Patent Description:
Chronic obstructive pulmonary disease (COPD), including emphysema and chronic bronchitis, is a significant medical problem currently affecting around <NUM> million people in the U. alone (about <NUM>% of the U. population). In general, two types of diagnostic tests are performed on a patient to determine the extent and severity of COPD: <NUM>) imaging tests; and <NUM>) functional tests. Imaging tests, such as chest x-rays, computerized tomography (CT) scans, Magnetic Resonance Imaging (MRI) images, perfusion scans, and bronchograms, provide a good indicator of the location, homogeneity and progression of the diseased tissue. However, imaging tests do not provide a direct indication of how the disease is affecting the patient's overall lung function and respiration. Lung function can be better assessed using functional testing, such as spirometry, plethysmography, oxygen saturation, and oxygen consumption stress testing, among others. Together, these imaging and functional diagnostic tests are used to determine the course of treatment for the patient.

One of the emerging treatments for COPD involves the endoscopic introduction of endobronchial occluders or one-way valve devices ("endobronchial valves" or "EBVs") into pulmonary passageways to reduce the volume of one or more hyperinflated lung compartments, thus allowing healthier compartments more room to breathe and perhaps reducing pressure on the heart. Examples of such a method and implant are described, for example, in <CIT> (<CIT>) and <CIT>. One-way valves implanted in airways leading to a lung compartment restrict air flow in the inhalation direction and allow air to flow out of the lung compartment upon exhalation, thus causing the adjoining lung compartment to collapse over time. Occluders block both inhalation and exhalation, also causing lung collapse over time.

It has been suggested that the use of endobronchial implants for lung volume reduction might be most effective when applied to lung compartments which are not affected by collateral ventilation. Collateral ventilation occurs when air passes from one lung compartment to another through a collateral channel rather than the primary airway channels. If collateral airflow channels are present in a lung compartment, implanting a one-way valve or occluder might not be as effective, because the compartment might continue to fill with air from the collateral source and thus fail to collapse as intended. In many cases, COPD manifests itself in the formation of a large number of collateral channels caused by rupture of alveoli due to hyperinflation, or by destruction and weakening of alveolar tissue.

An endobronchial catheter-based diagnostic system typically used for collateral ventilation measurement is disclosed in <CIT>, wherein the catheter uses an occlusion member to isolate a lung compartment and the instrumentation is used to gather data such as changes in pressure and volume of inhaled/exhaled air. Methods for collateral ventilation measurement are disclosed in <CIT> and <CIT>, <CIT>, and <CIT>, in which an isolation catheter is used to isolate a target lung compartment and pressure changes therein are sensed to detect the extent of collateral ventilation. The applications also disclose measurement of gas concentrations to determine the efficiency of gas exchange within the lung compartment. Similar methods are disclosed in <CIT>, wherein gas concentration changes in a catheter-isolated lung portion allow collateral ventilation to be determined.

<CIT> describes minimally invasive methods, systems and devices 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, volume and pressure. These measurements are used to determine the presence of collateral ventilation and to quantify such collateral ventilation. On the proximal end of the catheter, external to the body of the patient, a one-way valve, a flow-measuring device or/and a pressure sensor are placed in series so as to communicate with the catheter's inside lumen. The one-way valve prevents air from entering the target compartment from atmosphere but allows free air movement from the target compartment to atmosphere.

Quantifying collateral ventilation via collateral resistance measurement and calculations typically takes about two to five minutes. During this time, the physician must ensure the patient is tolerating sedation, manage secretions to prevent occlusion within the catheter lumen, and maintain balloon seal/position within the target airway. Any one of these factors may extend the assessment time and compromise the assessment results. Thus, there is a need to quantify the magnitude of collateral ventilation within a lung compartment (lobe, segment, sub-segment, or the like) more quickly and efficiently.

Therefore, it would be advantageous to have new diagnostic techniques for evaluating the state of lung disease progression, such as determining the presence and degree of collateral ventilation. At least some of these objectives will be met by the embodiments described herein.

This application discloses methods and systems for assessing the functionality of a lung compartment in a patient. In one aspect, a method of assessing the functionality of a lung compartment in a patient comprises introducing a diagnostic catheter into the lung compartment, inflating the occluding member to isolate the lung compartment, measuring CO<NUM> concentration within the isolated lung compartment over time, and determining whether collateral ventilation is present in the isolated lung compartment based on the measured CO<NUM> concentration within the isolated lung compartment over time. The proximal end of the diagnostic catheter is configured to be attached to a console, and data from the diagnostic procedure may be displayed on the console. In an embodiment, collateral ventilation can be determined to be present in the isolated lung compartment if the CO<NUM> concentration within the isolated lung compartment fluctuates with breathing. Collateral ventilation may be determined not to be present in the isolated lung compartment if the CO<NUM> concentration within the isolated lung compartment plateaus over time. In an embodiment, a degree of collateral ventilation may be determined based on the slopes of different regions of CO<NUM> concentration curves.

In another aspect, a method of assessing the functionality of a lung compartment in a patient comprises introducing a diagnostic catheter into the lung compartment, inflating the occluding member to isolate the lung compartment, measuring O<NUM> concentration within the isolated lung compartment over time, and determining whether collateral ventilation is present in the isolated lung compartment based on the measured O<NUM> concentration within the isolated lung compartment over time. The proximal end of the diagnostic catheter is configured to be attached to a console, and data from the diagnostic procedure may be displayed on the console. In an embodiment, collateral ventilation can be determined to be present in the isolated lung compartment if the O<NUM> concentration within the isolated lung compartment plateaus above a threshold value. Collateral ventilation may be determined not to be present in the isolated lung compartment if the O<NUM> concentration within the isolated lung compartment decreases below a threshold value. In an embodiment, a degree of collateral ventilation may be determined based on the degree of reduction of the O<NUM> concentration within the isolated lung compartment after isolation. Optionally, the methods may be performed while the patient is ventilated via an assisted ventilation device with air having an elevated O<NUM> concentration.

In yet another aspect, a method of assessing the functionality of a lung compartment in a patient comprises sealing a distal end of a catheter in an airway feeding the lung compartment by using an occluding member that is adapted to be expanded in an airway which feeds the lung compartment such that access to the lung compartment is provided only through a passage of the catheter when the occluding member is expanded, allowing air to enter the lung compartment through the passage in the catheter while the patient is inhaling, blocking air from being expelled from the lung compartment through the catheter passage while the patient is exhaling by using a one-way flow element adapted to be disposed within or in-line with the passage of the catheter so that flow in a proximal-to-distal direction is allowed and flow in a distal-to-proximal direction is inhibited or prevented, measuring flow into the lung compartment, and determining whether collateral ventilation is present in the lung compartment based on the measured measuring flow into the lung compartment. In an embodiment, it can be determined that no collateral ventilation is present if flow into the lung compartment decreases below a threshold value. It may also be determined that collateral ventilation is present if flow into the lung compartment remains above a threshold value. In an embodiment, a degree of collateral ventilation may be determined based on the measured flow into the lung compartment.

In another aspect, a method of assessing the functionality of a lung compartment in a patient comprises sealing a distal end of a catheter in an airway feeding the lung compartment by using an occluding member that is adapted to be expanded in an airway which feeds the lung compartment such that access to the lung compartment is provided only through a passage of the catheter when the occluding member is expanded, allowing air to enter the lung compartment through the passage in the catheter while the patient is inhaling, blocking air from being expelled from the lung compartment through the catheter passage while the patient is exhaling by using a one-way flow element adapted to be disposed within or in-line with the passage of the catheter so that flow in a proximal-to-distal direction is allowed and flow in a distal-to-proximal direction is inhibited or prevented, measuring pressure within the lung compartment and flow into the lung compartment, and determining whether collateral ventilation is present in the lung compartment based on the measured pressure within the lung compartment. In an embodiment, determining whether collateral ventilation is present in the isolated lung compartment comprises calculating a value of collateral resistance. A degree of collateral ventilation may be determined based on the calculated value of collateral resistance.

Further aspects and embodiments of the present disclosure are described in further detail below, with reference to the attached drawings.

Present embodiments have other advantages and features which will be more readily apparent from the following detailed description and the appended claims, when taken in conjunction with the accompanying drawings, in which:.

Although the detailed description contains many specifics, these should not be construed as limiting the scope of the disclosure but merely as illustrating different examples and aspects of the disclosure. It should be appreciated that the scope of the disclosure includes other aspects and embodiments not discussed herein. Various other modifications, changes and variations which will be apparent to those skilled in the art may be made in the arrangement, operation and details of the method, device, and system of the aspects and embodiments disclosed herein without departing from the scope of the disclosure as described here.

Throughout the specification and claims, the following terms take the meanings explicitly associated herein unless the context clearly dictates otherwise. The meaning of "a", "an", and "the" include plural references. The meaning of "in" includes "in" and "on. " Referring to the drawings, like numbers indicate like parts throughout the views. Additionally, a reference to the singular includes a reference to the plural unless otherwise stated or inconsistent with the disclosure herein.

" Any implementation described herein as "exemplary" is not necessarily to be construed as advantageous over other implementations.

The present application provides methods and systems for targeting, accessing and diagnosing diseased lung compartments. Such compartments could be an entire lobe, a segment, a sub-segment or any such portion of the lung. Diagnosis is achieved in the disclosed embodiments 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 lung disease.

The methods are minimally invasive in the sense that the required instruments are introduced through the mouth, a tracheostomy, or other site, typically via a bronchoscope, assisted ventilation device, or other non-surgical device passed through the mouth into the trachea and airways. In some embodiments, the patient is allowed to breathe normally during the procedures. Some embodiments may be used with assisted (or positive pressure) ventilation. 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 and/or to measure one or more other characteristics of a target lung compartment, such as oxygen saturation of tissue.

In some 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 <FIG> and <FIG>. Such a catheter has been disclosed in published <CIT> (<CIT>). As shown in <FIG>, the catheter <NUM> comprises a catheter body <NUM>, and an expandable occluding member <NUM> on the catheter body. The catheter body <NUM> has a distal end <NUM>, a proximal end <NUM>, and at least one lumen <NUM>, extending from a location at or near the distal end to a location at or near the proximal end.

The proximal end of catheter <NUM> is configured to be coupled with an external control unit (or "console," not shown), and optionally comprises an inflation port (not shown). The distal end of catheter <NUM> is adapted to be advanced through a body passageway such as a lung airway. The expandable occluding member <NUM> is disposed near the distal end of the catheter body and is adapted to be expanded in the airway which feeds the target lung compartment. In one embodiment, the occluding member <NUM> is a compliant balloon made of transparent material. The transparent material allows visualization using the bronchoscope through the balloon. The occluding member <NUM> is inflatable via a syringe that is configured to be coupled to the inflation port. Optionally, catheter <NUM> comprises visual markers at the proximal and distal ends of the balloon to identify the location of the occluding member <NUM> within the airway prior to inflation. The occluding member <NUM> material inflates and seals with inflation pressures between <NUM>-<NUM> psi to prevent balloon migration within the airway. This inflation pressure also aids the occluding member <NUM> in maintaining a symmetrical configuration within the airway, thereby ensuring that the catheter (which is centered within the occluding member <NUM>) will remain centered within the airway. The occluding member <NUM> material and attachment are also configured to minimize longitudinal movement of the occluding member <NUM> relative to the catheter body <NUM> itself. To accommodate the higher inflation pressure, the occluding member <NUM> is made of a polyurethane such as Pellethane 80A, but can be made of any material that is configured to maintain structural integrity at a high inflation pressure.

Additionally and optionally, catheter <NUM> further comprises at least one sensor <NUM> located within or in-line with the lumen <NUM> 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 <NUM>. Examples of sensors include pressure sensors, temperature sensors, air flow sensors, oxygen sensors, carbon dioxide sensors, gas-specific sensors, or other types of sensors. As shown in <FIG>, the sensors <NUM> may be located near the distal end <NUM> of the catheter <NUM>. Alternatively, the sensors <NUM> may be located at any one or more points along the catheter <NUM>, or in-line with the catheter <NUM> and within the control unit with one or more measuring components.

The system comprises a one-way flow element located within or in-line with the lumen <NUM>. Examples of one-way flow element are described in <CIT> (<CIT>). One-way flow elements may be configured to allow flow from an isolated lung compartment in a distal-to-proximal direction but inhibit or block flow back into the lung compartment in the proximal-to-distal direction. According to the present invention, the system comprises a one-way flow element configured such that flow in a proximal-to-distal direction is allowed and flow in a distal-to-proximal direction is inhibited or prevented.

As shown in <FIG>, at least a distal portion of the catheter body <NUM> is adapted to be advanced into and through the trachea (T). The catheter may optionally be introduced through or over an introducing device such as a bronchoscope. The distal end <NUM> of the catheter body <NUM> can then be directed to a lung lobe (LL) to reach an airway (AW) which feeds a target lung compartment (TLC), which is to be assessed. When the occluding member <NUM> is expanded in the airway, the corresponding compartment is isolated with access to and from the compartment provided through the lumen <NUM>.

The proximal end of the catheter <NUM> is configured to be coupled with a control unit (or "console") <NUM>, as shown in <FIG>. The control unit <NUM> comprises one or more measuring components (not shown) to measure lung functionality. The measuring components may take many forms and may perform a variety of functions. For example, the components may include a pulmonary mechanics unit, a physiological testing unit, a gas dilution unit, an imaging unit, a mapping unit, a treatment unit, a pulse oximetry unit or any other suitable unit. The components may be disposed within the control unit <NUM>, or may be attached to the unit <NUM> from an external source. The control unit <NUM> comprises an interface for receiving input from a user and a display screen <NUM>. The display-screen <NUM> will optionally be a touch-sensitive screen, and may display preset values. Optionally, the user will input information into the control unit <NUM> via a touch-sensitive screen mechanism. Additionally and optionally, the control unit <NUM> may be associated with external display devices such as printers or chart recorders. At least some of the above system embodiments will be utilized in the methods described below.

<FIG> is a flow diagram illustrating one embodiment of assessing the functionality of a lung compartment in a patient by measuring CO<NUM> concentration in the lung compartment. <FIG> shows CO<NUM> concentration where no collateral ventilation is present by using the method of <FIG>. <FIG> shows CO<NUM> concentration where collateral ventilation is present by using the method of <FIG>. At step <NUM> a diagnostic catheter is introduce into the lung compartment. At step <NUM> an occluding member is inflated to isolate the lung compartment. At step <NUM> CO<NUM> concentration within the isolated lung compartment is measured over time. At step <NUM> the system determines whether collateral ventilation is present in the isolated lung compartment based on the measured CO<NUM> concentration within the isolated lung compartment over time. As can be seen in <FIG> and <FIG> CO<NUM> concentration rises and falls with breathing before the occluding member is inflated in step <NUM>. When collateral ventilation is not present, as shown in <FIG>, after the lung compartment is isolated in step <NUM>, there is no fresh air wash out from collateral flow. The CO<NUM> concentration rises and plateaus over time. The system may be configured to detect a lack of collateral ventilation based on the plateau of CO<NUM> concentration within the isolated lung compartment over time. When collateral ventilation is present, as shown in <FIG>, after the lung compartment is isolated in step <NUM>, there is some fresh air wash out from collateral flow. The CO<NUM> concentration continues to rise and fall with breathing. The system may be configured to detect the collateral ventilation based on the fluctuation of CO<NUM> concentration within the isolated lung compartment. In an embodiment, a degree of collateral ventilation may be determined based on the slopes of different regions of CO<NUM> concentration curves after the lung compartment has been isolated.

<FIG> is a flow diagram illustrating one embodiment of the present disclosure. <FIG> shows O<NUM> concentration where no collateral ventilation is present by using the method of <FIG>. <FIG> shows O<NUM> concentration where collateral ventilation is present by using the method of <FIG>. At step <NUM> a diagnostic catheter is introduce into the lung compartment. At step <NUM> an occluding member is inflated to isolate the lung compartment. At step <NUM> O<NUM> concentration within the isolated lung compartment is measured over time. At step <NUM> the system determines whether collateral ventilation is present in the isolated lung compartment based on the measured O<NUM> concentration within the isolated lung compartment over time. When collateral ventilation is not present, as shown in <FIG>, after the lung compartment is isolated in step <NUM>, O<NUM> concentration continuously decreases as it enters the blood and is not replenished. O<NUM> concentration will drop to approximately the level of deoxygenated blood and remain low. The system may be configured to detect a lack of collateral ventilation if the O<NUM> concentration within the isolated lung compartment decreases below a threshold value. When collateral ventilation is present, as shown in <FIG>, after the lung compartment is isolated in step <NUM>, O<NUM> concentration reduces but establishes a lower plateau because O<NUM> would enter from other compartments through collateral channels. Eventually O<NUM> would be fed by neighboring compartments as fast as it is being used by target compartments. The system may be configured to detect collateral ventilation if the O<NUM> concentration within the isolated lung compartment plateaus above a threshold value. In an embodiment, a degree of collateral ventilation may be determined based on the degree of reduction of the O<NUM> concentration within the isolated lung compartment after isolation. A higher value of the O<NUM> concentration at the plateau indicates a higher degree of collateral ventilation. In an embodiment, the methods may be performed while the patient is ventilated via an assisted ventilation device with air having an elevated O<NUM> concentration. Elevated O<NUM> concentrations may be any concentration above the <NUM>% in normal air. Various embodiments may use elevated O<NUM> concentrations of approximately <NUM>%, <NUM>%, or <NUM>%.

<FIG> is a flow diagram illustrating an embodiment of a method of assessing the functionality of a lung segment in a patient. At step <NUM> a distal end of a catheter in an airway feeding the lung compartment is sealed by using an occluding member that is adapted to be expanded in an airway which feeds the lung compartment such that access to the lung segment is provided only through a passage of the catheter when the occluding member is expanded. At step <NUM>, air is allowed to enter the lung compartment through the passage in the catheter while the patient is inhaling. At step <NUM>, air is blocked from being expelled from the lung compartment through the catheter passage while the patient is exhaling by using a one-way flow element adapted to be disposed within or in-line with the passage of the catheter so that flow in a proximal-to-distal direction is allowed and flow in a distal-to-proximal direction is inhibited or prevented. In an embodiment the one-way flow element is a solenoid valve configured to close during exhalation and open during inhalation. At step <NUM>, flow into the lung compartment is measured. At step <NUM>, the system determines whether collateral ventilation is present in the isolated lung compartment based on the measured flow into the lung compartment. The system may be configured to determine that no collateral ventilation is present if flow into the lung compartment decreases below a threshold value. The system may also be configured to determine that collateral ventilation is present if flow into the lung compartment remains above a threshold value. In an embodiment, a degree of collateral ventilation may be determined based on the measured flow into the lung compartment. A baseline flow may be determined before the one-way flow element is actuated. A degree of collateral ventilation may be determined based on the difference between the baseline flow and the flow after the one-way flow element is actuated. A low difference in flow indicates that there is a high degree of collateral ventilation. A large difference in flow indicates very little collateral ventilation. Methods may be performed during unassisted breathing or with assisted ventilation.

<FIG> is a flow diagram illustrating an embodiment of a method of assessing the functionality of a lung segment in a patient. At step <NUM> a distal end of a catheter in an airway feeding the lung compartment is sealed by using an occluding member that is adapted to be expanded in an airway which feeds the lung compartment such that access to the lung segment is provided only through a passage of the catheter when the occluding member is expanded. At step <NUM>, air is allowed to enter the lung compartment through the passage in the catheter while the patient is inhaling. At step <NUM>, air is blocked from being expelled from the lung compartment through the catheter passage while the patient is exhaling by using a one-way flow element adapted to be disposed within or in-line with the passage of the catheter so that flow in a proximal-to-distal direction is allowed and flow in a distal-to-proximal direction is inhibited or prevented. In an embodiment the one-way flow element is a solenoid valve configured to close during exhalation and open during inhalation. At step <NUM>, pressure within the lung compartment and flow into the lung compartment are measured. At step <NUM>, the system determines whether collateral ventilation is present in the isolated lung compartment based on the measured pressure and flow. In an embodiment, determining whether collateral ventilation is present in the isolated lung compartment comprises calculating a value of collateral resistance. A degree of collateral ventilation may be determined based on the calculated value of collateral resistance. Methods may be performed during unassisted breathing or with assisted ventilation.

Claim 1:
Apparatus for assessing the functionality of a lung compartment in a patient, the apparatus comprising:
a catheter (<NUM>) having a distal end (<NUM> and a passage (<NUM>);
an occluding member (<NUM>) for sealing the distal end (<NUM>) of the catheter (<NUM>) in an airway feeding the lung compartment, the occluding member (<NUM>) being adapted to be expanded in an airway which feeds the lung compartment such that access to the lung compartment is provided only through the passage (<NUM>) of the catheter (<NUM>) when the occluding member (<NUM>) is expanded;
a one-way flow element adapted to be disposed within or in-line with the passage (<NUM>) of the catheter (<NUM>) so that flow in a proximal-to-distal direction is allowed and flow in a distal-to-proximal direction is inhibited or prevented, thereby allowing air to enter the lung compartment through the passage (<NUM>) in the catheter (<NUM>) while the patient is inhaling and blocking air from being expelled from the lung compartment through the catheter passage (<NUM>) while the patient is exhaling;
measuring means for measuring flow into the lung compartment; and
determining means for determining whether collateral ventilation is present in the lung compartment based on the measured flow into the lung compartment.