volume is increased; air pressure in the lung is reduced and atmospheric air pressure forces air into the lung. During expiration, the diaphragm and ribs are relaxed to allow the elastic properties of the lung to pull the chest cavity to a smaller volume and to force air out of the lungs.
• Chronic Obstructive Pulmonary Disease (“COPD”) is a progressive disease that causes lung parenchyma to lose elastic properties and lose surface area that is required to exchange gas such as O₂and CO₂. Lung tissue is eroded to leave large holes, typically in the upper lobes. The holes do not contribute to the elastic pulling forces required during expiration. Areas adjacent to the holes are more highly stressed. The stressed tissue stretches and loses recoil properties. These stretched regions fail to pull on and thus fail to suspend the major airways in a radial fashion to hold them open. As the disease progresses, the patient will eventually need to force expiration, which causes the major airways to collapse and block air flow. This effect is exacerbated with additional applied expiration pressure since the airways are ill-supported. During inspiration, these unsupported regions fill preferentially since they are floppy and have no resistance to expand (no elasticity). They preferentially consume the oxygenated air even though there is little remaining surface area to exchange O₂to the bloodstream.
• Normal lungs rarely present with collateral flow paths between lobules and between major lobes of the lung in the form of pores and leak paths. In COPD patients, damaged tissue forms vacuoles or holes, which grow in size (e.g., 2 μm to over 500 μm) and multiply to allow flow from numerous airway paths to supply these regions with air. As this tissue degradation occurs, numerous holes communicate with each other, and eventually the lobes communicate with each other, through means other than the normal airways.
• Lung volume reduction surgery (LVRS) is a procedure where the chest is opened and a target region of lung is cut out. This accomplishes several things. It removes damaged regions that contribute very little to gas exchange. More importantly, it removes lung volume so that the healthy portion of the lung that remains can be expanded beyond typical physiologic volume (expand healthy functioning alveoli) to fill the chest cavity with functioning lung. The procedure increases surface area of healthy tissue to increase gas exchange. It also stretches the remaining tissue to restore support of the major airways, and it improves expiration mechanics. The procedure also cuts off blood circulation through the removed regions that had little effective gas exchange. This prevents CO₂laden blood from mixing back into the left side of the heart and to the arteries.
• While the LVRS procedure is ideal in many ways, it requires major chest intervention that requires cutting the chest plate or major spreading of ribs. Pain associated with this causes interruption of normal breathing and difficulty to revive the patient from forced ventilation to normal breathing after the procedure. The procedure presents with high mortality rates and long recovery times.
• Another risk with LVRS is associated with cutting too much volume out. By cutting more than approximately one third of the expanded lung volume per side (one third of the chest cavity volume per side), the tissue may be over-stressed and rupture with expansion. These ruptures culminate as spontaneous pneumothorax events (leaks that vent vacuum holding the lung up to the chest wall and allow collapse of the lung). Also, adhesions between the lung and chest wall that occur naturally present stress points upon expansion that can cause ruptures.
• Tension pneumothorax complications can also be caused by the surgery. This is a condition that causes central chest organs to shift. The imbalance of force in the chest after expanding highly elastic lung tissue pulls the mediastinal region of the central thorax sufficiently to actually shift large vessels and cause flow restrictions. This condition can be very serious and warrant further surgeries.
• If lung volume reduction (“LVR”) could be accomplished less invasively, the complications and morbidity associated with the surgery could be nearly eliminated. In addition, the procedure would be open to many more patients who might not be able to or not desire to undergo a major thoracic surgical procedure. Current less invasive approaches to LVR have met with limited success, however.
• Bronchoscopically-placed LVR devices have been described which may be implanted into the lungs to block airways in an attempt to create a volume reduction effect distal to the blocking device to emulate LVRS. For example, plug and one-way air directing devices are introduced to block an area of the lung to cause oxygen depletion distally to cause volume reduction through a process known as atelectasis. These devices may provide some relief to the patient by blocking preferential filling of damaged lung tissue. All of these devices are inserted through the working channel of a flexible bronchoscope and are placed only as far as the third to the fifth subdivision or segment of bronchi.
• However, there are several problems with these earlier devices as they are currently used. Current blocking devices do not facilitate access to distal regions of the lung after deployment to allow for reoccurring interventions or treatments.
• In addition, current bronchoscope working channels are typically 2.0 mm in diameter; the blocking and one-way valve devices must be expanded to seat in airways that are as large as 15 mm in diameter. Therefore, the expansion ratio for these devices needs to sometimes be as high as 750%. Covered devices that are stretched to this extent are typically not robust air leak seals. Current devices are made small enough to fit down the working channel of the bronchoscope so they can be pushed out to self deploy. The devices are typically made of Nitinol alloys with long elastic range that drives recovery to an expanded state. This also requires that the device be scaled down to such a small diameter profile that the self expansion forces are extremely low to anchor the device and the covering materials must be thin and therefore fragile.
• Moreover, these devices block air from flowing in the major airways but are not effective if collateral flow paths exist. The collateral paths allow the distal region to fill and hyper-inflate. When collateral flow is not an issue, these devices block O₂and CO₂exchange, and yet the blood flow in the region still carries CO₂laden blood through the lungs to mix with systemic blood flow. Finally, uncontrolled atelectasis beyond a one third volume reduction may cause tension pneumothorax complications and stress ruptures within the lung wall, causing lung collapse.
SUMMARY OF THE INVENTION
• This invention provides methods for treating a lung, such as to treat a patient suffering from COPD. One aspect of the invention provides a method of treating a lung including the steps of: endotracheally delivering an expandable member (such as an inflatable member) to an air passageway of the lung with a delivery system; expanding the expandable member to make contact with a wall of the air passageway; and providing an open lumen through the expandable member to provide access to a portion of the lung distal to the expandable member. Some embodiments add the step of detaching the expandable member from the delivery system. Some embodiments add the step of contracting the expandable member after the expanding step, such as by deflating the expandable member. In some embodiments, the expandable member is repositioned and reexpanded after the repositioning step.
• Some embodiments add the step of plugging the lumen, such as by contacting a plug with the expandable member or closing a port in the lumen. Some embodiments include the step of unplugging the lumen, such as by moving a plug proximally or opening a port in the lumen.
• In some embodiments, the method includes the step of detecting fluid flow around the expandable member and/or detecting collateral fluid flow to the lung region distal to the expandable member. The step of detecting collateral flow may include: sealing an air passageway in the lung at a point proximal to the expanding member; introducing a detectable gas into a region between the proximal point and the expanding member; and sensing for the presence of the detectable gas distal to the expanding member. In embodiments in which the expandable member is a first expandable member, the step of sealing the air passageway includes the step of sealing the air passageway with a second expandable member having an open lumen, and sensing comprises sampling for detectable gas through the second expandable member open lumen; with the method further including the step of detaching the second expandable member from a delivery system. In some embodiments, the method includes the step of deploying a plurality of expanding members to isolate the portion of the lung, with the sealing step including the step of sealing the air passageway at a point proximal to the plurality of expanding members. In some embodiments the sensing step may be performed at a proximal end of a device delivery catheter and/or may include sensing gas flowing through the open lumen in the expandable member.
• Some embodiments of the invention include the step of reducing collateral flow around the expandable member and/or reducing collateral flow to lung regions distal to the expandable member, such as by delivering a collateral flow blocking agent through the lumen. The method may include the step of unplugging the lumen prior to the step of delivering a collateral flow blocking agent.
• Some embodiments include the step of causing the portion of the lung distal to the expandable member to reduce volume, such as by compressing the lung portion. The method may also include the step of promoting adhesion of tissue within the lung portion, such as by introducing an adhesion inducing material into the lung portion.
• In some embodiments, the method includes the step of permitting fluid to enter the lung portion when a difference between fluid pressure within the lung portion and fluid pressure in another portion of the lung exceeds about 2 mm Hg, about 10 mm Hg, about 20 mm Hg, or about 50 mm Hg.
INCORPORATION BY REFERENCE
• All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.
BRIEF DESCRIPTION OF THE DRAWINGS
• The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:
• FIG. 1 is a perspective view of an intra-bronchial device and delivery system according to one embodiment disposed within a patient's lung.
• FIG. 2 is a detail view of an intra-bronchial device and delivery system according to another embodiment of the invention.
• FIG. 3 is a cross-sectional view of an intra-bronchial device and deployment system according to yet another embodiment of the invention.
• FIG. 4 is a cross-sectional view of an intra-bronchial device and deployment system according to still another embodiment of the invention.
• FIG. 5 is a cross-sectional view of an intra-bronchial device and deployment system according to yet another embodiment of the invention.
• FIG. 6 shows the use of an intra-bronchial device to treat a patient.
• FIG. 7 shows yet another intra-bronchial device implanted in a patient's lung.
• FIG. 8 shows an agent dispensing mechanism for possible use with this invention.
• FIG. 9 shows a plug and delivery mechanism for use with an intra-bronchial device.
• FIG. 10 is partial cross-sectional view of a plug and delivery mechanism for use with an intra-bronchial device.
• FIG. 11 is a cross-sectional view of the intra-bronchial device ofFIG. 10 showing the plug in place.
• FIG. 12 is a cross-sectional view of another embodiment of an intra-bronchial device and delivery mechanism with a plug in place.
• FIG. 13 is a cross-sectional view of yet embodiment of an intra-bronchial device and delivery mechanism.
• FIG. 14 is a cross-sectional view of still embodiment of an intra-bronchial device and delivery mechanism with a tool passing through the device's plug.
• FIG. 15 is a schematic view of the plug of the device ofFIG. 14 in a closed position.
• FIG. 16 is a schematic view of the plug of the device ofFIG. 14 in an open position.
• FIG. 17 shows another embodiment of an intra-bronchial device opening mechanism in a closed position.
• FIG. 18 shows the embodiment ofFIG. 17 in an open position.
• FIG. 19 is an elevational view another embodiment of an intra-bronchial device opening mechanism.
• FIG. 20 is an elevational view of a ring for use with the mechanism ofFIG. 19.
• FIG. 21 is a perspective view of a blade for use with the mechanism ofFIG. 19.
• FIG. 22 is an elevational view of an actuating ring for use with the mechanism ofFIG. 19.
• FIG. 23 shows the mechanism ofFIG. 19, partially assembled.
• FIG. 24 is a partial perspective and partial cross-sectional view of yet another embodiment of an intra-bronchial device and deployment mechanism.
• FIG. 25 is a cross-sectional view of the embodiment ofFIG. 25 being expanded by the deployment mechanism.
• FIG. 26 is a perspective view of the intra-bronchial device ofFIG. 24 and a deflation mechanism.
• FIG. 27 is a cross-sectional view of the intra-bronchial device and deflation mechanism ofFIG. 26.
• FIG. 28 is a perspective view of a plug for use with the intra-bronchial device ofFIG. 24.
• FIG. 29 shows the plug ofFIG. 28 in place within an intra-bronchial device.
• FIG. 30 shows the use of a plurality of intra-bronchial devices to treat a patient's lung.
• FIG. 31 is a cross-sectional view of a pressure relief system for use with the invention.
• FIG. 32 shows the pressure relief system ofFIG. 31 in an open position.
DETAILED DESCRIPTION OF THE INVENTION
• The following tools may be used to treat COPD patients in a minimally invasive manner: Imaging and embolic devices to block blood flow through the target lung tissue; devices to help prepare the lung for devices and agents; a side wire delivery system that is advanced alongside the bronchoscope to guide and release several implants without removing the scope; a lung volume reduction implant device (Intra-Bronchial Device or IBD) that is controllably coupled to a delivery catheter that includes a working channel that runs through the center of the catheter and the implant; an inflator catheter that fits down the middle of the IBD and delivery catheter to inflate the IBD; an IBD plug element and delivery system; a deflation device to reposition or remove the IBD; a collateral flow detecting device; collateral flow blocking agents; adhesion promoting agents to maintain atelectasis; and a lung tissue compressing system. These items provide a reliable minimally invasive procedure for COPD patients and enable follow-on procedures to maintain a high degree of restored lung mechanics and gas exchange without causing tissue stress or blood chemistry complications that occur with current technology.
• Perfusion of air flow in the lungs can be imaged using MRI imaging equipment while the patient breathes water saturated air or agents that are comprised primarily of water. Moving water molecules produce a strong signal, whereas static air and water will not produce a signal. This distinction is important to determine where the degraded lung hole regions reside. Hyper-polarized gases such as helium, helium-3 and xenon-129 also work extremely well in the lung to find damaged tissue and identify collateral flow. Computed tomography has also worked very well to identify damaged tissue in lungs. These imaging modalities can be used in real time before, after or during the procedure to check the patient's condition. They can also be used to guide intervention in an iterative fashion between imaging sessions or in real time. Ventilation Scans via SPECT (Xe-133) may also be used.
• Specially-designed catheters can introduce lavage agents to the lung to wash mucus and surfactants. Mucus and naturally occurring surfactants trap solids and agents to block collateral flow paths and promote adhesions within the targeted lung region or portion. Cleaning these regions to remove fluids, mucus and surfactants improves distribution of these agents and enhances adhesion of glue compositions that may be infused into the region.
• Fluoroscopic x-ray imaging is very useful to determine where blood flows through COPD damaged lung tissue. By introducing radiopaque high contrast materials into the blood stream, and with the use of digital subtraction techniques, the flow paths can be imaged very clearly. Embolic devices and agents that are used to treat peripheral vasculature may be utilized to embolize the pulmonary veins and arteries that normally exchange gases through the regions of the lung that are going to be or have been blocked and treated by the devices and agents of this invention. Exemplary embolic devices include embolic polymeric implants such as Dacron fibers, metallic coils, alcohols, glutaraldehyde, gels, foams, and glue such as cyanoacrylates, PEG based glues and glutaraldehyde based glues.
• Embolizing this pulmonary vasculature will reduce or prevent CO₂mixing into the heart. Pressure probes such as piezo, thermal transfer flow wires or micro-electrical-mechanical system (MEMS) wave interference pressure and flow transducers may be introduced or implanted to monitor pulmonary hypertension as the blood flow paths are being blocked and to monitor results over a period of time. That way the procedure can be limited to prevent undue blood back pressure on the heart. The lung tissue in the region will still be supplied with oxygenated blood from a separate artery system that feeds pulmonary tissue. Implantable MEMS devices can be used to measure pressure, temperature, strain and stress on tissues that are affected by the lung volume reduction procedure. MEMS transducers are passive (no electronics or batteries on board) implantable devices that can be queried using magnetic wave transmitter/receiver probes outside the body.
• The design of the current invention resolves most of the deficiencies and issues related to the devices described above. The intra-bronchial device is placed in segments of bronchi that feed the diseased areas of the lung. As many as five to ten intra-bronchial devices could be placed in the bronchi of any one patient. The goal is to cause atelectasis in these areas and cumulatively expand the healthy portions of the lung, thereby replicating the results and benefits of LVRS, but without the morbidity and mortality.
• FIG. 1 shows anintra-bronchial device10 according to one embodiment of this invention disposed within abronchial tube12 of a patient's lung.Device10 is in contact with the inner wall ofbronchial tube12 and is preferably immobilized through a friction fit. In this embodiment,device10 includes anexpandable balloon14 with acentral lumen16 through which other devices or tools (such asguidewire18, as shown) may be passed.Device10 may be delivered and deployed via acatheter20 disposed within a working channel of abronchoscope22.
• FIG. 2 shows details of another embodiment of the invention.Device23 may be delivered and deployed via acatheter20 disposed within a working channel of abronchoscope22.Delivery catheter20 is connected to aninflatable balloon25 ofdevice23 via acoupler24 that may be connected and disconnected as desired. In this embodiment,catheter20 has a braided shaft, andballoon25 is a folded semi-elastic balloon made from polyethylene, polyvinyl, latex, etc. (Polyethylene is particularly preferable due to the its tissue ingrowth inhibition properties.)Balloon25 may also be a uniform elastic balloon made from, e.g., silicone or polyurethane. The device has a ring26 (made, e.g., from nitinol, stainless steel, polymer, Teflon, ceramic, composites, high density polyethylene, low density polyethylene, nylon, polyurethane) at its distal end marking the outlet of the balloon's central lumen.Catheter20 may be used to deliver the device to a target site within the patient'sbronchial tube12 and/or to inflateballoon25 once at the target site.
• FIG. 3 shows one embodiment of a balloon deployment mechanism. In this embodiment,catheter28 is coupled toballoon30 via a threadedcoupler32 cooperating withinternal threads34 within thecentral lumen36 ofballoon30. Once in place at the target site, a fluid (such as a hydrogel, silicone, water, saline solution, air, glue, multipart catalytic solutions, fluidized metal, suspended metal, fluoroscopic contrast medium, sodium HA) can be injected throughcatheter28 intolumen36. Aseal38 at the distal end ofcoupler32 prevents the injection fluid from passing through the distal end ofballoon lumen36. Instead, the fluid passes through one ormore ports40 in the wall oflumen36 intoballoon30 to inflate the balloon. A oneway flap42 prevents the fluid from passing back intolumen36 once the injection fluid pressure source is removed. After inflation of the balloon,catheter28 may be rotated to disengagecoupler32 and to removecoupler32 and seal38 from the balloon. As shown inFIG. 3, the target site for the balloon is a bronchial wall site betweenadjacent cartilage areas44 and46, enabling the inflation ofballoon30 to distend the bronchial wall to enhance the balloon's grip on the wall.
• FIG. 4 shows an alternative balloon deployment mechanism. In this embodiment, acatheter50 is coupled toballoon52 via a threadedcoupler54 cooperating with internal threads within thecentral lumen56 of the balloon. Afiller tube58 extends throughcatheter50 intolumen56 and through aport58 formed in the lumen wall to push open aflap60 to communicatefiller tube58 with the inside ofballoon52.Filler tube58 may be used to inflate the balloon with an injection fluid, such as one of the fluids listed above.Filler tube58 may also be used to remove fluid from the balloon to deflate the balloon for removal or repositioning of the balloon. After inflation of the balloon,catheter50 may be rotated to disengagecoupler54 fromballoon52.
• FIG. 5 shows yet another embodiment of the invention. In this embodiment,balloon70 is inflated so that it does not substantially distend the bronchial tube walls.Balloon70 is also longer than the balloons of the previous embodiments, extending, e.g., beyond adjacent cartilage sections of the bronchial tube wall. The balloon's configuration allows it to distort as the bronchial expands and contracts during the patient's breathing cycle.
• Balloon70 may be inflated using, e.g., the balloon deployment mechanisms described above with respect toFIGS. 3 and 4. Aport72 communicates the device'sinner lumen73 with the inside of the balloon through aflap74, as described above.
• FIG. 5 also shows yet another mechanism for releasably coupling a catheter to the device.Catheter76 has a splitdistal end78 with anannular engagement structure80 configured to engage with anannular channel82 formed on the proximal end of the device. Acoupler sleeve84 surroundingcatheter76 may be retracted proximally to permit the splitdistal end78 to expand outwardly, thereby disengaging the device, and may be advanced distally to pulldistal end78 radially inward to engage the device.
• FIG. 6 shows the use of an intra-bronchial device to treat a patient. An expandable intra-bronchial device100 (such as one of the balloon devices described above) has been deployed at a target site in a patient'sbronchial tube102 via, e.g., adelivery catheter104. Asecond catheter106 has been passed throughcatheter104 and the central lumen ofdevice100 to a treatment site108 further down into the patient's lung. The distal end110 ofcatheter106 may be lodged in the patient's bronchial at the treatment site.Catheter106 may then be used to induce atelectasis via, e.g., suction, vacuum, lavage with an anti-surfactant agent, mechanical compression, sclerosing agents (such as alcohol or other fluids or aerosols), etc.
• FIG. 7 shows the use of an intra-bronchial device to treat a patient in another manner. An expandable intra-bronchial device120 (such as one of the balloon devices described above) has been deployed at a target site in a patient'sbronchial tube122. A plurality ofwires124 are delivered through the central lumen ofdevice120 to place the wires' distal ends126 within a lobe orsection128 of the patient's lung. The wire ends are glued or anchored to the tissue withinlobe128. The proximal ends ofwires124 have one-way locks130 that may be pulled proximally through the device's120 central lumen after anchoring of the distal ends to collapselobe128 inwardly.Locks130hold wires124 in position, as shown.
• FIG. 8 shows an agent-dispensing mechanism for possible use with this invention. Adelivery catheter131 is mounted on aguidewire132 via asideport133. Agents such as glue or other substances may be delivered fromsyringe134 viacatheter131 through an intra-bronchial device to the lung region distal to the intra-bronchial device. (The length ofcatheter131 is shortened inFIG. 8 for illustration purposes. The catheter must be long enough for the syringe to be outside the patient's body and the distal end of the syringe extending into and through the intra-bronchial device.)
• After treatment of lung tissue distal to an intra-bronchial device, the device's central lumen may be closed. The device's central lumen may thereafter be opened should access to lung tissue distal to the device be desired.FIG. 9 shows one embodiment of anintra-bronchial device plug140 for deployment viacatheter142 to seal device144 (such as one of the balloon devices described above). Atether146 may be used to disengageplug140 after deployment indevice144.
• FIGS. 10 and 11 show another embodiment of anintra-bronchial device plug150 being delivered to device152 (such as one of the balloon devices described above) viadelivery catheter154.Plug150 is releasably held to a plug pusher orcatheter156 by atether158.Plug150 hasthreads160 that engage withthreads162 indevice152 whenplug150 is rotated bycatheter156 to seal the central lumen ofdevice152.
• FIG. 12 shows yet another embodiment of aplug170 for an intra-bronchial device172 (such as the balloon device described above with respect toFIG. 5).Plug170 has a stem174 (formed, e.g., from metal or plastic) passing through anocclusion element176 formed from an elastomeric polymer or gel. Plug170 may be advanced into position by compressing it through a narrowedproximal end182 of thecentral lumen184 ofdevice172 through the action of a pusher or catheter (not shown) coupled to acoupling surface180 formed on the proximal end ofstem174. To reopen thecentral lumen184 ofdevice172, plug170 may be advanced distally or retracted proximally.
• In alternative embodiments, the plug may attach to the device using notches, luer locks, press fit, tapers, etc.
• FIG. 13 shows yet anotherplug200 for anintra-bronchial device202. In this embodiment, plug200 forms an elastomeric seal around acentral opening204 through which tools or other devices may be inserted. Plug200 may be integral withdevice202 so that it does not have to be delivered separately fromdevice202.
• FIGS. 14-16 show anintra-bronchial device210 with anintegral seal212 having acentral opening213 formed by the cooperation of a plurality offlaps216.Seal212 may be integral with the central tube214 ofdevice210. Central tube214 and seal212 may be formed from an elastic metal or polymer or rubber to allowflaps216 to bend (as shown inFIG. 16) to permit devices or tools to be passed throughopening213.Flaps216 return to their sealing position ofFIG. 15 after the tool or device (such as guide wire215) has been removed.
• FIGS. 11-14 show plugged intra-bronchial devices attached to their respective catheters using releasable coupling mechanisms such as those described above with respect toFIG. 5. The coupling mechanisms help hold the device in place at the target site while the plug is being inserted.
• It may also be necessary after deployment of an intra-bronchial device to deflate the balloon and remove the device from the patient. In addition to the deflation method described above with respect toFIG. 4, deflation may be accomplished by, e.g., puncturing the balloon. Once the balloon is deflated, the device may be coupled to a catheter as shown inFIGS. 11-14 and removed from the patient and/or deployed at a different site.
• FIGS. 17-23 show alternative designs for intra-bronchial device openings formed, e.g., as actuatable iris-type shutters. As shown in detail in the alternative embodiment ofFIGS. 19-23, the shutter is formed from a plurality ofblades220 rotatably mounted on aring222 viapins224 inserted intoholes226 formed in the ring. The blades are arranged in an overlapping arrangement as shown inFIG. 19. The shutter is operated by anactuating ring228 havingslots230 interacting with a second set ofpins232 onblades220. Rotation ofring228 in one direction opens the shutter, and rotation ofring228 in the other direction closes the shutter.FIGS. 17 and 18 show a five-blade shutter design, whileFIGS. 19-23 show an eight-blade shutter design.
• FIGS. 24-29 show another embodiment of the invention (outside of the lung, for ease of illustration).Intra-bronchial device250 has acentral shaft252 surrounded by an expandable member, such asballoon254.Shaft252 has anopening256 communicating the shaft's central lumen with the interior ofballoon254 via aflexible flap valve258.Device250 may be delivered to an air passageway of a patient's lung using a delivery catheter in, e.g., a manner described above.
• Aninflation catheter260 may be used to inflateballoon254 from the unexpanded condition shown inFIG. 24 to the expanded state ofFIG. 25.Inflation catheter260 may be inserted into the patient through the delivery catheter (delivered together with thedevice250 or after it) or independent of the delivery catheter. Thedistal tip262 ofinflation catheter260 has a pointed end to help align the inflation catheter with the intra-bronchial device's shaft.Inflation catheter260 has anopening264 withseals266 and268 on either side. When inserted intoshaft252, opening264 aligns with the shaft'sopening256 when ashoulder270 oninflation catheter260 meets ashoulder272 formed on the proximal end ofdevice250.Seals266 and268 ensure that pressurized fluid delivered todevice250 viainflation catheter260 entersballoon254 viaopenings264 and256 andflap valve258 to inflateballoon254. When the inflation pressure ceases,flap valve258 closes to maintainballoon254 in its inflated state. Thedevice250 may be inflated in multiple steps, as needed.
• The inflation catheter may protrude through the distal end of the intra-bronchial device. By extending the inflation catheter tip length, we can provide a path to thread a delivery wire through the distal tip and out a side port to make the intra-bronchial device, intra-bronchial device delivery catheter and inflation catheter a rapid exchange system. Rapid exchange systems are catheter systems that can be threaded onto a short section of wire before the user can gain control of the wire end and the catheter system. By installing a catheter that does not provide a side port onto a wire, the user must advance the entire length of the catheter onto the wire before the user gains control of the end of the wire again. By providing a side port to any of the catheter devices required in the lung volume reduction kit, we enable the use of wires that are only long enough to extend outside the scope or patient and that provide for some extra length to be threaded into one or more devices and out the side port. Alternatively, the wire may be introduced into and out of a side port or it can be introduced in any combination of side, end or through lumen compartments.
• FIGS. 26 and 27 show adeflation catheter280 that may be used to deflate intra-bronchial device for removal or repositioning. Deflation catheter may be advanced through the device delivery catheter or independently. Deflation catheter has a plurality offingers282 separated byslots283 and arranged circumferentially around the catheter's distal end. When advanced intoshaft252, shoulders284 formed on the distal ends offingers282 cam radially inward to enable thecatheter280 to be advanced intodevice250. When one ormore shoulders284 line up with opening256 ofdevice250, their respective fingers move radially outward, displacingflap valve258 away from opening256 and permitting the balloon's inflation fluid to escape intocatheter280, thereby deflatingballoon254. Ashoulder286 meetsshoulder272 ofdevice250 whenfingers284 have been advanced distally to the proper position with respect toopening256.
• FIGS. 28 and 29 show aplug300 for an intra-bronchial device, such as the device described inFIGS. 24 and 25. For illustration,FIG. 29 showsballoon254 in a deflated state. A plurality offingers302 separated byslots304 are disposed at the distal end ofplug300. The distal end of eachfinger302 has an angledcamming surface306 facing distally and asteeper camming surface308 facing proximally. The plug has a radially symmetric coupling handle310 at its proximal end for attachment to a delivery and/or recapture catheter (not shown). When insertingplug300 into the intra-bronchial device, distal movement ofplug300 intoshaft252 causesfingers302 to cam radially inward until the distal end ofplug300 emerges from the distal end ofshaft252, at which pointfingers302 move outward to lockplug300 in place. A proximal shoulder (not shown) may be provided onplug300 to prevent the plug from advancing out the distal end of the intra-bronchial device. If removal ofplug300 is desired, a proximally directed force onplug300 will causefingers302 to cam inward to allow the plug to be withdrawn throughshaft252.
• FIG. 30 shows the use of the invention to compress a portion of a patient's lung. In this example, threeintra-bronchial devices150a,150band150care disposed in aportion320 of the patient's lung.Devices150aand150bhave been plugged and released from their delivery systems;device150cis still connected tocatheter322 which communicates with the still-open lumen324 of the device's central shaft. To compresslung portion320, pressurized fluid is introduced into the patient's lung throughsleeve326 surroundingcatheter322. An expandable (e.g., inflatable, expanding metallic frame or braid)cuff328 seals sleeve against the air passageway wall.Devices150a-cprevent the pressurized fluid from enteringlung portion320. Inflation of one or more portions of the lungadjacent portion320 will causeportion320 to collapse, venting any air inlung portion320 to the exterior of the patient throughcatheter322. These devices cause effective lung tissue compression with the application of more than 10 mm Hg pressure above atmospheric pressure. By applying more pressure, the effect is made more rapid and complete: 25 mm Hg is better, 45 mm Hg is better still and more than 55 mm Hg is best.
• The sleeve can be made of typical guide catheter materials with similar construction techniques and may be covered or comprised of silicone, polyurethane, biocompatible polymers, elastic balloon materials, semi-elastic balloon materials or a mesh composite. The balloon can be compliant or semi-compliant and can be made from polymers such as polyurethane or silicones. The cuff may be self expanding with the use of titanium alloys and these can be made from braid. Braided funnel shaped ends work very well to seal this device.
• It is also possible to cause the target portion of the lung to collapse naturally, without hyperinflation of other portions of the lung. Once a lung region has been isolated, oxygen is absorbed from the air in a greater volume than CO₂is deposited. This absorptive atelectasis or auto-atelectasis causes the isolated lung region to collapse, allowing remaining portions of the lung to expand into that space.
• Over-expansion of the remaining portions of a lung after collapse of one portion of the lung can cause tissue tears and other injuries.FIGS. 31 and 32 illustrate a pressure relief system that minimizes the risk of such injuries.Intra-bronchial device350 has apressure relief valve352 that opens (as shown inFIG. 32) when the differential pressure between the collapsing lung portion on the distal side ofdevice350 and the lung portions on the proximal side ofdevice350 exceeds a desired amount, such as, e.g., 2 mm Hg, 10 mm Hg, 20 mm Hg or 50 mm Hg. The greater the differential pressure, the greater the lung volume reduction, but also the greater the risk of complications. Alternatively, a maximum lung expansion may be targeted. For example, the pressure required to open the relief valve can be set such that the expanding lung tissue is not strained more than 150%. The pressure relief valve may also reside in an intra-bronchial device plug instead of being integral with the expandable intra-bronchial device itself.
• FIG. 30 also shows aspects of a collateral flow detection system for use with this invention. Prior to attempting hyperinflation of the lung to collapse the target portion of the lung, this system can be used to check for the existence of collateral flow paths from the targetedlung portion320 back to the remaining portions of the lung and the exterior of the patient. Air blended with a marker such as a detectable gas may be introduced into the lung throughsleeve326, and the air in thetarget region320 may be monitored throughcatheter322 by sniffing or sampling. If the marker gas is detected, collateral flow is occurring, either due to the presence of flow paths through degraded tissue, natural airways that still need to be plugged with intra-bronchial devices, or the failure of one or more implanted intra-bronchial devices. Gases that may be used for collateral flow detection are hyper-polarized gases such as helium, helium-3 and xenon-129. Other materials include Diethyl ether, Nitrous oxide, Chloroform, Cyclopropane, Trichloroethylene, Fluroxene, Halothane, Methoxyflurane, Enflurane, Isoflurane, Desflurane, Sevoflurane or components of these. Small amounts of CO can also be tolerated and used for this purpose.
• Upon detection of collateral flow paths, one or more agents to block and clog the collateral flow paths may be introduced, e.g., through the intra-bronchial device delivery catheter so that it is installed in the isolated lung region. The agent will flow through any such collateral flow path. This treatment is intended to block flow of collateral pathways that are created by the degenerative disease. As such, treatments may need to be repeated periodically to block pathways that are newly formed by the disease progression. This can be easily done by coupling a delivery catheter to the intra-bronchial device and then by removing the central cap from the intra-bronchial device. This provides a direct conduit to the distal isolated lung region.
• Microparticles can be used for blocking collateral flow in lung tissue. The microparticles preferably comprise a polymeric binder or other means to make controlled geometry particles. Suitable polymeric binder materials include poly(glycolic acid), poly-d, 1-lactic acid, poly-1-lactic acid, copolymers of the foregoing, poly(aliphatic carboxylic acids), copolyoxalates, polycaprolactone, polydioxanone, poly(ortho carbonates), poly(acetals), poly(lactic acid-caprolactone), polyorthoester, poly(glycolic acid-caprolactone), polyanhydrides, polyphosphazines, albumin, casein, and waxes. Poly (d, 1-lactic-co-glycolic acid) is commercially available from Alkermes, Inc. (Blue Ash, Ohio). A suitable product commercially available from Alkermes, Inc. is a 50:50 poly (d, 1-lactic-co-glycolic acid) known as MEDISORB.RTM. 5050 DL. This product has a mole percent composition of 50% lactide and 50% glycolide. Other suitable commercially available products are MEDISORB.RTM. 6535 DL, 7525 DL, 8515 DL and poly(d,l-lactic acid) (100 DL). Poly(lactide-co-glycolides) are also commercially available from Boehringer Ingelheim (Germany) under its Resomer.RTM. mark, e.g., PLGA 50:50 (Resomer.RTM. RG 502), PLGA 75:25 (Resomer.RTM. RG 752) and d,l-PLA (Resomer.RTM. RG 206), and from Birmingham Polymers (Birmingham, Ala.). These copolymers are available in a wide range of molecular weights and ratios of lactic acid to glycolic acid.
• Other materials include biocompatible polymers that are described in the US Pharmacopeia and include dextrans and other carbohydrate-based materials or derivatives thereof, polyethylene glycol, polyethylene oxide, polyvinyl alcohol, and starch. Additional materials include polyesters, such as polyglycolic acid, polylactic acid, poly-1,4-dioxa-2-one, polyoxaltes, polycarbonates, copolymers of polyglycolic acid and polylactic acid, polycaprolactone, poly-b-hydroxybutyrate, copolymers of epsilon-caprolactone and delta-valerolactone, copolymers of epsilon-caprolactone and DL-dilactide, and polyester hydrogels; polyvinylpyrrolidone; polyamides; gelatin; albumin; proteins; collagen; poly(orthoesters); poly(anhydrides); poly(alkyl-2-cyanoacrylates); poly(dihydropyrans); poly(acetals); poly(phosphazenes); poly(urethanes); poly(dioxinones); cellulose; agarose, agar, and starches, and derivatives of any of the aforementioned.
• Block copolymers are another class of materials that are suitable for the present invention.
• Protein microspheres are another class of materials that enables the present invention. For example, albumin can be cross-linked with a suitable cross-linker to generate particles for various applications including imaging. Other proteins suitable for enabling the present invention include recombinant or naturally occurring human, animal, or vegetable proteins, including collagen, gelatin, casein, soybean protein, vegetable protein, and keratin.
• Liposomes, proliposomes, or microparticles containing fatty acids, lipids, or derivatives thereof will also enable the invention.
• Synthetic polymeric particles comprised of HEMA (hydroxyethlymethacrylate), AEMA (aminoethyl methacrylate), DMEMA (N,N dimethyl amino) and other acrylates, acrylamides, methacrylamides, styrene, or any polymerizable material will also work in this application.
• A viscous solution that reduces or blocks collateral flow in lungs may also be used. Viscous solutions for the present invention are preferably biocompatible solutions such as hydrogels or other substances including glycerol and aqueous solutions containing water soluble materials including cellulose derivatives, dextrans, starches, and any carbohydrate or carbohydrate based material or derivative thereof. Other aqueous solutions may contain synthetic polymers including povidone, PEG (polyethylene glycol or polyethylene oxide), polyvinyl alcohol, and diethyl aminoethyl (DEAE)-sephadex. Aqueous solutions may also contain proteins such as collagen and albumin. Other viscous solutions may contain non-aqueous cosolvents such as ethanol. Buffers, salts, and excipients may also be part of the formulation of thixotropic viscous solutions.
• In one embodiment, a two-part sealant may be applied to areas of interest. One novel method involves applying one part of the sealant to a desired area in one lobe, and applying a second component to the other lobe. The two components may mix and solidify at a location between the lobes, or partially in both lobes such that flow is reduced. Sealant components for this application may include fibrin/thrombin, activated PEG/PEG-diamine, albumin/PEG, and albumin/glutaraldehyde sealants. The sealant is an implantable material that may contain hemostatic agents such as chitin derivatives including but not limited to carboxymethyl chitin and chitosan (1-100% deacetylated). The sealant components may also contain additives that affect viscosity, set time, adhesion, and biocompativility. The albumin component may be formulated in weight to weight ratios of 10-50% where the remaining mass balance is aqueous solutions of salts, buffers, and additives or combinations thereof. The other component of the sealant is a cross-linker containing glutaraldehyde or derivatives thereof in weight to volume ratios of 1-25% where the remaining balance is an aqueous solution with or without additives, salts, or buffers or combinations thereof. These solutions may be applied from dispensers that deliver a ratio of 1 unit volume of protein solution per 1 unit volume of cross-linker solution (1:1 protein:cross-linker) and may be applied in ratios up to 10 unit volumes of protein solution per unit volume of cross-linker solution. Furthermore, mixing may occur by passing the solutions through a static mixing tip with helical or other geometrical devices that enhance the mixing efficiency. Sealants prepared from these solutions contain 545% protein and 0.5-14% crosslinker.
• Other suitable sealants and other agents are described in US Pat. Appl. Publ. No. 2004/0052850; US Pat. Appl. Publ. No. 2004/0081676; U.S. Ser. No. 11/008,577; U.S. Ser. No. 11/008,092; U.S. Ser. No. 11/008,094; U.S. Ser. No. 11/008,578; U.S. Ser. No. 11/008,649; U.S. Ser. No. 11/008,777; U.S. Ser. No. 11/008,087; U.S. Ser. No. 11/008,093; U.S. Ser. No. 11/008,580; and U.S. Ser. No. 11/008,782.
• We have determined that many of these agents cause tissue binding to form localized adhesions or a bio-response that will help maintain a permanent volume reduction. With the introduction of these materials we are instigating one or more elements of a well understood tissue remodeling cascade process. The process includes tissue polymer decomposition and/or necrosis that leads to recruitment of cellular respondents that include one or more of the following: Neutrophils, white blood cells, macrophages, CD8+, MMP's, Interlukens, cytokins and protocylins. Then the tissue remodels to initiate tissue formation and thickening that culminates in the formation of tissue adhesions.
• Other materials that can initiate this effect are cadmium, smoke artifacts, tars, materials that irritate tissue such as alcohols, solvents, organic solvents, acids, materials that are basic and materials that are acidic. These include compounds or materials that have pH levels between 1 and 6.9 with materials closest to 1 being a preferable acid material. Additionally, compounds or materials that have pH levels between 7.5 and 14 work very well but materials closest to 14 work best.
• Materials that solidify such as glue compositions form a structure that is typically stiffer than the intrinsic stiffness of lung tissue. Specifically, pull tests of lung parenchema (comprised of alveoler sacks and collagen) sections show that the composite stiffness is very low. When we combine agents that form a stiffer structure than the underlying biomaterial or lung tissue, the modulus mismatch causes irritation, inflammation, tissue thickening, fibrosis, a remodeling cascade and adhesions that will promote and maintain lung volume reduction. Compositions that dry out or maintain viscosity levels above 2 centipoise (a measure of dynamic viscosity) generate shear and cause this stiffness mismatch to promote adhesions. Agents and hydrogel materials thicker than 10 centipoise work better. Our glutaraldehyde glue technology can produce compositions that have 15 centipoise viscosity and higher levels up to and beyond 150 centipoise. By increasing the glue cross linking properties, we can deliver agents that solidify to a gel or harder substance. Materials that gel to produce solids with a modulus greater than 10-20 centimeters of H₂O will produce this same effect. Materials that are stiffer in a range between 20 and 100 centimeter of H₂O are better. Materials that are stiffer than 100 cm H₂O are preferable. We have developed several implantable materials with viscosity enhancing agents to promote these effects.
• When applying an implantable hydrogel comprised of a biocompatible material, or an implantable liquid that undergoes a physical transition from a liquid to a gel or other solid such as solid adhesives, control of deposition is very important. Ways of controlling deposition include localized dispensing of the sealant through a suitable device containing a lumen, and also through the addition of agents that increase the viscosity of one or more components of the implantable material. Such agents include biocompatible materials with viscosities that are greater than those of water, and include glycerol, polymeric materials such as proteins, carbohydrate-based polymers and derivatives thereof, synthetic materials including polyethylene glycols (PEG), polyethylene oxides (PEO), polyvinyl pyrrolidone (PVP), polyvinyl alcohol and other components described in the “United States Pharmacopeia” and the “Handbook of Pharmaceutical Excipients”, edited by A. H. Kibbe. Other materials for controlling viscosity include oils, lipids, and fatty acids, including oleic acid, and phosphocholines. Phase separation can be controlled with emulsifiers including poly sorbate. For sealants prepared by mixing two or more components, the viscosities of one or more of the components can be modified by adding an appropriate agent to control spreading after application. Viscosities of these components can range from 1 to 1000 centistokes (a measure of kinematic viscosity).
• Deposition and control of spreading of sealants containing two or more components are also affected by the gel time, or set time, of the mixed sealant. Sealants with short set times are preferable to those with longer set times. Ideal set times for the present invention and method range from 1-600 seconds, and preferable from 1-60 seconds. Set time can be controlled by the addition of set time modifiers, including agents that reduce or increase the set time relative to the corresponding formulation lacking the set time modifier. An example of an agent that decreases the set time is carboxymethyl cellulose. An example of an agent that increases the set time is glycerol.
• Glutaraldehyde, as currently processed and used in some commercial sealants, undergoes reversible reactions that cause reoccurring inflammation. These properties can be improved by chemical modification of the glutaraldehyde. One such modification includes glutaraldehyde condensation reactions, as described in “Bioconjugate Techniques” by G. T. Hermanson. This condensation involves the formation of derivatives of glutaraldehyde in aqueous solutions containing acid or base. This reaction can be monitored by ultraviolet spectroscopy at or near 280 and 234 nanometers. At 280 nanometers, pure glutaraldehyde has significant absorbance, and little or no absorbance at 234 nanometers when measured as an aqueous solution at 0.5% weight to volume. When glutaraldehyde is chemically modified, it has significant absorbance at 234 nanometers. These derivatives are effective cross-linking agents when used with nucleophilic substrates such as proteins, including albumins. Furthermore, sealants prepared from glutaraldehyde derivatives are adhesive in vivo, through chemical or mechanical means, or a combination of chemical and mechanical means.
• Implantable materials for the present invention are any agents administered into tissue, including sealants, which may be comprised of hydrogels, proteins, or other biocompatible materials, that can be implanted into compromised tissue to benefit the patient. Examples of hydrogels include those prepared from natural sources including carbohydrate-based materials. Such materials include hyaluronans, hyaluronic acid, alginates, chitins, chitosans, and derivatives thereof. Proteins that enable the present invention include albumins, collagens, gelatins, and other proteins that can be cross-linked or that form solutions with viscosities greater than water. Other implantable materials include those prepared by mixing two or more components so that a viscous solution, gel, or solid is formed. Such implantable materials are prepared from a protein substrate where the protein is derived from natural, synthetic, or semi-synthetic processes. The protein may also be derived from recombinant DNA technology and may be isolated from cell-culture processes, as well as from transgenic plants and animals. Examples of proteins include albumins, collagens, and gelatins. Cross-linkers employed as part of the implantable material precursors include aldehydes, polyaldehydes, esters, and other chemical functionality suitable for cross-linking protein(s). Examples of homobifunctional cross-linking agents are described in “Bioconjugate Techniques” by G. T. Hermanson.
• The implant components, including the cross-linking agent and the substrate, can be formulated at a pH in the range of 5-10 by adjusting the pH and/or by adding suitable buffers in the range of 1-500 mM. Examples of buffers include phosphate, carbonate, bicarbonate, borate, or imidazole, or mixtures thereof. Additionally, additives or stabilizers may be added to improve the stability of one or more of the components. Furthermore, imaging agents may be added to allow for detection of the material. Such agents include iodine, iodine compounds, metals such as gadolinium, radioisotopes, and other compounds for gamma scintigraphy, magnetic resonance imaging, fluoroscopy, CT, SPECT and other imaging modalities. Additionally, the material may be formulated such that the mechanical properties are suitable for applications in the specific tissue to which the implantable material is applied. Such properties include elasticity, modulus, stiffness, brittleness, strain, cohesion, adhesion, and stress. Agents for modifying the properties include fillers, plasticizers, and adhesion modifiers. Furthermore, the implant may induce a natural adhesive mechanism with or without the addition of chemical agents which may be added to the implant to induce a natural response. Such agents include particles in the range of 100 nm to 1 millimeter. Agents include chemical or biochemical agents (proteins or nucleic acids) that induce a natural response. Examples of such agents include bleomycin, cytokines and chemokines, and single stranded RNA molecules.
• Intra-bronchial devices according to this invention may be delivered through the working channel of a bronchoscope. Alternatively, the lung access system described in the U.S. patent application filed of even date herewith titled “Lung Access Device and Method,” (attorney docket number 30689-702.201) may be used to deliver the devices to a patient's lung. This latter delivery method may be used when the diameter of a bronchoscope is too small for the device to be delivered. One advantage of using an intra-bronchial device with a larger, collapsed delivery diameter is that the expansion ratio from delivery diameter to deployed diameter may be made smaller than, e.g., 7.5, more preferably smaller than 6, more preferably smaller than 5, more preferably smaller than 4, and most preferably smaller than 3.
• Another advantage of using the alternative outside the scope delivery system is that the delivered devices are not limited in length since they can be delivered outside the constraints of the scope channel. The scope path to the upper airways, where the most tissue damage normally resides, requires very small radius bends to be formed in the bronchoscope to gain access. Long implant devices that would straighten the scope if delivered through the channel can now be delivered outside the channel while the target region continues to be imaged through the scope optics.
• In addition, it is desirable to make the implant longer than its diameter to provide stability from, e.g., rotating in the airway. These relative dimensions also make it much easier to capture the end of the device later to access the through-lumen or to recover or move the device. Implant devices that exceed 4 mm in length can now be delivered easily using this system. Devices longer than 5 mm will work better, devices longer than 10 mm are better, devices longer than 20 mm are preferable, devices longer than 25 mm, 30 mm, and 35 mm will anchor much better.
• These devices can be made from all biocompatible plastics, metals, ceramics, shape memory alloys and carbon based fiber or polymers. The catheter devices can be lined with fluoro polymers and reinforced with metal or polymer fiber or wire braid or by using coils of similar materials. The wire elements that guide devices can be made from steel or titanium alloys or other metals that do not present artifacts in MRI equipment. Other materials including shape memory alloys such as nickel- and titanium-based metals that are comprised of more than 40% titanium would perform well in that they can be made in an anisotropic way to provide different properties with bending and torque.
• In some embodiments, one or more of the delivery and deployment catheters may have multiple lumens. For example, a multi-lumen catheter could be used to both inflate the intra-bronchial device and deliver glue or another substance (such as those described above) outside of, and either distal or proximal to, the intra-bronchial device. Sheaths, needles and other devices may be used to deploy such substances.
• Another use of an extra-catheter lumen is as a return path. As long as the pressure drop over the return path is less than the pressure required to inflate the intra-bronchial device, air or the inflation fluid will preferentially flow down the return path. The pressure can be controlled with the delivery rate of the inflation fluid. This return path can also act as a pressure relief conduit to control the maximum inflation pressure applied to the balloon.
• While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims (31)

1. A method of treating a lung comprising:

endotracheally delivering an expandable member to an air passageway of the lung with a delivery system;

expanding the expandable member to make contact with a wall of the air passageway; and

providing an open lumen through the expandable member to provide access to a portion of the lung distal to the expandable member.

2. The method ofclaim 1 further comprising detaching the expandable member from the delivery system.

3. The method ofclaim 1 wherein the expanding step comprises inflating the expandable member.

4. The method ofclaim 1 further comprising contracting the expandable member after the expanding step.

5. The method ofclaim 4 wherein the contracting step comprises deflating the expandable member.

6. The method ofclaim 4 further comprising repositioning the expandable member and expanding the expandable member after the repositioning step.

7. The method ofclaim 1 further comprising plugging the lumen.

8. The method ofclaim 7 wherein the plugging step comprises contacting a plug with the expandable member.

9. The method ofclaim 7 wherein the plugging step comprises closing a port in the lumen.

10. The method ofclaim 7 further comprising unplugging the lumen.

11. The method ofclaim 10 wherein the unplugging step comprises moving a plug proximally.

12. The method ofclaim 10 wherein the unplugging step comprises opening a port in the lumen.

13. The method ofclaim 1 further comprising detecting fluid flow around the expandable member.

14. The method ofclaim 1 further comprising detecting collateral fluid flow to the lung region distal to the expandable member.

15. The method ofclaim 14 wherein the step of detecting collateral flow comprises:

sealing an air passageway in the lung at a point proximal to the expanding member;

introducing a detectable gas into a region between the proximal point and the expanding member;

and sensing for the presence of the detectable gas distal to the expanding member.

16. The method ofclaim 15 wherein the expandable member comprises a first expandable member, sealing the air passageway comprises sealing the air passageway with a second expandable member comprising an open lumen, and sensing comprises sampling for detectable gas through the second expandable member open lumen;

the method further comprising detaching the second expandable member from a delivery system.

17. The method ofclaim 15 further comprising deploying a plurality of expanding members to isolate the portion of the lung, the sealing step comprising sealing the air passageway at a point proximal to the plurality of expanding members.

18. The method ofclaim 14 wherein the sensing step is performed at a proximal end of a device delivery catheter.

19. The method ofclaim 14 wherein the sensing step comprises sensing gas flowing through the open lumen in the expandable member.

20. The method ofclaim 1 further comprising reducing collateral flow around the expandable member.

21. The method ofclaim 1 further comprising reducing collateral flow to lung regions distal to the expandable member.

22. The method ofclaim 21 wherein the reducing step comprises delivering a collateral flow blocking agent through the lumen.

23. The method ofclaim 22 further comprising unplugging the lumen prior to the step of delivering a collateral flow blocking agent.

24. The method ofclaim 1 further comprising causing the portion of the lung distal to the expandable member to reduce volume.

25. The method ofclaim 24 wherein the causing step comprises compressing the lung portion.

26. The method ofclaim 25 further comprising promoting adhesion of tissue within the lung portion.

27. The method ofclaim 26 wherein the step of promoting adhesion comprises introducing an adhesion inducing material into the lung portion.

28. The method ofclaim 1 further comprising permitting fluid to enter the lung portion when a difference between fluid pressure within the lung portion and fluid pressure in another portion of the lung exceeds about 2 mm Hg.

29. The method ofclaim 28 wherein the permitting step comprises permitting fluid to enter the lung portion when a difference between fluid pressure within the lung portion and fluid pressure in another portion of the lung exceeds about 10 mm Hg.

30. The method ofclaim 28 wherein the permitting step comprises permitting fluid to enter the lung portion when a difference between fluid pressure within the lung portion and fluid pressure in another portion of the lung exceeds about 20 mm Hg.

31. The method ofclaim 28 wherein the permitting step comprises permitting fluid to enter the lung portion when a difference between fluid pressure within the lung portion and fluid pressure in another portion of the lung exceeds about 50 mm Hg.

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