Clinicians’ Guide to Chronic Obstructive Pulmonary Disease by C. Donner and J. Wedzicha


545964716286c7a-261x361.jpg Author C. Donner and J. Wedzicha
Isbn 9780340816950
File size 1.45MB
Year 2005
Pages 144
Language English
File format PDF
Category medicine


 

CLINICIANS’ GUIDE TO CHRONIC OBSTRUCTIVE PULMONARY DISEASE This page intentionally left blank CLINICIANS’ GUIDE TO CHRONIC OBSTRUCTIVE PULMONARY DISEASE Timothy Q. Howes MA MBBS MRCPI MD Consultant Respiratory Physician Department of Respiratory Medicine, Colchester General Hospital, Colchester, UK With a contribution from David Bellamy MBE General Practitioner Bournemouth, UK Hodder Arnold A MEMBER OF THE HODDER HEADLINE GROUP First published in Great Britain in 2005 by Hodder Arnold, an imprint of Hodder Education, a member of the Hodder Headline Group, 338 Euston Road, London NW1 3BH http://www.hoddereducation.com Distributed in the United States of America by Oxford University Press Inc., 198 Madison Avenue, New York, NY10016 Oxford is a registered trademark of Oxford University Press © 2005 Timothy Q. Howes All rights reserved. Apart from any use permitted under UK copyright law, this publication may only be reproduced, stored or transmitted, in any form, or by any means with prior permission in writing of the publishers or in the case of reprographic production in accordance with the terms of licences issued by the Copyright Licensing Agency. In the United Kingdom such licences are issued by the Copyright Licensing Agency: 90 Tottenham Court Road, London W1T 4LP. Whilst the advice and information in this book are believed to be true and accurate at the date of going to press, neither the author[s] nor the publisher can accept any legal responsibility or liability for any errors or omissions that may be made. In particular, (but without limiting the generality of the preceding disclaimer) every effort has been made to check drug dosages; however it is still possible that errors have been missed. Furthermore, dosage schedules are constantly being revised and new side-effects recognized. For these reasons the reader is strongly urged to consult the drug companies’ printed instructions before administering any of the drugs recommended in this book. British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress ISBN-10: 0 340 816 953 ISBN-13: 978 0340 816 953 1 2 3 4 5 6 7 8 9 10 Commissioning Editor: Joanna Koster Project Editor: Heather Fyfe Production Controller: Lindsay Smith Cover Design: Sarah Rees Typeset in 11/13.5 Adobe Jenson by Charon Tec Pvt. Ltd, Chennai, India www.charontec.com Printed and bound in Italy What do you think about this book? Or any other Hodder Arnold title? Please send your comments to www.hoddereducation.com CONTENTS Preface vii Acknowledgements ix List of abbreviations xi 1. Definition and pathophysiology 1 2. Epidemiology of chronic obstructive pulmonary disease 13 3. Clinical diagnosis of chronic obstructive pulmonary disease 23 4. Disease prevention 41 5. Medical management 49 6. Chronic obstructive pulmonary disease exacerbations 81 7. Outcome measures 97 8. Chronic obstructive pulmonary disease at the primary–secondary care interface 105 9. Case studies 119 Index 123 This page intentionally left blank P R E FA C E Chronic Obstructive Pulmonary Disease, Chronic Obstructive Airways Disease, Chronic Bronchitis with Empysema, Chronic Airflow Limitation. The name changes but the disease goes on. Until recently the condition has hidden under the coat tails of asthma, but released from this constraint the momentum in this area of interest seems unstoppable. It is likely that this little book will be out of date in some areas almost before it is written. We hope however that it will offer a background for junior doctors and general practitioners as well as nurses and physiotherapists interested in respiratory disease. This condition is now of great interest to health economists and planners and it is hoped that they too will find subjects of interest. The book has sections on the management of chronic disease and acute exacerbations and a section on the management of patients in general practice. There are many sections of interest to specialist nurses and physiotherapists who are shouldering an increasing burden of these patients in pulmonary rehabilitation sessions. An attempt has been made to improve the flow of the text by removing references from the text and at the end of each chapter and adding a reading list for those readers needing further information in a particular area of interest. As progress in this field is so rapid, it is hoped that this will help readers to keep their knowledge up to date during the life of the text. This page intentionally left blank ACKNOWLEDGEMENTS Dr Howes is grateful for the support of all of the team at the publishers. They have been very tolerant of ever slipping deadlines and unexpected difficulties. Great thanks are also due to Professor Wisia Wedzicha at St Bartholomew’s Hospital for constant advice. Dr Howes is particularly grateful to his secretary Angela Humphreys for her help. This page intentionally left blank L I S T O F A B B R E V I AT I O N S ACE AMI AMP ATS BMI BTS CAL COAD COLD COPD CT CPAP DALY ECG FEV1 FiO2 FVC GM-CSF GOLD GP HRCT ICU IL-4 IL-5 IL-8 LTB4 LTOT MDI MEP MIP MMP MRC NCPAP NETT NHS angiotensin-converting enzyme acute myocardial infarction adenosine monophosphate American Thoracic Society body mass index British Thoracic Society chronic airflow limitation chronic obstructive airways disease chronic obstructive lung disease chronic obstructive pulmonary disease computerized tomography continuous positive airways pressure disability-adjusted life years electrocardiogram forced expiratory volume in 1 second fraction of inspired oxygen forced vital capacity granulocyte colony stimulating factor Global Initiative for Chronic Obstructive Lung Disease general practitioner high-resolution computerised tomography Intensive care unit interleukin 4 interleukin 5 interleukin 8 leukotriene B4 long-term oxygen therapy metered dose inhaler maximum expiratory pressures maximum inspiratory pressures matrix metalloproteases Medical Research Council nasal continuous positive airway pressure National Emphysema Treatment Trial National Health Service xii Abbreviations NICE NIPPV NSAIDs NRT PaCO2 PaO2 PCO2 PDE4 PE PEEPi PEF PEFR PO2 SaO2 SGRQ SIP SLIPI TNF-␣ V/Q WHO National Institute for Clinical Excellence nasal intermittent positive pressure ventilation non-steroidal anti-inflammatory drugs nicotine replacement therapy arterial partial pressure of carbon dioxide arterial partial pressure of oxygen partial pressure of carbon dioxide phosphodiesterase 4 pulmonary embolism intrinsic positive end expiratory pressure peak expiratory flow peak expiratory flow rate partial pressure of oxygen arterial oxygen saturation St George’s Respiratory Questionnaire Sickness Impact Profile secretory leukoproteinase inhibitor tumour necrosis factor-␣ ventilation/perfusion ratio World Health Organization CHAPTER DEFINITION AND PATHOPHYSIOLOGY INTRODUCTION It would be fair to say that chronic obstructive pulmonary disease (COPD) is a disease entity that, at the time of writing, is enjoying a renaissance of interest. It is also true to say that this condition has not received the attention in the past that it has deserved. There are many reasons for this. It has proved very difficult to compose a definition of the syndrome that encompasses the disease in a single sentence or even a single paragraph. It has even proved quite difficult to define the syndrome completely. Most definitions link COPD to the closely related syndrome of asthma. It is seen as asthma’s recalcitrant alter ego: irreversible rather than reversible, presenting in elderly rather than young patients and difficult to manage, with the result that patients block beds in hospitals and compete unfavourably for intensive care, compared with community-based asthmatics who come to hospital only when there is a failure in management. In short, something of a nuisance. In the last 5–10 years there has been a realization that there is a substantial therapeutic challenge to be met, that it can be met, and that overlooking this condition has contributed to a substantial rise in morbidity and mortality at a time when these numbers are falling for coronary artery disease and most major cancers. DEFINITION When COPD – also known as chronic obstructive airways disease (COAD), chronic obstructive lung disease (COLD) or chronic airflow limitation (CAL) – was initially described as a single unifying disease process in the early 1960s, it brought together three areas that had previously been described separately: 1. Chronic bronchitis, a disease process characterized by chronic productive cough; 2. Emphysema, an anatomical definition with radiological and structural changes in the lung characterized by enlarged air spaces and alveolar wall destruction; 3. Chronic asthma, which was added to this definition where asthma was incompletely reversible. 2 Definition and pathophysiology It has, therefore, over four decades, been somewhat overshadowed by respiratory syndromes that were more straightforward to define and therefore easier to research. It is the author’s experience that colleagues not in the field of respiratory medicine have, when admitting acutely dyspnoeic patients to hospital, a tendency to include asthma and COPD together in a single ‘catch-all’ syndrome of airways obstruction, and therefore fail to distinguish the separate nature of these conditions. Indeed, there is evidence that the increasing death rate from asthma apparent in the UK in the 1980s and early 1990s resulted from these errors being recorded in death certificates. It is therefore interesting that present understanding of COPD has been led in the large part by re-evaluation of the semantics to define the condition. Towards the end of the 1980s, the British Thoracic Society (BTS) and the American Thoracic Society (ATS) worked towards finding a form of words that clearly distinguished COPD and asthma, and all the definitions that have been forthcoming have emphasized the lack of variability over time of airways obstruction in COPD and the predominant reversibility of airflow limitation in asthma. Initially, this led to a rather negative approach to the management of COPD, perhaps because many clinicians felt that if a disease had been defined as being irreversible then no treatment would be effective. The renaissance in interest in COPD can therefore be attributed to the resurgence of interest in the acute exacerbation of COPD as an entity in need of research, and the discovery that frequent exacerbations (systemic flare-ups) are associated with a more rapid decline in patients with the condition. The discovery that early intervention may reduce the frequency and severity of exacerbations has led to a renewed research interest. To this extent, researchers in COPD are emulating research in cardiology in the 1990s. During that time risk factors for the development of heart failure were evaluated with large, well-run clinical trials. Interventions in acute myocardial infarction were assessed and long-term outcomes measured. In this way, researchers in the field have revolutionized the management of cardiac disease. Audits have shown reductions in mortality in acute myocardial infarction and increased survival in chronic heart failure. All these things can be attributed directly to the studies of the 1990s and the application of their results in everyday clinical practice. It is to this model that COPD research is looking in order to reduce mortality and morbidity. The acute exacerbation can be considered in the same way that cardiologists looked at the acute myocardial infarction, while research into the subsequent decline in spirometry in COPD can be compared with the investigation of treatments for the management of heart failure. At the time of writing these large research studies are in the future, but it is hoped that over the next decade there will be a major change in the management of this condition focusing on reduction in the frequency of exacerbations and the early recognition of the condition in sufferers. The current Global Initiative for Chronic Obstructive Lung Disease (GOLD, see page 59) guidelines define COPD as a disease state characterized by airflow limitation that is not fully reversible. This airflow limitation is usually both progressive and Pathophysiology associated with an abnormal inflammatory response of the lungs to noxious particles or gases. COPD can be defined as a disease characterized by: ■ gradual onset of shortness of breath ■ ■ presence of airflow limitation on spirometry testing ■ chronic cough and sputum production presence of risk factors for COPD (e.g. cigarette smoking, coal mining, other sources of smoke inhalation). Most current guidelines define the severity of COPD in terms of spirometry. The best available data would suggest that this is entirely reasonable but it is likely that the frequency of exacerbations and the rapidity of the decline in spirometry will appear in management guidelines in the near future. It is also likely that the exacerbation will increase in prominence in ‘event avoidance’ now that exacerbations are seen to have greater importance in decline in health status than was previously realized. PATHOPHYSIOLOGY Inhaled irritant particles and gases cause inflammation in the airways of susceptible individuals. Healing is impaired, and the elastic tissues in the lung are damaged, leading to increased mucus hypersecretion and airway narrowing. The end result is emphysema (Figure 1.1), which, in its final stage, involves respiratory muscle embarrassment and vascular bed reduction. These two factors lead to hypoxaemia, reduced renal salt excretion and fluid overload, and cor pulmonale. Noxious particles and gases Antioxidants Lung inflammation Oxidative stress Antiproteinases Proteinases Repair mechanisms COPD pathology Figure 1.1 Proposed inflammatory responses to inhaled airborne particles leading to chronic obstructive pulmonary disease (COPD). Understanding more about these pathways may help the development of new therapies in COPD. This figure first published on the GOLD website (http://www.goldcopd.com). 3 4 Definition and pathophysiology THE INFLAMMATORY PROCESS It is clear that the nature of the inflammatory process needs further discussion. Patients with asthma have an inflammatory process in their airways. In most cases, this responds promptly and efficiently to modest doses of inhaled steroids, and successful management is the outcome. The process in COPD is obviously different. Prompt response is not the byword: outcomes are more difficult to demonstrate with changes in physiology and this has led in the past to confusion over treatment. The first difference in COPD is that chronic inflammation is spread throughout the lungs, involving the lung parenchyma and the pulmonary vasculature as well as the airways. In asthma, the bulk of the inflammation is seen in the medium-sized airways. The severity and nature of the inflammation may also change during the disease process in COPD. A consequence of this widespread and fluctuating inflammatory process is a chronic imbalance in proteases and antiproteases in the lung. This process is particularly marked in ␣-1-antiprotease deficiency, an inherited condition that makes the sufferers more susceptible to oxidative stress of the type caused by cigarette smoking (see page 7). The pathological mechanisms described above mean that the inflammation becomes increasingly systemic during the course of the disease, with exacerbations occurring more frequently. Inflammatory cells Three types of inflammatory cell have been implicated in COPD: neutrophils, macrophages and T-lymphocytes (Table 1.1). Most research in this area has been carried out on ‘induced sputum’ or bronchoalveolar lavage specimens. Sputum is induced by the inhalation via a nebulizer of hypertonic saline or by physiotherapy treatment or a Table 1.1 Inflammatory cells implicated in chronic obstructive pulmonary disease Location Cell Large airways Macrophages T lymphocytes (especially CD8⫹) Neutrophils (severe disease only) Eosinophils (in some patients) Small airways Macrophages T lymphocytes (especially CD8⫹) Eosinophils (in some patients) Parenchyma Macrophages T lymphocytes (especially CD8⫹) Neutrophils Pulmonary arteries T lymphocytes (especially CD8⫹) Neutrophils Table modified from GOLD website (http://www.goldcopd.com). Pathophysiology combination of both. Bronchoalveolar lavage is carried out via a flexible bronchoscope. These techniques do not readily lend themselves to the acutely ill patient and so the bulk of the research has been in stable patients. Several studies suggest that the total number of inflammatory cells found in induced sputum or on bronchoalveolar lavage relates closely to the severity of the COPD or to the rate of decline in health status. Neutrophils Neutrophils are increasingly seen as a pivotal cell in the inflammatory process. They are found in stable COPD and in increased numbers during exacerbations. Induced sputum has also shown myeloperoxidase in increased quantities, indicating activation of neutrophils. Myeloperoxidase is a green enzyme and is the primary reason why sputum is coloured green in COPD. Patients reporting frequent episodes of green sputum production have a faster decline in health status. It is these enzymes that are the primary cause of tissue damage, impaired healing and the onset of emphysema. Macrophages The role of macrophages is less clear. There are definitely increased numbers of macrophages in all specimens obtained from the lungs of COPD patients but it is their localization in sites of alveolar cell wall damage which is the ‘smoking gun’ in regard to the importance of these cells in the pathological process. T-lymphocytes T-lymphocytes are also present in the lungs in COPD in increased numbers but there does not appear to be a unified hypothesis to explain their role in any pathological process. Eosinophils A number of well-carried out studies have demonstrated an increase in eosinophil numbers during exacerbations while others have shown no increase. However, studies showing increased eosinophils in COPD have failed adequately to exclude asthmatic patients from the study populations. A caveat is that in clinical practice chronic asthma is difficult to distinguish from COPD and both conditions are common and likely to occur together, frequently by chance. Thus, in practical terms, eosinophils need to be discussed on that basis. Epithelial cells In all bronchoalveolar studies, lavage specimens and induced sputum throw up copious numbers of epithelial cells from the lungs. There is a tendency to treat these as a nuisance and there are relatively few studies of them. Those studies that have considered these cells have generally looked at them in cell culture. In these studies there is an increase in E-selectin, which has been implicated in the recruitment of neutrophils. Therefore, it is possible that the activation of alveolar cells themselves may be important in the inflammatory process. 5 6 Definition and pathophysiology COPD OR ASTHMA? CHRONIC OBSTRUCTIVE PULMONARY DISEASE OR ASTHMA? Because inflammation plays a large part in the pathology of asthma and COPD it is tempting to think of these diseases as being very similar. It is, however, critical to stress the differences between the inflammatory processes in the two diseases. Asthma is a condition involving leukotriene D4 (LTD4), interleukins 4 and 5 (IL-4, IL-5) and a multitude of other mediators leading to an eosinophil and mast-cell response. Untreated, there can be thickening of the basement membrane or peribronchial fibrosis, but not the parenchymal damage seen in COPD. Treatment with corticosteroids briskly and effectively inhibits this inflammatory process. Long treatments with oral steroids or high doses of inhaled steroids are needed only rarely. Far too much research has been carried out with inadequate division of the patients into COPD and asthma, and there has been widespread confusion as a result. That said, because both conditions are common they often occur together. The striking thing about the inflammation in COPD is its poor response to steroids either oral or inhaled compared with asthma. The differences between COPD and asthma are summarized in Table 1.2. Table 1.2 Comparison of the inflammatory responses in COPD and asthma. The differences highlight possible future divergence in the management of the two conditions COPD Asthma Cells Neutrophils Large increase in macrophages Increase in CD8⫹ T lymphocytes Eosinophils Small increase in macrophages Increase in CD4⫹ Th2 lymphocytes Activation of mast cells Mediators LTB4 IL-8 TNF-␣ LTD4 IL-4, IL-5 (Plus many others) Consequences Squamous metaplasia of epithelium Parenchymal destruction Mucus metaplasia Glandular enlargement Fragile epithelium Thickening of basement membrane Mucus metaplasia Glandular enlargement Response to treatment Glucocorticosteroids have less effect Glucocorticosteroids have a large effect LTB4, leukotriene B4; TNF-␣, tumour necrosis factor-␣ IL-8, IL-4, IL-5, interleukin, 8, 4 and 5, respectively; Th2, T-helper cell 2. Table modified from GOLD website (http://www.goldcopd.com). Other inflammatory mediators Great interest has surrounded the inflammatory mediators found in stable COPD and during exacerbations. The possible development of a ‘magic bullet’ that would block the inflammation of COPD more effectively than corticosteroids and with fewer side-effects, Pathophysiology CELLS Macrophages Neutrophils CD8⫹ lymphocytes Eosinophils Epithelial cells Fibroblasts MEDIATORS LTB4 IL-8, GRO-1α MCP-1, MIP-1α GM-CSF Endothelin substance P PROTEINASES Neutrophil elastase Cathepsins Proteinase-3 MMPs EFFECTS Mucus hypersecretion Fibrosis Alveolar wall destruction Figure 1.2 Inflammatory responses to inhaled airborne particles, leading to chronic obstructive pulmonary disease (COPD). GM-CSF, granulocyte colony stimulating factor; GRO-1␣, growth related ongocene-1␣; IL, interleukin; MCP-1, macrophage chemostatic protein 1; MIP1, macrophage inflammatory protein 1; MMP, matrix metalloproteases.This figure first published on the GOLD website (http://www.goldcopd.com). Reproduced with permission. has driven research in this area. The main candidate targets are leukotriene B4 (LTB4), interleukin 8 (IL-8) and tumour necrosis factor-␣ (TNF-␣). These substances evoke a neutrophil, macrophage and CD8-lymphocyte cellular response ultimately leading to parenchymal damage (Figure 1.2). Only high doses of corticosteroids will blunt this response, if at all. A number of other mediators may reach prominence at some stage in future research. These include granulocyte colony stimulating factor (GM-CSF), various neuropeptides and fibrinogen. When specific blockers or drugs acting on these pathways become available, it is possible they will become the subject of clinical trials. ␣1-ANTIPROTEASE DEFICIENCY It is impossible to discuss the pathophysiology of COPD without at least mentioning the somewhat uncommon syndrome of ␣1-antiprotease deficiency (also known as ␣1-antitrypsin deficiency). Patients with this condition have an inherited incapacity to produce antiprotease in the liver. They develop an accelerated version of COPD, but only in conjunction with another risk factor such as smoking. Elastin, which is a major target of neutrophil proteolytic enzymes, is a fundamental structural component of alveolar and bronchiolar walls, and damage to these structures underlies the onset of emphysema. Since COPD progresses in the same way as ␣1-antiprotease deficiency, albeit at a slower pace, it is an attractive proposition that a similar imbalance in antiprotease levels exists in COPD patients. Two basic proposals are worth considering: too little antiprotease production or too much protease. The first proposal is obviously true of ␣1-antiprotease deficiency, while the second is clearly a distinct possibility in an ongoing inflammatory process involving neutrophils and macrophages, both of which are capable of releasing proteases of one 7

Author C. Donner and J. Wedzicha Isbn 9780340816950 File size 1.45MB Year 2005 Pages 144 Language English File format PDF Category Medicine Book Description: FacebookTwitterGoogle+TumblrDiggMySpaceShare Appropriate for the clinician managing COPD in either the primary or secondary care setting, Clinicians’ Guide to COPD considers epidemiology, diagnosis and management, concentrating on how patients really present to the clinician. Aspects of disease prevention, including lifestyle change, particularly smoking cessation, are discussed in detail. Acute exacerbations of COPD, currently a major cause of mortality and morbidity in these patients, are also examined. Illustrative ‘real-life’ case histories have been included throughout, and the book also incorporates ‘interesting asides’, for example the impact of COPD on a patient awaiting surgery. With its practical focus, a balanced, readable style and clear explanatory colour illustrations, this book provides invaluable advice for both the primary care and specialist clinician looking after patients with COPD.     Download (1.45MB) COPD: Chronic Obstructive Pulmonary Disease The Washington Manual Pulmonary Medicine Subspecialty Consult, 2nd Edition Pharmacotherapy in Chronic Obstructive Pulmonary Disease Clinical Management of Chronic Obstructive Pulmonary Disease (2nd edition) Non-invasive Ventilation and Weaning: Principles and Practice Load more posts

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