pulmonary drug delivery system pdf

The design and development of any powder drug-delivery system is a highly complex task. Pre-incubation of GP-682 micelles markedly enhanced the cell membrane permeability, and improved drug uptake in vitro . Pulmonary drug delivery “Pharmaceutical aerosol formulations are typically more sophisticated and less efficient than those for conventional routes of administration (e.g., oral and parenteral). Gene delivery may be divided into DNA, mRNA and siRNA delivery. So, despite the barriers to successful drug delivery that exist in the gastrointestinal tract (i.e., acid-induced hydrolysis in the stomach, enzymatic degradation throughout the gastrointestinal tract by several proteolytic enzymes, bacterial fermentation in the colon), the peroral route is still the most intensively investigated as it offers advantages of convenience and cheapness of administration, and potential manufacturing cost savings. Apart from various formulations, different delivery devices such as metered dose inhalers (MDI), dry powder inhalers (DPI), nebulizers, aerosolizers, etc. A small proportion of the dose gets reposed in the system, whereas the remaining drug particles or droplets get distributed to the pulmonary tract. The acute lung injury mouse model induced by the Pseudomonas aeruginosa PA 14 strain demonstrated that preinjection of GP-682 micelles before antibiotic administration resulted in a higher survival rate and anti-infective efficacy in vivo. The results were visualized using fluorescent dye tracing, transmission electron microscopy (TEM) observations and the lactate dehydrogenase (LDH) release assay. >> Mohammed Ali, in Handbook of Non-Invasive Drug Delivery Systems, 2010. They exhibit significant advantages compared to traditional pulmonary drug delivery systems. Found insideThis book meets that need. Comprehensive in its coverage, it spans relevant topics from early phase drug development right up to late-stage clinical trials. /ColorSpace /DeviceRGB This third edition contains a chapter on nanoscience and technology for drug delivery along with cutting-edge business intelligence and strategies. Its outcome, however, is majorly determined by drug formulation, device structure and patient's coordinating skill. Inhalational route for drug delivery and desired effects has been known since centuries. Dosage Term and near-term neonates with hypoxic respiratory failure . The differential diagnosis of diffuse lung disease on computed tomography is based on the recognition of characteristic patterns of abnormality and on the anatomic distribution of disease within the lung and the secondary pulmonary lobule. Get Your FREE Sleep Health Rating! Found inside – Page 1For more news and specials on immunization and vaccines visit the Pink Book's Facebook fan page Background: Nanoparticle-based pulmonary drug delivery systems are commonly developed and applied for drug-targeted delivery. It also caused reductions in pulmonary injury, bacterial invasion and cytokine expression compared with treatment with Lev alone. Ultrastructural and Immunohistochemical Studies on Uptake and Distribution of FITC-Conjugated PLGA N... Advances in Pulmonary Delivery of Nanoparticles, Polymeric nanocarriers for drug delivery to the lung. Rahul K. Verma, Mariam Ibrahim, and Lucila Garcia-Contreras. The mainstay of treating asthma and COPD is inhalation therapy of medications to the site of the diseased region in the lung. CPAP Humidifiers. requirement, and effectiveness for local and systemic delivery. This noninvasive mode is being increasingly studied for transfer of drugs for systemic action with promising results. Pulmonary Targeting of Different Dosage Formulations using Various Modes of Delivery, . 1 Pulmonary Drug Delivery Anatomy and Physiology of the Respiratory System Advantages of Pulmonary Delivery Lung epithelium at different sites within the lungs Pulmonary absorptive surfaces Systemic delivery of: Small hydrophobic drugs Small hydrophilic drugs Macromolecules drugs Pulmonary Drug Delivery … The self-assembled micelles were composed of a platycodon secondary saponin, 3-O-β-D-glucopyranosyl platycodigenin 682 (GP-682), via its specific amphiphilic structure. Tech-nology problems associated with pulmonary drug delivery are being overcome with advances in design. The use of drug delivery systems (DDS) for the treatment of pulmonary diseases is increasing because of their potential for localized topical therapy in the lungs. Costs for publishing images in color are a separate fee and are not included in the page charge total. For instance, globally, as of 9:39am CET, 22 December 2020, there have been 76,023,488 confirmed cases of COVID-19, including 1,694,128 deaths, reported to the World Health Organization. And good release profile follows first order release kinetics. The obtained benefits enhanced the distribution of levofloxacin (Lev) in mouse lung tissue and reduced antibiotics overdosing. CONTENTS. Under a single cover, this book brings together various aspects of functional bioengineered materials and nanostructured biomaterials including commonly used implants and sustained release nanodevices. This mode is effective, rapid and safe. Issue No #11 June 15th, 2007. For example, vasopressin, an anti-diuretic protein used in the treatment of diabetes insipidus, can be given in the form of a … Drug Delivery Carriers. In Part II of this review, the influence that the type of aerosol delivery system and drug formulation has on a drug’s therapeutic effectiveness will be discussed. Inhalation drug delivery system by ‐ dry powder inhalers 29. The local 2.1. There are various anatomical, physiological and immunological barriers that a ect the therapeutic e cacy of inhaled formulations. This paper reviews various nanopaticulate approaches in the form of lipids, polymers, metals, polysaccharides, or emulsions based for pulmonary drug delivery that could provide an increased biological efficacy and better local and systemic action. Inhalational route for drug delivery and desired effects has been known since centuries. The self-assembled micelles were composed of a platycodon secondary saponin, 3-O-β-D-glucopyranosyl platycodigenin 682 (GP-682), based on its specific amphiphilic structure. Journal of Aerosol Medicine and Pulmonary Drug Delivery. Accumulation of drug particles or droplets has been the first stage after inhalation. Interested in research on Pulmonary Drug Delivery? A Nebulizer System for Positron Emission Tomography Imaging of Aerosols and Nanoparticles for Use in Preclinical Pulmonary Drug Delivery Studies Andrew Sterling Butters Department of Nuclear Engineering Texas A&M University Research Advisor: Dr. Gamal Akabani Department of Nuclear Engineering Texas A&M University Some see a … Zeta potential shows good positive potentials. Pulmonary Drug Delivery. Carbopol, etc. Different strategies have been utilized for pulmonary delivery of drugs, including the use of lipid-based delivery systems (liposomes, ISCOMs, SLNs), use of polymeric matrix (PLGA, poly caprolactone, cynoacrylates, gelatin), development of polysaccharide particulates (chitosan, alginates, Successful delivery of nano-particles to the lung has to take account of the potential biological and pathophysiological barriers of the target organ. 9.3. Increased antibiotic resistance in the recent years indicates that current therapeutic strategies aimed at biofilm-associated infections are "failing", emphasizing the need to develop new and improved drug delivery systems with higher efficacy and efficiency. Astech Projects Ltd. Review of Product Characterization Requirements for Aerosol Products. Immunohistochemically, a, FITC-positive reaction was. For instance, globally, as of 9:39am CET, 22 December 2020, there have been 76,023,488 confirmed cases of COVID-19, including 1,694,128 deaths, reported to the World Health Organization. Sorry, preview is currently unavailable. 9.6 Conclusions. This book provides a comprehensive introduction to advanced drug delivery and targeting, covering their principles, current applications, and potential future developments. This comprehensive volume provides the reader valuable insight into the major areas of biomedical nanomaterials, advanced nanomedicine, nanotheragnostics, and cutting-edge nanoscaffolds. 25. An increasing number of drugs are protein- and peptide-based. However, developing a formulation for each drug is a time-consuming and laborious task. Pulmonary Disease Aerosol Delivery Devices, 3rd Edition To ensure effective drug delivery to the airways with a DPI, patients must be able to generate a minimum peak inspi-ratory flow rate of 30 L/min. In recent years the wide advances in drug delivery systems have enabled simpler routes of administration. This route is preferred broadly due to non-invasive technique, large surface area for absorption, high blood circulation, and permeability rate. based pulmonary drug delivery has been written by Prof. Souto and co-authors (Chapter 6: Lipid Nanoplatforms for Pulmonary Drug Delivery). Controlled Pulmonary Drug Delivery begins by examination of the foundations for pulmonary drug delivery: the macro and microstructure of the airways, lung clearance, airway absorption and transport, aerosol physics, and a historical overview of the field. The carriers can be made slowly degradable, stimuli-reactive (e.g., pH- or temperature-sensitive), and even targeted (e.g., by conjugating them with specific antibodies against certain characteristic components of the area of interest). /Width 851 Global Pulmonary Drug Delivery Systems Market Value (US$ Mn), and Y-o-Y Growth (%), 2019-2027. In spite of great advances in this field, more efforts are required to meet the unmet needs. In contemporary literature are described the methods for obtained multilamellar niosomes, large monolamellar niosomes and small monolamellar niosomes with the help of sonication, Research on pulmonary delivery of drugs is currently being focused for developing sustainable, effective, and economical methods for cure of diseases related to the respiratory tract including asthma, COPD, cystic fibrosis, tuberculosis, lung cancer, and pneumonia. Anthony Moran. Found insideWith over 400 drug monographs, this book covers the technical, practical and legal aspects that you should consider before prescribing or administering drugs via enteral feeding tubes. stream Hypersensitivity pneumonitis is often associated with fine centrilobular nodules. Title: Pulmonary Drug Delivery System: A Novel Approach for Drug Delivery VOLUME: 6 ISSUE: 2 Author(s):Anupama Singh, Rishabha Malviya and Pramod K. Sharma Affiliation:Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology,Bypass Road, Baghpat Crossing, NH-58, Meerut-250005, U.P., India. systemic drug delivery using mucoadhesive polymers to significantly improve the performance of many drugs has been of profound interest. Increasing prevalence of chronic respiratory disease along with the rapid growing geriatric population is considered as the key driver for the growth of the pulmonary drug delivery systems market. They exhibit significant advantages compared to traditional pulmonary drug delivery systems. Found inside"This is the most widely used textbook for teaching pharmacology to health professionals. This 11th edition is far superior to any previous editions. Pulmonary drug delivery (PDD) systems were recently introduced into the pharmaceutical field to treat both the local and the systemic type of lung diseases. PDD systems are known to be able to simply deliver the drug to the required site in the body directly or to other distant sites through the bloodstream. %&'()*456789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz��������������������������������������������������������������������������� In the kidneys, a positive reaction was observed in proximal tubular epithelial cells at 30 MAT; the reaction peaked at 60 MAT and was reduced at 24 HAT, while no positive reaction was seen in other sites. Emergence of Covid-19 is expected to offer lucrative growth opportunities for players in the global pulmonary drug delivery systems market. Followed by sonication for 5 min. Pulmonary drug delivery is used for management of COPD and Asthma only but due to advancement in application nowadays Pulmonary drug delivery is useful to treat Diabetes, angina pectoris, cancer, bone disorders, tuberculosis, migraine acute lung injury and others. From all these results it concludes that formulation No 2 is the best formulation and which is recommended for future studies like Nano dry powder preparation. It also caused reductions in pulmonary injury, bacterial invasion and cytokine expression compared with treatment with Lev alone. A strategy that could allow active targeting involves the surface functionalization of drug carriers with ligands that are selectively recognized by receptors on the surface of the cells of interest. Found insidePart one discusses the fundamentals and development of inhaler devices as well as drug formulations for inhalers. The treatment of asthma is also discussed. ! The obtained benefits enhanced the distribution of levofloxacin (Lev) in mouse lung tissue and reduced antibiotics overdosing. The Pulmonary Drug Delivery Systems market is projected to grow at a CAGR of 5.61% to reach US$51.538 billion by 2023, from US$37.145 billion in 2017. Although many of these offer exciting prospects for future biofilm therapeutics, there are also major challenges of this emerging field that need to be addressed. Emergence of Covid-19 is expected to offer lucrative growth opportunities for players in the global pulmonary drug delivery systems market. On the other hand, in both nanoparticle groups, lysosomes filled with nanoparticles appeared in alveolar macrophages from 30 MAT to 24 HAT. 1.2.1 Macro- and Microstructure of the Airways and Alveoli as It Pertains to Drug Delivery … In this article, we summarize the rationale behind the advances of pulmonary drug delivery system. Lives can be extended and improved when these diseases are prevented, detected, and managed. This volume summarizes current knowledge and presents evidence-based interventions that are effective, cost-effective, and scalable in LMICs. Found insideEssential Pharmaceutics is suited to this modern teaching style, and is the first book of its kind to provide the resources and skills needed for successful implementation of an active learning pharmaceutics course.This text offers a format ... Keywords: pulmonary arterial hypertension; prostacyclin; nanoparticle; drug delivery system 1. Journal of Drug Delivery Science and Technology. The present invention provides a method of improving the efficiency of absorption into the bloodstream of drugs delivered through the pulmonary route. Recent Advanced Approaches in Pulmonary Drug Delivery System: A Review DOI: 10.9790/3008-1404022227 www.iosrjournals.org 25 | Page ,shape of the particulate matter if it is a fiber and hygroscope also having profound influence on drug disposition through pulmonary route. Then, nanocarrier systems will be introduced and the challenges required to perform adequate pulmonary deposition analysed. In present study authors review all aspects of pulmonary drug delivery system; including need of drug delivery, different approaches for drug delivery and recent advancement in pulmonary drug delivery system. © 2008-2021 ResearchGate GmbH. It exhibits significant advantages compared to traditional pulmonary drug delivery systems. [2] (solid self-nanoemulsifying drug delivery system (S-SNEDDS) tablet). << This thoroughly revised and expanded reference provides authoritative discussions on the physiologic, pharmacologic, metabolic, molecular, cellular and physicochemical factors, influencing the efficacy and utilization of pharmaceutical ... Pulmonary drug delivery system for TCM to treat IPF. Biofilm-associated infections pose a huge burden on healthcare systems worldwide, with recurrent lung infections occurring due to the persistence of biofilm bacteria populations. D. Cornea 3. A spherical solid lipid particle prepared from physiological lipid, dispersed in water or in aqueous surfactant solution. Found insideMany books discuss these subjects, but not from a pharmaceutical point-of-view. This book covers novel approaches related to the modulation of microbial biofilms, antimicrobial therapy and encapsulate polyphenols as antioxidants. In this review, we explore the multidisciplinary approach of using current and novel MNPs as vehicles of drug delivery. To deliver the medicine to their specific target tissues, drug carriers (the substances that play crucial role in vital delivery and effectiveness of drugs) are used [55-62].A large variety of organic systems like liposomes, micelles, vesicles, … After freeze drying the Nanoparticles were collected. Pulmonary drug delivery is getting more and more magnitude. This is on account of the specific physiological environment of the lung as an absorption and treatment organ. The development of inhalable insulin can be perceived as a milestone in pulmonary drug delivery. "Completely revised and expanded throughout. Presents a comprehensive integrated, sequenced approach to drug dosage formulation, design, and evaluation. Pulmonary drug delivery has been in use since the early 1950s, with many drugs absorbed by inhalation, although technolog-ical problems have prevented more drugs being administered via this route. It shows good encapsulation efficiency. The self-assembled micelles were composed of a platycodon secondary saponin, 3-O-β-D-glucopyranosyl platycodigenin 682 (GP-682), via its specific amphiphilic structure. View pulmonarydrugdeliverysystem-160619063517.pdf from ENGI 600 at Rice University. In particular, pathological changes may have crucial impact on successful nano-carrier delivery. Although drug therapy using nano-drug delivery system for PAH have been described previously 9,20, the effect of drug delivery system on other organs has not been clearly elucidated. Recently the interest to develop pulmonary drug delivery system suitable for lung cancer has been increased. ), biocompatible metallic inorganic particles (iron, gold, zinc), etc. Inhalation drug delivery system by - metered dose inhalers 3. Since ligand–receptor interactions can be highly selective, this could allow a more precise targeting of the site of interest.The choice of a delivery route is driven by patient acceptability, the properties of the drug (such as its solubility), access to a disease location, or effectiveness in dealing with the specific disease. Careful attention to imaging technique is critical. Chitosan was dissolved in acetic acid aqueous solution at various concentrations; Drug was dispersed in above Chitosan solution kept over magnetic stirrer at room temperature for a period of 30 minute. Preincubation of GP-682 micelles markedly enhanced their cell membrane permeability and improved drug uptake in vitro. The computed tomography features of usual interstitial pneumonitis (reticular opacity and honeycombing with peripheral and basal predominance) are sufficient to make an accurate diagnosis in the correct clinical context. In this study, a universal lung-targeting nanoparticle was designed and constructed. The first step in drug profiling for delivery via the respiratory tract needs to address intrinsic physicochemical parameters and their impact on or correlation with absorption. Keywords:Pulmonary drug delivery, targeted drug delivery, delivery … /Type /XObject ���� Adobe d �� C As many nanosystems have reached the market over the past decade, this book proves their benefits to patients. It explores these new carriers and the advances in drug delivery they have facilitated. The book provides details of the different types of biomaterial available and their applications, including nanoparticles for biomedical applications, synergism effects during fiction and fretting corrosion experiments, application of ... We also describe here the various evaluation parameter for pulmonary drug devices. Other factors that are driving the growth of themarket are the emergence of novel inhaler designs and increased use of non-invasive drug delivery methods. A pulmonary drug delivery system (PDDS) delivers drugs to the lung to produce a local or systemic therapeutic effect. However, only scant information on the potential of spray-drying for submicron particle preparation is available. However, developing the formulation of each drug is a time-consuming and laborious task. The principle objective of formulation of lipid-based drugs is to enhance their bioavailability. Found inside – Page iThis text focuses on the basic concepts of drug delivery while thoroughly examining various topics such as: CNS delivery Gene delivery Ocular delivery World-wide research on drug delivery Recent advances in drug delivery A significant ... pulmonary drug delivery system can be analyzed and studied through this review. Pulmonary drug delivery is an important research area which impacts the treatment of illnesses including asthma, chronic obstructive pulmonary disease and various other diseases. Pulmonary drug delivery system: newer patents. Nebulizer Nebulizers used today for drug delivery to the respiratory tract and are particularly useful for the treatment of hospitalized or nonambulatory patients. The results were visualized using fluorescent dye tracing, transmission electron microscopy observation and a lactate dehydrogenase releasing assay. APPROACHES IN PULMONARY DRUG DELIVERY Targeted drug delivery to the lungs has evolved to be one of the most widely investigated systemic or local drug delivery approaches. They offer the greatest potential for more effective therapeutics, but they do not easily cross mucosal surfaces and biological membranes; they are easily denatured or degraded, prone to rapid clearance in the liver and other body tissues and require precise dosing. Pulmonary drug delivery system has been widely used since decades for the treatment of lung diseases and is acclaimed for the treatment of asthma and chronic obstructive pulmonary diseases. Download PDF. Examples of DPI Devices Under Development, All figure content in this area was uploaded by Rishabha Malviya, ... As low concentrations of compounds to biofilm infection sites are rapidly cleared from the lungs, a number of studies have investigated the drug delivery of liposomes to the lungs via inhalation as liquid or dry formulations, ... presents unique advantages based on unique physiological features, such as a large specific surface and minimal thickness for drug absorption and permeability, ... A pulmonary drug delivery system (PDDS) delivers drugs to the lung to produce a local or systemic therapeutic effect. CPAP Parts. The aerodynamic characteristics of both particle species revealed aerosol particle sizes suitable for deposition in the deep lungs (≤4μm). Introduction: Bronchial asthma (BA) is one of the commonest respiratory disorders, which is likely to keep the physician overworked in the coming century as … These results suggest that nanospray-drying is a convenient method to prepare submicron, controlled drug delivery vehicles useful for pulmonary application potentially allowing access to alveolar tissue. Consequently, in the last few years, techniques and new drug delivery devices intended to deliver drugs into the lungs have been widely developed. Respiratory systems offer unique advantages like large surface area, no first-pass metabolism, significant drug absorption, low dose, Numerous studies have addressed the controlled pulmonary drug delivery properties of colloidal particles. Pre-incubation of GP-682 micelles markedly enhanced the cell membrane permeability, and improved drug uptake in vitro. Next-generation of automated pulmonary delivery testing systems. The imaging signs of diffuse lung disease are nodules, lines, cysts, honeycombing, traction bronchiectasis/bronchiolectasis, pleural abnormalities, parenchymal opacification (consolidation or ground glass attenuation), crazy paving pattern, decreased lung attenuation, and mosaic pattern. "All services provided, including the advertisement, ordering, sale, delivery, instruction, and setup of the products, are performed solely by www.cpapsupplyusa.com and independently of the manufacturer." PULMONARY DRUG DELIVERY. Imaging is important in understanding the classification of the idiopathic interstitial pneumonias (usual interstitial pneumonia, desquamative interstitial pneumonitis, non-specific interstitial pneumonitis, acute interstitial pneumonia and cryptogenic organizing pneumonia). nano-encapsulation and pulmonary delivery will be discussed for small molecular drugs, usually having a fast release due to short diffusion distances. The respiratory system works with the circulatory system to deliver oxygen from the lungs to the cells and remove CO2 and return it to the lungs to be exhaled. While other books focus on the therapy, the primary emphasis in this book is on current technologies for DDS applications, including microfluidics, nanotechnology, biodegradable hydrogel and microneedles, with a special emphasis on wearable ... Results: The results were visualized using fluorescent dye tracing, transmission electron microscopy (TEM) observations and the lactate dehydrogenase (LDH) release assay. The Handbook of Non-Invasive Drug Delivery Systems encompasses the broad field of non-invasive drug delivery systems that include drug delivery via topical, transdermal-passive, transdermal-active (device- aided enhanced penetration), trans ... Found insideThis series reviews multifunctionality and applications of drug delivery systems, industrial trends, regulatory challenges and in vivo success stories. Magnetic nanoparticles (MNPs) have unique and favourable properties encompassing biocompatibility, biodegradability, magnetic and heat-mediated characteristics, making them suitable drug carriers. Inhalation drug delivery system by ‐ nebulizer 2. Pharmacokinetic processes following pulmonary drug delivery. The first book offering a global overview of fundamental microfluidics and the wide range of possible applications, for example, in chemistry, biology, and biomedical science. The GP-682 micelles exhibited a relatively stable zeta potential with a particle size between 60 and 90 nm, and the critical micelle concentration (CMC) value was approximately 42.3 μg/mL. Increasing incidence of chronic respiratory diseases is expected to accelerate the demand for Pulmonary Drug Delivery Systems (PDDS) in the near future. Pulmonary Drug Delivery Systems Market size was valued at USD 43.4 Billion in 2020 and is projected to reach USD 62.9 Billion by 2028, growing at a CAGR of 4.8% from 2021 to 2028.. Rise in prevalence of chronic diseases such as bronchitis, tuberculosis, and chronic obstructive pulmonary disease, … %PDF-1.5 By controlling the release of drugs, the therapeutic effect of pulmonary drug delivery systems, as well as patient convenience and compliance could be improved by reducing the number of times drugs need to be administered. Found inside – Page iThis book aims to provide a comprehensive and up to date understanding of the processes and mechanisms involved in inhalation drug delivery, with a strong focus on inhalation products, specific equipment and laboratory techniques. In addition to locally acting drugs, molecules that are intended to produce systemic effects can be delivered via the pulmonary route. CPAP Masks. Pulmonary drug delivery, absorption, metabolism, and clearance Drug delivery and distribution The respiratory system coordinates with the circulatory system to supply oxygen from the outside environment to cells of the body and remove carbon dioxide from the body. For the treatment of human diseases, nasal and pulmonary routes of drug delivery are gaining increasing importance. Review deals with drug targeting to pulmonary region for the treatment of various diseases such as chronic obstructive pulmonary disease, lung cancer, cystic fibrosis, tuberculosis, asthma, etc. Found insideThe book covers a wide range of biomaterials and nanotechnology techniques that have been used for the delivery of different biological molecules and drugs in the human body. Results: The present study designed and constructed a universal lung-targeting nanoparticle. Kaur SS (1). ABSTRACT. This can be explained by the increased pollution levels and drastic changes in the lifestyle of the people. The DPI offers good patient convenience, particularly for combination therapies, and also better compliance. Found insideUpdated and expanded second edition covers all aspects of capsule technology, including history, standards, methods and equipment used in manufacture, filling, printing, weighing, cleaning and inspecting of both hard and soft capsules. The market for pulmonary drug delivery systems is witnessing growth due to the rising prevalence of respiratory disorders such as asthma, COPD and other chronic illnesses. ous drug delivery systems considered for pulmonary application, nanocarriers show several advantages over other conventional approaches for the treatment of respiratory diseases, for example prolonged drug release and cell-specific targeted drug delivery. In the following part, drug delivery systems (DDSs) on the market or in clinical trials are described and, finally, new approaches of nanoparticles that have reached pre-clinical stage are enumerated. These systems can be best utilized for both local and systemic actions.Pulmonary drug delivery is an importantresearch area which impacts the treatment of illnesses including asthma, chronic obstructive pulmonary disease and various other diseases.
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