Methods for treating airways

Information

  • Patent Grant
  • 10278766
  • Patent Number
    10,278,766
  • Date Filed
    Tuesday, February 4, 2014
    10 years ago
  • Date Issued
    Tuesday, May 7, 2019
    5 years ago
Abstract
This relates to treating airways in a lung to decrease asthmatic symptoms. The also includes steps of measuring a parameter of an airway at a plurality of locations in a lung, identifying at least one treatment site from at least one of the plurality of locations based on the parameter, and applying energy to the treatment site to reduce the ability of the site to narrow.
Description
BACKGROUND OF THE INVENTION

The invention relates to a method of treating a lung having at least one symptom of reversible obstructive pulmonary disease, and more particularly, methods of treating airways in a lung to decrease asthmatic symptoms of the lung, by measuring a parameter of an airway at a plurality of locations in a lung, identifying at least one treatment site from at least one of the plurality of locations based on the parameter; and applying energy to the treatment site to reduce the ability of the site to narrow.


Reversible obstructive pulmonary disease includes asthma and reversible aspects of chronic obstructive pulmonary disease (COPD). Asthma is a disease in which (i) bronchoconstriction, (ii) excessive mucus production, and (iii) inflammation and swelling of airways occur, causing widespread but variable airflow obstruction thereby making it difficult for the asthma sufferer to breathe. Asthma is further characterized by acute episodes of airway narrowing via contraction of hyper-responsive airway smooth muscle.


The reversible aspects of COPD include excessive mucus production and partial airway occlusion, airway narrowing secondary to smooth muscle contraction, and bronchial wall edema and inflation of the airways. Usually, there is a general increase in bulk (hypertrophy) of the large bronchi and chronic inflammatory changes in the small airways. Excessive amounts of mucus are found in the airways and semisolid plugs of mucus may occlude some small bronchi. Also, the small airways are narrowed and show inflammatory changes.


In asthma, chronic inflammatory processes in the airway play a central role in increasing the resistance to airflow within the lungs. Many cells and cellular elements are involved in the inflammatory process, particularly mast cells, eosinophils T lymphocytes, neutrophils, epithelial cells, and even airway smooth muscle itself. The reactions of these cells result in an associated increase in sensitivity and hyper-responsiveness of the airway smooth muscle cells lining the airways to particular stimuli.


The chronic nature of asthma can also lead to remodeling of the airway wall (i.e., structural changes such as airway wall thickening or chronic edema) that can further affect the function of the airway wall and influence airway hyper-responsiveness. Epithelial denudation exposes the underlying tissue to substances that would not normally otherwise contact the underlying tissue, further reinforcing the cycle of cellular damage and inflammatory response.


In susceptible individuals, asthma symptoms include recurrent episodes of shortness of breath (dyspnea), wheezing, chest tightness, and cough. Currently, asthma is managed by a combination of stimulus avoidance and pharmacology.


Stimulus avoidance is accomplished via systematic identification and minimization of contact with each type of stimuli. It may, however, be impractical and not always helpful to avoid all potential stimuli.


Asthma is managed pharmacologically by: (1) long term control through use of anti-inflammatories and long-acting bronchodilators and (2) short term management of acute exacerbations through use of short-acting bronchodilators. Both of these approaches require repeated and regular use of the prescribed drugs. High doses of corticosteroid anti-inflammatory drugs can have serious side effects that require careful management. In addition, some patients are resistant to steroid treatment. The difficulty involved in patient compliance with pharmacologic management and the difficulty of avoiding stimulus that triggers asthma are common barriers to successful asthma management.


Asthma is a serious disease with growing numbers of sufferers. Current management techniques are neither completely successful nor free from side effects.


Accordingly, it would be desirable to provide an asthma treatment which improves airflow without the need for patient compliance.


In addition to the airways of the lungs, other body conduits such as the esophagus, ureter, urethra, and coronary arteries, are also subject to inflammation and periodic reversible spasms that produce obstruction to flow.


SUMMARY OF THE INVENTION

The present invention relates to methods for treating a lung, preferably having at least one symptom of reversible obstructive pulmonary disease, comprising the steps of advancing a treatment device into the lung and treating the lung with the device to at least reduce the ability of the lung to produce at least one symptom of reversible obstructive pulmonary disease and to decrease the resistance to the flow of air through the lung.


A variation of the invention includes the method described above further comprising the step of locating one or more treatment sites within an airway of the lung, selecting at least one of the treatment sites and treating at least one of the treatment sites selected in the selecting step. The invention may further include performing the steps while the lung is experiencing at least one symptom of either natural or artificially induced reversible obstructive pulmonary disease.


A further variation of the invention includes the method described above and further includes the steps of testing the lung for at least one pre-treatment pulmonary function value prior to the treating step, and re-testing the lung for at least one post-treatment pulmonary function value subsequent to the treating step.


A further variation of the invention includes the method described above further comprising identifying treatment sites within the airway being highly susceptible to either airway inflammation, airway constriction, excessive mucus secretion, or any other symptom of reversible obstructive pulmonary disease.


Another variation of the invention includes the method described above and the additional step of stimulating the lung to produce at least one artificially induced symptom of reversible obstructive pulmonary disease. The invention may further comprise the step of evaluating the results of the stimulating step.


Another variation of the invention includes the method described above where treating at least airway tissue within the lung further comprises the step of determining the effect of the treatment by visually observing the airway for blanching, or a change in appearance, of airway tissue.


Another variation of the invention includes the method described above where treating at least airway tissue at a treatment site within the lung further comprises the step of monitoring electrical impedance of tissue at one or more points.


Another variation of the invention includes the method described above where treating the lung includes sub-mucosal treatment of at least airway tissue in the lung.


Another variation of the invention includes the method described above where the treating step includes treating the lung by depositing a radioactive substance in at least one treatment site within the lung.


Another variation of the invention include the method described above further including the step of scraping tissue from a wall of an airway within the lung prior to the treating step. The invention may further comprise depositing a substance on the scraped wall of the airway.


Another variation of the invention includes the method described above where the treating step uses a modality selected from the group consisting of mechanical, chemical, radio frequency, radioactive energy, heat, and ultrasound.


Another variation of the invention includes the method described above further comprising pre-treating the lung to at least reduce the ability of the lung to produce at least one symptom of reversible obstructive pulmonary disease prior to the treating step, where at least one parameter of the pre-treating step is lesser than at least one parameter of the treating step.


Another variation of the invention comprises the method described above where the treating step includes separating the treating step into stages to reduce the healing load on the lung. The separating step may comprise treating different regions of the lung at different times or dividing the number of treatment sites into a plurality of groups of treatment sites and treating each group at a different time.


Another variation of the invention includes the method described above further comprising sensing movement of the lung and repositioning the treatment device in response to said sensing step.


Another variation of the invention includes the method described above further comprising reducing the temperature of lung tissue adjacent to a treatment site.


Another variation of the invention includes the method described above further comprising the step of providing drug therapy, exercise therapy, respiratory therapy, and/or education on disease management techniques to further reduce the effects of reversible obstructive pulmonary disease.


The invention further includes the method for reversing a treatment to reduce the ability of the lung to produce at least one symptom of reversible obstructive pulmonary disease comprising the step of stimulating re-growth of smooth muscle tissue in the lung.


The invention further includes the method of evaluating an individual having reversible obstructive pulmonary disease as a candidate for a procedure to reduce the ability of the individual's lung to produce at least one reversible obstructive pulmonary disease symptom by treating an airway within the lung of the individual, the method comprising the steps of assessing the pulmonary condition of the individual, comparing the pulmonary condition to a corresponding predetermined state; and evaluating the individual based upon the comparing step. The method may additionally comprise the steps of performing pulmonary function tests on the individual to obtain at least one pulmonary function value, comparing the at least one pulmonary function value to a corresponding predetermined pulmonary function value, and evaluating the individual based upon the comparing step.


The invention further comprises a method of evaluating the effectiveness of a procedure to reduce the ability of lung to produce at least one symptom of reversible obstructive pulmonary disease previously performed on an individual having reversible obstructive pulmonary disease, the method comprising the steps of assessing the pulmonary condition of the individual, comparing the pulmonary condition to a corresponding predetermined state; and evaluating the effectiveness of the procedure based upon the comparing step. The method may additionally comprise the steps of performing pulmonary function tests on the individual to obtain at least one pulmonary function value, treating the lung to at least reduce the ability of the lung to produce at least one symptom of reversible obstructive pulmonary disease, performing post-procedure pulmonary function tests on the individual to obtain at least one post-procedure pulmonary function value; and comparing the pulmonary function value with the post-procedure pulmonary function value to determine the effect of the treating step.





BRIEF DESCRIPTION OF THE DRAWINGS

The invention will now be described in greater detail with reference to the various embodiments illustrated in the accompanying drawings:



FIG. 1 is a cross sectional view of an airway in a healthy lung.



FIG. 2 shows a section through a bronchiole having an airway diameter smaller than that shown in FIG. 1.



FIG. 3 illustrates the airway of FIG. 1 in which the smooth muscle 14 has hypertrophied and increased in thickness causing reduction of the airway diameter.



FIG. 4A is a schematic view of the lungs being treated with a treatment device as described herein.



FIG. 4B illustrates one example of a treatment system for use with the methods described herein.



FIG. 4C illustrates another variation of a treatment system that applies the treatment externally to the lungs.



FIG. 5 illustrates a map to aid in treatment of the airways.



FIG. 6A illustrates a device that stimulates the airway into contracting.



FIGS. 6B-6F illustrate various modes of measuring parameters within the lungs to identify treatment sites.



FIG. 7 is a schematic side view of an embodiment of a treatment device with a balloon for heating of tissue.





DETAILED DESCRIPTION

The invention relates to methods for improving airflow through the airways of a lung having reversible obstructive pulmonary disease. It is intended that the invention is applicable to any aspect of reversible obstructive pulmonary disease, including but not limited to asthma. One way of improving airflow is to decrease the resistance to airflow within the lungs. There are several approaches to reducing this resistance, including but not limited to reducing the ability of the airway to contract, increasing the airway diameter, reducing the inflammation of airway tissues, and/or reducing the amount of mucus plugging of the airway. Another approach to reducing resistance is to increase the resting airway diameter of an airway such that any subsequent narrowing will not reduce the airway to a diameter such that obstruction to airflow is discernable by the patient. The present invention includes advancing a treatment device into the lung and treating the lung to at least reduce the ability of the lung to produce at least one symptom of reversible obstructive pulmonary disease. The following is a brief discussion of some causes of increased resistance to airflow within the lungs and the inventive treatment of the invention described herein. As such, the following discussion is not intended to limit the aspects or objective of the inventive method as the inventive method may cause physiological changes not described below but such changes still contributing to reducing or eliminating at least one of the symptoms of reversible obstructive pulmonary disease.


Reducing the Ability of the Airway to Contract


The inventive treatment reduces the ability of the airways to narrow or to reduce in diameter due to airway smooth muscle contraction. The inventive treatment uses a modality of treatments including, but not limited to the following: chemical, radio frequency, radioactivity, heat, ultrasound, radiant, laser, microwave, or mechanical energy (such as in the form of cutting, punching, abrading, rubbing, or dilating). This treatment reduces the ability of the smooth muscle to contract thereby lessening the severity of an asthma attack. The reduction in the ability of the smooth muscle to contract may be achieved by treating the smooth muscle itself or by treating other tissues which in turn influence smooth muscle contraction or the response of the airway to the smooth muscle contraction. Treatment may also reduce airway responsiveness or the tendency of the airway to narrow or to constrict in response to a stimulus.


The amount of smooth muscle surrounding the airway can be reduced by exposing the smooth muscle to energy which either kills the muscle cells or prevents these cells from replicating. The reduction in smooth muscle reduces the ability of the smooth muscle to contract and to narrow the airway during a spasm. The reduction in smooth muscle and surrounding tissue has the added potential benefit of increasing the caliber or diameter of the airways, which further reduces the resistance to airflow through the airways. In addition to the use of debulking smooth muscle tissue to open up the airways, the device used in the present invention may also eliminate smooth muscle altogether by damaging or destroying the muscle. The elimination of the smooth muscle prevents the contraction or spasms of hyper-reactive airways of a patient having reversible obstructive pulmonary disease. By doing so, the elimination of the smooth muscle may reduce some symptoms of reversible obstructive pulmonary disease.


The ability of the airway to contract can also be altered by treatment of the smooth muscle in particular patterns. The smooth muscle is arranged around the airways in a generally helical pattern with pitch angles ranging from about −38 to about +38 degrees. Thus, the treatment of the smooth muscle in appropriate patterns interrupts or cuts through the helical pattern of the smooth muscle at a proper pitch and prevents the airway from constricting. This procedure of patterned treatment application eliminates contraction of the airways without completely eradicating smooth muscle and other airway tissue. A pattern for treatment may be chosen from a variety of patterns including longitudinal or axial stripes, circumferential bands, helical stripes, and the like as well as spot patterns having rectangular, elliptical, circular or other shapes. The size, number, and spacing of the treatment bands, stripes, or spots are chosen to provide a desired clinical effect of reduced airway responsiveness while limiting insult to the airway to a clinically acceptable level.


The patterned treatment of the tissues surrounding the airways with energy provides various advantages. The careful selection of the portion of the airway to be treated allows desired results to be achieved while reducing the total healing load. Patterned treatment can also achieve desired results with decreased morbidity, preservation of epithelium, and preservation of a continuous or near continuous ciliated inner surface of the airway for mucociliary clearance. The pattern of treatment may also be chosen to achieve desired results while limiting total treatment area and/or the number of airways treated, thereby improving speed and ease of treatment.


Application of energy to the tissue surrounding the airways may also cause the DNA of the cells to become cross linked. The treated cells with cross linked DNA are incapable of replicating. Accordingly, over time, as the smooth muscle cells die, the total thickness of smooth muscle decreases because of the inability of the cells to replicate. The programmed cell death causing a reduction in the volume of tissue is called apoptosis. This treatment does not cause an immediate effect but causes shrinking of the smooth muscle and opening of the airway over time and substantially prevents re-growth. The application of energy to the walls of the airway may also be used to cause a cross linking of the DNA of the mucus gland cells thereby preventing them from replicating and reducing excess mucus plugging or production over time.


The ability of the airways to contract may also be reduced by altering mechanical properties of the airway wall, such as by increasing stiffness of the wall or by increasing parenchymal tethering of the airway wall. Both of these methods increase the strength of the airway wall and further oppose contraction and narrowing of the airway.


There are several ways to increase the stiffness of the airway wall. One way to increase stiffness is to induce fibrosis or a wound healing response by causing trauma to the airway wall. The trauma can be caused by delivery of therapeutic energy to the tissue in the airway wall, by mechanical insult to the tissue, or by chemically affecting the tissue. The energy is preferably delivered in such a way that it minimizes or limits the intra-luminal thickening that may occur.


Another way to increase the effective stiffness of the airway wall is to alter the submucosal folding of the airway upon narrowing. The mucosal layer includes the epithelium, its basement membrane, and the lamina propria, a subepithelial collagen layer. The submucosal layer may also play a role in airway folding. As an airway narrows, its perimeter remains relatively constant, with the mucosal layer folding upon itself. As the airway narrows further, the mucosal folds mechanically interfere with each other, effectively stiffening the airway. In asthmatic patients, the number of folds is fewer and the size of the folds is larger, and thus, the airway is free to narrow with less mechanical interference of mucosal folds than in a healthy patient. Thus, asthmatic patients have a decrease in airway stiffness and the airways have less resistance to narrowing.


The mucosal folding in asthmatic patients can be improved by treatment of the airway in a manner which encourages folding. Preferably, a treatment will increase the number of folds and/or decrease the size of the folds in the mucosal layer. For example, treatment of the airway wall in a pattern such as longitudinal stripes can encourage greater number of smaller mucosal folds and increase airway stiffness.


The mucosal folding can also be increased by encouraging a greater number of smaller folds by reducing the thickness of the mucosa and/or submucosal layer. The decreased thickness of the mucosa or submucosa may be achieved by application of energy which either reduces the number of cells in the mucosa or submucosal layer or which prevents replication of the cells in the mucosa or submucosal layer. A thinner mucosa or submucosal layer will have an increased tendency to fold and increased mechanical stiffening caused by the folds.


Another way to reduce the ability of the airways to contract is to improve parenchymal tethering. The parenchyma surrounds airways and includes the alveolus and tissue connected to and surrounding the outer portion of the airway wall. The parenchyma includes the alveolus and tissue connected to and surrounding the cartilage that supports the larger airways. In a healthy patient, the parenchyma provides a tissue network which connects to and helps to support the airway. Edema or accumulation of fluid in lung tissue in patients with asthma or COPD is believed to decouple the airway from the parenchyma reducing the restraining force of the parenchyma which opposes airway constriction. Energy can be used to treat the parenchyma to reduce edema and/or improve parenchymal tethering.


In addition, the applied energy may be used to improve connection between the airway smooth muscle and submucosal layer to the surrounding cartilage, and to encourage wound healing, collagen deposition, and/or fibrosis in the tissue surrounding the airway to help support the airway and prevent airway contraction.


Increasing the Airway Diameter


Hypertrophy of smooth muscle, chronic inflammation of airway tissues, and general thickening of all parts of the airway wall can reduce the airway diameter in patients with reversible obstructive pulmonary disease. Increasing the overall airway diameter using a variety of techniques can improve the passage of air through the airways. Application of energy to the airway smooth muscle of an asthmatic patient can debulk or reduce the volume of smooth muscle. This reduced volume of smooth muscle increases the airway diameter for improved air exchange.


Reducing inflammation and edema of the tissue surrounding the airway can also increase the diameter of an airway. Inflammation and edema (accumulation of fluid) of the airway are chronic features of asthma. The inflammation and edema can be reduced by application of energy to stimulate wound healing and regenerate normal tissue. Healing of the epithelium or sections of the epithelium experiencing ongoing denudation and renewal allows regeneration of healthy epithelium with less associated airway inflammation. The less inflamed airway has an increased airway diameter both at a resting state and in constriction. The wound healing can also deposit collagen which improves parenchymal tethering.


Inflammatory mediators released by tissue in the airway wall may serve as a stimulus for airway smooth muscle contraction. Therapy that reduces the production and release of inflammatory mediator can reduce smooth muscle contraction, inflammation of the airways, and edema. Examples of inflammatory mediators are cytokines, chemokines, and histamine. The tissues which produce and release inflammatory mediators include airway smooth muscle, epithelium, and mast cells. Treatment of these structures with energy can reduce the ability of the airway structures to produce or release inflammatory mediators. The reduction in released inflammatory mediators will reduce chronic inflammation, thereby increasing the airway inner diameter, and may also reduce hyper-responsiveness of the airway smooth muscle.


A further process for increasing the airway diameter is by denervation. A resting tone of smooth muscle is nerve regulated by release of catecholamines. Thus, by damaging or eliminating nerve tissue in the airways the resting tone of the smooth muscle is reduced, and the airway diameter is increased. Resting tone may also be reduced by directly affecting the ability of smooth muscle tissue to contract.


Reducing Plugging of the Airway


Excess mucus production and mucus plugging are common problems during both acute asthma exacerbation and in chronic asthma management. Excess mucus in the airways increases the resistance to airflow through the airways by physically blocking all or part of the airway. Excess mucus may also contribute to increased numbers of leukocytes found in airways of asthmatic patients by trapping leukocytes. Thus, excess mucus can increase chronic inflammation of the airways.


One type of asthma therapy involves treatment of the airways with energy to target and reduce the amount of mucus producing cells, ducts, and glands and to reduce the effectiveness of the remaining mucus producing cells and glands. The treatment can eliminate all or a portion of the mucus producing cells, ducts, and glands, can prevent the cells from replicating or can inhibit their ability to secrete mucus. This treatment will have both chronic benefits in increasing airflow through the airways and will lessen the severity of acute exacerbation of the symptoms of reversible obstructive pulmonary disease.


Application of Treatment


The following illustrations are examples of the invention described herein. It is contemplated that combinations of aspects of specific embodiments or combinations of the specific embodiments themselves are within the scope of this disclosure.



FIGS. 1 and 2 illustrate cross sections of two different airways in a healthy patient. The airway of FIG. 1 is a medium sized bronchus having an airway diameter D1 of about 3 mm. FIG. 2 shows a section through a bronchiole having an airway diameter D2 of about 1.5 mm. Each airway includes a folded inner surface or epithelium 10 surrounded by stroma 12 and smooth muscle tissue 14. The larger airways including the bronchus shown in FIG. 1 also have mucous glands 16 and cartilage 18 surrounding the smooth muscle tissue 14. Nerve fibers 20 and blood vessels 24 also surround the airway.



FIG. 3 illustrates the bronchus of FIG. 1 in which the smooth muscle 14 has hypertrophied and increased in thickness causing the airway diameter to be reduced from the diameter D1 to a diameter D3.



FIG. 4A is a schematic side view of the lungs being treated with a treatment device 38 according to the present invention. The treatment device 100 is an elongated member for treating tissue at a treatment site 34 within a lung. Although the invention discusses treatment of tissue at the airway wall surface it is also intended that the invention include treatment below an epithelial layer of the lung tissue. The invention may also rely on the use of an imaging device 36 to enable the identification of at least one treatments site from the plurality of possible treatment site locations. The imaging device may employ radiographic visualization such as fluoroscopy or other external visualization means such as computer aided tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), optical coherence tomography, or ultrasonic imaging. The imaging device may be external as shown. Alternatively, the imaging device may have a component that is affixed to the treatment system 32 or otherwise is inserted in to the body.



FIG. 4B represents one example of a treatment system 32 according to the present invention. In this variation, the system 32 delivers therapeutic energy to tissue of a patient via a device 100. Variations of devices are described in U.S. application Ser. Nos. 11/255,796 and 11/256,295 both filed Oct. 21, 2005 and the entirety of each of which is incorporated by reference.



FIG. 4B shows a schematic diagram of one example of a system 32 for delivering therapeutic energy to tissue of a patient for use with the device described herein. The illustrated variation shows, the system 32 having a power supply (e.g., consisting of an energy generator 112, a controller 114 coupled to the energy generator, a user interface surface 116 in communication with the controller 114). It is noted that the device may be used with a variety of systems (having the same or different components). For example, although variations of the device shall be described as RF energy delivery devices, variations of the device may include resistive heating systems, infrared heating elements, microwave energy systems, focused ultrasound, cryo-ablation, or any other energy deliver system. It is noted that the devices described should have sufficient length to access the tissue targeted for treatment. For example, it is presently believed necessary to treat airways as small as 3 mm in diameter to treat enough airways for the patient to benefit from the described treatment (however, it is noted that the invention is not limited to any particular size of airways and airways smaller than 3 mm may be treated). Accordingly, devices for treating the lungs must be sufficiently long to reach deep enough into the lungs to treat these airways. Accordingly, the length of the sheath/shaft of the device that is designed for use in the lungs should preferably be between 1.5-3 ft long in order to reach the targeted airways.


The particular system 32 depicted in FIG. 4B is one having a user interface as well as safety algorithms that are useful for the asthma treatment discussed above. Addition information on such a system may be found in U.S. Provisional application Nos. 60/674,106, and 60/673,876 both filed Apr. 21, 2005 the entirety of each of which is incorporated by reference herein.


Referring again to FIG. 4B, a variation of a device 100 described herein includes a flexible sheath 202, an elongate shaft 204 (in this example, the shaft extends out from the distal end of the sheath 202), and a handle or other operator interface 206 (optional) secured to a proximal end of the sheath 202. The distal portion of the device 100 includes an energy transfer element 208 (e.g., an electrode, a basket electrode, a resistive heating element, cryoprobe, etc.). Additionally, the device includes a connector 210 common to such energy delivery devices. The connector 210 may be integral to the end of a cable 212 as shown, or the connector 210 may be fitted to receive a separate cable 212. In any case, the device is configured for attachment to the power supply via some type connector 210. The elongate portions of the device 202 and 204 may also be configured and sized to permit passage through the working lumen of a commercially available bronchoscope or endoscope. As discussed herein, the device is often used within an endoscope, bronchoscope or similar device. However, the device may also be advanced into the body with or without a steerable catheter, in a minimally invasive procedure or in an open surgical procedure, and with or without the guidance of various vision or imaging systems.



FIG. 4B also illustrates additional components used in variations of the system. Although the depicted systems are shown as RF type energy delivery systems, it is noted that the invention is not limited as such. Other energy delivery configurations contemplated may include or not require some of the elements described below. The power supply (usually the user interface portion 116) shall have connections 120, 128, 130 for the device 100, return electrode 124 (if the system 32 employs a monopolor RF configuration), and actuation pedal(s) 126 (optional). The power supply and controller may also be configured to deliver RF energy to an energy transfer element configured for bipolar RF energy delivery. The user interface 116 may also include visual prompts 132, 160, 168, 174 for user feedback regarding setup or operation of the system. The user interface 116 may also employ graphical representations of components of the system, audio tone generators, as well as other features to assist the user with system use.


In many variations of the system, the controller 114 includes a processor 122 that is generally configured to accept information from the system and system components, and process the information according to various algorithms to produce control signals for controlling the energy generator 112. The processor 122 may also accept information from the system 110 and system components, process the information according to various algorithms and produce information signals that may be directed to the visual indicators, digital display or audio tone generator of the user interface in order to inform the user of the system status, component status, procedure status or any other useful information that is being monitored by the system. The processor 122 of the controller 114 may be digital IC processor, analog processor or any other suitable logic or control system that carries out the control algorithms.


In one variation of the system shown in FIG. 4B, the RF generator 112 generates RF energy at a frequency of about 400 kHz to about 500 kHz in with a wattage output sufficient to maintain a target tissue temperature of about 60 degrees C. to about 80 degrees C., specifically, about 60 degrees C. to about 70 degrees C. (when measuring at a surface of the electrode). The duration of the activation state for an embodiment of a single treatment cycle may be about 1 seconds to about 15 seconds, specifically, about 8 seconds to about 12 seconds. Alternatively, the duration of the activation state of the RF generator may also be set to not more than the duration required to deliver about 150 Joules of energy to the target tissue, specifically, not more than the duration required to deliver about 125 Joules of RF energy to target tissue.


Additional examples of devices for use with the methods of this invention are found in the following U.S. patent application Ser. Nos. 09/095,323 and 09/436,455; U.S. Pat. Nos. 6,488,675 and 6,411,852. The entirety of each of the aforementioned applications is incorporated by reference herein.



FIG. 4C represents another schematic side view of lungs being treated with a treatment device 100 according to the present invention. In this variation, the treatment device 100 and system 32 are external to the lungs and/or body but still applies energy to within the lungs. For example, such a treatment may use a high frequency ultrasound (commonly referred to as HIFU). As discussed above, the invention may also rely on the use of an imaging device 36.


The treatment of an airway with the treatment device may involve placing a visualization system such as an endoscope or bronchoscope into the airways. The treatment device is then inserted through or next to the bronchoscope or endoscope while visualizing the airways. Alternatively, the visualization system may be built directly into the treatment device using fiber optic imaging and lenses or a CCD and lens arranged at the distal portion of the treatment device. The treatment device may also be positioned using radiographic visualization such as fluoroscopy or other external visualization means. The treatment device which has been positioned with a distal end within an airway to be treated is energized so that energy is applied to the tissue of the airway walls in a desired pattern and intensity. The distal end of the treatment device may be moved through the airway in a uniform painting like motion to expose the entire length of an airway to be treated to the energy. The treatment device may be passed axially along the airway one or more times to achieve adequate treatment. The “painting-like” motion used to expose the entire length of an airway to the energy may be performed by moving the entire treatment device from the proximal end either manually or by motor. Alternatively, segments, stripes, rings or other treatment patterns may be used.


According to one variation of the invention, the energy is transferred to or from an airway wall in the opening region of the airway, preferably within a length of approximately two times the airway diameter or less, and to wall regions of airways distal to bifurcations and side branches, preferably within a distance of approximately twice the airway diameter or less. The invention may also be used to treat long segments of un-bifurcated airway.


The invention includes a method of advancing a treatment device into a lung and treating the lung with the device to, at least, reduce the ability of the lung to produce at least one symptom of reversible obstructive pulmonary disease. It is contemplated that the treatment may reduce all of the symptoms of reversible obstructive disease. Alternatively, the treatment may be selected to address specific symptoms of the disease. It is also intended that the treatment of the lung may sufficiently reduce the symptoms of reversible obstructive pulmonary disease such that the patient is able to function as those free from the disease. Alternatively, the treatment may be such that the symptoms are reduced to allow the patient to more easily manage the disease. It is also intended that the effects of the treatment may be either long term or short term with repeating treatment necessary to suppress the symptoms.


The methods of the invention described herein may be performed while the lung is experiencing natural symptoms of reversible obstructive pulmonary disease. One such example is where an individual, experiencing an asthma attack, or acute exacerbation of asthma or COPD, undergoes treatment to improve the individual's ability to breath. In such a case, the treatment, called ‘rescue,’ seeks to provide immediate relief for the patient.


The method may also include the steps of locating one or more treatment sites within an airway of the lung, selecting one of the treatment sites from the locating step and treating at least one of the selected treatment sites. As mentioned above, these steps may be, but are not necessarily, performed while the lung is experiencing symptoms of reversible obstructive pulmonary disease.


The invention may further comprise the step of stimulating the lung to produce at least one artificially induced symptom of reversible obstructive pulmonary disease. For example, stimulation of the lung would preferably increase the resistance to airflow within the lung, constrict airways within the lung, inflame/irritate airway tissues, increase edema and/or increase the amount of mucus plugging of the airway. Stimulation of the lung may occur at any point during the procedure or before the procedure. For example, the lung may be stimulated either prior to or after, the step of locating a treatment site. If the lung is stimulated prior to the step of locating a treatment site, the reaction of the stimulated tissue within the lung may be useful in determining which locations are to be selected as treatment sites. The lung tissue or airway tissue within the lung may be stimulated by a variety of methods including but not limited to pharmacological stimulation, (e.g., histamine, methacholine, or other bronchoconstricting agents, etc.), electrical stimulation, mechanical stimulation, or any other stimuli causing obstructive pulmonary symptoms. For example, electrical stimulation may comprise exposing airway tissue to electrical field stimulation. An example of such parameters include 15 VDC, 0.5 ms pulses, 0.5-16 Hz, and 70 VDC, 2-3 ms pulses, 20 HZ.


The locating step described above may be performed using a non-invasive imaging technique, including but not limited to, a bronchogram, magnetic resonance imaging, computed tomography, radiography (e.g., x-ray), and ventilation perfusion scans.


The invention further includes the steps of testing the lung for at least one pre-treatment pulmonary function value prior to treating the lung with the device. After the lung is treated, the lung is re-tested for at least one post-treatment pulmonary function value. Naturally, the two pulmonary function values may be compared to estimate the effect of the treatment. The invention may also include treating additional sites in the lung after the re-testing step to at least reduce the effect of at least one symptom of reversible obstructive pulmonary disease. The invention may also include stimulating the lung to produce at least one artificially induced symptom of reversible obstructive pulmonary disease. As mentioned above, the stimulation of the lung may occur at any point during, or prior to, the procedure. For example, stimulation of the lung may occur prior to the step of testing the lung for pre-treatment pulmonary values. In this case, the values would be determinative of pulmonary function values of a lung experiencing symptoms of reversible obstructive pulmonary disease. Accordingly, the objective is to treat the lung until acceptable pulmonary function values are obtained. One benefit of such a procedure is that the effect of the treatment on the patient is more readily observed as compared to the situation where a patient, having previously been treated, must wait for an attack of reversible obstructive pulmonary disease to determine the efficacy of the treatment.


Pulmonary function values are well known in the art. The following is an example of pulmonary function values that may be used. Other pulmonary function values, or combinations thereof, are intended to be within the scope of this invention. The values include, but are not limited to, FEV (forced expiratory volume), FVC (forced vital capacity), FEF (forced expiratory flow), Vmax (maximum flow), PEFR (peak expiratory flow rate), FRC (functional residual capacity), RV (residual volume), TLC (total lung capacity).


FEV measures the volume of air exhaled over a pre-determined period of time by a forced expiration immediately after a full inspiration. FVC measures the total volume of air exhaled immediately after a full inspiration. Forced expiratory flow measures the volume of air exhaled during a FVC divided by the time in seconds. Vmax is the maximum flow measured during FVC. PEFR measures the maximum flow rate during a forced exhale starting from full inspiration. RV is the volume of air remaining in the lungs after a full expiration.


The locating step described above may also comprise identifying treatment sites within the airway being susceptible to a symptom of reversible obstructive pulmonary disease. For example, symptoms may include, but are not limited to, airway inflammation, airway constriction, excessive mucous secretion, or any other asthmatic symptom. Stimulation of the lung to produce symptoms of reversible obstructive pulmonary disease may assist in identifying ideal treatment sites.


As noted above, the method of the present invention may include stimulating the lung to produce at least one artificially induced symptom of reversible obstructive pulmonary disease and further include the step of evaluating the result of stimulation of the lung. For example, the evaluating step may include visually evaluating the effect of the stimulating step on the airway using a bronchoscope with a visualization system or by non-invasive imaging techniques, such as those describe herein. The evaluating step may include measuring pressure changes in the airway before and after the stimulating step. Pressure may be measured globally (e.g., within the entire lung), or locally (e.g., within a specific section of the lung such as an airway or alveolar sac.) Also, the evaluating step may comprise measuring the electrical properties of the tissue before and after the stimulating step. The invention may also include evaluating the results of the stimulating step by combining any of the methods previously mentioned. Also, the invention may further comprise the step of selecting at least one treatment parameter based upon the results of the evaluating step. Such treatment parameters may include, but are not limited to, duration of treatment, intensity of treatment, temperature, amount of tissue treated, depth of treatment, etc.


The method may also include the step of determining the effect of the treatment by visually observing lung, airway or other such tissue for blanching of the tissue. The term “blanching” is intended to include any physical change in tissue that is usually, but not necessarily, accompanied by a change in the color of the tissue. One example of such blanching is where the tissue turns to a whitish color after the treatment of application of energy.


The invention may also include the step of monitoring impedance across a treated area of tissue within the lung. Measuring impedance may be performed in cases of monopolar or bipolar energy delivery devices. Additionally, impedance may be monitored at more than one site within the lungs. The measuring of impedance may be, but is not necessarily, performed by the same electrodes used to deliver the energy treatment to the tissue. Furthermore, the invention includes adjusting the treatment parameters based upon the monitoring of the change in impedance after the treatment step. For example, as the energy treatment affects the properties of the treated tissue, measuring changes in impedance may provide information useful in adjusting treatment parameters to obtain a desired result.


Another aspect of the invention includes advancing a treatment device into the lung and treating lung tissue to at least reduce the ability of the lung to produce at least one symptom of reversible obstructive pulmonary disease and further comprising the step of sub-mucosal sensing of the treatment to the lung tissue. The sub-mucosal sensing may be invasive such as when using a probe equipped to monitor temperature, impedance, and/or blood flow. Or, the sub-mucosal sensing may be non-invasive in such cases as infra-red sensing.


The invention may also include using the treatment device to deposit radioactive substances at select treatment sites within the lung. The radioactive substances, including, but not limited to Iridium (e.g. 192Ir.) either treat the lung tissue over time or provide treatment upon being deposited.


The invention also includes scraping epithelial tissue from the wall of an airway within the lung prior to advancing a treatment device into the lung to treat the lung tissue. The removal of the epithelial tissue allows the device to treat the walls of an airway more effectively. The invention further comprises the step of depositing a substance on the scraped wall of the airway after the device treats the airway wall. The substance may include epithelial tissue, collagen, growth factors, or any other bio-compatible tissue or substance, which promotes healing, prevents infection, and/or assists in the clearing of mucus. Alternatively, the treatment may comprise the act of scraping epithelial tissue to induce yield the desired response.


The invention includes using the treating device to pre-treat the lung to at least reduce the ability of the lung to produce at least one symptom of reversible obstructive pulmonary disease prior to the treating step. At least one of the parameters of the pre-treating step may differ than one of the parameters of the treating step. Such parameters may include time, temperature, amount of tissue over which treatment is applied, amount of energy applied, depth of treatment, etc.


The invention may also include advancing the treatment device into the lung and treating the lung tissue in separate stages. One of the benefits of dividing the treating step into separate stages is that the healing load of the patient is lessened. Dividing of the treating step may be accomplished by treating different regions of the lung at different times. Or, the total number of treatment sites may be divided into a plurality of groups of treatment sites, where each group of treatment sites is treated at a different time. The amount of time between treatments may be chosen such that the healing load placed on the lungs is minimized.


The invention may also include advancing a treatment device into the lung, treating the lung with the device and sensing movement of the lung to reposition the treatment device in response to the movement. This sensing step accounts for the tidal motion of the lung during breathing cycles or other movement. Taking into account the tidal motion allows improved accuracy in repositioning of the device at a desired target.


The invention may also include the additional step of reducing or stabilizing the temperature of lung tissue near to a treatment site. This may be accomplished for example, by injecting a cold fluid into lung parenchyma or into the airway being treated, where the airway is proximal, distal, or circumferentially adjacent to the treatment site. The fluid may be sterile normal saline, or any other bin-compatible fluid. The fluid may be injected into treatment regions within the lung while other regions of the lung normally ventilated by gas. Or, the fluid may be oxygenated to eliminate the need for alternate ventilation of the lung. Upon achieving the desired reduction or stabilization of temperature the fluid may be removed from the lungs. In the case where a gas is used to reduce temperature, the gas may be removed from the lung or allowed to be naturally exhaled. One benefit of reducing or stabilizing the temperature of the lung may be to prevent excessive destruction of the tissue, or to prevent destruction of certain types of tissue such as the epithelium, or to reduce the systemic healing load upon the patient's lung.


Also contemplated as within the scope of the invention is the additional step of providing therapy to further reduce the effects of reversible obstructive pulmonary disease or which aids the healing process after such treatment. Some examples of therapy include, drug therapy, exercise therapy, and respiratory therapy. The invention further includes providing education on reversible obstructive pulmonary disease management techniques to further reduce the effects of the disease. For example, such techniques may be instruction on lifestyle changes, self-monitoring techniques to assess the state of the disease, and/or medication compliance education.


There may be occurrences where it is necessary to reverse the effects of the treatment described herein. Accordingly, the invention further includes a method for reversing a treatment to reduce the ability of the lung to produce at least one symptom of reversible obstructive pulmonary disease comprising the step of stimulating re-growth of smooth muscle tissue. The re-stimulation of the muscle may be accomplished by the use of electro-stimulation, exercising of the muscle and/or drug therapy.


The invention further includes methods of evaluating individuals having reversible obstructive pulmonary disease, or a symptom thereof, as a candidate for a procedure to reduce the ability of the individual's lung to produce at least one symptom of reversible obstructive pulmonary disease. The method comprises the steps of assessing the pulmonary condition of the individual, comparing the pulmonary condition to a corresponding pre-determined state, and evaluating the individual as a candidate based upon the comparison.


In assessing the pulmonary condition, the method may comprise the steps of performing pulmonary function tests on the individual to obtain a pulmonary function value which is compared to a predetermined value. Examples of pre-determined values are found above.


The method of evaluating may further include the step of determining how the individual's tissue will react to treatment allowing the treatment to be tailored to the expected tissue response.


The method of evaluating may further comprises the step of pulmonary function testing using a gas, a mixture of gases, or a composition of several mixtures of gases to ventilate the lung. The difference in properties of the gases may aid in the pulmonary function testing. For example, comparison of one or more pulmonary function test values that are obtained with the patient breathing gas mixtures of varying densities may help to diagnose lung function. Examples of such mixtures include air, at standard atmospheric conditions, and a mixture of helium and oxygen. Additional examples of pulmonary testing include tests that measure capability and evenness of ventilation given diffusion of special gas mixtures. Other examples of gases used in the described tests, include but are not limited to, nitrogen, carbon monoxide, carbon dioxide, and a range of inert gases.


The invention may also comprise the step of stimulating the lung to produce at least one artificially induced symptom of reversible obstructive pulmonary disease. Stimulating the symptoms of the disease in an individual allows the individual to be evaluated as the individual experiences the symptoms thereby allowing appropriate adjustment of the treatment.


The method of evaluating may also comprise the step of obtaining clinical information from the individual and accounting for the clinical information for treatment.


The method may further comprise the selection of a patient for treatment based upon a classification of the subtype of the patient's disease. For example, in asthma there are a number of ways to classify the disease state. One such method is the assessment of the severity of the disease. An example of a classification scheme by severity is found in the NHLBI Expert Panel 2 Guidelines for the Diagnosis and Treatment of Asthma. Another selection method may include selecting a patient by the type of trigger that induces the exacerbation. Such triggers may be classified further by comparing allergic versus non-allergic triggers. For instance, an exercise induced bronchospasm (EIB) is an example of a non-allergenic trigger. The allergic sub-type may be further classified according to specific triggers (e.g., dust mites, animal dander, etc.). Another classification of the allergic sub-type may be according to characteristic features of the immune system response such as levels of IgE (a class of antibodies that function in allergic reactions, also called immunoglobulin). Yet another classification of allergic sub-types may be according to the expression of genes controlling certain interleukins (e.g., IL-4, IL-5, etc.) which have been shown to play a key role in certain types of asthma.


The invention further comprises methods to determine the completion of the procedure and the effectiveness of the reduction in the lung's ability to produce at least one symptom of reversible obstructive pulmonary disease. This variation of the invention comprises assessing the pulmonary condition of the individual, comparing the pulmonary condition to a corresponding predetermined state, and evaluating the effectiveness of the procedure based on the comparison. The invention may also comprise the steps of performing pulmonary function tests on the individual to obtain at least one pulmonary function value, treating the lung to at least reduce the ability of the lung to produce at least one symptom of reversible obstructive pulmonary disease, performing a post-procedure pulmonary function tests on the individual to obtain at least one post pulmonary function value and comparing the two values.


This variation of the invention comprises obtaining clinical information, evaluating the clinical information with the results of the test to determine the effectiveness of the procedure. Furthermore, the variation may include stimulating the lung to produce a symptom of reversible obstructive pulmonary disease, assessing the pulmonary condition of the patient, then repeating the stimulation before the post-procedure pulmonary therapy. These steps allow comparison of the lung function when it is experiencing symptoms of reversible obstructive pulmonary disease, before and after the treatment, thereby allowing for an assessment of the improved efficiency of the lung during an attack of the disease.


The medical practitioners performing the treatments described herein may wish to treat a limited number of sites in the lung to produce acceptable results in lessening the severity of asthmatic or reversible obstructive pulmonary disease symptoms. For example, if a patient requires an increasing amount of medication (e.g., sedatives or anesthesia) to remain under continued control for performance of the procedure, then a medical practitioner may limit the procedure time rather than risk overmedicating the patient. As a result, rather than treating the patient continuously to complete the procedure, the practitioner may plan to break the procedure in two or more sessions. Subsequently, increasing the number of sessions poses additional consequences on the part of the patient in cost, the residual effects of any medication, adverse effects of the non-therapeutic portion of the procedure, etc.


Accordingly, the invention includes methods of treating airways in a lung to decrease asthmatic symptoms. The methods include measuring a parameter of an airway at a plurality of locations in a lung, identifying at least one treatment site from at least one of the plurality of locations based on the parameter, and applying energy to the treatment site to reduce the ability of the site to narrow.


Identification of the treatment sites may comprise comparing the parameter to known or studied parameters and selecting those sites that meet or exceed specific criteria. Alternatively, or in combination, identification of treatment sites may comprise selecting the sites with the most significant parameters, or delivering a treatment specifically tailored to the parameters measured at each individual site. For example, if the parameter comprises measuring contractile force or the amount of contraction, then sites having the highest quantitative parameters may be selected as treatment sites. In another variation, the medical practitioner may simply rank the parameters in a desired order of value and treat those sites that are believed to provide the most benefit. For example, the medical practitioner may chose to treat the top 10% of sites having the most contraction, smooth muscle tissue, or other parameters as described herein. It is also contemplated that the diametrical size of the airway or the length of the airway segment may be correlated to the ability for that site to narrow. For example, when measuring a narrowed airway diameter relative to its natural diameter, the percentage change for a large diameter airway may be different than a percentage change for a smaller airway. In such a case, the medical practitioner may measure the airway diameter at each site for determining the course of treatment. In other words, the practitioner may deliver treatment to specific sites that meet certain criteria (e.g., sites having a certain diameter). Alternatively, or in combination, the practitioner may delivery treatment specifically tailored to each individual site based on a characteristic of the site (e.g., its diameter). For example, when delivering energy, the practitioner could deliver more energy to larger diameter airway, and less energy to smaller diameter airways (or vice versa).


In those cases where more than one treatment site is identified, the method may include the act of treating the new treatment site.


The method may also include correlating the treatment sites to a map 90, as shown in FIG. 5, the map may provide a graphical representation of a bronchial tree. As shown, the various bronchioles 92 decrease in size and have many branches 96 as they extend into the right and left bronchi 94. Accordingly, an efficient treatment may require identification of potential treatment sites, treated sites, and other areas of the bronchial tree.


This mapping may be performed for a variety of reasons. For example, prior to treatment, the correlation may identify general areas for treatment by the medical practitioner. Once the area is treated, the map may then be marked to indicate a completed treatment. The treatment plan provided by the map should allow the medical practitioner a guide so that it is possible to treat less than all of the lungs. The treatment plan or map also may assist in avoiding double treatment of a particular treatment site. It is contemplated that the map 90 may be an actual chart, whether in tangible form or electronic form. Furthermore, the map may be incorporated into the treatment system 32 or the user interface 116 as discussed above. It is also contemplated that the map may be a three dimensional computer model, wherein the position of completed treatment sites are recorded by storing the spatial coordinates of these sites as each treatment is completed. As subsequent treatments are made, the user may compare the current position of the catheter to the map, which will aid in determining which site to treat next.


The parameters to be measured in accordance with the methods described herein may be any parameter that is an indicator of or associated with symptoms of asthma. For example, the parameter may be a measure of pulmonary function values (see above), a measure of the contractile force at which the airway contracts, a thickness or amount of the airway smooth muscle at a particular location, eosinophil counts near or at the actual or potential treatment site, degree of airflow within the airway, degree of contraction of the airway during an asthma episode or after stimulation of the airway, metabolic rate to assess the presence of smooth muscle, electrical impedance to assess the nature of the airway tissue, and/or degree of wheezing at a particular location, etc. Other parameters indicative of asthma or a lack of airflow due to asthmatic symptoms are also intended to be within the scope of this disclosure.


Methods of the present invention include first stimulating the airway and then subsequently measuring the parameter. The stimulation may be performed electrically (such as by placing a device within the airway and stimulating using the settings described above). Alternatively, or in combination, the stimulation may be artificially induced using an agent, such as methacholine. For example, as shown in FIG. 6A, a device 150 may deliver the agent 152 into the airway 2.


Once the airway contracts, the contraction may be measured or assessed. Although not shown, the contraction may be measured or assessed without making contact with the airway wall (e.g., visually with a retical; or optically, via a camera). Alternatively, or in combination, as shown in FIG. 6B, a contraction measurement device 154 may be placed against the airway (either prior or during contraction) and expanded to measure a natural state of the airway. The contraction measurement device 154 then transmits information regarding the contraction of the airway using, for example, strain gauges 156 placed on moveable arms of the device. The contraction measurement device 154 may also deliver an agent to cause contraction of the airways. In this manner, the device 154 will be in place while the airway contracts.



FIG. 6C illustrates another variation where a balloon catheter 158 measures contraction of the airway. As the airway constricts, the balloon 160 increases in pressure. The pressure may then be characterized to determine the degree of contractile force of the airway. It should be noted that the balloon catheter 158 may also include fluid delivery ports to deliver an agent or have electrodes to induce the contraction. Other examples of devices that may be used to measure contraction of the airways are devices that measure the airway diameter mechanically or optically.


In another variation as shown in FIG. 6D, a device 162 (e.g., an ultrasound balloon catheter, a non-balloon ultrasound catheter, a catheter (balloon or non-balloon) that is equipped to measure impedance, etc.), may be expanded within the airway to measure the thickness of the adjacent airway smooth muscle 14. Alternatively, as described above, the measurement of the airway smooth muscle 14 may be achieved using the external imaging equipment 36 described above.


Another method of measuring parameters of an airway for identifying treatment sites comprises measuring eosinophil counts at the location. Eosinophils are white blood cells active in allergic diseases, parasitic infections, and other disorders. It is believed that cosinophils correlate to the amount of inflammation in an airway. FIG. 6E shows one way of obtaining an cosinophils count at a location in the lung. As shown, a device 164 advances a needle 166 within the airway to collect the eosinophils. Next, standard techniques are employed to measure the particular eosinophil count at the site.



FIG. 6F illustrates another variation of the invention where a device 168 measures airflow airflow at a location or near to a location for treatment. The device 168 may be a hot-wire amenometer, where the airflow causes the heated wire 170 to cool and the rate of cooling of the wire provides information regarding the airflow.


In additional variations of the method, the medical practitioner may deliver hyperpolarized helium or a radioactive isotope to aid in the imaging of the airways. External imaging, as shown FIGS. 4A and 4C may be used to assess ventilation in the lung and select the areas that constrict as treatment sites.


Alternatively, the external imaging may take a first image of the airways. Next, an agent is applied (either locally, systemically, or limited to a particular lobe) to induce contraction of the airways. The medical practitioner may then obtain a second image of the airways for comparison with the first to determine contraction of the airways.


In another variation of the invention, the parameter comprises assessing a metabolic rate at the location. If the measurement of the metabolic rate indicates the presence of a significant amount of smooth muscle tissue, then the area may be designated as a treatment site. The metabolic rate may be measured over a treatment site or over an area of the airways (e.g., a particular lobe or a section thereof.) The measurement of the metabolic rate may be performed using standard measuring techniques. For example, the device may deliver cool air to the treatment site and then measure the rate at which the tissue temperature returns to the original baseline temperature, thereby providing a measurement of the calories used to bring the tissue back to the baseline temperature. This would, in turn, provide a measure of the responsiveness of the smooth muscle tissue because more reactive or responsive tissue may correlate to a higher metabolic rate.


The treatment device of FIG. 7 is used to deliver radiant or heat energy to the airway. The treatment device of FIG. 7 can also deliver indirect radio frequency or microwave energy to the tissue. FIG. 7 shows an alternative embodiment of a balloon catheter treatment device 30k in which a fluid within the balloon 1126 is heated by internal electrodes 1128. The electrodes 1128 are illustrated in the shape of coils surrounding the shaft of the catheter, however, other electrode shapes may also be used. The electrodes 1128 may be used as resistance heaters by application of an electric current to the electrodes. Alternatively, radio frequency or microwave energy may be applied to the electrodes 1128 to heat a fluid within the balloon 1126. The heat then passes from an exterior of the balloon 1126 to the airway wall. The radio frequency or microwave energy may also be applied indirectly to the airway wall through the fluid and the balloon. In addition, hot fluid may be transmitted to the balloon 1126 from an external heating device for conductive heating of the airway tissue.


The invention herein is described by examples and a desired way of practicing the invention is described. However, the invention as claimed herein is not limited to that specific description in any manner. Equivalence to the description as hereinafter claimed is considered to be within the scope of protection of this patent.

Claims
  • 1. A method of treating a lung, the method comprising: stimulating an airway in the lung;after stimulating the airway, measuring a parameter of the airway;delivering a liquid to an enclosed volume via an energy delivery device; andbased on the measured parameter, applying energy from an electrode of the energy delivery device, through the enclosed volume of liquid, to tissue surrounding the airway to damage nerve tissue.
  • 2. The method of claim 1, wherein applying energy includes applying a radio frequency modality, and the energy delivery device is a monopolar device or a bipolar device.
  • 3. The method of claim 1, further including monitoring electrical impedance of the tissue surrounding the airway.
  • 4. The method of claim 1, wherein stimulating the airway causes the lung to produce at least one symptom of reversible obstructive pulmonary disease, and stimulating the airway increases the resistance to airflow in the lung or constricts one or more airways in the lung.
  • 5. The method of claim 1, wherein stimulating the airway includes introducing a pharmacological agent into the airway to induce constriction of the airway.
  • 6. The method of claim 1, wherein damaging nerve tissue reduces the resistance of the lung to airflow.
  • 7. The method of claim 1, wherein, after applying energy, the method further includes determining an effectiveness of applying energy by determining whether the lung has a reduced ability to produce at least one symptom of reversible obstructive pulmonary disease.
  • 8. The method of claim 1, wherein the energy delivery device includes a balloon that prevents the liquid from travelling distal of the energy delivery device within the airway.
  • 9. The method of claim 1, wherein stimulating the airway and measuring the parameter are both performed with the energy delivery device.
  • 10. A method of treating a lung, the method comprising: stimulating an airway in the lung to constrict the airway;after stimulating the airway, measuring a parameter of the airway;identifying a treatment site based on the measured parameter;applying energy to the identified treatment site from an electrode, through an enclosed volume of liquid, to damage nerve tissue to reduce the ability of the identified treatment site to respond to a stimulus; andafter applying energy to the identified treatment site, determining an effectiveness of applying energy to the identified treatment site by determining whether the lung has a reduced ability to produce at least one symptom of reversible obstructive pulmonary disease.
  • 11. The method of claim 10, wherein stimulating the airway includes contacting a portion of the airway with a pharmacological agent to induce constriction of the airway at the contacted portion of the airway, and identifying the treatment site based on the measured parameter includes selecting the contacted portion of the airway to receive energy from the electrode.
  • 12. The method of claim 10, wherein identifying the treatment site based on the measured parameter includes determining one or more portions of the airway to deliver energy from the electrode.
  • 13. The method of claim 12, wherein the enclosed volume of liquid is delivered to the airway via an energy delivery device that includes the electrode, and the energy delivery device includes a balloon that prevents the liquid from travelling distal of the energy delivery device within the airway.
  • 14. The method of claim 13, wherein stimulating the airway and measuring the parameter are both performed with the energy delivery device.
  • 15. A method of treating a lung, the method comprising: applying one or more diagnostic stimulations to the lung to constrict one or more airways of the lung;locating one or more treatment sites in the one or more airways of the lung by evaluating a reaction to the diagnostic stimulations; anddamaging nerve tissue via applying energy from an electrode, through an enclosed volume of liquid, in a manner that reduces the ability of the lung to produce a symptom of a lung disease in response to a stimulus.
  • 16. The method of claim 15, wherein applying diagnostic stimulations to the lung further includes exposing tissue surrounding the one or more airways to an electrical field stimulation.
  • 17. The method of claim 15, wherein locating the one or more treatment sites further includes measuring an electrical property of tissue surrounding the one or more airways before and after applying the diagnostic stimulations to the lung.
  • 18. The method of claim 15, wherein the electrode is a radio frequency electrode.
  • 19. The method of claim 15, wherein applying one or more diagnostic stimulations to the lung further includes introducing a pharmacological agent into the one or more airways to induce constriction of the one or more airways.
  • 20. The method of claim 15, wherein locating one or more treatment sites includes determining one or more portions of the one or more airways to deliver energy from the electrode.
CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No. 13/557,518 filed Jul. 25, 2012, which is a continuation of U.S. patent application Ser. No. 11/398,353 filed Apr. 4, 2006, now U.S. Pat. No. 8,251,070, which is a continuation-in-part of U.S. patent application Ser. No. 10/640,967 filed Aug. 13, 2003, now U.S. Pat. No. 7,273,055, which is a continuation of U.S. patent application Ser. No. 09/535,856 filed Mar. 27, 2000, now U.S. Pat. No. 6,634,363, the contents of each of which are incorporated herein by reference in their entirety.

US Referenced Citations (533)
Number Name Date Kind
612724 Hamilton Oct 1898 A
1155169 Starkweather Sep 1915 A
1207479 Bisgaard Dec 1916 A
1216183 Swingle Feb 1917 A
2072346 Smith Mar 1937 A
3320957 Sokolik May 1967 A
3568659 Karnegis Mar 1971 A
3667476 Muller Jun 1972 A
3692029 Adair Sep 1972 A
3995617 Watkins et al. Dec 1976 A
4095602 Leveen Jun 1978 A
4116589 Rishton Sep 1978 A
4129129 Amrine Dec 1978 A
4154246 Leveen May 1979 A
4461283 Doi Jul 1984 A
4502490 Evans et al. Mar 1985 A
4503855 Maslanka Mar 1985 A
4512762 Spears Apr 1985 A
4522212 Gelinas et al. Jun 1985 A
4557272 Carr Dec 1985 A
4565200 Cosman Jan 1986 A
4567882 Heller Feb 1986 A
4584998 McGrail Apr 1986 A
4612934 Borkan Sep 1986 A
4621642 Chen Nov 1986 A
4621882 Krumme Nov 1986 A
4625712 Wampler Dec 1986 A
4643186 Rosen et al. Feb 1987 A
4646737 Hussein et al. Mar 1987 A
4674497 Ogasawara Jun 1987 A
4683890 Hewson Aug 1987 A
4704121 Moise Nov 1987 A
4706688 Don Michael et al. Nov 1987 A
4709698 Johnston et al. Dec 1987 A
4729385 Juncosa et al. Mar 1988 A
4739759 Rexroth et al. Apr 1988 A
4754065 Levenson et al. Jun 1988 A
4754752 Ginsburg et al. Jul 1988 A
4765959 Fukasawa Aug 1988 A
4772112 Zider et al. Sep 1988 A
4773899 Spears Sep 1988 A
4779614 Moise Oct 1988 A
4784135 Blum et al. Nov 1988 A
4790305 Zoltan et al. Dec 1988 A
4799479 Spears Jan 1989 A
4802492 Grunstein Feb 1989 A
4817586 Wampler Apr 1989 A
4825871 Cansell May 1989 A
4827935 Geddes et al. May 1989 A
4846152 Wampler et al. Jul 1989 A
4862886 Clarke et al. Sep 1989 A
4895557 Moise et al. Jan 1990 A
4906229 Wampler Mar 1990 A
4907589 Cosman Mar 1990 A
4908012 Moise et al. Mar 1990 A
4920978 Colvin May 1990 A
4944722 Carriker et al. Jul 1990 A
4955377 Lennox et al. Sep 1990 A
4967765 Turner et al. Nov 1990 A
4969865 Hwang et al. Nov 1990 A
4976709 Sand Dec 1990 A
4985014 Orejola Jan 1991 A
4991603 Cohen et al. Feb 1991 A
5009636 Wortley et al. Apr 1991 A
5009936 Yamanaka et al. Apr 1991 A
5010892 Colvin et al. Apr 1991 A
5019075 Spears et al. May 1991 A
5027829 Larsen Jul 1991 A
5030645 Kollonitsch Jul 1991 A
5036848 Hewson Aug 1991 A
5053033 Clarke Oct 1991 A
5056519 Vince Oct 1991 A
5074860 Gregory et al. Dec 1991 A
5078716 Doll Jan 1992 A
5084044 Quint Jan 1992 A
5096916 Skupin Mar 1992 A
5100388 Behl et al. Mar 1992 A
5100423 Fearnot Mar 1992 A
5103804 Abele et al. Apr 1992 A
5105826 Smits et al. Apr 1992 A
5106360 Ishiwara et al. Apr 1992 A
5107830 Younes Apr 1992 A
5114423 Kasprzyk et al. May 1992 A
5116864 March et al. May 1992 A
5117828 Metzger et al. Jun 1992 A
5135517 McCoy Aug 1992 A
5152286 Sitko et al. Oct 1992 A
5165420 Strickland Nov 1992 A
5167223 Koros et al. Dec 1992 A
5170803 Hewson et al. Dec 1992 A
5174288 Bardy et al. Dec 1992 A
5188602 Nichols Feb 1993 A
5191883 Lennox et al. Mar 1993 A
5213576 Abiuso et al. May 1993 A
5215103 Desai Jun 1993 A
5231996 Bardy et al. Aug 1993 A
5232444 Just et al. Aug 1993 A
5234456 Silvestrini Aug 1993 A
5254088 Lundquist et al. Oct 1993 A
5255678 Deslauriers et al. Oct 1993 A
5255679 Imran Oct 1993 A
5265604 Vince Nov 1993 A
5269758 Taheri Dec 1993 A
5281218 Imran Jan 1994 A
5290550 Fisher et al. Mar 1994 A
5292331 Boneau Mar 1994 A
5293869 Edwards et al. Mar 1994 A
5309910 Edwards et al. May 1994 A
5313943 Houser et al. May 1994 A
5324284 Imran Jun 1994 A
5343936 Beatenbough et al. Sep 1994 A
5345936 Pomeranz et al. Sep 1994 A
5366443 Eggers et al. Nov 1994 A
5368591 Lennox et al. Nov 1994 A
5370644 Langberg Dec 1994 A
5370679 Atlee, III Dec 1994 A
5374287 Rubin Dec 1994 A
5383917 Desai et al. Jan 1995 A
5393207 Maher et al. Feb 1995 A
5394880 Atlee, III Mar 1995 A
5396887 Imran Mar 1995 A
5400778 Jonson et al. Mar 1995 A
5400783 Pomeranz et al. Mar 1995 A
5411025 Webster May 1995 A
5415166 Imran May 1995 A
5415656 Tihon et al. May 1995 A
5417687 Nardella et al. May 1995 A
5422362 Vincent et al. Jun 1995 A
5423744 Gencheff et al. Jun 1995 A
5423811 Imran et al. Jun 1995 A
5425023 Haraguchi et al. Jun 1995 A
5425703 Feiring Jun 1995 A
5425811 Mashita Jun 1995 A
5431696 Atlee, III Jul 1995 A
5433730 Alt Jul 1995 A
5437665 Munro Aug 1995 A
5443470 Stern et al. Aug 1995 A
5454782 Perkins Oct 1995 A
5456667 Ham et al. Oct 1995 A
5458596 Lax et al. Oct 1995 A
5465717 Imran et al. Nov 1995 A
5471982 Edwards et al. Dec 1995 A
5474530 Passafaro et al. Dec 1995 A
5478309 Sweezer et al. Dec 1995 A
5485841 Watkin et al. Jan 1996 A
5496271 Burton et al. Mar 1996 A
5496311 Abele et al. Mar 1996 A
5496312 Klicek Mar 1996 A
5500011 Desai Mar 1996 A
5505728 Ellman et al. Apr 1996 A
5505730 Edwards Apr 1996 A
5507791 Sit'ko Apr 1996 A
5509419 Edwards et al. Apr 1996 A
5522862 Testerman et al. Jun 1996 A
5531779 Dahl et al. Jul 1996 A
5540681 Strul et al. Jul 1996 A
5545161 Imran Aug 1996 A
5545193 Fleischman et al. Aug 1996 A
5547469 Rowland et al. Aug 1996 A
5549559 Eshel Aug 1996 A
5549655 Erickson Aug 1996 A
5549661 Kordis et al. Aug 1996 A
RE35330 Malone et al. Sep 1996 E
5558073 Pomeranz et al. Sep 1996 A
5562608 Sekins et al. Oct 1996 A
5570683 Zapol Nov 1996 A
5571074 Buckman et al. Nov 1996 A
5571088 Lennox et al. Nov 1996 A
5574059 Regunathan et al. Nov 1996 A
5578072 Barone et al. Nov 1996 A
5582609 Swanson et al. Dec 1996 A
5588432 Crowley Dec 1996 A
5588812 Taylor et al. Dec 1996 A
5595183 Swanson et al. Jan 1997 A
5598848 Swanson et al. Feb 1997 A
5599345 Edwards et al. Feb 1997 A
5601088 Swanson et al. Feb 1997 A
5605157 Panescu et al. Feb 1997 A
5607419 Amplatz et al. Mar 1997 A
5607462 Imran Mar 1997 A
5620438 Amplatz et al. Apr 1997 A
5623940 Daikuzono Apr 1997 A
5624439 Edwards et al. Apr 1997 A
5626618 Ward et al. May 1997 A
5630425 Panescu et al. May 1997 A
5630794 Lax et al. May 1997 A
5634471 Fairfax et al. Jun 1997 A
5641326 Adams Jun 1997 A
5647870 Kordis et al. Jul 1997 A
5660175 Dayal Aug 1997 A
5674483 Tu et al. Oct 1997 A
5678535 Dimarco Oct 1997 A
5680860 Imran Oct 1997 A
5681280 Rusk et al. Oct 1997 A
5681308 Edwards et al. Oct 1997 A
5687723 Avitall Nov 1997 A
5688267 Panescu et al. Nov 1997 A
5693078 Desai et al. Dec 1997 A
5694934 Edelman Dec 1997 A
5695471 Wampler Dec 1997 A
5699799 Xu et al. Dec 1997 A
5702386 Stern et al. Dec 1997 A
5707218 Maher et al. Jan 1998 A
5707336 Rubin Jan 1998 A
5707352 Sekins et al. Jan 1998 A
5722401 Pietroski et al. Mar 1998 A
5722403 McGee et al. Mar 1998 A
5722416 Swanson et al. Mar 1998 A
5725525 Kordis Mar 1998 A
5727569 Benetti et al. Mar 1998 A
5728094 Edwards Mar 1998 A
5730128 Pomeranz et al. Mar 1998 A
5730704 Avitall Mar 1998 A
5730726 Klingenstein Mar 1998 A
5730741 Horzewski et al. Mar 1998 A
5735846 Panescu et al. Apr 1998 A
5740808 Panescu et al. Apr 1998 A
5741248 Stern et al. Apr 1998 A
5752518 McGee et al. May 1998 A
5755714 Murphy-Chutorian May 1998 A
5755753 Knowlton May 1998 A
5759158 Swanson Jun 1998 A
5765568 Sweezer et al. Jun 1998 A
5769846 Edwards Jun 1998 A
5772590 Webster Jun 1998 A
5779669 Haissaguerre et al. Jul 1998 A
5779698 Clayman et al. Jul 1998 A
5782239 Webster Jul 1998 A
5782797 Schweich et al. Jul 1998 A
5782827 Gough et al. Jul 1998 A
5782848 Lennox Jul 1998 A
5782899 Imran Jul 1998 A
5792064 Panescu et al. Aug 1998 A
5795303 Swanson et al. Aug 1998 A
5800375 Sweezer et al. Sep 1998 A
5807306 Shapland et al. Sep 1998 A
5810757 Sweezer et al. Sep 1998 A
5810807 Ganz et al. Sep 1998 A
5817028 Anderson Oct 1998 A
5817073 Krespi Oct 1998 A
5820554 Davis et al. Oct 1998 A
5823189 Kordis Oct 1998 A
5827277 Edwards Oct 1998 A
5833651 Donovan et al. Nov 1998 A
5836905 Lemelson et al. Nov 1998 A
5836947 Fleischman et al. Nov 1998 A
5837001 Mackey Nov 1998 A
5843075 Taylor Dec 1998 A
5843077 Edwards Dec 1998 A
5846238 Jackson et al. Dec 1998 A
5848969 Panescu et al. Dec 1998 A
5848972 Triedman et al. Dec 1998 A
5849026 Zhou et al. Dec 1998 A
5855577 Murphy-Chutorian et al. Jan 1999 A
5860974 Abele Jan 1999 A
5863291 Schaer Jan 1999 A
5865791 Whayne et al. Feb 1999 A
5868740 Leveen et al. Feb 1999 A
5871443 Edwards et al. Feb 1999 A
5871523 Fleischman et al. Feb 1999 A
5873852 Vigil et al. Feb 1999 A
5873865 Horzewski et al. Feb 1999 A
5876340 Tu et al. Mar 1999 A
5876399 Chia et al. Mar 1999 A
5881727 Edwards Mar 1999 A
5882346 Pomeranz et al. Mar 1999 A
5891135 Jackson et al. Apr 1999 A
5891136 McGee et al. Apr 1999 A
5891138 Tu et al. Apr 1999 A
5893847 Kordis Apr 1999 A
5897554 Chia et al. Apr 1999 A
5899882 Waksman et al. May 1999 A
5904651 Swanson et al. May 1999 A
5904711 Flom et al. May 1999 A
5906636 Casscells, III et al. May 1999 A
5908445 Whayne et al. Jun 1999 A
5908446 Imran Jun 1999 A
5908839 Levitt et al. Jun 1999 A
5911218 Dimarco Jun 1999 A
5916235 Guglielmi Jun 1999 A
5919147 Jain Jul 1999 A
5919172 Golba Jul 1999 A
5924424 Stevens et al. Jul 1999 A
5928228 Kordis et al. Jul 1999 A
5931835 Mackey Aug 1999 A
5935079 Swanson et al. Aug 1999 A
5941869 Patterson et al. Aug 1999 A
5951494 Wang et al. Sep 1999 A
5951546 Lorentzen Sep 1999 A
5954661 Greenspon et al. Sep 1999 A
5954662 Swanson et al. Sep 1999 A
5954717 Behl et al. Sep 1999 A
5957961 Maguire et al. Sep 1999 A
5964753 Edwards Oct 1999 A
5964796 Imran Oct 1999 A
5971983 Lesh Oct 1999 A
5972026 Laufer et al. Oct 1999 A
5976175 Hirano et al. Nov 1999 A
5976709 Kageyama et al. Nov 1999 A
5979456 Magovern Nov 1999 A
5980563 Tu et al. Nov 1999 A
5984917 Fleischman et al. Nov 1999 A
5984971 Faccioli et al. Nov 1999 A
5991650 Swanson et al. Nov 1999 A
5992419 Sterzer et al. Nov 1999 A
5993462 Pomeranz et al. Nov 1999 A
5997534 Tu et al. Dec 1999 A
5999855 Dimarco Dec 1999 A
6001054 Regulla et al. Dec 1999 A
6003517 Sheffield et al. Dec 1999 A
6004269 Crowley et al. Dec 1999 A
6006755 Edwards Dec 1999 A
6008211 Robinson et al. Dec 1999 A
6009877 Edwards Jan 2000 A
6010500 Sherman et al. Jan 2000 A
6014579 Pomeranz et al. Jan 2000 A
6016437 Tu et al. Jan 2000 A
6023638 Swanson Feb 2000 A
6024740 Lesh et al. Feb 2000 A
6029091 De La Rama et al. Feb 2000 A
6033397 Laufer et al. Mar 2000 A
6036687 Laufer et al. Mar 2000 A
6036689 Tu et al. Mar 2000 A
6039731 Taylor et al. Mar 2000 A
6045549 Smethers et al. Apr 2000 A
6045550 Simpson et al. Apr 2000 A
6050992 Nichols Apr 2000 A
6053172 Hovda et al. Apr 2000 A
6053909 Shadduck Apr 2000 A
6056744 Edwards May 2000 A
6056769 Epstein et al. May 2000 A
6063078 Wittkampf May 2000 A
6071280 Edwards et al. Jun 2000 A
6071281 Burnside et al. Jun 2000 A
6071282 Fleischman Jun 2000 A
6083255 Laufer et al. Jul 2000 A
6090104 Webster Jul 2000 A
6092528 Edwards Jul 2000 A
6102886 Lundquist et al. Aug 2000 A
6106524 Eggers et al. Aug 2000 A
6123702 Swanson et al. Sep 2000 A
6123703 Tu et al. Sep 2000 A
6139527 Laufer et al. Oct 2000 A
6139571 Fuller et al. Oct 2000 A
6142993 Whayne et al. Nov 2000 A
6143013 Samson et al. Nov 2000 A
6149647 Tu et al. Nov 2000 A
6152143 Edwards Nov 2000 A
6152899 Farley et al. Nov 2000 A
6159194 Eggers et al. Dec 2000 A
6179833 Taylor Jan 2001 B1
6183468 Swanson et al. Feb 2001 B1
6198970 Freed et al. Mar 2001 B1
6200311 Danek et al. Mar 2001 B1
6200332 Del Giglio Mar 2001 B1
6200333 Laufer Mar 2001 B1
6210367 Carr Apr 2001 B1
6212433 Behl Apr 2001 B1
6214002 Fleischman et al. Apr 2001 B1
6216043 Swanson et al. Apr 2001 B1
6216044 Kordis Apr 2001 B1
6217576 Tu et al. Apr 2001 B1
6235024 Tu May 2001 B1
6241727 Tu et al. Jun 2001 B1
6245065 Panescu et al. Jun 2001 B1
6254598 Edwards et al. Jul 2001 B1
6258087 Edwards et al. Jul 2001 B1
6264653 Falwell Jul 2001 B1
6269813 Fitzgerald et al. Aug 2001 B1
6270476 Santoianni et al. Aug 2001 B1
6273907 Laufer Aug 2001 B1
6283988 Laufer et al. Sep 2001 B1
6283989 Laufer et al. Sep 2001 B1
6287290 Perkins et al. Sep 2001 B1
6287304 Eggers et al. Sep 2001 B1
6296639 Truckai et al. Oct 2001 B1
6299633 Laufer Oct 2001 B1
6322559 Daulton et al. Nov 2001 B1
6322584 Ingle et al. Nov 2001 B2
6327505 Medhkour et al. Dec 2001 B1
6338727 Noda et al. Jan 2002 B1
6338836 Kuth et al. Jan 2002 B1
6346104 Daly et al. Feb 2002 B2
6355031 Edwards et al. Mar 2002 B1
6379352 Reynolds et al. Apr 2002 B1
6409723 Edwards Jun 2002 B1
6411852 Danek et al. Jun 2002 B1
6416511 Lesh et al. Jul 2002 B1
6416740 Unger Jul 2002 B1
6423105 Iijima et al. Jul 2002 B1
6425895 Swanson et al. Jul 2002 B1
6433040 Dellamary et al. Aug 2002 B1
6440129 Simpson Aug 2002 B1
6442435 King et al. Aug 2002 B2
6458121 Rosenstock et al. Oct 2002 B1
6460545 Kordis Oct 2002 B2
6488673 Laufer et al. Dec 2002 B1
6488679 Swanson et al. Dec 2002 B1
6493589 Medhkour et al. Dec 2002 B1
6494880 Swanson et al. Dec 2002 B1
6496738 Carr Dec 2002 B2
6514246 Swanson et al. Feb 2003 B1
6526320 Mitchell Feb 2003 B2
6529756 Phan et al. Mar 2003 B1
6544226 Gaiser et al. Apr 2003 B1
6544262 Fleischman Apr 2003 B2
6547788 Maguire et al. Apr 2003 B1
6558378 Sherman et al. May 2003 B2
6572612 Stewart et al. Jun 2003 B2
6575623 Werneth Jun 2003 B2
6575969 Rittman, III et al. Jun 2003 B1
6582427 Goble et al. Jun 2003 B1
6582430 Hall Jun 2003 B2
6589235 Wong et al. Jul 2003 B2
6610043 Ingenito Aug 2003 B1
6610054 Edwards et al. Aug 2003 B1
6620159 Hegde Sep 2003 B2
6626903 McGuckin et al. Sep 2003 B2
6634363 Danek et al. Oct 2003 B1
6635056 Kadhiresan et al. Oct 2003 B2
6638273 Farley et al. Oct 2003 B1
6640120 Swanson et al. Oct 2003 B1
6645200 Koblish et al. Nov 2003 B1
6652548 Evans et al. Nov 2003 B2
6669693 Friedman Dec 2003 B2
6673068 Berube Jan 2004 B1
6692492 Simpson et al. Feb 2004 B2
6699243 West et al. Mar 2004 B2
6714822 King et al. Mar 2004 B2
6723091 Goble et al. Apr 2004 B2
6743197 Edwards Jun 2004 B1
6749604 Eggers et al. Jun 2004 B1
6749606 Keast et al. Jun 2004 B2
6767347 Sharkey et al. Jul 2004 B2
6770070 Balbierz Aug 2004 B1
6802843 Truckai et al. Oct 2004 B2
6805131 Kordis Oct 2004 B2
6837888 Ciarrocca et al. Jan 2005 B2
6840243 Deem et al. Jan 2005 B2
6849073 Hoey et al. Feb 2005 B2
6852091 Edwards et al. Feb 2005 B2
6852110 Roy et al. Feb 2005 B2
6866662 Fuimaono et al. Mar 2005 B2
6881213 Ryan et al. Apr 2005 B2
6893436 Woodard et al. May 2005 B2
6893439 Fleischman May 2005 B2
6895267 Panescu et al. May 2005 B2
6904303 Phan et al. Jun 2005 B2
6917834 Koblish et al. Jul 2005 B2
6939346 Kannenberg et al. Sep 2005 B2
6954977 Maguire et al. Oct 2005 B2
7027869 Danek et al. Apr 2006 B2
7043307 Zelickson et al. May 2006 B1
7104987 Biggs et al. Sep 2006 B2
7104990 Jenkins et al. Sep 2006 B2
7118568 Hassett et al. Oct 2006 B2
7122033 Wood Oct 2006 B2
7131445 Amoah Nov 2006 B2
7186251 Malecki et al. Mar 2007 B2
7198635 Danek et al. Apr 2007 B2
7200445 Dalbec et al. Apr 2007 B1
7241295 Maguire Jul 2007 B2
7255693 Johnston et al. Aug 2007 B1
7264002 Danek et al. Sep 2007 B2
7266414 Cornelius et al. Sep 2007 B2
7273055 Danek et al. Sep 2007 B2
7425212 Danek et al. Sep 2008 B1
7542802 Biggs et al. Jun 2009 B2
7556624 Laufer et al. Jul 2009 B2
7740017 Danek et al. Jun 2010 B2
7921855 Danek et al. Apr 2011 B2
8161978 Danek et al. Apr 2012 B2
8584681 Danek et al. Nov 2013 B2
8640711 Danek et al. Feb 2014 B2
9027564 Danek et al. May 2015 B2
20010031985 Gilboa et al. Oct 2001 A1
20030050631 Mody et al. Mar 2003 A1
20030051733 Kotmel et al. Mar 2003 A1
20030055331 Kotmel et al. Mar 2003 A1
20030065371 Satake Apr 2003 A1
20030069570 Witzel et al. Apr 2003 A1
20030187430 Vorisek Oct 2003 A1
20030236455 Swanson et al. Dec 2003 A1
20040153056 Muller et al. Aug 2004 A1
20040249401 Rabiner et al. Dec 2004 A1
20050010270 Laufer Jan 2005 A1
20050096644 Hall et al. May 2005 A1
20050171396 Pankratov et al. Aug 2005 A1
20050193279 Daners Sep 2005 A1
20050203503 Edwards et al. Sep 2005 A1
20050240176 Oral et al. Oct 2005 A1
20050251128 Amoah Nov 2005 A1
20060062808 Laufer et al. Mar 2006 A1
20060079887 Buysse et al. Apr 2006 A1
20060089637 Werneth et al. Apr 2006 A1
20060135953 Kania et al. Jun 2006 A1
20060137698 Danek et al. Jun 2006 A1
20060247617 Danek et al. Nov 2006 A1
20060247618 Kaplan et al. Nov 2006 A1
20060247619 Kaplan et al. Nov 2006 A1
20060247726 Biggs et al. Nov 2006 A1
20060247727 Biggs et al. Nov 2006 A1
20060247746 Danek et al. Nov 2006 A1
20060278243 Danek et al. Dec 2006 A1
20060278244 Danek et al. Dec 2006 A1
20060282071 Utley et al. Dec 2006 A1
20070074719 Danek et al. Apr 2007 A1
20070083194 Kunis et al. Apr 2007 A1
20070083197 Danek et al. Apr 2007 A1
20070100390 Danaek et al. May 2007 A1
20070102011 Danek et al. May 2007 A1
20070106292 Kaplan et al. May 2007 A1
20070106296 Laufer et al. May 2007 A1
20070106348 Laufer May 2007 A1
20070118184 Danek et al. May 2007 A1
20070118190 Danek et al. May 2007 A1
20070123958 Laufer May 2007 A1
20070123961 Danek et al. May 2007 A1
20070129720 Demarais et al. Jun 2007 A1
20080004596 Yun et al. Jan 2008 A1
20080097424 Wizeman et al. Apr 2008 A1
20080255642 Zarins et al. Oct 2008 A1
20090018538 Webster et al. Jan 2009 A1
20090030477 Jarrard Jan 2009 A1
20090043301 Jarrard et al. Feb 2009 A1
20090069797 Danek et al. Mar 2009 A1
20090112203 Danek et al. Apr 2009 A1
20090143705 Danek et al. Jun 2009 A1
20090143776 Danek et al. Jun 2009 A1
20090192505 Askew et al. Jul 2009 A1
20090192508 Laufer et al. Jul 2009 A1
20090306644 Mayse et al. Dec 2009 A1
20130035747 Danek et al. Feb 2013 A1
Foreign Referenced Citations (48)
Number Date Country
19529634 Feb 1997 DE
189329 Jun 1987 EP
280225 Mar 1989 EP
286145 Oct 1990 EP
282225 Jun 1992 EP
908713 Apr 1999 EP
908150 May 2003 EP
768091 Jul 2003 EP
1297795 Aug 2005 EP
2659240 Jul 1997 FR
2233293 Jan 1991 GB
59167707 Sep 1984 JP
7289557 Nov 1995 JP
9047518 Feb 1997 JP
9243837 Sep 1997 JP
10026709 Jan 1998 JP
2053814 Feb 1996 RU
2091054 Sep 1997 RU
545358 Feb 1977 SU
WO-1989011311 Nov 1989 WO
WO-9502370 Mar 1995 WO
WO-1995010322 Apr 1995 WO
WO-1996004860 Feb 1996 WO
WO-1996010961 Apr 1996 WO
WO-1997032532 Sep 1997 WO
WO-1997033715 Sep 1997 WO
WO-1997037715 Oct 1997 WO
WO-9740751 Nov 1997 WO
WO 9844854 Oct 1998 WO
WO-1998044854 Oct 1998 WO
WO-1998052480 Nov 1998 WO
WO-9856234 Dec 1998 WO
WO-1998056324 Dec 1998 WO
WO-1999003413 Jan 1999 WO
WO-1998058681 Mar 1999 WO
WO-1999013779 Mar 1999 WO
WO-9932040 Jul 1999 WO
WO-1999034741 Jul 1999 WO
WO-1999044506 Sep 1999 WO
WO-1999045855 Sep 1999 WO
WO-9964109 Dec 1999 WO
WO-2000051510 Sep 2000 WO
WO-0062699 Oct 2000 WO
WO-2001003642 Jan 2001 WO
WO-0232333 Apr 2002 WO
WO-0232334 Apr 2002 WO
WO-2009082433 Jul 2009 WO
WO-2009137819 Nov 2009 WO
Non-Patent Literature Citations (73)
Entry
Mitchell et al. “Video-imaging of lumen narrowing; muscle shortening and flow responsiveness in isolated bronchial segments of the pig.” Eur Respir J. Jul. 1994;7(7):1317-25.
Templeton et al. “Effects of S-salbutamol on Human Isolated Bronchus”. 11(1): 1-6. Pulmonary Pharmacology & Therapeutics Feb. 1998; 11(1): 1-6.
An S.S., et al., “Airway Smooth Muscle Dynamics: A Common Pathway of Airway Obstruction in Asthma,” European Respiratory Journal, 2007, 29 (5), 834-860.
Bel E.H., ““Hot stuff”: Bronchial Thermoplasty for Asthma,” American Journal of Respiratory and Critical Care Medicine, 2006, 173 (9), 941-943.
Brown R.H., et al., “Effect of Bronchial Thermoplasty on Airway Distensibility,” European Respiratory Journal, 2005, 26 (2), 277-282.
Brown R.H., et al., “In Vivo evaluation of the Effectiveness of Bronchial Thermoplasty with Computed Tomography,” Journal of Applied Physiology, 2005, 98 (5), 1603-1606.
Chhajed P.N., et al., “Will there be a Role for Bronchoscopic Radiofrequency Ablation”, Journal of Bronchology, 2005, 12 (3), 184-186.
Co-pending U.S. Appl. No. 09/095323, filed Jun. 10, 1998.
Co-pending U.S. Appl. No. 09/244173, filed Feb. 4, 1999.
Co-pending U.S. Appl. No. 12/640644, filed Dec. 17, 2009.
Co-pending U.S. Appl. No. 12/727156, filed Mar. 18, 2010.
Co-pending U.S. Appl. No. 12/765704, filed Apr. 22, 2010.
Cox G., et al., “Asthma Control during the Year after Bronchial Thermoplasty,” New England journal of medicine, 2007, 356 (13), 1327-1337.
Cox G., et al., “Asthma Intervention Research (AIR) Trial Evaluating Bronchial Thermoplasty: Early Results,” American Thoracic Society Annual Meeting, 2002, 1 page.
Cox G., et al., “Bronchial Thermoplasty for Asthma,” American Journal of Respiratory and Critical Care Medicine, 2006, 173 (9), 965-969.
Cox G., et al., “Bronchial Thermoplasty: Long-Term Follow-Up and Patient Satisfaction,” Chest, 2004, 126 (4), 822s.
Cox G., et al., “Bronchial Thermoplasty: One-Year Update, American Thoracic Society Annual Meeting,” American Journal of Respiratory and Critical Care Medicine, 2004, 169, A313.
Cox G., et al., “Clinical Experience with Bronchial Thermoplasty for the Treatment of Asthma,” Chest, 2003, 124, 106S.
Cox G., et al., “Development of a Novel Bronchoscopic Therapy for Asthma,” Journal of Allergy and Clinical Immunology, 2003, 113 (2), S33.
Cox G., et al., “Early Clinical Experience with Bronchial Thermoplasty for the Treatment of Asthma,” American Thoracic Society Annual Meeting, 2002, 1068.
Cox G., et al., “Impact of Bronchial Thermoplasty on Asthma Status: Interim Results from the AIR Trial,” 2006, 1 page.
Cox G., et al., “Radiofrequency Ablation of Airway Smooth Muscle for Sustained Treatment of Asthma: Preliminary Investigations,” European Respiratory Journal, 2004, 24 (4), 659-663.
Danek C.J., et al., “Bronchial Thermoplasty Reduces Canine Airway Responsiveness to Local Methacholine Challenge,” American Thoracic Society Annual Meeting, 2002, 1 page.
Danek C.J., et al., “Reduction in Airway Hyperresponsiveness to Methacholine by the Application of RF Energy in Dogs,” Journal of Applied Physiology, 2004, 97 (5), 1946-1953.
Dierkesmann R., “Indication and Results of Endobronchial Laser Therapy,” Lung, 1990, 168, 1095-1102.
Fazio F., et al., “Assessment of Regional Ventilation by Continuous Inhalation of Radioactive Krypton-81m,” British Medical Journal, 1975, vol. 3 (5985), pp. 673-676.
Global Strategy for Asthma Management and Prevention, National Institute of Health, National Heart, Lung and Blood Institute, 2002, 192 pages.
Hogg J. C., “The Pathology of Asthma,” APMIS, 1997, 105 (10), 735-745.
International Search Report for Application No. PCT/US00/05412, dated Jun. 20, 2000, 2 pages.
International Search Report for Application No. PCT/US00/18197, dated Oct. 3, 2000, 1 page.
International Search Report for Application No. PCT/US00/28745, dated Mar. 28, 2001, 6 pages.
International Search Report for Application No. PCT/US01/32321, dated Jan. 18, 2002, 2 pages.
International Search Report for Application No. PCT/US98/03759, dated Jul. 30, 1998, 1 page.
International Search Report for Application No. PCT/US98/26227, dated Mar. 25, 1999, 1 page.
International Search Report for Application No. PCT/US99/00232, dated Mar. 4, 1999, 1 page.
International Search Report for Application No. PCT/US99/12986, dated Sep. 29, 1999, 1 page.
Ivanyuta O.M., et al., “Effect of Low-Power Laser Irradiation of Bronchial Mucosa on the State of Systemic and Local Immunity in Patients with Chronic Bronchitis,” Problemy Tuberkuleza, 1991, 6, 26-29.
James A.L., et al., “The Mechanics of Airway Narrowing in Asthma,” American Review of Respiratory Diseases, 1989, 139 (1), 242-246.
Janssen L.J., “Asthma Therapy: How Far have We Come, Why did We Fail and Where should We Go Next”, European Respiratory Journal, 2009, 33 (1), 11-20.
Jeffery P.K, “Remodeling in Asthma and Chronic Obstructive Lung Disease,” American Journal of Respiratory and Critical Care Medicine, 2001, 164 (10), S28-S38.
Johnson S. R., et al., “Synthetic Functions of Airway Smooth Muscle in Asthma,” Trends Pharmacol. Sci., 1997, 18 (8), 288-292.
Kitamura S., “Color Atlas of Clinical Application of Fiberoptic Bronchoscopy,” 1990, Year Book Medical Publishers, 2 pages.
Kraft M., “The Distal Airways: Are they Important in Asthma”, European Respiratory Journal, 1999, 14 (6), 1403-1417.
Laviolette M., et al., “Asthma Intervention Research (Air) Trial: Early Safety Assessment of Bronchial Thermoplasty,” American Journal of Respiratory and Critical Care Medicine, 2004, 169, A314.
Leff A., et al., “Bronchial Thermoplasty Alters Airway Smooth Muscle and Reduces Responsiveness in Dogs: A Possible Procedure for the Treatment of Asthma,” American Thoracic Society Annual Meeting, 2002, 1 page.
Lim E.C., et al., “Botulinum Toxin: A Novel Therapeutic Option for Bronchial Asthma”, Medical Hypotheses, 2006, 66 (5), 915-919.
Lombard C.M., et al., “Histologic Effects of Bronchial Thermoplasty of Canine and Human Airways,” American Thoracic Society Annual Meeting, 2002, 1 page.
Macklem P. T., “Mechanical Factors Determining Maximum Bronchoconstriction,” European Respiratory Journal, 1989, 6, 516s-519s.
Mayse M.L., et al., “Clinical Pearls for Bronchial Thermoplasty,” Journal of Bronchology, 2007, 14 (2), 115-123.
Miller J.D., et al., “A Prospective Feasibility Study of Bronchial Thermoplasty in the Human Airway,” Chest, 2005, 127 (6), 1999-2006.
Miller J.D., et al., “Bronchial Thermoplasty is Well Tolerated by Non-Asthmatic Patients Requiring Lobectomy,” American Thoracic Society Annual Meeting, 2002, 1 page.
Mitzner W., “Airway Smooth Muscle the Appendix of the Lung,” American Journal of Respiratory and Critical Care Medicine, 2004, 169 (7), 787-790.
Mitzner W., “Bronchial Thermoplasty in Asthma,” Allergology International, 2006, 55 (3), 225-234.
Netter F.H., “Respiratory System: A Compilation of Paintings Depicting Anatomy and Embryology, Physiology, Pathology, Pathophysiology, and Clinical Features and Treatment of Diseases,In the CIBA Collection of Medical Illustrations M.B. Divertie, ed., Summit: New Jerse,” 1979, 7, 119-135.
Non-Final Office Action for U.S. Appl. No. 11/361,564, dated Apr. 29, 2010. 12 pages.
Non-Final Office Action for U.S. Appl. No. 11/361,564, dated Jan. 22, 2009. 8 pages.
Notice of final Rejection, Japanese Patent Application No. 2000-553172, dated Sep. 2, 2008, 5 pages.
Pitris C., et al., “High Resolution Imaging of the Upper Respiratory Tract with Optical Coherence Tomography: A Feasibility Study,” American Journal of Respiratory and Critical Care Medicine, 1998, vol. 157 (5 Pt 1), pp. 1640-1644.
Provotorov V.M., et al., “The Clinical Efficacy of Treating Patients with Nonspecific Lung Diseases Using Low-energy Laser Irradiation and Intrapulmonary Drug Administration,” Terapevticheskii Arkhiv, 1991, 62 (12), 18-23.
Rubin A., et al., “Bronchial Thermoplasty Improves Asthma Status of Moderate to Severe Perisstent Asthmatics Over and Above Current Standard-of-Care,” American College of Chest Physicians, 2006, 2 pages.
Seow C.Y., et al., “Historical Perspective on Airway Smooth Muscle: The Saga of a Frustrated Cell,” Journal of Applied Physiology, 2001, 91 (2), 938-952.
Shesterina M.V., et al., “Effect of Laser Therapy on Immunity in Patients with Bronchial Asthma and Pulmonary Tuberculosis,” Problemy Tuberkuleza, 1994, 5, 23-26.
Shore S.A., “Airway Smooth Muscle in Asthma—Not Just More of the Same,” New England Journal of Medicine, 2004, 351 (6), 531-532.
Solway J., et al., “Airway Smooth Muscle as a Target for Asthma Therapy,” New England Journal of medicine, 2007, 356 (13), 1367-1369.
Sterk P.J., et al., “Heterogeneity of Airway Hyperresponsiveness: Time for Unconventional, But Traditional, Studies,” Journal of Applied Physiology, 2004, 96 (6), 2017-2018.
Toma T.P., et al., “Brave New World for Interventional Bronchoscopy,” Thorax, 2005, 60 (3), 180-181.
Trow T.K., “Clinical Year in Review I: Diagnostic Imaging, Asthma, Lung Transplantation, and Interventional Pulmonology,” Proceedings of the American Thoracic Society, 2006, 3 (7), 553-556.
UNSW Embryo—Respiratory System [online], Embryology, 2007, [retrieved on Dec. 10, 2007]. Retrieved from the internet: (URL:http://embryology.med.unsw.edu.au/Refer/respire/sclect.htm).
Vasilotta P.L., et al., “I-R Laser: A New Therapy in Rhino-Sino-Nasal Bronchial Syndrome with Asthmatic Component,” American Society for Laser Medicine and Surgery Abstracts, 74. 1993.
Vorotnev A.I., et al., “The Treatment of Patients with Chronic Obstructive Bronchitis by Using a Low-power Laser at a General Rehabilitation Center,” Terapevticheskii Arkhiv, 1997, 69 (3), 17-19.
Wiggs B.R., et al., “On the Mechanism of Mucosal Folding in Normal and Asthmatic Airways,” Journal of Applied Physiology, 1997, 83 (6), 1814-1821.
Wilson S.R., et al., “Global Assessment after Bronchial Thermoplasty: The Patients Perspective,” Journal of Outcomes Research, 2006, 10, 37-46.
Wizeman W., et al., “A Computer Model of Thermal Treatment of Airways by Radiofrequency (RF) Energy Delivery,” American Thoracic Society Annual Meeting, 2007, 1 page.
Related Publications (1)
Number Date Country
20140148635 A1 May 2014 US
Continuations (3)
Number Date Country
Parent 13557518 Jul 2012 US
Child 14171973 US
Parent 11398353 Apr 2006 US
Child 13557518 US
Parent 09535856 Mar 2000 US
Child 10640967 US
Continuation in Parts (1)
Number Date Country
Parent 10640967 Aug 2003 US
Child 11398353 US