Systems, assemblies, and methods for treating a bronchial tree

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DESCRIPTION

Systems for treating a bronchial tree.

Cross references with related requests

This application claims the benefit under 35 USC § 119 (E) of US Provisional Patent Application No. 61 / 052,082 filed May 9, 2008; US Provisional Patent Application No. 61 / 106,490 filed October 17, 2008; and US Provisional Patent Application No. 61 / 155,449 filed February 25, 2009.

Background

Technical scope

The present invention relates generally to systems for treating a bronchial tree, and more particularly the invention relates to systems for obtaining a desired response.

Description of Related Art

Lung diseases can cause a wide variety of problems that negatively affect the performance of the lungs. Lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD), can lead to increased resistance to airflow in the lungs. Mortality, health-related costs, and population size negatively affected by lung disease are substantial. These diseases often negatively affect the quality of life. Symptoms are varied but often include coughing; difficulty breathing; and wheeze. In COPD, for example, shortness of breath can be noticed when doing somewhat strenuous activities, such as running, jogging, brisk walking, etc. As the disease progresses, shortness of breath may be noticeable with non-strenuous activities, such as walking. Over time, the symptoms of COPD can occur with less and less effort until it is present at all times, thereby severely limiting a person's ability to perform normal tasks.

Pulmonary diseases are often characterized by airway obstruction associated with blockage of an internal airway passage, thickening of an airway wall, alteration of structures within or around the airway wall, or combinations of the same. Airway obstruction can significantly decrease the amount of gases exchanged in the lungs, resulting in difficulty breathing. Blockage of an internal airway passage can be caused by excessive intraluminal mucus or edema fluid, or both. Airway wall thickening may be attributable to excessive airway smooth muscle contraction, airway smooth muscle hypertrophy, mucosal gland hypertrophy, inflammation, edema, or combinations thereof. Alteration of structures around the airways, such as destruction of the lung tissue itself, can lead to a loss of radial traction on the airway wall and subsequent narrowing of the airway.

Asthma can be characterized by airway smooth muscle contraction, smooth muscle hypertrophy, excessive mucus production, mucosal gland hypertrophy, and / or airway inflammation and swelling. These abnormalities are the result of a complex interaction of local inflammatory cytokines (chemicals released locally by immune cells located on or near the airway wall), inhaled irritants (for example, cold air, smoke, allergens, or other chemicals ), systemic hormones (chemicals in the blood such as anti-inflammatory cortisol and stimulant epinephrine), local input from the nervous system (neurons completely contained within the airway wall that can produce a local reflex stimulus of smooth muscle cells and mucosa glands), and input from the central nervous system (signals from the nervous system from the brain to smooth muscle cells and mucous glands transported through the vagus nerve). These conditions often cause temporary widespread tissue disturbances and initially reversible airflow obstruction that can ultimately lead to permanent tissue disruption and permanent airflow obstruction that makes it difficult for asthma sufferers to breathe. Asthma may further include episodes or acute attacks of further narrowing of the airways through contraction of the hyper-sensitive smooth muscle of the airways that significantly increases resistance to airflow. Symptoms of asthma include recurrent episodes of shortness of breath (for example, shortness of breath or dyspnea), wheezing, chest tightness, and coughing.

Emphysema is a type of COPD often characterized by disruption of the lung tissue that surrounds or is adjacent to the airways in the lungs. Emphysema can involve destruction of lung tissue (eg, alveolar tissue such as alveoli) leading to reduced gas exchange and reduced radial traction applied to the airway wall by the surrounding lung tissue. Destruction of alveolar tissue leaves emphysema lung areas with excessively large air spaces that are devoid of alveolar capillary and alveolar walls and thus ineffective in gas exchange. Air becomes trapped in these larger air spaces. This trapped air can cause hyperinflation of the lung, and in the limits of the chest it restricts the influx of oxygen-rich air and the

ES 2 398 052 T3 proper functioning of healthier tissue. This results in significant shortness of breath and can lead to low oxygen levels and high carbon dioxide levels in the blood. This type of destruction of lung tissue occurs as part of the normal aging process, even in healthy individuals. Unfortunately, exposure to chemicals or other substances (for example, tobacco smoke) can significantly accelerate the rate of tissue damage or destruction. Difficulty breathing can be further increased by airway obstruction. Reduced radial traction can cause the airway walls to become flexible such that the airway walls partially or completely collapse during exhalation. An individual with emphysema may be unable to deliver air out of their lungs due to this flattening of the airways and airway obstructions during exhalation.

Chronic bronchitis is a type of COPD that can be characterized by contraction of the smooth muscle of the airways, hypertrophy of smooth muscle, excessive mucus production, hypertrophy of the mucous gland, and inflammation of the airway walls. Like asthma, these abnormalities are the result of a complex interaction of local inflammatory cytokines, inhaled irritants, systemic hormones, the local nervous system, and the central nervous system. Unlike asthma in which respiratory obstruction can be largely reversible, airway obstruction in chronic bronchitis is primarily chronic and permanent. It is often difficult for a sufferer of chronic bronchitis to breathe due to chronic symptoms of shortness of breath, wheezing, and tightness in the chest, as well as a cough with mucus production.

Different techniques can be used to assess the severity and progression of lung diseases. For example, tests of lung function, exercise capacity, and quality of life questionnaires are often used to assess subjects. Lung function tests involve objective and reproducible measurements of basic, physiological, and pulmonary parameters, such as total airflow, lung volume, and gas exchange. Lung function test indices used to assess obstructive pulmonary disease include forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), ratio of FEV1 to FVC, total lung capacity (TLC) , airway resistance and arterial blood gas tests. FEV1 is the volume of air that a patient can exhale during the first second of a strong exhalation that begins with the lungs completely filled with air. FEV1 is also the average flow that occurs during the first second of a strong exhalation. This parameter can be used to assess and determine the presence and impact of any airway obstruction. The FVC is the total volume of air that a patient can exhale during a strong exhalation that begins with the lungs completely filled with air. The FEV1 / FVC is the fraction during the first second of all the air that can be exhaled during a strong exhalation. A FEV1 / FVC ratio of less than 0.7 after administration of at least one bronchodilator defines the presence of COPD. TLC is the total amount of air inside the lungs when the lungs are completely full and can increase when air is trapped inside the lungs of patients with obstructive lung disease. Resistance in the airways is defined as the pressure gradient between the alveoli and the mouth with the air flow regime between the alveoli and the mouth, similarly, the resistance of a given airway would be defined as the ratio of the gradient of pressure across the airway given with flow through the airway. Arterial blood gas tests measure the amount of oxygen and the amount of carbon dioxide in the blood and the most direct method is to assess the ability of the lungs and respiratory system to carry oxygen from the air into the blood and remove dioxide. carbon from the blood outside the body.

Exercise capacity tests are objective and reproducible measures of a patient's ability to perform activities. A six-minute walk test (6MWT) is an exercise capacity test in which a patient walks as far as possible on a flat surface in 6 minutes. Another test of exercise capacity involves measuring a patient's maximum exercise capacity. For example, a physician can measure the amount of power the patient can produce while on a cycle ergometer. The patient can breathe 30 percent oxygen and the workload can increase by 5 to 10 watts every 3 minutes.

Quality of life questionnaires assess the general health and well-being of a patient. The St. George's Breathing Questionnaire is a quality of life questionnaire that includes 75 questions designed to measure the impact of obstructive lung disease on general health, daily life, and perceived well-being. The efficacy of a treatment for lung diseases can be assessed using lung function tests, exercise capacity tests, and / or questionnaires. A treatment program can be modified based on the results of these tests and / or questionnaires.

Treatments, such as bronchial thermoplasty, involve destruction of smooth muscle tone by ablating the airway wall in a multitude of bronchial branches within the lung, thereby removing both smooth muscles and nerves in the walls. airway of the lung. Treated airways cannot respond favorably to inhaled irritants, systemic hormones, and inputs from the local and central nervous systems. Unfortunately, this destruction of nerve and smooth muscle tone in the airway wall can therefore adversely affect the performance of the lungs. For example, inhaled irritants, such as smoke or other noxious substances, normally stimulate lung irritant receptors to produce a cough and contract the smooth muscle of the airways. The elimination of nerves in the walls of the airways simultaneously removes the function

ES 2 398 052 T3 local nerve and central nervous input, thereby eliminating the lung's ability to expel harmful substances with a strong cough. Removal of airway smooth muscle tone can eliminate the airway's ability to contract, thereby allowing deeper penetration of unwanted substances, such as noxious substances, into the lung.

Additionally, methods for destroying smooth muscle tone by ablating pieces of the airway wall, such as bronchial thermoplasty, often have the following limitations: 1) inability to affect airways that are not ablated directly, typically airways less than about 3.0 mm that can also be narrowed in obstructive pulmonary diseases such as asthma, emphysema, and chronic bronchitis; 2) short-term swelling causing acute respiratory problems due to swelling during the operation in airways already narrowed by the effects of obstructive lung disease; 3) it may take hundreds of applications to the airways within the lungs to alter lung function as a whole; 4) since multiple generations of airways are treated within the lung (typically generations 2-8), it can be problematic to target pulmonary airways without omitting or overtreating specific sections of the pulmonary airways; and, 5) it may be necessary to separate the treatment stage into phases to reduce the healing burden on the lung, adding additional risks and costs with each additional bronchoscopy treatment session.

Asthma and COPD are serious diseases with a growing number of victims. Current management techniques, which include prescribed drugs, are not completely successful - they are free of side effects. Additionally, many patients do not adhere to the prescription drug dosage regimen. Accordingly, it would be desirable to provide a treatment that improves resistance to air flow without the need for patient compliance.

An apparatus having the constructive features of the first part of claim 1 is known from document US-B1-6 488 673. Document US-A-4658 836 relates to an applicator for electromagnetic radiation therapy. The system also comprises a cooling fluid supply and reservoir that are connected to a flexible cooling fluid portion of the applicator. The cooling means and the cooling portion of the applicator cooperate to cool the surface and near-surface layers of the area of ​​the body that is heated by irradiation, thereby allowing heating without excessive surface heating.

Compendium of the invention

The present invention is defined in independent claim 1. Preferred embodiments are specified by the dependent claim, the following description only serves to illustrate the present invention.

A treatment system can be directed through the airways, such as the main bronchi to the right and left of the lung root as well as the more distal airways within the lungs, to treat a wide variety of symptoms, conditions, and / or or lung diseases, including, without limitation, asthma, COPD and obstructive lung diseases, or other diseases that lead to increased resistance to airflow in the lungs. The treatment system can treat one or more target sites without treating non-target sites. Even if target anatomical features (eg, nerves, glands, membranes, and the like) of the main bronchi, lobar bronchi, segmental bronchi, or subsegmental bronchi are addressed, the non-target anatomical features may remain substantially unchanged. For example, the treatment system can destroy nerve tissue at target sites without destroying any significant expanses of non-target tissue that may remain functional after treatment is performed.

At least some embodiments described herein can be used to affect nerve tissue in nerve trunks outside the airway walls while maintaining the airway's ability to move (eg, contract and / or expand. ) in response to, for example, inhaled irritants, local nerve stimulation, systemic hormones, or combinations thereof. In some embodiments, the nerve tissue in the nerve trunks is destroyed without removing smooth muscle tone. After damaging the nerve trunks, the airways have at least some muscle tone such that the smooth muscles in the airways, if stimulated, can alter the diameter of the airways to help maintain lung function. appropriate. A wide variety of different physiological functions associated with smooth muscle tone can be maintained before, during and / or after treatment.

A method for treating one or more lung diseases is also described. The method includes damage to the nervous tissue of a vagus nerve trunk extending along the exterior of a bronchial tree airway to attenuate nervous system signals transmitted to a part of the bronchial tree. The nerve stem can be the main stem of a nerve, comprising a bundle of nerve fibers held together by a hard sheath of connective tissue. In some embodiments, nerve tissue is damaged while maintaining functionality of one or more anatomical features, such as blood vessels, which also extend.

ES 2 398 052 T3 next to the airways to preserve a respiratory function of the part of the bronchial tree after nerve tissue is damaged.

Conditions and symptoms associated with lung diseases can be reduced, limited, or substantially eliminated. For example, airway obstruction can be treated to obtain a reduction in resistance to air flow. Blood vessels or other tissue can remain intact and functional during and / or after treatment. Respiratory function that is preserved can include gas exchange, ciliary mucus transport, and the like. In some embodiments, nerve tissue, such as nerve tissue in nerve trunks located outside the airways, is damaged without damaging any significant extending part of the airway wall that is circumferentially adjacent to damaged nerve tissue. Consequently, the non-target tissue can be left substantially unaltered by damage to the nervous tissue of the airways.

Damaging nerve tissue may involve the delivery of energy to nerve tissue in such a way that the destroyed nerve tissue prevents or stops the transmission of signals from the nervous system to more distal nerves along the bronchial tree. Nervous tissue can be temporarily or permanently damaged by delivering different types of energy to nervous tissue. For example, nervous tissue can be thermally damaged by increasing a nervous tissue temperature to a first temperature (eg, an ablation temperature) while the airway wall is at a second temperature that is lower than the first temperature. A part of the airway wall located radially inward from the nervous tissue may be at the first temperature to avoid permanent damage to the part of the airway wall. The first temperature can be high enough to cause permanent destruction of nerve tissue. Nervous tissue is part of a nerve trunk located in the connective tissue outside the airway wall. Nerve tissue and smooth muscle in the airway wall can remain functional to maintain a desired level of smooth muscle tone. The airways can contract / dilate in response to stimulation (eg, stimulation caused by inhaled irritants, the local nervous system, or systemic hormones). Nerve tissue can be part of a nerve branch or nerve fibers in the wall of the airways. The nerve tissue of the nerve trunk and the nerve tissue of nerve branches / fibers can be damaged simultaneously or sequentially. Various types of elements that can be activated, such as ablation elements, can be used to deliver the energy.

The method of treating a subject comprises moving an elongated assembly along an internal passageway of an airway of a bronchial tree. The airways include a first tubular section, a second tubular section, a treatment site between the first tubular section and the second tubular section, and a rib extending along at least the first tubular section, the site of treatment and the second tubular section. The nerve can be inside or outside the airway wall. The nerve may be a nerve trunk outside the airway wall and connected to a vagus nerve.

The method may further include damaging a portion of the nerve at the treatment site to substantially prevent signals from traveling between the first tubular section and the second tubular section through the nerve. In some embodiments, blood flow can be maintained between the first tubular section and the second tubular section while damaging a portion of the nerve. Continuous blood flow can maintain the desired functionality of the distal lung tissue.

The second tubular section of the airway can dilate in response to nerve damage. As signals from the nervous system are not delivered to the smooth muscle in the airways of the second tubular section, the smooth muscle can relax to cause dilation of the airways, thereby reducing resistance to air flow, including resistance. to airflow associated with lung disease. In some embodiments, nerve tissue can be damaged to cause dilation of substantially all airways distal to the damaged tissue. The nerve can be a nerve trunk, nerve branch, nerve fibers, and / or other accessible nerves.

The method may further include detecting one or more attributes of an airway and assessing whether nerve tissue is damaged based on the attributes. Assessment includes comparing measured airway attributes (for example, comparing measurements taken at different times), comparing measured attributes and stored values ​​(for example, reference values), calculating values ​​based on measured attributes, monitoring attribute changes, combinations of the same or something similar.

The method of treating a subject may include moving an intraluminal device along an internal passageway of an airway of a bronchial tree. A part of the airway is denervated using the intraluminal device. In some embodiments, the portion of the airway is denervated without irreversibly damaging any significant extension of an interior surface of the airway. In some embodiments, a part of a bronchial tree is denervated without irreversibly damaging any significant stretches of nerve tissue (eg, nerve fiber tissue) within the airway walls of the bronchial tree. The inner surface can define the internal passage along which the intraluminal device was moved.

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The denervation process can be performed without destroying at least one artery that runs along the airways. In some embodiments, substantially all of the arteries that extend along the airways are preserved during the denervation process. In some embodiments, one or more nerves embedded in the airway wall can generally be left undamaged during the denervation process. The destroyed nerves can be nerve trunks outside the airways.

The denervation process can decrease airway smooth muscle tone to achieve a desired increase in airflow in and out of the lung. In some embodiments, the denervation process causes a sufficient decrease in smooth muscle tone to substantially increase airflow in and out of the lung. For example, the subject may have an increase in FEV1 of at least 10% over a baseline FEV1. As such, the subject may experience a significant improvement in lung function when engaging in normal daily activities, including strenuous activities. In some embodiments, the decrease in airway smooth muscle tone is sufficient to cause an increase in FEV1 in the range of about 10% to about 30%. Any number of treatment sites can be treated in either the main bronchi, segmental bronchi, or subsegmental bronchi to achieve the desired increase in lung function.

The elongated assembly for treating a lung is adapted to damage nervous tissue of a nerve trunk to attenuate signals from the nervous system transmitted to a more distal part of the bronchial tree. The tissue can be damaged while the elongated assembly extends along an internal passage of the bronchial tree. A delivery set can be used to provide access to nerve tissue.

The system for treating a subject includes an elongated assembly dimensioned to move along an internal passageway of an airway of a bronchial tree. The elongate assembly is adapted to attenuate signals transmitted by nerve tissue, such as nerve tissue from nerve trunks, while not irreversibly damaging any significant extension of an interior surface of the airway. The elongated assembly may include a recessed distal end having at least one operable element, such as an ablation element. The ablation element can ablate various types of nerve tissue when activated. In some embodiments, the ablation element includes one or more electrodes that can function to deliver radio frequency energy.

The method comprises damaging the nervous tissue of a first main bronchus to substantially prevent signals from the nervous system from traveling to substantially all of the distal bronchial branches connected to the first main bronchus. In some embodiments, most or all of the bronchial branches distal to the first main bronchus are treated. The nervous tissue, in certain embodiments, is located between a trachea and a lung through which the bronchial branches extend. The method further includes damaging the nervous tissue of a second main bronchus to substantially prevent signals from the nervous system from traveling to substantially all of the distal bronchial branches connected to the second main bronchus. A catheter assembly can be used to damage the nerve tissue of the first main bronchus and to damage the nerve tissue of the second main bronchus without removing the catheter assembly from a trachea connected to the first and second bronchi.

The method comprises denervating the majority of a part of a bronchial tree to substantially prevent signals from the nervous system from traveling to substantially all of the bronchial branches of the part. In certain embodiments, denervation procedures involve damaging nerve tissue using less than about 100 applications of energy, 50 applications of energy, 36 applications of energy, 18 applications of energy, 10 applications of energy, or 3 applications of energy. Each energy application can be at a different treatment site. In some embodiments, substantially all of the bronchial branches in one or both lungs are denervated by the application of energy.

One or more sensing elements can be used to detect airway attributes before, during and / or after therapy. A sensing element can physically contact an inner surface of the airways to assess physical properties of the airways. The sensing element can include one or more inflatable balloons that can be positioned distal to the target tissue.

Brief description of the various views of the drawings

In the Figures, identical reference numerals identify similar elements or acts.

Figure 1 is an illustration of the lungs, blood vessels, and nerves near and in the lungs.

Figure 2A is a schematic view of a treatment system located within a left main bronchus in accordance with one embodiment.

Figure 2B is a schematic view of a treatment system and instrument extending distally from the treatment system.

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Figure 3 is a cross-sectional view of an airway of a bronchial tree surrounding a distal end of a treatment system located along an internal airway passage according to one embodiment.

Figure 4 is a cross-sectional view of an airway of a bronchial tree surrounding a distal extremity of a treatment system when an airway smooth muscle is contracted and there is mucus in an airway lumen according to one embodiment. .

Figure 5A is a partial cross-sectional view of a treatment system having a delivery assembly and an elongated assembly extending through and out of the delivery assembly.

Figure 5B is an illustration of a distal end of the elongated assembly of Figure 5A positioned to affect the nervous tissue of a nerve trunk.

Figure 6 is a side elevational view of a delivery assembly in an inner passageway of a bronchial airway according to one embodiment.

Figure 7 is a side elevational view of a distal end of an elongated assembly moving through the delivery assembly of Figure 6.

Figure 8 is a side elevational view of the distal end of the elongated assembly exiting from the delivery assembly in accordance with one embodiment.

Figure 9 is an enlarged partial cross-sectional view of the distal end of Figure 8, wherein the distal end extends into a wall of the airway.

Figure 10A is a side elevation view of a self-expanding ablation assembly in an airway according to one embodiment.

Figure 10B is a front view of the ablation assembly of Figure 10A.

Figure 11A is a side elevational view of another embodiment of a self-expanding ablation assembly in an airway.

Figure 11B is a front view of the ablation assembly of Figure 11A.

Figure 12A is a partial cross-sectional view of a treatment system having a delivery assembly and a separate elongated assembly within the delivery assembly in accordance with one embodiment.

Figure 12B is a front view of the treatment system of Figure 12A.

Figure 13A is a cross-sectional view of a delivery assembly delivering energy to a treatment site in accordance with one embodiment.

Figure 13B is a front view of the delivery assembly of Figure 13A.

Figure 14A is a partial cross-sectional view of a treatment system having an elongated assembly with a hole located in an airway wall according to one embodiment.

Figure 14B is a front view of the treatment system of Figure 14A.

Figure 15A is a side elevational view of a treatment system having an expandable assembly.

Figure 15B is a cross-sectional view of the expandable assembly of Figure 15A.

Figure 16 is a graph of tissue depth versus tissue temperature.

Figure 17 is a side elevation view of the expandable assembly of Figure 15A in an airway.

Figure 18 is a cross-sectional view of the expandable assembly of Figure 15A and an airway surrounding the expandable assembly.

Figure 19A is a side elevation view of a treatment system having an expandable assembly, according to one embodiment.

Figure 19B is a cross-sectional view of the expandable assembly of Figure 19A.

Figure 20A is a side elevational view of a treatment system having an expandable assembly, according to another embodiment.

Figure 20B is a cross-sectional view of the expandable assembly of Figure 20A.

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Figure 21 is a cross-sectional view of the expandable assembly of Figure 20A and an airway surrounding the expandable assembly.

Detailed description

In the following description, certain specific details are set forth in order to provide a thorough understanding of various embodiments of the invention. However, one skilled in the art will understand that the invention can be practiced without these details. In other instances, well-known structures associated with catheter systems, delivery assemblies, actuables, circuitry, and electrodes have not been described in full detail to avoid unnecessary obscuring of descriptions of embodiments of the invention.

Unless the context requires otherwise, throughout the specification and claims that follow, the word "understand" and variations thereof, as understood and understood, are to be interpreted in an open and inclusive sense, that is, including but not limited to.

Figure 1 illustrates human lungs 10 having a left lung 11 and a right lung 12. A trachea 20 extends downward from the nose and mouth and divides into a left main bronchus 21 and a right main bronchus 22. The left main bronchus 21 and the right main bronchus 22 each branch to form lobar segmental bronchi, and sub-segmental bronchi, which have successively smaller diameters and shorter lengths in the outward direction (i.e., the distal direction). . A main pulmonary artery 30 originates in a right ventricle of the heart and passes in front of a pulmonary root 24. At pulmonary root 24, artery 30 branches into a left and a right pulmonary artery, which in turn branch to form a network of branching blood vessels. These blood vessels can extend alongside the airways of a bronchial tree 27. The bronchial tree 27 includes the left main bronchus 21, the right main bronchus 22, bronchioles and alveoli. The vagus nerves 41, 42 extend alongside the trachea 20 and branch to form nerve trunks 45.

The left and right vagus nerves 41, 42 originate in the brainstem, pass through the neck, and descend through the chest on either side of the trachea 20. The vagus nerves 41, 42 expand into the nerve trunks 45 that include the anterior and posterior pulmonary plexuses that wrap around the trachea 20, the left main bronchus 21 and the right main bronchus 22. Nerve trunks 45 also extend along and out of the airways that branch off the bronchial tree 27. Nerve trunks 45 are the main stem of a nerve, comprising a bundle of nerve fibers held together by a hard sheath connective tissue.

The main function of the lungs 10 is to exchange oxygen from the air with the blood and to exchange carbon dioxide from the blood to the air. The gas exchange process begins when oxygen-rich air is drawn into the lungs 10. Contraction of the diaphragm and the intercostal muscles of the chest wall cooperate to decrease the pressure within the chest to make oxygen-rich air flow through the lungs. through the airways of the lungs 10. For example, air passes through the mouth and nose, the trachea 20, and then through the bronchial tree 27. The air is finally delivered to the alveoli for the gas exchange process.

The oxygen-poor blood is pumped from the right side of the heart through the pulmonary artery 30 and is finally delivered to the alveolar capillaries. This oxygen-poor blood is rich in carbon dioxide waste. Semi-permeable membranes separate oxygen-poor blood in capillaries from oxygen-rich air in alveoli. These capillaries wrap around and extend between the alveoli. Oxygen from the air diffuses through the membranes into the blood, and carbon dioxide from the blood diffuses through the membranes into the air in the alveoli. The new oxygen-enriched blood then flows from the alveolar capillaries through the branching blood vessels of the pulmonary venous system to the heart. The heart pumps oxygen-rich blood through the body. The oxygen-depleted air in the lung is exhaled when the diaphragm and intercostal muscles relax and the lungs and chest wall elastically return to normal relaxed states. In this way, air can flow through branching bronchioles, bronchi 21, 22 and trachea 20 and is finally expelled through the mouth and nose.

A treatment system 198 of Figure 2A can be used to treat the lungs 10 to adjust airflow during expiration or aspiration, or both. For example, the airways can be widened (eg, dilated) to decrease resistance to air flow to increase gas exchange. Treatment system 198 can affect nervous tissue, such as nerve tissue in a nerve trunk, to dilate the airways.

In some embodiments, treatment system 198 targets the nervous system that provides communication between the brain and lungs 10 using electrical and chemical signals. A network of nervous tissue of the autonomic nervous system senses and regulates the activity of the respiratory system and the vascular system. Nervous tissue includes fibers that use chemicals and electrical signals to transmit sensory and motor information from one part of the body to another. For example, nervous tissue can transmit motor information in the form of inputs to the nervous system, such as a signal that causes muscle contraction or other responses. The

ES 2 398 052 T3 fibers can be composed of neurons. The nervous tissue can be surrounded by connective tissue, that is, epineurium. The autonomic nervous system includes a sympathetic system and a parasympathetic system. The sympathetic nervous system is largely involved in arousal functions during periods of stress. The parasympathetic nervous system is largely involved in vegetative functions during periods of energy conservation. The sympathetic and parasympathetic nervous systems are active simultaneously and generally have reciprocal effects in organ systems. While the innervation of the blood vessels originates from both systems, the innervation of the airways is largely parasympathetic in nature and travels between the lung and the brain on the right vagus nerve 42 and the left vagus nerve 41.

Treatment system 198 can perform any number of procedures on one or more of these nerve trunks 45 to affect the part of the lung associated with those nerve trunks. Because part of the nervous tissue in the network of nerve trunks 45 coalesces into other nerves (for example, nerves connected to the esophagus, nerves through the chest and abdomen, and the like), the treatment system 198 can treat specific sites to minimize, limit, or substantially eliminate unwanted damage to those other nerves. Some fibers from the anterior and posterior pulmonary plexuses join into small nerve trunks that run along the outer surfaces of the trachea 20 and the branching bronchi and bronchioles as they travel outward to the lungs 10. Along the Branching bronchi, these small nerve trunks continually branch off each other and deliver fibers to the walls of the airways, as explained with respect to Figures 3 and 4.

Treatment system 198 can affect specific nervous tissue, such as vagus nervous tissue, associated with particular sites of interest. Vagus nerve tissue includes efferent fibers and afferent fibers oriented parallel to each other within a nerve branch. Efferent nerve tissue transmits signals from the brain to effector cells in the airways, mostly airway smooth muscle cells and cells that produce mucus. Afferent nervous tissue transmits signals from sensory receptors in the airways, which respond differently to irritants and spread to the brain. While efferent nerve tissue innervates smooth muscle cells completely from trachea 20 to terminal bronchioles, innervation of afferent fibers is largely limited to trachea 20 and the larger bronchi. There is a constant basal tonic activity of the efferent tissues from the vagus nerve to the airways causing a basal level of smooth muscle contraction and mucous secretion.

Treatment system 198 can affect efferent and / or afferent tissues to control airway smooth muscle (eg, innervate smooth muscle) and mucous secretion. Airway smooth muscle contraction and excess mucous secretion associated with lung disease often result in relatively high resistance to airflow resulting in reduced gas exchange and reduced lung performance.

For example, treatment system 198 can attenuate the transmission of signals traveling through vagus nerves 41, 42 that cause muscle contractions, mucus production, and the like. Attenuation may include, without limitation, difficulty, limitation, blocking and / or interruption of signal transmission. For example, attenuation may include lowering the signal amplitude of nerve signals or weakening the transmission of nerve signals. Decreasing or stopping the supply of the nervous system to the distal airways can alter airway smooth muscle tone, airway mucus production, airway inflammation, and the like, thereby controlling airway flow. air in and out of lungs 10. In some embodiments, input from the nervous system can be decreased to correspondingly decrease airway smooth muscle tone. In some embodiments, airway mucus production may be decreased by a sufficient amount to cause a substantial decrease in cough and / or resistance to air flow. Signal attenuation can allow smooth muscles to relax and substantially prevent, limit, or eliminate mucus production by mucus-producing cells. In this way, healthy and / or diseased airways can be altered to adjust lung function. After treatment, various types of questionnaires or tests can be used to assess the subject's response to treatment. If needed or desired, additional procedures can be performed to reduce the frequency of coughing, decrease shortness of breath, decrease wheezing, and the like.

The main bronchi 21, 22 (ie, airway generation 1) of Figure 1 can be treated to affect the distal parts of the bronchial tree 27. In some embodiments, the left and right main bronchi 21, 22 are treated in locations along the roots of the left and right lung 24 and outside the left and right lungs 11, 12. Treatment sites can be distal to where vagus nerve branches connect to the trachea and main bronchi 21, 22 and proximal to the lungs 11, 12. A single treatment session involving two therapy applications can be used to treat most or all of the bronchial tree 27. Substantially all the bronchial branches extending to the lungs 11, 12 can be affected to provide a high level of therapeutic efficacy. Because the bronchial arteries in the main bronchi 21, 22 have relatively large diameters and a great capacity to dissipate heat, the bronchial arteries can be protected from inadvertent damage due to treatment.

In some embodiments, one of the left and right main bronchi 21, 22 is treated to treat one side of the bronchial tree 27. The other main bronchus 21, 22 can be treated based on the efficacy of the first

ES 2 398 052 T3 treatment. For example, the left main bronchus 21 can be treated to treat the left lung 11. The right main bronchus 22 can be treated to treat the right lung 12. In some embodiments, a single treatment system can damage the nervous tissue of one of the the bronchi 21, 22 and can damage the nervous tissue of the other main bronchus 21, 22 without removing the treatment system from the trachea 20. Nerve tissue located along the main bronchi 21, 22 can thus be damaged without removing the treatment system from the trachea 20. In some embodiments, a single procedure can be performed to conveniently treat substantially all, or by at least a significant part (eg, at least 50%, 70%, 80%, 90% of the bronchial airways), of the patient's bronchial tree. In other procedures, the treatment system can be removed from the patient after treating one of the lungs 11,

12. If needed, the other lung 11, 12 can be treated in a subsequent procedure.

Treatment system 198 of Figures 2A and 2B can treat airways that are distal to major bronchi 21, 22. For example, treatment system 198 can be placed in higher generation airways (eg, generations airway> 2) to affect remote distal parts of the bronchial tree 27. Treatment system 198 can be directed through the sinuous airways to perform a wide variety of different procedures, such as, for example, denervation of a part of a lobe, an entire lobe, multiple lobes, or a lung. or both lungs. In some embodiments, the lobar bronchi are treated to denervate the lung lobes. For example, one or more treatment sites along a lobar bronchus may be targeted to denervate an entire lobe connected to that lobar bronchus. The left lobar bronchi can be treated to affect the left upper lobe and / or the left lower lobe. The right lobar bronchi can be treated to affect the right upper lobe, the right middle lobe, and / or the right lower lobe. The lobes can be treated at the same time or sequentially. In some embodiments, a physician can treat a lobe. Based on the effectiveness of the treatment, the physician may treat an additional lobe (s) sequentially or concurrently. In this way, different isolated regions of the bronchial tree can be treated.

Treatment system 198 can also be used in segmental or subsegmental bronchi. Each segmental bronchus can be treated by delivering energy to a single treatment site along each segmental bronchus. For example, energy can be delivered to each segmental bronchus in the right lung. In some procedures, ten applications of energy can treat most or substantially all of the right lung. In some procedures, most or substantially all of both lungs are treated using fewer than thirty-six different applications of energy. Depending on the anatomical structure of the bronchial tree, the segmental bronchi can often be denervated using some energy applications.

Treatment system 198 can affect nervous tissue while maintaining the function of other tissue or anatomical features, such as mucous glands, cilia, smooth muscle, vessels of the body (eg, blood vessels), and the like. Nervous tissue includes neurons, nerve fibers, dendrites, and supporting tissue, such as neuroglia. Neurons transmit electrical impulses, and nerve fibers are long axons that conduct impulses. The electrical impulses are converted into chemical signals to communicate with effector cells or other neurons. By way of example, treatment system 198 is capable of denervating a portion of an airway in the bronchial tree 27 to attenuate one or more nervous system signals transmitted by nervous tissue. Denervation may include damage to all nerve tissue in a section of a nerve trunk along an airway to prevent substantially all signals from traveling through the damaged section of the nerve trunk to locations more distal to it. length of the bronchial tree. If a plurality of nerve trunks extend along the airways, each nerve trunk can be damaged. As such, supply to the nerve can be cut off along a section of the bronchial tree. When the signals are cut off, the distal airway smooth muscle can relax leading to airway dilation. This dilation of the airways reduces resistance to air flow to increase gas exchange in the lungs, 10 thereby reducing, limiting or substantially eliminating one or more symptoms, such as shortness of breath, wheezing, tightness in the chest and the like. The tissue surrounding or adjacent to the target nerve tissue may be affected but not permanently damaged. In some embodiments, for example, the bronchial blood vessels along the treated airways can deliver a similar amount of blood to the bronchial wall tissues and the pulmonary blood vessels along the treated airways can deliver a similar amount. of blood to the alveoli in the distal regions of the bronchial tree 27 before and after treatment. These blood vessels can continue to carry blood to maintain sufficient gas exchange. In some embodiments, the airway smooth muscle is not significantly damaged. For example, a relatively small section of smooth muscle in an airway wall can be reversibly altered that does not significantly impact respiratory function. If energy is used to destroy nerve tissue outside the airways, a therapeutically effective amount of energy does not reach a significant portion of the non-targeted smooth muscle tissue.

Treatment system 198 of Figure 2A includes treatment controller 202 and elongated intraluminal assembly 200 connected to controller 202. Elongated assembly 200 may be inserted into trachea 20 and directed into and through bronchial shaft 27 with or without use a delivery set. Elongated assembly 200 includes a distal end 203 capable of selectively affecting tissue.

ES 2 398 052 T3

Controller 202 of Figure 2A may include one or more processors, microprocessors, digital signal processors (DSP), field programmable gate array (FPGA), and / or application specific integrated circuits (ASICs), memory devices, buses, power supplies and the like. For example, controller 202 may include a processor in communication with one or more memory devices. The buses can link an internal or external power supply to the processor. The memories can take various forms, including, for example, one or more buffers, registers, random access memories (RAM), and / or read-only memories (ROM). Controller 202 may also include a display, such as a screen.

In some embodiments, controller 202 has a closed loop system or an open loop system. For example, controller 202 may have a closed loop system, whereby power to distal end 203 is controlled based on feedback signals from one or more sensors configured to transmit (or send) one or more signals indicative of a or more tissue characteristics, energy distribution, tissue temperature, or any other measurable parameter of interest. Based on those readings, the controller 202 can then adjust the operation of the distal end 203. Alternatively, the treatment system 198 can be an open loop system where the operation of the distal end 203 is set by input from the user. . For example, treatment system 198 can be put into a fixed power mode. It is contemplated that the treatment system 198 may be repeatedly switched between a closed loop system and an open loop system to treat different types of sites.

The distal end 203 of Figures 2A-4 may target various sites in the lungs 10, including, without limitation, nerve tissue (eg, vagus nerve tissue 41, 42, nerve trunks 45, etc.), tissue fibrous, diseased or abnormal tissues (eg, cancerous tissue, inflamed tissue, and the like), muscle tissue, blood, blood vessels, anatomical features (eg, membranes, glands, cilia, and the like), or other sites of interest. Various types of distal limbs are explained with respect to Figures 5A-14B.

Figure 3 is a cross-sectional view of a healthy airway 100, illustrated as a bronchial tube. The distal end 203 is positioned along an inner passage 101 defined by an inner surface 102 of the airway 100. The illustrated inner surface 102 is defined by a folded layer of epithelium 110 surrounded by stroma 112a. A layer of smooth muscle tissue 114 surrounds stroma 112a. There is a stromal layer 112b between muscle tissue 114 and connective tissue 124. Mucous glands 116, cartilage 118, blood vessels 120, and nerve fibers 122 are within stromal layer 112b. Bronchial artery branches 130 and nerve trunks 45 are exterior to a wall 103 of airway 100. The illustrated arteries 130 and nerve trunks 45 are within connective tissue 124 surrounding airway wall 103 and may be oriented generally parallel to airway 100. In Figure 1, for example, nerve trunks 45 originate from the vagus nerves 41, 42 and extend along the airway 100 towards the alveoli. Nerve fibers 122 are in airway wall 103 and extend from nerve trunks 45 to muscle tissue 114. Nervous system signals are transmitted from nerve trunks 45 to muscle 114 via nerve fibers 122.

The distal end 203 of Figure 3 may damage, excite, or otherwise elicit a desired response from cilia along epithelium 110 in order to control (eg, increase or decrease) mucus transport. When a person breathes in, many particles are inhaled and the airways act as a filter to remove the particles from the air. The ciliary mucus transport system functions as a self-cleaning mechanism for all airways through the lungs 10. Ciliary mucus transport is a primary method for cleaning mucus from the distal parts of the lungs 10, serving as thereby as a primary immune barrier for the lungs 10. For example, the inner surface 102 of Figure 3 may be covered with cilia and lined with mucus. As part of the ciliary mucus transport system, mucus traps many inhaled particles (for example, unwanted pollutants like tobacco smoke) and moves these particles into the larynx. The ciliary rhythm of the cilia moves a continuous carpet of mucus and trapped particles from the distal parts of the lungs 10 through the larynx and into the pharynx for expulsion from the respiratory system. The distal end 203 can damage the cilia to decrease ciliary mucus transport or excite the cilia to increase ciliary mucus transport.

In some embodiments, distal limb 203 selectively treats treatment target sites within airway wall 103 (eg, anatomical features at stromas 112a, 112b). For example, mucous glands 116 can be damaged to reduce mucus production by an amount sufficient to prevent mucus accumulation causing increased resistance to air flow while preserving sufficient mucus production to maintain effective mucus transport. ciliary mucus, if needed or desired. In some embodiments, for example, distal end 203 sends ablative energy traveling through the inner periphery of airway wall 103 to mucous glands 116. In other embodiments, distal end 203 is inserted into wall 103 of airway to place the distal limb 203 close to the mucous glands 116. The recessed distal end 203 then treats the mucous glands 116 while limiting the treatment of the surrounding tissue. The distal end 203 can also be used to destroy nerve branches / fibers that pass through the airway wall 103 or other anatomical features in the airway wall 103.

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If the airway 100 contracts excessively, the resistance to air flow of the airway 100 may be relatively high. Distal end 203 can relax muscle tissue 114 to dilate airway 100 to reduce resistance to air flow, thereby allowing more air to reach the alveoli for the gas exchange process. Various airways of the bronchial tree 47 may have muscles that contract in response to signals traveling through nerve trunks 45. Limb 203 can damage sites through lungs 10 to dilate contracted airways.

Figure 4 is a cross-sectional view of a portion of airway 100 having smooth muscle tissue 114 in a contracted state and mucus 150 from hypertrophied mucous glands 116. Contracted muscle tissue 114 and mucus 150 cooperate to obstruct partially lumen 101. Distal end 203 can relax smooth muscle tissue 114 and substantially reduce, limit, or eliminate mucus production from mucous glands 116. Airway 100 can then be dilated and the amount of mucus 150 can be reduced, to effectively enlarge internal passage 101.

The distal end 203 of Figures 3 and 4 can deliver different types of energy. As used herein, the term energy is broadly interpreted to include, without limitation, thermal energy, cryogenic energy (eg, cooling energy), electrical energy, acoustic energy (eg, ultrasonic energy), radio frequency energy. high voltage pulse energy, mechanical energy, ionizing radiation, optical energy (e.g. light energy) and combinations thereof, as well as other types of adequate energy to treat tissues. By way of example, thermal energy can be used to heat tissue. Mechanical energy can be used to pierce, tear, cut, crush, or otherwise physically damage tissue. In some embodiments, the distal end 203 applies pressure to the tissue in order to temporarily or permanently damage the tissue. Electrical energy is particularly well suited for damaging cell membranes, such as nerve stem tissue cell membranes or other target anatomical features. Acoustic energy can be emitted as continuous or pulsed waves, depending on the parameters of a particular application. Additionally, acoustic energy can be emitted in waveforms that have various shapes, such as sine waves, triangle waves, square waves, or other waveforms.

In some embodiments, a fluid (eg, a liquid, gas, or mixtures thereof) is used to damage tissue. The distal end 203 may include one or more flow elements through which fluid can flow to control the surface temperature of the flow element. The flow element can be one or more balloons, expandable members, and the like. The fluid can be heated / cooled saline, cryogenic fluids, and the like. Additionally or alternatively, distal end 203 may include one or more holes through which fluid flows to traumatize tissue.

In some embodiments, the distal end 203 delivers one or more substances (eg, radioactive seeds, radioactive materials, etc.), treatment agents, and the like. Non-limiting examples of treatment agents include, without limitation, one or more antibiotics, anti-inflammatory agents, pharmaceutically active substances, bronchoconstrictors, bronchodilators (eg, beta-adrenergic agonists, anticholinergics, etc.), nerve-blocking drugs, photoreactive agents or combinations thereof. For example, short-term or long-term nerve-gagging drugs (eg, anticholinergics) can be administered to nervous tissue to temporarily or permanently attenuate signal transmission. Substances can also be administered directly to nerves 122 or nerve trunks 45, or both, to chemically damage nerve tissue.

Figures 5A-14B illustrate embodiments for delivery along an internal passageway of an airway. The illustrated embodiments are just a few examples of the types of treatment systems capable of performing particular procedures. It should be recognized that each of the treatment systems described herein can be modified to treat tissue at different locations, depending on the treatment to be performed. Treatment can be performed on airways that are inside or outside the left or right lung. Figures 5A-13B illustrate treatment systems capable of delivering energy. These treatment systems can send energy continuously for a predetermined period of time while remaining stationary. Alternatively, the treatment systems can be pulsed, can be activated multiple times, or can be operated in a combination of any of these ways. Different patterns of energy application can be achieved by setting up the same treatment system or it can involve moving the treatment assembly or any of its components to different locations.

Referring to Figure 5A, a treatment system 198A includes an elongated assembly 200A having a distal end 203A located along the airway 100. The elongated assembly 200A extends through an internal working passage 401 of a delivery assembly 400 and includes a flexible stem 500 and a deployable ablation assembly 520 protruding from stem 500.

Stem 500 may be a generally straight stem that is bent as it moves along internal passage 401. In some embodiments, stem 500 has a preformed non-linear section 503 to direct ablation assembly 520 toward wall 103 airway. As shown in Figure 5A, the inner passage 401 may have a diameter that is significantly larger than the outer diameter of the stem 500. When the trunk 500 passes out of the delivery assembly 400, the trunk 500 adopts the preset configuration. Flexible stem 500 may be made, in whole or in part, of one or more metals, alloys (e.g., alloys

ES 2 398 052 T3 of steel such as stainless steel), plastics, polymers and combinations thereof, as well as other biocompatible materials.

In some embodiments, the trunk 500 is selectively moved between a delivery configuration and a treatment configuration. For example, stem 500 may have a substantially straight configuration for delivery and a curved configuration to engage tissue. In such embodiments, the trunk 500 can be made, in whole or in part, of one or more shape memory materials, which moves the trunk 500 between the delivery configuration and the treatment configuration when activated. Shape memory materials include, for example, shape memory alloys (eg, NiTi), shape memory polymers, ferromagnetic materials, and the like. These materials can be transformed from a first preset configuration to a second preset configuration when activated (eg, thermally activated).

Ablation assembly 520 includes protective section 524 and ablation element 525. When ablation element 525 is activated, ablation element 525 sends energy to targeted tissue. Protective section 524 inhibits or blocks energy sent to protect non-target tissue. Ablation element 525 and protective section 524 thus cooperate to provide localized delivery of energy to minimize, limit, or substantially eliminate additional unwanted trauma associated with the energy produced.

Ablation element 525 may be adapted to deliver energy that ablates tissue. The terms ablate or ablate, including derivatives thereof, include, without limitation, the substantial alteration of electrical properties, mechanical properties, chemical properties, or other properties of the tissue. In the context of lung ablation applications shown and described with reference to variations of the illustrative embodiments herein, ablation includes sufficiently altering the properties of nerve tissue to substantially block the transmission of electrical signals through ablated nerve tissue. .

The term element within the context of ablation element includes a discrete element, such as an electrode, or a plurality of discrete elements, such as a plurality of spaced electrodes, that are positioned for the purpose of collectively treating a region of tissue or treating discreet places. One type of ablation element emits energy that ablates tissue when the element is engaged and energized by an energy source. Examples of energy-emitting ablation elements include, without limitation, electrode elements that can be coupled to direct current (DC) sources or alternating current (AC) sources (eg, radio frequency (RF) current sources), antenna elements that can be powered by microwave energy sources, high voltage pulse sources, heating elements (for example, metallic elements or other thermal conductors that are energized to emit heat through convective heat transfer, conductive heat transfer, etc.), light-emitting elements (for example, optical fiber capable of transmitting enough light to perform ablation tissue when the optical fiber is coupled to a light source), light sources (e.g. lasers, light-emitting diodes, etc.), ultrasonic elements such as ultrasonic elements adapted to emit sufficient ultrasonic sound waves to ablate tissue when coupled to suitable sources of excitation), combinations thereof, and the like.

As used herein, the term ablate, including variations thereof, is interpreted to include, without limitation, permanently destroying or damaging, injuring or traumatizing tissue. For example, ablation can include localized tissue destruction, cell lysis, cell size reduction, necrosis, or combinations thereof.

In some embodiments, ablation assembly 520 may be connected to a power generator (eg, a radio frequency (RF) electrical generator) by electrical wires within trunk 500. For example, the RF electrical generator may be incorporated. in controller 202 of Figure 2A. In some embodiments, the RF electrical generator is incorporated into ablation assembly 520.

RF energy can be sent at a desired frequency based on treatment. Exemplary frequencies include, without limitation, frequencies in the range of about 50 kHz to about 1000 MHz. When RF energy is directed at tissue, the energy is converted within the tissue into heat that causes the tissue temperature to be within the range. range from about 40 ° C to about 99 ° C. RF energy can be applied for a time in the range of about 1 second to about 120 seconds. In some embodiments, the RF generator is single channel and delivers approximately 1 to 25 watts of RF energy and possesses continuous flow capability. Frequency, time and power send ranges can also be used.

The shield section 524 may be in the form of a shield made, in whole or in part, of a material that is not energy-transmissive to the ablation element 525. In some embodiments, the shield section 524 is comprised of one or more metals, optically opaque materials, and the like. If ablative element 525 sends out ablative energy, shield section 524 can block a sufficient amount of the ablative energy to prevent ablation of tissue directly adjacent to shield section 524. In this way, non-target tissue is not permanently damaged.

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A user can visually inspect the airway 100 using the delivery assembly 400 of Figures 5A and 5B to position and assess the treatment site (s) and non-target tissues before, during, and / or after performing a test. therapy. Delivery assembly 400 may be a catheter, delivery sheath, bronchoscope, endoscope, or other suitable device for guiding elongated assembly 200A. In some embodiments, delivery set 400 includes one or more display devices, such as optical display devices (eg, cameras), optical trains (eg, a lens set), and the like. For example, delivery assembly 400 may be in the form of a bronchoscope having one or more lights for illumination and optical fibers for transmitting images. By way of another example, delivery assembly 400 may have an ultrasound display device, as explained with respect to Figures 11A and 11B.

Figures 6-9 show an example method for using treatment system 198A. Generally, the treatment system 198A can alter the nervous tissue of the airway 100 to control the supply of the nervous system to a part of the lung while not damaging any significant extent of other lung structures.

As shown in Figure 6, delivery assembly 400 is moved along internal passage 101 of airway 100, as indicated by arrow 560. Elongated assembly 200A is carried in delivery assembly 400 to avoid injuries to airway 100 during placement of delivery set 400.

Figure 7 shows elongated assembly 200A moving along internal passage 401 toward an opening 564, as indicated by arrow 568. As elongated assembly 200A is moved through delivery assembly 400 (shown in cross section) the ablation assembly 520 (shown in imaginary line) may be housed within trunk 500 to prevent damage to airway 100 or delivery assembly 400, or both. A user can push the trunk 500 out of the delivery assembly 400 toward the airway wall 103.

Figure 8 shows a distal end 570 of stem 500 proximate wall 103. Sharpened ablation assembly 520 is deployed from stem 500 and contacts wall 103. Ablation assembly 520 is then advanced through the wall. 103 until exposed ablation element 525 is embedded within wall 103, as shown in Figure 9. The position of ablation assembly 520 relative to airway wall 103 can be adjusted by extending or retracting ablation assembly 520. Because ablation assembly 520 is relatively slender, wall 103 can experience a negligible amount of trauma.

The illustrated ablation assembly 520 is connected to one wire of the RF generator and the other wire of the RF generator can be connected to an external electrode. When the RF generator is activated, ablation element 525 delivers RF energy to tissue that contacts or is adjacent to ablation element 525. RF energy flows through tissue and is converted into heat. The heat can be concentrated on the outside of the airway wall 103. For example, ablation element 525 of Figure 5B sends RF energy causing damage to nerve trunks 45. In some embodiments, a sufficient amount of RF energy is delivered to nerve trunk 45 to destroy an entire longitudinal section. of the nerve trunk 45 while maintaining the amount of energy reaching the lower blood vessels 130 of an amount that causes tissue destruction. Damage to other non-target regions (eg, the epithelium) can also be kept below an acceptable level. In this way, therapies can be performed without damaging any significant extensions of other regions of the airway 100, even regions that are adjacent to the treatment site.

The body's natural functions can help prevent, reduce, or limit tissue damage. If the bronchial artery branches 130 are heated by the treatment system 198A, the blood within the blood vessels 130 can absorb the thermal energy and then the thermal energy can be carried away from the heated section of the branches 130. In this way, thermal energy is transferred to the blood. After the treatment has been performed, the bronchial artery branches 130 can continue to maintain the health of the lung tissue.

This procedure can be repeated to damage additional tissue of nerve trunks 45 located outside the circumference of wall 103. In some embodiments, all of the nerves around airway 100 can be treated to prevent signals from passing between a proximal section 572 of airway 100 and a distal section 573 of airway 100, as shown in Figure 5A. Because signals are not transmitted to distal section 573, distal section 573 can be dilated. Airway 100 may also remain generally intact to maintain the health of distal section 573. Upon completion of the treatment process, ablation assembly 520 is retracted back into trunk 500 for removal from airway 100 or for removal. placement in other treatment locations.

Efficacy of treatment can be assessed based at least in part on one or more airway attributes, lung function tests, exercise capacity tests, and / or questionnaires. Patients can be assessed to track and monitor their progress. If needed or desired, additional procedures can be performed until the desired responses are achieved.

Different types of instruments can be used to assess airway attributes with treatment systems. During ablation, the reaction of an instrument can indicate whether the target tissue has been subjected to

ES 2 398 052 T3 ablation. Once the target tissue is ablated, therapy can be interrupted to minimize or limit collateral damage, if any, to healthy non-target tissue. Figure 2B shows an instrument 199 with a sensing element in the shape of a balloon. Fluid (eg, air, saline, or something similar) can be used to inflate the balloon to assess airway attributes. Instrument 199 may be a conventional instrument for airway dilation, airway occlusion, or the like. Instruments available for purchase from numerous medical vendors, including Ackrad Laboratories, Cranford, New Jersey, and Erich Jaeger, Hoechberg, Germany, can be used or modified for use with the treatment systems described herein. Instruments can be delivered through treatment systems (eg, through a central lumen of the treatment system) to position a sensing element distal to the treatment system.

Airway attributes evaluated by the instrument may include, without limitation, airway physical properties (e.g., airway compliance, contractile properties, etc.), airway resistance, internal airway passage dimensions (e.g. e.g. airway shapes, airway diameters, etc.), airway responsiveness (e.g. responsiveness to stimulation), muscle characteristics (for example, muscle tone, muscle tension, etc.) or something similar. In some embodiments, changes in airway muscle characteristics can be monitored by measuring changes in pressure of the intraluminal balloon that is inflated to a known pressure. Based on pressure changes in the balloon, a physician determines the effects, if any, of the treatment, including, without limitation, whether the target tissue has been stimulated, damaged, ablated, or the like. For example, the balloon can be positioned distal to the target tissue. When nerve tissue is damaged, muscle tension in the airways surrounding the balloon is reduced causing the airways to expand as well as the balloon to expand. The pressure in the balloon decreases as the balloon expands.

Instrument 199 and treatment system 198 can be delivered through different internal steps in a delivery device, including, without limitation, an internal multi-step catheter, delivery sheath, bronchoscope, endoscope, or other suitable device. to manage and guide multiple devices. The delivery device may be selected based on the location of the treatment site (s), the configuration of the treatment system, or the like.

Decreases in airway resistance may indicate that airway passages are opening, for example, in response to attenuation of the nervous system's input to those airways. The decrease in airway resistance associated with treatment of lower-generation airways (eg, main bronchi, lobar bronchi, segmental bronchi) may be greater than the amount of decrease in airway resistance associated with treatment. high-generation airways (eg, sub-segmental bronchioles). Appropriate airways can be selected for treatment by a physician to achieve a desired decrease in airway resistance and can be measured in a patient's mouth, a bronchial branch that is close to the treatment site, a trachea, or any other proper location. Airway resistance can be measured before therapy, during therapy, and / or after therapy. In some embodiments, airway resistance is measured at a location within the bronchial tree, for example, using a ventilated treatment system that allows breathing from areas that are more distal to the treatment site.

Figures 10A-14B illustrate treatment assemblies that may be generally similar to treatment assembly 198A discussed with respect to Figures 5A-9, except for the following details. Figure 10A illustrates a treatment system 198B that includes an elongated flexible stem 610 and a plurality of radially deployed ablation assemblies 620. Ablation assemblies 620 may collapse inward when stem 610 is pulled proximally with delivery assembly 400 (shown in cross section). When the plurality of ablation assemblies 620 are pushed out of delivery assembly 400, ablation assemblies 620 self-expand biasing radially outward.

Each electrode assembly 620 includes a tapered tip for piercing the airway wall 103 and includes sharp retractable and extensible ablation elements 625. Ablation assemblies 620 are preferably isolated except for exposed ablation elements 625. Ablation assemblies 620 may be connected to an electrical RF generator by electrical cables that travel within the trunk 610. While treatment system 198B is being delivered, ablation assemblies 620 can be positioned within stem 610. Ablation assemblies 620 can be moved out of stem 610 and brought into contact with wall 103. Ablation assemblies 620 can be simultaneously moved through airway wall 103 until the desired lengths of ablation elements 625 are within airway wall 103.

As shown in Figure 10B, the plurality of ablation elements 625, illustrated as electrodes, may be circumferentially spaced from one another along the airway wall 103. The ablation elements 625 may be unevenly or evenly spaced from one another.

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All ablation sets 620 can be connected to one RF generator lead and the other RF generator lead can be connected to an external electrode 623 (shown in imaginary line), so that current flows between the ablation sets 620 and / or between one or more of ablation assemblies 620 and external electrode 623. In some embodiments, a selected number of ablation sets 620 are connected to one RF generator lead while the other ablation sets 620 are connected to the other RF generator lead such that current flows between ablation sets 620. .

When the RF generator is activated, current flows through the tissue and generates a desired amount of heat. Heat can be concentrated outside the airway wall 103 to damage peripheral tissue. For example, the temperature of the connective tissue may be higher than the temperatures of the stroma, smooth muscles and / or the epithelium. By way of example, the temperature of the connective tissue may be high enough to cause damage to the nerve tissues in the nerve trunks 45 while other non-target tissues of the airway 100 are maintained at a lower temperature to avoid or limit damage to non-target tissues. In other embodiments, heat may be concentrated in one or more of the inner layers (eg, the stroma) of the airway wall 103 or the inner periphery (eg, the epithelium) of the airway wall 103. .

As shown in Figure 10B, one or more vessels in the bronchial artery branches 130 may be relatively close to ablation elements 625. The heat generated by ablation elements 625 can be controlled such that the blood flowing through bronchial artery branches 130 protects those branches 130 from thermal injury while nerve tissue is damaged, even if nerve tissue it is next to the artery branches 130. Upon completion of the treatment process, ablation assemblies 620 are retracted back into trunk 610 for removal from airway 100 or for placement at other treatment locations.

Figures 11A and 11B illustrate a treatment system 198C that includes an elongated flexible stem 710 and a plurality of extendable and retractable ablation assemblies 720. When ablation assemblies 720 are deployed, ablation assemblies 720 bias radially outward and upon contact with a tubular section 719 of the airway 100. Ablation elements 725 of ablation assemblies 720 may be axially and circumferentially distributed over a treatment length LT of section 719.

Ablation assemblies 720 can include shield sections 721 and exposed ablation elements 725. Shield sections 721 can extend from trunk 710 to an interior surface of airway 100. Ablation elements 725 protrude from corresponding shield sections 721 The ablation assemblies 720 may be connected to a radio frequency (RF) electrical generator by electrical cables that travel within the trunk 710.

Treatment system 198C is delivered to the desired treatment location within airway 100. While treatment system 198C is being delivered, ablation assemblies 720 are retracted into trunk 710 so as not to damage airway 100 or the delivery device 400, or both. Once in position, the sharp ablation elements 725 are brought into contact with the airway wall 103. Elements 725 are then advanced through airway wall 103 until ablation elements 625 are embedded within airway wall 103. Substantially all of the ablation assemblies 720 may be connected to one RF generator lead and the other RF generator lead may be connected to an external electrode, so that current flows between the ablation assemblies 720 and the external electrode. Alternatively, selected individual ablation sets 720 may be connected to one RF generator lead while other ablation sets 720 may be connected to the other RF generator lead so that current can flow between ablation sets 720. .

Figure 12A illustrates the elongated assembly 200A of Figures 5A and 5B passing through a delivery assembly 400A, illustrated as a bronchoscope, having an imaging device 850. The imaging device 850 is located at an end 413A of the delivery assembly 400A. In some embodiments, the imaging device 850 includes an array of ultrasound transducers with an operating frequency between about 1 MHz and about 250 MHz and Doppler capabilities. The wavefronts 860 sent by the imaging device 850 are illustrated in Figures 12A and 12b.

When used, the delivery device 400A is advanced to the desired treatment region of the airway 100. The imaging device 850 is then used to image at least a portion of the airway wall 103 , thereby locating anatomical structures, such as nerve trunks 45 and / or bronchial artery branches 130, that are located in connective tissue 124 outside of the airway wall. For example, the imaging device 850 can be used to circumferentially image the airway 100. In some modes of operation, the target tissues (eg, nerve trunks 45, mucous glands 116, and the like) are located such that only the portion of wall 103 immediately adjacent to the target tissues and connective tissue 124 is treated. In other modes of operation, non-target tissues (eg, bronchial artery branches 130) are located and all other regions of wall 103 and connective tissue 124 are treated.

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In treating the nerve trunks 45, the end 413 of the delivery device 400A can be guided and positioned close to a selected nerve trunk 45. Once in position, sharp ablation element 525 is brought into contact with wall 103. Ablation element 525 is then advanced through wall 103 until ablation elements 525 are embedded. The illustrated exposed ablation elements 525 are adjacent to the nerve stem in the connective tissue 124. The RF generator is activated and current flows between the ablation assembly 520 and the tissue in wall 103. The current causes the tissues of the nerve trunks 45 increase in temperature until the heated tissue is damaged. By positioning ablation assembly 520 near nerve stem 45, nerve stem 45 is selectively damaged while minimizing injury to non-target tissues, such as bronchial arteries 130. This procedure can be repeated to damage additional nerve branches. 45 located around the circumference of wall 103 at or adjacent to connective tissue 124.

Various types of devices can be used to treat target tissues remotely. Figures 13A and 13B illustrate a treatment system 200E in the form of a bronchoscope having a 950 array of high energy ultrasound transducers located at its end 413E. The array 950 of ultrasound energy transducers can be positioned to image the desired treatment site. The array 950 of ultrasound transducers is then used to circumferentially image wall 103 to locate nerve trunks 45 and / or bronchial arteries 130. In some modes of operation, nerve trunks 45 are located and only treat the area of ​​the wall 103 of the airway 100 and the connective tissue 124 around the nerve trunks 45 using ultrasound energy. In other modes of operation, the bronchial arteries 130 are located and all other areas of the wall 103 of the airway 100 and connective tissue 124 are treated using ultrasound energy.

The array 950 of ultrasound transducers can emit highly focused sound waves 960 into the connective tissue 124 to damage the nerve trunks 45 and minimize or avoid injury to the bronchial arteries 130. The end 413E of the bronchoscope 400B can be positioned such that the energy sent is directed away or does not reach the branches 130 of the bronchial artery. This procedure for treating tissue remotely can be repeated to damage additional nerve trunks 45 located around the circumference of wall 103 in connective tissue 124, as desired. The bronchoscope 400B can be used to damage all or at least some of the nerve trunks 45 in a particular section of the airway 100.

Figures 14A 14B illustrate a treatment system 198F that includes an elongated assembly 200F. Elongated assembly 200F includes an elongated stem 1110 and an extensible and retractable piercing tip 1120. The piercing tip 1120 is adapted to pass through tissue and includes at least one hole 1130. The illustrated piercing tip 1120 includes a single side hole 1130 for delivery of flowable substances. An internal passage may extend proximally from port 1130 through stem 1110. A fluid substance may flow distally through the internal passage and out of port 1130. Examples of substances that may flow include, without limitation, one or more heated liquids, refrigerated liquids, heated gases, refrigerated gases, chemical solutions, drugs, and the like, as well as other substances that can cause tissue damage. For example, saline (eg, heated or cooled saline) or cryogenic fluids can be delivered through port 1130.

The elongated assembly 200F of Figures 14A and 14B can be delivered to the desired treatment location using the delivery assembly 400. While the elongated assembly 200F is being delivered, the piercing tip 1120 is retracted into the stem 1110 so as not to damage the stem. airway 100 and / or delivery assembly 400. Once in position, hollow tapered tip 1020 is brought into contact with airway wall 103. Tip 1020 is then advanced through airway wall 103 until side port 1130 is in or adjacent to connective tissue 124. Flowable substance is delivered through tip 1020 and out of port 1130 and flows against the tissue of the airway 100. In some embodiments, the expelled substance cuts, crushes, or otherwise damages the tissue. In some embodiments, the flowable substance includes at least one long-acting nerve blocking drug that completely or partially blocks nerve conduction in nerve trunks 45.

Figures 15A-19B illustrate treatment systems that may be generally similar to treatment system 198A discussed with respect to Figures 5A-9, except for the following details. Figure 15A is a longitudinal side view of a treatment system 2000 in the form of an expandable balloon fluid-cooled / heated electrode catheter. Figure 15B is a cross-sectional view of an expandable assembly 2001 of the system 2000. The illustrated expandable assembly 2001 is in an expanded state. The flow lines 2100 represent the movement of fluid through the expanded set 2001. The expanded set 2001 includes an expandable member 2002 and an ablation electrode 2004. The ablation electrode 2004 may collapse inward when the treatment system 2000 is moved (eg, pulled proximally or pushed distally) through a delivery assembly. When treatment system 2000 is pushed out of the delivery assembly, ablation electrode 2004 can expand outwardly by inflating expandable member 2002.

Treatment system 2000 generally includes expandable member 2002 (illustrated in the form of a thermally conductive expandable balloon), ablation electrode 2004, conductive element 2031, inflow line 2011, and exit line 2021. The ablation electrode 2004 is expandable and is connected to a

ES 2 398 052 T3 distal end 2033 of conductive element 2031. A proximal end 2035 of conductive element 2031 is connected to electrical connector 2038. Energy is transferred from electrical connector 2038 to expandable electrode 2004 through conductive element 2031. conductive element 2031 may include, without limitation, one or more cables, conduits, or the like.

A 2009 proximal end of the 2011 inflow line has a 2012 inline valve. A 2015 proximal end of the 2021 outlet line also has a 2022 outlet valve. The 2011 inline valve can be connected to a fluid supply, such as a source of refrigerant, through a 2018 connector. The fluid flows through the 2011 inflow line into the 2002 balloon, and exits the 2002 balloon through the 2021 exit line. The fluid may include, without limitation, temperature controlled fluid, such as water, saline, or other fluid suitable for use in a patient.

A 2017 inner passage of the 2011 inflow line and a 2019 inner passage of the 2021 outlet line provide fluid communication with the 2002 balloon. The fluid can flow through the 2017 inner passage into the 2002 balloon. The fluid circulates within the balloon 2002 and flows out of balloon 2002 through inner passage 2019. Fluid can pass through connector 2028 to a fluid return system, which can cool the fluid and recirculate the fluid to the fluid supply.

Different types of materials can be used to form the different components of the system 2000. In some embodiments, the balloon 2002 is made, in whole or in part, of a chemically inert, non-toxic, electrically insulating and thermally conductive extensible material. For example, balloon 2002 can be made of polymers, plastics, silicon, rubber, polyethylene, combinations thereof, or something similar. In some embodiments, the 2011 inflow line and the 2021 exit line are made, in whole or in part, of some suitable flexible, chemically inert, and non-toxic material to withstand operating pressures without significant expansion. The 2011 inflow line and the 2021 exit line can be of adequate length to be passed to the lung and the bronchial tree. For example, lines 2011, 2021 can be about 80 cm long. Other lengths are also possible.

Figure 15B shows the 2011 inflow line and the 2021 outlet line arranged to minimize, reduce or substantially prevent cross-flow, siphoning or backflow between the two lines 2011, 2021. The illustrated 2011 inflow line carries the globe 2004. The 2011 inflow line may enter a proximal end

2003 of balloon 2002, extend the length of balloon 2002, and reach a distal end 2007 of balloon 2002. The illustrated inflow line 2011 is connected to distal end 2007 to maintain balloon 2002 in an elongated configuration.

A 2005 limb exits the 2002 balloon. The 2005 illustrated limb is an atraumatic limb located opposite the end of the 2011 inflow line. Near the 2005 limb, the 2011 inflow line has a 2013 opening that releases fluid into the 2002 balloon. Fluid flows into balloon 2002 and is collected in outlet line 2021. The illustrated outlet line 2021 has an opening 2023 to receive fluid. Opening 2023 is generally at the distal end of a portion of outlet line 2021 in balloon 2002 and collects fluid from any direction. Because the openings 2013, 2023 are at opposite ends of balloon 2002, fluid can generally flow in one direction through balloon 2002. This ensures that fluid at a desired temperature will fill balloon 2002.

The 2004 electrode and 2002 balloon shapes can be selected such that the 2004 electrode and balloon

2004 they expand / deflate together. When balloon 2002 is inflated, electrode 2004 is expanded with balloon 2002. When balloon 2002 is deflated, electrode 2004 contracts with balloon 2002. Electrode 2004 can be coupled to an outer surface or inner surface of balloon 2002 and can be made of different types of conductive materials, including, without limitation, any chemically inert, non-toxic, structurally elastic, electrically conductive material. In some embodiments, electrode 2004 is attached to the exterior of balloon 2002 and is made, in whole or in part, of a highly conductive, deformable material. The energy sent by electrode 2004 is sent directly to airway wall 100 without passing through balloon wall 2002. Electrode 2004 can be a thin wire or band made mostly or entirely of copper. The wire can be coated or uncoated depending on the application. In other embodiments, electrode 2004 is recessed in the wall of balloon 2002. Any number of electrodes 2004 may be placed along balloon 2002. For example, a separate spaced electrode array may be placed across the balloon to treat a length of an airway.

The conductive electrical element 2031 travels alongside and generally parallel to one or both of the lines 2011, 2021. The electrode 2004 can be connected through the conductive electrical element 2031 and the electrical connector 2038 to a power source, such as an electrical generator. RF. If the power source is an RF electrical generator, a cable can be attached to connector 2038. The other wire of the RF generator can be connected to an external electrode, such as the external electrode 623 shown in imaginary line in Figure 10B, so that current flows between the expandable electrode 2004 and the external electrode.

The fluid cooled expandable balloon electrode catheter 2000 can be delivered to the lung airways with the balloon 2002 deflated and the electrode 2004 contracted. Electrode 2004 can

ES 2 398 052 T3 maintained in a collapsed or closed configuration to allow catheter 2000 to pass easily through the lungs. Catheter 2000 is moved through the airways until electrode 2004 is in the desired treatment position. Once in position, the fluid (eg, coolant) is allowed to flow through the 2011 inflow line and into the 2002 balloon. The fluid inflates the 2002 balloon which in turn expands the 2004 electrode. The exit of the fluid through the exit line 2021 can be regulated such that the balloon 2002 continues to inflate until the electrode 2004 is brought into contact with or close to the wall of the airway.

Treatment can begin with activation of the RF generator. When the RF generator is activated, RF energy is transmitted through electrical connector 2038, through electrical connection element 2031, through expanded electrode 2004, and into the tissues of the airways. RF energy heats the tissue (eg, superficial and deep tissue) of the airway wall and the 2100 fluid (eg, a coolant) flowing through the 2002 balloon cools the tissue (eg, surface tissues) of the airway wall. The net effect of this surface and deep heating by RF energy and surface cooling by circulating refrigerant 2100 through balloon 2002 is the concentration of heat in the outer layers of the airway wall 100. The refrigerant can be a cooled liquid. The temperature of the connective tissue may be higher than the temperatures of the epithelium, stroma, and / or smooth muscle. For example, the temperature of the connective tissue may be high enough to cause damage to the nerve trunk while other non-target tissues of the airway are kept at a lower temperature to avoid or limit damage to non-target tissues. they are the goal. In other embodiments, heat can be concentrated in one or more of the inner layers (eg, the stroma) of the airway wall or the inner lining (eg, the epithelium) of the airway wall.

Figures 16 and 17 show the effect produced by surface and deep heating by RF energy and surface cooling circulating 2100 refrigerant in balloon 2002. Figure 16 shows a cross-section of the temperature profile taken along the dotted line 2200 of Figure 15B which is perpendicular to the long axis of balloon 2002. Figures 16 and 17 are explained in full detail below.

Figure 16 is a graph with a horizontal axis that corresponds to the depth in the tissue of the airway wall of the contact point or the area of ​​contact with the electrode 2004 in millimeters with a vertical axis that corresponds to the temperature of the tissue. in degrees Centigrade. Point 0 on the graph corresponds to the point or area of ​​contact between ablation electrode 2004 and the airway wall tissue. Three curves A, B and C are shown in the graph and correspond to three different levels of radio frequency energy power that is being delivered to the tissue. The temperature on the graph is up to approximately 100 ° C. The temperature of about 100 ° C, or slightly less, has been shown because it is considered an upper limit for tissue temperature during RF ablation. At approximately 90 ° C, the tissue fluids begin to boil and the tissue coagulates and char at the 2004 ablation electrode, thereby greatly increasing its impedance and compromising its ability to transfer RF energy to the tissue in the via wall. respiratory. Thus, it may be desirable to have tissue temperatures remain below about 90 ° C. At about 50 ° C, a line 2201 represents the temperature above which tissue cell death occurs and below which tissue does not suffer substantial long-term effects (or no long-term effects).

Curve A shown in FIGURE 16 represents what occurs with and without cooling of the ablation electrode 2004 at a relatively low power level, eg, about 10 watts of RF energy. Curve A is divided into three segments A1, A2 and A3. The broken line segment A2 represents a continuation of the exponential curve A3 when no cooling is applied. As can be seen from curve A, the temperature of the uncooled electrode-tissue interface reaches 80 ° C and decreases exponentially as the distance in tissue from the airway 100 increases. As shown, curve A3 crosses the tissue cell death boundary at 50 ° C represented by line 2201 at a depth of approximately 5 millimeters. Thus, without electrode cooling, the depth of cell death that would occur would be approximately 5 millimeters as represented by distance d1. Additional cell death would stop at this power level.

If active cooling is used, the temperature drops to a much lower level, for example about 35 ° C, as represented by curve A1 at the electrode-tissue interface 0 millimeters away. Since this temperature is below 50 ° C, cell death will not begin to occur until a distance of d2 at the point where curve A2 crosses the cell death line at 50 ° C, for example, a depth of 3 millimeters from the surface. Cell death will occur at depths of 3 millimeters to 5 millimeters as represented by the distance d3. Such a refrigerated ablation procedure is advantageous because it allows cell death and tissue destruction to occur at a distance (or a range of distances) from the electrode-tissue interface without destroying the epithelium and tissue immediately underlying it. . In some embodiments, the nerve tissues that run along the exterior of the airways can be ablated without damaging the underlying epithelium or structures, such as the stroma and smooth muscle cells.

ES 2 398 052 T3

Curve B represents what happens with and without electrode cooling at a higher power level, for example, 20 watts of RF energy. Segment B2 of curve B represents a continuation of the exponential curve of segment B3 without cooling. As can be seen, the temperature at the electrode-tissue interface approaches 100 ° C, which may not be desirable because it is a temperature at which tissue fluid boiling and tissue coagulation and charring occur at the interface. of tissue-electrode, thereby appreciably increasing the impedance of the tissue and compromising the ability to deliver additional RF energy to the airway wall. By providing active cooling, curve B1 shows that the temperature at the electrode-tissue interface drops to approximately 40 ° C and that cell death occurs at depths of two millimeters as represented by d4 at a depth of approximately 8 millimeters where curve B3 crosses 50 ° C. Thus, it can be seen that it is possible to provide a much deeper and larger region of cell death using the highest level of power without reaching an undesired high temperature (e.g. a temperature that would result in coagulation and charring). tissue at the electrode-tissue interface). The systems can be used to achieve cell death below the surface of airway epithelia so that the surface does not have to be destroyed, thus facilitating early recovery of the patient undergoing treatment.

Curve C represents an even higher level of power, for example 40 watts of RF energy. Curve C includes segments C1, C2 and C3. The broken line segment C2 is a continuation of the exponential curve C3. Segment C2 shows that the temperature at the electrode-tissue interface far exceeds 100 ° C, and would be inadequate without active cooling. With active cooling, the temperature at the electro-tissue interface approaches 80 ° C, gradually rising to and approaching about 95 ° C, and then dropping exponentially to cross the 2201 line of 50 ° C cell death at a distance of approximately 15 millimeters from the electrode-tissue interface on the epithelial surface of the airways represented by the distance d6. Because the onset temperature is above the 2201 cell death line of 50 ° C, tissue cell death will occur from the epithelial surface at a depth of approximately 15 millimeters to provide large and deep regions of destruction. of tissue.

Figure 17 is a cross-sectional view of the fluid cooled expandable balloon electrode catheter 2000. Flow lines 2100 represent the movement of refrigerant through the expanded balloon 2002. The isotherm curves show the temperatures that are reached at the 2004 electrode on the outer surface of the 2002 balloon and at different depths on the airway wall 100 of the electrode-tissue interface when power is applied to the 2004 electrode and the coolant (for example, a saline solution at room temperature) is delivered to the balloon 2002. By adjusting the rate of power delivery to the electrode 2004, the rate at which saline is passed into the balloon 2002, the temperature of the saline solution, and the size of the balloon 2002, the exact contour and temperature of the tubes can be modified. individual isotherms. For example, by selecting the proper temperature and flow rate of saline and the rate of power delivery to the electrode, it is possible to achieve temperatures where the isotherms A = 60 ° C, B = 55 ° C, C = 50 ° C, D = 45 ° C, E = 40 ° C and F = 37 ° C. Additional settings make it possible to achieve temperatures where the isotherms A = 50 ° C, B = 47.5 ° C, C = 45 ° C, D = 42.5 ° C, E = 40 ° C and F = 37 ° C. Only the areas contained within the 50 ° C isotherm will be heated sufficiently to induce cell death. By extrapolating in 3 dimensions the isotherms shown in Figure 17, a circumferential band 2250 of tissue will potentially be heated above 50 ° C, reserving the tissue near the epithelial 110 of the airway 100. Different temperatures and isotherms can also be achieved.

Figure 18 is a cross-sectional view of a portion of airway 100 and electrode catheter 2000 with fluid-cooled expandable balloon located in airway 100. Due to the undulating shape of expandable electrode 2004, the electrode appears like a multitude of ovals. The balloon 2002 is inflated to accommodate the expandable electrode 2004 and the epithelial surface of the airway 100. Electrode 2004 can be pressed against airway 100. When expanded electrode 2004 transmits RF energy to tissues in airway 100 and balloon 2002 is filled with flowing coolant 2100, RF energy heats deep and superficial tissue of the airway wall 100 and connective tissue 124 while refrigerant 2100 cools the surface tissues of the airway wall 100. The net effect of this surface and deep heating by RF energy and surface cooling by circulating refrigerant 2100 is the concentration of heat in the outer layers of airway wall 100, such as connective tissue 124. A band 2250 of tissue can be selectively heated above 50 ° C. For example, the temperature of connective tissue 124 may be higher than the temperatures of epithelium 110, stroma 112 and / or smooth muscle 114. In addition, one or more of the vessels in the bronchial artery branches 130 may be within band 2250. The heat generated using electrode 2004 can be controlled such that blood flowing through the bronchial artery branches 130 they protect those branches 130 from thermal injury while nerve stem tissue 45 is damaged, even if the nerve tissue is adjacent to the artery branches.

Electrode catheter 2000 can treat tissue without forming an airway wall perforation at the treatment site to prevent or reduce the frequency of infections. It can also facilitate faster healing for the patient of tissue near the cell death region. Catheter 2000 can produce relatively small regions of cell death. For example, a 2 to 3 millimeter band of tissue can be destroyed in the middle of the airway wall 100 or along the outer surface of the airway wall 100.

ES 2 398 052 T3 respiratory. By proper application of power and proper removal of heat from the electrode, lesions can be created to any desired depth without damaging the inner surface of the airway.

Upon completion of the treatment process, the influx of refrigerant into balloon 2002 can be stopped. Balloon 2002 is deflated by causing expandable electrode 2004 to recede away from airway wall 100. When balloon 2002 is fully deflated, fluid-cooled, expandable balloon electrode catheter 2000 can be repositioned to treat other locations in the lung or be removed from airway 100 entirely.

Figures 19A and 19B illustrate a treatment system that may be generally similar to catheter 2000 discussed with respect to Figures 15A-18. A fluid heatsink, expandable balloon electrode catheter 2500 has a single refrigerant line 2511 with associated in-line valve 2512 and a connector 2518 that provides alternate inflow and outflow of heat sink fluid into and out of a balloon 2502.

The fluid heat sink expandable balloon electrode catheter 2500 can be delivered to the lung airways with the balloon 2502 deflated and the electrode 2504 contracted. Catheter 2500 can be moved within the airways until electrode 2504 is in a desired treatment position. Once in position, the heat sink fluid is passed through line 2511 and into balloon 2502, thereby inflating balloon 2502 and expanding electrode 2504. The fluid is passed into balloon 2502 until electrode 2504 is carried away. upon contact with the airway wall 100.

The heat sink fluid passed to the balloon 2502 of the electrode catheter 2500 is generally static and acts as a heat sink to stabilize the temperature of the electrode 2504 and the surface tissues of the airway wall 100. The static heatsink provided by the fluid in balloon 2502 can produce temperature profiles and isotherms similar to those shown in Figures 16 and 17. For example, the electrode catheter 2500 can produce a band of tissue cell death in the connective tissue of the airway while the epithelium, stroma and / or smooth muscle are relatively uninjured. In this way, nerve tissue can be damaged while protecting the other, non-target tissues of the airways.

Figures 20A-21 illustrate a treatment system that may generally be similar to the fluid cooled expandable balloon electrode catheter 2000 shown in Figures 15A-18. Figure 20A is a longitudinal side view of a fluid cooled radial ultrasound guided electrode catheter 3000. Figure 20B is a partial longitudinal sectional view of the fluid-cooled radial ultrasound-guided electrode catheter 3000 taken through balloon 3002 with flow lines 3100 depicting the movement of coolant through expanded balloon 3002 and wave fronts. 3047 ultrasound imaging device to guide the ablation device.

Electrode catheter 3000 generally includes a thermally conductive expandable balloon 3002, an electrode 3004, a conductive element 3031, an influx line 3011, an outlet line 3021, and an ultrasound probe 3045. The expandable electrode 3004 is connected to one end. distal of conductive element 3031. A proximal end of conductive element 3031 is connected to an electrical connector 3038 for transmission of energy (eg, RF energy) to electrode 3004. The proximal end of the refrigerant inflow line 3011 has an in-line valve The proximal end of the refrigerant outlet line 3021 also has an outlet valve 3022. The inflow valve 3012 can be connected to a refrigerant source via the connector 3018. The inflow line internal passage 3011 and the outlet line internal passage 3021 allow fluid to flow from the fluid source into the balloon 3002 and the fluid to flow through another connector 3028 to the refrigerant return, where the refrigerant can be re-cooled and recirculated to the fluid supply.

Inflow line 3011 and exit line 3021 are of adequate length to be passed into the lung and bronchial tree. For example, catheter 3000 may have a length of approximately 80 cm. Figure 20B shows a catheter 3000 adapted to substantially reduce, limit or prevent cross flow, siphoning or back flow between the two lines within balloon 3002. Inflow line 3011 enters the proximal end of balloon 3002, extends the length of balloon 3002, reaches the distal end of balloon 3002, and connects to balloon 3002. Inflow line 3011 has an opening 3013 near a tip 3005 that releases refrigerant into balloon 3002. Fluid flows into balloon 3002 and is then collected in outlet line 3021 through opening 3023. Opening 3023 is generally at the distal end of outlet line 3021 and collects coolant from either direction.

Electrode 3004 is located on a surface of balloon 3002 such that when balloon 3002 is inflated using fluid, electrode 3004 is brought into contact with airway wall 100. The conductive electrical element 3031 travels on one side and parallel to the inflow line 3011, the outlet line 3021 and the ultrasound sheath 3041. The electrode 3004 can be connected through the conductive electrical element 3031 and the electrical connector 3038 to a generator RF. The other wire of the RF generator can be connected to an external electrode so that current flows between the expandable electrode 3004 and the external electrode.

The 3045 ultrasound probe may be an integral part of the fluid cooled ultrasound guided electrode catheter 3000 or it may be a standard independent radial probe such as an ultrasound probe.

ES 2 398 052 T3

Olympus UM-2R-3 or UM-3R-3 driven by a standard Olympus UE-M60 processor, with the fluid cooled radial ultrasound guided electrode catheter 3000 configured to slide over the standard radial ultrasound probe.

The ultrasound system may include a broadband ultrasound transducer operating with a center frequency between about 7 MHz and about 50 MHz. If the 3045 ultrasound probe is an integral part of the 3000 electrode catheter, the 3045 ultrasound probe can be contained within an acoustically matched ultrasound cover 3041 and be connected to an ultrasound drive unit and the processor by the ultrasound connector 3048. In operation, the ultrasound probe 3045 is rotated about its longitudinal axis within the ultrasound cover 3041 by the ultrasound drive unit and the processor through the ultrasound connector 3048 allowing images to be taken (e.g., radial images of 360 °). These images can be taken in a direction perpendicular to the long axis of the 3045 ultrasound probe. Fluid in balloon 3002 can acoustically couple ultrasound probe 3045 to the airway wall.

Electrode catheter 3000 can be delivered to the lung airways with balloon 3002 in a deflated state. Catheter 3000 is placed into the airway near or at the desired treatment location. Once positioned, fluid flows through inflow line 3011 and into balloon 3002. Balloon 3002 inflates to bring electrode 3004 into contact with the epithelial surface of the airway. The outlet of fluid through outlet line 3021 can be regulated such that balloon 3002 continues to inflate until electrode 3004 is brought into contact with airway wall 100.

The ultrasonic drive unit and processor can be activated. The 3045 ultrasound probe can capture images. For example, probe 3045, within ultrasound shroud 3041, can be rotated about its longitudinal axis to produce 360 ​​° radial images of airway and airway wall vessel structures. The electrical connection cable 3031 can serve as a guide over the ultrasound images at the location of the electrode 3004. A section of the wire 3031 that extends along (for example, over the surface) of the balloon 3002 can be visible in the ultrasound imaging. Wire section 3031 can therefore indicate the location of electrode 3004. In some embodiments, the nerve trunks and bronchial blood can be identified on the ultrasound images and the fluid-cooled ultrasound-guided electrode catheter 3000 can be rotated until the electrode 3004 is brought into the vicinity of the first nerve trunk. Four. Five.

When the RF generator is activated, the generator transmits RF energy through electrical connector 3038, through electrical connection cable 3031, through expanded electrode 3004, and to airway tissues. The RF energy heats the surface and deep tissue of the airway wall 100 and the connective tissue 124 in the area immediately overlying the electrode 3004 and the coolant flowing 3100 through the balloon 3002 cools the surface tissues of the wall 100 airway. The net effect of this surface and deep RF energy heating and surface cooling by circulating refrigerant 3100 through balloon 3002 is the concentration of heat in the outer layers of airway wall 100 immediately overlying electrode 3004. For example, the temperature of connective tissue 124 in the area of ​​a single nerve trunk 45 may be higher than the temperatures of epithelium 110, stroma 112, and / or smooth muscle 114. For example, the temperature of the connective tissue may be high enough to cause nerve tissue damage 45 while other non-target tissues of the airway 100 are kept at a lower temperature to avoid or limit damage to the tissues that they are not the goal. Treatment can be repeated in other areas as needed.

Figure 21 is a cross-sectional view of a portion of airway 100 and fluid-cooled ultrasound-guided electrode catheter 3000 in airway 100. The cross-section is taken through electrode 3004 itself.

Balloon 3002 can be matched to electrode 3004 and airway epithelial surface 100. When RF energy is transmitted through electrode 3004 to airway tissues and balloon 3002 is filled with flowing coolant 3100, the RF energy heats the surface and deep tissue of the airway wall 100 immediately overlying the electrode 3004. Refrigerant 3100 flows to control the temperature of the surface tissues of the airway wall 100. The net effect is the concentration of heat in the outer layers of the airway wall 100 immediately above the electrode 3004 producing a single target volume 3250 of heated tissue above a treatment temperature (eg, approximately 50 ° C). . For example, the temperature of connective tissue 124 in the region of a single nerve stem 45 in the area immediately above electrode 3004 may be higher than the temperatures of epithelium 110, stroma 112, and / or smooth muscle 114.

The vessels of the bronchial artery branches 130 may be within or near the volume of heating produced during the application of RF energy. The heat generated by electrode 3004 can be controlled in such a way that blood flowing through bronchial artery branches 130 protects those branches 130 from thermal injury while nerve tissue 45 is damaged, even if nerve tissue is damaged. next to the artery branches.

ES 2 398 052 T3

The embodiments described herein can be used in the respiratory system, in the digestive system, in the nervous system, in the vascular system, or in other systems. For example, the elongated assemblies described herein can be delivered through blood vessels to treat the vascular system. The treatment systems and their components described herein can be used as an adjunct during another medical procedure, such as minimally invasive procedures, open procedures, semi-open procedures, or other surgical procedures (eg, lung volume reduction surgery) that preferably provide access to a desired target location. Various surgical procedures on the chest can provide access to lung tissue. The access techniques and procedures that are used to provide access to a target region can be performed by a surgeon and / or a robotic system. Those skilled in the art recognize that there are many different ways to access a target region.

The elongated assemblies described herein can be used with guidewires, delivery sleeves, optical instruments, introducers, trocars, biopsy needles, or other suitable medical equipment. If the target treatment site is at a distant location in the patient (eg, a treatment site near the lung root 24 of Figure 1), a wide variety of instruments and techniques can be used to access the site. The flexible elongated assemblies can be easily positioned within the patient using, for example, steerable delivery devices, such as endoscopes and bronchoscopes, as discussed above.

Elongated semi-rigid or rigid assemblies can be delivered using trocars, access ports, rigid delivery sleeves using semi-open procedures, open procedures, or other delivery tools / procedures that provide a somewhat straight delivery path. Advantageously, the rigid or semi-rigid elongated assemblies can be rigid enough to access and treat remote tissue, such as the vagus nerve, nerve branches, nerve fibers, and / or nerve trunks along the airways, without administering the elongated sets through the airways. The embodiments and techniques described herein can be used with other procedures, such as bronchial thermoplasty.

The various embodiments described above can also be combined to provide additional embodiments. These and other changes to the embodiments can be made in light of the detailed description above. The embodiments, features, systems, devices, materials, methods, and techniques described in this specification may, in some embodiments, be similar to one or more of the embodiments, features, systems, devices, materials, methods, and techniques described in the application. US Provisional Patent No. 61 / 052,082 filed May 9, 2008; US Provisional Patent Application No. 61 / 106,490 filed October 17, 2008; and US Provisional Patent Application No. 61 / 155,449 filed February 25, 2009. In addition, the embodiments, features, systems, devices, materials, methods, and techniques described in this specification may, in certain embodiments, be applied to or used with respect to one or more of the embodiments, features, systems, devices, materials, methods. and techniques described in the aforementioned US Provisional Patent Application No. 61 / 052,082 filed May 9, 2008; US Provisional Patent Application No. 61 / 106,490 filed October 17, 2008; and U.S. provisional patent application No. 61 / 155,449 filed on February 25, 2009.