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Patent US20060278244 - Methods of reducing mucus in airways - Google PatentsSearch Images Maps Play YouTube News Gmail Drive More »Sign inAdvanced Patent SearchPatentsThis relates to treating an asthmatic lung and more particularly, relates to advancing a treatment device into the lung and treating the lung with the device. This also includes additional steps of treating the airway wall, applying energy or heat to the airway wall in an asthmatic lung....http://www.google.com/patents/US20060278244?utm_source=gb-gplus-sharePatent US20060278244 - Methods of reducing mucus in airwaysAdvanced Patent SearchPublication numberUS20060278244 A1Publication typeApplicationApplication numberUS 11/425,345Publication dateDec 14, 2006Filing dateJun 20, 2006Priority dateJun 10, 1998Also published asCA2370223A1, CA2370223C, DE60023283D1, DE60023283T2, EP1173103A2, EP1173103B1, US6634363, US7264002, US7273055, US7542802, US8443810, US8534291, US8733367, US20040031494, US20040182399, US20060278243, US20070062545, US20070118190, US20130211402, US20130218158, WO2000062699A2, WO2000062699A3Publication number11425345, 425345, US 2006/0278244 A1, US 2006/278244 A1, US 20060278244 A1, US 20060278244A1, US 2006278244 A1, US 2006278244A1, US-A1-20060278244, US-A1-2006278244, US2006/0278244A1, US2006/278244A1, US20060278244 A1, US20060278244A1, US2006278244 A1, US2006278244A1InventorsChristopher Danek, Michael Biggs, Bryan Loomas, Michael Laufer, Gary Kaplan, Kelly ShrinerOriginal AssigneeAsthmatx, Inc.Export CitationBiBTeX, EndNote, RefManPatent Citations (2), Referenced by (2), Classifications (57), Legal Events (2) External Links: USPTO, USPTO Assignment, EspacenetMethods of reducing mucus in airways
DETAILED DESCRIPTION The invention relates to methods for improving airflow through the airways of a lung having reversible obstructive pulmonary disease. It is intended that the invention is applicable to any aspect of reversible obstructive pulmonary disease, including but not limited to asthma. One way of improving airflow is to decrease the resistance to airflow within the lungs. There are several approaches to reducing this resistance, including but not limited to reducing the ability of the airway to contract, increasing the airway diameter, reducing the inflammation of airway tissues, and/or reducing the amount of mucus plugging of the airway. The present invention includes advancing a treatment device into the lung and treating the lung to at least reduce the ability of the lung to produce at least one symptom of reversible obstructive pulmonary disease. The following is a brief discussion of some causes of increased resistance to airflow within the lungs and the inventive treatment of the invention described herein. As such, the following discussion is not intended to limit the aspects or objective of the inventive method as the inventive method may cause physiological changes not described below but such changes still contributing to reducing or eliminating at least one of the symptoms of reversible obstructive pulmonary disease. Reducing the Ability of the Airway to Contract The inventive treatment reduces the ability of the airways to narrow or to reduce in diameter due to airway smooth muscle contraction. The inventive treatment uses a modality of treatments including, but not limited to the following: chemical, radio frequency, radioactivity, heat, ultrasound, radiant, laser, microwave, or mechanical energy (such as in the form of cutting, punching, abrading, rubbing, or dilating). This treatment reduces the ability of the smooth muscle to contract thereby lessening the severity of an asthma attack. The reduction in the ability of the smooth muscle to contract may be achieved by treating the smooth muscle itself or by treating other tissues which in turn influence smooth muscle contraction or the response of the airway to the smooth muscle contraction. Treatment may also reduce airway responsiveness or the tendency of the airway to narrow or to constrict in response to a stimulus. The amount of smooth muscle surrounding the airway can be reduced by exposing the smooth muscle to energy which either kills the muscle cells or prevents these cells from replicating. The reduction in smooth muscle reduces the ability of the smooth muscle to contract and to narrow the airway during a spasm. The reduction in smooth muscle and surrounding tissue has the added potential benefit of increasing the caliber or diameter of the airways, this benefit reduces the resistance to airflow through the airways. In addition to the use of debulking smooth muscle tissue to open up the airways, the device used in the present invention may also eliminate smooth muscle altogether by damaging or destroying the muscle. The elimination of the smooth muscle prevents the contraction or spasms of hyper-reactive airways of a patient having reversible obstructive pulmonary disease. By doing so, the elimination of the smooth muscle may reduce some symptoms of reversible obstructive pulmonary disease. The ability of the airway to contract can also be altered by treatment of the smooth muscle in particular patterns. The smooth muscle is arranged around the airways in a generally helical pattern with pitch angles ranging from about −38 to about +38 degrees. Thus, the treatment of the smooth muscle in appropriate patterns interrupts or cuts through the helical pattern of the smooth muscle at a proper pitch and prevents the airway from constricting. This procedure of patterned treatment application eliminates contraction of the airways without completely eradicating smooth muscle and other airway tissue. A pattern for treatment may be chosen from a variety of patterns including longitudinal or axial stripes, circumferential bands, helical stripes, and the like as well as spot patterns having rectangular, elliptical, circular or other shapes. The size, number, and spacing of the treatment bands, stripes, or spots are chosen to provide a desired clinical effect of reduced airway responsiveness while limiting insult to the airway to a clinically acceptable level. The patterned treatment of the tissues surrounding the airways with energy provides various advantages. The careful selection of the portion of the airway to be treated allows desired results to be achieved while reducing the total healing load. Patterned treatment can also achieve desired results with decreased morbidity, preservation of epithelium, and preservation of a continuous or near continuous ciliated inner surface of the airway for mucociliary clearance. The pattern of treatment may also be chosen to achieve desired results while limiting total treatment area and/or the number of airways treated, thereby improving speed and ease of treatment. Application of energy to the tissue surrounding the airways may also cause the DNA of the cells to become cross linked. The treated cells with cross linked DNA are incapable of replicating. Accordingly, over time, as the smooth muscle cells die, the total thickness of smooth muscle decreases because of the inability of the cells to replicate. The programmed cell death causing a reduction in the volume of tissue is called apoptosis. This treatment does not cause an immediate effect but causes shrinking of the smooth muscle and opening of the airway over time and substantially prevents re-growth. The application of energy to the walls of the airway may also be used to cause a cross linking of the DNA of the mucus gland cells thereby preventing them from replicating and reducing excess mucus plugging or production over time. The ability of the airways to contract may also be reduced by altering mechanical properties of the airway wall, such as by increasing stiffness of the wall or by increasing parenchymal tethering of the airway wall. Both of these methods increase the strength of the airway wall and further oppose contraction and narrowing of the airway. There are several ways to increase the stiffness of the airway wall. One way to increase stiffness is to induce fibrosis or a wound healing response by causing trauma to the airway wall. The trauma can be caused by delivery of therapeutic energy to the tissue in the airway wall, by mechanical insult to the tissue, or by chemically affecting the tissue. The energy is preferably delivered in such a way that it minimizes or limits the intra-luminal thickening that may occur. Another way to increase the effective stiffness of the airway wall is to alter the submucosal folding of the airway upon narrowing. The mucosal layer includes the epithelium, its basement membrane, and the lamina propria, a subepithelial collagen layer. The submucosal layer may also play a role in airway folding. As an airway narrows, its perimeter remains relatively constant, with the mucosal layer folding upon itself. As the airway narrows further, the mucosal folds mechanically interfere with each other, effectively stiffening the airway. In asthmatic patients, the number of folds is fewer and the size of the folds is larger, and thus, the airway is free to narrow with less mechanical interference of mucosal folds than in a healthy patient. Thus, asthmatic patients have a decrease in airway stiffness and the airways have less resistance to narrowing. The mucosal folding in asthmatic patients can be improved by treatment of the airway in a manner which encourages folding. Preferably, a treatment will increase the number of folds and/or decrease the size of the folds in the mucosal layer. For example, treatment of the airway wall in a pattern such as longitudinal stripes can encourage greater number of smaller mucosal folds and increase airway stiffness. The mucosal folding can also be increased by encouraging a greater number of smaller folds by reducing the thickness of the mucosa and/or submucosal layer. The decreased thickness of the mucosa or submucosa may be achieved by application of energy which either reduces the number of cells in the mucosa or submucosal layer or which prevents replication of the cells in the mucosa or submucosal layer. A thinner mucosa or submucosal layer will have an increased tendency to fold and increased mechanical stiffening caused by the folds. Another way to reduce the ability of the airways to contract is to improve parenchymal tethering. The parenchyma surrounds airways and includes the alveolus and tissue connected to and surrounding the outer portion of the airway wall. The parenchyma includes the alveolus and tissue connected to and surrounding the cartilage that supports the larger airways. In a healthy patient, the parenchyma provides a tissue network which connects to and helps to support the airway. Edema or accumulation of fluid in lung tissue in patients with asthma or COPD is believed to decouple the airway from the parenchyma reducing the restraining force of the parenchyma which opposes airway constriction. Energy can be used to treat the parenchyma to reduce edema and/or improve parenchymal tethering. In addition, the applied energy may be used to improve connection between the airway smooth muscle and submucosal layer to the surrounding cartilage, and to encourage wound healing, collagen deposition, and/or fibrosis in the tissue surrounding the airway to help support the airway and prevent airway contraction. Increasing the Airway Diameter Hypertrophy of smooth muscle, chronic inflammation of airway tissues, and general thickening of all parts of the airway wall can reduce the airway diameter in patients with reversible obstructive pulmonary disease. Increasing the overall airway diameter using a variety of techniques can improve the passage of air through the airways. Application of energy to the airway smooth muscle of an asthmatic patient can debulk or reduce the volume of smooth muscle. This reduced volume of smooth muscle increases the airway diameter for improved air exchange. Reducing inflammation and edema of the tissue surrounding the airway can also increase the diameter of an airway. Inflammation and edema (accumulation of fluid) of the airway are chronic features of asthma. The inflammation and edema can be reduced by application of energy to stimulate wound healing and regenerate normal tissue. Healing of the epithelium or sections of the epithelium experiencing ongoing denudation and renewal allows regeneration of healthy epithelium with less associated airway inflammation. The less inflamed airway has an increased airway diameter both at a resting state and in constriction. The wound healing can also deposit collagen which improves parenchymal tethering. Inflammatory mediators released by tissue in the airway wall may serve as a stimulus for airway smooth muscle contraction. Therapy that reduces the production and release of inflammatory mediator can reduce smooth muscle contraction, inflammation of the airways, and edema. Examples of inflammatory mediators are cytokines, chemokines, and histamine. The tissues which produce and release inflammatory mediators include airway smooth muscle, epithelium, and mast cells. Treatment of these structures with energy can reduce the ability of the airway structures to produce or release inflammatory mediators. The reduction in released inflammatory mediators will reduce chronic inflammation, thereby increasing the airway inner diameter, and may also reduce hyper-responsiveness of the airway smooth muscle. A further process for increasing the airway diameter is by denervation. A resting tone of smooth muscle is nerve regulated by release of catecholamines. Thus, by damaging or eliminating nerve tissue in the airways the resting tone of the smooth muscle is reduced, and the airway diameter is increased. Resting tone may also be reduced by directly affecting the ability of smooth muscle tissue to contract. Reducing Plugging of the Airway Excess mucus production and mucus plugging are common problems during both acute asthma exacerbation and in chronic asthma management. Excess mucus in the airways increases the resistance to airflow through the airways by physically blocking all or part of the airway. Excess mucus may also contribute to increased numbers of leukocytes found in airways of asthmatic patients by trapping leukocytes. Thus, excess mucus can increase chronic inflammation of the airways. One type of asthma therapy involves treatment of the airways with energy to target and reduce the amount of mucus producing cells and glands and to reduce the effectiveness of the remaining mucus producing cells and glands. The treatment can eliminate all or a portion of the mucus producing cells and glands, can prevent the cells from replicating or can inhibit their ability to secrete mucus. This treatment will have both chronic benefits in increasing airflow through the airways and will lessen the severity of acute exacerbation of the symptoms of reversible obstructive pulmonary disease. Application of Treatment The following illustrations are examples of the invention described herein. It is contemplated that combinations of aspects of specific embodiments or combinations of the specific embodiments themselves are within the scope of this disclosure. FIGS. 1 and 2 illustrate cross sections of two different airways in a healthy patient. The airway of FIG. 1 is a medium sized bronchus having an airway diameter D1 of about 3 mm. FIG. 2 shows a section through a bronchiole having an airway diameter D2 of about 1.5 mm. Each airway includes a folded inner surface or epithelium 10 surrounded by stroma 12 and smooth muscle tissue 14. The larger airways including the bronchus shown in FIG. 1 also have mucous glands 16 and cartilage 18 surrounding the smooth muscle tissue 14. Nerve fibers 20 and blood vessels 24 also surround the airway. FIG. 3 illustrates the bronchus of FIG. 1 in which the smooth muscle 14 has hypertrophied and increased in thickness causing the airway diameter to be reduced from the diameter D1 to a diameter D3. FIG. 4 is a schematic side view of the lungs being treated with a treatment device 38 according to the present invention. The treatment device 38 is an elongated member for treating tissue at a treatment site 34 within a lung. Although the invention discusses treatment of tissue at the surface it is also intended that the invention include treatment below an epithelial layer of the lung tissue. An example of devices for use with the methods of this invention are found in the following U.S. patent applications Ser. No. 09/095,323—Methods and Apparatus for Treating Smooth Muscles in the Walls of Body Conduits; Ser. No. 09/349,715—Method of Increasing Gas Exchange of a Lung now U.S. Pat. No. 6,488,675; and Ser. No. 09/296,040—Devices for Modification of Airways By Transfer of Energy now U.S. Pat. No. 6,411,852; Ser. No. 09/436,455 Devices for Modification of Airways by Transfer of Energy. The entirety of each of the aforementioned applications is incorporated by reference herein. The treatment of an airway with the treatment device may involve placing a visualization system such as an endoscope or bronchoscope into the airways. The treatment device is then inserted through or next to the bronchoscope or endoscope while visualizing the airways. Alternatively, the visualization system may be built directly into the treatment device using fiber optic imaging and lenses or a CCD and lens arranged at the distal portion of the treatment device. The treatment device may also be positioned using radiographic visualization such as fluoroscopy or other external visualization means. The treatment device which has been positioned with a distal end within an airway to be treated is energized so that energy is applied to the tissue of the airway walls in a desired pattern and intensity. The distal end of the treatment device may be moved through the airway in a uniform painting like motion to expose the entire length of an airway to be treated to the energy. The treatment device may be passed axially along the airway one or more times to achieve adequate treatment. The “painting-like” motion used to exposed the entire length of an airway to the energy may be performed by moving the entire treatment device from the proximal end either manually or by motor. Alternatively, segments, stripes, rings or other treatment patterns may be used. According to one variation of the invention, the energy is transferred to or from an airway wall in the opening region of the airway, preferably within a length of approximately two times the airway diameter or less, and to wall regions of airways distal to bifurcations and side branches, preferably within a distance of approximately twice the airway diameter or less. The invention may also be used to treat long segments of un-bifurcated airway. The invention includes a method of advancing a treatment device into a lung and treating the lung with the device to, at least, reduce the ability of the lung to produce at least one symptom of reversible obstructive pulmonary disease. It is contemplated that the treatment may reduce all of the symptoms of reversible obstructive disease. Alternatively, the treatment may be selected to address specific symptoms of the disease. It is also intended that the treatment of the lung may sufficiently reduce the symptoms of reversible obstructive pulmonary disease such that the patient is able to function as those free from the disease. Alternatively, the treatment may be such that the symptoms are reduced to allow the patient to more easily manage the disease. It is also intended that the effects of the treatment may be either long term or short term with repeating treatment necessary to suppress the symptoms. The methods of the invention described herein may be performed while the lung is experiencing natural symptoms of reversible obstructive pulmonary disease. One such example is where an individual, experiencing an asthma attack, or acute exacerbation of asthma or COPD, undergoes treatment to improve the individual's ability to breath. In such a case, the treatment, called ‘rescue,’ seeks to provide immediate relief for the patient. The method may also include the steps of locating one or more treatment sites within an airway of the lung, selecting one of the treatment sites from the locating step and treating at least one of the selected treatment sites. As mentioned above, these steps may be, but are not necessarily, performed while the lung is experiencing symptoms of reversible obstructive pulmonary disease. The invention may further comprise the step of stimulating the lung to produce at least one artificially induced symptom of reversible obstructive pulmonary disease. For example, stimulation of the lung would preferably increase the resistance to airflow within the lung, constrict airways within the lung, inflame/irritate airway tissues, increase edema and/or increase the amount of mucus plugging of the airway. Stimulation of the lung may occur at any point during the procedure or before the procedure. For example, the lung may be stimulated either prior to or after, the step of locating a treatment site. If the lung is stimulated prior to the step of locating a treatment site, the reaction of the stimulated tissue within the lung may be useful in determining which locations are to be selected as treatment sites. The lung tissue or airway tissue within the lung may be stimulated by a variety of methods including but not limited to pharmacological stimulation, (e.g., histamine, methacholine, or other bronchoconstricting agents, etc.), electrical stimulation, mechanical stimulation, or any other stimuli causing obstructive pulmonary symptoms. For example, electrical stimulation may comprise exposing airway tissue to electrical field stimulation. An example of such parameters include 15 VDC, 0.5 ms pulses, 0.5-16 Hz, and 70 VDC, 2-3 ms pulses, 20 HZ. The locating step described above may be performed using a non-invasive imaging technique, including but not limited to, a bronchogram, magnetic resonance imaging, computed tomography, radiography (e.g., x-ray), and ventilation perfusion scans. The invention further includes the steps of testing the lung for at least one pre-treatment pulmonary function value prior to treating the lung with the device. After the lung is treated, the lung is re-tested for at least one post-treatment pulmonary function value. Naturally, the two pulmonary function values may be compared to estimate the effect of the treatment. The invention may also include treating additional sites in the lung after the re-testing step to at least reduce the effect of at least one symptom of reversible obstructive pulmonary disease. The invention may also include stimulating the lung to produce at least one artificially induced symptom of reversible obstructive pulmonary disease. As mentioned above, the stimulation of the lung may occur at any point during, or prior to, the procedure. For example, stimulation of the lung may occur prior to the step of testing the lung for pre-treatment pulmonary values. In this case, the values would be determinative of pulmonary function values of a lung experiencing symptoms of reversible obstructive pulmonary disease. Accordingly, the objective is to treat the lung until acceptable pulmonary function values are obtained. One benefit of such a procedure is that the effect of the treatment on the patient is more readily observed as compared to the situation where a patient, having previously been treated, must wait for an attack of reversible obstructive pulmonary disease to determine the efficacy of the treatment. Pulmonary function values are well known in the art. The following is an example of pulmonary function values that may be used. Other pulmonary function values, or combinations thereof, are intended to be within the scope of this invention. The values include, but are not limited to, FEV (forced expiratory volume), FVC (forced vital capacity), FEF (forced expiratory flow), Vmax (maximum flow), PEFR (peak expiratory flow rate), FRC (functional residual capacity), RV (residual volume), TLC (total lung capacity). FEV measures the volume of air exhaled over a pre-determined period of time by a forced expiration immediately after a full inspiration. FVC measures the total volume of air exhaled immediately after a full inspiration. Forced expiratory flow measures the volume of air exhaled during a FVC divided by the time in seconds. Vmax is the maximum flow measured during FVC. PEFR measures the maximum flow rate during a forced exhale starting from full inspiration. RV is the volume of air remaining in the lungs after a full expiration. The locating step described above may also comprise identifying treatment sites within the airway being susceptible to a symptom of reversible obstructive pulmonary disease. For example, symptoms may include, but are not limited to, airway inflammation, airway constriction, excessive mucous secretion, or any other asthmatic symptom. Stimulation of the lung to produce symptoms of reversible obstructive pulmonary disease may assist in identifying ideal treatment sites. As noted above, the method of the present invention may include stimulating the lung to produce at least one artificially induced symptom of reversible obstructive pulmonary disease and further include the step of evaluating the result of stimulation of the lung. For example, the evaluating step may include visually evaluating the effect of the stimulating step on the airway using a bronchoscope with a visualization system or by non-invasive imaging techniques, such as those describe herein. The evaluating step may include measuring pressure changes in the airway before and after the stimulating step. Pressure may be measured globally (e.g., within the entire lung), or locally (e.g., within a specific section of the lung such as an airway or alveolar sac.) Also, the evaluating step may comprise measuring the electrical properties of the tissue before and after the stimulating step. The invention may also include evaluating the results of the stimulating step by combining any of the methods previously mentioned. Also, the invention may further comprise the step of selecting at least one treatment parameter based upon the results of the evaluating step. Such treatment parameters may include, but are not limited to, duration of treatment, intensity of treatment, temperature, amount of tissue treated, depth of treatment, etc. The method may also include the step of determining the effect of the treatment by visually observing lung, airway or other such tissue for blanching of the tissue. The term “blanching” is intended to include any physical change in tissue that is usually, but not necessarily, accompanied by a change in the color of the tissue. One example of such blanching is where the tissue turns to a whitish color after the treatment of application of energy. The invention may also include the step of monitoring impedance across a treated area of tissue within the lung. Measuring impedance may be performed in cases of monopolar or bipolar energy delivery devices. Additionally, impedance may be monitored at more than one site within the lungs. The measuring of impedance may be, but is not necessarily, performed by the same electrodes used to deliver the energy treatment to the tissue. Furthermore, the invention includes adjusting the treatment parameters based upon the monitoring of the change in impedance after the treatment step. For example, as the energy treatment affects the properties of the treated tissue, measuring changes in impedance may provide information useful in adjusting treatment parameters to obtain a desired result. Another aspect of the invention includes advancing a treatment device into the lung and treating lung tissue to at least reduce the ability of the lung to produce at least one symptom of reversible obstructive pulmonary disease and further comprising the step of sub-mucosal sensing of the treatment to the lung tissue. The sub-mucosal sensing may be invasive such as when using a probe equipped to monitor temperature, impedance, and/or blood flow. Or, the sub-mucosal sensing may be non-invasive in such cases as infra-red sensing. The invention may also include using the treatment device to deposit radioactive substances at select treatment sites within the lung. The radioactive substances, including, but not limited to Iridium (e.g. 192Ir.) either treat the lung tissue over time or provide treatment upon being deposited. The invention also includes scraping epithelial tissue from the wall of an airway within the lung prior to advancing a treatment device into the lung to treat the lung tissue. The removal of the epithelial tissue allows the device to treat the walls of an airway more effectively. The invention further comprises the step of depositing a substance on the scraped wall of the airway after the device treats the airway wall. The substance may include epithelial tissue, collagen, growth factors, or any other bio-compatible tissue or substance, which promotes healing, prevent infection, and/or assists in the clearing of mucus. Alternatively, the treatment may comprise the act of scraping epithelial tissue to induce yield the desired response. The invention includes using the treating device to pre-treat the lung to at least reduce the ability of the lung to produce at least one symptom of reversible obstructive pulmonary disease prior to the treating step. At least one of the parameters of the pre-treating step may differ than one of the parameters of the treating step. Such parameters may include time, temperature, amount of tissue over which treatment is applied, amount of energy applied, depth of treatment, etc. The invention may also include advancing the treatment device into the lung and treating the lung tissue in separate stages. One of the benefits of dividing the treating step into separate stages is that the healing load of the patient is lessened. Dividing of the treating step may be accomplished by treating different regions of the lung at different times. Or, the total number of treatment sites may be divided into a plurality of groups of treatment sites, where each group of treatment sites is treated at a different time. The amount of time between treatments may be chosen such that the healing load placed on the lungs is minimized. The invention may also include advancing a treatment device into the lung, treating the lung with the device and sensing movement of the lung to reposition the treatment device in response to the movement. This sensing step accounts for the tidal motion of the lung during breathing cycles or other movement. Taking into account the tidal motion allows improved accuracy in repositioning of the device at a desired target. The invention may also include the additional step of reducing or stabilizing the temperature of lung tissue near to a treatment site. This may be accomplished for example, by injecting a cold fluid into lung parenchyma or into the airway being treated, where the airway is proximal, distal, or circumferentially adjacent to the treatment site. The fluid may be sterile normal saline, or any other bio-compatible fluid. The fluid may be injected into treatment regions within the lung while other regions of the lung normally ventilated by gas. Or, the fluid may be oxygenated to eliminate the need for alternate ventilation of the lung. Upon achieving the desired reduction or stabilization of temperature the fluid may be removed from the lungs. In the case where a gas is used to reduce temperature, the gas may be removed from the lung or allowed to be naturally exhaled. One benefit of reducing or stabilizing the temperature of the lung may be to prevent excessive destruction of the tissue, or to prevent destruction of certain types of tissue such as the epithelium, or to reduce the systemic healing load upon the patient's lung. Also contemplated as within the scope of the invention is the additional step of providing therapy to further reduce the effects of reversible obstructive pulmonary disease or which aids the healing process after such treatment. Some examples of therapy include, drug therapy, exercise therapy, and respiratory therapy. The invention further includes providing education on reversible obstructive pulmonary disease management techniques to further reduce the effects of the disease. For example, such techniques may be instruction on lifestyle changes, self-monitoring techniques to assess the state of the disease, and/or medication compliance education. There may be occurrences where it is necessary to reverse the effects of the treatment described herein. Accordingly, the invention further includes a method for reversing a treatment to reduce the ability of the lung to produce at least one symptom of reversible obstructive pulmonary disease comprising the step of stimulating re-growth of smooth muscle tissue. The re-stimulation of the muscle may be accomplished by the use of electro-stimulation, exercising of the muscle and/or drug therapy. The invention further includes methods of evaluating individuals having reversible obstructive pulmonary disease, or a symptom thereof, as a candidate for a procedure to reduce the ability of the individual's lung to produce at least one symptom of reversible obstructive pulmonary disease. The method comprises the steps of assessing the pulmonary condition of the individual, comparing the pulmonary condition to a corresponding pre-determined state, and evaluate the individual as a candidate based upon the comparison. In assessing the pulmonary condition, the method may comprise the steps of performing pulmonary function tests on the individual to obtain a pulmonary function value which is compared to a predetermined value. Examples of pre-determined values are found above. The method of evaluating may further include the step of determining how the individual's tissue will react to treatment allowing the treatment to be tailored to the expected tissue response. The method of evaluating may further comprises the step of pulmonary function testing using a gas, a mixture of gases, or a composition of several mixtures of gases to ventilate the lung. The difference in properties of the gases may aid in the pulmonary function testing. For example, comparison of one or more pulmonary function test values that are obtained with the patient breathing gas mixtures of varying densities may help to diagnose lung function. Examples of such mixtures include air, at standard atmospheric conditions, and a mixture of helium and oxygen. Additional examples of pulmonary testing include tests that measure capability and evenness of ventilation given diffusion of special gas mixtures. Other examples of gases used in the described tests, include but are not limited to, nitrogen, carbon monoxide, carbon dioxide, and a range of inert gases. The invention may also comprise the step of stimulating the lung to produce at least one artificially induced symptom of reversible obstructive pulmonary disease. Stimulating the symptoms of the disease in an individual allows the individual to be evaluated as the individual experiences the symptoms thereby allowing appropriate adjustment of the treatment. The method of evaluating may also comprise the step of obtaining clinical information from the individual and accounting for the clinical information for treatment. The method may further comprise the selection of a patient for treatment based upon a classification of the subtype of the patient's disease. For example, in asthma there are a number of ways to classify the disease state. One such method is the assessment of the severity of the disease. An example of a classification scheme by severity is found in the NHLBI Expert Panel 2 Guidelines for the Diagnosis and Treatment of Asthma. Another selection method may include selecting a patient by the type of trigger that induces the exacerbation. Such triggers may be classified further by comparing allergic versus non-allergic triggers. For instance, an exercise induced bronchospasm (EIB) is an example of a non-allergenic trigger. The allergic sub-type may be further classified according to specific triggers (e.g., dust mites, animal dander, etc.). Another classification of the allergic sub-type may be according to characteristic features of the immune system response such as levels of IgE (a class of antibodies that function in allergic reactions, also called immunoglobulin). Yet another classification of allergic sub-types may be according to the expression of genes controlling certain interleukins (e.g., IL-4, IL-5, etc.) which have been shown to play a key role in certain types of asthma. The invention further comprises methods to determine the completion of the procedure and the effectiveness of the reduction in the lung's ability to produce at least one symptom of reversible obstructive pulmonary disease. This variation of the invention comprises assessing the pulmonary condition of the individual, comparing the pulmonary condition to a corresponding predetermined state, and evaluating the effectiveness of the procedure based on the comparison. The invention may also comprise the steps of performing pulmonary function tests on the individual to obtain at least one pulmonary function value, treating the lung to at least reduce the ability of the lung to produce at least one symptom of reversible obstructive pulmonary disease, performing a post-procedure pulmonary function tests on the individual to obtain at least one post pulmonary function value and comparing the two values. This variation of the invention comprises obtaining clinical information, evaluating the clinical information with the results of the test to determine the effectiveness of the procedure. Furthermore, the variation may include stimulating the lung to produce a symptom of reversible obstructive pulmonary disease, assessing the pulmonary condition of the patient, then repeating the stimulation before the post-procedure pulmonary therapy. These steps allow comparison of the lung function when it is experiencing symptoms of reversible obstructive pulmonary disease, before and after the treatment, thereby allowing for an assessment of the improved efficiency of the lung during an attack of the disease. The invention herein is described by examples and a desired way of practicing the invention is described. However, the invention as claimed herein is not limited to that specific description in any manner. Equivalence to the description as hereinafter claimed is considered to be within the scope of protection of this patent. Patent CitationsCited PatentFiling datePublication dateApplicantTitleUS7992572 *Nov 7, 2006Aug 9, 2011Asthmatx, Inc.Methods of evaluating individuals having reversible obstructive pulmonary diseaseUS8251070 *Apr 4, 2006Aug 28, 2012Asthmatx, Inc.Methods for treating airways* Cited by examinerReferenced byCiting PatentFiling datePublication dateApplicantTitleUS7906124Sep 30, 2004Mar 15, 2011Asthmatx, Inc.Inactivation of smooth muscle tissueUS8828945Feb 1, 2011Sep 9, 2014Asthmatx, Inc.Inactivation of smooth muscle tissueClassifications U.S. Classification128/898International ClassificationA61M16/10, A61N1/05, A61F7/08, A61N5/04, A61B18/12, A61F2/84, A61N5/06, A61B18/18, A61M25/00, A61B18/00, A61M29/00, A61B17/24, A61B18/14, A61B17/00, A61B18/08, A61F7/12, A61B17/22, A61B18/04Cooperative ClassificationA61B2018/0022, A61B18/14, A61B18/08, A61B2018/00083, A61B2018/00678, A61B2018/00654, A61B18/1492, A61M2210/1039, A61B2018/00797, A61B2017/00292, A61B2018/1807, A61B2018/00267, A61B18/00, A61B2017/003, A61M29/00, A61B2017/00115, A61B2018/00761, A61B2018/00791, A61B2018/044, A61M25/0043, A61M2025/0096, A61B2018/00803, A61B17/22004, A61B2019/5217, A61B2018/046, A61N5/0601, A61B2017/22062, A61B2018/00214, A61B2018/00666, A61B2018/00541, A61B18/12, A61B18/1485European ClassificationA61B18/14V, A61B18/08, A61N5/06B, A61M25/00S, A61B18/00, A61M29/00Legal EventsDateCodeEventDescriptionJul 26, 2007ASAssignmentOwner name: ASTHMATX, INC., CALIFORNIAFree format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:DANEK, CHRISTOPHER JAMES;BIGGS, MICHAEL;LOOMAS, BRYAN;AND OTHERS;REEL/FRAME:019611/0729;SIGNING DATES FROM 20000830 TO 20031226Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:DANEK, CHRISTOPHER JAMES;BIGGS, MICHAEL;LOOMAS, BRYAN;AND OTHERS;SIGNING DATES FROM 20000830 TO 20031226;REEL/FRAME:019611/0729Owner name: ASTHMATX, INC., CALIFORNIAFree format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:DANEK, CHRISTOPHER JAMES;BIGGS, MICHAEL;LOOMAS, BRYAN;AND OTHERS;SIGNING DATES FROM 20000830 TO 20031226;REEL/FRAME:019611/0729Aug 31, 2010ASAssignmentOwner name: BRONCUS TECHNOLOGIES, INC., CALIFORNIAFree format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:DANEK, CHRISTOPHER JAMES;BIGGS, MICHAEL;LOOMAS, BRYAN;AND OTHERS;SIGNING DATES FROM 20000830 TO 20000831;REEL/FRAME:024920/0110Owner name: ASTHMATX, INC., CALIFORNIAFree format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:BRONCUS TECHNOLOGIES, INC.;REEL/FRAME:024920/0149Effective date: 20031226RotateOriginal ImageGoogle Home - Sitemap - USPTO Bulk Downloads - Privacy Policy - Terms of Service - About Google Patents - Send FeedbackData provided by IFI CLAIMS Patent Services

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Monroe County Court house, Stroudsburg, Pa. | Library of Congress
Photo, Print, Drawing Monroe County Court house, Stroudsburg, Pa.
JPEG (7.0 KB) GIF (14.6 KB) JPEG (114.8 KB) JPEG (301.9 KB) TIFF (20.0 MB) TIFF (160.1 MB)
- Corresponding glass transparency (with same series code) available on videodisc frame 1A-30377.
- "578" on negative.
- Detroit Publishing Co. no. 018717.
LC-D4-18717 [P&P]
det 4a12788 //hdl.loc.gov/loc.pnp/det.4a12788
2016799955
LC-DIG-det-4a12788 (digital file from original)
https://lccn.loc.gov/2016799955
Detroit Publishing Co., Copyright Claimant, and Publisher Detroit Publishing Co. Monroe County Court house, Stroudsburg, Pa . Pennsylvania Stroudsburg Stroudsburg. United States, ca. 1905. Photograph. https://www.loc.gov/item/2016799955/.
Detroit Publishing Co, C. C. & Detroit Publishing Co, P. (ca. 1905) Monroe County Court house, Stroudsburg, Pa . Pennsylvania Stroudsburg Stroudsburg. United States, ca. 1905. [Photograph] Retrieved from the Library of Congress, https://www.loc.gov/item/2016799955/.
Detroit Publishing Co., Copyright Claimant, and Publisher Detroit Publishing Co. Monroe County Court house, Stroudsburg, Pa . Photograph. Retrieved from the Library of Congress, <www.loc.gov/item/2016799955/>.
Summit of Barlow's knoll, Gettysburg 1 negative : glass ; 8 x 10 in.
The Jeffersonian. Catalog Record - Electronic Resource Available Weekly Vol. 13, no. 28 (May 5, 1853) ; -70th year, no. 36 (Mar. 16, 1911). "Republican," <1876>. Supplements accompany some issues. Archived issues are available in digital format as part of...
Jeffersonian Republican. Catalog Record - Electronic Resource Available Weekly Vol. 1, no. 1 (Jan. 15, 1840)-v. 13, no. 27 (Apr. 28, 1853). Publishers: Theodore Schoch & Thomas L. Kollock, <1843>; Theodore Schoch & F.E. Spering, 1843-<1844>; Theodore Schoch, <1850>. Published...

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Amazon.com: biblezine
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Amazon.co.uk:Customer reviews: Collins Complete DIY Manual
See all 481 positive reviews›
4.0 out of 5 starsContents - photos
ByMr. J. Kennyon 21 February 2018
I searched online and could not find what this book actually covers. Many reviewers have said it covers pretty much everything, but there was no online contents table that I could find. As I've since bought this book, I attach the contents table as photos and hope this helps others. I gave the book 4 stars with a view to increasing to 5 once I've done more DIY.
3.0 out of 5 starsA good book, but would recommend just using YouTube!
ByMr Thomas W Watsonon 10 April 2018
A great book for basic understanding, but theres nothing you can't get a detailed video from YouTube for, which I usually revert to anyway
ByKateon 3 June 2017
A family member recommended this book as we have recently brought our own house and are doing it up and we wouldn't of been able to do it with out this book it tell you how to do all Diys and it great detail
ByMRS RACHEL WILLIAMSon 6 May 2017
Brilliant,really pleased with it, Easy to use, great quality, good price, quick delivery would definitely recommend and would buy again, great tips, simple, good read, examples fab. Love it
Bygina readon 9 June 2017
Ordered as a gift but it arrived too late, however, it was worth waiting for, Contains so much information. Amazing.How to do just about everything. Reckon you could build an entire house using the knowledge from this one book. Excellent value for money.
5.0 out of 5 starsExactly what you would hope for.
ByR Bon 19 April 2013
I made a very poor call and bought a similar type book from a well known DIY chain store. That was a big mistake, and despite being a hefty book it was very disappointing in its content.
In contrast, this book is what I wanted all along. It is well divided and well laid out, with good graphical representations. Some of the information I was not expecting, but is very much welcome (for instance, exact measurements for what someone would need to take off their coat in a hall comfortably, or dry themselves after a shower).
Even having only given it a casual read I am better informed on several topics. The only drawback for me is that being in Ireland some of the legal/planning sections are not applicable, but that's no fault of the authors and I would recommend it to overseas purchasers nonetheless.
Bylauraon 18 January 2018
Great book and went down a treat for my partner at christmas ! very informative and full of everyday DIY tasks aswell as some more complex jobs. Would highly recommend
5.0 out of 5 starsGreat gift for newbie DIY-ers!
ByRascal Fanon 22 February 2018
Gave this to my son for Christmas--he's used it many times while doing up his new home, and says that he finds it really useful. Everything is clearly laid out, with good instructions and illustrations.
ByMaurice Don 19 September 2017
Had the earlier version of this book and this one is updated with planning and building regulations advice, very useful.
5.0 out of 5 starsLots of advice, help and tips
ByMuttion 15 February 2018
Bought this for my son in law to go with the drill I got him for his birthday. This is a good comprehensive book and will hopefully help him with DIY jobs now they are home owners
ByJambo Bobon 17 October 2017
This is THE book to get. If you're fed up paying unfeasibly large bills and thought you were handless, read this book and go for it. You will save the cover price many times over with your first job. Just follow what they say exactly and you'll do a better job than the professionals.
4.6 out of 5 stars523
byJulian Cassell
‹ See all details for Collins Complete DIY Manual


text:
Fortino's Garage Door Service - Gilroy, CA | Groupon
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Patent US7103456 - PCMCIA card for remotely communicating and interfacing with aircraft ... - Google PatentsSearch Images Maps Play YouTube News Gmail Drive More »Sign inPatentsA method and corresponding system use a Personal Computer Memory Card International Association (PCMCIA) card to remotely communicate and interface with flight performance data on an aircraft. The PCMCIA card can be plugged into an Aircraft Condition Monitoring Systems (ACMS) using a card interface....http://www.google.com/patents/US7103456?utm_source=gb-gplus-sharePatent US7103456 - PCMCIA card for remotely communicating and interfacing with aircraft condition monitoring systemsAdvanced Patent SearchTry the new Google Patents, with machine-classified Google Scholar results, and Japanese and South Korean patents.Publication numberUS7103456 B2Publication typeGrantApplication numberUS 10/821,846Publication dateSep 5, 2006Filing dateApr 12, 2004Priority dateApr 12, 2004Fee statusPaidAlso published asEP1763813A2, EP1763813A4, EP1763813B1, US20050228559, WO2005101284A2, WO2005101284A3, WO2005101284B1Publication number10821846, 821846, US 7103456 B2, US 7103456B2, US-B2-7103456, US7103456 B2, US7103456B2InventorsLaurent Bloch, Jean-Michel ToussaintOriginal AssigneeSagem Avionics, Inc.Export CitationBiBTeX, EndNote, RefManPatent Citations (32), Non-Patent Citations (1), Referenced by (40), Classifications (18), Legal Events (7) External Links: USPTO, USPTO Assignment, EspacenetPCMCIA card for remotely communicating and interfacing with aircraft condition monitoring systems
Examples of the wireless network 280 includes very high frequency (VHF) radio links, high frequency (HF) radio links, satellite communication links, and wireless spread spectrum links, such as wireless-fidelity (Wi-Fi) 802.11b. Wi-Fi 802.11b is easy to setup with low transmission cost. Any products tested and approved as “Wi-Fi Certified�” by the Wi-Fi Alliance are certified as interoperable with each other, even if they are from different manufacturers. A user with a “Wi-Fi Certified�” product can use any brand of access point with any other brand of client hardware that is also certified. Any Wi-Fi product using the same radio frequency (for example, 2.4 GHz for 802.11b or 11 g, 5 GHz for 802.11a) may work with one other, even if not “Wi-Fi Certified�.”
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Inc.Reconfigurable wireless modem adapter including diversity/mimo modemsUS20120034882 *Feb 9, 2012Honeywell International Inc.Reconfigurable wireless modem adapterUS20140059242 *Oct 16, 2012Feb 27, 2014Ge Aviation Systems LimitedMethod and system of implementing data load protocols* Cited by examinerClassifications U.S. Classification701/3, 701/36, 340/945International ClassificationG08B21/00, G07C5/08, G07C5/00, G06F19/00, G01C23/00, G08G5/00, G08B23/00Cooperative ClassificationG07C5/0858, G08G5/0021, G07C5/008, G08G5/0013European ClassificationG07C5/00T, G07C5/08R2B, G08G5/00B2, G08G5/00A4Legal EventsDateCodeEventDescriptionApr 12, 2004ASAssignmentOwner name: SAGEM AVIONICS, INC., TEXASFree format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:BLOCK, LAURENT;TOUSSAINT, JEAN-MICHEL;REEL/FRAME:015212/0008Effective date: 20040412Oct 21, 2004ASAssignmentOwner name: SAGEM AVIONICS, INC., TEXASFree format text: CORRECTIVE ASSIGNMENT TO CORRECT THE CONVEYING PARTY, PREVIOUSLY RECORDED AT REEL 015212, FRAME 0008;ASSIGNORS:BLOCH, LAURENT;TOUSSAINT, JEAN-MICHEL;REEL/FRAME:015926/0393Effective date: 20040412Mar 31, 2010SULPSurcharge for late paymentMar 31, 2010FPAYFee paymentYear of fee payment: 4Apr 18, 2014REMIMaintenance fee reminder mailedAug 6, 2014FPAYFee paymentYear of fee payment: 8Aug 6, 2014SULPSurcharge for late paymentYear of fee payment: 7RotateOriginal ImageGoogle Home - Sitemap - USPTO Bulk Downloads - Privacy Policy - Terms of Service - About Google Patents - Send FeedbackData provided by IFI CLAIMS Patent Services


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SAMSUNG 3 LCD 14 2MP WB700 BLACK DIGITAL CAMERA 18X ZOOM SCHNEIDER KREUZNACH B | eBay Please enable JavaScript Our new search experience requires JavaScript to be enabled. Please enable JavaScript on your browser, then try again.
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Patent US5220625 - Information search terminal and system - Google PatentsSearch Images Maps Play YouTube News Gmail Drive More »Sign inPatentsAn information search terminal apparatus and information search system for performing information search by using a variety of windows assure high manipulatability for the user by making available information of the results of searches performed in the past and the current system state. The information...http://www.google.com/patents/US5220625?utm_source=gb-gplus-sharePatent US5220625 - Information search terminal and systemAdvanced Patent SearchTry the new Google Patents, with machine-classified Google Scholar results, and Japanese and South Korean patents.Publication numberUS5220625 APublication typeGrantApplication numberUS 07/914,334Publication dateJun 15, 1993Filing dateJul 17, 1992Priority dateJun 14, 1989Fee statusPaidPublication number07914334, 914334, US 5220625 A, US 5220625A, US-A-5220625, US5220625 A, US5220625AInventorsAtsushi Hatakeyama, Hiroe Ando, Kanji Kato, Satoshi Asakawa, Hisamitsu KawaguchiOriginal AssigneeHitachi, Ltd.Export CitationBiBTeX, EndNote, RefManPatent Citations (16), Non-Patent Citations (4), Referenced by (139), Classifications (17), Legal Events (4) External Links: USPTO, USPTO Assignment, EspacenetInformation search terminal and system
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Inc.System and method for law practice information management* Cited by examinerClassifications U.S. Classification715/809, 715/804, 707/E17.082, 707/E17.062, 707/999.004International ClassificationG06F17/30, G06K9/72, G06K9/62Cooperative ClassificationY10S707/99934, G06F17/30696, G06F17/30637, G06K9/62, G06K9/72European ClassificationG06F17/30T2V, G06K9/72, G06F17/30T2F, G06K9/62Legal EventsDateCodeEventDescriptionJul 17, 1992ASAssignmentOwner name: HITACHI, LTD. A CORP. OF JAPAN, JAPANFree format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNORS:HATAKEYAMA, ATSUSHI;ANDO, HIROE;KATO, KANJI;AND OTHERS;REEL/FRAME:006189/0538Effective date: 19920709Sep 30, 1996FPAYFee paymentYear of fee payment: 4Sep 28, 2000FPAYFee paymentYear of fee payment: 8Sep 30, 2004FPAYFee paymentYear of fee payment: 12RotateOriginal ImageGoogle Home - Sitemap - USPTO Bulk Downloads - Privacy Policy - Terms of Service - About Google Patents - Send FeedbackData provided by IFI CLAIMS Patent Services


text:
Bayardo Perez-Ordóñez - Semantic Scholar
Bayardo Perez-Ordóñez
Ilan Weinreb67
Jonathan C. Irish56
Brian O'Sullivan52
Patrick J. Gullane50
John N Waldron43
75Ilan Weinreb
51Fei-Fei Liu
47John N Waldron
Bayardo Perez-Ordóñez, Mathieu Beauchemin, Richard Jordan
Squamous cell carcinoma of the head and neck (HNSCC) is a heterogeneous but largely preventable disease with complex molecular abnormalities. It arises from a premalignant progenitor followed by outgrowth of clonal populations associated with cumulative genetic alterations and phenotypic progression to invasive malignancy. These genetic alterations result… (More)
BACKGROUND A recently developed probe-based technology, the NanoString nCounter™ gene expression system, has been shown to allow accurate mRNA transcript quantification using low amounts of total RNA. We assessed the ability of this technology for mRNA expression quantification in archived formalin-fixed, paraffin-embedded (FFPE) oral carcinoma samples. … (More)
MicroRNAs (miRs) are non-coding RNA molecules involved in cancer initiation and progression. Deregulated miR expression has been implicated in cancer; however, there are no studies implicating an miR signature associated with progression in oral squamous cell carcinoma (OSCC). Although OSCC may develop from oral leukoplakia, clinical and histological… (More)
Cristina R Antonescu, Nora Katabi, +10 authors Ilan Weinreb
Hyalinizing clear-cell carcinoma (HCCC) is a rare, low-grade salivary gland tumor with distinctive clear-cell morphology and pattern of hyalinization as well as focal mucinous differentiation. However, histological overlap exists with other salivary gland tumors, such as epithelial-myoepithelial carcinoma (EMCa), salivary myoepithelial carcinoma, and… (More)
The tumor suppressor Programmed Cell Death 4 (PDCD4) has been found to be under-expressed in several cancers and associated with disease progression and metastasis. There are no current studies characterizing PDCD4 expression and its clinical relevance in Oral Squamous Cell Carcinoma (OSCC). Since nodal metastasis is a major prognostic factor in OSCC, we… (More)
Wei Lin Shi, Hisayuki Kato, +13 authors Fei-Fei Liu

value: This website is an artificial-intelligence backed search engine for academic publications developed at the Allen Institute for AI and publicly released in November 2015. It uses advances in natural language processing to provide summaries for scholarly papers.


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text: . >> the suv ruptured a gas line and three homes were temporarily evacuated. >>> the fbi unveiled a nationwide billboard campaign this week in hopes of capturing a fugitive from the bay area. they asked drivers to be on the lookout for daniel andreas san diego who is from berkeley. san diego has been on the run for a decade. he is accused of setting off bombs at two companies in the east bay. the fbi needs the public's help now more than ever. >> the fbi has plastered giant photographs like this one of daniel andri s san diego near the bay bridge, and all across the country. he is the first domestic terrorism fugitive added to the fbi's most wanted terrorist list. fbi spokesperson peter lee says the bureau is casting a wide net to arrest him. >> anyone with eyes out there can help the fbi. and that's why we targeted not only northern california but also major port cities you know miami miami, tampa and orlando. >> seven states have put up these billboards to ramp up the hunt. last december fbi agent went door to door in this neighborhood where san diego has family ties. the fbi has tips san Search Results 0 to 0 of about 1

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