Pulmonary Immunotoxicology is a comprehensive exploration of the effects of various inhaled materials upon the immune system of the respiratory tract. It will be useful to investigators in the field of pulmonary toxicology and immunotoxicology, and to those involved in administration and regulation of matters related to inhaled materials. It can also serve as a textbook for a course in pulmonary immunotoxicology at graduate or advanced undergraduate level. Pulmonary Immunotoxicology comprises four sections. The first provides basic background concepts essential for understanding pulmonary immunotoxicology, including discussions of the normal structure and function of the respiratory system, its basic immunology, and the manner by which inhaled particles and gases are removed from the air and deposited upon respiratory tract surfaces. The second section provides an overview of the major types of pathological consequences which can arise from immunomodulation within the respiratory tract, including hypersensitivity and asthma, inflammation and fibrosis, as well as immunosuppression and autoimmunity. The third section, which comprises the largest portion of the book, deals specifically with major classes of airborne agents that are known to alter the immune function of the respiratory tract. These are arranged into major classes: organic agents, metals, gases, particles, biologics, and complex mixtures. The fourth and final section of the book explores the area of risk assessment, including discussions of the basic concepts of risk assessment as they apply specifically to immunotoxicologic effects upon the lungs, and the use of biomarkers as indices of potential pulmonary immunotoxic responses to inhaled materials.

It is a pleasure to contribute a brief foreword to this new, comprehensive 1980s saw an explosion of knowledge in pul text on the pneumonias. The is every reason to expect it to continue through monary science, and there the end of the century. As a result, it is becoming increasingly difficult to keep up with all the important advances, even in a restricted area of interest. For this reason, books such as the present one that collate the latest findings on an important clinical topic in a convenient, readable form provide a valuable service. This book is a salutary reminder that there is life beyond molecular and cell biology. Important though these disciplines are, some of us regret the lemming-like rush into these fashionable fields at the expense of more traditional pulmonary science. One result of this rush has been an increas ingly large number of residents and fellows who are unable to interpret the results of blood gas assays or who are completely at sea when presented with a patient who requires mechanical ventilation. The present perception that research funding is available only in molecular and cell biology has produced some unfortunate distortion of training programs. I pity the poor medical student in some of our most prestigious medical schools who is taught by a molecular biologist or neurophysiologist how the lung works. I wish the book well."

Pulmonary rehabilitation programmes are a fundamental part of the clinical management of patients with chronic respiratory diseases. This comprehensive reference book places pulmonary rehabilitation within the wider framework of respiratory disease. Now in six parts, it includes new sections on the development of PR as a discipline, global perspectives on quality control, new chapters on early PR post exacerbation and personalized rehabilitation, innovative approaches to exercise, PR in interstitial lung disease and lung transplantation, and the latest research into the application of music, dance and yoga. Key Features Global contributions compare practice around the world where differences have developed. New six Part structure covers new approaches to exercise testing, interstitial lung diseases and other diseases, and add-on interventions drawing on new technologies. Contains recommendations of the large collaborative ERS/ATS task forces on guidelines for PR as well as suggested policies for its implementation and use. Covers the important topic of balance impairment as a focus of rehabilitation for the at-risk patient and a new chapter on monitoring physical activity. The voices of patients and caregivers describe the impact of chronic respiratory disease on their lives. Features an exclusive chapter on COVID-19 that discusses the short- and long-term pathophysiological consequences, provides information about the potential role of physiotherapy in the management of hospitalized patients with confirmed or suspected COVID-19, and details on who, where, and how to deliver programs to COVID-19 and non COVID-19 patients in the lockdown and post lockdown era.

The publication of Bronchoalveolar Mast Cells and Asthma marks the emergence of The Bloomsbury Series in Clinical Science, an important and novel series that will highlight, review and record major areas of research, development and practice in the field of clinical science. A number of other monographs are now in an advanced state of preparation and their release will establish not only their individual significance but that of the series as a whole. My thanks are due to the Editorial Board who have provided the ideas and selected the authors and whose continuing enthu siasm is so vital to the success of the series. Michael Jackson of Springer-Verlag merits special thanks for initially realising the potential of such a series and then guiding us all through to the time of its launch. Marianne Williams has supported us all and has provided the important link between Editorial Board and pub lisher. The author of this first publication, Kevin Flint, was tragically killed during its preparation, and we hope that the book will serve as a tribute to the memory of Kevin for all who were lucky enough to know him. Barry Hudspith has been of enormous help in finalising the work and in shaping the form of the book."

The Fourth International Workshop on "In Vitro Effects of Mineral Dusts on Cells" was held on September 20 - 23, 1988 in Auberge Estrimont, Orford, Quebec, Canada. The emphasis of the N. A. T. O. Advanced Research Workshop was the use of cell and organ culture and lavage cell populations obtained from man and laboratory animals to elucidate cellular and molecular events occur ring after their interaction with fibrous and nonfibrous particulates, including metal compounds. In seven sessions, an international representation of scientists from 17 countries (Austria, Belgium, Canada, France, Federal Republic of Germany, India, Japan, Netherlands, Norway, Poland, Portugal, Union of South Africa, Sweden, Switzerland, United Kingdom, United States of America, and Yugoslavia) presented recent research findings in the following areas: Epithelial cell injury and proliferation by minerals. Physico-chemical properties of minerals in relation to their biologic effects. Mechanisms of dust-induced pneumoconioses. Clinical and experimental studies. Mechanisms of cytotoxicity, mutagenicity and carcinogenicity. Oxidants, cytotoxicity and disease. Mechanisms of mineral-induced inflammation. Mechanisms of carcinogenesis. A session on "Questions, risk and public policy" provided a lively discussion on the relevance of in vitro experiments to carcinogenicity studies in man and their implications in the formation of regulatory policies. VI The organizing committee for this workshop was: Co-Chairs: B. T. Mossman (USA) and R. Begin (Canada) E. G. Beck (FRG) A. Lange (Poland) A. Brody (USA) P. Nettesheim (USA) R. C. Brown (UK) Q. Rahman (India) J. Bignon (France) K. Robock (FRG) Fisher G.

Considerable progress in understanding how inhaled minerals cause disease in man has been made in the past two decades. This is mostly due to the great amount of human, animal and cell multidisciplinary studies carried out on silica, asbestos and asbestiforms all around the world. Two previous NATO Workshops on "In Vitro Effects of Mineral Dusts on Cells", have been published in the NATO ASI Series (1985 and 1989). The present NATO-INSERM workshop has focused specifically on a group of silicates, named phyllosilicates because of their sheet structure, of which health related effects have been poorly and sporadically investigated. These silicates are presently largely used as filling materials (kaolin, talc, chlorite), insulating materials (vermiculite, micas), adsorbants (sepiolite, attapulgite) and in many other industrial applications. The estimated annual world production is presently 5.5 million tons of talc (1.8 million for Europe) and only in the United Kingdom about 3.5 million tons of kaolin.

The interrelated syndromes of shock and the adult respiratory distress to attract the attention of both clinical and syndrome (ARDS) continue laboratory scientists. This reflects both the size of the problem and its unresponsiveness to current lines of treatment. Doubtless, a greater appreciation of the underlying pathophysiological disturbances during the past two decades has led to appropriate action and increased survival in the early stages but once established these syndromes have remained remarkably immune to a wide spectrum of therapeutic modalities. This observation stresses the importance of prevention but also indicates the need for continued research into the nature of the established syndromes and the means whereby they may be reversed. Drs Kox and Bihari are to be congratulated on bringing together within the covers of this volume many of the acknowledged European experts in these two fields of investigation. Each author has provided an up-to-date account of his current experimental and clinical research, and their com bined contributions makes fascinating reading. Undoubtedly, these are exciting times in the development of understanding of shock and ARDS. Inevitably, more questions are raised than answers provided, but the accumulated knowledge presented here adds significantly to our under standing of this complex biological jigsaw. From this corporate endeavour will come the clinically useful developments of the future and with them the ultimate hope that the term 'refractory' shock may be finally removed from our vocabulary.

The simple reason for creating this book was my impression that the law is having an increasing impact on the practice of medicine. There is hardly a physician I know who has not been deeply troubled by legal problems professionally, economically, and most important of all, psychologically. The past decade has seen medical practice premiums steadily rising. Multimillion dollar verdicts have not been unusual. Having disregarded these vital issues for many years, physicians have suddenly become very aware of litigation-related problems. Having been interested for a long time in the logic ofthe law and the romance of legal research, I thought it would be useful to create a book that would result in the blending of great minds in law and medicine. It has been my long standing observation and belief that the approach of professors of medicine, and that of learned members of the bar and bench, when put together, produce unique results. Putting these views together has been the real challenge in editing this book."

The International Life Sciences Institute (ILSI), a nonprofit, public foundation, was established in 1978 to advance the sciences of nutrition, toxicology, and food safety. ILSI promotes the resolution of health and safety issues in these areas by sponsoring research, conferences, publications, and educational programs. Through ILSI's programs, scientists from government, academia, and industry unite their efforts to resolve issues of critical importance to the public. As part of its commitment to understanding and resolving health and safety issues, ILSI is pleased to sponsor this series of monographs that consolidates new scientific knowledge, defines research needs, and provides a background for the effective application of scientific advances in toxicology and food safety. Alex Malaspina President International Life Sciences Institute Contents Series Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi Part I. Approaches to Assessing the Toxicity of Airborne Toxicants Chapter 1. Standard-Setting as an Integrative Exercise: Alchemy, Juggling, or Science? . . . . . . . . . . . . . . . . . . . . . . . 1 D. v. Bates Chapter 2. Species Differences in Inhalation Toxicology: Variations in Exposure-Dose Relationships and Macrophage Function. . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 J. D. Brain Chapter 3. Cell Populations of the Respiratory System: Interspecies Diversity in Composition, Distribution, and Morphology . . . . . . . . . . . . . . . . . . . . . . . . 25 e. G. Plopper, A. Mir, J. St. George, N. Tyler, A. Mariassy, D. Wilson, S. Nishio, D. Cranz, J. Heidsiek, and D. Hyde Chapter 4. Comparative Metabolic Basis for the Disposition and Toxic Effects of Inhaled Materials . . . . . . . . . . . . . . . . . 41 A. R. Dahl Part II. Methodological Issues in Designing and Conducting Studies with Laboratory Animals Chapter 5. Exposure Facilities and Aerosol Generation and Characterization for Inhalation Experiments. . . . . . . . . .

Where do you begin to look for a recent, authoritative article on the diagnosis or management of a particular malignancy? The few general oncology textbooks are generally out of date. Single papers in specialized journals are informative but seldom comprehensive; these are more often preliminary reports on a very limited number of patients. Certain general journals frequently publish good indepth reviews of cancer topics, and published symposium lectures are often the best overviews available. Un fortunately, these reviews and supplements appear sporadically, and the reader can never be sure when a topic of special interest will be covered. Cancer Treatment and Research is a series of authoritative volumes which aim to meet this need. It is an attempt to establish a critical mass of oncology literature covering virtually all oncology topics, revised frequently to keep the coverage up-to-date, easily available on a single library shelf or by a single personal subscription. We have approached the problem in the following fashion. First, by dividing the oncology literature into specific subdivisions such as lung cancer, genitourinary cancer, pediatric oncology, etc. Second, by asking eminent authorities in each of these areas to edit a volume on the specific topic on an annual or biannual basis. Each topic and tumor type is covered in a volume appearing frequently and predictably, discussing current diagnosis, staging, markers, all forms of treatment modalities, basic biology, and more.

High pressure in the lungs, or pulmonary hypertension, is most commonly due to smoking-related lung disease and conditions affecting the left heart, for example, high blood pressure in the arteries, faulty heart valves, and a weakened heart muscle. Pulmonary arterial hypertension (PAH), is a rare and complex disease, associated with many different medical conditions, which is caused by a growth of cells lining the inside of the lung arteries, resulting in high pressure in areas of the body. Both conditions lead to strain and potential failure of the right heart, and therefore awareness and early diagnosis of the condition is needed to lead to better outcomes: however this depends on education of all specialists and primary care clinicians about PAH. This practical handbook covers both PH and PAH, providing information required by the wide range of clinicians who will encounter these conditions, including cardiologists, respiratory physicians, rheumatologists, specialists in liver and AIDS medicine, and haematologists. It covers what it is, who it is likely to affect, how it is diagnosed, including the pitfalls of the various diagnostic tests, the different and evolving forms of treatment, long term management of this often devastating chronic disease, and the crucial role of multidisciplinary management in optimizing clinical care of these patients who usually have multi-system diseases. It also covers the up new classification for both PH and PAH, and new drugs that have recently become available.

These are the proceedings of the international symposium on "Experi- mental Respiratory Carcinogenesis and Bioassays", held from 23 to 26 June 1974 at the Battelle Seattle Research Center, Seattle, Wash., USA. Human lung cancer is already very common in industrialized countries, and its incidence is increasing. This increase involves mainly epi- dermoid and small-cell carcinoma. Evidence is accumulating that these tumors are associated with such exogenic factors as automobile exhaust, asbestos, chemicals, cigarette smoke, and radionuclides. These pro- ceedings are concerned with finding the most suitable experimental designs for investigating the genesis of these particular types of tumor, and with the development of specific bioassays to test sus- pected carcinogens. Spontaneous epidermoid and small-cell carcinomas are extremely rare in the respiratory organs of animals, and it has proved rather diffi- cult until recently to produce them experimentally. Epidermoid carci- nomas are now readily obtained by using methods of intratracheal in- stillation of carcinogens with particulate materials such as that described by SAFFIOTTI and co-workers, which is the technique most frequently mentioned in these proceedings. While the experimental production of small-cell carcinomas has remained difficult, it is described by two authors in this volume.

What are the different muscarinic acetylcholine receptor subtypes and how are they distributed in the airways and molecular signalling mechanisms? What is their function in neurogenic and non-neurogenic control of the airways and in inflammatory mechanisms? How is their gene expression regulated? The great importance of muscarinic acetylcholine receptors for the pathophysiology and treatment of chronic inflammatory obstructive airways diseases calls for a comprehensive and integrated overview of the current knowledge to address such questions, to discuss the role of these receptor subtypes in diseases such as asthma and COPD, and to present novel perspectives on antimuscarinic drug development. The present book is the worthy result of this need. It points out innovative insights into the hitherto poorly understood role of postjunctional muscarinic M2 receptors in airway smooth muscle contraction and sheds some light on the novel concepts of antimuscarinic drug development, with special reference to the l

Written by world-renowned experts in COPD A refresher for GPs and hospital doctors with practical diagnostic and treatment advice Reviews clinical developments and guidelines, and places them into everyday clinical practice Stresses the importance of early intervention, therapies and patient education Managing COPD is an in-depth guide on the management of patients with COPD concentrating on the impact of COPD on a patient as well as how healthcare professionals can intervene and educate the patient at an early stage and thereby slow the onset of severe symptoms. This book has been designed to increase physician awareness of the pathological processes involved in the aetiology of COPD which underpins effective disease management.

On 15 November 1997, the first international symposium "Neural and Chemical Control of Breathing: Pharmacological and Clinical Aspects" was held at Leiden University Medical Center on the occasion of the retirement of one of the members of the Control of Breathing Research Group of the Departments of Physiology and Anesthesiology, Dr. Aad Berkenbosch. Among others, Dr. Berkenbosch, played an important role in this research group, which made a large and significant contribution to scientific research on the regulation of breathing. This book presents the proceedings of that meeting together with papers of several authors who have strong bonds with the Leiden Departments of Physiology and Anesthesiology. All studies represent state of the art work on the subject of respiratory control and cardiovascular medicine, with emphasis on the physiological, pharmacological and anesthesiological aspects of both fields. The book is divided in several sections: Oxygen Physiology. Prof. John Severinghaus presents among other things his ideas on oxygen sensing and high altitude related diseases. Prof. Honda gives results from studies in a unique set of subjects without carotid bodies. The findings of Honda's group support the idea that an intact hypoxic drive from the carotid bodies is necessary for the generation of central hypoxic depression. Dr. Hans van Beek discusses the effects of hypoxia and hypercapnia on cardiac contractility in animal models. Prof. Oeseburg demonstrates the feasibility of Near Infra Red Oximetry for monitoring tissue oxygenation in patients. Central Chemoreception.

Asthma is a very common chronic disease involving the respiratory system in which the airways occasionally constrict, become inflamed, and are lined with excessive amounts of mucus, often in response to one or more triggers. In children, the most common triggers are viral illnesses, such as those that cause the common cold and identifiable allergies. This airway narrowing causes symptoms such as wheezing, shortness of breath, chest tightness, and coughing. While measurement of airway function is possible for adults, most new cases are diagnosed in children who are unable to perform such tests. Diagnosis in children is based on a careful compilation and analysis of the patient's medical history and subsequent improvement with an inhaled bronchodilator medication. This 2nd edition will provide clinicians with an update on the management of asthma, and will include new sections covering paediatric asthma, new treatment strategies, and updated management guidelines (including new British Thoracic Society BTS] guidelines).

Acute lung injury (ALI) impacts patient care in every ICU in the world. Our collective understanding of this condition has grown immensely over the past decade but morbidity and mortality remain unacceptably high. To enhance the understanding of clinicians and researchers, this book addresses the pathophysiology of acute lung injury from a molecular and cellular standpoint; includes animal models of acute lung injury and points to potential therapeutic advances based on scientific findings. It is a concise compendium of the multiple pathways, mechanisms and molecules involved in the pathophysiology of acute lung injury and is intended to help caregivers understand the process and thus care for patients more effectively.

The field of neural control of breathing has advanced rapidly in the past two decades, with the emergence of many new and promising research directions of increasing sophistication. The complexity and diversity of the current methodologies signify its remarkable vivacity, albeit at the price of much confusion. Captured in this book are the broad and intricate nature of the field and its multifaceted frontiers, including aspects of genetics, cell and molecular biology, comparative biology, neurophysiology, neurochemistry, neuroanatomy, imaging, human physiology in health and disease, and influence of environmental factors. Major topics include chemosensitivity, respiratory sensation, respiratory neurons, rhythmogenesis, plasticity, development, chemoreflex and exercise, respiratory instability and variability with behavioral and sleep states, etc., which are systematically laid out in the book for easy referencing.

This volume deals specifically with those antituberculosis drugs which passed the preclinical phase and have been or are used in the treatment of tuberculosis and other mycobacterial diseases (except leprosy) in at least some parts of the world. Despite this restriction, there are 14 such drugs, and as a result this volume has reached rather large proportions. To prevent it from becoming even larger and more unwidely, most derivatives of antituberculotics have been omitted, especially where it is claimed that they provide only better bioavailibility or tolerability. Only in the chapter on the chemotherapy of diseases due to so-called atypical mycobacteria is the clinical use of the drugs described to a certain extent. In addition to antituberculotics, also discussed are antimicrobials which have been found to be effective against these mycobacteria. The sequence in which the drugs are described is historical, reflecting not the time of discovery but rather the first clinical application. This order was selected for reasons which are now no longer relevant. In this volume less emphasis is placed on detection, biological or synthetic production of antituberculotics, and structure-activity relationships. In contrast, emphasis is put on the degree, type, and mechanism of antimyco bacterial activity, pharmacokinetics, and biotransformation in animals and man, on experimental pharmacodynamics, and on the toxicity of antituberculotics used therapeutically.

The International Life Sciences Institute (ILSI), a nonprofit, public foundation, was established in 1978 to advance the sciences of nutrition, toxicology, and food safety. ILSI promotes the resolution of health and safety issues in these areas by sponsoring research, conferences, publications, and educational programs. Through ILSI's programs, scientists from government, academia, and industry unite their efforts to resolve issues of critical importance to the public. As part of its commitment to understanding and resolving health and safety issues, ILSI is pleased to sponsor this series of monographs that consolidates new scientific knowledge, defines research needs, and provides a background for the effective application of scientific advances in toxicology and food safety. Alex Malaspina President International Life Sciences Institute Contents Series Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . xiii . . . . . . . . . . . . . Part I. Integrative Approach to Assessing Human Health Risk: Two Contemporary Problems Chapter 1. Integrating Diverse Data Sets to Assess the Risks of Airborne Pollutants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 R.o. McClellan, R.G. Cuddihy, w.e. Griffith, and J. L. Mauderly Chapter 2. Risk Assessment for Radon Inhalation Based on Animal Exposure Data and Human Epidemiology . . . . . . . 23 . F. Steinhausler Part II. Types of Evidence: General Strengths and Weaknesses Section 1. Epidemiological Chapter 3. Inhalation Hazards: The Interpretation of Epidemiologic Evidence. . . . . . . . . . . . . . . . . . . . 39 . . . . . . . J.e. Bailar Chapter 4. Problems in Interpreting Epidemiological Data 49 P.N. Lee Section 2. Animal Chapter 5. Rodent Carcinogenicity Studies: Their Value and Limitations. . . . . . . . . . . . . . . . . . . . . . . . . . 61 . . . . . . . . . .

Presented here are recent data on the mechanisms of action of different dusts and fibres of industrial interest. Emphasis is placed on the use of cell and organ culture and lavage cell populations obtained from man and laboratory animals to elucidate cellular and molecular events occurring after their interaction with fibrous and non-fibrous particulates including metal compounds. In four sections, the volume provides research findings in the following areas: - Cellular and Metabolic Changes Caused by Mineral Dusts - Molecular Changes and DNA Alterations Produced by Mineral Dusts - In Vivo Dust-Related Pathological Processes. Correlations Between in Vitro and in Vivo Data - Physico-Chemical Properties of Minerals in Relation to Their Biological Effects.

Most studies on autonomic innervation of smooth muscle have focused on the short-term mechanisms involved in neurotransmission in physiological and pathophysiological conditions. However recent obser vations of the long-term plasticity of this system, i. e. its capacity for regeneration and for compensatory change in pattern of innervation and expression of cotransmitters and receptors in ageing, following surgery, trauma or in disease, have indicated that an understanding of the mechanisms involved could influence the design of therapeutic regimes. There is increasing evidence for long-term communication between nerves and smooth muscle cells during development and throughout adult life. To date, the trophic interactions between nerves and airway musculature have attracted little interest, consequently, much of the information presented here is drawn from studies using other smooth muscles. However, the questions posed about trophic interactions dur ing development apply as much to airways smooth muscle neuroeffector systems as to other autonomic neuroeffector systems. These are: i) How do developing nerve fibres know where to go and how do they reach their target sites? ii) What determines the density and pattern of inner vation at reaching the effector? iii) How do the nerves survive and maintain their position once established? iv) What factors influence neurochemical differentiation such that genetically multipotential neu rones are triggered to synthesize one or combinations of neurotransmit ters? v) What influence do nerves have on the structure, function and receptor expression of their effector cells? vi) How do diseases interrupt these processes? - see 1]."

Defining the Lung Cancer Problem 1 Lung cancer is the leading cause of cancer death in the world. It kills almost as many Americans as cancers of the breast, prostate, colon, rectum, pancreas, and 2 kidney combined, and accounts for 28.6% of all US cancer deaths. With an increase in the 5-year relative survival rate from 13% to only 16% in the more than 2 30 years from 1974 to the present, it will take us another 840 years to eradicate lung cancer deaths if we do not improve the current rate of progress. As discussed in this text, lung cancer prevention has received substantial att- tion. The decrease in smoking in recent decades has helped, but smoking is not the only problem. Lung cancer in people who have never smoked is currently the 5th 3 leading cause of cancer death in the United States. Several factors contribute to the lethality of lung cancer, including the rapidity of tumor growth, advanced stage at diagnosis (due to nonspecificity of early sy- toms and the uncertain efficacy of screening), early development of metastases, and resistance to therapy. Several chapters in this book discuss new molecular targets that may be potentially exploitable in the future, as well as discussing our track record to date in exploiting them.