1. Field of the Invention
This invention relates generally to medical methods and systems and more specifically to methods for assessing the functionality of lung compartments and treating diseased compartments of the lung.
2. Description of the Related Art
Lung diseases are a problem affecting several millions of people. Chronic obstructive pulmonary disease (COPD), for example, is a significant medical problem affecting 16 million people or about 6% of the U.S. population. Lung cancer, as another example, is among the most prevalent forms of cancer, and causes more than 150,000 deaths per year. In general, two types of diagnostic tests are performed on a patient to determine the extent and severity of lung disease: 1) imaging tests and 2) functional tests. Imaging tests, such as chest x-rays, computed tomography (CT) scans, magnetic resonance imaging (MRI), perfusion scans, and bronchograms, provide a good indicator of the location, homogeneity and progression of the diseased tissue. However, these tests do not give a direct indication of how the disease is affecting the patient's overall lung function and respiration capabilities. This can be measured with functional testing, such as spirometry, plethysmography, oxygen saturation, and oxygen consumption stress testing, among others. Together, these diagnostic tests are used to determine the course of treatment for the patient.
However, the diagnostic tests for COPD are limited in the amount and type of information that may be generated. For example, diagnostic imaging may provide information to the physician regarding which lung regions “appear” more diseased, but in fact a region that appears more diseased may actually function better than one that appears less diseased. Similarly, functional testing is performed on the lungs as a whole. Thus, the information provided to the physician is generalized to the whole lung and does not provide information about functionality of individual lung compartments, which may be diseased. Thus, physicians may find it difficult to target interventional treatments to the compartments most in need and to avoid unnecessarily treating compartments that are least in need of treatment. Therefore, in general, using conventional imaging or functional testing, the diseased compartments cannot be differentiated, prioritized for treatment, or assessed after treatment for their level of response to therapy.
One particular need is the diagnosis of lung compartments that would be candidates for lung volume reduction (LVR). LVR typically involves resecting diseased portions of the lung. Resection of diseased portions of the lungs both promotes expansion of the non-diseased regions of the lung and decreases the portion of air which is inhaled into the lungs but is not used to transfer oxygen to the blood. Lung reduction is conventionally performed in open chest or thoracoscopic procedures where the lung is resected, typically using stapling devices having integral cutting blades. While effective in many cases, conventional lung reduction surgery is significantly traumatic to the patient, even when thoracoscopic procedures are employed. Further, such procedures often result in the unintentional removal of relatively healthy lung tissue or leaving behind of relatively diseased tissue, and frequently result in air leakage or infection.
One of the emerging methods of lung volume reduction involves the endoscopic introduction of implants into pulmonary passageways. Such a method and implant is described in U.S. patent application Ser. No. 11/682,986. The implants will typically restrict air flow in the inhalation direction, causing the adjoining lung compartment to collapse over time. This method has been suggested as an effective approach for treating lung compartments that are not subject to collateral ventilation.
There is a need for a quick and convenient method of determining whether a diseased lung portion is suitable for placement of an implant for effective LVR. This depends on the presence of collateral channels which often reduce the effectiveness of LVR using an implant. Collateral channels are sometimes naturally present in the lungs because of gaps in the natural membranes separating the lobes and segments. In many cases, however, COPD manifests itself in the formation of a large number of collateral channels caused by rupture of the air sacs because of hyperinflation, or by destruction and weakening of alveolar tissue, leading to many pathways for air to flow between lung segments. The presence of these collateral channels impedes LVR treatment using one-way valves and implants to induce collapse of a lung segment. This is because the collateral channels allow air to flow into the lung compartment from an adjacent compartment. This replenishes the air in the compartment and prevents the lung compartment from collapsing. If collateral channels exist, options other than LVR may be explored. The selection of this method of LVR as a treatment option would thus be based on the presence or absence of collateral channels. There is thus a need to determine the presence of collateral channels, or at least ventilation due to collateral channels (i.e., collateral ventilation).
Further, if collateral channels are present, regardless of whether LVR is chosen as a treatment option, it would be further desirable to discern their ancillary characteristics, such as the extent of a compartment's hyperinflation, the size of the collateral channels, and the perfusion rate through the pathways and the particular lobes or segments of the lung that are connected by these pathways. Discerning such characteristics enables the treatment to be tailored to the nature and quality of the collateral channels. For example, depending on the nature and size of the collateral channels, different agents may have to be used to seal the collateral channels. There is therefore a need for accurately determining the presence of collateral pathways as well as the characteristics of such pathways.
Various methods for determining collateral ventilation have been proposed. For example, Morrel et al. (1994) analyzed gas compositions in lungs of emphysematous patients. After occluding a lung compartment, they introduced an O2—He mixture as a breathing gas into the isolated lung compartments. The helium gas content in the isolated lung was measured, as was the CO2 content. They correlated the rise of helium within the isolated compartment to the extent of collateral ventilation. They also measured significantly lower PCO2, in the occluded segments in emphysematous patients, but could not conclude definitively on the state of collateral ventilation using these measurements.
More recently, a number of methods for determining collateral ventilation have been disclosed, as in co-pending U.S. Published Patent Applications 2003/0051733, 2003/0055331, 2007/0142742, 2006/0264772 and 2008/0200797. U.S. Patent Application 2003/0055331 discloses a non-invasive method of diagnosing the presence of disease in various parts of the lung using imaging and computerized integration of the imaging data. The methods described help determine which lung portions are the most severely affected and which lung channels will respond effectively to isolation treatment.
An endobronchial catheter-based diagnostic system is disclosed in U.S. Patent Application 2003/0051733, wherein the catheter uses an occlusion member to isolate a lung segment and the instrumentation is used to gather data such as changes in pressure and volume of inhaled/exhaled air. The data collected is used to diagnose the extent of hyperinflation, lung compliance, etc., in the lung segment. The Application also discloses the use of radiopaque gas and polarized gas that would enable the presence of collateral channels to be identified using radiant imaging and MRI, respectively. A similar method is disclosed in U.S. Patent Application 2008/0027343 in which an isolation catheter is used to isolate a targeted lung compartment and pressure changes therein are sensed to detect the extent of collateral ventilation.
U.S. Patent Application 2007/0142742 discloses further methods of diagnosis of collateral ventilation in a lung using pressure/volume changes in an isolated lung compartment with and without a valve installed therein. It further discloses detecting the propagation of an inert gas such as helium outside the isolated lung compartment to indicate the presence of such collateral channels. These measurements are targeted at quantitative measurements of the extent of collateral flow prevalent in the lung region of interest. Similarly, U.S. Patent Application 2005/0288702 to McGurk et al. discloses a method by which air containing a marker gas is inhaled by the patient and its presence detected in the isolated lung compartment to detect the presence of collateral ventilation.
A method for detecting the extent of hyperinflation in an isolated lung compartment is disclosed in U.S. Patent Application 2006/0264772, wherein the drop in air exhaled through a one-way valve is monitored. The Application also discloses methods of measuring lung compliance and the extent of blood flow and volumetric blood flow to a particular lung segment, the latter method using a tracer gas that would be dissolved in the blood. U.S. Patent Application 2008/0200797 discloses a method of temporarily isolating several feeding channels of a portion of a lung to observe its effects on lung function. The Application also discloses monitoring of CO2 and oxygen within the isolated lung compartment to indicate the efficiency of gas exchange within the compartment.
A slightly different approach to measuring collateral ventilation is disclosed in U.S. Patent Application 2006/0276807. Here, the airway leading to the section of lung to be evaluated is sealed using a catheter with a sealing element and a sudden pressurization or evacuation is applied. Change of pressure within the isolated section is sensed through the catheter. Presence of collateral ventilation is indicated by a change in pressure of the isolated section after the airway is pressurized or evacuated.
Alternative methods and devices for assessing collateral ventilation and other lung function parameters are still being sought. Ideally, such methods and devices may allow a user to choose a diagnostic test that is best tailored to an individual patient's needs. For example, it would be desirable to be able to acquire more quantitative information on the nature and extent of collateral flow between different lung compartments. It would also be desirable to be able to better determine spatial location of collateral pathways within a lung, thereby reducing the treatment cycle time and damage to healthy tissue. At least some of these objectives will be met by the embodiments described herein.
In one aspect of the present invention, a method for assessing lung function in a patient may first involve introducing a catheter comprising a distal end and a proximal end with at least one lumen therebetween into an airway leading to a targeted compartment of one of the patient's lungs. The distal end of the catheter may include an expandable occluding element configured to sealingly engage a wall of the airway. The proximal end of the catheter may include an inflation port to expand the occluding element and an access port fluidly connected to the lumen. The method may further involve: isolating the targeted lung compartment by expanding the occluding element; introducing into the lung an inhaled gas of known composition; analyzing a composition of an exhaled gas exhaled from the lung; comparing the composition of the exhaled gas to the composition of the inhaled gas; and assessing function of the lung based on the comparison of exhaled and inhaled gases.
In various embodiments, the known composition may include but is not limited to oxygen, methane, carbon monoxide, helium, carbon dioxide and/or sulfur hexafluoride. In one embodiment, the inhaled gas is introduced into the targeted lung compartment. Alternatively, the inhaled gas may be introduced into a lung compartment other than the targeted lung compartment. In one embodiment, the exhaled gas is exhaled from the targeted lung compartment. In an alternative embodiment, the exhaled gas may be exhaled from a lung compartment other than the targeted lung compartment.
In some embodiments, analysis of the gas includes measuring the composition of the exhaled gas. For example, measuring the composition of the exhaled gas may be performed within the targeted lung compartment in some embodiments. Alternatively, the composition of the exhaled gas may be measured outside the targeted lung compartment but within the lung. In yet another embodiment, composition of the exhaled gas may be measured ex-vivo. In one embodiment, the assessing step involves determining a degree of perfusion of the lung. Alternatively or additionally, assessing may involve determining a degree of collateral ventilation in the lung.
In another aspect, a method for assessing lung function in a patient may first involve introducing a catheter as described above into an airway leading to a targeted compartment of one of the patient's lungs. The method may then involve: sampling gases from the lung compartment with the occluding element in an unexpanded configuration to measure a baseline CO2 content of the lung compartment; isolating the lung compartment by expanding the occluding element; measuring accumulated CO2 content within the isolated lung compartment over time; and assessing function of the lung by evaluating a change between the baseline CO2 content and the accumulated CO2 content over time. In some embodiments, the assessing step may include determining a degree of collateral ventilation in the lung.
In another aspect, the invention may include a method for assessing lung function in a patient. This method may involve introducing a catheter with an expandable occluding element into an airway leading to a lung compartment, isolating the lung compartment by expanding the occluding element at the end of an inspiratory cycle, and assessing lung function by monitoring a change in pressure within the isolated lung compartment over a period of time to measure a parameter that indicates lung function. In some embodiments, the parameter may include a rate of perfusion between the isolated lung compartment and a second lung compartment. Additionally or alternatively, the parameter may include a resistance of collateral channels between the isolated lung compartment and a second lung compartment.
In another aspect, a method for assessing lung function in a patient may include: introducing a catheter with an expandable occluding element into an airway leading to a targeted lung compartment; isolating the targeted lung compartment by expanding the occluding element; obtaining a range of CO2 values by measuring CO2 content within the isolated lung compartment over one or more respiratory cycles; and assessing lung function by comparing the magnitude of the range of CO2 values against a predetermined threshold. In some embodiments, the threshold may be established by using population data. Alternatively, the threshold may be obtained from a second lung compartment in the same patient.
In another aspect, a method for assessing lung function in a patient may include: introducing a catheter with an expandable occluding element into an airway leading to a targeted lung compartment; isolating the targeted lung compartment by expanding the occluding element; measuring CO2 content and airflow within the isolated lung compartment over one or more respiratory cycles; and determining a relationship between CO2 content and airflow to determine disease progression.
In another aspect, a device for endobronchial diagnostics may include a catheter and a gas composition measurement device coupled with the catheter to measure composition of at least one gas inhaled into or exhaled out of the lung. The catheter may include a distal end, a proximal end, a sampling lumen and an auxiliary lumen. The distal end may include an expandable occluding element configured to sealingly engage a wall of an airway leading to a targeted compartment of a lung, and the proximal end may include a hub with an inflation port connected to the auxiliary lumen to expand the occluding element and an access port fluidly connected to the sampling lumen wherein the diameter of the sampling lumen is configured to decrease from the proximal end to the distal end.
In some embodiments, the diameter of the sampling lumen may vary continuously between the proximal end and the distal end. Alternatively, the diameter of the sampling lumen may vary discontinuously between the proximal end and the distal end. In some embodiments, the sampling lumen includes a combination of sections varying continuously or discontinuously in diameter. In some embodiments, the gas composition measurement device may be configured to measure at least one gas, including but not limited to oxygen, methane, carbon monoxide, helium, carbon dioxide and/or sulfur hexafluoride.
Although the detailed description contains many specifics, these should not be construed as limiting the scope of the invention but merely as illustrating different examples and aspects of the invention. Various modifications, changes and variations may be made in the arrangement, operation and details of the methods and systems of the present invention disclosed herein without departing from the spirit and scope of the invention as described.
Various methods and systems for targeting, accessing and assessing diseased lung compartments are described herein. Such lung compartments may be an entire lobe of a lung, a segment, a subsegment or even smaller compartments. Assessment is generally achieved by isolating a lung compartment to obtain various measurements to determine lung functionality. Though COPD is mentioned as an example, the applicability of these methods for treatment and diagnosis is not limited to COPD, but can be applicable to any disease of the lung.
The methods are minimally invasive in the sense that the required instruments are introduced orally, and the patient is allowed to breathe normally during the procedures. The methods involve detecting the presence or characteristics (e.g., concentration or pressure) of one or more naturally occurring or introduced gases to determine the presence of collateral ventilation. Naturally occurring gases include those found in the regular breathing cycle (e.g., O2 and CO2). Introduced gases include suitable marker gases such as oxygen, helium, methane, carbon monoxide and sulfur hexafluoride, among others. The relative proportion of these gases in the inhaled and exhaled air is used to derive information on the size and extent of collateral channels. One embodiment of the present invention involves introducing air or a tailored mixture of gases into one or more areas of the lung, isolating a targeted lung compartment and then sampling the exhalate from either the targeted lung compartment or the rest of the lung volume to effect measurement. A second embodiment involves restricting inhalatory air into a lung compartment and measuring the concentration of CO2 buildup in the lung compartment. A third embodiment involves restricting inhalatory air into a lung compartment and measuring the pressure buildup in the compartment. A fourth embodiment involves restricting inhalatory air into a specific lung compartment and determining whether the rate of change of CO2 approximates a known concentration of CO2 in alveolar gas.
Turning to the figures, in each of the present embodiments, isolation of the lung comprises sealingly engaging a distal end of a catheter in an airway feeding a lung compartment, as shown in
In alternative embodiments shown in
In another embodiment shown in
Additionally and optionally, catheter 100 further comprises at least one gas sensor 140 located within or in-line with the lumen 130 for sensing characteristics of various gases in air communicated to and from the lung compartment. The sensors may comprise any suitable sensors or any combination of suitable sensors, and are configured to communicate with control unit 200, or any intermediary. Exemplary sensors include pressure sensors, temperature sensors, air flow sensors, gas-specific sensors, or other types of sensors. As shown in
As shown in
The proximal end of the catheter 100 is configured to be associated with a control unit 200, as shown in
In one embodiment, catheter 100 is introduced into the targeted lung compartment TLC, which is then isolated by inflating the occlusion element 120. Control unit 200 is used to introduce a mixture of gases containing oxygen and one or more marker gases such as methane, carbon monoxide, helium or sulfur hexafluoride into the targeted lung compartment through catheter 100. The patient breathes normally through several respiratory cycles with the TLC exposed to the tailored gas composition.
After the particular gas mixture is introduced into the isolated TLC over several respiratory cycles, analysis of exhaled gas from the rest of the lung (outside the TLC) is carried out using an external sensor that is placed between the occlusion site and the mouth or nose where the expired air is released from the body. The sensor at the mouth or nose could be provided via any suitable apparatus, for example, a mask. The presence of a marker gas, such as helium, detected in the exhaled gas outside the isolated compartment would indicate the presence of collateral channels.
Alternatively, once the TLC is isolated, the gas mixture can be introduced into the rest of the lung from outside the TLC using any suitable method (for example, through the mouth using a mask). Gas from within the TLC would thereafter be analyzed for presence of the markers, to thereby deduce the presence of collateral ventilation.
In another alternative embodiment, the gas mixture may be introduced into the TLC and exhaled gas is sampled from the TLC. If collateral ventilation is present, that would result in a diffusion of some marker gases to locations outside the TLC, thereby resulting in a decrease in concentration of those marker gases in the exhaled volume. Analysis of the change in exhaled gas composition from within the lung compartment over several respiratory cycles would therefore indicate collateral ventilation. Similarly, the tailored gas composition may be introduced to the rest of the lung outside the TLC and exhaled gas from outside the TLC could be analyzed for change in composition over several respiratory cycles.
Additionally or alternatively, besides determining the presence of collateral channels and collateral ventilation, the above embodiment may be used to determine the perfusion efficiency of the collateral channels. Specifically, when gases are introduced into the TLC and are measured from the TLC, the rate of change of the gas composition can be correlated to the perfusion efficiency of the collateral channels feeding the TLC.
Additionally, the method is useful in determining the size of the collateral channels. The gases introduced are intended to vary in molecular size, such that the variation would enable the determination of size and relative proportion of the collateral channels. As molecules diffuse across the collateral channels, their rate of diffusion will depend upon the size of the collateral channel. For example, small molecules will be able to travel across similarly sized collateral channels, whereas larger molecules will be impeded. A determination of the ratio of inhaled to exhaled content of the marker gases would reveal which marker gases were able to travel across, thereby allowing determination of the corresponding size of collateral channels that connect the TLC to the rest of the lung. Additionally and optionally, a feedback control system may be used to vary the ratio of the gaseous components in the mixture. Specifically, the proportion of marker gases in the mixture and the flow rate or pressure at which the gas mixture is introduced may be controlled using the feedback-controlled system, thereby allowing a dynamically adjustable assessment of the sizes and relative proportions of the collateral channels.
In each of the above methods, analysis of gas from within the TLC is performed in-situ using sensors 140 located at the distal end of the catheter. Alternatively, the measurement may be carried out ex-vivo at the control unit 200 by sampling gas within the TLC through catheter lumen 130, or via an external sensor that is placed between the occlusion site and the mouth or nose, where the exhaled air is released out of the body.
In another embodiment shown in
In another embodiment, the catheter 100 with an expandable occluding element 120 is introduced into a body passageway leading to a targeted lung compartment TLC (such as shown in
The variation of CO2 content, with and without collateral flow, is illustrated in
In another embodiment, the measurements of CO2 concentration and flow volume can be used to assess the functional state or destruction of tissue in diseased lung compartments. This is accomplished using the ratio of peak CO2 concentration to that of the flow volume for each respiratory cycle in a particular lobe. In a normal lung, the peak CO2 concentration (which typically occurs at the end of the inspiration phase) is high due to good gaseous exchange in the alveolar tissue. This would also be accompanied by a relatively high flow volume compared to a diseased lung portion. Thus, a high CO2 concentration and a high flow rate signify a normally functioning lung compartment.
In a diseased lung compartment with poor perfusion and/or hyperinflation, the CO2 levels are also likely to be high (in the same range as found in normal lung); however, the average CO2 levels are also likely to be high (compared to the average CO2 levels found in normal lung) due to poor gas exchange or circulation. For these same reasons of poor circulation and exchange, however, the flow volume is likely to be low. Thus, average flow volume in a breathing cycle is a marker of disease progression. By correlating the average flow volume with peak lobar CO2 levels, lung function can be determined, which can thus lead to identification of diseased and poorly functioning lung compartments and can be used with peak lobar CO2 levels to determine lung function.
While the above is a complete description of various alternative embodiments, further alternatives, modifications, and equivalents may be used. Therefore, the above description should not be taken as limiting the scope of the invention which is defined by the appended claims.
This application claims the benefit of Provisional Application No. 61/289,868 (Attorney Docket No. 017534-004700US), filed on Dec. 23, 2009, the full disclosure of which is incorporated herein by reference.
Number | Date | Country | |
---|---|---|---|
61289868 | Dec 2009 | US |