Device, method, and system for treating chronic bronchitis

Abstract

To provide an improved system for treating a pulmonary airway wall of a patient.SOLUTION: A system of the present invention includes: a bronchoscope configured to be advanced inside the lung of a patient, having a flexible body part, a bronchoscope tip equipped with a camera, and a working channel outlet port; a treatment device having a long-sized member, the long-sized member being configured to be introduced inside the pulmonary airway of the patient through the working channel outlet port of the bronchoscope, and having an expandable grinding feature part; and means for generating vibration movement, linear movement, or expansion in the grinding feature part so that the grinding feature part grinds the epithelia in a non-traumatic manner along the wall of the pulmonary airway of the patient.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to devices, methods and systems for treating chronic bronchitis. [Background technology]

[0002] The airways of the lungs are made up of various layers, each containing one or more types of cells. The innermost cell layer of the airway wall is the epithelium or epithelial layer, which contains pseudostratified columnar epithelial cells PCEC, goblet cells, and basal cells. Goblet cells are responsible for secreting mucus, and the inner wall of the airway is entirely lined with mucus. The pseudostratified columnar epithelial cells have cilia that extend into this mucus covering. The cilia, which are attached to the epithelium, move towards the nose and mouth, pushing the mucus up the airway to be cleared.

[0003] The basal cells are attached to the basement membrane, and beneath it lies the submucosa or lamina propria. The lamina propria contains various types of cells and tissues, including smooth muscle. Smooth muscle is involved in bronchial constriction and dilation. The lamina propria LP also contains the submucosal glands, which are involved in many of the inflammatory responses to pathogens and foreign bodies. In addition, nerves are present. Branches of the vagus nerve are located on the outside of the airway wall or extend into the airway wall to innervate mucous glands, airway smooth muscle, connective tissue, and various types of cells, including fibroblasts, lymphocytes, and mast cells. Finally, beneath the lamina propria lies the cartilage layer. The pseudostratified columnar epithelial cells and goblet cells are connected to each other by tight junctions and adherens junctions. The pseudostratified columnar epithelial cells and goblet cells are connected to the basal cells by desmosomes. The basal cells are connected to the basement membrane by hemidesmosomes.

[0004] Pulmonary problems Chronic bronchitis is characterized by persistent airflow obstruction, chronic cough and sputum production for more than 3 months per year for 2 consecutive years. Airway inflammation occurs in conjunction with a thickening of the epithelial layer.

[0005] A variety of pulmonary disorders and diseases can cause pulmonary obstruction, some of which are briefly described below. Chronic obstructive pulmonary disease (COPD) Chronic obstructive pulmonary disease (COPD) is a common disease characterized by chronic and irreversible airflow obstruction and persistent inflammation due to harmful environmental stimuli such as cigarette smoke or other pollutants. COPD includes a variety of diseases with chronic bronchitis that primarily affect the airways, whereas emphysema affects the alveoli, the air sacs that carry out gas exchange. Some people experience features of both.

[0006] In chronic bronchitis, the structure and function of the airways are altered. In chronic bronchitis, harmful stimuli such as inhaled cigarette smoke or pollutants are recognized as foreign by the airways, triggering an inflammatory cascade. Neutrophils, lymphocytes, macrophages, cytokines and other inflammatory markers are found in the airways of people with long-term exposure to stimuli, and chronic inflammation and tissue repair of the airways occur. Goblet cells may undergo hyperplasia, increasing the number of cells, or hypertrophy, increasing the size of the goblet cells. In general, in response to inflammatory stimuli, goblet cells secrete more mucus to remove inhaled toxins. Excess mucus further narrows the airway lumen, making obstructions more likely. Harmful stimuli damage the cilia, so excess mucus remains in the airway lumen, impeding proximal-to-apical airflow during inspiration and distal-to-proximal airflow during expiration. Smooth muscle may become hypertrophied and thickened, causing bronchoconstriction. Submucosal glands may also undergo hyperplasia and hypertrophy, increasing the overall thickness of the airway wall, further constricting the luminal diameter.

[0007] In addition to the reduction in the luminal diameter of the airways, hypersecretion of mucus can lead to exacerbations and a deterioration in general health. As a result of excess mucus and damage to the cilia, pathogens such as bacteria (e.g., Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Staphylococcus aureus, Pseudomonas aeruginosa, Burkholderia cepacia, opportunistic gram-negative bacteria, Mycoplasma pneumoniae, Chlamydia pneumoniae, etc.), viruses (rhinoviruses, influenzae parainfluenza viruses, respiratory syncytial viruses, coronaviruses, herpes simplex viruses, adenoviruses) and other microorganisms (fungi, etc.) may proliferate and cause exacerbations, resulting in a range of symptoms. These include worsening cough, congestion, increased sputum volume, changes in sputum quality and / or shortness of breath. Treatment of acute exacerbations may require oral or intravenous steroids, antibiotics, oxygen, endotracheal intubation and mechanical ventilation.

[0008] Chronic obstructive pulmonary disease (COPD) is a common, progressive, debilitating, and often life-threatening lung disease. COPD patients are diagnosed with emphysema, chronic bronchitis, or more commonly, a combination of both. Symptoms of COPD include persistent coughing, especially a mucus-producing cough, shortness of breath (especially during exercise), wheezing while breathing, barrel chest deformation, and chest muscle tension due to chest expansion with barrel chest deformation. In the end stage, the disease eventually almost completely blocks the outflow of gas from the lungs, resulting in a condition more similar to slow and persistent suffocation. These symptoms may initially only mildly interfere with daily life, but then speech and basic breathing may become difficult. COPD reduces gas exchange between oxygen and carbon dioxide, resulting in circulatory problems, such as reduced oxygen levels in the blood, brain, and heart muscle. This adversely affects mental alertness and increases the strain on the heart, causing it to beat very quickly.

[0009] According to the National Institutes of Health, COPD is the third leading cause of death in the United States. The American Lung Association reports that more than 12 million people in the United States have been diagnosed with COPD. However, approximately 24 million more people may have the disease without knowing it. Approximately 65 million people worldwide have COPD.

[0010] COPD can develop in people with a genetic disorder called alpha-1 antitrypsin deficiency (A1AT deficiency) or by breathing air under environmental conditions such as air pollution, polluted air, or less than ideal working conditions. However, COPD most commonly develops in people over 40 years old who have a history of smoking. Cigarette smoke is made up of over 4000 chemicals, many of which are toxic. Both the smoke that the smoker inhales (through the filter) and the smoke from the burning end are toxic. The three main components that are harmful to health are tar, nicotine, and carbon monoxide. Tar is deposited in the lungs and promotes a series of changes that lead to obstructive pulmonary disease and lung cancer. Nicotine is an addictive component of tobacco that stimulates the nervous system, reduces the diameter of arterioles, and releases adrenaline, increasing heart rate and blood pressure. In addition, nicotine increases the stickiness of platelets, increasing the risk of blood clotting. Carbon monoxide binds irreversibly to hemoglobin, preventing it from binding oxygen effectively. As a result, greater pressure is required to deliver the same amount of oxygen, placing a strain on the heart muscle.

[0011] Tobacco smoke and secondhand smoke enter the bronchi through the trachea. The toxic smoke then travels to the bronchioles, which contain tiny collections of air sacs called alveoli. Within the alveoli are tiny blood capillaries. In healthy people, oxygen moves from the alveoli into the capillaries and bloodstream during inspiration, and oxygen-rich blood is then distributed to the entire body via the arterial system. At the same time, carbon dioxide is carried from the blood flowing to the capillaries via the venous system into the alveoli to be expelled from the body with exhaled air. This process is called gas exchange. Healthy air sacs are elastic enough to allow this exchange to occur as the lungs change volume with the breathing cycle. However, inhaling smoke eventually destroys this elasticity and the lung tissue itself.

[0012] Chronic obstructive pulmonary disease (COPD) is a lung disease in which narrowing of the airways restricts the flow of air in and out of the lungs, causing shortness of breath. COPD includes both chronic emphysema and chronic bronchitis and is primarily caused by an abnormal inflammatory response in the lungs caused by harmful particles or gases, most commonly smoking or polluted air. Other causes of COPD include intensive or prolonged exposure to workplace dust, such as in coal or gold mining or in the cotton textile industry, which contain chemicals such as cadmium and isocyanates, and exposure of non-smokers to welding fumes and harmful particles and gases emitted by smokers. Lung damage, inflammation of the lung airways (alveoli), and clogged bronchial passages with mucus are symptoms of bronchitis and emphysema.

[0013] In general, in lungs affected by COPD, enlargement of the bronchi and alveoli is observed. Alveoli are tiny grape-shaped air sacs located at the ends of the smallest bronchi. They are the site of gas exchange and are considered the main functional unit of the lungs. They are densely covered with capillaries extending from the capillaries around the bronchi, and blood is delivered to the capillaries by the pulmonary arteries and removed by the pulmonary veins. When the alveoli expand with inhaled air, oxygen diffuses into the blood in the capillaries to reach the tissues of the body. Carbon dioxide diffuses from the blood to the lungs to be exhaled.

[0014] asthma Asthma is a disease of the airways characterized by airway hyperresponsiveness. In asthma, epithelial hyperplasia, mucus hypersecretion due to excessive secretion from goblet cells and submucosal glands, and smooth muscle hyperplasia can occur. As described herein, mucus hypersecretion or excess mucus can allow pathogens to thrive and cause infection.

[0015] Interstitial pulmonary fibrosis Interstitial pulmonary fibrosis is thought to be caused by acute injury to lung tissue that induces chronic and abnormal inflammation. In response to the inflammation, fibroblasts become activated, leading to pulmonary fibrosis, scarring and deterioration of lung function. Only 20-30% of patients survive for five years after diagnosis.

[0016] Cystic fibrosis Cystic fibrosis is a genetically-driven systemic disease with pulmonary manifestations. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene result in thickened secretions that cannot be excreted. Chronic inflammation leads to airway tissue repair and hypersecretion by goblet cells and submucosal glands, resulting in airway narrowing and infections that are difficult to completely resolve.

[0017] Bronchiectasis Bronchiectasis refers to a condition in which airways become enlarged, thickened, and scarred. It is typically caused by infection, other conditions that damage the airway walls and prevent the airways from clearing mucus, or both. This can progress to recurrent infections as the airways lose their ability to clear mucus. Each infection causes more damage, eventually resulting in moderate airflow obstruction. Bronchiectasis can be caused by genetic disorders such as primary ciliary dyskinesia, but can also be idiopathic.

[0018] lung treatment In some cases, the most effective treatment for lung damage is lifestyle changes, especially smoking cessation. This is especially true for COPD. However, many patients are unable or unwilling to quit smoking. A variety of treatments currently exist to alleviate the symptoms of lung damage.

[0019] dosage COPD can be managed with one or more medications, such as short-acting beta agonists (SABAs), long-acting beta agonists (LABAs), long-acting anticholinergics (LAMAs), steroids, chronic antibiotic therapy, and PDE4 inhibitors such as roflumilast. SABAs and LABAs act on beta receptors in airway smooth muscle to dilate the bronchodilation. LAMAs act via anticholinergic pathways to inhibit the release of acetylcholine to dilate the bronchodilation. LABAs and LAMAs have been shown to reduce the frequency of shortness of breath and exacerbations and improve quality of life, but their effect on reducing mortality has not been confirmed. The LAMA tiotropium slows the rate of decline in lung function and increases the time to exacerbation. Inhaled corticosteroids directly target inflammation. Inhaled corticosteroids have been shown to reduce exacerbations, but have little effect on lung function or mortality. Combinations of LABAs, LAMAs, and inhaled corticosteroids have already been developed. Inhaled oxygen is known to reduce shortness of breath and improve mortality, but these results are limited to advanced disease as defined by strict criteria and require long-term administration via nasal cannula or alternative devices.

[0020] COPD can also be addressed with one or more oral medications, such as PDE4 inhibitors, steroids, or antibiotics. Roflumilast is an oral medication and is a selective, long-acting inhibitor of the PDE4 enzyme. It has a very strong anti-inflammatory effect, but is poorly tolerated and has adverse effects such as diarrhea, weight loss, nausea, loss of appetite, and abdominal pain. To treat acute inflammation during exacerbations, patients can be prescribed oral steroids such as prednisone. Patients have been known to continue oral steroids for extended periods if cessation of the medication would cause an exacerbation to reoccur. Oral steroids have various side effects, such as weight gain, insomnia, thyroid dysfunction, and osteoporosis. Long-term administration of azithromycin or antibiotics has been shown to reduce the frequency of COPD exacerbations. This effect of antibiotics is achieved by antibacterial effects through the killing of pathogens causing the exacerbation and other mechanisms such as the reduction in mucus secretion, which has been seen with macrolide antibiotics. Side effects of long-term antibiotic use include hearing loss and antibiotic resistance.

[0021] Many patients are non-adherent to prescribed respiratory medications. Inhalation therapy requires deep inspiration along with synchronization with inspiration, which many patients, especially the elderly, cannot perform. Others may omit medications due to cost, experience of side effects, or both. Thus, all of the above factors can lead to inappropriate and inconsistent medication use.

[0022] Asthma is a disease that can range in severity from mild to persistent in adult patients. Mild asthma can be adequately managed by avoiding causative factors and taking short-acting beta agonists (SABAs). On the other hand, the mainstream treatment for persistent asthma is inhaled glucocorticoids. Clinical trials have confirmed that regular use of inhaled glucocorticoids reduces the need for rescue inhalers, improves lung function, relieves symptoms, and prevents exacerbations. Some patients benefit from the addition of leukotriene modifiers or LABAs. Tiotropium can be used as another option to improve lung function over inhaled glucocorticoids alone. Particularly severe cases may require temporary or long-term treatment with oral corticosteroids.

[0023] There is no known cure for interstitial pulmonary fibrosis (IPF). The mainstay of treatment is supplemental oxygen when needed and preventative measures such as vaccinations. Pirfenidone is an antifibrotic drug approved for IPF that aims to slow the formation of fibroblast foci, collagen deposition, and inflammatory cell infiltration in the disease. In clinical trials, pirfenidone has been shown to slow the decline in vital capacity (a measure of lung function) and has demonstrated a reduction in all-cause mortality. Nintedanib is another drug approved for IPF that acts via a receptor blocker against multiple tyrosine kinases that mediate the synthesis of fibrogenic growth factors (e.g., platelet-derived growth factor, vascular endothelial growth factor, fibroblast growth factor). Nintedanib has been shown to slow the rate of disease progression in IPF. No device therapy has yet been approved for IPF.

[0024] Treatment of cystic fibrosis has rapidly evolved from chest physical therapy and supplemental oxygen therapy to therapies targeting the underlying defect in the CFTR gene. Ivacaftor is a CFTR enhancer that improves chloride transport through ion channels and is FDA approved for some CFTR gene mutations. Clinical trials have confirmed that it improves FEV1 and reduces the frequency of exacerbations. In addition, it improves mucociliary and cough clearance. However, when used alone in patients with the most common delta F508 deletion, it has not improved outcomes. Other targeted therapies are in clinical trials. Chronic antibiotics, including azithromycin, which has anti-inflammatory effects, and inhaled tobramycin, which is used to treat Pseudomonas aeruginosa, are commonly prescribed for CF. As with other obstructive diseases, CF patients benefit from bronchodilators, including FABAs and FAMAs. Medications that promote airway secretion clearance include inhaled DNasc, which reduces mucus viscosity, inhaled hypertonic saline, which draws water in mucus from the airways, and inhaled N-acetylcysteine, which breaks disulfide bonds in mucus glycoproteins. Oral steroids are used in the event of an exacerbation, but guidelines recommend against long-term use of inhaled corticosteroids.

[0025] Bronchiectasis is an anatomical sign of the host response to injury, resulting in hyperdilation of the airway lumen diameter. For this reason, treatment is often directed at the cause of the underlying disease; for example, nontuberculous mycobacterial infections, primary immunodeficiencies, allergic bronchopulmonary, and aspergillosis. Treatment of acute exacerbations focuses on treating the harmful bacterial pathogens with antibiotics. Macrolide and nonmacrolide antibiotics have been shown to reduce the frequency of exacerbations. The use of inhaled antibiotics in the absence of CF is unclear, as is the use of mucolytic agents. Bronchodilators can also be administered to patients who show signs of airway obstruction on spirometry.

[0026] Treatment of primary ciliary dyskinesia (PCD) is aimed at improving secretion clearance and reducing respiratory infections with daily chest physiotherapy and prompt treatment of respiratory infections. The role of nebulized DNase and other mucolytic agents is unclear.

[0027] Respiratory tract infections caused by pathogens in the respiratory tract can occur in conjunction with the above diseases and are usually treatable with antibiotics. Unfortunately, drug development in this field has declined and currently available treatments are very limited. One problem is that there is no single drug that can treat the wide variety of pathogens present in a patient. Saliva tests can be performed to determine resident pathogens, but this may require obtaining specimens by bronchoscopy using special techniques to avoid sample contamination, and often other collection methods and modalities. Another problem is that currently available drugs are not always effective, as pathogens may develop resistance to these therapies.

[0028] Bronchitis is an inflammation of the bronchi, the airways that carry air to the lungs. When the cells lining the bronchi become irritated, the tiny hairs (cilia) that normally trap and remove airborne particles stop working. The formation of substances (mucus and phlegm) associated with the irritation (inflammation) also increases, causing the passages to become blocked. The mucus / phlegm, along with inflammation of the bronchial lining, constrict the airways, making them smaller and narrower and making it harder for air to get in and out of the lungs. A persistent, severe cough develops as the body responds to clear the mucus / phlegm from the narrowed airways. Chronic bronchitis is often misdiagnosed or overlooked until it has progressed.

[0029] Compared to normal bronchi, the lining of bronchi affected by chronic bronchitis is thickened, resulting in a reduced diameter of the airway lumen. When air is inhaled, irritants in the air cause the lining of the bronchi to thicken or expand. When the lining of the bronchi becomes inflamed, the tiny hairs (cilia) that normally protect the bronchi from foreign objects no longer function. As a result, mucus and phlegm form in response to the irritation (inflammation), reducing the diameter of the airways and causing the passages to become clogged and narrow. The reduced diameter of the airway lumen prevents proper flow of air in and out of the lungs, inhibiting the lungs' natural function.

[0030] With repeated irritation, the lung epithelium produces more goblet cells which increase the amount of mucus. The mucus is transported by the lung cilia to the central airways, from where it is expelled by coughing. This is the lung's primary mechanism for removing harmful particles and pollutants. With repeated episodes of inflammation, the airway walls become damaged and the cilia are unable to regenerate, eliminating the primary means of transporting mucus from the lungs. With reduced mucus transport, mucus accumulates in the airways, where bacteria collect and remain, leading to repeated infections. The infection causes coughing, which further inflames the airways. This cycle continues, as the body produces more goblet cells and other cells in the airway walls to combat the invasion, inflammation, and infection. This cycle also causes the patient to cough for extended periods of time, or even continuously. This cycle results in standard tissue wound healing in the airway walls, and constant tissue repair with the production of more goblet cells and other cells that secrete mucus. This causes airflow to be restricted by increasingly thicker airway walls.

[0031] Emphysema refers to a condition in which the walls of the alveoli collapse or are destroyed, causing them to become abnormally enlarged. In lungs affected by emphysema, the alveoli are enlarged and congested. When the alveoli collapse or are destroyed, the surface area available for the exchange of oxygen and carbon dioxide during breathing is reduced, leading to poor oxygenation (a condition in which the body has low levels of oxygen and high levels of carbon dioxide). In addition, the lungs themselves lose their elasticity, causing a loss of the support structures within the lungs that maintain the airways, often causing the airways to collapse, further restricting airflow.

[0032] In emphysema, individual alveoli become enlarged and congested because their deterioration or destruction causes the surrounding tissue to lose elasticity. Due to the loss of elasticity of the surrounding tissue, the abnormally enlarged alveoli fill with air easily during inspiration but are unable to empty the lungs during expiration.

[0033] In both chronic bronchitis and emphysema COPD, airflow is most reduced when breathing out (expiration / breath) because air pressure in the lungs tends to compress rather than expand the airways. COPD patients may not be able to completely exhale before the next breath is required. At the start of the next breath, a small amount of air from the previous breath remains in the lungs. The lungs fill easily but cannot empty adequately, resulting in progressive overexpansion or dynamic hyperinflation, which makes the respiratory mechanics less efficient. The combination of reduced oxygenation and overexpansion / hyperinflation of the lungs makes breathing increasingly difficult.

[0034] To compensate for the lack of breathing, patients with advanced COPD may breathe faster, which often results in dyspnea (chronic shortness of breath). Patients who are less short of breath can tolerate low oxygen and high carbon dioxide levels in their body, but eventually develop headaches, drowsiness, high blood pressure, and even heart failure. Severe COPD can also lead to non-pulmonary complications, such as depression, muscle loss, weight loss, pulmonary hypertension, osteoporosis, and heart disease.

[0035] Currently, there is no cure for chronic bronchitis. Most treatments focus on reducing the severity of symptoms and preventing further damage. The most common types of treatments include lifestyle changes, medications, and supplemental oxygen. Examples of medications include bronchodilators, which open up the airways; corticosteroids, which reduce inflammation, swelling, and phlegm production; and expectorants, which stop the coughing that often occurs with chronic bronchitis.

[0036] Lung volume reduction surgery (LVRS) is a treatment option for patients with severe emphysema. In LVRS, doctors remove about 20-35% of the damaged lung or the compromised space that occupies the lung tissue from each lung. By making the lungs smaller, the remaining lungs and the surrounding muscles can function more efficiently, making breathing easier.

[0037] Generally, LVRS is performed through techniques such as thoracoscopic surgery, sternotomy, and thoracotomy. Thoracoscopic surgery is a minimally invasive technique in which three small incisions (approximately 1 inch each) are made between the ribs on each side. A video-assisted thoracic surgery (VATS) instrument or a video endoscope is placed through one of the incisions, allowing the surgeon to visualize the lung. Specialized surgical staplers / graspers are inserted through the other incisions, which are used to cut away the damaged portion of the lung and reclose the remaining portion of the lung so that blood and air do not leak out. The incisions are closed with dissolvable sutures. Thoracoscopic surgery can be used to treat one or both lungs, allowing evaluation and removal of any portion of the lung. This technique also allows parts of the lung to be laser treated under a thoracoscopic procedure. On the other hand, thoracoscopic laser treatment can only remove emphysematous tissue at the lung surface, but cannot be applied to both lungs simultaneously.

[0038] In sternotomy, or open thoracotomy, an incision is made through the sternum to expose both lungs. In this procedure, both lungs are sequentially reduced in size. The sternum is wired together and the skin is then closed. This method is the most invasive and is used when thoracoscopic surgery is not appropriate. Generally, this technique is only applied to upper lobe disease of the lungs.

[0039] Thoracotomy is often performed when the surgeon cannot clearly see the lungs with a thoracoscope or when dense adhesions (scar tissue) are present. A 5-12 inch (12.7-30.48 cm) long incision is made between the ribs. The ribs are separated without being destroyed to expose the lungs. In this technique, only one lung is reduced, and the muscle and skin are closed with sutures. Summary of the Invention [Problem to be solved by the invention]

[0040] Although the goal of surgical treatment of COPD is to prolong life by relieving shortness of breath, preventing secondary complications, and improving functional status to improve quality of life, LVRS for COPD is a riskier procedure than cardiac surgery. Other risks associated with LVRS include, but are not limited to, air leakage from the lung tissue into the pleural cavity at the suture line, pneumonia, bleeding, stroke, heart attack, and death (due to the worsening of any of the aforementioned complications). Due to the risks associated with LVRS, despite advances in medical therapy, a significant number of patients with severe COPD face a worsening quality of life and a significantly higher risk of death. Over the years, many minimally invasive methods have been developed as alternatives to LVRS that address the problems associated with LVRS and focus on selective destruction of specific areas of unwanted tissue. These methods include cryosurgery, nonselective chemical ablation, radiofrequency (RF), ultrasound, microwave, laser, and thermoelectric ablation. However, these developments have been plagued by many surgery-related obstacles, including the large and difficult to manipulate operating mechanisms and lack of control over the treatment of the affected area. This is because the traditionally used ablation techniques are non-selective, mediating cell death, such as by using extreme heat or cold. Such methods of localized destruction of the affected area have been found to have non-selective adverse effects on blood vessels, nerves, and connective structures adjacent to the ablation area. Destruction of nerves locally impairs the body's natural ability to sense and regulate homeostasis and repair processes in and around the ablation area. Destruction of blood vessels prevents the removal of debris and debris. As a result, repair systems are halted or limited, immune system elements are prevented from returning, and normal blood flow, which carries substances such as hormones to the target area, is generally inhibited. In the absence of a steady introduction of new or natural materials to the damaged area, remodeling of blood vessels and airway linings is delayed, as repositioning of cellular material is inefficient or impossible. Thus, the state of tissue following traditional ablation treatment is not optimal for self-repair to regenerate the target area.

[0041] Advances in medical equipment and techniques have rekindled interest in the surgical treatment of COPD. The effects of surgical treatment of COPD are very similar to those of LVRS, but with fewer risks and complications associated with traditional LVRS techniques. These recent developments have allowed for improved regenerative processes after treatment. One such technique is irreversible electroporation (IRE), a pioneering technique in the field of surgery that allows for improved tissue ablation treatments. IRE has the distinct advantage of inducing cell necrosis non-thermally, without increasing / decreasing the temperature of the ablation area. This avoids some of the adverse effects of temperature changes that occur in ablation techniques such as radiofrequency (RF) ablation, microwave ablation, and even cryoablation. IRE also allows for focused and localized treatment of the affected area. This focused and localized treatment makes it useful for treating delicate and complex organs such as the lungs. However, this technique requires the application of extremely high voltages to the lungs, which are in close proximity to the heart. This can disrupt the signals that activate the myocardium and can interfere with pacemakers or other sensitive electronic devices present in the patient's body.

[0042] As is apparent from the above, there is a need for non-thermal, non-cryo-ablative, non-electromagnetically excited devices and methods for inducing cellular necrosis in lung tissue and airway lumens. It is also desirable that these devices and methods be easily delivered and deployed in lung tissue. These devices and methods should efficiently kill mucus-secreting cells and effect wound healing of lung tissue in a manner that regenerates the tissue with fewer mucus-secreting cells compared to the tissue that was replaced. [Means for solving the problem]

[0043] The present invention relates to devices and methods for performing ERS (epithelial replacement surgery), a minimally invasive technique in which a device with an abrasive surface or abrasive features is pressed against a target lung tissue or unwanted tissue, and the application of force creates a relative movement to the tissue or to the point of contact with the tissue, resulting in abrasive cellular necrosis of the target tissue without destroying vital structures of the target tissue, such as intact airway walls, tubes, blood vessels, and nerves. More specifically, the devices and methods allow for the en bloc removal of mucus- and phlegm-producing cells, which causes cell membrane loss and cell death, potentially resulting in the disruption of homeostasis and autoregulation of the lung epithelium, while leaving behind structures and tissues for connection and support. Thus, the destruction of unwanted tissue is achieved in a controlled, localized area, while leaving surrounding healthy tissue, organs, etc. By using the devices and methods to damage or remove epithelial cells, the epithelium is replaced, healed, or regenerated by structures that include normal and healthy replacement tissue or abnormal scar tissue. In either case, the new tissue has a reduced number of mucus-producing cells. This differs from other devices and methods that use light, thermal ablation, cryoablation or electromagnetic energy, which are known to completely destroy cells and other vital surrounding organs and body structures.

[0044] The devices, systems, and methods described herein are used to treat or manipulate lung tissue and treat lung diseases or disorders such as COPD or COPD-related (e.g., chronic bronchitis, emphysema), asthma, interstitial pulmonary fibrosis, cystic fibrosis, bronchiectasis, primary ciliary dyskinesia (PCD), acute bronchitis, and / or other lung diseases or disorders. One or more features of these embodiments may be combined with one or more features of one or more other embodiments to form new embodiments within the scope of the present disclosure. Examples of lung tissue include, but are not limited to, epithelium (goblet cells, pseudostratified ciliated columnar epithelial cells, and basal cells), lamina propria, submucosa, submucosal glands, basement membrane, smooth muscle, cartilage, nerves, pathogens present near or within the tissue, or combinations thereof.

[0045] The methods, devices and systems disclosed herein treat lung tissue by delivery of energy characterized by manual motion, linear or rotational pulses and combinations of these motions to the target tissue using an abrasive instrument or surface with an abrasive media to remove the target tissue without causing a clinically significant inflammatory healing response. However, in other embodiments, some degree of inflammatory healing response is tolerated. Also, healthy new target tissue is regenerated within a few days of treatment. In other embodiments, the nature of the energy delivery and abrasive action destroys or otherwise removes pathogens present in the airways without substantially affecting or damaging other airway structures.

[0046] In some embodiments, selective treatment includes selectively removing specific cells from the airway wall. In some embodiments, removal includes cell detachment. For example, cell detachment is achieved by scraping the lumen of the diseased airway. In some embodiments, removal includes cell death. For example, cell death is achieved by disrupting the cell wall of epithelial cells. Alternatively, cell death may occur by other mechanisms. Similarly, removal may include abrasion, sloughing, injury, or a combination of other mechanisms.

[0047] In some embodiments, the particular cells include epithelial cells but do not include basal cells. For example, the epithelial cells include abnormal or hyperplastic goblet cells. Alternatively, the epithelial cells include abnormal pseudostratified ciliated columnar epithelial cells.

[0048] In some embodiments, the specific cells include cells of a basement membrane and the selective treatment comprises modifying cells of the basement membrane to modify the permeability of the basement membrane. In some embodiments, the specific cells include submucosal glands and the selective treatment comprises causing cell death of the submucosal glands. In some embodiments, the specific cells include pathogens and the selective treatment comprises causing cell death of the pathogens. In some embodiments, the selective treatment comprises selectively modifying specific cells to alter mucus secretion.

[0049] In some embodiments, the cells comprise epithelial cells and do not comprise basal cells. For example, the epithelial cells comprise abnormal or hyperplastic goblet cells. Alternatively, the epithelial cells comprise abnormal pseudostratified ciliated columnar epithelial cells.

[0050] In some embodiments, the cells comprise lymphocytes, macrophages, eosinophils, fibroblasts, plasma cells, mast cells, leukocytes, or combinations thereof. In some embodiments, the cells comprise submucosal glands and removing comprises causing cell death of the submucosal glands. In other embodiments, the cells comprise pathogens.

[0051] The present invention includes novel medical devices, methods of use, systems, methods of patient selection, methods of determining whether retreatment is recommended, and means of assessing patient health to achieve improved quality of life and increased longevity for individuals with chronic obstructive pulmonary disease (COPD). More specifically, the present invention relates to devices and methods for disrupting, killing, and / or removing epithelial and mucus-secreting cells by specific methods that allow for regeneration of these tissues while limiting the number of mucus-secreting cells. The devices described herein may use blades, sharp corners, edges to cut, scrape, shear, slice, microtome, or other abrasive methods, vibrate rough surfaces against tissue, or use textured materials, bristles, needles, brush tips, or other shapes that cause abrasive destruction of living cells. These devices may aspirate tissue from the patient to promote tissue regeneration, improve lung function, and reduce complications associated with other procedures that deliver cryogenic fluids or procedures that deliver thermal or electromagnetic energy.

[0052] In one aspect of the present invention, a therapeutic device is provided for abrasive contact with the walls of animal or human lung airways to inhibit mucus secretion. In some aspects of the invention, the abrasive contact is provided by abrasive media, abrasive mesh and / or blades, abrasive features such as edges, triangles, squares or circles.

[0053] In another aspect of the invention, a device is provided that cuts, scrapes, cuts, scrapes, slices, microtomes or otherwise abrades using blades, sharp corners, edges, rough materials, uneven materials, bristles, needles, brush tips or other shapes that cause abrasive disruption of living cells.

[0054] In another aspect of the invention, a therapeutic device is provided that comes into abrasive contact with the luminal walls of airways in animal or human lungs to damage mucus-secreting tissue or the connective tissue that forms attachment points for mucus-secreting tissue. In another aspect of the invention, a therapeutic device is provided that makes abrasive contact with airway walls in animal or human lungs to damage mucus-secreting tissue while destroying less than the entire airway wall.

[0055] In another aspect of the invention, a therapeutic device is provided that makes abrasive contact with the luminal wall of an airway in an animal or human lung to damage mucus-secreting tissue while destroying less than the entire airway wall. In another aspect of the invention, a therapeutic device is provided that makes abrasive contact with the inner wall of an animal or human lung airway lumen to damage mucus-secreting tissue while disrupting less than the entire airway wall.

[0056] In another aspect of the invention, a therapeutic device is provided that makes abrasive contact with at least a portion of an animal or human pulmonary airway luminal wall to produce one or more of the following changes in the treated patient:

[0057] 1. Relieve the symptoms caused by bronchitis in patients. 2. Reducing the thickness of the airway wall in the treated tissue. 3. Reducing the level of inflammation in the patient's airway walls.

[0058] 4. Reduce the frequency of coughing in patients with bronchitis. 5. Reduce the frequency of coughing episodes in patients with bronchitis. 6. Reduce the number of cough episodes per year in patients with bronchitis.

[0059] 7. Reduces phlegm production in bronchitis patients. 8. Reduce the frequency of lung infections in patients with bronchitis. 9. Reducing the number of bacterially infected sites in the patient's airways or lungs.

[0060] 10. Reduce the amount of bacteria formation in the patient's saliva. 11. Altering the composition of the patient's mucus, phlegm or saliva. 12. Reduces the amount of mucus secreted in the treated lungs.

[0061] 13. Decrease the flow, rate, amount, time course, quality and mass of mucus secreted in the treated lung or lungs. 14. Reduces the hydration level of mucus secreted by the patient.

[0062] 15. Increases the hydration level of mucus secreted by the patient. 16. Reduces the number of goblet cells remaining in the lungs. 17. Reduce the number of goblet cells regenerating in the lungs.

[0063] 18. Reduce the number of goblet cells regenerated in the lungs over the 30, 60, 180, 360 or 540 days following treatment. 19. Reduces the density of remaining goblet cells in the lungs.

[0064] 20. Thins the lining of the airway epithelium. 21. Reduces the volume of the airway epithelial lining. 22. Deterioration or death of connective tissue that keeps epithelium and / or goblet cells healthy.

[0065] 23. Deterioration or death of tissues that supply nutrients to the airway epithelium and / or goblet cells. 24. Lift the diaphragm relative to the rib reference position. 25. As a result of treatment, measure the lift of the diaphragm relative to a reference rib position while the patient maintains exhalation.

[0066] 26. Lift the base of at least one lung toward the patient's upper thorax. 27. Reduce coughing. 28. Reduces mucus secretion.

[0067] 29. Reduces coughing caused by trapped air or mucus. 30. Reduces glottal closure reflex. 31. Enhances the patient's ability to clear mucus from the lungs.

[0068] 32. Increases arterial oxygen concentration in the bloodstream. 33. Increases the proportion of arterial oxygen in the bloodstream. 34. Arterial CO in the bloodstream 2 Reduce the concentration of.

[0069] 35. Arterial CO in the bloodstream 2 Reduce the proportion of. 36. Increase mobility as measured by the now standard 6-minute walk test. 37. Increase the number of meters a patient can walk in 6 minutes.

[0070] 38. Increase the internal diameter of pulmonary airways as measured using high-resolution CT. 39. Increase airway diameter. 40. Increases pulmonary output during expiration.

[0071] 41. Increase the diameter of the airway lumen. 42. Provides radial outward support to the airway. 43. Helps in reducing lung volume during expiration.

[0072] 44. Reduce the volume of at least one lung. 45. Reduce the volume of the lung lobes. 46. ​​Reduce the volume of both lungs.

[0073] 47. Reduce the volume of the lung pairs. 48. Reduce TLC in lung pairs. 49. Apply tissue compression.

[0074] 50. Compressing the tissue of the lung lobes. 51. Remove slack in lung tissue. 52. Return the elastic recoil of the lung tissue to physiological function with lung distension pressures of 2-200 cmH2O.

[0075] 53. Increases elastic recoil of the lungs. 54. Reduces lung compliance. 55. Changing the shape of the pressure volume curve obtained by measuring the patient's respiration.

[0076] 56. Zoom in on the area within the pressure-volume curve representing the patient’s breathing. 57. Post-processing of CT images comparing inhalation and exhalation data to shift the location of the crack seen in the image.

[0077] 58. Delaying airway closure during exhalation. This is determined by comparing pre- and post-treatment airway volumes in similar regions of the lung using post-processed CT imaging data. 59. Reduce lung volume.

[0078] 60. Reduce airway resistance. 61. Reduce the volume of one or more of the patient's lungs. 62. Reduce inspiratory effort as measured by pulse transit time or respiratory inductance plethysmography.

[0079] 63. Reduce dynamic hyperinflation as measured by CT, 6-minute walk test or plethysmography. 64. Reduce end-expiratory lung volume.

[0080] 65. Reduce functional residual capacity. 66. Reduce the incidence of respiratory failure. 67. Increase the time between COPD exacerbations.

[0081] 68. Increase the time the airway remains open during expiration. 69. Increase forced expiratory volume in 1 second (FEV1). 70. Increase forced vital capacity (FVC).

[0082] 71. Increase the FEV1 / FVC ratio. 72. Reduces mood swings. 73. Reduces pressure on the heart.

[0083] 74. Reduces pressure on the coronary arteries. 75. Reduces high blood pressure. 76. Reduces excessive tension in the lungs.

[0084] 77. Reduces high blood pressure in the blood vessels that supply blood to the heart muscle. 78. Lowers systolic and / or diastolic blood pressure. 79. Slow down your heart rate.

[0085] 80. Lowers systolic blood pressure. 81. Increases the ejection fraction of the heart. 82. Reduce pulmonary artery pressure.

[0086] 83. Reduce lung tissue density (from 800 to 810-1000 HU (Hounsfield Units)). 84. Make lung tissue density more uniform (adjust the difference in mean lobar density between lung lobes to be between 1 and 200 Hounsfield units).

[0087] 85.Increase forced expiratory volume during expiration. 86. Reduce the residual volume (RV) remaining in the lungs during or after expiration. 87. Reduce the amount of gas trapped in the lungs during or after exhalation.

[0088] 88. Reduces the amount of gas trapped in the lung lobes during or after expiration. 89. Increase the variation in resting expiratory volume during tidal breathing at rest.

[0089] 90. Increase inspiratory reserve volume during tidal breathing at rest. 91. Reduce the patient's respiratory rate. 92. Slow the patient's heart rate.

[0090] 93. Increase the patient's cardiac ejection fraction. 94. Reduce the patient's total lung capacity. 95. Reduces lung compliance.

[0091] 96. Reduces compliance of a lobe or area of ​​lung tissue. 97. Increase uniformity of lung tissue compliance between upper and lower lobes. 98. Increase uniformity of lung tissue compliance between the patient’s lung lobes.

[0092] 99. Increase uniformity of lung tissue compliance between lobar segments. 100. Reduce inspiratory effort. 101. Reduce total lung capacity (TLC).

[0093] 102. Decrease the RV / TLC ratio. 103. Increases the volume of the lobar airways during inspiration. 104. Increases the volume of the lobar airways during expiration.

[0094] 105. Reduces the difference in volume of the lung airways of the lung lobes during breathing. 106. Treatment increases the total blood volume in the patient's lungs or lobes. 107. In patients with emphysema, the local blood volume in severely damaged lung tissue is reduced to reduce the amount of deoxygenated blood that mixes with normal blood.

[0095] 108. Increase the change in lobar volume between inspiration and expiration of the respiratory cycle. 109. Reduce the amount of air trapped in the lung lobes after expiration. 110. Reduces lung expiratory volume after treatment.

[0096] 111. Increase the volume of one or more lung lobes during expiration. 112. Increase the volume in the distal airways of one or more lung lobes. 113. Increase the volume within the central airways of one or more lung lobes.

[0097] 114. Lower impedance in the central airways of one or more lung lobes. 115. Reduce impedance of one or both lungs. 116. Reduce resistance to flow in one or more lobes of the lungs.

[0098] 117. Reduce resistance to flow in one or both lungs. 118. Increase vascularity in one or more lung lobes. 119. Increase the number of blood vessels per liter of lung lobe volume.

[0099] 120. Increase the volume of the airway wall of one or more lung lobes. 121. Increase the volume of the airway wall of the central airways of one or more lung lobes. 122. Reduce the percentage of damaged tissue per liter of lung volume in one or more lobes.

[0100] 123. Prolong the open airway to increase the rate of aerosol transport in one or more lung lobes. 124. Prolong the open airway to increase the local concentration of an aerosol-delivered drug in one or more lung lobes.

[0101] Measuring one or more fissures that have moved more than 125.2 mm indicates that the volume of the lobe has changed. 126. A change in lung volume is indicated by measuring one or more gaps that have shifted more than 2 mm relative to the ribs in the chest wall.

[0102] 127. Reduce the proportion of low-attenuating lung tissue in one or more lung lobes. 128. Reduce the volume of low-attenuating lung tissue in one or more lobes. 129. Reduce the proportion of low density tissue >950HU in one or more lung lobes.

[0103] 130. Reduce the volume of low-density tissue >950HU in one or more lobes. In another aspect of the present invention, a therapy device is provided that is delivered directly to a treatment location without the assistance of a delivery system.

[0104] In another aspect of the present invention, a therapeutic device is provided that is delivered to a treatment location guided by a guidewire. In another aspect of the invention, a therapeutic device is provided that is delivered directly to a treatment location via a lumen of a catheter.

[0105] In another aspect of the present invention, a therapy device is provided that is delivered directly to a treatment location through a lumen of an endoscope. In another aspect of the present invention, a therapy device is provided that is delivered directly to a treatment location through a lumen of a bronchoscope.

[0106] In another aspect of the present invention, a therapeutic device is provided that is delivered directly to a treatment location using any combination of the components of the delivery system described herein. In another aspect of the invention, a therapy device is provided that provides treatment while expanding a device at a fixed position relative to a point along the longitudinal axis of an airway.

[0107] In another aspect of the invention, a therapy device is provided that provides treatment while advancing the therapy device to a point along a longitudinal axis of an airway. In another aspect of the invention, a therapy device is provided that provides treatment from any location in a lung airway while moving the device along the longitudinal axis of the airway toward the trachea.

[0108] In another aspect of the present invention, a therapy device is provided that provides therapy while rotating the therapy device within a lumen of an airway. In another aspect of the invention, a therapy device is provided that provides therapy within a lumen of an airway while rotating the therapy device about a longitudinal axis of the airway.

[0109] In another aspect of the invention, a therapy device is provided that is driven within the lumen of the airway by a physician or by an electromagnetic motor or transducer to provide therapy while linearly moving an abrasive surface against the airway wall in a vibrating state.

[0110] In another aspect of the invention, a therapy device is provided that performs treatment by rotating an abrasive surface against the airway wall to generate circumferential vibrational abrasion in the airway lumen. The vibrations can be driven by a physician or an electromagnetic motor or transducer to generate a steady, constant motion, allowing the physician or a robotic closed loop system to control the location in the bronchial tree and the treatment area within the airway tissue.

[0111] In another aspect of the invention, a device is provided that causes tissue contact, abrasion and cell death in the airway lumen wall at a controlled depth of 0.1-3 mm, and in some embodiments more preferably 0.5-0.68 mm. In some examples, the controlled depth is about 0.02 mm, or about 20 microns. In some examples, the controlled depth is 1 micron to 500 microns. In some examples, the controlled depth is 10-100 microns. In some examples, the controlled depth is 10-50 microns.

[0112] Another aspect of the invention provides a device that induces tissue contact, grinding and cell death at a controlled depth by a method that does not allow for continuous motion that results in continuous erosion of the airway lumen wall over time. One example of such a device includes a large balloon that is fixed to the tip of a catheter. The balloon is expanded against the airway lumen to continuously contact the entire inner circumference of the airway lumen. The balloon can be rotated, moved linearly along the axis of the airway, or both motions can be performed simultaneously. The motion can be oscillatory in nature, with the frequency of the vibration being between 1 and 500 million Hertz, and more preferably between 40 and 300 cycles per second in some embodiments. In some examples, the operating frequency is selected to avoid or inhibit the grinding features from catching the tissue and to facilitate the sliding of the grinding features along the tissue. The motion can be powered by an electromechanical drive mechanism, such as a speaker motor or a rotary motor. The motor can be powered using a power source, such as alternating current from a power station, or can be powered using a rechargeable direct current battery. The grinding media may be permanently attached to the outer surface of the balloon and configured to project radially outward from the outer surface of the balloon and spaced apart from the outer surface to have a particular rough surface. The projection may be 0.5-0.68 mm, or may be greater to grind to a depth of 0.5-0.68 mm into the airway wall while still removing accumulated biological material. As the balloon expands and expands against the tissue, motion occurs, the grinding surface scrapes off the surface of the tissue, causing cell death. In this manner, an apparatus and means for causing cell death are provided. Additionally, the grinding media may be attached to the balloon outer surface in a predetermined pattern or area ratio such that only a portion of the outside of the balloon makes abrasive contact with the airway wall tissue. The area ratio is set such that 0.1-99 percent of the area of ​​the balloon outer surface is covered by the grinding media. More preferably, 2-50 percent of the balloon outer surface is covered by the grinding media. The remainder of the balloon outer surface may be smooth and lubricated. By providing the device in this configuration, the smooth portion of the balloon can be placed on the tissue as a support or depth limiting element, and this portion of the balloon will not erode into the lung tissue.Adjacent areas on the surface of the balloon where the abrasive media is attached will erode tissue to only a limited depth. This is an example of a device that can perform controlled depth erosion of lung tissue. The abrasive material may be attached to the balloon in continuous circumferential stripes so that the entire circumference of the airway lumen or inner wall is subjected to the abrasive action. As the device advances or retreats along the axis of the airway, the entire circumference and length along the path of travel of the device is completely treated. This is important because the goal of the treatment is to completely kill the epithelium of the airway to eliminate mucus-secreting cells and promote tissue repair. If localized areas are left untreated, the locally remaining mucus-secreting cells may regenerate and proliferate, which may exacerbate the original problem. In this example, a device is provided that causes complete cell death along the length of the epithelial surface of the lung airway without destroying the underlying structures or membranes of the lung airway.

[0113] In another aspect of the present invention, a therapy device is provided that provides treatment while performing any combination of the exercises described herein. In another aspect of the present invention, a therapeutic device is provided that expands to contact at least a portion of the inner circumference of the airway lumen wall and / or moves the device in accordance with the methods described herein to cause grinding and cell death to reduce mucus secretions in the lungs.

[0114] In another aspect of the present invention, a therapeutic device is provided that makes abrasive contact with lung tissue by generating expansion and / or motion powered by pneumatic or hydraulic pressure. In another aspect of the present invention, a therapeutic device is provided that makes grinding contact with lung tissue by generating a driven expansion and / or movement utilizing elastic strain energy stored in materials, such as materials used to form the spring elements, including, for example, one or more of Nitinol, steel, ferrous or non-ferrous metals, polymers, elastomers, ceramics such as carbon and carbon fiber, or CMC materials (ceramic matrix composites).

[0115] In another aspect of the present invention, a therapeutic device is provided that makes grinding contact with lung tissue by generating expansion and / or motion driven by mechanical means using linkages, torque-driven cables or wires, push rods, pull rods, or tethers.

[0116] In another aspect of the invention, a therapeutic device is provided that makes abrasive contact with lung tissue by generating expansion and / or motion driven by pneumatic pressure, hydraulic pressure, stored strain energy, or mechanical actuation means. The expansion or motion is driven or controlled by heat, pressure, force, light, voltage, current, stored strain energy, friction, optically coupled sensors or actuators, electrically actuated sensors, actuators using components such as piezoelectric crystal actuators, linear or rotary magnetic actuators, linear or rotary motors, capacitors, inductors, crystals, fluids, elements or combinations of elements that are elements or combinations of elements from the periodic table of chemical elements that change in response to voltage, current, magnetic field, light, pressure, sound, heat, or other stimuli to actuate the device into contact with the lung airway wall or move the device to effect abrasive destruction of cells.

[0117] In another aspect of the present invention, a therapeutic device is provided that creates an abrasive contact with lung tissue by generating an expansion and / or movement of a brushing device that contacts the entire circumference of the airway wall, causing abrasion of surface cells, damage to goblet cells, intentional tissue repair of the pulmonary airway lining, and / or other destruction to reduce mucus secretions as a treatment for chronic bronchitis and COPD.

[0118] In another aspect of the present invention, a therapeutic device is provided that provides abrasive contact with lung tissue by generating an expansion and / or movement of a brush, the brush being mechanically actuated and expanded to contact multiple sites on the inner circumference of the lung airway.

[0119] In another aspect of the invention, a therapeutic device is provided that provides abrasive contact with lung tissue, the device comprising mechanically actuated brushes that expand or move while maintaining constant pressure against the lung tissue.

[0120] In another aspect of the invention, a therapeutic device is provided that provides abrasive contact with lung tissue and includes an inflatable structure that is pneumatically actuated to expand or move while maintaining a constant pressure against the lung tissue.

[0121] In another aspect of the invention, a therapeutic device is provided that provides grinding contact with lung tissue and includes an expansion structure that is pneumatically actuated to expand or move while maintaining a constant pressure against the lung tissue even as the expansion diameter changes during treatment.

[0122] In another aspect of the present invention, a therapeutic device is provided that has an air-actuated expansion structure that expands or moves while maintaining a constant pressure against the lung tissue even as the expansion diameter changes during treatment, and in which air pressure or pressure relief is required to maintain the constant pressure against the lung tissue.

[0123] In another aspect of the present invention, a therapeutic device is provided that provides grinding contact with lung tissue by generating expansion and / or motion driven by pneumatic or hydraulic pressure, or by elastic strain energy using materials capable of storing elastic strain energy (Nitinol, steel, metals, polymers, elastomers, ceramics such as carbon and carbon fiber, CMC materials (ceramic matrix composites)).

[0124] In another aspect of the invention, a therapeutic device is provided that provides abrasive contact with lung tissue by generating expansion and / or motion that is mechanically driven using components such as linkages, torque drive mechanisms, push tethers, pull tethers, optically coupled sensors and actuators, electrically actuated sensors or drive mechanisms, piezoelectric, magnetic, motor, capacitor and inductor components, that rotate or move to expand an abrasive element to contact at least a portion of the airway wall and generate cell death.

[0125] In another aspect of the invention, a therapy device is provided for generating expansion and / or motion to provide abrasive contact with lung tissue, the device comprising a brush system having bristles arranged in a helical or staggered pattern such that the entire circumference of the airway is affected when the brush is drawn longitudinally along the airway axis.

[0126] In another aspect of the present invention, a therapeutic device is provided that makes abrasive contact with lung tissue by generating expansion and / or motion driven by a balloon. The balloon is inflatable to abut against the airway wall and is drawn proximally so that an abrasive material attached to the outside of the balloon surface contacts the airway wall and kills mucus-secreting cells. Abrasive materials include abrasive media used in sandpaper and industrial applications, such as alumina, carbide, sand, quartz, glass, metal, ceramic, plastic, forms of carbon such as diamond, oxides, silicon carbide particles, metal particles, polymer particles, particles with diameters of 2-3000 μm, and biocompatible materials that generally produce abrasives. Abrasives and other abrasive materials that can be used in embodiments of the present invention are described in U.S. Pat. Nos. 4,214,877, 4,828,582, 4,916,869, 5,066,335, 5,094,672, and 5,367,024. The contents of each of these patents are incorporated herein by reference. Exemplary abrasives or other grinding materials include silicon carbide, aluminum oxide, co-fused alumina zirconia, garnet, flint, diamond, cubic boron nitride, glass, tungsten carbide, cobalt, alumina, glassy polysaccharides, sintered sol-gels, styrene acrylonitrile copolymers, silicon carbide, alumina zirconia, garnet, emery, chromium (III) oxide, and the like. In some embodiments, the size of the abrasive grains ranges from 5 microns average grain size to 2000 microns average grain size.

[0127] In another aspect of the present invention, a therapeutic device is provided that makes abrasive contact with lung tissue by generating expansion and / or motion driven by the release of stored strain energy. The therapeutic device abuts against the airway wall such that an abrasive material attached to the tissue contacting surface contacts the airway wall to kill mucus-secreting cells. Abrasive materials include sandpaper and grinding media used in industrial applications such as alumina, carbide, sand, quartz, glass, metal, ceramic, plastic, forms of carbon such as diamond, oxides, silicon carbide particles, metal particles, polymer particles, particles with diameters of 2-3000 μm, and biocompatible materials that generally produce abrasive effects.

[0128] In another aspect of the invention, a therapeutic device for abrasive contact with lung tissue is provided, the therapeutic device comprising a balloon that expands blade elements that are mounted on the outside of the balloon and function as scraping elements when expanded and as the balloon is drawn along the longitudinal axis of the airway.

[0129] In another aspect of the invention, a therapeutic device for abrasive contact with lung tissue is provided that includes a balloon that expands to force abrasive particles of a specific size against the lung tissue and penetrate into the tissue only a preset and controlled distance.

[0130] In another aspect of the invention, a therapeutic device for abrasive contact with lung tissue is provided, the therapeutic device comprising a balloon that expands an abrasive mesh material, such as an abrasive polymeric, metal or composite mesh material, into the airway wall.

[0131] In another aspect of the present invention, a therapeutic device is provided that makes abrasive contact with lung tissue by generating expansion and / or motion against an expanding balloon that drives abrasive brush fibers against an airway wall.

[0132] In another aspect of the invention, a therapeutic device is provided that creates expansion and / or motion to create grinding contact with lung tissue using a balloon made from a highly elastic polymer that allows the balloon to conform to the various diameters of the airway as it moves along the longitudinal axis of the airway.

[0133] In another aspect of the invention, a therapy device is provided that creates abrasive contact with lung tissue by generating balloon expansion and / or motion. The balloon is expanded using a constant volume of fluid or gas. The balloon can be expanded using an open loop system that maintains a constant pressure, or a closed loop system that feedbacks volume or pressure data to maintain one or the other while the device is providing therapy to the patient.

[0134] In another aspect of the invention, a therapeutic device is provided that creates expansion and / or motion to effect abrasive contact with lung tissue. The therapeutic device includes an aspiration catheter having an open tip and a distally protruding stylet having an abrasive material attached thereto. The device is configured such that suction draws the airway toward the side of the distal stylet, and the device is pulled proximally to abrade the epithelium and simultaneously aspirate material from the patient.

[0135] In another aspect of the present invention, a therapeutic device is provided that makes grinding contact with lung tissue by generating expansion and / or motion using a closed or open loop system used to control suction pressure, volume, or both during treatment.

[0136] In another aspect of the invention, a therapeutic device for abrasive contact with lung tissue is provided, the therapeutic device comprising a catheter having a blocked tip and at least one open side port for delivering suction to draw the airway into contact with at least a portion of the side of the catheter and an abrasive or grinding edge that scrapes off to cause cell death to reduce mucus secretions.

[0137] In another aspect of the invention, a therapeutic device is provided that makes abrasive contact with lung tissue by providing a catheter with an outer surface that is mixed with or coated with an abrasive material, whereby cell death is induced by contact of the abrasive material with a single point on the wall of the airway lumen as the device is moved to another location in the lung while maintaining contact between the abrasive material and the airway wall.

[0138] In another aspect of the invention, a therapeutic device is provided that makes abrasive contact with pulmonary tissue by providing at least one abrasive surface that includes a mixture of abrasive material that is attached to a portion of the surface of the device that contacts the pulmonary tissue to enhance the abrasive effect.

[0139] In another aspect of the invention, a therapeutic device is provided that makes abrasive contact with lung tissue by providing catheters with varying diameters such that the tissue can be aspirated to a preferred diameter and the penetration depth of the abrasive material in contact with the tissue can be controlled.

[0140] In another aspect of the invention, a therapeutic device is provided that provides for abrasive contact with lung tissue by providing a catheter with a large step-wise difference in outer diameter, such as between 0.2 and 20 mm, and more preferably between 0.5 and 3 mm.

[0141] In another aspect of the invention, a therapeutic device is provided that makes abrasive contact with lung tissue by providing a catheter, mechanical structure or balloon with an abrasive surface that is located at the widest point of the device to increase the pressure of penetration where the abrasive surface contacts the tissue and to increase the speed and efficiency of treatment.

[0142] In another aspect of the invention, a therapeutic device is provided that makes abrasive contact with lung tissue by providing a catheter, mechanical structure or balloon with an abrasive surface that is not located at the widest point of the device to reduce the pressure of penetration where the abrasive surface meets the tissue and to limit the speed and efficiency of treatment.

[0143] In another aspect of the invention, a therapeutic device is provided that makes abrasive contact with lung tissue by providing a catheter, mechanical structure or balloon with an abrasive surface that is not located at the largest diameter portion of the device to limit the depth of penetration where the abrasive surface contacts the tissue and to limit the speed and efficiency of treatment.

[0144] In another aspect of the invention, a therapeutic device is provided that makes abrasive contact with lung tissue by providing a catheter, mechanical structure or balloon with an abrasive surface, the contact of the abrasive surface with the tissue being achieved using a low pressure source such as air suction or vacuum.

[0145] In another aspect of the present invention, a therapeutic device is provided that makes abrasive contact with lung tissue by providing a catheter, one or more balloons secured to the catheter, and an abrasive surface, the contact of the abrasive surface with the lung tissue being achieved using a low pressure source such as air suction or vacuum.

[0146] In another aspect of the invention, a therapeutic device is provided that makes abrasive contact with lung tissue by providing a catheter, conduits and ports for communicating low pressure gas or fluid, and an abrasive surface located at a selected location on the catheter. A low pressure source, such as air suction or vacuum, is communicated through the conduits and ports of the catheter to contact the lung tissue at the selected location, including the abrasive surface, to cause cell death in the lung tissue.

[0147] In another aspect of the invention, a therapeutic device is provided that makes abrasive contact with lung tissue by providing a catheter, mechanical structure or balloon that is driven to oscillate or rotate using a brushless rotary motor or linear motor drive mechanism.

[0148] In another aspect of the invention, a therapeutic device is provided that makes abrasive contact with lung tissue by providing a catheter, mechanical structure or balloon that is driven to vibrate or rotate using electrical energy supplied by an electrical circuit that includes a removable plug between the device and a source of electrical energy that drives the device.

[0149] In another aspect of the invention, a therapeutic device is provided that makes abrasive contact with lung tissue by providing a catheter, mechanical structure or balloon that is driven to vibrate or rotate using electrical energy supplied by an electrical circuit that includes a battery.

[0150] In another aspect of the invention, a therapeutic device is provided that makes abrasive contact with lung tissue by providing a catheter, mechanical structure or balloon that is driven to vibrate or rotate using electrical energy supplied by an electrical circuit that includes a secondary battery.

[0151] In another aspect of the present invention, a therapeutic device system is provided that makes abrasive contact with lung tissue by providing a catheter, mechanical structure or balloon with at least one abrasive surface that is driven to rotate or oscillate within the lung airway, a rotational or oscillating drive mechanism powered by electrical energy, and an electrical circuit having a battery and charger.

[0152] In another aspect of the present invention, a therapeutic device system is provided that makes abrasive contact with lung tissue by providing a catheter, mechanical structure or balloon with at least one abrasive surface that is driven to rotate or oscillate within the lung airway, a rotational or oscillating drive mechanism powered by air pressure or vacuum, and a pneumatic circuit having an air pressure or vacuum source.

[0153] In another aspect of the present invention, a therapeutic device system is provided that makes abrasive contact with lung tissue by providing a catheter, mechanical structure or balloon with at least one abrasive surface that is driven to rotate or vibrate within the lung airway and a rotational or vibration drive mechanism powered by dimensional changes in crystals such as quartz and crystal.

[0154] In another aspect of the invention, a therapy device system is provided that makes abrasive contact with lung tissue by providing an abrasive surface that exerts an abrasive action against the lung tissue. In some examples, the abrasive action is achieved by inflating and / or deflating a balloon on which the abrasive features are disposed, or by inflating or deflating a feature on which the abrasive features are disposed. The abrasive action occurs as a result of the balloon or feature expanding / expanding and / or contracting / contracting as the diameter of the balloon or feature increases and / or decreases, and / or the linear length of the balloon or feature increases and / or decreases. Such expansion / expansion and / or contraction / contraction creates relative motion between the abrasive surface and the tissue surface, thereby contributing to the abrasive action.

[0155] In another aspect of the invention, a therapy device system is provided that makes abrasive contact with lung tissue by providing an abrasive surface that exerts an abrasive action on the lung tissue, the device being capable of self-regulating the abrasion depth.

[0156] In yet another aspect, embodiments of the present invention include a tissue therapy device having an elongate member, an abrasive feature disposed on or coupled to the elongate member, and a control mechanism in communication with the elongate member. In some examples, the control mechanism is configured to generate a vibrational motion on the abrasive feature. Such vibrational motion functions to abrade tissue along a lumen wall of a patient. In some examples, the elongate element is provided as or includes a balloon catheter shaft, a balloon body, a balloon, a catheter shaft, a catheter, a distal abrasive body, an abrasive element shaft, an abrasive brush, an elongate element, or the like. In some examples, the abrasive feature is provided as or includes an abrasive grain, an abrasive grain pattern, an abrasive mesh, a raised edge, an extended abrasive surface, a band having abrasive grains, an abrasive material, one or more abrasive edges, a wire, an abrasive media, a raised abrasive edge, an abrasive bristles, an extended or expandable foam, a sponge, a ribbon structure or bundle, or the like. In some examples, the control mechanism is provided as or includes a motor assembly, a motion drive handpiece, a handpiece, or the like. In some examples, the oscillatory motion includes a rotational oscillatory motion. In some examples, the oscillatory motion includes a linear oscillatory motion. In some examples, the oscillatory motion includes a rotational oscillatory motion and a linear oscillatory motion. In some examples, the device is configured to grind the tissue to a controlled depth. In some examples, the controlled depth is about 20 microns. In some examples, the device further includes a vacuum mechanism that functions to draw the tissue toward the grinding feature. In some examples, the vacuum mechanism is provided as or includes a vacuum source. In some examples, the vacuum mechanism functions to remove the ground tissue from the lumen of the patient.In some examples, the grinding features include grinding meshes, grinding features, or grinding media, and the grinding media is selected from the group consisting of alumina, carbide, sand, quartz, glass, metal, ceramic, plastic, carbon, diamond, oxide, silicon carbide, polymer, silicon carbide, aluminum oxide, co-fused alumina zirconia, garnet, flint, diamond, cubic boron nitride, tungsten carbide, cobalt, glassy polysaccharides, sintered sol-gel, styrene acrylonitrile copolymer, alumina zirconia, garnet, emery, and chromium (III). In some examples, the grinding media has a particle size ranging from about 2 microns average particle size to 3000 microns average particle size. In some examples, the elongated member includes an expandable mechanism, and the grinding features are disposed on the expandable mechanism.

[0157] In yet another aspect, an embodiment of the invention encompasses a method of treating a wall of a lumen of a patient. An exemplary method may include introducing an elongate member of a treatment device having an abrasive feature into a lumen of a patient and generating a vibrational motion at the abrasive feature to abrade tissue along a wall of the lumen of the patient. In some examples, the vibrational motion includes a rotational vibrational motion. In some examples, the vibrational motion includes a linear vibrational motion. In some examples, the vibrational motion includes a rotational vibrational motion and a linear vibrational motion. In some examples, the abrading step includes abrading the tissue to a controlled depth. In some examples, the controlled depth is about 20 microns. In some examples, the method includes drawing the tissue toward the abrasive feature using a vacuum mechanism. In some examples, the method includes removing the abraded tissue from the lumen using a vacuum mechanism. In some examples, the grinding features include grinding meshes, grinding features, or grinding media, and the grinding media is selected from the group consisting of alumina, carbide, sand, quartz, glass, metal, ceramic, plastic, carbon, diamond, oxide, silicon carbide, polymer, silicon carbide, aluminum oxide, co-fused alumina zirconia, garnet, flint, diamond, cubic boron nitride, tungsten carbide, cobalt, glassy polysaccharides, sintered sol-gel, styrene acrylonitrile copolymer, alumina zirconia, garnet, emery, and chromium (III). In some examples, the grinding media has a particle size ranging from about 2 microns average particle size to 3000 microns average particle size. In some examples, the elongated member includes an expandable mechanism, the grinding features are disposed on the expandable mechanism, and the method includes expanding the expandable mechanism.

[0158] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated by reference.

[0159] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention can be obtained by reference to the following detailed description that sets forth illustrative embodiments in which the principles of the invention are utilized and the accompanying drawings. [Brief description of the drawings]

[0160] [Figure 1] A diagram showing a typical bronchoscope. [Diagram 2] Diagram showing the bronchial tree of the human lung. [Diagram 3] A cross-section of the airway wall in a human lung. [Figure 4] Diagram showing a cross section of healthy human epithelium. [Diagram 5] Diagram showing a cross section of human epithelium from a patient with bronchitis. [Figure 6] FIG. 1 illustrates an embodiment of a pulmonary treatment device comprising an elongated balloon catheter having an abrasive surface in contact with tissue. [Figure 7A] 1A-1C show embodiments of a pulmonary treatment device, a control method, and an abrasive surface expanded to contact tissue. [Figure 7B] 1A-1C show embodiments of a pulmonary treatment device, a control method, and an abrasive surface expanded to contact tissue. [Figure 7C] 1A-1C show embodiments of a pulmonary treatment device, a control method, and an abrasive surface expanded to contact tissue. [Figure 7D] 1A-1C show embodiments of a pulmonary treatment device, a control method, and an abrasive surface expanded to contact tissue. [Figure 8A] FIG. 1 illustrates a pulmonary treatment device in a readily deliverable, undeployed configuration. [Figure 8B] FIG. 1 illustrates a pulmonary treatment device in a deployed configuration. [Figure 9] FIG. 1 illustrates a pulmonary treatment system delivered through a bronchoscope with accessories. [Figure 10] FIG. 1 illustrates a pulmonary treatment system with an expandable grinding basket. [Figure 11] FIG. 13 illustrates a pulmonary treatment system with twisted elastic strands and an expansion pull wire. [Figure 12] FIG. 13 is a side view of a pulmonary treatment device with ground spring elements. [Figure 13] FIG. 13 is a top view of a pulmonary treatment device with ground spring elements. [Figure 14] FIG. 1 illustrates a pulmonary treatment system including a ground guidewire and a suction catheter. [Figure 15] FIG. 1 illustrates a pulmonary treatment system including an abrasive catheter. [Figure 16] FIG. 1 illustrates a pulmonary treatment system with an abrasive brush and a suction catheter. [Figure 17] FIG. 1 illustrates a pulmonary treatment system including an abrasive brush and a brush guide catheter. [Figure 18] FIG. 1 illustrates an embodiment of a motor drive assembly that generates oscillatory rotation. [Figure 18A] FIG. 1 illustrates an embodiment of a motor drive assembly that generates oscillatory rotation. [Figure 19] FIG. 1 illustrates a motor drive assembly that generates linear oscillatory motion. [Figure 20] FIG. 1 illustrates a bronchoscope and pulmonary treatment device. [Figure 21] FIG. 1 illustrates a treatment device for treating a patient without the use of a bronchoscope. [Figure 22] FIG. 1 illustrates a guidewire having multiple wire configurations. [Diagram 23] A diagram showing an expansion device. [Figure 24] FIG. 13 shows an expander having a curved tip. [Diagram 25] FIG. 13 illustrates an expander having a tip that includes multiple curves. [Figure 26] FIG. 1 illustrates an embodiment of a pulmonary treatment system including a multi-lumen catheter. [Figure 27] FIG. 13 illustrates a treatment device with an expandable foam scrubbing element. [Figure 28] FIG. 13 illustrates a treatment device with an extended foam scrubbing element. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0161] Particular embodiments of the disclosed devices, delivery systems and methods are described below with reference to the drawings: Nothing in this detailed description is intended to imply that any particular component, feature or step is essential to the invention.

[0162] The exemplary systems, devices and methods disclosed herein are highly suitable for use in treating the pulmonary airways of a patient. In some examples, the ablation techniques and systems disclosed herein can be used to treat unwanted lesions, surfaces or growths occurring in the peripheral vasculature (e.g., arteries or veins) of a patient, the coronary vasculature (e.g., arteries or veins) of a patient, the walls of an organ or lumen of a patient, and the tissue surfaces of a patient.

[0163] Bronchitis Treatment Delivery Overview The pulmonary treatment devices described herein are sized and configured to be delivered by a delivery device configured to be inserted into the lungs, such as a steerable bronchoscope (e.g., bronchoscope 1) as shown in FIG. 1. In some embodiments, the pulmonary treatment device 13 is configured to be delivered through a lumen of the delivery device, for example, by pushing the treatment device through the lumen of a bronchoscope, catheter, introducer, sheath, sleeve, or similar device. In other embodiments, the pulmonary treatment device 13 is configured to be delivered by being mounted on the outside of a delivery device, such as a bronchoscope, catheter (such as a balloon catheter), introducer, sheath, sleeve, guidewire, or similar device. In some embodiments, when mounted on the outside of a delivery device, the treatment device 13 is free to slide along the length of the delivery device. It is noted that the pulmonary treatment device 13 may be configured to be delivered using a combination of components of the delivery devices described above, for example, the treatment device 13 may be attached to a guidewire or balloon catheter shaft and the assembly delivered through the lumen of a bronchoscope. When a guidewire is used, the delivery system may be configured as over-the-wire (OTW) or rapid exchange (RX), where the guidewire may exit the delivery system at a location specific to the configuration. For example, in an OTW design, the guidewire exits the delivery system at its proximal end, where the guidewire runs along the entire length of the delivery instrument. On the other hand, in an RX design, the guidewire runs only along a short section (approximately 25 cm) of the delivery instrument and exits through a side port. This design saves time compared to configurations where the guidewire is advanced the entire length of the delivery instrument. In some embodiments, a delivery system or instrument 16 for delivering a therapeutic device 13 includes a bronchoscope 1, a guidewire, a guide catheter, a handpiece, and / or additional elements as described herein.Exemplary over-the-wire (OTW) features that may be used with embodiments of the systems and methods of the present invention are described in U.S. Pat. Nos. 4,540,404, 5,163,911, 5,382,234, 5,470,315, 5,891,110, 5,951,568, 6,171,279, 6,610,068, and 8,372,054. Additionally, exemplary rapid exchange (RX) features usable with embodiments of the systems and methods of the present invention are described in U.S. Patent Nos. 5,334,147, 5,336,184, 5,383,853, 5,413,560, 5,458,613, 5,620,417, 5,690,642, 5,738,667, 5,814,061, 6,371,961, 6,371,940, 7,815,600, 8,043,256, 8,758,325, and 10,245,410, the contents of each of which are incorporated herein by reference.

[0164] In some embodiments, the therapeutic device 13 is placed in the bronchoscope port 7 and the bronchoscope 1 is advanced through the bronchial tree to a target location in the lung. In patients with advanced COPD, the lung tissue and airways are inflamed, prone to bleeding, and sensitive to minor trauma such as advancement of a guidewire or catheter. Thus, in this embodiment, unlike conventional endobronchial valves and coils, the device 13 can be delivered without the use of a guidewire and / or catheter. In this embodiment, the device 13 is placed in the bronchoscope port 7 with the distal end 14 of the device 13 directed distally from the channel exit port 11 and the proximal end 15 of the device 13 extending proximally from the bronchoscope port 7. The bronchoscope 1 is maneuvered atraumatically within the airway so that the tip does not pierce the airway wall. The tip 14 can have a variety of shapes, such as a looped, coiled, ball, bullet, teardrop, cone, or tapered tip, to minimize tissue trauma. Typically, the tip of the bronchoscope 1 will advance into or well beyond the fourth generation airway into areas of the lungs that contain severely damaged tissue. This is easily accomplished if the bronchoscope has an outer diameter of less than 4.5 mm in diameter. Typically, bronchoscopes with channels and ports of 2.0 mm in diameter are often used. However, the therapy device described herein may be advanced through a narrower bronchoscope with an outer diameter of less than 3.0 mm and a channel lumen of less than 1.5 mm. Treatment of larger airways located more centrally can be accomplished using a wider bronchoscope with a working channel of 2.5 mm or more. However, generally, bronchoscopes with working channels in the range of 1.8 to 3.2 mm are most preferred.

[0165] The bronchoscope shown in FIG. 1 is generally used to deliver therapeutic elements to the lungs. The bronchoscope tip 9 is bent up and down by the physician operating the control handle 4 up and down. Once the bronchoscope is rotated 90 degrees by grasping and rotating the bronchoscope body 6, the bronchoscope can be moved left and right by operating the handle. The user can advance the flexible body 8 through the patient's mouth, trachea and lungs while operating the bronchoscope. Electronic image data files are acquired by the camera 10, processed by the camera head 3, and sent to the monitor 138 via the data cable 2, as shown in FIG. 9. As shown in FIG. 14, a hose for suction from the hospital's vacuum system may be attached to the suction port 5, so that mucus, bacteria and other foreign matter are sucked from the lung airways into the channel exit port 11, and from the suction port 5 into the filter trap 231. At the tip of the bronchoscope, the bronchoscope tip 9 is provided with a working channel exit port 11 and a light source 12. The light source 12 is typically the polished end of a light-transmitting fiber bundle capable of transmitting light energy. Additionally, the camera 10 is located at the bronchoscope tip 9 to provide an unobstructed view of the path traveled by the bronchoscope. Once the physician advances the flexible body 8 into the patient's body so that the bronchoscope tip 9 is positioned near or adjacent to the treatment site, the tip 14 of the pulmonary treatment device 13 is inserted into the bronchoscope channel insertion port 7. The device 13 is advanced until it exits the channel exit port 11. Following treatment, the device is removed from the bronchoscope channel and the bronchoscope 1 is removed from the patient. Terms such as "therapy device," "treatment device," "pulmonary treatment device," and "tissue treatment device" are used interchangeably throughout this specification.

[0166] FIG. 2 shows the bronchial tree of a typical human lung. The trachea 20 is the main airway leading to the lung. The trachea 20 is also called the zeroth generation of the airway. Typically, the trachea has a diameter of about 18-25 mm and a length of about 120 mm. At the carina 21, the trachea branches into a left main bronchus 22 and a right main bronchus 23, which are called the first generation airway. The main bronchi 22, 23 are typically 12-15 mm in diameter and about 50 mm in length. The main bronchi 22, 23 branch into lobar bronchi 24, also called the second generation airway. The lobar bronchi 24 is typically 8-12 mm in diameter and about 20 mm in length. The lobar bronchi branch into segmental bronchi 25, also called the third generation airway. These airways are typically 5-8 mm in diameter and about 8 mm in length. The segmental bronchi 25 branch into subsegmental bronchi 26, also referred to as 4th generation airways, with diameters between 4 and 5 mm, and finally, the subsubsegmental bronchi, also referred to as 5th generation airways, branch off from the subsegmental bronchi. These may be as small as 2 mm in diameter. The treatment methods described herein are intended to treat all of the above airways, including the 6th, 7th, and 8th generations of the bronchial tree (which may also be referred to as a portion of the terminal bronchioles, including airways with 5th to 16th generations). In some instances, it is also possible to treat tissues of airways up to 30 generations. In exemplary embodiments, treatment is performed in airways with 3rd, 4th, 5th, and / or 6th generation airways. In some embodiments, treatment is performed in airways where goblet cells are located.

[0167] The bronchial tree is the anatomical and functional part of the respiratory system that conducts air from the larger upper airways to the lung parenchyma. It is composed of various tracheal and intrapulmonary airways, such as bronchi, bronchioles, and terminal bronchioles. The trachea and bronchi are thick and fibrous in structure, with cartilaginous walls, which maintain their patency during breathing. The bronchi undergo multiple branches, eventually becoming the terminal bronchioles, which by definition do not have cartilage. The most distal respiratory bronchioles and alveoli allow gas to enter and leave the bloodstream.

[0168] As the bronchiole branch into smaller airways, the airway epithelium undergoes histological changes and terminal bronchioles are formed. The 17th to 19th generation of bronchioles form the transitional zone. These bronchioles enter the pyramidal pulmonary lobules, which are separated from each other by thin septa. The apex of the pulmonary lobule is directed toward the hilum and contains 5 to 7 terminal bronchioles. The last 2 or 3 generations of bronchioles have alveoli in their walls and constitute the respiratory zone. The region of the lung apical to the terminal bronchioles is called the acinus. The last branch is called the respiratory bronchioles, which further branch into multiple alveolar ducts. The alveoli, the functional unit of the respiratory system, emerge from the respiratory bronchiolar stage and are where the majority of gases are exchanged. The important point is that the majority of healthy lung volume is composed of alveolar tissue. The airway network branches from the trachea through various parts of the lungs to supply large amounts of oxygen and expel carbon dioxide from the alveoli, which are present almost everywhere in the lungs. The bronchial tree and the arterial network that carries blood from the right side of the heart through the lungs to the left side of the heart occupy a small volume in the lungs.

[0169] Figure 3 shows a cross section of a typical airway wall 34. The main structure of the airway is supported by cartilage 42 located on the distal side of the airway wall along with layers of glands 41 and smooth muscle 40. The lamina propria 39 separates the smooth muscle 40 from the basement membrane 38. Mucus 35 and epithelium 36 line the lumen of the pulmonary airway. The epithelium contains goblet cells 37 that secrete mucus 35.

[0170] Figure 4 shows a cross-section of a typical healthy epithelium 50. In a healthy human body, the basement membrane 38, basal cells 57, and ciliated cells 52 form the basal layer of the airway. Cilia 55 grow on the surface of the epithelium 50, except where the goblet cells 37 are exposed to the airway lumen 51. The goblet cells 37 have MCVs 54 that produce and secrete a mucus layer 56 on the surface of the airway lumen 51.

[0171] FIG. 5 shows a cross section of epithelium 65 in the setting of bronchitis. With long-term smoking, the airways become chronically irritated. With repeated irritation, the lung epithelium 65 increases the number of goblet cells, resulting in goblet cell hyperplasia 67, which increases the amount of mucus secreted (e.g., mucus 56 in FIG. 4). In FIG. 5, the increased mucus secretion is shown as a hypersecretory mucus layer 66. Normally, cilia 55 function to transport mucus (e.g., mucus 56 in FIG. 4) toward the trachea (trachea 20 in FIG. 2), from where it is coughed out. This is the lung's primary mechanism for eliminating harmful particles and pollutants. With repeated episodes of inflammation, the airway walls become damaged and the cilia 55 are unable to regenerate, resulting in the loss of the primary means of transporting mucus (e.g., mucus 56 in FIG. 4) from the lungs. The reduced mucus transport leads to the accumulation of mucus (e.g., mucus 56 in FIG. 4), where bacteria can collect and remain, resulting in repeated infections. The infection causes coughing, which further inflames the airway. This cycle continues as the body forms goblet cell hyperplasia 67 and other cells in the airway walls to combat the intrusion, inflammation, and infection. This cycle also causes the patient to cough for extended periods of time or even continuously. This cycle results in standard tissue wound healing in the airway walls, with constant tissue repair resulting in the production of more goblet cell hyperplasia 67 and other cells that secrete mucus (such as mucus 56 in FIG. 4). This results in a progressively thicker airway wall that restricts airflow. Goblet cell hyperplasia 67 impairs the cilia 55 coating of the surfaces of the airway lumen 51, further exacerbating the symptoms of bronchitis. These patients remain chronically infected with little means to expel secreted mucus (such as mucus 56 in FIG. 4). This continued inflammation in the patient's lungs reduces breathing ability, almost completely eliminates the possibility of normal healing, and increases mucus secretion resulting in the formation of a hypersecretory mucus layer 66. As can be seen from Figures 4 and 5, the bronchitis epithelium 65 of Figure 5 has significantly fewer cilia 55 compared to the healthy normal epithelium 50 of Figure 4.

[0172] FIG. 6 shows an airway cross section 75 with bronchitis, with the pulmonary treatment device 13 positioned in the airway 75. An epithelial layer 83 attached to a proximal airway lumen wall 76 requires treatment due to goblet cell hyperplasia (such as hyperplasia 67 in FIG. 5) caused by bronchitis. The pulmonary treatment device 13 includes a balloon body 80, and abrasive grains 82 are attached to a balloon surface 81 of the balloon body 80. The balloon body 80 is connected to a balloon catheter shaft 79 that has been advanced over a guidewire 78. The pulmonary treatment device 13 can rotate, move distally or proximally along the longitudinal axis of the airway, and / or rotate or oscillate linearly within the airway 75 while advancing or retracting. For example, the pulmonary treatment device 13 shown in FIG. 6 is pulled proximally and retracted (as shown by arrow A) while rotating and oscillating (as shown by arrow B). In some instances, the treatment includes forcing the device 13 distally in a direction opposite to arrow A to create an abrasive action between the abrasive grains 82 and the airway tissue. As shown in FIG. 6, the abrasive grains 82 scrape away the epithelial layer 83. The wall of the distal airway lumen 77 is stripped of the epithelial layer 83. This is shown as the airway wall 84 being scraped away to expose the basement membrane 85. The pulmonary treatment device 13 scrapes away the epithelial layer 83 and causes tissue repair of the epithelial layer 83 to a configuration in which the number of goblet cells (e.g., goblet cells 37 of FIG. 4) is reduced (e.g., to normal, healthy numbers). Treatment to eliminate goblet cells and goblet cell hyperplasia (e.g., goblet cell hyperplasia 67 of FIG. 5) reduces mucus (e.g., mucus 35 of FIG. 4) and / or hypersecretory mucus layer (e.g., hypersecretory mucus layer 66 of FIG. 5) and associated bacteria, which can promote drying of the patient's bronchial tree and promote wound healing. These reduce inflammation in the patient, resulting in the post-treatment changes in the patient described in the Summary of the Invention herein. In some examples, the balloon catheter shaft 79 and / or balloon body 80 (e.g., FIGS. 6 and 7A-7D) may be referred to as elongate members. In some examples, the abrasive grains 82 may be referred to as grinding features.

[0173] FIG. 7A shows a pulmonary treatment device 13 having a balloon body 80 joined to a balloon catheter shaft 79. The pulmonary treatment device 13 is deliverable over a guidewire or guidewire shaft 78 with a guidewire hub 90. The balloon body 80 is inflated with a gas or fluid, such as water, saline, silicone, other biocompatible fluids, air, nitrogen, oxygen, other biocompatible gases, etc., delivered through a balloon inflation hose 91. In this manner, the hose 91 supplies pressurized gas to the balloon. The gas or fluid can be maintained at a constant pressure by adjusting a pressure regulator 92 with a pressure gauge. The pressure may be cyclically changed in a pulsed manner to cause the balloon to oscillate in a transition state between two or more diameters. This allows grinding to be performed while minimizing large movements and tissue trauma. The change in diameter within each pressure pulse cycle may be, for example, within a range of a minimum of 0.01 mm to a maximum of 28 mm, and in an exemplary embodiment, between 0.1 and 15 mm. The frequency of the pulses may be, for example, 0.25 to 5000 cycles per second, and in an exemplary embodiment, 1 to 50 Hz. The pressure is controlled and varied in a range of about 0.001 to 600 pounds per square inch. The pressure is maintained low for compliant balloons and high for non-compliant balloons. The pressure is provided using a pump 93. In some examples, the pump 93 is an electric pump. The pump is powered using direct current energy, which may be a battery 94. In some examples, the pump 93 operates in a pulsating manner, such that the pressure within the balloon body 80 increases and decreases in a cyclic, oscillatory, or sinusoidal manner. In some examples, the pump 93 operates to create an oscillatory motion on the surface of the balloon body 80. The bonded abrasive grain patterns 95 are intersecting linear abrasive grain patterns 95 that are configured to enhance the abrasive effect on the lung airway lumen (such as the airway lumen 51 of FIG. 5) when the balloon body 80 is inflated and expanded. The abrasive grain pattern 95 contacts the airway wall epithelial layer (such as airway wall epithelial layer 83 in FIG. 6) and grinds the wall so that only exposed basement membrane (such as exposed basement membrane 85 in FIG. 6) remains.In some examples, the abrasive effect can be generated or increased by linearly moving the balloon body 80 as shown by arrow A and / or by rotating and oscillating the balloon body 80 as shown by arrow B. Embodiments of the present invention have any of a variety of shapes of bonded abrasive grain patterns 95, such as rings, stripes, curves, lines, chevrons, sinusoidal lines, circular spots, non-circular spots, etc. In some examples, the expansion and / or contraction of the balloon body 80 moves, shifts or otherwise changes the pattern 95, thereby enhancing the abrasive action of the abrasive grain pattern 95. For example, the angle and / or alignment of the intersecting linear abrasive grain patterns 95 change. In some embodiments, the balloon body 80 does not need to be linearly and / or rotationally moved to scrape off tissue, since simply expanding and / or contracting the balloon body 80 provides sufficient abrasive action for treatment. In some examples, the abrasive grain patterns 95 may be referred to as abrasive features.

[0174] FIG. 7B shows a pulmonary treatment device 13 having a balloon body 80 bonded to a balloon catheter shaft 79. The pulmonary treatment device 13 is deliverable via a guidewire 78. The balloon body 80 is inflated with a gas or fluid, such as water, saline, silicone, other biocompatible fluids, air, nitrogen, oxygen, other biocompatible gases, etc., transferred via a balloon inflation hose 91. The gas or fluid can be maintained at a constant pressure by adjusting a pressure regulator 92. The pressure is provided using a pump 93. The pump is powered using alternating current energy, and the power source may be power provided from a power system grid, such as through a common wall outlet. As shown in FIG. 7B, the energy is provided via an electrical cable 135 and a wall electrical plug 100. The grinding media bonded to the balloon body 80 is a band having an abrasive mesh 101 made from any expandable polymer or film. The abrasive mesh 101 includes a material having the properties of abrasive grains 82. In some examples, the abrasive mesh 101 is a flexible, thin steel or metal filament with sharpened ends. The raised edges of the abrasive media 125 contact and abrade the airway wall epithelial layer (such as airway wall epithelial layer 83 in FIG. 6) so that only the exposed basement membrane (such as basement membrane 85 in FIG. 6) remains. In some examples, the abrasive effect can be generated or increased by linearly moving the balloon body 80 as shown by arrow A and / or by rotary-oscillatory movement as shown by arrow B.

[0175] As shown in FIG. 7B, the abrasive mesh 101 occupies a relatively small percentage (e.g., less than 30%) of the surface area of ​​the balloon body 80. In some examples, the percentage of the surface area of ​​the balloon body 80 that is occupied by the abrasive mesh 101 affects the abrasive depth of the device 13. For example, when the uncovered portion of the balloon body 80 contacts and / or presses against the airway wall, the mesh 101 stretches or contracts due to the expansion / contraction of the balloon body 80. In some examples, the uncovered proximal and / or distal surfaces 86 and / or 87 of the balloon body 80 function as a support surface against the airway wall. In some examples, the uncovered proximal and / or distal surfaces 86 and / or 87 of the balloon body 80 function to limit the depth to which the mesh 101 penetrates the airway wall. In some examples, the abrasive mesh 101 may be referred to as an abrasive feature.

[0176] FIG. 7C shows a pulmonary treatment device 13 having a balloon body 80 bonded to a balloon catheter shaft 79. The pulmonary treatment device 13 is deliverable via a guidewire 78. The balloon body 80 is inflated with a gas or fluid, such as water, saline, silicone, other biocompatible fluids, air, nitrogen, oxygen, other biocompatible gases, etc., transferred via a balloon inflation hose 91. The gas or fluid can be maintained at a constant pressure by adjusting a pressure regulator 92. The pressure is provided using a pump 93. The pump is powered using alternating current energy, and the power source may be power provided from a power system grid, such as through a common wall outlet. As shown in FIG. 7C, the energy is provided via an electrical cable 135 and a wall electrical plug 100. The grinding media bonded to the balloon body 80 is a band having mixed size abrasive grains 103. The mixed size abrasive grains 103 are bonded to the balloon body 80 as bands 104 of irregularly sized grains, so that as the expanded balloon body 80 rotates, the contact points with the airway epithelial layer (such as epithelial layer 83 in FIG. 6) change. The mixed size abrasive grains 103 contact and grind the airway wall epithelial layer (such as airway wall epithelial layer 83 in FIG. 6) so that only the exposed basement membrane (such as basement membrane 85 in FIG. 6) remains. In some examples, the grinding effect can be generated or increased by moving the balloon body 80 linearly as shown by arrow A and / or in a rotational oscillatory manner as shown by arrow B. In some examples, the abrasive grains 104 may be referred to as grinding features.

[0177] In some examples, the size, distribution and / or composition of the mixed size abrasive grains 103 can be selected to configure a depth control feature. For example, the composition of the abrasive grains 103 can be configured to perform a deep cut or a shallow cut. If the size of the abrasive grains 103 is too small, little or no cutting may occur. If the size of the abrasive grains 103 is too large, the abrasive grains may dig into and damage the surface of the airway wall too much.

[0178] As shown in FIG. 7C, the abrasive band 104 occupies a relatively small percentage (e.g., less than 30%) of the surface area of ​​the balloon 80. In some examples, the percentage of the surface area of ​​the balloon body 80 that the abrasive band 104 occupies affects the grinding depth of the device 13. For example, when the uncovered portion of the balloon body 80 contacts and / or presses against the airway wall, the balloon body 80 expands / contracts, causing the abrasive band 104 to stretch or contract. In some examples, the uncovered proximal and / or distal surfaces 86 and / or 87 of the balloon body 80 act as a support surface against the airway wall. In some examples, the uncovered proximal and / or distal surfaces 86 and / or 87 of the balloon body 80 act to limit the depth to which the abrasive band 104 penetrates the airway wall. The embodiment shown in FIG. 7C has a single abrasive band 104. In some embodiments, the treatment device has multiple bands of abrasive.

[0179] FIG. 7D shows a pulmonary treatment device 13 having a balloon body 80 joined to a balloon catheter shaft 79. The pulmonary treatment device 13 is deliverable via a guidewire 78. The balloon body 80 is inflated with a gas or fluid, such as water, saline, silicone, other biocompatible fluids, air, nitrogen, oxygen, other biocompatible gases, etc., delivered via a balloon inflation hose 91. Pressure for the gas or fluid is provided using a syringe pressure source 105. In some examples, the syringe pressure source 105 is a manual device. In use, the syringe 105 is pumped or actuated one or more times to inflate the balloon body 80, and the pressure source 105 is locked to maintain a constant amount of pressure within the balloon body 80. The balloon body 80 is pulled within the airway (e.g., via a motor-driven mechanism operably coupled to the balloon catheter shaft 79) and / or oscillated rotationally and / or linearly. The grinding media bonded to the balloon body 80 is a series of metals, plastics, ceramics, hard rubber, rope, glass or other biocompatible materials that form a raised edge 106. The raised edge 106 scrapes off the epithelial layer (such as the epithelial layer 83 in FIG. 6) when the balloon body 80 is expanded, rotated or translated. The raised edge 106 contacts and scrapes the airway wall epithelial layer (such as the airway wall epithelial layer 83 in FIG. 6) so that only the exposed basement membrane (such as the exposed basement membrane 85 in FIG. 6) remains. In some examples, the grinding effect can be generated or increased by moving the balloon body 80 linearly as shown by arrow A and / or in a rotational oscillatory manner as shown by arrow B. In some examples, the raised edge 106 is a feature of a blade element. The blade element is attached to the outside of the balloon and acts as a scraping element when the balloon is expanded or pulled along the longitudinal axis of the airway. In some examples, the raised edge 106 may also be referred to as a grinding feature.

[0180] In some embodiments, the balloon body (such as balloon body 80) is compliant, non-compliant (i.e., rigid), or semi-compliant (i.e., semi-rigid). When exposed to a certain amount of atmospheric pressure, a compliant balloon body will have a larger diameter compared to a non-compliant balloon, which will have a smaller diameter. Thus, in a device with a relatively more compliant balloon body, the bonded abrasive grains 82, abrasive grain pattern 95, abrasive mesh 101, abrasive grain bands 104, raised edges 106, or other abrasive features or elements disclosed herein will be driven deeper or with greater force into the airway wall compared to a device with a relatively less compliant balloon body.

[0181] In some instances, as the balloon body 80 expands, only the abrasive elements or features contact and penetrate the airway wall, i.e., the proximal and distal surfaces 86, 87 of the balloon body 80 do not contact the airway wall until the desired abrasion depth, depending on the depth of the abrasive elements or features, is achieved.

[0182] FIG. 8A illustrates aspects of a pulmonary treatment device 13 according to an embodiment of the present invention. As illustrated, the treatment device 13 is inserted into the flexible body 8 of the bronchoscope 1 and advanced until it exits the channel exit port 11 at the bronchoscope tip 9 of the bronchoscope 1. As illustrated, the bronchoscope 1 includes a camera 10 and a light source 12. The treatment device 13 includes or can be disposed within a guide catheter 120, and includes a balloon catheter shaft 79, a balloon 121 in an uninflated state, and an abrasive mesh 122 in a folded state coupled to the balloon 121. Additionally, the treatment device 13 includes or is disposed along a guidewire 78. In some examples, the guidewire 78 is optionally disposed. The guide catheter 120 functions to guide the delivery of the balloon 121. In some examples, the bronchoscope 1 is used as a catheter across the vocal cords as the treatment device 13 is delivered to a treatment site within the patient's pulmonary airway. In some instances, the bronchoscope 1 can remain in place during the treatment procedure and the bronchoscopist, physician, surgeon or other operator can replace the treatment device 13 with another device during the procedure. In some instances, a radiologist performs the treatment procedure without the use of the bronchoscope 1.

[0183] 8A, a guidewire 78 is placed through a guide catheter 120. In this manner, the surgeon or operator advances the catheter 120 deep into the bronchial tree, places the balloon catheter shaft 79 over the guidewire 78, and advances the balloon catheter shaft 79 through the guide catheter 120. Such an approach can limit damage to the airway wall.

[0184] 8B illustrates aspects of a pulmonary treatment device 13 according to an embodiment of the present invention. As shown, the treatment device 13 is inserted through the flexible body 8 of the bronchoscope 1 and advanced until it exits the channel exit port 11 at the bronchoscope tip 9 of the bronchoscope 1. As shown, the bronchoscope 1 includes a camera 10 and a light source 12. The treatment device 13 includes a guide catheter 120 or can be disposed within the guide catheter 120 and includes a balloon catheter shaft 79, an inflated balloon 123, and an expanded abrasive mesh 124 coupled to the balloon 123. The expanded abrasive mesh 124 includes a raised edge 125 of the abrasive media. Additionally, the treatment device 13 includes a guidewire 78 or is disposed along the guidewire 78. In some examples, the guidewire 78 is optional. As can be seen in Figures 8A and 8B, the uninflated balloon 121 of Figure 8A can be inflated to the inflated balloon 123 of Figure 8B, which results in the folded abrasive mesh 122 of Figure 8A being unfolded and expanded to the expanded abrasive surface 124 of Figure 8B. The expansion of the mesh allows for the abrasion of the epithelial layer of the airway wall. As shown in Figure 8B, the inflated balloon 123 can be moved linearly as shown by arrow A and / or in a rotational oscillatory manner as shown by arrow B to generate or increase the abrasive effect. In some examples, the balloon catheter shaft 79 and / or the balloon 123 (e.g., Figures 8A and 8B) may be referred to as an elongated member. In some examples, the expanded abrasive surface 124 may be referred to as an abrasive feature.

[0185] FIG. 9 illustrates an embodiment of a system 200 for treating a patient. The system 200 includes a bronchoscope 1 having a flexible body 8 with a working channel exit port 11. As shown, a treatment device 13 (or other endobronchial instrument) is inserted into a channel insertion port 7 of the bronchoscope 1 and advanced through the flexible body 8 of the bronchoscope 1 until it exits the channel exit port 11 at the bronchoscope tip of the bronchoscope 1. The bronchoscope 1 has a control handle 4 and is connected to a video monitor 138 via a data cable 2. As shown, the monitor 138 can display a bronchoscopic image 137, allowing the operator to see what is happening within the patient (e.g., within the lung airways). The treatment device 13 includes a balloon 80 with mixed size abrasive grains 103 bonded thereto, positioned along a guidewire 78. The system 200 also includes a syringe pressure source 105 for the balloon 80, which is connected to a balloon inflation hose 91. In some examples, the balloon catheter shaft 79 has a separate lumen for inflating and / or deflating the balloon 80. As shown, the system 200 includes a balloon catheter hub 130 and a motor assembly 131 having a trigger switch 132. In use, an operator manipulates the switch 132 to control the motor assembly 131. This manipulation can cause the balloon 80 to oscillatorily or oscillately rotate, translate, and / or inflate / deflate as described herein. A guidewire 78 extends proximally from the balloon catheter hub 130 and distally from the balloon 80. As shown, the balloon catheter hub 130 is coupled to the balloon catheter shaft 78, which is inserted into the channel insertion port 7 of the bronchoscope 1. The motor assembly 131 is coupled to a battery 134 via a power cable 133. The battery 134 functions to power the motor assembly 131. A wall outlet plug 136 is coupled to the battery 134 via an electrical cable 135. In some examples, the battery 134 is a secondary battery. In some examples, the system 200 includes an AC / DC converter in place of the battery 134.When the wall outlet plug 136 is inserted into a wall outlet, electricity from the wall outlet charges the battery 134 or directly powers the motor assembly 131. In the embodiment shown in Figure 9, the system 200 does not have a guide catheter (such as the guide catheter 120 of Figures 8A and 8B). In some examples, the balloon catheter shaft 79 and / or the balloon 80 (such as Figure 9) may be referred to as an elongate member. In some examples, the band with mixed size abrasive grains 103 may be referred to as a grinding feature.

[0186] FIG. 10 illustrates an embodiment of a system 200 for treating a patient. The system 200 includes a bronchoscope 1 having a flexible body 8 with a working channel exit port 11. As illustrated, a treatment device 13 is inserted through the flexible body 8 of the bronchoscope 1 and advanced until it exits the channel exit port 11 at the bronchoscope tip of the bronchoscope 1. The treatment device 13 includes an expandable grinding tool 167. The grinding tool 167 includes a distal end 151, a proximal end 152, and a plurality of resilient spring elements 153 disposed between the distal end 151 and the proximal end 152. Additionally, the expandable grinding tool 167 includes an abrasive material 155 disposed on the resilient spring elements 153 with gaps 154 between adjacent resilient spring elements 153. In some examples, the abrasive material 155 is bonded or bonded to the resilient spring elements 153. The abrasive material 155 defines a raised grinding edge 156. In some examples, the abrasive edge 156 is configured by a cut or etched shape or pattern in the spring element 153 (e.g., without the need for a separate abrasive 155). For example, the abrasive shape or pattern of the abrasive edge 156 is formed by cutting or arc welding the spring element 153. In some examples, the patterning or etching forms a sharp indentation on the spring element 153. The expandable abrasive tool 167 is disposed within the airway lumen 162 proximal to the airway branch 163 and the next generation airway 164. The proximal end 152 of the expandable abrasive tool 167 is coupled to the abrasive catheter shaft 158 ​​via a connector hub 157. The abrasive catheter shaft 158 ​​is coupled to a motion drive handpiece 159. In some embodiments, the abrasive catheter shaft 158 ​​is made of a metal or polymeric material. In some examples, the handpiece 159 is gripped by a user to manually apply linear and / or rotational forces.

[0187] As shown, the motion drive handpiece 159 has a slider switch 160, a guidewire exit port 161, and a pull wire actuated switch 165 having an actuated switch button or slider 166. In use, an operator operates the switch 165 to control the motion drive handpiece 159. This actuation may cause the expandable grinding instrument 167 to rotate, translate, and / or expand / contract in an oscillatory or oscillatory manner, as described herein. In some examples, actuation of the button or slider 166 adjusts the frequency, amplitude, and / or direction that the expandable grinding instrument 167 vibrates, oscillates, or moves.

[0188] The guidewire 78 extends proximally from a guidewire exit port 161 of the motion drive handpiece 159 and distally from the tip 151 of the expandable grinding instrument 167. The motion drive handpiece 159 is coupled to a battery 134 via a power cable 133. The battery 134 functions to power the motion drive handpiece 159. The wall outlet plug 136 is coupled to the battery 134 via one or more electrical cables 135. In some examples, the electrical cables 135 include or are connected by a connector 150. In some examples, the battery 134 is a secondary battery. In some examples, the system 200 includes an AC / DC converter in place of the battery 134. When the wall outlet plug 136 is plugged into a wall outlet, electricity from the wall outlet charges the battery 134 or directly powers the motion drive handpiece 159.

[0189] In some examples, the spring element 153 is formed from a round wire, and in some embodiments, one or more portions of the round wire are flattened. Similarly, in other embodiments, the spring element is formed from a ribbon that already has a flattened shape. In this case, the ribbon may be twisted. In some examples, the spring element 153 is constructed from a laser cut tube (e.g., a slit tube), a Nitinol material, a spring steel material, or any shape memory material. As shown, upon expansion of the expandable grinding device 167, the shape of the device 167 becomes similar to the shape of a balloon in an expanded or inflated state as described herein. In some examples, the balloon catheter shaft 79 and / or the balloon body 123 (e.g., FIGS. 8A and 8B) may be referred to as an elongate member. In some examples, the grinding material 155 or grinding edge 156 may be referred to as a grinding feature.

[0190] FIG. 11 illustrates an embodiment of a system 200 for treating a patient. The system 200 includes a bronchoscope 1 having a flexible body 8 with a working channel exit port 11. As illustrated, a treatment device 13 is inserted through the flexible body 8 of the bronchoscope 1 and advanced until it exits the channel exit port 11 at the bronchoscope tip of the bronchoscope 1. The treatment device 13 includes a connector hub 157, an expandable grinding tool 167, and a pull wire 175. The expandable grinding tool 167 includes a tip 151, a plurality of grinding strands 176 disposed between the tip 151 and the connector hub 157, and a raised edge of the grinding media 125 disposed along the grinding strands 176. The grinding strands 176 are coupled to a grinding catheter shaft 158 ​​via the connector hub 157. The grinding catheter shaft 158 ​​is coupled to a motion drive handpiece 159. As shown, the motion drive handpiece 159 includes a slider switch 160, a guidewire exit port 161, and a pullwire actuation switch 165 having an actuation switch button 166 that controls actuation of the pullwire 175. The guidewire 78 extends proximally from the guidewire exit port 161 of the motion drive handpiece 159 and distally from the tip 151 of the expandable grinding instrument 167. The motion drive handpiece 159 is connected to a battery (such as a secondary battery) or an AC / DC converter as described herein. In some examples, the handpiece 159 is held by a user to manually apply linear and / or rotational forces.

[0191] In some embodiments, the grinding tool 167 is configured as a wire basket made of Nitinol. In some examples, the grinding wire 176 has a grinding edge that is configured by a shape or pattern cut or etched into the wire 176 (e.g., without the need for a separate grinding media 125). For example, the grinding edge is formed by cutting or arc welding the wire 176. In some examples, sharp indentations are formed on the wire 176 by patterning or etching. In some examples, the wire 176 is formed from a round wire, and in some embodiments, one or more portions of the round wire are flattened. Similarly, in other embodiments, the wire 176 is formed from a ribbon that already has a flattened shape. In this case, the ribbon may be twisted. The wire 176 may be formed from a wire, such as a wire with a circular cross section, or a ribbon with a square or rectangular cross section. In some embodiments, the wire 176 is configured into various shapes, such as a helical shape, a random shape, a whisk shape, a sinusoidal shape, a troposkein shape, and the like. By manipulating the pull wire 175, the overall shape and / or diameter of the abrasion tool 167 can be changed. In some embodiments, the pull wire 175 is manipulated to expand the diameter of the abrasion tool 167, for example, by pulling the tip 151 towards the connector hub 157, and then the abrasion tool 167 is vibrated and / or pulled proximally along the airway as described herein.

[0192] As shown, the motion drive handpiece 159 has a slider switch 160, a guidewire exit port 161, and a pull wire actuated switch 165 having an actuated switch button or slider 166. In use, an operator operates the switch 165 to control the motion drive handpiece 159. This actuation may cause the expandable grinding instrument 167 to rotate, translate, and / or expand / contract in an oscillatory or oscillatory manner, as described herein. In some examples, actuation of the button or slider 166 adjusts the frequency, amplitude, and / or direction that the expandable grinding instrument 167 vibrates, oscillates, or moves.

[0193] The strands 176 of the grinding tool 167 may be made of or include any of a variety of materials, including, but not limited to, metal wires (such as stainless steel, titanium, nitinol, or other nickel-based alloys), monofilament or multifilament fibers, braids, polymeric or ceramic or glass fibers (such as Kevlar®, carbon fiber, nylon, polyurethane, polypropylene, or other durable materials), or organic materials such as carbon fiber, ceramic, plastic, glass, or combinations thereof. In some examples, the catheter shaft 158 ​​(e.g., FIGS. 10 and 11) may be referred to as an elongate member. In some examples, the strands 176 and / or grinding media 125 may be referred to as grinding features.

[0194] FIG. 12 illustrates an embodiment of a system 200 for treating a patient. The system 200 includes a bronchoscope 1 having a flexible body 8 with a working channel exit port 11. As shown, a treatment device 13 is inserted through the flexible body 8 of the bronchoscope 1 and advanced until it exits the channel exit port 11 at the bronchoscope tip of the bronchoscope 1. Along a proximal-to-distal direction, the treatment device 13 includes a motion drive hub 187, a proximal grinding body 186, a distal grinding body 185, a crimping hub 188, a ribbon 189, a flat support surface 191, a raised grinding edge 190 (grinding media 194 in FIG. 13), a transition section 193, a flat support surface 191, a raised grinding edge 190, and a distal support section 192. In use, the raised grinding edge 190 functions to contact and grind the airway wall epithelial layer 83. In this manner, the epithelial layer 83 can be peeled off from the airway lumen wall (shown here as airway wall cross section 34). The distal support 192 can be formed into a variety of shapes, such as a coil, ball, distal loop, cone, cylinder, or other blunt or atraumatic tip shape that minimizes irritation to the tissue during the treatment procedure. In some embodiments, the treatment device 13 is configured to expand within the patient's airway. For example, the treatment device 13 has a pull wire coupled to the distal support 192. In another example, the treatment device 13 is spring-loaded to expand radially outwardly and push against the airway wall. The motion drive hub 187 may be coupled to a motor coupler as described herein. In some examples, the treatment device 13 is configured as a disposable device. In some examples, the distal abrasive 185 may be referred to as an elongated member. In some examples, the raised edge 190 may be referred to as an abrasive feature.

[0195] FIG. 13 is a plan view (e.g., top or bottom) corresponding to the elevation view (e.g., right or left) of FIG. 12. As shown in FIG. 13, the system 200 includes a bronchoscope 1 having a flexible body 8 with a working channel exit port 11. As shown, the treatment device 13 is inserted through the flexible body 8 of the bronchoscope 1 and advanced until it exits the channel exit port 11 at the bronchoscope tip of the bronchoscope 1. The treatment device 13 includes, in a proximal-to-distal direction, a motion drive hub 187, a proximal grinding body 186, a distal grinding body 185, a crimping hub 188, a ribbon 189, a flat support surface 191, a grinding media 194 (forming the raised grinding edge portion 190 of FIG. 12), a transition portion 193, and a distal support portion 192. In use, the treatment device 13 is advanced into the airway lumen 162 and the abrasive media 194 functions to contact and abrade the airway wall epithelial layer 83. In this manner, the epithelial layer 83 may be peeled off from the airway lumen wall (shown here as airway wall cross section 34). In some examples, the distal abrasive body 185 may be referred to as an elongated member. In some examples, the abrasive media 194 may be referred to as an abrasive feature.

[0196] 14 illustrates an embodiment of a system 300 for treating a patient. The system 300 includes a treatment device 13 having an abrasive element shaft 225 and a vacuum hub 226 coupled to a hollow catheter 238. A distal end 239 of the catheter 238 is inserted into the proximal airway lumen 76 and the abrasive element shaft 225 extends through the catheter 238 into the proximal airway lumen 76. A proximal end 240 of the catheter 238 is coupled to the vacuum hub 226 via a connector 237. A proximal end 235 of the abrasive element shaft 225 is coupled to a motion drive hub 187 which is coupled to a motor coupler 195 which is coupled to a motion drive handpiece 159. As illustrated, the motion drive handpiece 159 includes a slider switch 160. The motion-driven handpiece 159 is coupled to the battery 134 via a power cable 133 (or multiple power cables 133 coupled via one or more connectors 150). The battery 134 functions to power the motion-driven handpiece 159. The wall outlet plug 136 is coupled to the battery 134 via one or more electrical cables 135. In some examples, the electrical cables 135 have or are connected by a connector 150. In some examples, the battery 134 is a secondary battery. In some examples, the system 300 has an AC / DC converter in place of the battery 134. When the wall outlet plug 136 is plugged into a wall outlet, electricity from the wall outlet charges the battery 134 or directly operates the motion-driven handpiece 159. In some examples, the handpiece 159 is held by a user to manually apply linear and / or rotational forces.

[0197] The vacuum hub 226 further includes a seal 227. As shown, the grinding element shaft 225 extends through the seal 227 and the bearing 234. The grinding element shaft 225 is coupled or secured to the bearing 234. Thus, in operation, the grinding element shaft 225 and the bearing 234 are inserted into the vacuum hub, for example, until the bearing 234 contacts or is close to the proximal end of the catheter 238, and the seal 227 is placed on the grinding element shaft 225 and coupled to the distal end of the vacuum hub 226. The system 300 also includes a filter 230 coupled to the vacuum hub 226 via a hose 229 and a luer hub 228. As shown, the luer hub 228 is coupled to a luer taper connection 241 of the vacuum hub 226. The filter 230 can be connected to a vacuum source 233 via the hose 229 and a coupler 232. The filter 230 can retain the collection material 231. In some instances, the vacuum source 233 is operated by the physician or operator using a foot pedal.

[0198] In use, the tip 236 of the grinding element shaft 225 is placed in the distal airway lumen 77 and suction is applied via the vacuum hub 226, causing the airway portion distal to the tip 239 of the catheter 238 to contract. This results in the epithelium 83 being drawn against the raised edge 125 of the abrasive grain or grinding media 82. The raised grinding edge 125 acts to contact and grind the airway wall epithelial layer 83. In this manner, the epithelial layer 83 is stripped from the airway lumen wall (shown here as airway wall cross section 34) exposing the basement membrane 85. The operator controls the motion drive handpiece 159 to rotate and / or translate the grinding element shaft 225 in an oscillatory or oscillating manner as described herein. In some examples, the frequency, amplitude and / or direction in which the grinding element shaft 225 vibrates, oscillates or moves is adjusted by operation of the button or slider 166. In some instances, the airway surface can be abraded to the desired state by simply pulling the catheter 238 in a proximal direction, without the need to vibrate the abrasive element shaft 225. Suction from the vacuum source 233 drives the abraded epithelium through the hollow catheter 238, the vacuum hub 226, and the hose 229 into the filter or filter trap 230, where it remains as collection 231. In some instances, the vacuum source 233 is operated by the physician or operator using a foot pedal. As described herein (e.g., with respect to Figs. 27 and 28), in some instances, the system 300 includes a foam mechanism instead of or in addition to the abrasive edge 125 and / or the abrasive grain 82. In some instances, the abrasive element shaft 225 may be referred to as an elongated member. In some instances, the raised abrasive edge 125 may be referred to as an abrasive feature.

[0199] 15 illustrates an embodiment of a system 300 for treating a patient. The system 300 includes a treatment device 13 having an abrasion catheter 250 and a motion drive handpiece 159, a vacuum hub 226, and a filter 230. The abrasion catheter 250 includes a tip 251, a distal port 258, a raised abrasive edge 125, a proximal port 257, a distal bearing 255, a hub port 259, a proximal bearing 254, a motion drive shaft 253, a proximal end 252, and a motion drive hub 187. The distal bearing 255 and the proximal bearing 254 function to prevent the treatment device 13 from dislodging from the vacuum hub 226. The motion drive hub 187 is coupled to a motor coupler 195, which is coupled to the motion drive handpiece 159. As illustrated, the motion drive handpiece 159 includes a slider switch 160. The motion-driven handpiece 159 is coupled to the battery 134 via a power cable 133 (or multiple power cables 133 coupled via one or more connectors 150). The battery 134 functions to power the motion-driven handpiece 159. The wall outlet plug 136 is coupled to the battery 134 via one or more electrical cables 135. In some examples, the electrical cables 135 have or are connected by a connector 150. In some examples, the battery 134 is a secondary battery. In some examples, the system 300 has an AC / DC converter in place of the battery 134. When the wall outlet plug 136 is plugged into a wall outlet, electricity from the wall outlet charges the battery 134 or directly operates the motion-driven handpiece 159. In some examples, the handpiece 159 is held by a user to manually apply linear and / or rotational forces.

[0200] The vacuum hub 226 further includes a seal 256 (e.g., an O-ring). As shown, the grinding element shaft 225 extends through the seal 256. The filter 230 is coupled to the vacuum hub 226 via a hose 229 and a luer hub 228. The filter 230 may be connected to a vacuum source 233 via a hose 229 and a coupler 232. The filter 230 may retain the collection material 231. In some examples, the vacuum source 233 is operated by a physician or operator using a foot pedal. When the grinding catheter 250 is pulled proximally or when the treatment device 13 is otherwise operating, the abraded debris is removed and aspirated from the airway and sucked into the filter 230.

[0201] In use, the tip 251 of the abrading catheter 250 is placed in the distal airway lumen 77 and suction is applied via the vacuum hub 226, causing a portion of the airway to retract between the proximal and distal ports 257 and 258 of the abrading catheter 250. This draws the epithelium 83 against the raised edge 125 of the abrading catheter 250. The raised abrading edge 125 acts to contact and abrade the airway wall epithelial layer 83. In this manner, the epithelial layer 83 is stripped from the airway lumen wall (shown here as airway wall cross section 34) exposing the basement membrane 85. The operator controls the motion drive handpiece 159 to rotate and / or translate the catheter 250 in an oscillatory or oscillating manner as described herein. In some examples, actuation of the button or slider 166 adjusts the frequency, amplitude and / or direction in which the catheter 250 vibrates, oscillates or moves. In some instances, the catheter 250 can be simply pulled proximally to abrade the airway surface as desired, without the need to vibrate the catheter 250. Suction from the vacuum source 233 forces the abraded epithelium through the abrading catheter 250, hub port 159, and hose 229 into the filter or filter trap 230, where it remains as collection 231. In some instances, the raised abrasive edge 125 comprises an abrasive edge that is configured by a cut or etched shape or pattern on the catheter 250. For example, the abrasive shape or pattern of the abrasive edge is formed by cutting or arc welding the catheter 250. In some instances, sharp indentations are formed on the catheter 250 by patterning or etching. By providing spacing between the distal and proximal ports 258 and 257, the force with which the raised abrasive edge 125 abrades against the epithelial layer 83. Increasing the spacing between the ports reduces the pressure, while decreasing the spacing between the ports increases the pressure and abrasive action. In some embodiments, the ports are spaced at least 0.01 mm to 50 mm apart from one another, and in exemplary embodiments, are spaced 1 mm to 35 mm apart. The catheter can have 1 to 3000 ports. The ports have diameters of 0.010 mm to 6 mm.In some examples, the catheter 250 may be referred to as an elongate member. In some examples, the raised grinding edges 125 may be referred to as grinding features.

[0202] FIG. 16 illustrates an embodiment of a system 300 for treating a patient. The system 300 includes a treatment device 13 having an abrasive brush 270 and a motion drive handpiece 159, a vacuum hub 226 coupled to a hollow catheter 238, and a filter 230. The abrasive brush 270 has a distal end 272, abrasive bristles 275, a proximal end 271, and a motion drive hub 187. As shown, the abrasive brush 270 may include a wire having a twist 274 in the brush wire. The motion drive hub 187 is coupled to a motor coupler 195, which is coupled to the motion drive handpiece 159. As shown, the motion drive handpiece 159 includes a slider switch 160. The motion drive handpiece 159 is coupled to a battery 134 via a power cable 133 (or multiple power cables 133 coupled via one or more connectors 150). The battery 134 functions to power the motion-driven handpiece 159. The wall outlet plug 136 is coupled to the battery 134 via one or more electrical cables 135. In some examples, the electrical cables 135 include or are connected by a connector 150. In some examples, the battery 134 is a secondary battery. In some examples, the system 300 includes an AC / DC converter in place of the battery 134. When the wall outlet plug 136 is plugged into a wall outlet, electricity from the wall outlet charges the battery 134 or directly powers the motion-driven handpiece 159. In some examples, the handpiece 159 is held by a user to manually apply linear and / or rotational forces.

[0203] The vacuum hub 226 further includes a seal 227, a seal bearing 273, and a bearing 234. A distal end 239 of a catheter 238 is inserted into the proximal airway lumen 76, and an abrasive brush 270 extends through the catheter 238 into the proximal airway lumen 76. A proximal end 240 of the catheter 238 is coupled to the vacuum hub 226 via a coupling 237. As shown, the abrasive brush 270 extends through the seal bearing 273 and the bearing 234. A filter 230 is coupled to the vacuum hub 226 via a hose 229 and a luer hub 228. The filter 230 may be connected to a vacuum source 233 via a hose 229 and a coupler 232. The filter 230 may retain the collection material 231. In some examples, the vacuum source 233 is operated by the physician or operator using a foot pedal.

[0204] In use, the tip 272 of the abrasive brush 270 is placed in the distal airway lumen 77 and suction is applied via the vacuum hub 226 to contract the airway distal to the tip 239 of the catheter 238, drawing the epithelium 83 against the abrasive bristles 275. The abrasive bristles 275 function to contact and abrade the airway wall epithelial layer 83. In this manner, the epithelial layer 83 is stripped from the airway lumen wall (shown here as airway wall cross section 34) exposing the basement membrane 85. Suction from the vacuum source 233 drives the abraded epithelium through the hollow catheter 238, the vacuum hub 226 and the hose 229 into the filter or filter trap 230 where it remains as collection 231. In some instances, the vacuum source 233 is operated by the physician or operator using a foot pedal. In some instances, the abrasive brush 270 may be referred to as an elongated member. In some examples, the abrasive bristles 275 may also be referred to as abrasive features.

[0205] FIG. 17 illustrates an embodiment of a system 300 for treating a patient. The system 300 includes a treatment device 13 having an abrasive brush 270 and a motion drive handpiece 159, and a brush guide catheter 305. In some embodiments, the system 300 includes a vacuum hub, filters, and other associated elements, as shown, for example, in FIG. 15. The brush guide catheter 305 includes a distal end 301, a port 303, and a proximal end 302. The abrasive brush 270 includes a distal end 272, abrasive bristles 275, a proximal end 271, and a motion drive hub 187. As shown, the abrasive brush 270 may include a wire with a twist 274 in the brush wire. The motion drive hub 187 is coupled to a motor coupler 195, which is coupled to the motion drive handpiece 159. As shown, the motion drive handpiece 159 includes a slider switch 160. The motion-driven handpiece 159 is coupled to the battery 134 via a power cable 133 (or multiple power cables 133 coupled via one or more connectors 150). The battery 134 functions to power the motion-driven handpiece 159. The wall outlet plug 136 is coupled to the battery 134 via one or more electrical cables 135. In some examples, the electrical cables 135 have or are connected by a connector 150. In some examples, the battery 134 is a secondary battery. In some examples, the system 300 has an AC / DC converter in place of the battery 134. When the wall outlet plug 136 is plugged into a wall outlet, electricity from the wall outlet charges the battery 134 or directly operates the motion-driven handpiece 159. In some examples, the handpiece 159 is held by a user to manually apply linear and / or rotational forces. In some examples, the treatment device 13 is configured such that the strands of abrasive bristles 275 extend radially beyond the circumference defined by the catheter 305. In some examples, the treatment device 13 is configured such that the strands of abrasive bristles 275 do not extend radially beyond the circumference defined by the catheter 305.

[0206] In use, the tip 301 of the brush guide catheter 305 is placed in the distal airway lumen 77. The abrasive bristles 275 function to contact and abrade the airway wall epithelial layer 83. In this manner, the epithelial layer 83 is stripped from the airway lumen wall (shown here as airway wall cross section 34) and the basement membrane 85 is exposed. Suction from the vacuum source causes the abraded epithelium to pass through the brush guide catheter 305, the vacuum hub and the hose into the filter or filter trap, where it remains as a collection, as shown, for example, in FIG. 15. As described herein (e.g., with respect to FIGS. 27 and 28), in some examples, the system 300 includes a foam mechanism instead of or in addition to the abrasive bristles 275. In some examples, the abrasive brush 270 may be referred to as an elongated member. In some examples, the abrasive bristles 275 may be referred to as an abrasive feature.

[0207] Each of the embodiments shown in Figures 1 and 6-17 may incorporate any of the features of the vibration control mechanism shown in Figures 18-19. In some embodiments, the control mechanism or vibration control mechanism includes any one or more features disclosed herein with respect to the motor assembly or handpiece (e.g., a motion drive handpiece).

[0208] FIG. 18 illustrates an embodiment of a system 400 for treating a patient. The system 400 includes a motor 325, a motor drive shaft 326, an eccentric drive hub 327 (such as a rotating disk), an eccentric drive pin 328, a rotary oscillating hub 329, a rotary drive slot 330, an output shaft 331, a kinematic drive hub 187, and a rotary oscillating coupler key 332. As illustrated, the system 400 further includes a power cable 133 disposed between the motor 325 and a slider switch 160. In addition, the system 400 also includes a battery 134 coupled to the slider switch 160. In some examples, the slider switch 160 is coupled to the battery 134 via the power cable 133 (or multiple power cables 133 coupled via one or more connectors 150). The battery 134 functions to power the motor 325. A wall outlet plug 136 is coupled to the battery 134 via one or more electrical cables 135. In some examples, the electrical cable 135 includes or is connected by a connector 150. In some examples, the battery 134 is a secondary battery. In some examples, the system 300 includes an AC / DC converter in place of the battery 134. When the wall outlet plug 136 is inserted into a wall outlet, electricity from the wall outlet charges the battery 134 or directly powers the motor 325. As shown, operation of the motor 325 causes the rotary-oscillating coupler key 332 to oscillatorily rotate about a rotational axis 333, as indicated by arrow A.

[0209] FIG. 18A illustrates an exemplary embodiment of the vibrational motion that can be provided by the motion drive hub 187. As shown by arrow A, the motion drive hub 187 can rotationally oscillate through a range of motion of approximately 60 degrees. Similarly, as shown by arrow B, the motion drive hub 187 can rotationally oscillate through a range of motion of approximately 180 degrees. Additionally, as shown by arrow C, the motion drive hub 187 can rotationally oscillate through a range of motion of approximately 350 degrees. The treatment system can be configured to set any value or range of values ​​for the rotational oscillation. In some examples, the drive hub 187 (or the grinding balloon or grinding tool) oscillates through a rotational range of 5 degrees. In some examples, the drive hub 187 (or the grinding balloon or grinding tool) oscillates through a rotational range of 10 degrees. In some examples, the drive hub 187 (or the grinding balloon or grinding tool) oscillates through a rotational range of 0 to 360 degrees. The abrasive treatment device has the advantage that the vibration motion allows for the abrasion of controlled portions of the airway wall, ranging from a narrow area (e.g., an area corresponding to the range of a 1 degree vibration motion) to the entire inner circumference of the airway wall (e.g., an area corresponding to the range of a 360 degree vibration motion), without the need for manual rotation of the treatment device itself.

[0210] FIG. 19 illustrates an embodiment of a system 400 for treating a patient. The system 400 includes a motor 325, a motor drive shaft 326, an eccentric drive hub 327, an eccentric drive pin 328, an oscillating drive slide 336, a linear drive slot 337, an output shaft 331, a kinematic drive hub 187, and a linear oscillating coupler key 338. As illustrated, the system 400 further includes a power cable 133 disposed between the motor 325 and a slider switch 160. In addition, the system 400 also includes a battery 134 coupled to the slider switch 160. In some examples, the slider switch 160 is coupled to the battery 134 via the power cable 133 (or multiple power cables 133 coupled via one or more connectors 150). The battery 134 functions to power the motor 325. A wall outlet plug 136 is coupled to the battery 134 via one or more electrical cables 135. In some examples, the electrical cable 135 includes or is connected by a connector 150. In some examples, the battery 134 is a secondary battery. In some examples, the system 300 includes an AC / DC converter in place of the battery 134. When the wall outlet plug 136 is inserted into a wall outlet, electricity from the wall outlet charges the battery 134 or directly powers the motor 325. As shown, operation of the motor 325 can cause the linear oscillating coupler key 338 to oscillate and linearly translate along a translation axis 334, as indicated by the direction of the motion arrow 335.

[0211] Thus, when considering Figures 18 and 19 alone or in combination, it can be seen that a variety of oscillatory motions can be achieved. In some examples, elements of Figure 18 are used to achieve a rotational oscillatory motion. In some examples, elements of Figure 19 are used to achieve a linear translational oscillatory motion. In some examples, elements of Figures 18 and 19 are used in combination to achieve both rotational and linear translational oscillatory motion. In some examples, these three options are combined with pulling and / or pushing the treatment device along the longitudinal axis of the airway. In a combined device, the components shown in Figure 18 are combined with the components shown in Figure 19. For example, a rotary drive motor (such as motor 325 in Figure 18) is placed on a linear drive slide (such as drive slide 336 in Figure 19). In this way, the rotary drive motor (and the connected distal components) can be linearly oscillated.

[0212] It should be noted that Figures 6-19 may not necessarily be drawn to scale, and that the distal and proximal ends of the delivery instruments and / or treatment devices or other system elements may be exaggerated to provide focus and detail. Additionally, the catheters and / or treatment devices are much longer than shown, and are configured to be advanced through the bronchi and into the various airways, such that they can be advanced along airways beyond the fourth generation. Similarly, the airways are illustrated as being bisected to clearly show the devices and delivery instruments positioned therein.

[0213] FIG. 20 illustrates an embodiment of a system 500 for treating a patient. The system 500 includes a pulmonary treatment device 513 and a delivery instrument 501, such as a bronchoscope. The pulmonary treatment device 513 is sized and configured for delivery by the delivery instrument 501. The delivery instrument 501 is configured to be inserted into the lung. In some embodiments, the pulmonary treatment device 513 is configured to be delivered through a lumen of the delivery instrument, for example, by pushing the treatment device through a lumen of a bronchoscope, catheter, introducer, sheath, sleeve, or similar instrument. In some embodiments, the treatment device 513 is placed into a port 507 and the delivery instrument 501 is advanced through the bronchial tree to a target location within the lung. In some instances, the device 513 is placed into the bronchoscope port 507, a tip 514 of the device 513 is directed distally from the channel exit port 511, and a proximal end 515 of the device 513 extends proximally from the bronchoscope port 507.

[0214] As shown, the treatment device 513 includes a catheter 516 with a guidewire or dilator 517 inserted therethrough, which serves to guide the catheter 516. This configuration prevents the catheter 516 from scraping the airway wall or lung tissue as it advances through the airway lumen. The positioning of the guidewire or dilator 517 facilitates delivery of the catheter 516 to a desired anatomical location, such as a particular branch, airway branch, airway lumen, etc. In some examples, the tip 518 of the guidewire or dilator 517 includes a curved portion. In some examples, the curved portion can be rotated to direct the catheter 516 into the branch and advance the catheter 516 into the branch. In some examples, the rounded end of the tip 518 serves to guide a thicker tube, such as the catheter 516. In some examples, the tip 518 of the guidewire or dilator 517 includes a radiopaque material. In some examples, the tip of the catheter includes a radiopaque material.

[0215] In some examples, as shown in FIG. 21, the treatment device 513 is introduced into the patient P without the use of a bronchoscope. In some examples, the catheter 516 is introduced into the patient P using a guidewire or dilator 517. In some examples, the catheter 516 is introduced into the patient P without the use of a guidewire or dilator. Any of the treatment devices disclosed herein, such as the treatment device 513, may be delivered through a bronchoscope, may be delivered using only the lumen of a tracheal tube (such as a tracheal tube commonly used for ventilating a patient or accessing the patient's airway beyond the vocal cords), may be guided only along a guidewire, or may be delivered without being guided by a tube or wire. In some examples, a blunt tip at the distal end of the guidewire or dilator 517 helps to guide a thicker tube, such as the catheter 516.

[0216] FIG. 22 illustrates aspects of an exemplary guidewire 617 according to an embodiment of the present invention. In some examples, the guidewire 617 includes a twisted cable wire, a braided wire, a counter-rotated twisted wire, or any combination thereof. In some examples, the diameter D of the wire 620 ranges from about 1 mm to about 10 mm. Although the wire 620 may bend when advanced or retreated through the patient's airway (e.g., around corners or other obstacles or anatomical features), in some examples, the wire 620 is configured such that when the wire 620 is bent, there are no gaps between the strands 621 of the wire 620. In this case, no gaps are formed that could pinch tissue when the wire 620 is pulled back to a straight state during a treatment procedure. Gaps between the strands 621 of the wire may pinch tissue when the gaps close, causing the wire 620 to get caught in the patient, or tearing tissue when the guidewire 617 is removed. In the continuous wire embodiment shown in FIG. 22, the wire 620 does not open when bent. The above gap is a drawback of some guidewires with thin core wires. In some examples, the value of the diameter D of the wire 620 is about 1.5 mm. In some examples, the wire 620 is composed of a plurality of individual wire strands or wire cables 621. Such a multi-strand or multi-cable wire structure can form a smooth wire with high flexibility. In some examples, the wire 620 is composed of about 375 individual wire strands or cables 621. In some examples, the number of strands or cables 621 in the wire 620 or a portion thereof is reduced to improve pushability. For example, the number of cables or strands in the proximal portion 622 of the wire 620 ranges from about 4 to about 50. In some examples, the number of strands or cables 621 in the wire 620 or a portion thereof is increased to improve flexibility. For example, the number of cables or strands in the distal portion 623 of the wire 620 ranges from about 50 to about 1000. Thus, the guidewire 617 shown in FIG. 22 has a hybrid construction with two separate sections with different pushability / flexibility characteristics.Guidewire 617 has a proximal hub 618, a pushable proximal section 622, a flexible distal section 623, a connection 624 between proximal section 622 and distal section 623, and a distal termination 625. In some examples, connection 624 is a welded connection. In some examples, distal termination 625 is a distal welded termination. In some examples, distal termination 625 is formed into a particular shape during welding. In some examples, distal termination 625 is ball-shaped. In some examples, the diameter of the ball shape is about 2 mm. In some examples, the diameter of the ball shape is a value ranging from about 1 mm to about 10 mm. Wire 620 functions to transmit a rotational force without kinking, a drawback of thin core wire guidewires. In some examples, wire 620 is imparted with a rotational force by hub 618. In some examples, wire 620 is imparted with a rotational force from anywhere along the shaft of wire 620. This differs from thin core wire guidewires, where the outer coil floats above the core and rotational force must be applied from the hub. Wire 620 has the advantage that rotational force can be applied as needed and does not require the user to return to the proximal end every time they need to apply rotational force to the wire. In some instances, the rounded end of distal end 625 is useful for guiding a thicker tube, such as a catheter. In some instances, distal end 625 includes a radiopaque material.

[0217] FIG. 23 illustrates an embodiment of an exemplary dilator 717 according to an embodiment of the present invention. In some embodiments, the dilator 717 is configured as a solid plastic dilator. In some examples, the rounded end of the dilator 717 is useful for guiding a larger tube, such as a catheter. FIG. 24 illustrates an embodiment of an exemplary dilator 817 according to an embodiment of the present invention. As shown, the dilator 817 has a tip portion 823 with a curved shape. In some examples, the rounded end of the dilator 817 is useful for guiding a larger tube, such as a catheter. FIG. 25 illustrates an embodiment of an exemplary dilator 917 according to an embodiment of the present invention. As shown, the dilator 917 has a tip portion 923 with a curved shape that curves in two directions on the same plane. In some examples, the rounded end of the dilator 917 is useful for guiding a larger tube, such as a catheter.

[0218] FIG. 26 illustrates an embodiment of a system 1000 for treating a patient. The system 1000 includes a treatment device (not shown) and a vacuum hub 1226 coupled to a catheter 1238. The treatment device may have any one or more features of the treatment devices disclosed herein, such as the treatment devices shown in FIGS. 6-14, 16, 17, 27, and 28. A distal end 1239 of the catheter 1238 is inserted into the airway lumen, and the treatment device extends through the catheter 1238 and into the airway lumen. A proximal end 1240 of the catheter 1238 is coupled to the vacuum hub 1226 via a connection 1237. The system 1000 also includes a filter coupled to the vacuum hub 1226 via a hose 1229 and a vacuum source. Exemplary filter and / or vacuum source embodiments that may be incorporated into the system 1000 are illustrated in FIGS. 14-16. In use, the treatment device is placed within the catheter 1238 and irrigation fluid is delivered from the irrigation fluid source 1810 through the irrigation fluid conduit 1820 and the port conduit 1892 of the irrigation fluid port 1890 to the proximal portion 1252 of the outer lumen 1250 of the catheter 1238 and out the distal portion 1254 of the outer lumen. This causes the irrigation fluid to flow into the airway lumen L. Suction is applied, for example, from the vacuum source 1133 through the hose 1229 and through the vacuum hub 1226 to draw the irrigation fluid into the inner lumen 1260 of the catheter 1238. Additionally, as previously described, suction from the vacuum source 1133 can draw abraded epithelium and / or other tissue or debris from the airway through the catheter inner lumen 1260 and the hose 1229 into a filter or filter trap to remain as a collection. In some examples, the vacuum source 1133 is operated by the physician or operator using a foot pedal.

[0219] Thus, embodiments of the present invention encompass dual or multi-lumen catheter configurations that allow for suction and fluid delivery. Such embodiments allow for the delivery of a treatment or therapy device into the inner lumen 1260 (e.g., through the seal 1227). In some instances, the seal 1227 functions to close the rear opening or proximal portion 1262 of the inner lumen 1260 until a treatment device is introduced into the inner lumen 1260. In this manner, irrigation fluid can be injected through the fluid delivery port 1890 and the outer lumen 1250, after which the irrigation fluid can be aspirated out of the patient's body by action through the inner lumen 1260, the suction port 1241 of the vacuum hub 1226, the hose 1229, and the vacuum source 1133. In some embodiments, the system 1000 injects saline or other fluids to provide the irrigation fluid into the patient's airways. This irrigation fluid may be aspirated from the patient's body, for example, when a vacuum is applied to draw airway tissue or walls toward the catheter 1238 and to aspirate debris from the airway lumen L.

[0220] In some embodiments, a system such as system 2000 can be used to inject fluids containing antibiotics, antifungals, or other drugs into the lungs to minimize irritation of the airway walls and infections associated with mucus present in the airways. Other drugs, such as steroids, wound healing drugs, etc., can also be introduced into catheter 1238 (or secondary lumen 1250) to reduce or control the rate of inflammatory responses to cutting, grinding, or treatment of the airway walls. Injecting such fluids or saline during suction can create a flow path in and out of the patient's airway. This can move debris and other contaminants out of the airway to improve healing, tissue repair of the airway walls, and breathing. In some examples, the injected fluid has a desired or predetermined temperature. For example, the fluid is heated to a particular temperature before injection or cooled to a particular temperature before injection.

[0221] 27 and 28 show aspects of a treatment device 2000 according to an embodiment of the present invention. As shown, the treatment device 2000 includes an elongate element 2010 coupled to a tip portion 2020. The treatment device 2000 is delivered via a catheter 3000 to a desired location within a patient, for example, into an airway lumen L of the patient's lungs. In some embodiments, the tip portion 2020 includes or is made of an expandable and compressible material. For example, the tip portion 2020 includes an expandable foam material. In an exemplary embodiment, the tip portion performs a scrubbing function. In some examples, the tip portion performs a brushing function. In some examples, the tip portion 2020 includes an expandable open-cell foam or scrubbing material, similar to a plastic dishwashing tool. In some examples, the tip portion is formed from a material that has a hardness that allows it to abrade the epithelium. In some examples, the tip portion 2020 includes any of a variety of silicones, nylons, and / or other open-cell plastics. As shown in FIG. 28, as the tip section 2020 advances distally of the distal opening 3010 of the catheter 3000, the size and / or diameter of the tip section 2020 increases. For example, the amount of expansion of the diameter of the tip section ranges from about 2 mm to about 10 mm. During or after expansion, the tip section 2020 is moved axially or rotated, either slowly or periodically, either manually or using a motor at a speed of 100 Hz, or a combination of both. The delivery catheter can perform suction simultaneously while the tip section 2020 is scrubbing. Alternatively, a procedure is performed to aspirate mucus before deploying the tip section 2020 or scrubbing element, during scrubbing if necessary, and then after removing the tip section 2020 or scrubbing element from the catheter 3000 (e.g., after retracting proximally). In some examples, the elongate element 2010 may be referred to as an elongate member. In some examples, the tip portion 2020 may also be referred to as a grinding feature.

[0222] In some embodiments, the tip section 2020 includes various expandable polymers, metal meshes of ferrous and non-ferrous metals, and / or composites of metal and polymer combinations used as the expandable element. In some examples, the tip section 2020 can be expanded against the airway wall by advancing from the distal opening 3010 of the catheter, and then used to scrape the airway to remove epithelium and goblet cells. Control of the depth of action can be achieved by following a controlled motion pattern and controlling the abrasive performance of the abrasive material. In some examples, depth control can be achieved or adjusted by performing micro-motion of the treatment device.

[0223] In some examples, the distal portion 2020 includes any of a variety of polymers, including any crystalline or amorphous form of thermoplastic, thermoset, and elastomeric materials. Exemplary materials that can be used to manufacture the distal portion 2020 include, but are not limited to, low density polyethylene (LDPE), high density polyethylene (HDPE), polypropylene (PP), polyvinyl chloride (PVC), polystyrene (PS), nylon, nylon 6, nylon 6,6, Teflon (polytetrafluoroethylene), thermoplastic polyurethane (TPU), silicone, vinyl polysiloxane (PVS), or natural polymers. Natural polymers may be made from proteins and nucleic acids present in the human body, such as cellulose, natural rubber, silk, wool, starch, and natural rubber derived from latex. In some examples, the material of the distal portion 2020 includes looped wires or filaments. In some examples, such looped wires or filaments form edges that enhance the scraping action of the distal portion. In an exemplary embodiment, the tip portion 2020 is made of a material that allows the passage of fluid, tissue particles, and / or debris. In some examples, the tip portion 2020 includes one or more types of abrasive materials.

[0224] In some examples, the treatment device 2000 and / or catheter 3000 are introduced into the patient P using a guidewire or dilator. In some examples, the treatment device 2000 and / or catheter 3000 are introduced into the patient P without the use of a guidewire or dilator. Any of the treatment devices disclosed herein may be delivered through a bronchoscope, may be delivered using only the lumen of a tracheal tube (e.g., a bronchial tube commonly used to ventilate a patient or access a patient's airway beyond the vocal cords), may be guided only along a guidewire, or may be delivered without being guided by a tube or wire. In some examples, the treatment device 2000 is introduced into the patient's airway using only the catheter 3000. In some examples, the catheter 3000 is coupled to or introduced by a bronchoscope. In some examples, the treatment device 2000 is introduced into the patient's airway using only the bronchoscope, without the use of a catheter.

[0225] In some examples, the diameter of the inner lumen of the catheter 2000 ranges from about 6 mm to about 10 mm. The catheters or flexible bodies of the embodiments disclosed herein can all have similarly sized inner lumens.

[0226] In some examples, the distal portion 2020 has a cylindrical shape or profile. In some examples, the distal portion 202 has a spherical shape or profile. In some examples, the distal portion 2020 has a conical shape or profile. In some examples, the distal portion has a larger distal diameter and cross-section and a smaller proximal diameter and cross-section.

[0227] In some instances, the expansion ratio value of the tip portion is about 10:1 (eg, by comparing the uncompressed dimensions shown in FIG. 28 with the compressed dimensions shown in FIG. 27). In some examples, the elongate element 2010 is a twisted cable, a braided cable, or any of the embodiments described herein with reference to FIG. 22. In some examples, the distal portion 2020 is disposed closer to a proximal or central portion of the elongate element, such as at or near the junction 624 shown in FIG. 22. In some examples, the distal portion 2020 is bonded to the elongate element 2010. In some examples, the distal portion of the elongate element 2010 comprises a radiopaque material.

[0228] In some embodiments, the foam (e.g., the expandable foam material of the tip portion 2020) is manufactured to have open cell pores with diameter values ​​ranging from about 10 μm to about 5 mm. In some examples, the open cell pores have one or more dimensions (e.g., width, length, or height) with diameter values ​​ranging from about 10 μm to about 5 mm.

[0229] In some examples, a densely compressed foam or coarse sponge structure (such as FIG. 27) can be expanded to a less compressed or uncompressed foam or coarse sponge structure (such as FIG. 28). As can be seen in FIG. 27, the foam or coarse sponge is held in a compressed state by being confined inside the catheter 3000. As shown in FIG. 28, the foam structure of the tip section 2020 has a network of intact expanded loops (or circles) connected in a central or inner region, with cut strands or edges protruding from the outer edge or surface of the foam structure. The cut strands can act as bristles and provide additional scrubbing action. The exposed edges of the loops or circles (e.g., defining the open cell pores) located on the outer surface of the tip section 2020 can also provide a scraping action.

[0230] In some examples, the foam element or tip section 2020 is formed from or includes strands of ribbon intertwined in aligned or unaligned bundles. The ribbons include, are manufactured from, or are plated with any of a variety of materials, such as stainless steel, aluminum, tantalum, tungsten, silver (or other bacteriostatic or bactericidal materials), gold (or other highly radiopaque materials), titanium, iron or non-ferrous metal alloys such as Nitinol or other similar shape memory alloys, carbon, polymers, synthetic or natural fibers such as silk, or any combination of the above. In some embodiments of the ribbon bundle, the bundle is bent within the range of elastic deformation of any material (e.g., material used to manufacture the ribbon), and when the bundle is released from the lumen of the catheter 3000, the bundle expands from a first diameter to a second diameter. In some examples, after the bundle is released from the lumen of the catheter, the bundle expands from a diameter of 2 mm in the guide catheter to a diameter of 15 mm or more.

[0231] Some embodiments of the present invention are designed to anticipate the significant tissue damage experienced by patients with severe COPD, and provide therapeutic methods and devices specifically designed to treat such patients and the particularly damaged lung tissue within the patient. Such tissue damage is often not identified or recognized in prior treatment plans, resulting in inadequate treatment or undesirable outcomes. In particular, the present invention determines the extent of tissue damage and the location of the damage in one or more lung lobes in determining the treatment plan. The extent and distribution of tissue damage is used to determine the optimal location at which to administer the therapy. These data are also used to evaluate the patient over time to determine whether a treatment should be administered to the same location targeted in a previous treatment to consolidate or restore improvements achieved in the first treatment, or to determine whether a therapeutic treatment would best be administered to a new location not previously treated to restore the benefits of the original treatment.

[0232] Overall, patients often experience improvement in a variety of symptoms, including reduced coughing (e.g., coughing up trapped air and mucus), increased ability to clear mucus by opening the passageways larger and for longer periods of time, improved mobility (e.g., as measured by the now standard 6-minute walk test), reduced respiratory effort, reduced mood swings, reduced respiratory rate, reduced glottal closure reflex (clearing mucus reduces inflammation and reduces coughing), reduced incidence of respiratory failure, and increased time between COPD exacerbations.

[0233] Embodiments of the pulmonary therapy device include a variety of features and design elements for achieving the above-mentioned therapeutic benefits and clinical goals. Moreover, such features and design elements can be configured in a variety of variations, some of which are described herein.

[0234] Various aspects of the pulmonary therapy device are described in more detail herein. Although various aspects and features are described, it is understood that an embodiment of the device may have any combination of these aspects and features. Similarly, some embodiments may not include all of the described aspects and features.

[0235] In some embodiments, one or more components of the therapeutic system are configured for controlled delivery of an agent, such as a drug, which in some instances reduces the rate of wound healing, tissue repair, inflammation, granulation tissue formation, hyperplasia, and the like.

[0236] Various approaches are described herein. For example, the therapeutic device may be introduced through a lumen of the delivery instrument (either by pushing or pulling the device itself within the lumen, by being placed within an introducer, or by being attached to an additional instrument such as a catheter or guidewire advanceable within the lumen), or the therapeutic device may be introduced attached to an external portion of the delivery instrument (e.g., on the insertion cord tip of a bronchoscope or on a catheter), or the therapeutic device may be pushed or pulled from its attached position by an inner or outer sleeve or instrument.

[0237] The guidewire has a configuration suitable for advancement within the lung tissue, specifically configured to contact the lung tissue in a manner that limits or prevents accidents or damage. In some embodiments, the guidewire includes a wire cable, wire bundle, continuous braid, twisted wire, twisted wire bundle shaft structure, etc., having a blunt tip (typically formed by crimping, gluing, or welding the tip of the guidewire shaft structure). In some embodiments, the guidewire has a diameter in the range of 0.005 to 0.100 inches, preferably about 0.018 to 0.070 inches. Typically, the guidewire occludes the lumen of the catheter such that there is no or only a very small gap when the guidewire curves or bends during delivery. In some embodiments, the guidewire is configured such that when a bend of a radius of 0.5 inches or less occurs, the gap in the portion of the guidewire that contacts the tissue does not exceed 0.030 inches, and more preferably is in the range of 0 to 0.020 inches, to prevent tissue from becoming caught in the gap.

[0238] The above and related guidewire feature aspects can be further understood with reference to any one or more of the guidewire embodiments disclosed herein (e.g., FIGS. 6, 7A-7D, 8A-8B, 9, 10, 11, and 20-25). In some examples, the guidewires described herein include, are made of, or are plated with any of a variety of materials, such as stainless steel, aluminum, tantalum, tungsten, silver (or other bacteriostatic or bactericidal materials), gold (or other highly radiopaque materials), titanium, iron or non-ferrous metal alloys such as Nitinol or other similar shape memory alloys, carbon, polymers, synthetic or natural fibers such as silk, or any combination of the above.

[0239] Medical imaging can be used to visualize the delivery or operation of any of the system or device embodiments disclosed herein. Medical imaging includes the use of any form of equipment that allows real-time imaging, recording, or computer processing to visualize devices, organs, or tissues within the human body using the line of sight of the human eye without exposing the devices, organs, or tissues. Such medical imaging techniques typically utilize low to high frequency electromagnetic or acoustic energy emissions, such as one or more video cameras on a bronchoscope, computed tomography machines, biplane imagers, fluoroscopy machines, ultrasound machines, or standard planar x-ray machines. In some embodiments, the pulmonary treatment devices are placed in the lungs by a surgical technique, such as a video-assisted minimally invasive skin incision or laparotomy. Many of the pulmonary treatment devices described herein can be placed in any lung, lobe, main segment, segment, subsegment, or further down the bronchial tree. Similarly, many of the devices can be inserted directly into the lungs through the chest wall, and may also be inserted through the walls of the main bronchi to reach pockets of disrupted parenchyma. Many of the devices can be implanted through open chest surgery or any type of endoscope. The respiratory function tests described herein are excellent indicators of a good and adequate response.

[0240] All features of the described systems and devices are applicable to the described methods, mutatis mutandis, and vice versa.Embodiments of the present invention include kits having one or more components of the therapeutic systems disclosed herein.In some embodiments, the kits include one or more therapeutic systems or one or more components of the therapeutic systems, and instructions for using the system, e.g., according to any of the methods disclosed herein.

[0241] Although preferred embodiments of the present invention have been described, such embodiments are merely exemplary. Numerous variations, changes, and substitutions may occur to those skilled in the art without departing from the present invention. Various alternatives to the embodiments of the present invention described herein may be employed in the practice of the present invention. The scope of the present invention is defined by the following claims. Methods and structures within the scope of these claims and their equivalents are within the scope of the claims.

Claims

1. 1. A system for treating a wall of a lung airway of a patient, comprising: a bronchoscope configured to be advanced into the patient's lungs, the bronchoscope having a flexible body, a bronchoscope tip with a camera, and a working channel exit port; a treatment device having an elongate member, the elongate member configured to be introduced through the working channel exit port of the bronchoscope and into the patient's pulmonary airways, the elongate member having an expandable grinding feature; and means for generating vibrational motion, linear motion, or expansion on the abrasive features such that the abrasive features atraumatically abrade epithelium along a wall of the patient's pulmonary airway.

2. the means including means for generating a vibration motion in the grinding feature; The system of claim 1 , wherein the oscillatory motion comprises a rotational oscillatory motion.

3. the means including means for generating a vibration motion in the grinding feature; The system of claim 1 , wherein the oscillatory motion comprises a linear oscillatory motion.

4. the means including means for generating a vibration motion in the grinding feature; The system of claim 1 , wherein the oscillatory motion includes a rotational oscillatory motion and a linear oscillatory motion.

5. The system of claim 1 , wherein the abrasive features atraumatically abrade the epithelium to a controlled depth.

6. The system of claim 5 , wherein the controlled depth is approximately 20 microns.

7. The system of claim 1 , further comprising a vacuum source configured to draw the epithelium towards the abrasive features.

8. 10. The system of claim 1, wherein the grinding features comprise grinding mesh, grinding features or grinding media selected from the group consisting of alumina, carbide, sand, quartz, glass, metal, ceramic, plastic, carbon, diamond, oxide, silicon carbide, polymer, aluminum oxide, co-fused alumina zirconia, garnet, flint, cubic boron nitride, tungsten carbide, cobalt, glassy polysaccharides, sintered sol-gel, styrene acrylonitrile copolymer, alumina zirconia, emery and chromium (III).

9. the grinding feature includes the grinding media; 10. The system of claim 8, wherein the grinding media has a particle size ranging from about 2 microns average particle size to 3000 microns average particle size.

10. The system of claim 1 , wherein the elongate member has an expandable mechanism and the abrasive features are disposed on the expandable mechanism.

11. The system of claim 1 , further comprising a vacuum source configured to draw biological material removed from the abraded epithelium into a filter trap.

12. The system of claim 1 , further comprising a vacuum source configured to draw debris removed from the abraded epithelium into a filter trap.

13. The system of claim 1 , wherein the expandable abrasive feature is attached to a guidewire.

14. The system of claim 13 , wherein the guidewire includes a blunt tip.

15. The system of claim 13 , wherein the guidewire is advanced into zero or more airways within the patient.

16. The system of claim 13 , wherein the guidewire comprises a wire cable.

17. 14. The system of claim 13, wherein the guidewire has a diameter in the range of 0.005 inches to 0.100 inches.

18. The system of claim 1 , wherein the elongate member comprises a guidewire.

19. The treatment device comprises a catheter; the abrasive feature comprises an expandable sponge structure; The system of claim 1 , wherein the expandable sponge structure is in a compressed state when confined within the catheter and in a non-compressed state when disposed outside the catheter.

20. The treatment device includes a catheter having a side port; The system of claim 1 , wherein a portion of the abrasive feature is configured to extend radially through the side port beyond a circumference defined by the catheter.

21. the elongate member is a catheter having a distal port disposed distal to the abrasive feature and a proximal port disposed proximal to the abrasive feature; The system of claim 1 , wherein suction is applied through the distal and proximal ports to draw tissue against the abrasive features.

22. The treatment device comprises a catheter; The system of claim 1 , wherein suction from a suction source drives biological material through the catheter and into a filter trap.

23. The system of claim 1 , wherein the expandable abrasive feature is coupled to a catheter.

24. The system of claim 1 , wherein the grinding feature is configured to be pulled in a proximal direction to impart linear motion to the grinding feature.

25. The system of claim 2 , wherein the rotational oscillatory motion spans a range of motion of 350 degrees or less.

26. The system of claim 1 , wherein the abrasive feature comprises a tip coil.

27. The system of claim 1 , wherein the abrasive feature comprises a blunt tip.

28. The system of claim 1 , wherein the grinding feature comprises a wire.

29. 30. The system of claim 28, wherein the strands comprise wire.

30. 30. The system of claim 28, wherein the strands include a cross-section selected from the group consisting of a circular cross-section, a square cross-section, and a rectangular cross-section.

31. 30. The system of claim 28, wherein the strands include a shape selected from the group consisting of a helical shape, a random shape, a whisk shape, a sinusoidal shape, and a troposkein shape.

32. 30. The system of claim 28, wherein the strands comprise a member selected from the group consisting of stainless steel wire, titanium wire, nitinol wire, nickel-based alloy wire, monofilament fibers, multifilament fibers, braids, polymer fibers, ceramic fibers, glass fibers, and organic material fibers.

33. The system of claim 1 , wherein the grinding feature comprises a plurality of strands.

34. The system of claim 1 , wherein the abrasive feature comprises a laser cut tube.

35. The system of claim 1 , wherein the abrasive features comprise Nitinol.

36. The system of claim 1 , wherein the grinding features include one or more resilient spring elements.

37. The system of claim 1 , wherein the abrasive features include one or more resilient spring elements, each of the resilient spring elements having an abrasive edge provided in the absence of a separate abrasive material.

38. The system of claim 1 , wherein the grinding features include one or more resilient spring elements, each of the resilient spring elements including a round wire.

39. The system of claim 1 , wherein the grinding features include one or more resilient spring elements, each of the resilient spring elements including a flattened shape.

40. The system of claim 1 , wherein the abrasive features comprise a shape memory material.

41. The system of claim 1 , wherein the abrasive features are operable to expand and push against a wall of the lung airway.

42. 10. The system of claim 1, wherein the abrasive features are operable to expand and push against a wall of the lung airway, the diameter of the lung airway being within a range of about 2 mm to about 25 mm.

43. The system of claim 1 , wherein the grinding feature is operable to change diameter from a first value to a second value within a range of 0.01 mm to 28 mm.

44. The system of claim 1 , wherein the abrasive features are operable to expand upon manipulation.

45. The system of claim 1 , wherein the grinding features are operable to expand by manipulation of a pull wire.

46. The system of claim 1 , wherein the system is operable to treat a patient exhibiting goblet cell hyperplasia.

47. The system of claim 1 , wherein the system is operable to treat a patient exhibiting bronchitis.

48. The system of claim 1 , wherein the system is operable to treat a patient exhibiting frequent coughing.

49. The system of claim 1 , wherein the system is operable to treat a patient exhibiting low arterial oxygen in the bloodstream.

50. 10. The system of claim 1, wherein the system is operable to treat a patient with a short six minute walk distance.

51. The system of claim 1 , wherein the system is operable to treat a patient exhibiting low forced expiratory volume.

52. The system of claim 1 , wherein the system is operable to treat a patient exhibiting a high residual load.

53. The system of claim 1 , wherein the system is operable to treat a patient with a high amount of gas trapped in the lungs during or after expiration.

54. The system of claim 1 , wherein the system is operable to treat a patient exhibiting a high RV / TLC ratio.

55. The system of claim 1 , wherein the system is operable to treat a patient exhibiting low lobar volume during inspiration.

56. The system of claim 1 , wherein the bronchoscope is steerable.

57. The system of claim 1 , wherein the bronchoscope has a working channel of 3.2 mm or less.

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