Patent Publication Number: US-2013245484-A1

Title: Minimally invasive determination of collateral ventilation in lungs

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a divisional of U.S. patent application Ser. No. 12/972,225 (Attorney Docket No. 20920-714.301), filed Dec. 17, 2010, which is a divisional of U.S. patent application Ser. No. 11/296,951 (Attorney Docket No. 20920-714.501) filed Dec. 7, 2005, which is a continuation-in-part of U.S. patent application Ser. No. 10/241,733 (Attorney Docket 20920-709.201) filed Sep. 10, 2002, which claims priority to U.S. Provisional Patent Application No. 60/318,539 (Attorney Docket 20920-709.101) filed Sep. 10, 2001, and this application claims the benefit and priority of U.S. Provisional Patent Application No. 60/645,711 (Attorney Docket 20920-714.101), filed Jan. 20, 2005, U.S. Provisional Patent Application No. 60/696,940 (Attorney Docket 20920-714.102), filed Jul. 5, 2005, and U.S. Provisional Patent Application No. 60/699,289 (Attorney Docket 20920-715.101), filed Jul. 13, 2005, the full disclosures of all of which are hereby incorporated herein by reference. 
    
    
     BACKGROUND OF THE INVENTION 
     Field of the Invention 
     The present invention relates generally to respiratory medicine and more specifically to the field of assessing collateral ventilation pathways in the lung and quantitatively determining the resistance of these collateral ventilation pathways in the course of diagnosing and treating lung disease. 
     Because of recent advances in the treatment of chronic obstructive pulmonary disease (COPD) there has been a heightened interest in collateral ventilation. Various COPD treatments involve the removal of trapped air to reduce the debilitating hyperinflation caused by the disease and occlusion of the feeding bronchus to maintain the area at a reduced volume. The concept guiding these approaches is that aspiration and/or absorption atelectasis of emphysematous lung regions can reduce lung volume without the need to remove tissue. One such type of COPD treatment is Endobronchial Volume Reduction (EVR) uses a catheter-based system to reduce lung volume. With the aid of fiberoptic visualization and specialty catheters, a physician can selectively collapse a segment or segments of the diseased lung. An occlusal stent is then positioned within the lung segment to prevent the segment from reinflating. 
       FIGS. 1A-1C  illustrate an example of such an EVR procedure targeting the right upper lobe RUL of the right lung RL of a patient. Here, the right upper lobe RUL is hyperinflated. A catheter  2  is advanced through the trachea T into the lung passageways feeding the right upper lobe RUL. The right upper lobe RUL is then reduced in volume, as illustrated in  FIG. 1B , and a plug, valve or occlusal stent  4  is placed within the lung passageway reducing the volume of the right upper lobe RUL. However, as shown in  FIG. 1C , collateral channels CH may be present connecting the right upper lobe RUL with the right middle lobe RML and/or the right lower lobe RLL. Consequently, the EVR may only be temporarily successful as the right upper lobe RUL re-expands or re-hyperinflates due to refill through the collateral channels CH over time. In some instances, effective EVR may not even be temporarily successful in that appropriate volume reduction may be impossible due to volume being drawn from neighboring lobes via the collateral channels CH. 
       FIGS. 2A-2B  schematically illustrate example collateral channels CH in the right lung RL.  FIG. 2A  illustrates a variety of inter-lobar collateral channels CH between the right upper lobe RUL, right middle lobe RML and right lower lobe RLL.  FIG. 2B  illustrates intra-lobar or inter-segmental collateral channels CH which connect individual lung segments (e.g. S, S 1 , S 2 ) within the lung lobes. These inter-segmental collateral channels allow the periphery of each of the lung compartments to communicate with one another and include well-known collateral pathways such as Martin&#39;s Channels, pores of Kohn and Lambert&#39;s canals. However, in healthy lungs, the main lobes (e.g RUL, RML, RLL) of the lung are typically separated from one another by impermeable fissures comprised of a double layer of infolded reflections of visceral pleura. Thus, in healthy lungs collateral channels CH between the lungs are considered not present or are minimal. Various anatomic studies have shown, however, that interlobar fissures frequently do not extend completely to the mediastinum or hilum and are, therefore, incomplete. In fact, various studies have described the major fissures to be incomplete in 18% to 73% of cases. As a result, there are varying degrees of fusion between lobes, and consequently, these areas of parenchymal fusion may provide a pathway for the spread of disease between lobes and a pathway for collateral air drift or inter-lobar collateral ventilation. 
     Further, a lesser known or rather overlooked fact is that, in the presence of COPD and emphysema, pathways also develop that traverse through the fissures thus interconnecting neighboring lung compartments. This has been demonstrated histologically by the use of tantalum gas. Tantalum dust has been shown to accumulate at gaps in the alveolar wall at the lobar junction and to pass through this area in isolated human lungs, some of which were from emphysema patients. Furthermore, there may be sufficient collateral air drift across incomplete major fissures in the dog to prevent atelectasis. Most importantly, the collateral airflow across incomplete major fissures has been measured in normal and emphysematous excised human lungs and it has been found that in emphysema it is markedly increased. The mechanism that allows for the creation of these inter-compartment collateral channels has not yet been documented in the scientific literature, however likely contributing factors are the elastin destruction that occurs in COPD and the tissue stretching that occurs with hyperinflation. 
     A method of measuring inter-compartment collateral ventilation has been to measure resistance to collateral ventilation (R coll ). Assessment of the relationship between steady-state flow through collateral channels (Q coll ) and the pressure drop across them is a direct way for measuring the resistance to collateral ventilation (R coll ). Many investigators have attempted to use this approach in the past but the most simple and versatile way to make this measurement was first described by Hilpert (Hilpert P. Kollaterale Ventilation Habilitationsschirift, aus der Medizinischen. Tubingen, West Germany: Tubingen Universitatsklinik, 1970. Thesis). This method is schematically illustrated in  FIGS. 3A-3C  and includes supplying a constant positive pressure of air (P) to a target area or sealed target compartment C s . The positive pressure of air is supplied by a positive pressure generator  5  through a double-lumen isolation catheter  6  having an isolation cuff  7  which is wedged into a peripheral airway and seals the compartment C s . Therefore, any airflow out of the compartment C s  is through collateral channels CH.  FIG. 3B  illustrates a state of steady pressure P. The method also includes determining the required airflow rate (V coll ) to maintain that pressure P. The airflow rate is measured by a flowmeter  8  disposed along the isolation catheter  6 . The ratio of P over V coll  provides a quantitative measure for the resistance to collateral ventilation. It may also be conceived that a constant airflow (Q coll ) may be injected through one lumen of the isolation catheter  6  while air pressure (P b ) at the site of bronchial obstruction is measured through the other lumen. Under steady-state conditions, the ratio between P b  and Q coll  equals the resistance through the collateral system, which includes the resistance in the collateral channels R coll  and the resistance in the small airways R saw  of the isolated compartment C s  between the collateral channels CH and the distal end of the catheter  6 . In either case, this technique can be somewhat useful as an experimental tool, however it has significant limitations experimentally and its clinical use poses an additional risk to the patient. Namely, applying positive pressure or constant air flow to a diseased area of the lung can be hazardous if not done correctly. For example in the presence of bullous emphysema, the pressure could enlarge the bullae or create new bulla, or could lead to increased hyperinflation or pneumothorax. 
     In another technique, the presence of inter-compartment collateral ventilation can be assessed by isolation of the target segment and subsequent introduction of the subject to breath normally with Heliox (21% O 2 /79% He). Detection of tracer gas in the target segment indicates the presence of collateral channels communicating that area with the rest of the lung. 
     Experimental attempts to detect the presence of inter-compartmental collateral ventilation have also been described recently in excised deflated lungs wherein a lung area is cannulated, sealed and insufflated with air while separate neighboring lung areas are concurrently sealed, and observed to determine whether they inflate. Although this technique can prove very useful in the described experimental setting, its clinical practicality is undoubtedly severely limited for obvious reasons. 
     Another technique is described in US Patent Application US2003/0228344A1 in which a one-way valve is placed in the feeding bronchus of a area targeted for treatment such that air cannot pass in the inspiratory direction but can escape in the expiratory direction. The area is then observed radiographically to determine if absorption atelectasis eventually occurs; atelectasis would indicate the absence of collateral ventilation channels and the lack of atelectasis is alleged to be indicative of the presence of the collateral channels. Unfortunately this technique is difficult to practice because the one-way valve may not generate atelectasis for a variety of reasons such as mucus plugging of the valve, leakage, improper placement and the lack of a pressure gradient to force trapped air proximally across the valve. 
     Another method that imposes lesser risk to the patient, relatively to Hilpert&#39;s method, has been described by Woolcock and Macklem (Woolcock, A. J, and P. T. Macklem. Mechanical factors influencing collateral ventilation in human, dog, and pig lungs. J. Appl. Physiol. 30:99-115, 1971). This method involves the rapid injection of an air bolus beyond the wedged catheter into the target lung segment, and the rate at which pressure falls as the obstructed segment empties into the surrounding lung through collateral channels is governed by the time constant for collateral ventilation τ coll  (the time it takes for the pressure change produced by the air bolus injection to drop to about 37 percent of its initial value). Here R coll  is indirectly measured as the ratio between τ coll  and the compliance of the target segment C s . Calculations of R coll  via this method, however, are highly dependent on several questionable assumptions, including homogeneity within the obstructed segment and in the surrounding lung. Values for R coll  reported in the literature using either Hilpert&#39;s method or other methods range from approximately 10 −1  to 10 +2  cmH 2 O/(ml/s) for normal human lungs and from approximately 10 −3  to 10 −1  cmH 2 O/(ml/s) for emphysematous human lungs. 
     A direct, accurate, simple and minimally invasive method of assessing collateral flow in lungs is desired, which also poses minimal risk to the patient. In addition, methods and devices for quantitatively determining the resistance of these collateral ventilation pathways in the course of diagnosing and treating lung disease is also desired. At least some of these objectives will be met by the present invention. 
     BRIEF SUMMARY OF THE INVENTION 
     Minimally invasive methods, systems and devices are provided for qualitatively and quantitatively assessing collateral ventilation in the lungs. In particular, collateral ventilation of a target compartment within a lung of a patient is assessed by advancement of a catheter through the tracheobronchial tree to a feeding bronchus of the target compartment. The feeding bronchus is occluded by the catheter and a variety of measurements are taken with the use of the catheter in a manner which is of low risk to the patient. Examples of such measurements include but are not limited to flow rate and pressure. These measurements are used to determine the presence of collateral ventilation and to quantify such collateral ventilation. Collateral ventilation refers to flow or passage of air from the target lung compartment into one or more adjacent components through passage(s) in or through the natural barriers which form the components. 
     Consequently, the lungs of a patient may be analyzed for appropriateness of various treatment options prior to treatment. For example, levels of collateral ventilation may be mapped to various target compartments so that the practitioner may determine the overall condition of the patient and the most desired course of treatment. If it is desired to perform Endobronchial Volume Reduction (EVR) on a lung compartment, the lung compartment may be analyzed for collateral ventilation prior to treatment to determine the likelihood of success of such treatment. Further, if undesired levels of collateral ventilation are measured, the collateral ventilation may be reduced to a desired level prior to treatment to ensure success of such treatment. Thus, methods, systems and devices of the present invention provide advantages over conventional trial-and-error methodologies in which treatment plans are determined blindly, without such diagnostic information. This increases the likelihood of successful treatment and reduces time, cost and complications for the patient. 
     In a first aspect of the present invention, methods are provided for diagnosing collateral ventilation between a target lung compartment and adjacent lung compartment(s) in a patient. In some embodiments, the method comprises isolating a target lung compartment from at least one adjacent lung compartment(s) usually all adjacent compartments, and allowing the patient to breathe air free from the introduced markers and detecting air flow or accumulation from the isolated lung compartment over time. Typically, isolating comprises introducing a catheter transtracheally to a main bronchus feeding into the target lung compartment and deploying an occlusion member on the catheter to isolate the target lung compartment in the main passageway leading into that compartment. In some instances, detecting may comprise measuring air flow through a lumen in the catheter while the patient exhales, wherein said air entered the isolated compartment via collateral passages while the patient inhaled. In other instances, detecting comprises accumulating air from the isolated compartment air from the isolated compartment through the catheter over a number of successive breathing cycles, wherein a continuous increase in accumulated air volume indicates collateral flow into the isolated compartment. 
     In another aspect of the present invention, methods are provided for determining the function or malfunction of an endobronchial prosthesis positioned within a lung passageway of a patient. In some embodiments, the method comprises occluding the lung passageway proximally of the endobronchial prosthesis, allowing the patient to breathe air without any markers, and measuring air flow or accumulation from the lung passageway over time wherein said measurement is correlative to the function or malfunction of the endobronchial prosthesis. 
     In a further aspect of the present invention, systems are provided for detecting collateral ventilation into a lung compartment in a patient. In some embodiments, the system comprises a catheter adapted to be introduced transtracheally to a bronchus leading to a target lung compartment, an occlusion member on a distal region of the catheter, said occlusion member being adapted to selectively occlude the bronchus, and a flow measurement sensor on the catheter to detect flow of air from the isolated compartment as the patient exhales. 
     In yet another aspect of the present invention, systems are provided for detecting collateral ventilation into a lung compartment in a patient. In some embodiments, the system comprises a catheter adapted to be introduced transtracheally to a bronchus leading to a target lung compartment, an occlusion member or a distal region of the catheter, said occlusion member being adapted to selectively occlude the bronchus and an accumulator connectable to the catheter to accumulate air exhaled from the catheter over time. Examples of accumulators include a slack collection bag which has substantially no resistance to filling with air. 
     In another aspect of the present invention, methods are provided for evaluating a target lung compartment of a patient. In some embodiments, the method comprises positioning an instrument within a lung passageway leading to the target lung compartment so that the target lung compartment is isolated, injecting an inert gas into the isolated target lung compartment, generating at least one measurement of pressure within the target lung segment, generating at least one measurement of concentration of inert gas within the target lung segment, and analyzing the at least one target lung compartment with the use of the at least one measurement of pressure and the at least one measurement of concentration of inert gas. Analyzing may comprise determining a degree of hyperinflation. In such instances, the method may further comprise determining a treatment plan at least partially based on the determined degree of hyperinflation. Alternatively or in addition, analyzing may comprise determining a state of compliance. In such instances, the method may further comprise determining a treatment plan at least partially based on the determined state of compliance. Likewise, analyzing may comprise determining a collateral resistance. In such instances, the method may further comprise determining a treatment plan based on the determined collateral resistance. 
     In some embodiments, generating the at least one measurement of pressure comprises generating a plurality of measurements of pressure over a predetermined time period. The predetermined time period may comprise, for example, approximately one minute. In some embodiments, generating the at least one measurement of concentration of inert gas comprises generating a plurality of measurements of concentration of inert gas over a predetermined time period. The predetermined time period may comprise, for example, approximately one minute. Further, the inert gas may comprise helium. 
     In another aspect of the present invention, systems are provided for evaluating a target lung compartment comprising an instrument positionable within a lung passageway leading to the target lung compartment so that the target lung compartment is isolated, wherein the instrument includes a mechanism for injecting an inert gas to the target lung segment, at least one sensor which generates measurement data reflecting pressure within the target lung segment, and at least one sensor which generates measurement data reflecting concentration of an inert gas within the target lung segment. In some embodiments, the system further comprises a processor which performs computations with the use of the measurement data reflecting pressure and the measurement data reflecting concentration of inert gas. In these embodiments, the computations may include calculating a degree of hyperinflation of the target lung compartment, calculating a state of compliance of the target lung compartment, and/or calculating collateral resistance of the target lung compartment. The measurement data reflecting pressure may comprise generating a plurality of measurements of pressure over a predetermined time period. In some instances, the predetermined time period comprises approximately one minute. The measurement data reflecting concentration of inert gas may comprise generating a plurality of measurements of concentration of inert gas over a predetermined time period. In some instances, the predetermined time period comprises approximately one minute. In addition, the inert gas may comprise helium. 
     In another aspect of the present invention, treatment guides are provided to determine a course of treatment for a lung compartment of a patient. In some embodiments, the guide comprises a plurality of hyperinflation values, each hyperinflation value representing a degree of hyperinflation of the lung compartment, and/or a plurality of compliance values, each compliance value representing a degree of compliance of the lung compartment, and a plurality of treatment options, wherein each treatment option is correlated to a hyperinflation value and/or a compliance value. Typically, the guide comprises a computer program. In such instances, the computer program includes at least one mathematical computation to generate the plurality of hyperinflation values and/or the plurality of compliance values. The mathematical computation may utilize, for example, pressure and concentration of inert gas values. 
     In still another aspect of the present invention, methods of evaluating collateral ventilation of a target lung compartment of a patient are provided. In some embodiments, the method includes positioning an instrument within a lung passageway leading to the target lung compartment so that the target lung compartment is isolated, allowing the patient to inhale air, generating at least one measurement of at least one characteristic of the inhaled air within or exiting the target lung compartment with the use of the instrument, and determining a level of collateral ventilation into the target lung compartment based on the at least one measurement. Typically, the at least one characteristic includes volumetric flow rate and pressure. Determining a level of collateral ventilation may include calculating a value of collateral resistance. The method may further comprise determining a treatment plan based on the level of collateral ventilation. 
     In yet another aspect of the present invention, methods are provided for evaluating a patient for treatment of a target lung compartment, the method comprising generating at least one measurement associated with the target lung compartment while the patient is breathing air, calculating a level of collateral ventilation into the target lung compartment based on the at least one measurement, and treating the patient based on the calculated level of collateral ventilation. Treating the patient may comprise aspirating the target lung compartment. Alternatively or in addition, treating the patient may comprise occluding a lung passageway feeding the target lung compartment. Typically, occluding comprises positioning an occlusal stent within the lung passageway. Calculating may comprise calculating a value of collateral resistance based on the at least one measurement. 
     In a further aspect of the present invention, additional treatment guides are provided to determine a course of treatment for a lung compartment of a patient. In some embodiments, the guide comprises a plurality of collateral resistance values, each value representing degree of collateral ventilation of the lung compartment, and a plurality of treatment options, wherein each treatment option is correlated to a collateral resistance value. Typically, the guide comprises a computer program. In such instances, the computer program may include at least one mathematical computation to generate the plurality of collateral resistance values. The mathematical computation may utilize pressure and volumetric flow rate values. In some embodiments, the guide also includes a visual display showing a curve representing a relationship between the collateral resistance values and a combination of the pressure and volumetric flow rates. 
     Other objects and advantages of the present invention will become apparent from the detailed description to follow, together with the accompanying drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIGS. 1A-1C  illustrate an example of an EVR procedure targeting the right upper lobe of the right lung of a patient. 
         FIGS. 2A-2B  schematically illustrate example collateral channels in the right lung. 
         FIGS. 3A-3C  schematically illustrates a method of supplying constant positive pressure of air to a target compartment. 
         FIGS. 4A-4D  illustrate an embodiment of a minimally invasive method in which a catheter is advanced to the feeding bronchus of a target compartment. 
         FIGS. 5A-5D ,  6  illustrate embodiments of a catheter connected with an accumulator. 
         FIGS. 7A-7B  depict a graphical representation of a simplified collateral system of a target lung compartment. 
         FIGS. 8A-8C  illustrate measurements taken from the system of  FIGS. 7A-7B . 
         FIGS. 9A-9C  illustrate a circuit model representing the system of  FIGS. 7A-7B . 
         FIGS. 10A-10B  illustrate measurements taken from the system of  FIGS. 7A-7B . 
         FIGS. 11A-11D  illustrate graphical comparisons yielded from the computational model of the collateral system illustrated in  FIGS. 7A-7B  and  FIGS. 9A-9B . 
         FIG. 12A  illustrates a two-compartment model which is used to generate a method quantifying the degree of collateral ventilation. 
         FIG. 12B  illustrates an electrical circuit analog model. 
         FIGS. 12C-12E  illustrate the resulting time changes in volumes, pressures and gas concentrations in the target compartment and the rest of the lobe. 
         FIGS. 13A-13C  illustrate changes in measured variables based on degree of effort. 
         FIGS. 14A-14B  illustrate changes in measured variables based on frequency of effort. 
         FIGS. 15 ,  16 A- 16 B illustrate the use of continuous positive airway pressure to assist in the detection of collateral ventilation. 
         FIG. 17  illustrates a single breath technique. 
         FIGS. 18A-18C  illustrate example flow, volume and pressure measurement curves respectively. 
         FIG. 19  illustrates flow measured via a catheter wherein differences in the waveform characteristic of inspiration versus exhalation facilitate determining whether collateral ventilation exists. 
         FIGS. 20A-20B  illustrate an embodiment of an isolation catheter including a bronchoscope. 
         FIGS. 21A-21C  illustrate the performance of a collateral ventilation test through an occlusal stent. 
         FIGS. 22A-22C  illustrate the use of carbon dioxide to indicate collateral flow. 
         FIGS. 23A-23C  illustrate the use of tracer gas to indicate collateral flow. 
         FIGS. 24A-24C  illustrate the use of oxygen to indicate collateral flow. 
         FIGS. 25A-25C  illustrate methods and devices for seal testing of an isolation catheter. 
         FIG. 26  illustrates an embodiment of a system of the present invention for measuring collateral ventilation in one or more lung passageways. 
         FIG. 27  illustrates an embodiment of a screen indicating collateral ventilation measurements and mapping. 
         FIG. 28  illustrates an embodiment of a method of treating a patient. 
         FIG. 29  illustrates an example iterative process of reducing collateral ventilation prior to EVR. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Minimally invasive methods, systems and devices are provided for qualitatively and quantitatively assessing collateral ventilation in the lungs.  FIGS. 4A-4D  illustrate an embodiment of a minimally invasive method in which a catheter  10  is advanced through a tracheobronchial tree to the feeding bronchus B of the target area C s , the compartment targeted for treatment or isolation. The catheter  10  comprises a shaft  12  having at least one lumen therethrough and an occlusion member  14  mounted near its distal end. The catheter  10  is equipped to seal the area between the catheter shaft  12  and the bronchial wall such that only a lumen inside the catheter which extends the entire length of the catheter is communicating with the airways distal to the seal. The seal, or isolation, is accomplished by the use of the occlusion member  14 , such as an inflatable member, attached to the distal tip of the catheter  10 . 
     On the opposite end of the catheter  10 , external to the body of the patient, a one-way valve  16 , a flow-measuring device  18  or/and a pressure sensor  20  are placed in series so as to communicate with the catheter&#39;s inside lumen. The one-way valve  16  prevents air from entering the target compartment C s  from atmosphere but allows free air movement from the target compartment C s  to atmosphere. When there is an absence of collateral channels connecting the targeted isolated compartment C s  to the rest of the lung, as illustrated in  FIGS. 4A-4B , the isolated compartment C s  will unsuccessfully attempt to draw air from the catheter lumen during inspiration of normal respiration of the patient. Hence, during exhalation no air is returned to the catheter lumen. In the presence of collateral channels, as illustrated in  FIGS. 4C-4D , an additional amount of air is available to the isolated compartment C s  during the inspiratory phase of each breath, namely the air traveling from the neighboring compartment(s) C through the collateral channels CH, which enables volumetric expansion of the isolated compartment C s  during inspiration, resulting during expiration in air movement away from the isolated compartment C s  to atmosphere through the catheter lumen and the collateral channels CH. Thus, air is expelled through the catheter lumen during each exhalation and will register as positive airflow on the flow-measuring device  18 . This positive airflow through the catheter lumen provides an indication of whether or not there is collateral ventilation occurring in the targeted compartment C s . 
     This technique of measuring collateral flow in a lung compartment is analogous to adding another lung compartment, or lobe with infinitely large compliance, to the person&#39;s lungs, the added compartment being added externally. Depending on the system dynamics, some air may be expelled through the catheter lumen during exhalation in the absence of collateral channels, however at a different rate, volume and trend than that in the presence of collateral channels. 
     In other embodiments, the catheter  10  is connected with an accumulator or special container  22  as illustrated in  FIGS. 5A-5D ,  6 . The container  22  has a very low resistance to airflow, such as but not limited to e.g. a very compliant bag or slack collection bag. The container  22  is connected to the external end or distal end  24  of the catheter  10  and its internal lumen extending therethrough in a manner in which the inside of the special container  22  is communicating only with the internal lumen. During respiration, when collateral channels are not present as illustrated in  FIGS. 5A-5B , the special container  22  does not expand. The target compartment Cs is sealed by the isolation balloon  14  so that air enters and exits the non-target compartment C. During respiration, in the presence of collateral channels as illustrated in  FIGS. 5C-5D , the special container  22  will initially increase in volume because during the first exhalation some portion of the airflow received by the sealed compartment C s  via the collateral channels CH will be exhaled through the catheter lumen into the external special container  22 . 
     The properties of the special container  22  are selected in order for the special container  22  to minimally influence the dynamics of the collateral channels CH, in particular a highly inelastic special container  22  so that it does not resist inflation. Under the assumption that the resistance to collateral ventilation is smaller during inspiration than during expiration, the volume in the special container  22  will continue to increase during each subsequent respiratory cycle because the volume of air traveling via collateral channels CH to the sealed compartment C s  will be greater during inspiration than during expiration, resulting in an additional volume of air being forced through the catheter lumen into the special container  22  during exhalation. 
     Optionally, a flow-measuring device  18  or/and a pressure sensor  20  may be included, as illustrated in  FIG. 6 . The flow-measuring device  18  and/or the pressure sensor  20  may be disposed at any location along the catheter shaft  12  (as indicated by arrows) so as to communicate with the catheter&#39;s internal lumen. When used together, the flow-measuring device  18  and the pressure sensor  20  may be placed in series. A one-way valve  16  may also be placed in series with the flow-measuring device  18  or/and pressure sensor  20 . It may be appreciated that the flow-measuring device  18  can be placed instead of the special container  22  or between the special container  22  and the isolated lung compartment, typically at but not limited to the catheter-special container junction, to measure the air flow rate in and out of the special container and hence by integration of the flow rate provide a measure of the volume of air flowing through the catheter lumen from/to the sealed compartment C s . 
     It can be appreciated that measuring flow can take a variety of forms, such as but not limited to measuring flow directly with the flow-measuring device  18 , and/or indirectly by measuring pressure with the pressure sensor  20 , and can be measured anywhere along the catheter shaft  12  with or without a one-way valve  16  in conjunction with the flow sensor  18  and with or without an external special container  22 . 
     Furthermore, a constant bias flow rate can be introduced into the sealed compartment C s  with amplitude significantly lower than the flow rate expected to be measured due to collateral flow via the separate lumen in the catheter  10 . For example, if collateral flow measured at the flow meter  18  is expected to be in the range of 1 ml/min, the bias flow rate can be, but not limited to one tenth (0.1) or one one-hundredth (0.01) of that amount of equal or opposite amplitude. The purpose of the bias flow is to continuously detect for interruptions in the detection circuit (i.e., the working channel of the bronchoscope and any other tubing between the flow meter and catheter) such as kinks or clogs, and also to increase response time in the circuit (due to e.g. inertia). Still, a quick flush of gas at a high flow rate (which is distinguished from the collateral ventilation measurement flow rate) can periodically be introduced to assure an unclogged line. 
     In addition to determining the presence of collateral ventilation of a target lung compartment, the degree of collateral ventilation may be quantified by methods of the present invention. In one embodiment, the degree of collateral ventilation is quantified based on the resistance through the collateral system R coll . R coll  can be determined based on the following equation: 
     
       
         
           
             
               
                 
                   
                      
                     
                       
                         
                           P 
                           b 
                         
                         _ 
                       
                       
                         
                           Q 
                           fm 
                         
                         _ 
                       
                     
                      
                   
                   = 
                   
                     
                       R 
                       coll 
                     
                     + 
                     
                       R 
                       saw 
                     
                   
                 
               
               
                 
                   ( 
                   1 
                   ) 
                 
               
             
           
         
       
     
     where R coll  constitutes the resistance of the collateral channels, R saw  characterizes the resistance of the small airways, and  P b    and  Q fm    represent the mean pressure and the mean flow measured by a catheter isolating a target lung compartment in a manner similar to the depictions of  FIGS. 4A-4D . 
     For the sake of simplicity, and as a means to carry out a proof of principle,  FIGS. 7A-7B  depict a graphical representation of a simplified collateral system of a target lung compartment C s . A single elastic compartment  30  represents the target lung compartment C s  and is securely positioned inside a chamber  32  to prevent any passage of air between the compartment  30  and the chamber  32 . The chamber  32  can be pressurized to a varying negative pressure relative to atmosphere, representing the intrathoracic pressure P p1 . The elastic compartment  30 , which represents the target compartment in the lung C s , communicates with the atmospheric environment through passageway  40 . In addition, the elastic compartment  30  also communicates with the atmospheric environment through collateral pathway  41 , representing collateral channels CH of the target compartment of the lung C s . 
     A catheter  34  is advanceable through the passageway  40 , as illustrated in  FIGS. 7A-7B . The catheter  34  comprises a shaft  36 , an inner lumen  37  therethrough and an occlusion member  38  mounted near its distal end. The catheter  34  is specially equipped to seal the area between the catheter shaft  36  and the passageway  40  such that only the lumen  37  inside the catheter  34 , which extends the length of the catheter  34 , allows for direct communication between the compartment  30  and atmosphere. On the opposite end of the catheter  34 , a flow-measuring device  42  and a pressure sensor  44  are placed in series to detect pressure and flow in the catheter&#39;s inside lumen  37 . A one-way valve  48  positioned next to the flow measuring device  42  allows for the passage of air in only one direction, namely from the compartment  30  to atmosphere. The flow measuring device  42 , the pressure sensor device  44  and the one-way valve  48  can be placed anywhere along the length of the catheter lumen, typically at but not limited to the proximal end of the catheter shaft  36 . It should be appreciated that measuring pressure inside the compartment  30  can be accomplished in a variety of forms, such as but not limited to connecting the pressure sensor  44  to the catheter&#39;s inside lumen  37 . For instance, it can also be accomplished by connecting the pressure sensor  44  to a separate lumen inside the catheter  34 , which extends the entire length of the catheter  34  communication with the airways distal to the seal. 
     At any given time, the compartment  30  may only communicate to atmosphere either via the catheter&#39;s inside lumen  37  representing R saw  and/or the collateral pathway  41  representing R coll . Accordingly, during inspiration, as illustrated in  FIG. 7A , P p1  becomes increasingly negative and air must enter the compartment  30  solely via collateral channels  41 . Whereas during expiration, illustrated in  FIG. 7B , air may leave via collateral channels  41  and via the catheter&#39;s inside lumen  37 . 
       FIGS. 8A-8C  illustrate measurements taken from the system of  FIGS. 7A-7B  during inspiration and expiration phases.  FIG. 8A  illustrates a collateral flow curve  50  reflecting the flow Q coll  through the collateral pathway  41 .  FIG. 8B  illustrates a catheter flow curve  52  reflecting the flow Q fm  through the flow-measuring device  42 . During inspiration, air flows through the collateral pathway  41  only; no air flows through the flow-measuring device  42  since the one-way valve  48  prevents such flow. Thus,  FIG. 8A  illustrates a negative collateral flow curve  50  and  FIG. 8B  illustrates a flat, zero-valued catheter flow curve  52 . During expiration, a smaller amount of air, as compared to the amount of air entering the target compartment Cs during inspiration, flows back to atmosphere through the collateral pathway  41 , as illustrated by the positive collateral flow curve  50  of  FIG. 8A , while the remaining amount of air flows through the catheter lumen  37  back to atmosphere, as illustrated by the positive catheter flow curve  52  of  FIG. 8B . 
     The volume of air flowing during inspiration and expiration can be quantified by the areas under the flow curves  50 ,  52 . The total volume of air V 0  entering the target compartment  30  via collateral channels  41  during inspiration can be represented by the colored area under the collateral flow curve  50  of  FIG. 8A . The total volume of air V 0  may be denoted as V 0 =V 1 +V 2 , whereby V 1  is equal to the volume of air expelled via the collateral channels  41  during expiration (indicated by the grey-colored area under the collateral flow curve  50  labeled V 3 ), and V 2  is equal to the volume of air expelled via the catheter&#39;s inside lumen  37  during expiration (indicated by the colored area under the catheter flow curve  52  of  FIG. 8B  labeled V 4 ). 
     The following rigorous mathematical derivation demonstrates the validity of these statements and the relation stated in Eq. 1: 
     Conservation of mass states that in the short-term steady state, the volume of air entering the target compartment  30  during inspiration must equal the volume of air leaving the same target compartment  30  during expiration, hence 
         V   0 =−( V   3   +V   4 )  (2)
 
     Furthermore, the mean rate of air entering and leaving the target compartment solely via collateral channels during a complete respiratory cycle (T resp ) can be determined as 
     
       
         
           
             
               
                 
                   
                     
                       Q 
                       coll 
                     
                     _ 
                   
                   = 
                   
                     
                       
                         
                           V 
                           0 
                         
                         + 
                         
                           V 
                           3 
                         
                       
                       
                         T 
                         resp 
                       
                     
                     = 
                     
                       
                         V 
                         2 
                       
                       
                         T 
                         resp 
                       
                     
                   
                 
               
               
                 
                   ( 
                   3 
                   ) 
                 
               
             
           
         
       
     
     where V 2  over T resp  represents the net flow rate of air entering the target compartment  30  via the collateral channels  41  and returning to atmosphere through a different pathway during T resp . Accordingly, V 2  accounts for a fraction of V 0 , the total volume of air entering the target compartment  30  via collateral channels  41  during T resp , hence V 0  can be equally defined in terms of V 1  and V 2  as 
         V   0   =V   1   +V   2   (4)
 
     where V 1  represents the amount of air entering the target compartment  30  via the collateral channels  41  and returning to atmosphere through the same pathway. Consequently, substitution of V 0  from Eq. 4 into Eq. 3 yields 
         V   1   =−V   3   (5)
 
     and substitution of V 0  from Eq. 2 into the left side of Eq. 4 following substitution of V 1  from Eq. 5 into the right side of Eq. 4 results in 
         V   4   =V   2   (6)
 
     Furthermore, the mean flow rate of air measured at the flowmeter  42  during T resp  can be represented as 
     
       
         
           
             
               
                 
                   
                     
                       Q 
                       fm 
                     
                     _ 
                   
                   = 
                   
                     
                       V 
                       4 
                     
                     
                       T 
                       resp 
                     
                   
                 
               
               
                 
                   ( 
                   7 
                   ) 
                 
               
             
           
         
       
     
     where substitution of V 4  from Eq. 6 into Eq. 7 yields 
     
       
         
           
             
               
                 
                   
                     
                       Q 
                       fm 
                     
                     _ 
                   
                   = 
                   
                     
                       - 
                       
                         
                           V 
                           2 
                         
                         
                           T 
                           resp 
                         
                       
                     
                     = 
                     
                       - 
                       
                         
                           Q 
                           coll 
                         
                         _ 
                       
                     
                   
                 
               
               
                 
                   ( 
                   8 
                   ) 
                 
               
             
           
         
       
     
     Ohms&#39;s law states that in the steady state 
           P     s =(    Q   coll   · R   coll )  (9)
 
     where  P s    represents the mean inflation pressure in the target compartment required to sustain the continuous passage of  Q coll    through the resistive collateral channels represented by R coll . Visual inspection of the flow and pressure signals ( FIG. 8C ) within a single T resp  shows that during the inspiratory time, P b  corresponds to P s  since no air can enter or leave the isolated compartment  30  via the catheter&#39;s inside lumen  37  during the inspiratory phase. During expiration, however, P b ═O since it is measured at the valve opening where pressure is atmospheric, while P s  must still overcome the resistive pressure losses produced by the passage of Qf m  through the long catheter&#39;s inside lumen  37  represented by R saw  during the expiratory phase effectively making  P s    less negative than  P b    by  Q fm   ·R saw  Accordingly 
           P   s   =    P   b   +    Q   fm   · R   saw   (10)
 
     and substitution of P s  from Eq. 9 into Eq. 10 results in 
           P   b   =    Q   coll   · R   coll −    Q   fm   · R   saw   (11)
 
     after subsequently solving for P b . Furthermore, substitution of  Q coll    Eq. 8 into Eq. 11 yields 
           P   b   =−    Q   fm   ·( R   coll   +R   saw )  (12)
 
     and division of Eq. 12 by  Q fm    finally results in 
     
       
         
           
             
               
                 
                   
                     
                       
                         P 
                         b 
                       
                       _ 
                     
                     
                       
                         Q 
                         fm 
                       
                       _ 
                     
                   
                   = 
                   
                     - 
                     
                       ( 
                       
                         
                           R 
                           coll 
                         
                         + 
                         
                           R 
                           saw 
                         
                       
                       ) 
                     
                   
                 
               
               
                 
                   ( 
                   13 
                   ) 
                 
               
             
           
         
       
     
     where the absolute value of Eq. 13 leads back to the aforementioned relation originally stated in Eq. 1. 
     The system illustrated in  FIGS. 7A-7B  can be represented by a simple circuit model as illustrated in  FIGS. 9A-9C . The air storage capacity of the alveoli confined to the isolated compartment  30  representing C s  is designated as a capacitance element  60 . The pressure gradient (P s -P b ) from the alveoli to atmosphere via the catheter&#39;s inside lumen  37  is caused by the small airways resistance, R saw , and is represented by resistor  64 . The pressure gradient from the alveoli to atmosphere through the collateral channels is generated by the resistance to collateral flow, R coll , and is represented by resistor  62 . 
     Accordingly, the elasticity of the isolated compartment  30  is responsible for the volume of air obtainable solely across R coll  during the inspiratory effort and subsequently delivered back to atmosphere through R saw  and R coll  during expiration. Pressure changes during respiration are induced by the variable pressure source, P p1  representing the varying negative pleural pressure within the thoracic cavity during the respiratory cycle. An ideal diode  66  represents the one-way valve  48 , which closes during inspiration and opens during expiration. Consequently, as shown in  FIGS. 10A-10B , the flow measured by the flow meter (Q fm ) is positive during expiration and zero during inspiration, whereas the pressure recorded on the pressure sensor (P b ) is negative during inspiration and zero during expiration. 
     Evaluation of Eqs. 1 &amp; 8 by implementation of a computational model of the collateral system illustrated in  FIGS. 7A-7B  and  FIGS. 9A-9C  yields the graphical comparisons presented in  FIGS. 11A-11D .  FIG. 11A  displays the absolute values of mean Q fm (|  Q fm   |) and mean Q coll (|  Q coll   |) while the  FIG. 11B  shows the model parameters R coll +R saw  plotted together with |  P b   /  Q coll   | as a function of R coll . The values denote independent realizations of computer-generated data produced with different values of R coll  while R saw  is kept constant at 1 cmH 2 O/(ml/s).  FIG. 11A  displays the absolute values of |  Q fm   | and |  Q coll   | while  FIG. 11C  shows the model parameters R coll +R saw  plotted together with |  P b   /  Q coll   | as a function of R saw . The values denote independent realizations of computer-generated data produced with different values of R saw  while R coll  is kept constant at 1 cm H 2 O/(ml/s). It becomes quite apparent from  FIGS. 11A-11B  that the flow is maximal when R coll≈ R saw  and diminishes to zero as R coll  approaches the limits of either “overt collaterals” or “no collaterals”. Accordingly, small measured flow Q fm  can mean both, very small and very large collateral channels and hence no clear-cut decision can be made regarding the existence of collateral ventilation unless R coll +R saw  is determined as |  P b   /  Q fm   |. The reason for this is that when R coll  is very small compared to R saw , all gas volume entering the target compartment via the collateral channels leaves via the same pathway and very little gas volume is left to travel to atmosphere via the small airways as the isolated compartment empties. The measured pressure P b , however, changes accordingly and effectively normalizes the flow measurement resulting in an accurate representation of R coll +R saw , which is uniquely associated with the size of the collateral channels and the correct degree of collateral ventilation. 
     Similarly,  FIGS. 11C-11D  supplement  FIGS. 11A-11B  as it shows how the measured flow Q fm  continuously diminishes to zero as R saw  becomes increasingly greater than R coll  and furthermore increases to a maximum, as R saw  turns negligible when compared to R coll . When R saw  is very small compared to R coll , practically all gas volume entering the target compartment via the collateral channels travels back to atmosphere through the small airways and very little gas volume is left to return to atmosphere via the collateral channels as the isolated compartment empties. Thus, determination of |  P b   /  Q fm   | results in an accurate representation of R coll +R saw  regardless of the underlying relation amongst R coll  and R saw . In a healthy human, resistance through collateral communications, hence R coll , supplying a sublobar portion of the lung is many times (10-100 times) as great as the resistance through the airways supplying that portion, R saw  (Inners 1979, Smith 1979, Hantos 1997, Suki 2000). Thus in the normal individual, R coll  far exceeds R saw  and little tendency for collateral flow is expected. In disease, however, this may not be the case (Hogg 1969, Terry 1978). In emphysema, R saw  could exceed R coll  causing air to flow preferentially through collateral pathways. 
     Therefore, the above described models and mathematical relationships can be used to provide a method which indicates the degree of collateral ventilation of the target lung compartment of a patient, such as generating an assessment of low, medium or high degree of collateral ventilation or a determination of collateral ventilation above or below a clinical threshold. In some embodiments, the method also quantifies the degree of collateral ventilation, such generating a value which represents R coll . Such a resistance value indicates the geometric size of the collateral channels in total for the lung compartment. Based on Poiseuille&#39;s Law with the assumption of laminar flow, 
         R ∝(η× L )/ r   4   (14)
 
     |  P b   /  Q fm   | wherein η represents the viscosity of air, L represents the length of the collateral channels and r represents the radius of the collateral channels. The fourth power dependence upon radius allows an indication of the geometric space subject to collateral ventilation regardless of the length of the collateral channels. 
       FIG. 12A  illustrates a two-compartment model which is used to generate a method quantifying the degree of collateral ventilation, including a) determining the resistance to segmental collateral flow R coll , b) determining the state of segmental compliance C s , and c) determining the degree of segmental hyperinflation q s . Again, C s  characterizes the compliance of the target compartment or segment. C L  represents the compliance of the rest of the lobe. R coll  describes the resistance to the collateral airflow.  FIG. 12B  provides an electrical circuit analog model. In this example, at time t=t 1 , approximately 5-10 ml of 100% inert gas such as He (q he ) is infused. After a period of time, such as one minute, the pressure (P S ) &amp; the fraction of He (F he     s   ) are measured. 
     The dynamic behavior of the system depicted in  FIGS. 12A-12B  can be described by the time constant t coll   
     
       
         
           
             
               
                 
                   
                     t 
                     coll 
                   
                   = 
                   
                     
                       R 
                       coll 
                     
                     · 
                     
                       
                         
                           C 
                           s 
                         
                          
                         
                           C 
                           L 
                         
                       
                       
                         
                           
                             C 
                             s 
                           
                           + 
                           
                             C 
                             L 
                           
                         
                         
                            
                           
                             C 
                             s 
                           
                         
                       
                     
                   
                 
               
               
                 
                   ( 
                   15 
                   ) 
                 
               
             
           
         
       
     
     At time t 1 =30 s, a known fixed amount of inert gas (q he : 5-10 ml of 100% He) is rapidly injected into the target compartment C s , while the rest of the lobe remains occluded, and the pressure (P S ) and the fraction of He (F he     s   ) are measured in the target segment for approximately one minute (T=60 s).  FIGS. 12C-12E  illustrate the resulting time changes in volumes, pressures and gas concentrations in the target compartment C s  and the rest of the lobe C L . Eqs. 16-21 state the mathematical representation of the lung volumes, pressures and gas concentrations at two discrete points in time, t 1  and t 2 . 
     
       
         
           
             
               
                 
                   
                     
                       q 
                       s 
                     
                      
                     
                       ( 
                       
                         t 
                         1 
                       
                       ) 
                     
                   
                   = 
                   
                     
                       
                         q 
                         s 
                       
                        
                       
                         ( 
                         0 
                         ) 
                       
                     
                     + 
                     
                       q 
                       he 
                     
                   
                 
               
               
                 
                   ( 
                   16 
                   ) 
                 
               
             
             
               
                 
                   
                     
                       
                         q 
                         s 
                       
                        
                       
                         ( 
                         
                           t 
                           2 
                         
                         ) 
                       
                     
                     + 
                     
                       
                         q 
                         L 
                       
                        
                       
                         ( 
                         
                           t 
                           2 
                         
                         ) 
                       
                     
                   
                   = 
                   
                     
                       
                         q 
                         s 
                       
                        
                       
                         ( 
                         0 
                         ) 
                       
                     
                     + 
                     
                       
                         q 
                         L 
                       
                        
                       
                         ( 
                         0 
                         ) 
                       
                     
                     + 
                     
                       q 
                       he 
                     
                   
                 
               
               
                 
                   ( 
                   17 
                   ) 
                 
               
             
             
               
                 
                   
                     
                       P 
                       S 
                     
                      
                     
                       ( 
                       
                         t 
                         1 
                       
                       ) 
                     
                   
                   = 
                   
                     
                       q 
                       he 
                     
                     
                       C 
                       s 
                     
                   
                 
               
               
                 
                   ( 
                   18 
                   ) 
                 
               
             
             
               
                 
                   
                     
                       P 
                       S 
                     
                      
                     
                       ( 
                       
                         t 
                         2 
                       
                       ) 
                     
                   
                   = 
                   
                     
                       q 
                       he 
                     
                     
                       
                         C 
                         s 
                       
                       + 
                       
                         C 
                         L 
                       
                     
                   
                 
               
               
                 
                   ( 
                   19 
                   ) 
                 
               
             
             
               
                 
                   
                     
                       F 
                       
                         he 
                         s 
                       
                     
                      
                     
                       ( 
                       
                         t 
                         1 
                       
                       ) 
                     
                   
                   = 
                   
                     
                       q 
                       he 
                     
                     
                       q 
                       
                         s 
                          
                         
                           ( 
                           
                             t 
                             1 
                           
                           ) 
                         
                       
                     
                   
                 
               
               
                 
                   ( 
                   20 
                   ) 
                 
               
             
             
               
                 
                   
                     
                       F 
                       
                         he 
                         s 
                       
                     
                      
                     
                       ( 
                       
                         t 
                         2 
                       
                       ) 
                     
                   
                   = 
                   
                     
                       q 
                       he 
                     
                     
                       
                         
                           q 
                           s 
                         
                          
                         
                           ( 
                           
                             t 
                             1 
                           
                           ) 
                         
                       
                       + 
                       
                         
                           q 
                           L 
                         
                          
                         
                           ( 
                           
                             t 
                             2 
                           
                           ) 
                         
                       
                     
                   
                 
               
               
                 
                   ( 
                   21 
                   ) 
                 
               
             
           
         
       
     
     As a result, the following methods may be performed for each compartment or segment independently: 1) Assess the degree of segmental hyperinflation, 2) Determine the state of segmental compliance, 3) Evaluate the extent of segmental collateral communications. 
     Segmental Hyperinflation 
     The degree of hyperinflation in the target segment, q s (O), can be determined by solving Eq. 16 for q s (0) and subsequently substituting q s (t 1 ) from Eq. 20 into Eq. 16 after appropriate solution of Eq. 20 for q s (t 1 ) as 
     
       
         
           
             
               
                 
                   
                     
                       q 
                       S 
                     
                      
                     
                       ( 
                       0 
                       ) 
                     
                   
                   = 
                   
                     
                       q 
                       he 
                     
                     · 
                     
                       ( 
                       
                         
                           1 
                           - 
                           
                             
                               F 
                               
                                 he 
                                 S 
                               
                             
                              
                             
                               ( 
                               
                                 t 
                                 1 
                               
                               ) 
                             
                           
                         
                         
                           
                             F 
                             
                               he 
                               S 
                             
                           
                            
                           
                             ( 
                             
                               t 
                               1 
                             
                             ) 
                           
                         
                       
                       ) 
                     
                   
                 
               
               
                 
                   ( 
                   22 
                   ) 
                 
               
             
           
         
       
     
     Segmental Compliance 
     The state of compliance in the target segment, C S , can be determined simply by solving Eq. 18 for C S  as 
     
       
         
           
             
               
                 
                   
                     C 
                     S 
                   
                   = 
                   
                     
                       q 
                       he 
                     
                     
                       
                         P 
                         S 
                       
                        
                       
                         ( 
                         
                           t 
                           1 
                         
                         ) 
                       
                     
                   
                 
               
               
                 
                   ( 
                   23 
                   ) 
                 
               
             
           
         
       
     
     Segmental Collateral Resistance 
     A direct method for the quantitative determination of collateral system resistance in lungs, has been described above. Whereas, the calculation below offers an indirect way of determining segmental collateral resistance. 
     The compliance of the rest of the lobe, C L , can be determined by solving Eq. 19 for C L  and subsequently substituting C S  with Eq. 23. Accordingly 
     
       
         
           
             
               
                 
                   
                     C 
                     L 
                   
                   = 
                   
                     
                       q 
                       he 
                     
                     · 
                     
                       
                         
                           
                             P 
                             S 
                           
                            
                           
                             ( 
                             
                               t 
                               1 
                             
                             ) 
                           
                         
                         - 
                         
                           
                             P 
                             S 
                           
                            
                           
                             ( 
                             
                               t 
                               2 
                             
                             ) 
                           
                         
                       
                       
                         
                           
                             P 
                             S 
                           
                            
                           
                             ( 
                             
                               t 
                               1 
                             
                             ) 
                           
                         
                          
                         
                           
                             P 
                             S 
                           
                            
                           
                             ( 
                             
                               t 
                               2 
                             
                             ) 
                           
                         
                       
                     
                   
                 
               
               
                 
                   ( 
                   24 
                   ) 
                 
               
             
           
         
       
     
     As a result, the resistance to collateral flow/ventilation can alternatively be found by solving Eq. 15 for R coll  and subsequent substitution into Eq. 15 of C S  from Eq. 24 and C L  from Eq. 25 as 
     
       
         
           
             
               
                 
                   
                     R 
                     coll 
                   
                   = 
                   
                     
                       t 
                       coll 
                     
                     
                       C 
                       eff 
                     
                   
                 
               
               
                 
                   ( 
                   25 
                   ) 
                 
               
             
           
         
       
     
     where C eff  is the effective compliance as defined in Eq. 15. 
     Additional Useful Calculation for Check and Balances of all Volumes 
     The degree of hyperinflation in the rest of the lobe, hence q L (O), can be determined by solving Eq. 17 for q L (0) and subsequently substituting q s (t 2 )+q L (t 2 ) from Eq. 21 into Eq. 17 after appropriate solution of Eq. 21 for q s (t 2 )+q L (t 2 ). Thus 
     
       
         
           
             
               
                 
                   
                     
                       q 
                       L 
                     
                      
                     
                       ( 
                       0 
                       ) 
                     
                   
                   = 
                   
                     
                       q 
                       he 
                     
                     · 
                     
                       ( 
                       
                         
                           
                             
                               F 
                               
                                 he 
                                 S 
                               
                             
                              
                             
                               ( 
                               
                                 t 
                                 1 
                               
                               ) 
                             
                           
                           - 
                           
                             
                               F 
                               
                                 he 
                                 S 
                               
                             
                              
                             
                               ( 
                               
                                 t 
                                 2 
                               
                               ) 
                             
                           
                         
                         
                           
                             
                               F 
                               
                                 he 
                                 S 
                               
                             
                              
                             
                               ( 
                               
                                 t 
                                 1 
                               
                               ) 
                             
                           
                            
                           
                             
                               F 
                               
                                 he 
                                 S 
                               
                             
                              
                             
                               ( 
                               
                                 t 
                                 2 
                               
                               ) 
                             
                           
                         
                       
                       ) 
                     
                   
                 
               
               
                 
                   ( 
                   26 
                   ) 
                 
               
             
           
         
       
     
     Equation 26 provides an additional measurement for check and balances of all volumes at the end of the clinical procedure. 
     Regardless of the method of quantifying collateral ventilation, the magnitude of collateral ventilation is dependent on the patient&#39;s respiratory mechanics. For instance, a patient that is breathing very shallow at −2 cmH 2 O of pleural pressure creates a minimal amount of lung compartment expansion and hence the collateral channels remain somewhat resistive. The measured collateral ventilation will therefore be correspondingly low. Conversely, if a patient is breathing deep at −10 cm H 2 O of pleural pressure, a lot of lung expansion takes place which stretches the effective cross-sectional area of the collateral channels and hence the collateral channels become less resistive to flow resulting in a commensurate increase in collateral ventilation (references where Rcoll=f(V) as in Woolcock&#39;s 1971 or Inners&#39; 1979, and references with and Rcoll=f(P) as in Robinson&#39;s 1978 and Olsen&#39;s 1986). Even in the ideal situation where the resistance to collateral channels remains independent of effort, greater effort translates into greater airflow (Baker&#39;s 1969 paper). 
     Therefore, an aspect of the present invention includes measuring the patient breathing effort so that the collateral ventilation measurement can be calculated as a function of the degree and/or frequency of that effort, in effect normalizing the measurement to any situation. The breathing effort can be measured in terms of tidal volume inspired by the patient, or by inspiratory flow rate, peak inspiratory flow rate, pleural pressure created (for example as measured by an esophageal pressure transducer), upper airway pressure, work-of-breathing in joules of energy exerted per liter of air inspired, thoracic cavity expansion (such as measured by chest wall expansion) or other means.  FIGS. 13A-13C  illustrate changes in measured variables based on degree of effort, i.e. during shallow and deep breathing. For example,  FIG. 13A  illustrates pressure measurements in a target lung compartment. At t=0 (t 0 ), there is a change in respiratory effort so that the depth of inspiration is increased. Consequently the amplitude of the pressure wave is increased. Similarly, referring to  FIG. 13B , the corresponding volumetric flow rate wave also increases in amplitude at t=0 (t 0 ) with a larger mean flow rate leaving the target lung compartment as a result. And, referring to  FIG. 13C , the volume leaving the target lung compartment and accumulated over time, such as within a specialized container, may be calculated by integration of the volumetric flow rate data from  FIG. 13B . As shown, the slope of the volume curve changes at t=0 (t 0 ). The slope denoting the change in volume over time corresponds to the mean flow rate. 
     In some embodiments, a specially configured breathing effort sensor is provided. Such sensors include but are not limited to a mouthpiece that allows for simultaneous passage through the mouth of the isolation catheter  10  and measurement of airflow through the mouthpiece (around the outside of the catheter shaft). 
       FIGS. 14A-14B  illustrate changes in measured variables based on frequency of effort, i.e. during fast and slow breathing. For example,  FIG. 14A  illustrates volumetric flow rate measurements in a target lung compartment. At t=0 (t 0 ), there is a change in respiratory frequency so that the frequency of respiration is decreased or slowed down resulting in a smaller mean flow rate leaving the target lung compartment. Similarly, referring to  FIG. 14B , the volume accumulated over time, such as within a specialized container, may be calculated by integration of the volumetric flow rate data from  FIG. 14A . As shown, the slope of the volume curve changes at t=0 (t 0 ) indicating smaller volumetric increases per breath. The slope denoting the change in volume over time corresponds to the mean flow rate. 
     The units of measure of the collateral ventilation variable, which takes into account the degree and/or frequency of the involved respiratory effort, are therefore reported in units of A/B where A is the measurement of collateral ventilation and B is the measurement of respiratory drive. The result of the normalized collateral ventilation variable can be reported, for example, as but not limited to an average, a peak value or a range. Thus, it should be recognized that the desired measurement and reporting of the collateral ventilation normalized result includes a mathematical relation and in its most convenient form, a system and the necessary devices to acquire all the needed measured parameters in a single instrument to apply the said mathematical relation to perform the calculation. 
     It should be appreciated that the normalization technique subject to this invention is independent of the exact collateral ventilation measurement method; any collateral ventilation measurement method can be used with this novel normalization technique. 
     In some embodiments, detection of collateral ventilation is assisted with the application of medically safe continuous positive airway pressure (CPAP), as illustrated in  FIG. 15 . As shown, the targeted lung compartment is isolated as previously described with the placement of an isolation catheter into the targeted lung compartment of the patient P. In this embodiment, the isolation catheter is placed with the use of a bronchoscope  60  providing an endoscopic view with the use of a monitor  62 . CPAP is administered via a nasal or oral-nasal non-invasive mask  64 , positionable over the patient&#39;s face, which is connected to a CPAP ventilator  66 . This specially configured mask  64  simultaneously allows for the administration of CPAP, the passage of the isolation catheter, and optionally breath sensors to measure breathing effort. The isolated target lung compartment is not subjected directly to CPAP, however if collateral channels are present, the detection of these channels is facilitated because the CPAP amplifies the degree of airflow across the channels due to simple pressure gradient laws. Further hyperinflation due to air trapping is prevented using safe pressure levels and I:E ratios. Therefore, CPAP increases the measurement sensitivity of the collateral ventilation measurement technique of using an externally placed but communicating flow meter or special container. 
       FIG. 16A  illustrates example collateral flow measurements recorded by a flow meter. At t=0 (t 0 ), the CPAP mask is positioned on the patient and shortly thereafter CPAP is started resulting in an amplified signal. Thus, prior to t=0 (t 0 ) the flow signal  70  is relatively weak showing spontaneous breathing without CPAP. After t=0 (t 0 ), the flow signal  70 ′ is stronger showing an amplification of the flow rate signal due to CPAP. Similarly,  FIG. 16B  illustrates example pressure measurements taken in lung compartments that are not isolated by the isolation catheter (the pressure in the isolated lung compartment is less, closer to normal). At t=0 (t 0 ), the CPAP mask is positioned on the patient and shortly thereafter CPAP is started resulting in an amplified signal. Thus, prior to t=0 (t 0 ) the pressure signal  72  is relatively weak showing spontaneous breathing without CPAP. After t=0 (t 0 ), the pressure signal  72 ′ is stronger showing an amplification of the pressure signal due to CPAP. 
     In some embodiments, a single breath technique is used wherein the collateral ventilation and, if so measured, the patient&#39;s breathing effort, are measured for a single breath. Referring to  FIG. 17 , the targeted lung compartment C s  is cannulated and isolated with an externally communicating catheter  10  as previously described. Here, the patient P is shown having the catheter  10  advanced into the targeted lung compartment C s  and the flowmeter  18  and/or pressure sensor  20  and one-way valve  16  residing outside of his mouth. The flowmeter  18  and/or pressure sensor  20  is linked to a computer  80  which acquires the appropriate data. Example flow rate  82  and pressure curves  84  are shown. The cooperative patient P is instructed to breath out as much air as possible with a forced and extended exhalation effort (t 1 ), and at the end of exhalation (which is detectable with the breath sensing devices) the target lung compartment C s  is isolated (t 2 ). The patient then initiates a maximal inspiratory effort (t 3 ) and starts a deep exhalation (t 4 ) which then ends at (t 5 ). It is presumed that any air exiting the isolation catheter  10  during the deep exhalation (t 4 -t 5 ) would be from collateral ventilation. If collaterals were present, a flow peak  86  and a pressure peak  88 . 
     The collateral ventilation (and breathing effort if so measured) can be measured and reported as a function of a single breath peak inspiratory effort. Results can be reported normalized or unnormalized for the complete breath, a peak value during the breath, an average value during the breath, the value during a portion of the breath, for example but not limited to the first one second of the breath, an average value of a number of separate single breath measurements or maneuvers. The processing unit in the case of this embodiment includes the requisite algorithms and control systems to obtain and process the measurement as needed. 
     In additional embodiments, airflow measurements are made both before, during and after isolation of the targeted lung compartment C s , wherein such measurements are analyzed to evaluate collateral ventilation. For example, an external flow measuring device is configured to measure flow into and out of a targeted lung compartment C s  via an externally communicating catheter  10  placed into the compartment C s , as previously described. First, the compartment C s  is cannulated with the catheter  10 , but without isolating the bronchus. Referring to  FIG. 18A , the flow measurement through the catheter lumen is made, resulting in a flowrate curve  90  at baseline. Second, while the flow measurement continues, the bronchus is isolated by inflating the occluder balloon and the amplitude of the flowrate curve  90  increases if there is collateral flow. Then, while the flow measurement continues, the occluder balloon is deflated and the flowrate curve  90  decreases back to baseline. Corresponding volume and pressure measurement curves are shown in  FIG. 18B  and  FIG. 18C  respectively. Comparison of the airflow magnitude and direction as measured at the external flow-sensing device provides additional information about the collateral channels in the target compartment and/or verification of the system&#39;s integrity. For example, comparison of the amplitudes before and after isolation can also be used to quantify/or normalize the degree of flow via collateral channels and/or check for adequate isolation of the target compartment. This aspect of the invention includes the requisite systems and devices for processing the pre and post airflow measurements and may include an automatic isolation system controlled by instrumentation embedded in the processing unit. 
     In an additional embodiment of the present invention, as illustrated in  FIG. 19 , flow is measured via a catheter  10  as previously described. The occlusion member  14  is positioned and inflated to isolate the target lung compartment C s . As the patient breathes, both the target lung compartment C s  and the non-target compartment C expand and recoil as shown. The measured flow data  92  is closely inspected to compare the waveforms obtained during inspiration and exhalation (inhalation waveform=VI, exhalation waveform=VE). The ratio VINE in the presence of collateral ventilation differs from the ratio VINE in the absence of collateral ventilation. These and other differences in the waveform characteristics of inspiration versus exhalation shall facilitate determining whether collateral ventilation exists. 
     In some embodiments, as illustrated in  FIGS. 20A-20B , the isolation catheter  10  includes a fiberoptic endoscope, or bronchoscope  100 , with optional built-in imaging, illumination and/or steering.  FIG. 20A  illustrates the bronchoscope  100  inserted into an external sheath  102  having an occlusion member  104  and joined at a sheath proximal connector  106 . Exemplary embodiments of suitable external sheaths having inflation cuffs for use with bronchoscopes or other endoscopic instruments are described in U.S. Pat. No. 6,585,639, incorporated herein by reference for all purposes.  FIG. 20B  provides a more detailed illustration of the distal end of the bronchoscope  100  and sheath  102  of  FIG. 20A . Thus, a working channel  103  of the bronchoscope  100  is shown along with imaging features  105 . Referring back to  FIG. 20A , the bronchoscope  100  and sheath  102  are advanced down the trachea T of the patient P to the target lung compartment C s  so that the inflation cuff  104  is positioned to isolate the target lung compartment C s . The sheath  102  also includes a cuff inflation line/valve  108  which can be used to measure cuff pressure. The bronchoscope  100  includes an imaging cable  110  and light cable  112 , as shown. Optionally, a suction line  114  may also be connected with the bronchoscope  100 . The shaft of the bronchoscope includes a lumen extending most of its length to which a flow-measuring device  116  is connected external to the patient P. As shown, the flow-measuring device  116  has a power cord  118  and a signal to main processor  120 . Tubing  122  connects the bronchoscope  100  to an inlet  124  of the flow-measuring device  110 , wherein a check valve  126  is present along the tubing  122 . Air, gasses or other measured entities are released from the flow-measuring device  116  via an outlet  128 . The sheath  102  or an outer sleeve may be equipped with additional lumens that extend across the occlusion member  104  for the purpose of measuring flow or other respiratory or physiological parameters, or for delivering agents or tracer gases. 
     Alternatively, in the absence of a sheath  102  having an occlusion member  104 , a special catheter may be inserted into the lumen of the bronchoscope  100  and can be used to access the targeted lung compartment C s . The catheter may to create the isolation seal by any appropriate means, including creating an isolation seal with an inflatable element mounted on the distal end of the catheter or by connecting with or passing through an occlusal stent which is positioned to seal the bronchial lumen. For example,  FIGS. 21A-21C  illustrate the performance of a collateral ventilation test through an occlusal stent  130 . Referring to  FIG. 21A , an occlusal stent  130  is shown sealing a bronchial lumen leading to a target lumen compartment C s . A bronchoscope  100  is shown advanced to a position near the occlusal stent  130 . Referring to  FIG. 21B , a catheter  132  is advanced through the bronchoscope  100  and through the occlusal stent  130 , accessing the target lung compartment C s . The occlusal stent  130  includes a valve which allows the catheter  132  to advance therethrough while maintaining isolation of the target lung compartment C s . Measurements of pressure, flow or other respiratory or physiological parameters are then taken, with or without a one-way valve and/or external special container, either at the tip of the catheter  132  in the targeted lung compartment C s  or at the proximal end of the catheter  132 , external to the patient, through a lumen in the catheter  132  that extends the catheter&#39;s length. When accessing through an occlusal stent  130 , volume reduction therapy may then be performed by aspirating through the catheter  132  and stent  132 , as illustrated in  FIG. 21C . The catheter  132  is then removed and the volume reduction maintained. 
     In a similar but further embodiment, gas temperature is measured at some point along the catheter lumen either instead of the flow rate measurement or to complement the flow rate measurement, in order to further interpret the data being collected and/or to further distinguish between expiratory flow and inspiratory flow through the catheter lumen. 
     In a still further embodiment of the present invention, respiratory gas composition of the target lung compartment C s  is measured to facilitate further interpretation of the airflow data gathered by a flow measuring device. Such measurement may be taken separately or simultaneously with the flow rate measurements. For example, a certain decay rate of O 2  composition in the gas at the external end of the catheter may be indicative of no or little collateral flow, whereas a slower or no decay rate of O 2  may be indicative of collateral flow since fresh oxygen inspired by the patient can enter the target compartment C s  via the collateral channels. Other gases, for example CO 2 , can also be measured, as illustrated in  FIGS. 22A-22C .  FIG. 22A  illustrates a catheter  140  advanced through a bronchoscope  100  having an occlusion member  142  which seals a bronchial lumen leading to a target lumen compartment C s . The catheter  140  is connected with a flow sensing device  144 , as described above. In addition, the catheter  140  is connected with a gas sensing device  146 , such as a capnographer, having a gas sensor  148 . Measurements of flow or other respiratory or physiological parameters are then taken, with or without a one-way valve  149  and/or external special container, either at the tip of the catheter  140  in the targeted lung compartment C s  or at the proximal end of the catheter  140 , external to the patient, through a lumen in the catheter  140  that extends the catheter&#39;s length.  FIG. 22B-22C  illustrate example flow measurements  150  recorded by the flow sensing device  144 , along with corresponding CO 2  concentration measurements  152 .  FIG. 22B  illustrates a situation wherein there is no collateral flow between the target compartment C s  and a neighboring compartment C.  FIG. 22C  illustrates a situation wherein there is collateral flow between the target compartment C s  and the neighboring compartment C. As illustrated, differences can be seen in both the flow measurements  150  and CO 2  concentration measurements  152 . Therefore, measurement of various gases can be used to complement flow measurements for data interpretation. The gas composition together with the flow data can also be used to normalize the collateral flow measurement as previously described. 
     In yet another embodiment of the present invention, tracer gas infusion and measurement may be used to facilitate further interpretation of the airflow data gathered by a flow measuring device. Measurement of the composition of tracer gas, simultaneous with the measurement of airflow as previously described, will facilitate distinguishing between air from a neighboring lung compartment C entering through collateral channels and air that was native to the targeted isolated lung compartment C s . Typically the tracer gas is inert and is not absorbed by the tissue or blood stream in order to eliminate that variable in the collateral flow measurement, however optionally the gas can be a diffusible or absorbable gas for purposes described later.  FIG. 23A  illustrates a catheter  154  advanced through a bronchoscope  100  having an occlusion member  156  which seals a bronchial lumen leading to a target lumen compartment C s . The catheter  154  is connected with a flow sensing device  158 , as described above. In addition, the catheter  154  is connected with a tracer gas sensing device  160  and a tracer gas injection device  162 , such as a syringe. Measurements of flow or other respiratory or physiological parameters are then taken, with or without a one-way valve and/or external special container, either at the tip of the catheter  154  in the targeted lung compartment C s  or at the proximal end of the catheter  154 , external to the patient, through a lumen in the catheter  154  that extends the catheter&#39;s length.  FIG. 23B-23C  illustrate example flow measurements  164  recorded by the flow sensing device  166 , along with corresponding tracer gas concentration measurements  168 .  FIG. 23B  illustrates a situation wherein there is no collateral flow between the target compartment C s  and a neighboring compartment C. As shown, tracer gas concentration remains steady.  FIG. 22C  illustrates a situation wherein there is collateral flow between the target compartment C s  and the neighboring compartment C. As illustrated, the tracer gas concentration decays due to leakage through collateral channels. The tracer gas decay rate and flow measurements may be compared arithmetically to determine if collateral channels are present and/or the magnitude or size of the channels. 
     In still another embodiment of the present invention, absorbable gas infusion and measurement may be used to facilitate further interpretation of the airflow data gathered by a flow measuring device. Measurement of the composition of absorbable gas (such as oxygen), simultaneous with the measurement of airflow as previously described, will facilitate distinguishing between air from a neighboring lung compartment C entering through collateral channels and air that was native to the targeted isolated lung compartment C s .  FIG. 24A  illustrates a catheter  170  advanced through a bronchoscope  100  having an occlusion member  172  which seals a bronchial lumen leading to a target lumen compartment C s . The catheter  170  is connected with a flow sensing device  174 , as described above. In addition, the catheter  170  is connected with a gas delivery system  176  and gas source  178 . The gas delivery system  176  and flow sensing device  174  are connected with the catheter  170  via a switching valve  180  which allows the flow sensing device  174  to monitor collateral flow after the absorbable gas is delivered. Measurements of flow or other respiratory or physiological parameters are then taken, with or without a one-way valve and/or external special container, either at the tip of the catheter  170  in the targeted lung compartment C s  or at the proximal end of the catheter  170 , external to the patient, through a lumen in the catheter  170  that extends the catheter&#39;s length.  FIG. 23B-23C  illustrate example flow measurements  182  recorded by the flow sensing device  174 , along with corresponding absorbable concentration measurements  184 .  FIG. 23B  illustrates a situation wherein there is no collateral flow between the target compartment C s  and a neighboring compartment C. As shown, absorbable gas concentration decays via blood diffusion.  FIG. 22C  illustrates a situation wherein there is collateral flow between the target compartment C s  and the neighboring compartment C. As illustrated, the absorbable gas concentration decays at a faster rate due to diffusion and leakage through collateral channels. The absorbable gas decay rate and flow measurements may be compared arithmetically to determine if collateral channels are present. 
     To assist in accuracy of collateral flow measurements and other measurements, devices and methods are provided for seal testing of the isolation catheter.  FIG. 25A  illustrates a distal end of an isolation catheter  10  having an occlusion member  14  mounted thereon. The occlusion member  14  is shown inflated within a lung passageway LP. It is desired that the occlusion member  14  seals effectively to occlude the passageway LP, otherwise leakage by the occlusion member  14  may, for example, be mistaken for collateral flow thereby introducing error to the collateral flow measurements. Therefore, leak-testing may be performed to ensure appropriate seal. In one embodiment, the isolation catheter  10  includes a gas delivery lumen  200  and a gas sampling lumen  202 . The gas delivery lumen  200  exits the catheter  10  distally of the occlusion member  14 , such as through a delivery port  204 , as illustrated. The gas sampling lumen  202  exits the catheter  10  proximally of the occlusion member  14 , such as through sampling port  206 .  FIG. 25B  illustrates a cross-sectional view of  FIG. 25A  and shows the gas delivery lumen  200  and gas sampling lumen  202  extending through the wall of the catheter  10  while a main lumen  208  extends throughout the length of the catheter  10 . An inert gas is introduced through the isolation catheter  10  and is delivered through the delivery port  204 . As illustrated in  FIG. 25C , concentration of the inert gas within the lung passageway LP (or within a target compartment to which the lung passageway is connected) remains steady immediately after introduction of the gas, as indicated by curve  210 . A vacuum is applied to the sampling lumen  202 , as indicated by curve  212 . In the case of an insufficient seal, gas leakage between the occlusion member  14  and the wall of the lung passageway LP will be suctioned into the sampling lumen  202  and measured, as indicated by curve  214 . Such a leak test may be manual, automatic, or semi-automatic. Any processing/control unit external to the body for collateral ventilation testing may include the requisite controls and measuring devices for such leakage measurements. 
     It may be appreciated that in other embodiments, seal testing may alternatively or in addition be achieved by monitoring pressure within the occlusion member  14 . Referring back to  FIG. 25B , an inflation lumen  216  is shown extending through the wall of the isolation catheter  10 . Typically, the inflation lumen  216  extends to the occlusion member  14  to pass fluid to the occlusion member  14  for inflation. However, in this embodiment the inflation lumen  216  is attached at its proximal end to a pressure gauge to measure pressure within the occlusion member  14 . If the measured pressure falls below a desired level for adequate sealing, the pressure may be increased automatically or manually. Such pressure measurements may be taken continuously or semi-continuously. 
       FIG. 26  illustrates an embodiment of a system of the present invention for measuring collateral ventilation in one or more lung passageways of a patient. Here, the system includes a bronchoscope  100  inserted into an external sheath  102  having an occlusion member  104  and joined at a sheath proximal connector  106 . A working channel  103  extends within the bronchoscope  100  to a side port  231  (for introduction of a catheter or other instrument to the working lumen  103 ) and a connector  230 . A suction line  232  connects the working channel  103  with wall suction via the connector  230 . In addition, the connector  230  is used to connect the working channel  103  with a control valve  236 . The control valve  236  is in turn connected with an electronic unit  238  which includes an electronic control module, a signal acquisition unit and a signal processing unit. In this embodiment, the electronic unit  238  also houses an oxygen delivery compartment  240  containing oxygen for delivery through an oxygen line  242  to the control valve  236  and to the working lumen  103  of the bronchoscope  100 . In addition, a carbon dioxide sensor  246  is provided which is connected to a carbon dioxide line  248  which also connects with the control valve  236  and the working lumen  103 . Further, a flow meter  250  is connected to a collateral ventilation line  252  which also connects with the control valve  236  and the working lumen  103 . The control valve  236  is manipulated by control signals  254  sent from the electronic unit  238 . A display  256  is also connected with the electronic unit  238  for visual display of measurement data. In this embodiment, the system also includes a pressure transducer  258  which is connected with the occlusion member  104  via an inflation line  260 . The inflation line  250  also includes an inflation port  262  for introducing an inflation fluid to the occlusion member  104 . The system of  FIG. 26  may be used to perform a variety of the methods, measurements and treatments described herein. 
     It may be appreciated that any and all possible combinations of the embodiments described herein can be employed. For example, an external special container filled with O 2  connected to a targeted compartment via an isolation catheter is included at least by means of using the constituent parts of separate embodiments. Or, for example two of the above embodiments can be combined such that two external special containers are filled with different tracer gases and the special containers connected each to separate isolation catheters that are each isolating neighboring lung areas; analysis of the flow and gas composition in the special containers after a number of breaths may be correlative to collateral ventilation between the areas. 
     Systems, methods and devices of the present invention may be used to evaluate any number of target compartments C s  within the lungs of a patient. In particular, levels of collateral ventilation may be mapped to the target compartments so that the practitioner may determine the overall condition of the patient and the most desired course of treatment. For example, the right upper lung lobe (RUL) may be isolated and tested for collateral ventilation between it and the neighboring right middle lobe (RML). After the measurement is taken, the isolation catheter may be advanced deeper into the tracheobronchial tree to, for example, the apical segment of the right upper lobe and that segment can be tested for collateral ventilation between it and the neighboring anterior segment and posterior segments. As such, the diagnostic techniques described herein can be used to diagnostically map an area of the lung, or the complete lung with respect to collateral ventilation.  FIG. 27  illustrates an embodiment of a screen  280  indicating such measurements and mapping, wherein such a screen  280  may be seen on the display  256  of  FIG. 26 . Here, the screen  280  shows bar graphs  282  indicating a numerical value of collateral ventilation (or collateral ventilation resistance) between specific lung areas. For example, a bar graph  282  is shown between the RUL and RML indicating the numerical value of collateral ventilation between these two lobes. In addition, bar graphs  282  are shown between individual segments within each lobe. For example, the RUL has target compartments denoted B 1 , B 2 , B 3 , the RML has target compartments denoted B 4 , B 5 , B 6 , and B 7 , and the right lower lobe (RLL) has target compartments denoted B 8 , B 9 , and B 10 . Likewise, the left upper lobe (LUL) has target compartments denoted B 1 , B 2 , B 3 , B 4 , B 5 , and B 6 , and the left lower lung (LLL) has target compartments denoted B 8 , B 9 , B 10 . A bar graph  282  extending between B 1  and B 2  within the RUL indicates a numerical value of collateral ventilation (or collateral ventilation resistance) between the specific B 1  and B 2  target compartments. In addition, the screen  280  includes a visual depiction  284  of at least a portion of the lungs mapping the collateral ventilation data to the appropriate areas of the lungs. For example, the visual depiction  284  may include fissures between the lobes or target compartments wherein the shading of the fissure indicates the completeness of the fissure. In some embodiments, a darker fissure indicates a complete fissure and a lighter fissure indicates an incomplete fissure. Alternatively or in addition, a user may select an area of interest to display a cut-away view of the fissures in the selected area of interest. In addition, the screen  280  may include a link button  286  which changes the screen  280  to another screen  280 ′ depicting measurement data of other variables, such as gas exchange data or other diagnostic measurement data. Thus, the practitioner may use some or all of the visual information provided to assess the condition of the patient and determine the treatment plan. 
       FIG. 28  illustrates an embodiment of a method  300  of treating a patient. In this embodiment, the patient is referred by a non-specialist to a specialist in lung disease and treatment  302 . The patient then undergoes computed tomography (CT)  304  to produce detailed images of structures inside the body, particularly the lungs. A CT scanner directs a series of X-ray pulses through the body. Each X-ray pulse lasts only a fraction of a second and represents a “slice” of the organ or area being studied. The slices or pictures are recorded on a computer and can be saved for further study or printed out as photographs. The patient also undergoes pulmonary function testing (PFT) 304. PFT is a breathing test or series of tests to determine, for example, maximum volume of air the lungs can hold, how fast the patient can move air into and out of their lungs, and how easy it is for gas to pass from the lungs to the blood and the surface area available for gas movement. Bronchoscopy with collateral ventilation testing  306  is then performed on the patient. If no collateral ventilation (or a level of collateral ventilation below a threshold) is measured, Endobronchial Volume Reduction (EVR)  308  may be performed on the patient. If collateral ventilation (or a level of collateral ventilation above a threshold) is measured, some or all of the collateral flow channels may be treated  310  (e.g. obliterated or closed), such as with the use of RF, NaCl, sticky substances, perflubron, HF ultrasound, sclerosing agents, heating agents or the like. 
     Bronchoscopy with collateral ventilation testing  306  may then be performed again on the patient. If no collateral ventilation (or a level of collateral ventilation below a threshold) is measured, Endobronchial Volume Reduction (EVR)  308  may be performed on the patient. If collateral ventilation (or a level of collateral ventilation above a threshold) is still measured, some or all of the collateral flow channels may be additionally be treated  310 .  FIG. 29  illustrates an example iterative process of reducing collateral ventilation prior to EVR. An example limit  290  of collateral flow that is desired for successful EVR (i.e. the measurement of collateral flow should be below this level in order to perform EVR) is illustrated. Flow curve  292  prior to t 1  shows collateral flow that is above the limit  290 . The collateral flow channels are then treated. As shown, the flow curve  292  between t 1  and t 2  is reduced but still above the limit  290 . The collateral flow channels are then further treated. As shown, the flow curve  292  between t 2  and t 3  is further reduced but still above the limit  290 . The collateral flow channels are then further treated. As shown, the flow curve  292  beyond t 3  is now below the limit  290  and the patient may be treated with EVR. 
     Referring back to  FIG. 28 , in addition to bronchoscopy with collateral ventilation testing  306 , lung mapping  312  may be performed. If the lung mapping indicates no collateral ventilation (or a level of collateral ventilation below a threshold), Endobronchial Volume Reduction (EVR)  308  may be performed on the patient. If the lung mapping indicates collateral ventilation (or a level of collateral ventilation above a threshold) is measured, some or all of the collateral flow channels may be treated  310 . Such mapping may be repeating after repeated bronchoscopy with collateral ventilation testing  306 . 
     Devices, systems and methods of the present invention may also be useful to assess the sealing or valving performance of any endobronchial prosthesis, such as occlusal stents, plugs, one-way valves or other devices used in endobronchial lung volume reduction procedures. Examples of such devices are described in U.S. Pat. No. 6,287,290, “METHODS, SYSTEMS AND KITS FOR LUNG VOLUME REDUCTION”, and U.S. Pat. No. 6,527,761, “METHODS AND DEVICES FOR OBSTRUCTING AND ASPIRATING LUNG TISSUE SEGMENTS”, each incorporated herein by reference for all purposes. Devices, systems and methods of the present invention may also be useful to assess the lung for leaks communicating with the pleural space (such as leaks arising from lung volume reduction surgery, other lung surgeries, or spontaneous pneumothorax). In either case, this may be achieved by introducing a catheter to and isolating the lung compartment of interest as previously described and performing the flow measurement as previously described, with or without a check valve. For example in the case of a bronchial occlusal stent, the flow measurement will indicate no inspiratory or expiratory flow if the stent is effectively sealing, but will show flow if the stent is not sealing. One-way valves can be assessed similarly. If the valve is intended to allow expiratory flow but prevent inspiratory flow, the flow measuring device should detect flow during exhalation but not detect flow in the expiratory direction. Should flow be detected during inspiration, the valve may be inadvertently leaking Should no flow be detected in the exhalation direction (assuming the valved area is not atelectatic), the valve may be inadvertently plugged. 
     Although the foregoing invention has been described in some detail by way of illustration and example, for purposes of clarity of understanding, it will be obvious that various alternatives, modifications and equivalents may be used and the above description should not be taken as limiting in scope of the invention which is defined by the appended claims.