Respiratory disease

Targets for the prevalence of smoking in 2010 are embarrassingly modest The Risk Factor Prevalence Survey conducted by the National Heart Foundation in Australian capital cities in 1989 revealed that, for the first time ever, there were more ex-smokers than current smokers among Australian adults of working age. This major landmark in public health went unnoticed, and, well over a decade later, has still not been achieved in Britain. How can it be that the cradle of epidemiology and the home of the British Doctors Study (and all that it has taught us about the harm done by smoking) is itself doing so poorly in tobacco control? The UK has undeniably made a huge contribution to the science behind effective tobacco control When a survey of over 9000 Londoners in 2002 revealed that 29% were smokers and 27% were ex-smokers, it comes as no surprise that one of the first comments regularly made by visitors from “Down Under” concerns the high ambient levels of tobacco smoke — from the halls of Heathrow onwards. Smoke-free policies are in place on London buses and the Underground, but there are still some smoking carriages on long-distance trains, and many shopping centres permit smoking. Waiting in a crowd for a commuter train at peak-hour is decidedly unpleasant for non-smokers, while pubs and restaurants can comply fully with the “Public Places Charter on Smoking” simply by displaying a sign saying “Smoking permitted throughout”. Despite the recommendation of the International Union Against Cancer (UICC) that tobacco control should combine legislation, education and cessation activities, the Blair Government has until very recently put all of its eggs in the “cessation” basket. Having nicotine replacement therapies and bupropion available on the National Health Service is undeniably important in removing economic barriers to effective aids to quitting smoking, and supporting this with publicly funded smoking-cessation clinics is unprecedented. However, the “ring-fence” around funding for these clinics is not necessarily permanent, and the overall approach remains decidedly unbalanced when judged against the UICC’s recommendation. The UK government has conspicuously failed to take a strong lead, either nationally or within Europe, in adopting the regulatory strategies on smoking and the tobacco industry that are now taken for granted in Australia and New Zealand. UK newspapers and billboards continued to carry advertisements for cigarettes until February 2003, a decade after they disappeared in Australia. Sophisticated, community-wide health promotion using prime-time electronic media, now an export industry for Australia, remains virtually unknown as a tobacco-control activity here, with embryonic campaigns only just beginning to emerge. Evidence that the major tobacco manufacturers are well aware of diversion of significant fractions of their outputs into smuggling operations has not prompted effective official action. Consequently, tax has not been paid on perhaps a third of cigarettes sold in London, significantly undermining the use of price as a disincentive to smoking. The minimum age at which children can purchase cigarettes is stuck at 16 years, and packets of 10, known to appeal especially to school-age smokers because of their low price and greater ease of concealment, are still on the market. Warnings on cigarette packets have been enlarged in size and range, but this is a small advance in an environment that, by standards now well established in Australia, remains otherwise remarkably permissive of smoking. The UK has undeniably made a huge contribution to the science behind effective tobacco control and, beginning with the first report on smoking from the Royal College of Physicians in 1962, has been a pioneer in collating and publishing authoritative, independent expert reviews of the accumulating epidemiological and clinical data as a stimulus to official public health action. It also gave the world the prototypic advocacy organisation Action on Smoking and Health (ASH). Seen through “colonial” eyes, however, it doesn’t have the teeth that have regularly been bared by its Australian counterpart (ASH Australia), the Cancer Council of Victoria, or the Australian Council on Smoking and Health. Meanwhile, the UK Department of Health apparently feels no pressing need to adopt international best practice in tobacco control. A further consequence of the dearth of effective advocacy is the tolerant attitude of the media, up to and including the BBC. For example, the opinions of vested interests that the wider introduction of smoke-free policies would bring an end to commercial and civilised life as we know it are reported uncritically, and seemingly without any effort to find examples that disprove such assertions. Radio audiences are much more likely to be treated to an aside that smoke-free policies in bars in France have been an abject failure than to one that reminds listeners that active smoking accounts for 30% of avoidable cancers, or that passive smoking measurably increases the risk of lung cancer and heart attack, for example among non-smoking staff in bars. The coverage of smoking issues is truly meagre — it takes 4444 deaths from smoking to generate a newspaper story, but only 0.375 deaths from measles, 1.5 from variant Creutzfeldt–Jakob disease, and 22.5 from HIV/AIDS.1 It feels like a time-warp — the British media now are where the Australian media were a generation ago — which is what the overall figures for the prevalence of smoking show, too. But, it also demonstrates an interesting point — the apparent gullibility of the media here is not so much a case of “who pays the piper, calls the tune” (since advertisements for cigarettes have disappeared from newspapers), but the failure of government and health interests to generate and maintain vigorous discussion about the hazards of smoking, active and passive. While no less an expert than Professor Sir Richard Peto argues, with good foundation, that smoking-cessation activities will save lives much faster than waiting to create a whole new generation of non-smokers, this view has allowed the UK government to avoid facing up to the need for a comprehensive tobacco control policy. Its targets for the prevalence of smoking in 2010 are embarrassingly modest. They concentrate on short-term indicators for smoking-cessation services without a population focus, and these are likely to be reached simply as an extension of the background downwards trend of an absolute reduction of around 0.25% per annum. Meanwhile, Britons continue to die from smoking at the rate of one every 5 minutes. Roll on 1989!

Konrad Jamrozik DPhil, FAFPHM, MFPH · David P Weller PhD, FRACGP, FAFPHM · Richard F Heller MD, FRCP, FRACP, FAFPHM

Objective: To determine the change in prevalence of asthma, eczema and allergic rhinitis in Australian schoolchildren between 1993 and 2002.Design: Questionnaire based survey, using the protocol of the International Study of Asthma and Allergy in Childhood.Setting: Metropolitan Melbourne primary schools within a 20 km radius of the GPO in 1993 and 2002.Subjects: All children in school years 1 and 2 (ages 6 and 7) attending a random sample of 84 schools in 1993 and 63 schools in 2002.Main outcome measures: Parent-reported symptoms of atopic disease; treatment for asthma; country of birth.Results: There was a 26% reduction in the 12-month period prevalence of reported wheeze, from 27.2% in 1993 to 20.0% in 2002. The magnitude of reduction was similar for boys (27%) and girls (25%). The 12-month period prevalence of reported eczema increased from 11.1% in 1993 to 17.2% in 2002, and rhinitis increased from 9.7% to 12.7%. There were reductions in the proportion of children attending an emergency department for asthma in the previous year (3.6% to 2.3%), the proportion admitted to hospital (1.7% to 1.1%) and the proportion taking asthma medication (18.5% to 13.4%). Of those who reported frequent wheeze, there was an increase in the proportion taking regular inhaled steroids (34.5% to 40.9%).Conclusion: There has been a significant reduction in the prevalence of reported asthma in Melbourne schoolchildren, whereas the prevalence of eczema and allergic rhinitis has continued to increase.

Colin F Robertson MD, FRACP · Mary F Roberts BAppSci · Johanna H Kappers BNursSci

Objective: To explore the reasons why individuals recurrently present with asthma to hospital emergency departments.Design: A predominantly qualitative study in which participants were interviewed in-depth about their asthma. Data on medication use, respiratory health and asthma knowledge were also collected, and asthma severity was determined from medical records.Setting: A tertiary teaching hospital and a suburban hospital emergency department (ED) from 1 March to 30 April 2000, and a rural hospital ED from 1 July to 31 August 2000.Participants: The participation rate was 32% of an initial 195 ED attendees (183 of whom were eligible) aged 18–70 years: 32 had presented to an ED for asthma care on more than one occasion over the preceding 12 months (reattendees), and 29 were non-reattendees.Results: Two-thirds (22/32) of reattendees had chronic severe asthma and presentation to ED was deemed appropriate for 18 of these, indicated by recurrent severe asthma attacks despite seeking prior medical intervention. Reasons for re-presentation identified in a third of all reattendees included poor asthma knowledge, and financial and other barriers to medication use.Conclusions: We identified potentially preventable issues in about a third of patients (most of whom had mild to moderate asthma) who recurrently presented to EDs for treatment. The remainder of the participants sought emergency asthma treatment appropriately after failing to respond to medical care, and this was frequently in accordance with their asthma management plans.

Dianne P Goeman MA, GradDipSoc · Francis C K Thien MD, FRACP · Jo A Douglass MD, FRACP · Rosalie A Aroni PhD · Michael J Abramson PhD, FRACP · Susan M Sawyer MD, FRACP · Kay Stewart PhD, BPharm(Hons)

Michael South Paediatrician, General Medicine, Royal Children’s Hospital, Flemington Road, Parkville, VIC 3052. mike.southATrch.org.au To the Editor: The recent study by Wilson,1 and its accompanying editorial by Walters and colleagues,2 highlight a number of issues about written asthma action plans (AAPs). The utility of AAPs is controversial. However, a number of points are more certain: AAPs will achieve nothing unless they are part of a comprehensive program of therapy, patient education and review. AAPs must be individualised, and must cover several aspects of self-management, including ongoing maintenance therapy and future acute episode treatment (including the current episode if this has triggered the patient’s attendance). AAPs cannot improve patient care if doctors don’t take the time and effort to write them, and if patients don’t have them available at the time of need, particularly during acute episodes. AAPs are a useful communication tool, and an aid in consistency of care, provided patients and all their doctors have up-to-date copies of the same plan. To help with the complex and time-consuming task of producing customised AAPs, we developed a computerised AAP generator which runs in a standard web browser. Individualised AAPs are produced with minimal typing and a few mouse clicks in less than 45 seconds. All plans have sections for future acute episodes. Sections for preventer medications and the current episode only appear when selected. All asthma medications currently available in Australia are selectable from drop-down menus, and these lists are updated regularly. There are several prompts to encourage best-practice care. Enough copies are produced for the family, school, kindergarten, child minder, grandparents, general practitioner, and hospital notes. The AAP generator was made available on the Royal Children’s Hospital intranet in July 1999. This intranet version logs, in detail, all use of the plan and the recommended therapies, without any patient identification. About 19 500 plans have been generated since. We have not formally evaluated this system, but we do know, from informal feedback and from our records showing that many of them have used it hundreds of times each, that our staff find it useful. AAPs are only a part of the “education package” required for patients with asthma. If it is quick and easy to generate good AAPs, it is to be hoped this will encourage doctors to produce them, while also giving them more time to concentrate on the explanation and discussion of care. The AAP generator is available for free download from our website (www.rch.org.au/clinicalguide/asthmaPlanRequest.php).

Michael South

Re: “Nocardia asteroides pneumonia with bacteraemia”, a letter by Figgis PA, Glanville AR, Harkness JL, in the 4 August 2003 issue of the Journal (Med J Aust 2003; 179: 171-172). The image in Box 3 should have shown the histological appearance of a liver biopsy, not the published lung biopsy. The correct image appears in the Box. The html and pdf versions of this article published on the eMJA website were corrected on 20 October 2003. 3: Liver biopsy in a patient with Nocardia asteroides pneumonia Core biopsy of liver, showing a granuloma within the central portal triad (arrow); the portal ducts are expanded and fibrosed with a patchy lymphocytic infiltrate (original magnification x 40; haematoxylin and eosin stain).

Patricia A Figgis · John L Harkness · Allan R Glanville

Croup affects about 2% of preschool-aged children every year. Most children have mild croup and are managed at home, often after review by a general practitioner, who may decide that a single dose of oral corticosteroid is indicated (eg, if a risk factor for hospital admission exists). A minority of children develop moderate or severe croup. They should be reviewed in an emergency department and may need hospital admission. More liberal use of systemic corticosteroids for croup (in both primary care and emergency department settings) has been associated with reduced rates of hospital admission, reduced admissions to the intensive care unit and a reduced need for endotracheal intubation. We discuss the assessment and evidence-based management of a child with mild croup presenting to a GP and a child with moderately severe croup presenting to an emergency department. We present a flow chart summarising an approach to assessing and treating croup in the emergency department.

Dominic A Fitzgerald MB BS, PhD, FRACP · Henry A Kilham MB BS, FRACP

Patricia A Figgis,* Allan R Glanville,† John L Harkness‡ * Thoracic Registrar (currently, Senior Registrar, General Intensive Care, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW, 2050); † Head of Thoracic Medicine, ‡ Director of Microbiology, St Vincent's Hospital, Darlinghurst, NSW. patriciafiggisAThotmail.com To the Editor: A previously well 57-year-old man presented to the emergency department with a 3-day history of severe dyspnoea. Six weeks earlier he had noticed coryzal symptoms with subsequent lethargy, reduced appetite with weight loss, and a non-productive cough. He then developed ankle swelling and increasing abdominal girth. He had a background of excessive alcohol consumption, but had abstained for 10 years. On examination, he was febrile and in respiratory distress, with a respiratory rate of 35 per minute, pulse rate of 130 bpm, and blood pressure of 130/85 mmHg. Chest auscultation revealed bilateral diffuse coarse crackles. The chest x-ray is shown in Box 1, and results of additional investigations in Box 2. Despite treatment with broad-spectrum antibiotics (intravenous ceftriaxone, dicloxacillin and erythromycin), the patient’s condition deteriorated rapidly, and he required intubation within 24 hours of presentation. Trap sputa contained abundant thin, partially acid-fast, beaded, branching filaments, suggesting Nocardia asteroides, which was later confirmed on culture using conventional biochemical testing. Several blood cultures taken on admission also grew N. asteroides. All cultures for mycobacteria were negative. The patient was treated with intravenous trimethoprim–sulfamethoxazole for a total of 5 weeks and oral minocycline for 14 weeks. He spent 6 weeks in hospital. Liver biopsy, performed because of persistently abnormal hepatic function at follow-up 8 weeks after hospital discharge, showed central fibrosis and non-caseating granulomatous hepatitis (Box 3). The patientn received no further treatment and remained well 18 months later, with almost normal hepatic function and a clear chest x-ray. Nocardia bacteraemia is rare, although the incidence appears to be increasing in the immunosuppressed. Nocardia spp. are seldom isolated in blood cultures, with one study finding that blood was the source of only 8% of all Nocardia isolates.1 Up to 30% of patients with Nocardia bacteraemia have coexistent infection with gram-negative bacteria.1,2 There has been one previous report of Nocardia pneumonia associated with positive blood cultures and liver disease. However, this patient had documented end-stage chronic liver disease at presentation, was taking prednisolone, and developed nocardiosis after prolonged hospitalisation with gram-negative sepsis.1 Granulomatous reactions are well described in Nocardia infection. Although granulomatous hepatitis is also described in sarcoidosis, it is rare and usually presents with itch and obstructive abnormalities of liver function.4 In our patient, acute N. asteroides infection was the most likely cause of both the pulmonary infiltrate and the granulomatous hepatitis. Not only were results of modified acid-fast stains consistent with Nocardia spp., but cultures from multiple trap sputa and blood specimens also grew N. asteroides, suggesting a large load of this organism. No other organisms were isolated despite prolonged incubation of cultures, and the patient recovered after specific treatment directed at Nocardia spp. Furthermore, he remained well with no further treatment at 18-month follow-up, with near-normal hepatic function and no new abnormalities. We conclude that N. asteroides infection can present as a fulminant community-acquired pneumonia with bacteraemia in the absence of immunosuppression or coexistent infection. Our case illustrates the potential hepatic sequelae of Nocardia bacteraemia. 1: Chest x-ray of a patient with Nocardia asteroides pneumonia Chest x-ray taken on admission to hospital, showing widespread non-symmetrical interstitial and airspace infiltrates. 2: Results of investigations Result Reference range At presentation Arterial blood gases* pH 7.37 7.35 –7.45 pCO2 (mmHg) 43 35 – 45 pO2 (mmHg) 60 75 –105 Bicarbonate (mmol/L) 24 24 – 31 Base excess 0 − 3 to 3 White cell count Total (x 109/L) 31.5† 4 –11 Neutrophils (x 109/L) 30.2 2 – 7.5 Lymphocytes (x 109/L) 0.7 2 – 4 Follow-up at 8 weeks Liver function tests‡ Bilirubin (μmol/L) 9 < 18 Alkaline phosphatase (U/L) 124 30 –100 γ-Glutamyl transferase (U/L) 153 < 35 Iron studies Serum ferritin (μg/L) 446 30 – 400 Serum iron (μmol/L) < 3 10 – 30 Transferrin (g/L) 1.9 2.0 – 3.5 Transferrin saturation < 6% 15%–50% Vitamin B12 (pmol/L) 376 > 126 Immunological tests HIV antibodies Negative Hepatitis B and C§ Negative Autoantibody screen¶ Negative Complement C3 (g/L) 1.07 0.82 –1.45 Complement C4 (g/L) 0.25 0.15–0.45 * Breathing 10 L/min oxygen. † Occasional myelocytes, toxic granulation. ‡ Levels of alanine and aspartate aminotransferase were in the reference range. § Including hepatitis B surface antigen and hepatitis C antibody. ¶ Including antinuclear, extractable nuclear antigen, double-stranded DNA and antineutrophil cytoplasmic antibodies. 3: Liver biopsy in a patient with Nocardia asteroides pneumonia Core biopsy of liver, showing a granuloma within the central portal triad (arrow); the portal ducts are expanded and fibrosed with a patchy lymphocytic infiltrate (original magnification x 40; haematoxylin and eosin stain).

Patricia A Figgis · Allan R Glanville · John L Harkness

John M Weiner Allergist, Department of Respiratory Medicine, St Vincent’s Hospital, Fitzroy, VIC 3065. jmweinerATallergynet.com.au To the Editor: Any doubts that many Australian doctors are prescribing inhaled fluticasone for asthma at inappropriately high doses are dispelled by the three reports in the 3 March issue of the Journal.1-3 Fluticasone has a flat dose–response curve for efficacy and a steep dose–response curve for adverse effects;1 individuals with asthma are receiving high doses of inhaled fluticasone;2 and there is a potential for the effects to be lethal.3 Each of these reports restricted its advice to negative recommendations about drug treatment (DON’T overtreat, BACK-titrate), but this is the right time to also promote positive recommendations about asthma management. All individuals with persistent asthma requiring daily therapy should have either skin testing or in-vitro testing to determine the presence of specific IgE antibodies to inhalant allergens.4 This might allow the option of allergen avoidance. In some studies, dust mite reduction was found to ameliorate asthma symptoms in sensitised individuals (National Health and Medical Research Council Level II evidence), although those findings are not supported by a meta-analysis. Repeated low-dose exposure to cat allergen in cat-allergic individuals with asthma leads to increased non-specific bronchial hyperreactivity (Level II evidence).5 Allergen desensitisation in carefully selected cases with consultant supervision can lead to a significant reduction in medication requirement, and reduced specific bronchial hyperreactivity (Level I evidence).6 Treatment of concomitant rhinitis can itself lead to easier asthma control. A checklist of the “A,B,C...” of asthma triggers does not take long and often yields useful tertiary prevention strategies: Allergy (seasonality, dust, pets), Bronchial infection, Cold air/exercise, Drugs, Emotion/stress, Food and food additives, Gastro-oesophageal reflux, Hormones and pregnancy, Irritants including cigarette smoke, and the Job. Inhaled anti-inflammatory treatment using cromolyns or corticosteroids, with or without consideration of oral montelukast, remains the cornerstone of asthma control when the disease is frequent or persistent. However, the search for allergic and other triggers by healthcare workers, individuals with asthma, and their carers can instil into the entire group a culture of prevention, which naturally leads to a brake on overtreatment. Such a culture is firmly entrenched in continental Europe and the United States. In Australia, there has been outstanding research into the epidemiology and immunology of asthma, but it’s at the coalface where the individual with asthma gets advice. A diligent search for triggers, with appropriate management, should start at the first consultation, as the pen (or mouse) is poised to prescribe.

John M Weiner

Re: "Asthma symptoms associated with depression and lower quality of life: a population survey?", the Research article by Robert D Goldney, Richard Ruffin, Laura J Fisher and David H Wilson in the 5 May issue of the Journal (Med J Aust 2003; 178: 437-441), in which variables in Box 1 were incorrectly labelled. "Male sex" should have been "Female sex", and "Overseas born" should have been "Australian born". The corrected table is shown. The html and pdf versions of the article were corrected online on 30 June 2003. Predictors of asthma determined by logistic regression Variable Odds ratio (95% CI) P Female sex 1.55 (1.22–1.99) 0.003 Depression 1.40 (1.04–1.88) 0.026 Australian born 1.60 (1.18–2.18) 0.003

Robert D Goldney MD, FRANZCP · Richard Ruffin MD, FRACP · David H Wilson MPH, PhD · Laura J Fisher BA(Hons)

Clinical record At 11: 30 on 8 April 2003, a 64-year-old man presented to the National University Hospital emergency department (ED) complaining of light headedness for 3 days, and dry cough and body aches for 2 days. His general practitioner had recorded a temperature of 37.7°C. On further enquiry in the ED, he described mild dyspnoea and palpitations. For over 40 years, he had smoked 25 cigarettes a day, ...

Dale A Fisher MB BS, FRACP, DTMH · Madeleine H L Chew MB BS · Yean-Teng Lim MRCP, FRCP · Paul A Tambyah MB BS

Re: "The SARS epidemic: lessons for Australia", by Cameron PA, Rainer TH, De Villiers Smit P, in the 2 June 2003 issue of the Journal. The Box with the World Health Organization case definitions of "suspected" and "probable" SARS (severe acute respiratory syndrome) was omitted from the print version of this editorial (Med J Aust 2003; 178: 478-479), but was included with the rapid ...

Peter A Cameron MB BS, FACEM, MD · Timothy H Rainer MB BCh, FHKCEM, MD, FHKAM · Pieter De Villiers Smit MB ChB, FACEM

Action plans are not a "quick fix", but only part of a care package requiring doctors' time and commitment Providing an individualised written asthma "action plan" is a particularly high-profile part of Step 6 of the Australian Asthma Management Plan: "Educate and review regularly". The idea of a written action plan is that the patient is given a set of rules by which to alter therapy, dependent on either peak expiratory flow monitoring or symptom levels. The implication is that an appropriate, early response to deterioration will prevent dangerous exacerbations and will generally improve health-related quality of life. Written action plans for asthma are perceived to be so important that they became one of the two Australian Council on Healthcare Standards Performance Indicators for quality assessment of acute respiratory medicine in Australian hospitals. However, the evidence — whether from research or from clinical practice — that written action plans, in themselves, are effective is equivocal. There are now a number of Cochrane Collaboration Airway Group systematic reviews that examine this area, but the outcomes are inconsistent. Gibson et al analysed up to 36 studies comparing self-management, education plus regular practitioner review against usual care.1,2 They found that active intervention significantly reduced hospitalisation, emergency room visits, unscheduled visits to the GP, days off work or school, nocturnal attacks of asthma, and quality of life, but that lung function was not altered. Self-management programs that involved a written action plan were more effective than those that did not, but regular doctor review seemed to be most important. Indeed, a review by Toelle et al failed to find consistent evidence that written plans, of themselves, have any effect on asthma control.3 Powell and Gibson found that optimising asthma control through adjustment of inhaled corticosteroid dose could be as well achieved by written guidelines for the patient as by seeing their doctor to adjust the dose.4 Somewhat paradoxically, there was evidence that removing regular doctor visits from a management plan was deleterious. Verbal and written instructions to patients seemed equally valuable: the intensity of education seemed to be more important than the format of the advice. But is the proof of the pudding in the eating? If so, ownership of written action plans seems to be falling in Australia although it was never particularly popular in the asthma community. A community sample in South Australia showed a fall from 42.3% in self-reported ownership of written plans in 1995 to 22.2% in 2001, as reported in this issue of the Journal (page 483).5 Furthermore, a large epidemiological study conducted recently in Melbourne also indicated a fall in written action plan use, albeit from an even lower base: in 1999 just 13.3% of Victorians with self-reported asthma had ever been given such a plan, compared with 19.9% in 1993.6 The current situation and available facts therefore raise more questions than they answer.7 Why is uptake of written action plans so disappointing? If written action plans work, why are they not more popular? What is their main purpose — is it to prevent exacerbations or to control day-to-day levels of disease activity? Studies have shown that written action plans are viewed positively by patients, but in practice, they modify their plans according to their own perceptions and experience of asthma.8 It is important that doctors realise this and give patients time to explore such issues and then incorporate them into an agreed plan. Indeed, the role of doctors is very important — their degree of empathy with patients and the amount of time they give to management issues have significant outcome effects in asthma.9 Presumably this "doctor effect" will extend to the uptake and usefulness of asthma action plans. What seems certain is that action plans cannot be used as a substitute for regular detailed review and comprehensive education of patients with asthma. Developing long-term relationships with their doctors, accompanied by being involved in discussion and decision making is important.9,10 Data suggest it is the "process" not the written action plan per se that is currently at fault. Complicating the delivery of asthma care is the poor training of doctors in creating or delivering care packages involving negotiated action plans. Indeed, the main reason for patients not having a written asthma action plan is that they are not given one by their doctor!8 Longitudinal studies are needed to evaluate the effects of enhancing physicians' "participatory decision making" style9 on outcomes of patients with asthma, especially in general practice, where most such patients are managed. This is particularly so in light of the year-old Commonwealth Government-funded national initiative for asthma management in the community, in which a 3+ visit plan in general practice11 provides a framework for optimising treatment and education. This plan includes a written action plan for patients with moderate-to-severe asthma. This needs to be rigorously assessed in routine clinical practice, as even the best ideas and most worthy initiatives from professional "enthusiasts" can be confounded through lack of sufficient time and commitment. Evidence shows that patients will not cooperate with any intervention that is less than fully backed by the time and authentic personal commitment of their doctors. Yet, in a pressurised fee-for-service system, it can be difficult to sustain interest and enthusiasm in the long term. In conclusion, the uptake of asthma action plans in Australia is disappointing, especially as we know they can be useful as part of the right package. Perhaps the management of chronic diseases like asthma needs different sorts of practitioners in a different professional and funding milieu. Yet another challenge for our beleaguered healthcare system?

E Haydn Walters MADM BCh FRACP · Julia AE Walters BM BCh · Richard Wood-Baker DM FRACP

Forewarned is forearmed Severe Acute Respiratory Syndrome (SARS) is now a global phenomenon, but it remains heavily clustered in mainland China, Hong Kong, Toronto, Singapore and Hanoi.1-5 The world is fearing a global pandemic, but it is not happening as initially predicted. Although there are some uncertainties regarding particular clusters of cases, such as the Amoy Garden Estate in Hong Kong (where about 300 people in one block of flats were affected), the primary mode of spread appears to be by infected droplets, and healthcare staff taking strict barrier precautions appear to be protected. There is some evidence that the virus is present in all body fluids, including faeces and urine, so taking precautions with waste disposal are also recommended. World Health Organization case definitions of severe acute respiratory syndrome (SARS) The WHO case definitions of SARS, revised as of 1 April 2003, for a suspected and a probable case of SARS: 6,7 A "suspected" case of SARS is a person presenting after 1 November 2002, who gives a history of high fever (> 38°C), and cough or breathing difficulty and one or more of the following exposures during the 10 days before the onset of symptoms — close contact with a person suspected of having SARS, or a history of travel to or residing in an affected area. A "probable" case of SARS pneumonia is a suspected case (as defined above), with radiographic evidence of infiltrates on chest x ray consistent with pneumonia or respiratory distress syndrome, or a suspect case with autopsy findings consistent with the pathology of respiratory distress syndrome, but without an identifiable cause. The World Health Organization case definitions of "suspected" and "probable" SARS are given in the Box. The clinical course of the disease follows a 2–16-day incubation period,4,5 with high fevers, chills, rigors and myalgia. In contrast to the WHO definition, respiratory symptoms are not prominent and many cases have presented with diarrhoea, abdominal pain and loss of appetite (unpublished observations). There are very few patients with abnormal findings on chest examination at presentation, but these changes develop in severe cases after admission to hospital.5 Laboratory tests typically show a reduced white cell and lymphocyte count, with a mild increase in the platelet count. Usually after 2–3 days of symptoms, x-ray changes become apparent. Typically, the changes are air-space consolidation, predominantly peripheral and often unifocal initially, but progressing over days to bilateral, multifocal changes. At around 7–10 days, about 20%–30% of cases deteriorate and require admission to an intensive care unit. Of these, about half require assisted ventilation. The overall mortality rate is 3%–5%, but may be higher in elderly people. Treatment has been largely empirical and usually has included an antiviral agent, such as ribavirin, and steroids.5 High-dose steroids have been effective in reducing fever and progression of x-ray changes, with the clinical response and radiological features suggesting bronchiolitis obliterans organising pneumonia as the possible underlying pathology.5,8 It is unclear whether any of these treatments alter the ultimate course of the disease. Intravenous administration of convalescent plasma has also been trialled, in the belief that antibodies may halt the progression of the disease,5 despite a theoretical risk of introducing another viral load. Currently, there are a number of possible aetiological candidates, with corona virus being the most likely;9-11 however, a metapneumovirus from the paramyxovirus group12 has also been suggested. Unfortunately, in our experience, field testing for the viruses has so far been unconvincing. It is unlikely that, in the short term, there will be a reliable diagnostic test or vaccine, although work is progressing at a rapid rate. In Australia, the response to SARS has been dichotomous — varying from panic that SARS will be another pandemic to complacency that this is another region's problem. It is likely that Australia will be less affected than countries with open land borders and crowded cities with poor hygiene control. However, the outbreak in Toronto shows that any Western city may have to manage such an outbreak.3 If this disease spreads in clusters rather than sweeps through communities, then the public-health response must be different. It is clear that hospitals and healthcare workers are particularly at risk. In Hong Kong, in the first weeks of the outbreak, 25% of patients with SARS were healthcare workers.5 The healthcare sector has to be particularly prepared, as this is most likely where a cluster will start. Revision of infection control, with meticulous attention to detail, is important. At the Prince of Wales Hospital, Hong Kong, it took three weeks to bring the secondary infections in staff down to near zero. Despite this experience, other hospitals in the region did not take heed, and many more staff in these hospitals became infected because of suboptimal infection control procedures. It is to be hoped that hospitals in Australia will learn from this experience. Screening potential cases of SARS is particularly difficult, as the signs and symptoms are vague and consistent with virtually any viral illness. Following up patients over a number of days is the only way of ascertaining whether they have SARS. The question of whether to admit all suspected cases to hospital is also an issue. If suspected cases are admitted, they may actually contract the disease in hospital. If they are discharged, they may infect their families and friends. In our recent experience of screening about 1000 people with suspected SARS, we uncovered over 100 confirmed SARS cases. We found that there was no secondary spread among the suspected cases followed at home with strict quarantine instructions. All people with confirmed SARS were admitted to hospital. Guidelines for screening high-risk contact and low-risk non-contact subjects have recently been published, although there are no good studies evaluating their utility or the quality of the supporting evidence.13 SARS will fundamentally change the interaction between primary healthcare workers and patients, in much the same way that AIDS changed the way we handle blood products, with universal precautions to protect ourselves from potential HIV infection. It is likely that, in the future, all healthcare providers in regions where SARS is endemic will use the standard droplet precautions of a mask, goggles, gown and gloves for all patient contact. SARS has the potential to totally disrupt the healthcare system of cities or states. Apart from the potential to use hundreds of general ward beds — a disaster in itself given the bed capacity of most Australian hospitals — the biggest threat is the need for intensive care unit (ICU) beds. If 20%–30% of cases required care in ICU, and a cluster of 200 cases occurred in Melbourne or Sydney, there would be little likelihood of finding 50 ICU beds at short notice. A further problem is that ICU staff are likely to contract the disease (unpublished data). If a number of staff contract the disease in an already overstretched ICU system, this may precipitate a fall in morale and staff departures. Furthermore, many nurses are of child-bearing age, and the antiviral agents and high-dose steroids used in the treatment of SARS are likely to be teratogenic. Health authorities need to think about their ability to provide "surge capacity" — not only in terms of ventilators, but also in terms of trained staff. This might include multiple-skills training for nurses and doctors working in non-intensive-care areas. Some healthcare epidemiologists have suggested that this disease is no more serious than the usual winter influenza outbreaks, and not nearly as serious as a new mutation of the influenza virus would be.14 The difference is that previously we have not seen a healthcare system paralysed for a period of months from the impact of one infectious agent. The annual reported death toll from influenza is mostly due to its impact on elderly people, who may die anyway. SARS puts young healthy people into ICU, and otherwise healthy people die. The death toll from SARS is undoubtedly higher in the elderly, and we have not yet seen what may eventuate if a SARS outbreak occurs in a retirement home. The sensible response of Australian health authorities is to remain on high alert, review infection control procedures within hospitals, develop contingency plans for a possible surge in demand for general and ICU beds, and develop an evidence-based approach to screening and quarantine procedures for potential cases.

Peter A Cameron MB BS, FACEM, MD · Timothy H Rainer MB BCh, FHKCEM, MD, FHKAM · Pieter De Villiers Smit MB ChB, FACEM

Objectives: To assess trends in the prevalence of self-reported doctor-diagnosed asthma, associated asthma related morbidity, and the uptake of written asthma action plans in South Australia, 1990–2001.Design, setting and participants: Surveys by telephone interview of the South Australian population between 1990 and 2001, and interview of participants in their own homes by trained health interviewers.Main outcome measures: Asthma prevalence, percentage of patients with written action plans, and asthma associated morbidity.Results: The reported prevalence of doctor-diagnosed asthma has increased from 8% (95% CI, 6.4%–9.6%) in 1990 to 12.8% (95% CI, 11.4%–14.2%) in 2001. Morbidity, as measured by wakening at night (daily or weekly) and days lost from normal activities because of asthma, has remained constant over the decade. The percentage of patients with written asthma action plans increased to a peak of 42.3% (95% CI, 40.3%–44.3%) in 1995, but then declined to 22.2% (95% CI, 20.7%–23.7%) in 2001.Conclusions: The prevalence of asthma has increased while morbidity has remained constant, indicating that the burden of asthma has increased. The associated decline in the percentage of patients with asthma action plans in recent years is cause for concern.

David H Wilson PhD · Robert J Adams MD · Sarah L Appleton BSc · Graeme Hugo PhD · Janet Hiller PhD · Philip Ryan MD · Richard E Ruffin MD · David Wilkinson MD, PhD · Julianne Cheek PhD

Objectives: To describe the short-term outcomes in Aboriginal children admitted to hospital with radiological alveolar lobar changes; and determine whether predischarge chest radiography can predict respiratory morbidity found at follow-up.Design, participants, setting: Prospective cohort study of Aboriginal children admitted to Alice Springs Hospital between October 2000 and April 2001 with alveolar lobar abnormalities (area of consolidation, ≥ 1 cm) on chest radiographs. Participants were to have a predischarge radiograph and be followed up for 12 months.Main outcome measures: Comorbidities, follow-up rate, and new respiratory disease found at follow-up.Results: Of 113 children hospitalised with radiological alveolar lobar changes, 109 were Aboriginal. Their median age was 1.8 years (range, 0.2 months–13.3 years), and 124 episodes were recorded. Comorbidities were common in these children (anaemia, 51.5%; suppurative otitis media, 37.3%). The follow-up rate one year after admission was 83.1% of episodes. New treatable chronic respiratory morbidity was found in 20 (25.6%) of the 78 children with completed follow-up. Predischarge chest radiographs were predictive of all chronic respiratory morbidity when they showed no or minimal resolution (0–20% resolution) (relative risk, 7.43; 95% CI, 2.07–26.60).Conclusions: Central Australian Aboriginal children admitted to hospital with alveolar changes on chest radiographs have a substantial burden of chronic respiratory illness, and should be clinically followed up for early detection and management of chronic respiratory morbidity. A predischarge radiograph is useful, and patients whose radiograph shows no or minimal resolution should have a follow-up x-ray film.

Anne B Chang MPHTM, PhD, FRACP · John P Masel MB BS, FRACR · Naomi C Boyce BNursing · Paul J Torzillo MB BS, FRACP, FFICM

This is the first time I have felt threatened by the work that I do It begins on Tuesday afternoon, 11 March, with another bothersome call from hospital administration. They want to take over our Emergency Department (ED) observation ward because the Department of Medicine has a couple of doctors who feel ill. They think that this illness may be contagious to other staff and patients, so a ward with a separate entrance and separate air-conditioning would be ideal. I make them aware that this action would severely hamper operations within the ED and that they should manage these doctors the same way we have treated the five ED doctors who, at the moment, have some viral illness: send them home. My answer to their request: no way. A short time later, the Professor of Medicine and the hospital's CEO visit my office — a very unusual event. They say they are very concerned because not just two but up to eight medical staff and a number of nurses are febrile and feel unwell. Being a pragmatic ED doctor, I point out that we have to make sure that this illness isn't just one of the many benign URTIs we see at this time of the year. After all, about 20% of our ED attendances relate to URTIs. So, we all agree to callback 40 medical and nursing staff and have them examined that evening. If it turns out they are suffering from some unusual disease, I will be more than happy to hand over the observation ward. I go home at 7 pm in the certain knowledge that I will have a relaxed evening with my family and will turn up to work tomorrow to greet a red-faced professor, apologising profusely for trying to disrupt our emergency service. But, at 9 pm, I take a call from the medical team: they have screened the first few patients and all have high fevers and pneumonic change on chest x ray. Within hours, 20 staff are patients in the observation ward, not desperately unwell but a little anxious about what will happen next. An over-reaction?The following day, we held a meeting of all the chiefs of clinical services to discuss what we should do next. Among many of the senior people, there was a fair degree of scepticism and more than a suggestion that we were over-reacting to this mystery illness. Could it just be that influenza or mycoplasma infection was affecting a disproportionate number of our staff? An over-reaction to the usual round of spring respiratory infections? We had heard of an outbreak of atypical pneumonia in Guangzhou, but the reports were that this was now under control, although rumours suggested otherwise. Certainly, the features of the illness were typical of the reports of severe acute respiratory syndrome (SARS) in Vietnam. We decided to work on the assumption that all three of the illness clusters were related in some way. The ED staff who had been away from work with a "viral illness" were assumed to have the same disease. Despite their protests that it was just another minor illness, they were forced to come in and be admitted to hospital. More medical and nursing staff became ill, as did patients from the same hospital ward. A number of senior staff refused to come into hospital until they became very ill; this resulted in the spread of the infection to their families. Early scareDespite treatment, the condition of all the patients seemed to deteriorate over the first few days. It was not clear whether anyone was going to improve. Only five days after the illness first became apparent in our hospital, I was facing the real prospect that a member of my own staff would die. One of my residents, gravely sick, now required intensive care; even with 100% oxygen, he could not maintain adequate arterial oxygen saturations. I prepared myself for his death and let my other staff know that it was likely that he would die. Overnight, he was given high-dose steroids; he improved marginally. By some miracle, his condition continued to improve and he survived. However, at this stage of the outbreak, eight other staff from my ED, as well as over 50 other healthcare workers, were still patients in hospital. This illness looked like it could eventually involve all the hospital staff; potentially, any or all of us could end up in the ICU. Empirical experienceMedical treatment was largely empirical because the causative agent responsible for the illness was unknown to us. Patients were initially treated with oseltamivir and broad-spectrum antibiotics to cover all likely known pathogens. Ribavirin and steroids were used, but there was no way of knowing whether this was altering the basic course of the disease. With experience, it became apparent that high-dose steroids had a major impact in halting deterioration late in the illness. Managing an illness that you know little about, under the scrutiny of your colleagues (as your patients), is very difficult. The pressures on all medical units and ancillary staff were enormous. The whole medical department was involved in treating the patients, and the number of staff affected grew steadily to more than 150. After considerable negotiation with the health authorities, normal operations within the hospital were suspended. Fortunately, there was a high degree of altruism and cooperation among the medical staff; all departments contributed to both staffing (in a high-risk situation) and to the overall management of this disaster. There were daily meetings of chiefs of services and forums for regular staff. Daily, factually accurate updates were posted electronically. It was simply incredible to see staff turning up to work each day despite the fact that, in the first two weeks of this experience, each day about four or five more staff members would succumb to the illness. From Day 1, all staff wore masks and gowns but we were still getting breakthrough cases. With meticulous attention to infection control, watched over by infection control "police" in each ward, we were able to reduce this occurrence to near zero. Like a stakeoutAt a personal level, this is the first time I have felt threatened by the work that I do. Perhaps, it's a similar experience to that of a policeman on his first "stakeout", when he realises he might get shot. As a doctor, you know you are potentially vulnerable to the getting of all sorts of illnesses, but rarely a devastating, life-threatening one. I was worried about going home in case I would infect my family. When I did get home, I felt physically exhausted and emotionally drained, and didn't really want to talk to anyone. I would not and could not touch my wife or children for fear of giving them the disease. I slept in a separate bedroom; I ate separately. Clothes and fomites were washed separately and chlorine bleach was everywhere. My youngest boy developed a nervous twitch as he was told tales of the disease and harassed to wash his hands and wear a mask. Some of my colleagues began sleeping in their offices, refusing to go to their homes at all for fear of infecting their families. It wasn't a situation I could go on living with. My wife and I decided it would be easier for all of us if my family returned to Australia. A couple of weeks after they left, I realised how isolated I had become outside of my work setting. No one wanted to come near me for fear of getting the disease; any social encounters became uncomfortable. Even in the carpark, people would skirt around me to avoid close contact. There was little time off work, anyway, because of the constant meetings and service commitments occasioned by the outbreak. By strange coincidence, news of the Iraqi war was being broadcast continuously on television. Disturbing as the images of this war were, I realised that the battle we were fighting here might well have a more long-lasting, devastating impact. Missing the pointWhen I spoke with friends in Australia, I was struck by how little they had heard about the outbreak in the first weeks and how little preparation authorities seemed to have undertaken. Some "armchair experts" were even saying that it was irrelevant to Australia, just another "beat-up". In their minds, influenza was much more important. I tried to remember the last time influenza had put 250 healthcare workers into hospital, with 20% of them in an ICU. I tried to remember the last time all the ICU beds in a city had been filled by influenza cases. As far as I was concerned, these "experts" had clearly missed the point. Also, initially there seemed to be a high degree of misinformation about the symptoms, signs and mode of spread of this disease. In general, the only definite symptom was fever. In the early stages of the illness, cough, rhinitis and other URTI symptoms were actually less prevalent in the SARS group than in other patients. I believe that information being promulgated by WHO and the Centers for Disease Control and Prevention (CDC) was, in some instances, inaccurate and at other times misleading. For example, early enthusiasm surrounding diagnostic tests proved misplaced when we found only a 10% positivity rate. I felt compelled to make time for some radio and television interviews to raise awareness of SARS. Late warningsIn Hong Kong itself, I believe the authorities were initially very keen to keep the public "in the dark". This was followed by an attempt to blame the hospital (and staff) for allowing the disease to spread. Initially, for fear of creating pandemonium, no moves were made to educate the public about preventive measures. We tried, through official channels, to get these messages out; unfortunately, most officials seemed to me to be more concerned with protecting the economy and preventing panic than containing disease. Unfortunately, this response seems to have been the typical one in some other jurisdictions as well. Although the Hong Kong government has since adopted widespread public health measures, at time of writing it still maintains that there is no crisis. I do not agree; there is no obvious end in sight. More and more of the public are becoming infected. There is a high likelihood that more healthcare workers will be struck down. It is distinctly possible that if the numbers of affected patients continue to rise the whole public health system may collapse. The most likely pressure point will be the intensive care setting: with over 100 cases already requiring intensive care, it is inevitable that untrained staff will have to manage critically ill patients. Also, hospitals will have to "triage" patients, allocating intensive care beds and technology to those most likely to benefit before those with a lesser or low chance of survival. Today, despite my concerns for the community, my personal fear has receded. I feel more capable of managing this threat than I did in my first fortnight's experience of it. Although I am not 100% sure of the cause of this illness (despite the confident reports from scientists), I do understand something about its course and how to control its spread, at least within the hospital. I know that most people will survive the disease. However, I remain extremely frustrated that others are not learning the lessons that we have learnt regarding the need for stringent infection control. Most medical staff think they know about infection control and how to manage a crisis, and are unwilling to take advice. As a result of this attitude, and despite direct knowledge of our experience, I believe that about 20 staff at another hospital in Hong Kong have contracted the disease. As a healthcare worker, the likelihood of contracting an infectious disease that will kill you is usually quite small. When a new, mysterious illness smites down a whole hospital and its workers, it hits at the heart of the health system.

Peter A Cameron MB BS, FACEM, MD

Objective: To identify any association between asthma and depression and quality of life.Design and setting: A face-to-face Health Omnibus Survey of a random and representative sample of the South Australian population in August 1998.Participants: 3010 randomly selected participants aged 15 years and over.Main outcome measures: Prevalence of doctor-diagnosed asthma, and scores for depression (measured by PRIME-MD instrument) and quality of life (measured by SF-36) in affected participants.Results: The prevalence of asthma was 9.9%. The prevalence of major depression was significantly higher for those who experienced dyspnoea, wakening at night with asthma, and morning symptoms of asthma. Quality-of-life scores were also lower for the same groups.Conclusions: Depression is a serious but potentially remediable comorbidity with asthma that may affect appropriate diagnosis and outcome.

Robert D Goldney MD, FRANZCP · Richard Ruffin MD, FRACP · David H Wilson MPH, PhD · Laura J Fisher BA(Hons)

Careful assessment of car accident risk in patients with sleep disorders should guide advice Alcohol and excessive speed, often combined with inexperience and youthfulness, are the most widely recognised causes of motor vehicle accidents (MVAs). There is, however, increasing recognition that fall-asleep MVAs contribute significantly to road accident statistics.1-5 The typical fall-asleep accident involves a sole driver driving at night or in the early afternoon "siesta" period at relatively high speed.1 As with other causes of MVAs, fall-asleep accidents are more common in men under 30 years.1,3,5 In this issue (page 396), Desai and colleagues6 describe seven cases of fall-asleep fatal MVAs, and highlight the inconsistent way in which the New South Wales legal system dealt with these cases. They also draw attention to the role of sleepiness and sleep disorders in these cases, five of which involved under-treated or unrecognised obstructive sleep apnoea. These case studies are, by any measure, tragic, involving as they do serious injury, loss of life and, in several instances, imprisonment of the driver. They raise the question as to what role the medical profession might have in the prevention of such accidents. Obstructive sleep apnoea is the most common clinical sleep disorder leading to daytime sleepiness. About 26% and 10% of the Australian adult male population have ≥ 5 and ≥ 10 sleep apnoeas or hypopnoeas per hour, respectively.7 However, it is important to maintain perspective when thinking about this issue. First, while obstructive sleep apnoea is very common, most people with sleep apnoea will never have an accident due to sleepiness or be at significant risk for an accident.8 The relative risk for MVAs among all people with obstructive sleep apnoea is about 2–7 compared with the general population. This seems high, but is similar to the increased risk associated with driving at night,1 or for young drivers compared with older drivers. Second, sleep restriction (lack of sleep) is at least as common and is possibly of greater concern with respect to fall-asleep MVAs.5 The drivers with sleep apnoea described by Desai and colleagues all had mild-to-moderate obstructive sleep apnoea, which normally would not be associated with a high risk of an MVA,9 but, as acknowledged by the authors, the commercial drivers in particular were probably also sleep-deprived. In one case, prior sleep deprivation appeared to be the sole cause of the fall-asleep MVA. Nevertheless, there are patients with obstructive sleep apnoea who constitute a real and immediate risk to other road users. How does a medical practitioner identify and advise these patients, to try to prevent the tragedies so graphically described by Desai et al? The approach I would advise is as follows. First, establish good rapport with your patient and his or her family. A confrontational approach or immediately raising the possibility of revoking the driver's licence will lose you the patient. The emphasis should be on maintaining doctor–patient confidentiality, appealing to the patient's social responsibility, and the fact that, with appropriate diagnosis and treatment, most patients with sleep disorders can drive unrestricted. Assessing the effect of a patient's sleepiness on their driving Ask about instances of falling asleep while driving (eg, wheels on the verge or hitting the "cats eyes", lane drifting, previous fall-asleep crash) Seek corroborative history from the spouse or partner Ask patient to fill out the Epworth Sleepiness Scale questionnaire,10 which takes about five minutes. It requires patients to rate their chance of dozing in eight specific situations. The normal value is < 10 out of a maximum possible score of 24. A score > 15 indicates severe sleepiness and has been associated with substantially increased risk of fall-asleep MVAs.3 Consider additional causes of daytime sleepiness. Sleep restriction is very common and sleeping for less than five or six hours for even one night significantly increases the risk of a fall-asleep MVA.3,5 Second, make an assessment about the level of sleepiness and its possible impact on driving risk in your patient (Box). It would be unreasonable and totally impractical to send all patients with obstructive sleep apnoea for daytime sleep latency tests to determine level of sleepiness. Third, consider your patient to be in a "high-risk" category if there is a history of (1) a recent fall-asleep accident, (2) repeated "near-miss" fall asleep episodes while driving, (3) repeatedly falling asleep in other active situations (eg, during conversation, at meal table), or if your patient has a very high score on the Epworth Sleepiness Scale.10 Current Australian guidelines for healthcare professionals11 indicate that such "high-risk" patients should be instructed to stop driving immediately while referral to a sleep specialist and further investigation and treatment is arranged. If you consider that your patient is sleepy but does not fit the above "high-risk" categories, it may nevertheless be wise to advise him or her to reduce the risk of an MVA by avoiding night or country driving and by abstaining from all alcohol before driving. Fourth, keep careful notes. Ideally, all patients with obstructive sleep apnoea should be informed verbally, and in writing (eg, a pamphlet) if possible, about the increased risk of fall-asleep MVAs and the need to exercise care while driving. Special provisions apply if your patient wishes to apply for or renew a commercial or heavy vehicle driver's licence. Current Australian guidelines for healthcare professionals12 recommend that the licence be withheld if obstructive sleep apnoea (of any severity) is diagnosed, unless and until it is successfully treated. A conditional licence should be recommended (ie, restrictions imposed) if the driver has sleep apnoea symptoms of any severity until these symptoms are investigated. Thus, the burden of proof of driver safety has been deliberately increased for commercial drivers who have or are suspected of having obstructive sleep apnoea. Current uniform national driver licensing laws in Australia place the legal responsibility on drivers to notify their State/Territory licensing authority that they have a medical condition likely to affect their driving. If effective treatment for obstructive sleep apnoea (or any other sleep disorder) cannot be instituted within a reasonable time frame, and if your patient refuses to restrict driving as advised, you should remind him or her of this obligation. Finally, what is your ethical and legal responsibility if you have reason to believe that, against your advice, your patient is continuing to drive while seriously impaired? I believe at this point public safety takes precedence over patient confidentiality. Also, you could be found liable in the case of serious injury or death in the event of a fall-asleep accident should you fail to take reasonable steps to prevent your patient driving in a dangerous manner. You should advise the patient that, in the interests of public safety, you must inform the licensing authority. This action can and will annoy some patients, but legislation in all Australian States and Territories (Western Australian legislation is under review) provides medical practitioners with legal indemnity under these circumstances. The National Road Transport Commission will soon release new medical standards for drivers of all vehicle types. These will provide specific advice for medical practitioners relevant to licensing and driver safety across a wide range of medical conditions, including obstructive sleep apnoea.

R Doug McEvoy MD, FRACP

Obstructive sleep apnoea is associated with an increased risk of sleep-related motor vehicle accidents. Seven recent legal cases of fatal motor vehicle accidents on NSW roads are presented, where the driver who caused the accident was suffering from an unrecognised or under-treated sleep disorder. The legal outcomes in these cases were variable: some of the drivers have been acquitted and others have been jailed. All remained licensed to drive immediately after their accidents. In some of the cases, the driver was cleared of any culpable driving offence because of a defence of sleepiness or a sleep attack without warning ("Jiminez defence"). This appears at odds with current medical research and legal opinion in other countries. More research is needed to understand the relation between sleep disorders and awareness of sleepiness. Medical practitioners need to be aware of current advice and guidelines with respect to obstructive sleep apnoea and driving.

Anup V Desai MB BS, FRACP · Ronald R Grunstein PhD, FRACP · Elizabeth Ellis PhD, MHL · John R Wheatley PhD, FRACP

ForewordChronic obstructive pulmonary disease (COPD) is a major cause of disability, hospital admission and premature death. More than half a million Australians are estimated to have moderate to severe disease,1 and, as the population ages, the burden of COPD is likely to increase. In Australia, only heart disease and stroke contribute more to the overall burden of disease,2 while, in New Zealand, COPD is second only to stroke. COPD ranks fourth among the common causes of death in Australian men and sixth in women. In New Zealand, it ranks third in men and fourth in women.3 Smoking is the most important risk factor for COPD. Further, smoking-related diseases are increasing substantially in women, and death rates from COPD in women are expected to overtake those in men. The death rate from COPD among Indigenous Australians is five times that for non-Indigenous Australians, and smoking is a leading cause of healthy years lost by indigenous people both in Australia and New Zealand. COPD costs the Australian community an estimated $818–$898 million annually.4 This is a conservative estimate, based on 1993–1994 figures extrapolated to the year 2001. The addition of hidden costs, such as those related to carer burden, loss of productivity from absenteeism and early retirement, could increase the estimate to more than $1 billion per annum. Because it is considered incurable, self-inflicted and relatively resistant to treatment, a sense of nihilism about COPD prevails. However, much can be done to improve quality of life, increase exercise capacity, and reduce morbidity and mortality in affected individuals. This guideline was developed according to the principles of the National Health and Medical Research Council,5 but differs from previous guidelines on COPD in that it draws from the recently published international Guideline for the Management of Obstructive Lung Disease6 as the primary evidence base. These Australian and New Zealand guidelines have a strong emphasis on the use of objective measures of function, the role of non-pharmacological interventions and promotion of self-management. The key recommendations are summarised in the "COPDX Plan": Confirm diagnosis, Optimise function, Prevent deterioration, Develop a self-management plan and manage eXacerbations. The COPD guidelinesThese guidelines are the outcome of a joint project of the Thoracic Society of Australia and New Zealand and the Australian Lung Foundation. The guidelines aim to: effect changes in clinical practice based on sound evidence; and shift the emphasis from a predominant reliance on pharmacological treatment of COPD to a range of interventions which include patient education, self-management of exacerbations and pulmonary rehabilitation. These guidelines deal mainly with the management of established disease and exacerbations. However, this is only one element of the COPD Strategy of the Australian Lung Foundation, which has the long-term goals of: primary prevention of smoking; improving rates of smoking cessation; early detection of airflow limitation in smokers before disablement; and improved management of stable disease and prevention of exacerbations. In May 2001 a multidisciplinary steering committee was convened by the Thoracic Society of Australia and New Zealand (TSANZ) and the Australian Lung Foundation in accordance with the National Health and Medical Research Council recommendations for guideline development.5 The Committee agreed to use the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop Report6 as the prime evidence base, together with systematic reviews and meta-analyses from the Cochrane Database. The GOLD Report, released in April 2001, was produced by an international panel of experts in collaboration with the United States National Heart, Lung, and Blood Institute (NHLBI) and the World Health Organization (WHO). The levels of evidence in the current guidelines were assigned according to the system developed by the NHLBI (Box 1). The Guidelines Steering Committee supervised the development of specific items such as the COPDX Plan and a management handbook for primary care clinicians. Drafts of these documents were widely circulated to key stakeholder groups and professional organisations. In addition, the draft guidelines were published on the Internet (http://www.lungnet.com.au/copd.html), and access to them was advertised in a national newspaper. The draft guidelines were circulated to all members of the TSANZ and Australian Divisions of General Practice. All comments received were reviewed by the Steering Committee. Logistical and financial support for the development of these guidelines was provided by the Australian Lung Foundation as part of its COPD program. This program is funded by grants from Boehringer Ingelheim Pty Ltd (North Ryde, NSW), GlaxoSmithKline Australia Pty Ltd (Boronia, VIC), Air Liquide Healthcare Pty Ltd (Annandale, NSW) and BOC Medical (BOC Gases Australia Limited, North Ryde, NSW). Levels of evidenceThe key recommendations and levels of evidence incorporated in the COPDX guidelines are based largely on the Global Initiative for Chronic Obstructive Lung Disease (GOLD), which used the evidence ranking system of the US National Heart, Lung and Blood Institute (NHLBI).6 The NHLBI scheme is shown in Box 1. For comparison, the National Health and Medical Research Council (NHMRC)5 levels of evidence are also shown, along with the equivalent NHLBI categories. 1: Levels of evidence a) National Heart, Lung, and Blood Institute (NHLBI) categories NHLBI category Sources of evidence Definition A Randomised controlled trials (RCTs) — extensive body of data Evidence is from endpoints of well-designed RCTs that provide a consistent pattern of findings in the population for which the recommendation is made. Category A requires substantial numbers of studies involving substantial numbers of participants. B Randomised controlled trials (RCTs) — limited body of data Evidence is from endpoints of intervention studies that include only a limited number of patients, post-hoc or subgroup analysis of RCTs, or meta-analysis of RCTs. In general, category B pertains when few randomised trials exist, they are small in size, they were undertaken in a population that differs from the target population of the recommendation, or the results are somewhat inconsistent. C Non-randomised trials, observational studies Evidence is from outcomes of uncontrolled or non-randomised trials or from observational studies. D Panel consensus, judgement The panel consensus is based on clinical experience or knowledge that does not meet the above criteria. b) National Health and Medical Research Council (NHMRC) levels of evidence and corresponding National Heart, Lung, and Blood Institute categories NHLBI category NHMRC level Basis of evidence A I Evidence obtained from a systematic review of all relevant randomised controlled trials. B II Evidence obtained from at least one properly designed randomised controlled trial. C III-1 Evidence obtained from well-designed pseudorandomised controlled trials (alternate allocation or some other method). C III-2 Evidence obtained from comparative studies (including systematic reviews of such studies) with concurrent controls and allocation not randomised, cohort studies, case-control studies, or interrupted time series with a control group. C III-3 Evidence obtained from comparative studies with historical control, two or more single-arm studies, or interrupted time series without a parallel group. C IV Evidence obtained from case series, either post-test or pre-test/post-test. Summary of the COPDX guidelines C: Confirm diagnosis and assess severity Evidence level Smoking is the most important risk factor for COPD A Consider COPD in patients with other smoking-related diseases A Consider COPD in all smokers and ex-smokers older than 35 years B The diagnosis of COPD rests on the demonstration of airflow limitation which is not fully reversible B If airflow limitation is fully or substantially reversible, the patient should be treated as for asthma D O: Optimise function Inhaled bronchodilators provide symptom relief in patients with COPD and may increase exercise capacity A Long-acting bronchodilators provide sustained relief of symptoms in moderate to severe COPD A Long term use of systemic glucocorticoids is not recommended A Inhaled glucocorticoids should be considered in patients with a documented response or those who have severe COPD with frequent exacerbations B Identify and treat hypoxaemia and pulmonary hypertension A Prevent or treat osteoporosis A Pulmonary rehabilitation reduces dyspnoea, anxiety and depression, improves exercise capacity and quality of life and may reduce hospitalisation A In selected patients, a surgical approach may be considered for symptom relief C P: Prevent deterioration Smoking cessation reduces the rate of decline of lung function A General practitioners and pharmacists can help smokers quit A Treatment of nicotine dependence is effective and should be offered to smokers A Pharmacotherapies double the success of quit attempts; behavioural techniques further increase the quit rate by up to 50% A Influenza vaccination reduces the risk of exacerbations, hospitalisation and death A No medication has yet been shown to prevent the long-term decline in lung function A Long-term oxygen therapy (> 15 h/day) prolongs life in hypoxaemic patients (Pao2 < 55 mmHg, or 7.3 kPa) A Inhaled glucocorticoids are indicated for patients with a documented response or who have severe COPD with frequent exacerbations B Mucolytics may reduce the frequency and duration of exacerbations B D: Develop support network and self-management plan Pulmonary rehabilitation increases patient/carer knowledge base, reduces carer strain and develops positive attitudes towards self-management and exercise A COPD imposes handicaps which affect both patients and carers B Multidisciplinary care plans and individual self-management plans may help to prevent or manage crises B Enhancing quality of life and reducing handicap requires a support team C Patients and their family/friends should be actively involved in a therapeutic partnership with a range of professional disciplines C Patients should be encouraged to take appropriate responsibility for their own management C X: Manage eXacerbations Inhaled bronchodilators are effective treatments for acute exacerbations A Systemic glucocorticoids reduce the severity of and shorten recovery from acute exacerbations A Non-invasive positive pressure ventilation is effective for acute hypercapnic ventilatory failure A Exacerbations with clinical signs of infection (increased volume and change in colour of sputum and/or fever, leukocytosis) benefit from antibiotic therapy B Multidisciplinary care may assist home management B Early diagnosis and treatment may prevent admission C Controlled oxygen delivery (28% or 0.5–2 L/min) is indicated for hypoxaemia C Involving the patient's general practitioner in a case conference and developing a care plan may facilitate early discharge C C: Confirm diagnosis and assess severity Aetiology and natural history — Diagnosis — History — Physical examination — Spirometry — Flow volume tests — Assessing the severity of COPD — Assessing acute response to bronchodilators — Confirm or exclude asthma — Specialist referral — Complex lung function tests — Exercise testing — Sleep studies — Chest x-rays — High resolution computed tomography — Ventilation and perfusion scans — Transcutaneous oxygen saturation — Arterial blood gas measurement — Sputum examination — Haematology and biochemistry — Electrocardiography and echocardiography Smoking is the most important risk factor in the development of COPD7,8 [evidence level A] Chronic obstructive pulmonary disease (COPD) is characterised by airway inflammation and airflow limitation that is not fully reversible. It is a progressive, disabling disease with serious complications and exacerbations that are major burdens for healthcare systems. Small-airway narrowing (with or without chronic bronchitis) and emphysema caused by smoking are the common conditions resulting in COPD. Chronic bronchitis is daily sputum production for at least three months of two or more consecutive years. Emphysema is a pathological diagnosis, and consists of alveolar dilatation and destruction. Breathlessness with exertion, chest tightness and wheeze are the results of airway narrowing and impaired gas exchange. The loss of lung elastic tissue in emphysema may result in airway wall collapse during expiration, leading to dynamic hyperinflation and consequent increased work of breathing. The irreversible component of airflow limitation is the end result of inflammation, fibrosis and remodelling of peripheral airways. Airflow limitation leads to non-homogeneous ventilation, while alveolar wall destruction and changes in pulmonary vessels reduce the surface area available for gas exchange. In advanced COPD there is a severe mismatching of ventilation and perfusion leading to hypoxaemia. Hypercapnia is a late manifestation and is caused by a reduction in ventilatory drive. Pulmonary hypertension and cor pulmonale are also late manifestations, and reflect pulmonary vasoconstriction due to hypoxia in poorly ventilated lung, vasoconstrictor peptides produced by inflammatory cells and vascular remodelling.6 The clinical features and pathophysiology of COPD can overlap with asthma, as most COPD patients have some reversibility of airflow limitation with bronchodilators. By contrast, some non-smokers with chronic asthma develop irreversible airway narrowing. The overlap between chronic bronchitis, emphysema and asthma and their relationship to airflow obstruction and COPD are illustrated in Box 2. Patients with chronic bronchiolitis, bronchiectasis and cystic fibrosis may also present with similar symptoms and partially reversible airflow limitation. 2: Overlap of bronchitis, emphysema and asthma within chronic obstructive pulmonary disease (COPD) This non-proportional Venn diagram shows the overlap of chronic bronchitis, emphysema and asthma within COPD. Chronic bronchitis, airway narrowing and emphysema are independent effects of cigarette smoking, and may occur in various combinations. Asthma is, by definition, associated with reversible airflow obstruction. Patients with asthma whose airflow obstruction is completely reversible do not have COPD. In many cases it is impossible to differentiate patients with asthma whose airflow obstruction does not remit completely from persons with chronic bronchitis and emphysema who have partially reversible airflow obstruction with airway hyperreactivity. Aetiology and natural historyCigarette smoking is the most important cause of COPD.7,8 There is a close relationship between the amount of tobacco smoked and the rate of decline in forced expiratory flow in one second (FEV1 ), although individuals vary greatly in susceptibility.7 Around half of all smokers develop some airflow limitation, and 15%–20% will develop clinically significant disability.7 Smokers are also at risk of developing lung cancer, and cardiovascular disease such as ischaemic heart disease and peripheral vascular disease. In susceptible smokers cigarette smoking results in a steady decline in lung function, with a decrease in FEV1 of 25–100 mL/year.7 While smoking cessation may lead to minimal improvements in lung function, more importantly it will slow the rate of decline in lung function and delay the onset of disablement. At all times smoking cessation is important to preserve remaining lung function.7 Impairment increases as the disease progresses, but may not be recognised because of the slow pace of the disease. The time course of development of COPD and disability and the influence of smoking cessation are illustrated in Box 3. Other factors that can contribute to the development of COPD9 include: occupational dust and fume exposure; outdoor and indoor air pollution (including environmental tobacco smoke); α1-antitrypsin deficiency; genetic predisposition; recurrent respiratory infections in childhood; and bronchial hyperresponsiveness. The single best predictor of mortality in COPD is FEV1 .7,10 In one study the five-year survival rate was only about 10% for those with an FEV1 < 20% predicted, 30% for those with FEV1 of 20%–29% predicted and about 50% for those with an FEV1 of 30%–39% predicted.10 Continued smoking and airway hyperresponsiveness are associated with accelerated loss of lung function.11 However, even if substantial airflow limitation is present, cessation of smoking may result in some improvement in lung function and will slow progression of disease. The development of hypoxaemic respiratory failure is an independent predictor of mortality, with a three-year survival of about 40%.12 Long term administration of oxygen increases survival to about 50% with nocturnal oxygen12 and to about 60% with oxygen administration for more than 15 hours a day13 (see also section P, page S21). Admission to hospital with an infective exacerbation of COPD complicated by hypercapnic respiratory failure is associated with a poor prognosis. A mortality of 11% during admission and 49% at two years has been reported in patients with a partial pressure of carbon dioxide (Pco2 ) > 50 mmHg.14 For those with chronic carbon dioxide retention (about 25% of those admitted with hypercapnic exacerbations), the five-year survival was only 11%.14 3: Time-course of chronic obstructive pulmonary disease (COPD)7 The figure (adapted from Fletcher and Peto7) shows the rate of loss of forced expiratory flow in one second (FEV1 ) for a hypothetical, susceptible smoker, and the potential effect of stopping smoking early or late in the course of COPD. Other susceptible smokers will have different rates of loss, thus reaching "disability" at different ages. The normal FEV1 ranges from below 80% to above 120%, so this will affect the starting point for the individual's data (not shown). DiagnosisHistoryConsider COPD in all smokers and ex-smokers over the age of 35 years 7 [evidence level B] The main symptoms of COPD are breathlessness, cough and sputum production.15 Patients often attribute breathlessness to ageing or lack of fitness. A persistent cough, typically worse in the mornings with mucoid sputum, is common in smokers. Other symptoms such as chest tightness, wheezing and airway irritability are common.16 Acute exacerbations, usually infective, occur from time to time and may lead to a sharp deterioration in coping ability. Fatigue, poor appetite and weight loss are more common in advanced disease. The functional limitation from breathlessness due to COPD can be quantified easily in clinical practice17 (see Box 4). 4: Medical Research Council grading of functional limitation due to dyspnoea17 Grade Symptom complex 1 "I only get breathless with strenuous exercise". 2 "I get short of breath when hurrying on the level or walking up a slight hill". 3 "I walk slower than most people of the same age on the level because of breathlessness or have to stop for breath when walking at my own pace on the level". 4 "I stop for breath after walking about 100 yards or after a few minutes on the level". 5 "I am too breathless to leave the house" or "I am breathless when dressing". Physical examinationThe sensitivity of physical examination for detecting mild to moderate COPD is poor.18 Wheezing is not an indicator of severity of disease and is often absent in stable, severe COPD. In more advanced disease, physical features commonly found are hyperinflation of the chest, reduced chest expansion, hyperresonance to percussion, soft breath sounds and a prolonged expiratory phase. Right heart failure may complicate severe disease. During an acute exacerbation, tachypnoea, tachycardia, use of accessory muscles, tracheal tug and cyanosis are common. The presence and severity of airflow limitation are impossible to determine by clinical signs.18 Objective measurements such as spirometry are strongly recommended. Peak expiratory flow (PEF) is not a sensitive measure of airway function in COPD patients, as it is effort dependent and has a wide range of normal values.19 SpirometryThe diagnosis of COPD rests on the demonstration of airflow limitation which is not fully reversible 20 [evidence level B] Spirometry is the gold standard for diagnosing, assessing and monitoring COPD (see Box 5). Most spirometers provide predicted ("normal") values obtained from healthy population studies, and derived from formulas based on height, age, sex and ethnicity. Airflow limitation is non-reversible when, after administration of bronchodilator medication, the ratio of FEV1 to forced vital capacity (FVC) is < 70% and the FEV1 is < 80% of the predicted value. The ratio of FEV1 to vital capacity (VC) is a sensitive indicator for mild COPD. Indications for spirometry include: breathlessness that seems inappropriate; chronic (daily for two months) or intermittent, unusual cough; frequent or unusual sputum production; relapsing acute infective bronchitis; and risk factors such as exposure to tobacco smoke, occupational dusts and chemicals, and a strong family history of COPD. 5: Maximal expiratory flow-volume curves in severe chronic obstructive pulmonary disease (COPD) and chronic asthma The patient with COPD has reduced peak expiratory flow, and severely decreased flows at 25%, 50% and 75% of vital capacity compared with the normal range (vertical bars), and shows minimal response to bronchodilator (BD). By comparison, the patient with chronic asthma shows incomplete, but substantial, reversibility of expiratory flow limitation across the range of vital capacity. After BD the forced expiratory volume in one second (FEV1 ) was within the normal range (82% predicted). Absolute and per cent predicted values for FEV1 and forced vital capacity (FVC) before and after BD are shown for each patient. Flow volume testsElectronic spirometers allow for the simultaneous measurement of flow and volume during maximal expiration. Reduced expiratory flows at mid and low lung volumes are the earliest indicators of airflow limitation in COPD and may be abnormal even when FEV1 is within the normal range (> 80%). Assessing the severity of COPDSpirometry is the most reproducible, standardised and objective way of measuring airflow limitation, and FEV1 is the variable most closely associated with prognosis.10 The grades of severity according to FEV1 and the likely symptoms and complications are shown in Box 6. However, it should be noted that patients with an FEV1 > 80% predicted, although within the normal range, may have airflow limitation (FEV1 /FVC ratio < 70%). 6: Classification of severity of chronic obstructive pumonary disease (COPD)6 COPD severity Factor Mild Moderate Severe Spirometry findings — postbronchodilator FEV1 60%–80% predicted 40%–59% predicted < 40% predicted Functional assessment (activities of daily living) Few symptoms No effect on daily activities Breathless on moderate exertion Increasing dyspnoea Breathless on the flat Increasing limitation of daily activities Dyspnoea on minimal exertion Daily activities severely curtailed Complications No Exclude complications; consider sleep apnoea if there is pulmonary hypertension Severe hypoxaemia (Pao2 < 60 mmHg, or 8 kPa) Hypercapnia (Paco2 > 45 mmHg, or 6 kPa) Pulmonary hypertension Heart failure Polycythaemia FEV1 = forced expiratory volume in one second. Pao2 = partial pressure of oxygen, arterial. Paco2 = partial pressure of carbon dioxide, arterial. Assessing acute response to bronchodilatorsThe response to bronchodilators is determined to: assign a level of severity of airflow obstruction (post-bronchodilator); help confirm or exclude asthma; and help decide role of bronchodilator therapy. The details for this assessment are outlined in Box 7. The change in FEV1 after an acute bronchodilator reversibility test indicates the degree of reversibility of airflow limitation. This is often expressed as a percentage of the baseline measurement (eg, 12% increase). An increase in FEV1 of more than 12% and 200 mL is greater than average day-to-day variability and is unlikely to occur by chance.21 However, this degree of reversibility is not diagnostic of asthma and is frequently seen in patients with COPD (eg, the FEV1 increases from 0.8 L to 1.0 L when the predicted value is, say, 3.5 L). The diagnosis of asthma relies on an appropriate history and complete, or at least substantial, reversibility of airflow limitation (see also below). 7: Assessment of acute response to inhaled β-agonist at diagnosis Preparation Patients should be clinically stable and free of respiratory infection. Withhold inhaled short-acting bronchodilators in the previous six hours, long-acting β-agonists in the previous 12 hours, or sustained-release theophyllines in the previous 24 hours. Spirometry Measure baseline spirometry (pre-bronchodilator). An FEV1 < 80% predicted and FEV1 /FVC ratio < 0.70 shows airflow limitation. Give the bronchodilator by metered dose inhaler (MDI) through a spacer device or by nebuliser. Give short-acting β-agonist, at a dose selected to be high on the dose–response curve (eg, 200–400 μg salbutamol from MDI and spacer). Repeat spirometry 15–30 minutes after bronchodilator is given and measure degree of reversibility. FEV1 = forced expiratory flow in one second. FVC = forced vital capacity. Confirm or exclude asthmaIf airflow limitation is fully or substantially reversible, the patient should be treated as for asthma [evidence level D] Asthma and COPD are usually easy to differentiate. Asthma usually runs a more variable course and dates back to a younger age. Atopy is more common and the smoking history is often relatively light (eg, less than 15 pack-years). Airflow limitation in asthma is substantially, if not completely, reversible, either spontaneously or in response to treatment. By contrast, COPD tends to be progressive, with a late onset of symptoms and a moderately heavy smoking history (usually > 15 pack-years) and the airflow obstruction is not completely reversible. However, there are some patients in whom it is difficult to distinguish between asthma and COPD as the primary cause of their chronic airflow limitation. Long-standing or poorly controlled asthma can lead to chronic, irreversible airway narrowing even in non-smokers. Specialist referralConfirmation of the diagnosis of COPD and differentiation from chronic asthma, other airway diseases or occupational exposures that may cause airway narrowing or hyper-responsiveness, or both, often requires specialised knowledge and investigations. Indications for which consultation with a respiratory medicine specialist is recommended are shown in Box 8. 8: Referral to respiratory medicine specialist Circumstances possibly requiring specialist review Role of respiratory specialist 1. Moderate or severe chronic obstructive pulmonary disease (COPD) Confirm diagnosis and optimise therapy. Cease inappropriate or ineffective therapies. Assess side effects. Determine need for nebulised therapy. Assess complications. 2. Uncertain diagnosis (< 10 pack-year smoking history or < 40 years of age or rapid decline in FEV1 ) Confirm diagnosis and exclude other diagnoses (eg, asthma, bronchiolitis obliterans, pulmonary embolism, cancer, heart failure, pneumothorax, anaemia). Determine other aetiological factors. Determine if the patient is predisposed (eg, α1-antitrypsin deficiency). 3. Recurrent infections, exacerbations Exclude other conditions (eg, bronchiectasis, cystic fibrosis, immunological abnormality, aspiration). 4. Symptoms out of proportion to lung function impairment Exclude complications of COPD or comorbidities (eg, pulmonary hypertension, cardiac disease). Consider sleep study. 5. Cor pulmonale Confirm diagnosis and optimise treatment, including assessment for oxygen or other ventilatory support. 6. Suspect chronic hypoxaemia Confirm chronic hypoxaemia or nocturnal hypoxaemia. Assess for ambulatory oxygen therapy. 7. Bullous lung disease or severe emphysema Determine suitability for bullectomy or lung volume reduction surgery. 8. Severe disability or respiratory failure Determine suitability for lung volume reduction surgery or lung transplantation or home ventilation. COPD = chronic obstructive pulmonary disease. FEV1 = forced expiratory volume in one second. Complex lung function testsMeasurement of airways resistance, static lung volumes and diffusing capacity of lungs for carbon monoxide assists in the assessment of patients with more complex respiratory disorders. Exercise testingCardiopulmonary exercise tests may be useful to differentiate between breathlessness resulting from cardiac or respiratory disease, and may help to identify other causes of exercise limitation (eg, hyperventilation, musculoskeletal disorder). Sleep studiesSpecialist referral is recommended for COPD patients suspected of having a coexistent sleep disorder or with hypercapnia or pulmonary hypertension in the absence of daytime hypoxaemia, right heart failure or polycythaemia. Overnight pulse oximetry may be indicated in patients receiving long-term domiciliary oxygen therapy to assess its efficacy. Chest x-raysA plain posteroanterior and lateral chest x-ray helps to exclude other conditions such as lung cancer. The chest x-ray is not sensitive in the diagnosis of COPD, and will not exclude a small carcinoma (< 1cm). High resolution computed tomographyHigh resolution computed tomography (HRCT) scanning gives precise images of the lung parenchyma and mediastinal structures. The presence of emphysema and the size and number of bullae can be determined. This is necessary if bullectomy or lung reduction surgery is being contemplated. HRCT is also appropriate for detecting bronchiectasis. Vertical reconstructions can provide a virtual bronchogram. Spiral computed tomography (CT) scans with intravenous contrast should be used in other circumstances, such as for investigating and staging lung cancer. CT pulmonary angiograms are useful for investigating possible pulmonary embolism, especially when the chest x-ray is abnormal. Ventilation and perfusion scansThe ventilation and perfusion (V/Q) scan may be difficult to interpret in COPD patients, because regional lung ventilation may be compromised leading to matched defects. If pulmonary emboli are suspected, a CT pulmonary angiogram may be more useful. Quantitative regional V/Q scans are helpful in assessing whether patients are suitable for lung resection and lung volume reduction surgery. Transcutaneous oxygen saturationOximeters have an accuracy of plus or minus 2%, which is satisfactory for routine clinical purposes. Oximetry does not provide any information about carbon dioxide status and is inaccurate in the presence of poor peripheral circulation (eg, cold extremities, cardiac failure). Arterial blood gas measurementArterial blood gas analysis should be considered in all patients with severe disease, those being considered for domiciliary oxygen therapy (eg, whose FEV1 is < 40% predicted or < 1 L, whose oxygen saturation as measured by pulse oximetry [Spo2 ] is < 92%), those with pulmonary hypertension, and those with breathlessness out of proportion to their clinical status). Respiratory failure is defined as a Pao2 < 60 mmHg (8 kPa) or Paco2 > 50 mmHg (6.7 kPa). Sputum examinationRoutine sputum culture in clinically stable patients with COPD is unhelpful and unnecessary. Sputum culture is recommended when an infection is not responding to antibiotic therapy or when a resistant organism is suspected. Haematology and biochemistryPolycythaemia should be confirmed as being secondary to COPD by blood gas measurement confirming the presence of hypoxaemia. The possibility of sleep apnoea or hypoventilation should be considered if polycythaemia is present, but the oxygen saturation is normal when the patient is awake. Hyperthyroidism and acidosis are associated with breathlessness. Hyperventilation states are associated with respiratory alkalosis. Hypothyroidism aggravates obstructive sleep apnoea. Electrocardiography and echocardiographyMultifocal atrial tachycardia is a frequent finding. Atrial fibrillation commonly develops when pulmonary artery pressure rises, leading to increased right atrial pressure. Echocardiography is useful if cor pulmonale is suspected, when breathlessness is out of proportion to the degree of respiratory impairment or when ischaemic heart disease, pulmonary embolus and left heart failure are suspected. Consider COPD in patients with other smoking-related diseases 22 [evidence level A] Patients with COPD are prone to other conditions associated with cigarette smoking, including accelerated cardiovascular, cerebrovascular and peripheral vascular disease, and oropharyngeal, laryngeal and lung carcinoma. Conversely, there is a high prevalence of COPD among patients with ischaemic heart disease, peripheral vascular disease and cerebrovascular disease and smoking-related carcinomas.22 These patients should be screened for symptoms of COPD, and spirometry should be performed. O: Optimise function Symptom relief — Inhaled bronchodilators — Long-acting bronchodilators — Theophyllines — Assessment of response and continuation of bronchodilator therapy — Short-course oral glucocorticoids — Combination inhaled glucocorticoid/long-acting bronchodilator therapy — Optimise inhaler technique — Surgery — Bullectomy — Lung volume reduction surgery — Lung transplantation — Identify and treat aggravating factors — Sleep apnoea, hypoventilation and hypoxaemia — Gastro-oesophageal reflux — Aspiration — Alcohol and sedatives — Hypoxaemia and pulmonary hypertension — Treatment — Osteoporosis — Improve function — Pulmonary rehabilitation — Exercise training — Patient education — Psychosocial support — Comprehensive integrated rehabilitation — Chest physiotherapy — Weight management and nutrition The principal goals of therapy are to stop smoking, to optimise function through symptom relief with medications and pulmonary rehabilitation, and to prevent or treat aggravating factors and complications. Symptom reliefInhaled bronchodilators provide symptom relief and may increase exercise capacity23-30 [evidence level A] Inhaled bronchodilatorsThe two classes of inhaled bronchodilators — selective β-adrenoceptor agonists and anticholinergic agents — target airway smooth muscle contraction, which is one cause of the physiological and functional deficits in COPD.23-25 All bronchodilators have been shown to variably improve exercise capacity.26-29 However, changes in simple measurements of airway function (FEV1 , FVC) are not closely correlated with symptomatic improvement or changes in measures of quality of life.30,31 The failure to achieve a large therapeutic response should not necessarily trigger the use of higher doses.23,24 Nebulisers are not recommended for routine use in stable disease32 [evidence level C]. The duration of action of short-acting inhaled anticholinergic agents is greater than that of short-acting β-agonists32 [evidence level A]. The combination of β-agonists and anticholinergics may be more effective and better tolerated than higher doses of either agent used alone32-37 [evidence level A]. The use of bronchodilators according to the severity of COPD6 is shown in Box 9. Appendices 1 and 2 list available products, formulations and delivery devices. Patients must be asked to show that they have effective inhaler technique. Efforts to maintain or regain physical fitness may match or exceed the benefits of bronchodilator use (see the discussion of pulmonary rehabilitation on page S19).6 Use of a short-acting bronchodilator before an exercise session may reduce dynamic hyperinflation and allow better training effects to be achieved.26 9: Initial treatment with short-acting bronchodilators* Severity FEV1 Suggested treatment Mild COPD 60%–80% Intermittent bronchodilator — salbutamol (200 μg) or ipratropium bromide (40 μg) as needed before exercise Moderate COPD 40%–59% Intermittent or regular bronchodilator — salbutamol (200–400 μg four times daily) or ipratropium bromide (40 μg four times daily). Combination bronchodilators may be considered Severe COPD < 40% Regular combination bronchodilator — salbutamol (200–400 μg four times daily) and ipratropium bromide (40–80 μg four times daily) * Modified from GOLD6 [evidence level D]. FEV1 = forced expiratory volume in one second. COPD = chronic obstructive pulmonary disease. Long-acting bronchodilatorsLong-acting bronchodilators provide sustained relief of symptoms in moderate to severe COPD38-44 [evidence level A] Long-acting β-agonists (eg, salmeterol and eformoterol) provide bronchodilation for 12 hours38-41 and are widely used for asthma. They are not currently subsidised under the Pharmaceutical Benefits Scheme for patients with COPD, although they improve exercise endurance, improve health-related quality of life and reduce both the exacerbation rate and number of hospitalisations. Salmeterol (50 μg twice daily) has a favourable effect on measures of health-related quality of life.41 The dose–response relationship is low, so, compared with the standard dose, the higher dose of 100 μg twice daily does not further improve quality of life41 [evidence level B]. Eformoterol (12 μg twice daily) improves lung function and symptoms.40 Tiotropium (18 μg daily), a new inhaled anticholinergic agent, has a duration of effect of over 24 hours and is used once daily. It is subsidised under the Pharmaceutical Benefits Scheme for use in patients with COPD. Compared with placebo and regular ipratropium, it reduces dyspnoea and exacerbation rate and improves health status42-44 (see Appendix 1). TheophyllinesTheophyllines are rarely used because of their narrow therapeutic index and potential for significant side effects45 [evidence level A]. Some patients with disabling breathlessness may derive benefit from their use.46-48 Theophyllines may have an anti-inflammatory effect or reduce muscle fatigue.49,50 Evidence supports only the slow-release formulation. Dosage should be adjusted according to trough serum levels.51 Assessment of response and continuation of bronchodilator therapyIn some patients a response to bronchodilator therapy may require treatment for up to two months. Parameters for assessing long term responsiveness are outlined in Box 10. Symptomatic and functional benefits can often be demonstrated in the absence of an increase in FEV1 . Other objective measurements, such as an increase in exercise capacity (eg, six-minute walk distance) or an increased inspiratory reserve capacity, may be useful indicators of physiological improvement. Subjective measurements, such as quality of life, breathlessness and functional limitation (eg, MRC Dyspnoea Scale; see page S8), can determine the patient's perception of benefit. If there is no improvement: check inhaler technique; consider psychosocial issues and deconditioning; and exclude other causes of exercise impairment (consider specialist referral or a cardiopulmonary exercise test). 10: Assessing long term medication response At diagnosis Measure and record FEV1 and FVC after administration of β-agonist Record MRC Dyspnoea Scale score Prescribe trial medications as per dosage protocols At next visit Remeasure spirometry and MRC Dyspnoea Scale score to determine response to medications If FEV1 and/or FVC increases more than 15% and more than 300 mL after a treatment trial, and/or MRC Dyspnoea Scale score improves more than 1 unit, the tested medication should be included as ongoing treatment If FEV1 and/or FVC reverse completely or substantially with inhaled or oral glucocorticoids, consider asthma If there is no significant response to the medication being tested, it could be ruled out for ongoing treatment MRC = Medical Research Council. FEV1 = forced expiratory volume in one second. FVC = forced vital capacity. Short-course oral glucocorticoidsLong term use of systemic glucocorticoids is not recommended52-56 [evidence level A] The long-term use of systemic glucocorticoids in COPD is not recommended52-56 [evidence level A]. Indeed, caution in the long term use of systemic glucocorticoids is necessary because of limited efficacy and potential toxicity in elderly patients. Some patients with stable COPD show a significant response to oral glucocorticoids (on spirometry or functional assessment). Therefore, a short course (two weeks) of prednisolone (20–50 mg daily) may be tried with appropriate monitoring. A negative bronchodilator response does not predict a negative steroid response.6,57 If there is a response to oral steroids, continued treatment with inhaled glucocorticoids is indicated, but these may fail to maintain the response.57,58 Patients who have a negligible response to glucocorticoids should not use them. Inhaled glucocorticoids should be considered in patients with a documented response or those who have severe COPD with frequent exacerbations 57-61 [evidence level B] Inhaled glucocorticoids do not influence the rate of decline in FEV1 in patients with no significant acute reversibility.57-61 Smoking cessation remains the only effective means to affect the decline in lung function for these patients (see Section P). Patients with clinically significant acute bronchodilator reversibility may benefit from long-term inhaled glucocorticoid therapy. Long term inhaled therapy with glucocorticoids is also indicated in patients with COPD who have significant reversibility of airway function after a more prolonged trial of bronchodilators or glucocorticoids.57-59 In one large RCT of patients with severe non-reversible COPD (mean FEV1 about 40% predicted), high-dose inhaled glucocorticoid (fluticasone, 1000 μg daily) slowed the rate of decline in quality of life over three years and the rate of acute exacerbations without affecting overall decline in lung function.60 Similar results may be expected from high doses of other inhaled glucocorticoids, but are yet to be documented in RCTs. In another large RCT in patents with milder COPD, medium-dose budesonide had no significant impact.59 Some systemic absorption may occur, so the modest benefits of inhaled glucocorticoids must be weighed against the potential risks of easy bruising, cataract formation and possible contribution to osteoporosis. The response should be assessed with spirometry and measures of performance status, quality of life or both. They should be trialled for three to six months in patients with moderate to severe COPD, and continued if there is objective benefit. Combination inhaled glucocorticoid/long-acting bronchodilator therapyThere is currently insufficient published evidence to determine the role of combination therapy with inhaled glucocorticoid and long-acting bronchodilators. Optimise inhaler techniqueInhaler devices must be explained and demonstrated for patients to achieve optimal benefit. It is necessary to check regularly that the patient has the correct inhaler technique. Elderly and frail patients, especially those with cognitive deficits, may have difficulty with some devices. The range of devices currently available, the products and dosage, as well as their advantages or disadvantages, are listed in Appendix 2. SurgeryIn selected patients, a surgical approach may be considered for symptom relief 62-72 [evidence level C]. None of the current surgical approaches in patients with COPD provides a survival advantage.6,62 In view of the potential for serious morbidity and mortality, all surgical treatments require careful assessment by an experienced thoracic medical and surgical team. BullectomyThis operation involves resection of large bullae (larger than 5 cm). The procedure is most successful where there are very large cysts compressing adjacent apparently normal lung.63-65 Lung volume reduction surgeryLung volume reduction surgery (LVRS) involves resection of the most severely affected areas of emphysematous, non-bullous lung.66 This can improve lung elastic recoil and diaphragmatic function.67 LVRS is still an experimental, palliative, surgical procedure. Several large randomised multicentre studies are under way to investigate the effectiveness and cost–benefit of this procedure.68 Surgery is performed electively after a pulmonary rehabilitation program, to remove about 25% of each lung. Physiological improvement (eg, a 40% improvement in FEV1 from about 25% predicted to 35% predicted, and six-minute walk from about 300 to 420 metres) takes weeks to months. The duration of the improvement is 2–4 years. These gains should be weighed against risks of operative and postoperative mortality (around 5%–15%), morbidity and cost.68 However, the natural history of patients with COPD of this severity is a progressive decline in function and early mortality. Lung transplantationIn patients with COPD, this procedure usually involves replacement of one diseased lung with a normal lung from an organ donor.69,70 Detailed medical and psychological assessment and counselling are required to avoid excessive morbidity and mortality. Malnutrition, severe weakness and steroid and ventilator dependence predict a poor outcome.71,72 The procedure is most successful when lung disease is the recipient's only medical problem and is usually offered to younger patients (eg, those with α1-antitrypsin deficiency). Physiological improvement takes weeks to months, and would typically translate to a large improvement in FEV1 (from about 20% to 60% predicted for a single lung transplant), exercise performance and quality of life.69-72 Identify and treat aggravating factorsSleep apnoea, hypoventilation and hypoxaemiaCOPD has adverse effects on sleep quality, resulting in poor sleep efficiency, delayed sleep onset, multiple wakenings with fragmentation of sleep architecture, and a high arousal index. Arousals are caused by hypoxia, hypercapnia, nocturnal cough and the pharmacological effects of methylxanthines and β-adrenergic agents.73 Intranasal oxygen administration has been shown to improve sleep architecture and efficiency, as well as oxygen saturation during sleep.74 Indications for full diagnostic polysomnography in patients with COPD include persistent snoring, witnessed apnoeas, choking episodes and excessive daytime sleepiness. In subjects with daytime hypercapnia, monitoring of nocturnal transcutaneous carbon dioxide levels should be considered to assess nocturnal hypoventilation. Patients with COPD with a stable wakeful Pao2 of more than 55 mmHg (7.3 kPa) who have pulmonary hypertension, right heart failure or polycythaemia should also be studied. Overnight pulse oximetry is also useful in patients with COPD in whom long-term domiciliary oxygen therapy is indicated (stable Pao2 < 55 mmHg, or 7.3 kPa) to determine an appropriate oxygen flow rate during sleep. The overlap syndrome: The combination of COPD and obstructive sleep apnoea (OSA) is known as the "overlap syndrome". The prevalence of COPD in unselected patients with OSA is about 10%, while about 20% of patients with COPD also have OSA.75 Patients with COPD who also have OSA have a higher prevalence of pulmonary hypertension and right ventricular failure than those without OSA.75 There is frequently a history of excessive alcohol intake. While oxygen administration may diminish the degree of oxygen desaturation, it may increase the frequency and severity of hypoventilation and lead to carbon dioxide retention. As in other patients with OSA, weight reduction, alcohol avoidance and improvement of nasal patency are useful in those with COPD. Nasal continuous positive airway pressure (CPAP) is the best method for maintaining patency of the upper airway and may obviate the need for nocturnal oxygen. If nasal CPAP is not effective, then nocturnal bilevel positive airway pressure ventilation should be considered, although the benefits of this in chronic stable COPD remain to be established. The role of other OSA treatments, such as mandibular advancement splinting, remains to be evaluated in the overlap syndrome. Gastro-oesophageal refluxIn patients with COPD, hyperinflation, coughing and the increased negative intrathoracic pressures of inspiration may predispose to reflux, especially during recumbency and sleep. Microaspiration of oesophageal secretions (possibly including refluxed gastric content) is a risk, especially with coexistent snoring or OSA. Reflux and microaspiration exacerbate cough, bronchial inflammation and airway narrowing. Diagnosis may be confirmed by 24-hour monitoring of oesophageal pH, modified barium swallow or gastroscopy. However, a therapeutic trial of therapy with H2 -receptor antagonists or a proton-pump inhibitor may obviate the need for invasive investigations. Lifestyle changes, including stopping smoking, reduced intake of caffeine and alcohol, weight loss and exercise, will also help. Elevation of the head of the bed is also recommended. AspirationAspiration of food and liquid is common in COPD and may be the cause of recurrent exacerbations and complications, such as pneumonia and patchy pulmonary fibrosis. Diagnosis is usually easy with an adequate history from patients and their partners or carers. Dry biscuits and thin fluids cause the most difficulty. Confirmation rests with assessment by a speech therapist and a modified barium swallow. Treatment involves retraining in safe swallowing techniques, which may include: avoiding talking when eating; sitting upright; taking small mouthfuls; chewing adequately; drinking with dry foods; using a straw; and drinking thickened fluids. Alcohol and sedativesPatients with COPD have impaired gas exchange and an exaggerated fall in Po2 with recumbency and sleep onset.74,75 Excessive use of alcohol and sedatives exacerbates this and predisposes to sleep-disordered breathing. Heavy cigarette smoking is associated with misuse of other substances in many individuals. Nicotine, caffeine and alcohol also predispose to gastro-oesophageal reflux. Hypoxaemia and pulmonary hypertensionIdentify and treat hypoxaemia and pulmonary hypertension 76-85 [evidence level A] Pulmonary hypertension in patients with COPD results mainly from vasoconstriction of pulmonary arterioles in response to local hypoxia, usually resulting from impaired ventilation, and vasoconstrictor peptides produced by inflammatory cells.76-79 The vasoconstriction minimises blood flow through poorly ventilated lung, reducing the mismatch of ventilation and perfusion. While this compensatory mechanism initially helps to maintain blood gas levels, the price is increased pulmonary vascular resistance, ultimately leading to right ventricular strain and failure (cor pulmonale). The vascoconstriction is reversible initially, but vascular remodelling occurs eventually and the condition becomes irreversible. In pulmonary emphysema there is also an anatomical disruption of capillaries in alveolar walls. Right ventricular hypertrophy is seen in about 40% of patients with an FEV1 less than 1.0 L and in 70% of those with an FEV1 less than 0.6 L. The presence of hypercapnia is strongly associated with cor pulmonale. When pulmonary hypertension and cor pulmonale seem out of proportion with the severity of airway narrowing, the additional factors that need to be considered include: sleep apnoea (central and obstructive); polycythaemia; and recurrent pulmonary thromboembolism. The development of pulmonary hypertension and peripheral oedema is a poor prognostic sign in COPD.80 If untreated, the five-year survival rate is about 30%. Pulmonary hypertension is difficult to detect on clinical evaluation in patients with COPD. Chest x-rays may show enlargement of proximal pulmonary arteries, but right ventricular enlargement is difficult to detect because of hyperinflation. Right axis deviation and P pulmonale on ECG may be difficult to detect because of low voltage traces (also a result of hyperinflation). Multifocal atrial tachycardia and atrial fibrillation are common. Echocardiography is the best non-invasive method of assessing pulmonary hypertension, but image quality is reduced by hyperinflation. Echocardiography is indicated in patients with severe disease, or when symptoms seem out of proportion to the severity of airflow limitation. Estimation of pressure relies on at least some tricuspid regurgitation. Other findings include mid-systolic closure of the pulmonic valve and increased right ventricular wall thickness. TreatmentTreat underlying lung disease: The logical first step is to optimise lung function and treat all potential aggravating conditions. Oxygen therapy: Long term, continuous (> 15 h/day) oxygen therapy to treat chronic hypoxaemia prolongs survival of patients with COPD, presumably by reducing pulmonary hypertension.12,13,80-82 (For a detailed description of oxygen therapy in COPD see Section P, page S21). Ventilatory support: For patients with COPD who also have sleep apnoea or hypoventilation, ventilatory support with continuous positive airway pressure (CPAP) or non-invasive positive pressure ventilation (NIPPV) may be more appropriate than oxygen therapy (for more details see Section X, page S29). The efficacy of NIPPV for long-term treatment has not yet been proven.74,83-85 Diuretics: Diuretics may reduce right ventricular filling pressure and oedema, but excessive volume depletion must be avoided. Volume status can be monitored by measuring serum creatinine and urea levels. Diuretics may cause metabolic alkalosis resulting in suppression of ventilatory drive. Digoxin: Digoxin is not indicated in the treatment of cor pulmonale and may increase the risk of arrhythmia when hypoxaemia is present.6 It may be used to control the rate of atrial fibrillation. Vasodilators: Vasodilators (hydralazine, nitrates, nifedipine, verapamil, diltiazem, angiotensin-converting enzyme [ACE] inhibitors) do not produce sustained relief of pulmonary hypertension in patients with COPD.86,87 They can worsen oxygenation (by increasing blood flow through poorly ventilated lung) and result in systemic hypotension. However, a cautious trial may be used in patients with severe or persistent pulmonary hypertension not responsive to oxygen therapy. Some vasodilators (eg, calcium antagonists) have been shown to reduce right ventricular pressure with minimal side effects and increased well-being, at least in the short term. Nitric oxide worsens V/Q mismatching and is therefore contraindicated in patients with COPD.86,87 OsteoporosisPrevent or treat osteoporosis 88 [evidence level A] Patients with COPD have high rates of bone fracture (11%–14%) and bone mineral density (BMD) an average of 10% lower compared with control patients.88 A 10% drop in BMD equates to a 2.6-fold increase in fracture risk.88 Greater deficits are seen in patients with more severe disease. The risk factors for low BMD in patients with COPD include periods of immobilisation or hospitalisation, low FEV1 , use of corticosteroids, decreased weight-bearing activity, and smoking. Other risk factors relevant to the general population also apply. These include low calcium intake, low body mass index, alcohol abuse and hypogonadism. All patients who take corticosteroids should be advised to undertake regular, weight-bearing exercise (eg, walking and light resistance training). Those who have had long-term steroid therapy at lower doses and who have other risk factors should be screened. Intervention should be targeted at men and women who are taking more than 15 mg daily of prednisolone or who have several risk factors for osteoporosis and whose BMD is < 1.5 standard deviations below the young adult mean.88 Oral bisphosphonates, particularly risedronate, have been shown to be effective in preventing and treating bone loss in men and women taking corticosteroids.88 However, most patients in these studies did not have respiratory disease. The studies also showed a reduction in risk of spinal fracture, especially in postmenopausal women. Other agents that have been used with some success in patients with respiratory disease include calcium, vitamin D and medroxyprogesterone acetate. Selecting patients with COPD who may be at increased risk of osteoporosis is most appropriately done on the basis of conventional risk factors. Further refining of clinical predictors and more evidence for the cost-effectiveness of such programs still needs to be resolved before recommendations on a screening strategy in patients with COPD can be made. For more information on prevention and treatment of osteoporosis, see the current Australian guidelines.88 Improve functionPulmonary rehabilitationPulmonary rehabilitation reduces dyspnoea, anxiety and depression, improves exercise capacity and quality of life and may reduce hospitalisation 89-107 [evidence level A] Pulmonary rehabilitation is one of the most effective interventions in COPD89-93 and has been shown to reduce symptoms, disability and handicap and to improve functioning by: improving cardiovascular fitness, muscle function and exercise endurance;89,90,93-99 enhancing the patient's self-confidence and coping strategies, and improving medication adherence and use of respiratory treatment devices;89-91,95,100-103 improving mood by controlling anxiety and panic, decreasing depression, and reducing social impediments.89,90,104 Pulmonary rehabilitation should be offered to patients with moderate to severe COPD, but can be relevant for people with any long-term respiratory disorder characterised by dyspnoea.101,102 Exercise programs alone have clear benefits,103 while the benefits of education or psychosocial support without exercise training are less well documented.101,104-106 Comprehensive programs incorporating all three interventions have the greatest benefits (see below). Most research has been undertaken with hospital-based programs, but there is increasing evidence of benefit from rehabilitation in the community.95,100 Exercise trainingNumerous randomised controlled trials in moderate to severe COPD have shown decreased symptoms (breathlessness and fatigue) and improved cardiovascular fitness, exercise endurance, health-related quality of life and mood following exercise conditioning alone103 [evidence level A]. Improvements in muscle strength and self-efficacy have also been reported.89-100,103 The evidence for benefit from high-intensity training of the respiratory muscles is less convincing.101,103,104 Some very disabled patients are shown how to reduce unnecessary energy expenditure for activities of daily living.101 Some patients may benefit from portable oxygen (see section P, page S21). Maintenance of activities is essential for continuing the benefits from the initial training program. Home- or community-based exercise should be encouraged6,105 [evidence level D]. Patient educationThere is limited evidence that education alone can improve self-management skills, mood and health-related quality of life105-107 [evidence level C]. Providing information and tools to enhance self-management in an interactive session is more effective than didactic teaching.105,108 The single most important intervention is assistance with smoking cessation.6 Good nutrition; task optimisation for more severely disabled patients; access to community resources; help with control of anxiety, panic or depression; instruction on effective use of medications and therapeutic devices (including oxygen where necessary); relationships; end-of-life issues; continence; safety for flying; and other issues may be addressed.6,101,102 Psychosocial supportImproved exercise tolerance, mood, self-efficacy and health-related quality of life have been reported from cognitive behavioural therapy alone102,105 [evidence level C]. Depression, anxiety and panic are frequent complications of chronic disabling breathlessness, with dependence and social isolation being common.109 General support, specific behavioural training and the use of appropriate antidepressant medications may enhance quality of life for the patient, and for the spouse or carer. Comprehensive integrated rehabilitationComprehensive pulmonary rehabilitation,89-103,110-116 which includes all the components discussed above, enhances health-related quality of life and self-efficacy, improves exercise performance, and reduces breathlessness and healthcare use [evidence level A]. It is possible to provide these comprehensive programs in the community,95,100-102 as well as in larger hospitals.114 Lung support groups may provide patients and carers with emotional support, social interaction, and other social outlets, and help them gain new knowledge and coping strategies. More than 80 groups throughout Australia can be contacted via LungNet (toll-free phone number, 1800 654 301; Internet address, http://www.lungnet.com.au. In New Zealand, contact the Asthma and Respiratory Foundation of New Zealand (phone (04) 499 4592; Internet address, http://www.asthmanz.co.nz). Chest physiotherapyA systematic review in COPD and bronchiectasis showed a significant increase in sputum clearance with no change in lung function or health status117 [evidence level B]. The aims of chest physiotherapy are to assist sputum removal and improve ventilation without increasing the distress of the patient.117 Auscultation plus chest x-ray findings help determine the regions of the lung to be treated. Bronchodilator therapy before treatment may result in a more effective treatment. If patients are hypoxaemic (Spo2 , < 88%), supplemental oxygen is given during treatment. Various techniques and devices are available to aid sputum removal. The choice of technique depends on the volume of sputum, the patient's condition (eg, extent of airflow limitation, severity of breathlessness), patient preference and the cognitive status of the patient. Weight management and nutritionIn patients with COPD, both excess and low weight are associated with increased morbidity. Excessive weight increases the work of breathing and predisposes to sleep apnoea — both central hypoventilation and upper-airway obstruction. Progressive weight loss (body mass index < 20) is an important prognostic factor for poor survival118,119 [evidence level A]. This may be the result of a relative catabolic state (related to high energy demands of increased work of breathing) added to disturbance of nutritional intake (related to breathlessness while eating). Deleterious consequences include combined protein–energy malnutrition,119 and possibly mineral or essential vitamin and antioxidant deficiencies.119 Randomised controlled trials of nutritional support in COPD have not shown significant improvements in nutrition, exercise capacity or other outcomes [evidence level B]. Patients with COPD should not eat large meals, as this can increase dyspnoea. Several small nutritious (high energy, high protein) meals are better tolerated. Snacks may provide a useful addition to energy and nutrient intake. Referral to a dietitian for individual advice may be beneficial. P: Prevent deterioration Risk factor reduction — Smoking cessation — Nicotine replacement therapy — Bupropion — Prevent smoking relapse — Influenza vaccination — Pneumococcal vaccination — Antibiotics — Glucocorticoids — Mucolytic agents — Regular review — Oxygen therapy — Fitness to fly Reducing risk factors for COPD is a priority, and smoking is the most important of these. Reduction of exposure to occupational dust, fumes and gases and to indoor and outdoor air pollutants is also recommended6 [evidence level D]. Influenza vaccination reduces the risk of exacerbations and death [evidence level A], while long term oxygen therapy reduces mortality [evidence level A]. Risk factor reductionSmoking cessationSmoking cessation reduces the rate of decline of lung function 6,7 [evidence level A] A successful smoking cessation strategy involves integration of public policy, information dissemination programs and health education through the media and schools.6 Smoking prevention and cessation programs should be implemented and be made readily available6,120 [evidence level A]. Smoking cessation (see Box 3) has been shown to halt the accelerated decline in lung function seen with COPD6,7 [evidence level A]. People who continue to smoke despite having pulmonary disease are highly nicotine dependent and may require treatment with pharmacological agents to help them quit.121,122 Smoking cessation interventions have been shown to be effective in both sexes, in all racial and ethnic groups tested, and in pregnant women.6 International data show that smoking cessation strategies are cost effective, but with a 10-fold range in cost per life-year gained depending on the intensity of the program and the use of pharmacological therapies.6 General practitioners and pharmacists can help smokers quit.123-125 Relapse is common [evidence level A] Brief counselling is effective [evidence level A] and every smoker should be offered at least this intervention at every visit.6 Currently accepted best practice is summarised in the 5-A strategy: 6 Ask and identify smokers. Advise smokers about the risks of smoking and benefits of quitting and discuss options. Assess the degree of nicotine dependence and motivation or readiness to quit. Assist cessation — this may include specific advice about pharmacological interventions or referral to a formal cessation program if available. Arrange follow-up to reinforce messages. Cessation of smoking is a process rather than a single event, and smokers cycle through the stages of being not ready, unsure, ready, quitting and relapsing before achieving long-term success. The aim of initial intervention is to advance one stage in the cessation cycle. The most strenuous efforts should be made with those smokers ready to quit or quitting. Cessation rates increase with the amount of support and intervention, including practical counselling and social support arranged outside of treatment. Treatment of nicotine dependence is effective and should be offered to smokers in addition to counselling 124-132 [evidence level A] Pharmacotherapies for nicotine dependence, including nicotine replacement and bupropion (sustained-release), are effective [evidence level A].124-132 At least one of them should be added to counselling if necessary and in the absence of contraindications6 [evidence level A]. Caution is recommended in people with medical contraindications, light smokers (< 10 cigarettes a day) who may become dependent on nicotine replacement therapy, pregnant women and adolescent smokers.6 All forms of nicotine replacement therapy (NRT) appear to be useful in aiding smoking cessation.126 NRT is most suitable for highly dependent smokers who are motivated to quit. There is little evidence for its role in those who smoke up to 15 cigarettes daily. The choice of type of NRT depends on patient preference, needs and tolerance. NRT is more effective when combined with counselling and behavioural therapy.131 NRT is safe in patients with stable cardiac disease such as angina pectoris [evidence level A].6,122 NRT produces lower peak levels of nicotine than active smoking, so, theoretically, should be safer than smoking, even in patients with unstable disease. Nicotine replacement therapyNicotine transdermal patch: A steady nicotine level (about half that of smoking) is maintained to reduce withdrawal symptoms. However, the patch does not provide the peak nicotine levels of smoking which reinforce the addiction. Addition of a self-administered form of nicotine, such as gum, inhaler or lozenge, improves abstinence rates.126,127 The strength of patch used depends on the degree of nicotine dependence, indicated by number and strength of cigarettes smoked daily. Three strengths are available — 7 mg, 14 mg and 21 mg — and both 24-hour and 16-hour patches are available. The 24-hour patches achieve higher blood nicotine levels and provide more relief of morning cravings, but both patches have about the same efficacy. Patch use doubles the success rates of attempts to quit compared with placebo. Six to eight weeks of use are generally required, with tapering of the nicotine dose every two weeks.128 The only significant side effect is skin irritation, which is generally mild and rarely leads to cessation of use. Nicotine gum: Nicotine is rapidly absorbed through the oral mucous membrane, so gum should be chewed only two to three times per minute to avoid excessive salivation, swallowing of nicotine and gastrointestinal side effects. The blood levels achieved by nicotine chewing gum are one-third (2 mg gum) or two-thirds (4 mg gum) those of smoking. Patients should taper the dose gradually, but dependence on the gum can occur in up to 20% of users. Most patients should have stopped using the gum within three months. Nicotine lozenge: Nicotine lozenges are available in 2 mg and 4 mg doses. No special technique is required — the lozenge is held in the mouth and moved around periodically until it dissolves. As the lozenge dissolves, it releases about 25% more nicotine than the equivalent dose of gum. Patients should reduce the number of lozenges they are using over 12 weeks, remaining on the same strength lozenge throughout. Lozenges may be preferable for denture wearers who wish to use oral NRT. Nicotine inhaler: The nicotine inhaler consists of a plastic mouthpiece and cartridge containing 10 mg of nicotine. The inhaler produces nicotine concentrations that are a third those achieved with smoking. The inhaler is useful for smokers who miss the hand-to-mouth action of smoking, or who have problems with the gum. The recommended maximum period of use is 16 weeks. BupropionBupropion hydrochloride (Zyban sustained-release tablets), in conjunction with counselling and support, doubles the quit rates achieved by placebo, with or without nicotine replacement therapy as an adjunct.129-132 It is recommended as first-line pharmacotherapy for smoking cessation alongside NRT [evidence level A],6 but there are currently insufficient data to recommend its use in preference to NRT, or vice versa. The recommended dose is 150 mg orally once daily for three days, then 150 mg twice daily (at least eight hours apart) for between seven and nine weeks, in combination with counselling. A quit date should be set (eg, Day 5–10). The drug works equally well in smokers with and without a past history of depression. It is also effective in people who have relapsed and are motivated to quit again. Bupropion is contraindicated in patients with epilepsy, bulimia or a history of head trauma. It may interact with other antidepressants, especially monoamine oxidase inhibitors, which require a 14-day washout. There is a relative contraindication in other conditions that may lower the seizure threshold, such as diabetes mellitus. It should only be prescribed to patients at an advanced stage of readiness to quit. Some deaths have been reported in patients taking bupropion in routine clinical practice, but there is no evidence that bupropion was responsible for these deaths.122 The contradictions and adverse effects for bupropion hydrochloride are shown in Box 11. 11: Advantages and disadvantages of pharmacological treatments for smoking cessation6,121-132 Treatment Advantages Disadvantages Nicotine patch Easy to use, few compliance problems. Available over the counter. Half of the users have skin reactions. Some sleep disturbances with the 24-hour patch. Nicotine gum 2 mg strength available over the counter; good to use as a safety valve in times of stress. Provides oral substitute for smoking. Need to spend time explaining correct use. Common adverse effects are mouth soreness, hiccups, dyspepsia and jaw ache. Effectiveness limited by under-use and excessive chewing. Patients can become dependent on the gum. Nicotine lozenges Easy to use; useful for denture wearers as alternative to gum. No special technique. Hiccups Nicotine inhaler Mimics hand-to-mouth behaviour of cigarette smoking. Low nicotine levels. Mild throat irritation and cough. Bupropion hydrochloride Non-nicotine; can be used with patch. Reduces urge to smoke and withdrawal symptoms. Contraindicated in patients with history of seizures, significant head injury, drugs which lower seizure threshold and alcohol abuse. Adverse effects are mild insomnia and dry mouth, headache, rash and tremor. These are generally transient. Prevent smoking relapsePharmacotherapies double the success of quit attempts. Behavioural techniques further increase the quit rate121-125,132 [evidence level A] Counselling sessions, possibly involving professional psychological support and use of nicotine patches and bupropion, increase the chances of successful quitting by 5%–30% compared with control groups.6 Family, friends and workmates should be advised of the intention to quit and provide understanding and support. The relapse rate is increased if there are other smokers in the household. Success is more likely if all the smokers agree to quit together. Suggest the patient ring the Quit Line or other local services (Australia, 131 848; NZ, 0800 778 778). Ex-smokers who attend for follow-up are more likely to be successful in the long term. Support is most needed in the first few weeks, so regular follow-up visits then and over the first three months should be encouraged. Influenza vaccinationInfluenza vaccination reduces the risk of exacerbations, hospitalisation and death 133,134 [evidence level A] Annual influenza vaccination reduces by about 50% the development of severe respiratory complications and hospitalisation or death from both respiratory disease and all causes133,134 [evidence level A]. The vaccine used in Australia does not contain a live virus and cannot cause an infection. Side effects include a sore arm the following day and possibly a mild fever and arthralgia at five to eight days caused by the immune response. The vaccine usually contains three strains (2A and 1B), which are adjusted annually based on epidemiological data. It should be given in early autumn to all patients with moderate to severe COPD.133,134 A second vaccination in winter increases antibody levels.6 Pneumococcal vaccinationPneumococcal vaccination is known to be highly effective in preventing invasive bacteraemic pneumococcal pneumonia, but may be less effective in elderly or immunosuppressed patients.135 There is no direct evidence of its efficacy in preventing pneumococcal exacerbations of COPD, but prevention of pneumonia in these patients with already reduced respiratory reserve is a worthy goal in its own right,135-137 so pneumococcal vaccination (polyvalent covering 23 virulent serotypes) is recommended in this group [evidence level B].6 The vaccination should be repeated five-yearly. There is no evidence or rationale for vaccinating more frequently in COPD. AntibioticsCurrent evidence does not support long-term antibiotic use to prevent exacerbations in patients with COPD138,139 [evidence level A]. However, they should be used in exacerbations with an increase in cough, dyspnoea, sputum volume or purulence (see Section X, page S29). GlucocorticoidsNo medication has yet been shown to prevent the long-term decline in lung function6,57-61 [evidence level A]. Inhaled glucocorticoids are indicated for patients with a documented response or those who have severe COPD with frequent exacerbations58-61 [evidence level B] In patients with severe COPD, high-dose inhaled corticosteroids may reduce the rate of acute exacerbations and slow the rate of decline of quality of life60 [evidence level B]. However, they have not been shown to reduce the rate of decline of lung function.6 Cessation of therapy is recommended if no benefit is seen. Detailed discussion appears in section O, page S15, and section X page S29. Mucolytic agentsMucolytics may reduce the frequency and duration of exacerbations 140 [evidence level B] Drugs that decrease the viscosity of sputum (eg, bromhexine, N-acetylcysteine, ambroxol, potassium iodide and glycerol guaiacolate) may play a useful role, but criteria for predicting a response have not been established. A Cochrane Review concluded that, in patients with COPD or chronic bronchitis who have a higher than average rate of exacerbations, treatment with mucolytic agents was associated with a small, but significant, reduction in acute exacerbations and total number of days of disability.140 Regular reviewRegular review, with objective measures of function and medication review, is recommended in the hope that this may reduce complications and the frequency or the severity (or both) of exacerbations and admissions to hospital.6 Oxygen therapyLong-term oxygen therapy (more than 15 h/day) prolongs life in hypoxaemic patients (Pao2 < 55 mmHg, or 7.3 kPa) 12,13,80-82,141-143 [evidence level A] Long term oxygen therapy reduces mortality in COPD.12,13,81-82,141-143 It may also have a beneficial impact on haemodynamics, haematological status, exercise capacity, lung mechanics and mental state.80,82,143 Although effective, it is a potentially expensive therapy that should only be prescribed for those in whom there is evidence of benefit (see below). Information on prescribing oxygen therapy is given in Appendix 3. Long-term continuous oxygen therapy (at least 15 hours a day) is appropriate for patients who have Pao2 consistently ≤ 55 mmHg (7.3 kPa; Spo2 88%)12,13 when breathing air, at rest and awake [evidence level A]. If oxygen is prescribed when the patient's condition is unstable (eg, during an exacerbation), then the requirement for it should be reviewed four to eight weeks after initiation. At assessment for ongoing therapy, the patient's condition must be stable, all potentially reversible factors must have been treated and the patient must have stopped smoking at least one month previously. Polycythaemia (haemoglobin level > 170 g/L), clinical or electrocardiographic evidence of pulmonary hypertension, as well as episodes of right heart failure, are consistent with the systemic effects of chronic hypoxaemia, and continuous oxygen should be supplied if the stable Pao2 is 55–59 mmHg (7.3–7.9 kPa; Spo2 < 90%)141,142 [evidence level D]. Continuous oxygen therapy is of most benefit for patients with increased arterial Paco2 (> 45 mmHg, or 6 kPa).13 Government funding is available on the basis that the prescribing doctor is an approved prescriber (usually a respiratory physician). Oxygen is usually supplied to patients meeting specific criteria and means testing by state or regional health departments in Australia and New Zealand. Intermittent oxygen therapy: Available evidence does not allow any firm conclusions to be made about the effectiveness of intermittent ambulatory domiciliary oxygen therapy in patients with COPD.144 However, use of intermittent oxygen therapy may be considered for: People who experience oxygen desaturation on exertion144 [evidence level C]. Supplementary oxygen may improve exercise capacity. The benefit cannot be predicted by a resting test; acute benefit may be established by comparing exercise endurance when breathing oxygen and when breathing air, while using a treadmill, a stationary bicycle, in a six-minute walk test or shuttle. Patients living in isolated areas or prone to sudden life-threatening episodes while they are awaiting medical attention or evacuation by ambulance. Patients travelling by air. Flying is generally safe for patients with chronic respiratory failure who are on long-term oxygen therapy, but the flow rate should be increased by 1–2 L/minute during the flight (see also below). Nocturnal oxygen therapy: Patients with hypoxaemia during sleep may require nocturnal oxygen therapy. Nocturnal hypoxaemia should be considered in patients whose arterial gas tensions are satisfactory when awake, but who have daytime somnolence, polycythaemia or right heart failure. Oxygen is indicated for patients whose nocturnal arterial oxygen saturation repeatedly falls below 88% [evidence level D]. Sleep apnoea should be excluded. Fitness to flyCommercial aircraft operate at altitudes of up to 12 500 metres, with the plane's interior pressurised to 2100–2400 metres. At this "altitude" the alveolar Pao2 for healthy individuals decreases from 103 mmHg (13.7 kPa) to 64 mmHg (8.5 kPa) and oxygen saturation declines from 97% to 93%. As a general rule, supplemental oxygen is unlikely to be required if the resting oxygen saturation is 95% or higher, and likely to be required if oxygen saturation is 88% or lower. Patients with oxygen saturation values between these levels might require specialist assessment. Before flying, patients should ideally be clinically stable. Patients recovering from an acute exacerbation are particularly at risk. Those already on long-term oxygen therapy need an increase in flow rate of 1–2 L per minute during flight. Careful consideration should be given to any comorbidity that may impair delivery of oxygen to the tissues (eg, cardiac impairment, anaemia). Exertion during flight will exacerbate hypoxaemia. The American Thoracic Society currently recommends that Pao2 during air travel should be maintained at more than 50 mmHg (6.7 kPa). At altitude, Pao2 can be estimated from Pao2 at sea level by means of published nomograms. If the Pao2 at sea level is less than 70 mmHg (9.3 kPa), Pao2 at 2300 metres is less than 50 mmHg (6.7 kPa). The natural conclusion is that all patients with a Pao2 less than 70 mmHg (9.3 kPa) at rest at ground level should receive supplemental oxygen.142,145 Many lung function laboratories perform assessments for fitness to fly. These may include measurement of arterial blood gas levels or transcutaneous oxygen saturation while breathing a mixture of 15% oxygen and 85% nitrogen, which mimics conditions at 2800 metres. D: Develop support network and self-management plan Pulmonary rehabilitation — Support team — General practitioner — Nurse/respiratory educator — Physiotherapist — Occupational therapist — Social worker — Clinical psychologist — Speech pathologist/therapist — Pharmacist — Dietitian — Non-medical care agencies — Multidisciplinary care plans — Self-management plans — Maintenance therapy — Exacerbations and crises — Treat anxiety and depression — Referral to a support group — End-of-life issues COPD imposes handicap which affects both patients and carers 89-92,102 [evidence level B] In the early stages of disease, patients with COPD will often ignore mild symptoms. As the disease progresses, impairment and disability increase. As a health state, severe COPD has the third-highest perceived "severity" rating, on a par with paraplegia and first-stage AIDS.2 Depression, anxiety, panic disorder, and social isolation add to the burden of disease as complications and comorbidities accumulate. Patients with COPD often have neuropsychological deficits suggestive of cerebral dysfunction. The deficits are with verbal and visual short-term memory, simple motor skills, visuomotor speed and abstract thought processing. People with chronic conditions are usually cared for by partners or family members. In populations where the patient's chronic disease is non-respiratory, there is evidence that the psychological health status of carers and patients is linked. In one small population of patients with COPD, levels of loneliness, social isolation and depression were similar among carers and their patients. The quality of care received from family carers is linked with the health of those carers, so that poor carer health status has been found to be associated with high rates of health service use, including hospitalisation, in patients with COPD. It is not surprising that significant psychological and physical consequences occur in carers of patients with chronic diseases. One of the most effective means of improving the patient's functional and psychological state and reducing carer strain is pulmonary rehabilitation. Pulmonary rehabilitationPulmonary rehabilitation increases patient/carer knowledge base, reduces carer strain and develops positive attitudes toward self-management and exercise89-108,111-116,141,142 [evidence level A] The primary goal of pulmonary rehabilitation is to restore the patient to the highest possible level of independent functioning. Benefits are wide-ranging and there are minimal risks (see Section O, page S15). Health education can play a role in improving skills, ability to cope with illness and health status.105-107 It is aimed at improving compliance with pharmacological treatments and maintaining an exercise program after pulmonary rehabilitation, undertaking and sustaining smoking cessation, and using devices such as nebulisers, spacers and oxygen concentrators properly. Education is most effective when it is interactive and conducted in small workshops.6 Pulmonary rehabilitation, including health education for patients, has also been shown to improve the coping ability and psychological functioning of carers.105-108 Support teamEnhancing quality of life and reducing handicap requires a support team 142 [evidence level C] In advanced disease, the many comorbidities, social isolation and disability mean that a multidisciplinary approach to coordinated care may be appropriate. The multidisciplinary team, depending on local resources, may include the members listed below. The role of respiratory specialists is outlined in Section C. General practitionerAs the primary healthcare provider, the GP is uniquely placed to identify smokers and help them quit, diagnose COPD in its early stages and coordinate care as the disease progresses. Smoking cessation: A doctor's advice is an important motivator for smoking cessation, especially if the doctor is the family physician. The GP can help initiate the cycle of change by repeated brief interventions. There are several smoking cessation programs that have been developed for use in general practice (outlined in the RACGP "Green Book"146). The GP is also the appropriate health professional to recommend or prescribe nicotine replacement therapy and pharmacological treatment of nicotine addiction (for a detailed discussion of smoking cessation interventions, see Section P, page S21). Early diagnosis: Most people visit a GP about once a year. Simple questions relating to smoking history, daily cough and degree of breathlessness should lead to lung function testing. Coordinate investigation and management: GPs will manage patients with mild to moderate COPD. Referral to a respiratory physician may be indicated to confirm the diagnosis, exclude complications and aggravating factors, and to help develop a self-management plan (Section C, Box 8). Coordinate care in advanced disease: GPs play a crucial role coordinating services provided by a range of healthcare professionals and care agencies (the "multidisciplinary team"). Patients and their family/friends should be actively involved in a therapeutic partnership with a range of professional disciplines89,90,92,105-108 [evidence level C] Nurse/respiratory educatorSpecific aspects of care provided by nurses in COPD may include: respiratory assessment, including spirometry and pulse oximetry; implementation of, or referral for, interventions such as smoking cessation, sputum clearance strategies, oxygen therapy; skills training with inhalation devices; education to promote better self-management (eg, medications and response to worsening of symptoms); organisation of multidisciplinary case conferences and participation in care-plan development; and assessment of the home environment. PhysiotherapistPhysiotherapists are involved in a broad range of areas, including exercise training, sputum clearance, breathing retraining, mobility, non-invasive positive pressure ventilation, postoperative respiratory care (eg, after LVRS), and assessment and treatment of musculoskeletal disorders commonly associated with COPD. Occupational therapistOccupational therapists provide specific skills in task optimisation and prescription of adaptive equipment and home modifications. Some therapists also teach energy conservation for activities of daily living and can help in the set-up of home and portable oxygen. Social workerSocial workers can provide counselling for patients and their carers, organisation of support services, respite and long-term care. Clinical psychologistAnxiety and depression are common comorbidities in patients with COPD. Panic disorder is also frequent, and can be disabling and out of proportion to the impairment of lung function. Clinical psychologists can use techniques such as counselling and cognitive behavioural therapy to help address anxiety and depression. They may also advise whether pharmacological treatment may be appropriate. Speech pathologist/therapistSpeech pathologists can be involved in the assessment and management of recurrent aspiration, swallowing and eating difficulties caused by shortness of breath, and dry mouth associated with some pharmaceuticals, age and mouth breathing. PharmacistPharmacists are involved in education about medications and supply of medications. They can help smokers quit by advising about nicotine replacement and can counsel patients requesting over-the-counter salbutamol. They are well placed to monitor for medication problems and complications and suggest solutions (eg, individual dosing dispensers). DietitianExcessive weight-loss is a common problem in patients with end-stage COPD. Conversely, obesity in patients with COPD is associated with sleep apnoea, CO2 retention and cor pulmonale. Dietitians play a central role in managing these problems. Non-medical care agenciesMany patients with COPD have difficulties with activities of daily living and may require a range of non-medical support services, including governmental and non-governmental organisations. Availability of services varies between states and between areas within states (eg, urban, rural, remote). Some examples include: financial support and organisation of oxygen, CPAP machines, nebulisers, etc; Homecare; government-supported assistance with activities of daily living (showering, cleaning, shopping, etc); home maintenance; Meals on Wheels; exercise programs; and support groups. Multidisciplinary care plansMultidisciplinary care plans and individual self-management plans may help to prevent or manage crises 108 [evidence level B] A multidisciplinary care plan involves documentation of the various medical, paramedical and non-medical services required to keep a patient functioning in the community. Various generic and disease-specific proformas are available (see http://www.lungnet.com.au/copd.html for examples). The care plan may be initiated in the context of a multidisciplinary case conference involving the GP and at least two other health professionals (one of whom is not a doctor). GPs are remunerated for their involvement in case conferences. This is supported by Extended Primary Care (EPC) item numbers, which vary according to the level of involvement of the GP and the location of the patient. The GP may participate by telephone. A consultant physician is also entitled to claim rebates for organising or participating in case conferences. Further information about item numbers is available at http://www.health.gov.au/epc. The multidisciplinary care plan may include a component of self-management with appropriate support. Self-management plansPatients should be encouraged to take appropriate responsibility for their own management108,142,147-149 [evidence level C] Patients with chronic illness who participate in self-management have better outcomes, including reduced healthcare costs, than those who do not.108 This study included some people with COPD. In COPD, behavioural education alone is effective, although less effective than integrated pulmonary rehabilitation programs that include an exercise component.105 In patients with COPD, most exacerbations evolve over days rather than hours, but even small changes can precipitate a major deterioration in functional status. Psychosocial factors such as depression, anxiety, panic or lack of a carer have also been shown to influence the model of care. The traditional approach to exacerbations of moderate to severe COPD has been admission to hospital. Recent work exploring the concept of hospital-at-home has shown that many patients can be managed at home by appropriately qualified staff.147-149 Whether such treatment is cost-effective remains controversial.147-149 The concept of self-management plans for patients with COPD is derived from their success in asthma management indicating doses and medications to take for maintenance therapy and for exacerbations. Instructions for crises are often also included. However, pharmacological treatment of COPD is generally less effective, as the condition is, by definition, non-reversible. Some interventions have strong support (eg, use of bronchodilators and systemic glucocorticoids for exacerbations and antibiotics if there is purulent sputum). They might be more effective if instituted early in an exacerbation, thereby preventing crisis and hospital admission. The primary care team needs to develop systems to identify those with more severe COPD who might benefit from more intensive education and training in self-management skills. GP involvement in review of self-management plans (including medications) may be undertaken in the context of Domiciliary Medication Management/Review (DMMR), for which a Medicare Benefits Schedule fee is applicable (EPC Item 900). This requires the involvement of an accredited pharmacist and patient consent. The plan should be reviewed after any exacerbation to make adjustments as appropriate. Patients should be encouraged to start additional treatment at the earliest sign of an impending exacerbation. Maintenance therapyDetailed discussion of the maintenance therapy for COPD appears in Section O, page S15. In general, the use of drugs in COPD does not involve back-titration, which is a core principle in asthma management. The exception is when oral glucocorticoids have been given for an acute exacerbation. Exacerbations and crisesDetailed discussion of the management of exacerbations is found in Section X, page S26. For mild to moderate exacerbations, an increase in inhaled bronchodilator therapy and an increase in, or introduction of, inhaled glucocorticoid therapy may be beneficial. For severe exacerbations there is evidence for the use of bronchodilators, antibiotics, systemic glucocorticoids and supplemental oxygen (if patients are hypoxaemic). Selected patients may benefit from early intervention with these agents according to a predetermined plan developed by a GP or respiratory specialist. Some patients can be instructed to start using a "crisis medication pack" while awaiting medical review. They may also be instructed to contact a particular member of the multidisciplinary care team as part of their overall care plan. Controlled trials are required to document the efficacy of self-management plans in patients with stable COPD, but, drawing on the success of asthma action plans, education of patients with COPD in self-management is recommended [evidence level D]. Written plans are usually required to complement such interventions (see examples at http://www.lungnet.com.au/copd.html). Treat anxiety and depressionThe strong relationship between anxiety and COPD has long been established.105 Anxiety symptoms lead to repeated presentations for hospital admission for many patients, at a significant financial cost. Anxiety and mood disturbances can often be exacerbated by respiratory drugs (eg, theophylline and steroids, respectively). Identifying individuals at risk for clinical anxiety and developing effective interventions for treating, or, ideally, preventing panic disorder in COPD should be priorities. There are many outcome trials showing the effectiveness of cognitive behavioural therapy in treating panic disorder when no respiratory disease is present. Cognitive behavioural therapy should also be an effective intervention for treating patients with COPD-related panic disorder. Depression is common in patients with chronic illness, and COPD is no exception.109 Pharmacological treatment of depression in COPD may be hampered by poor tolerance of side effects such as sedation, which may cause respiratory depression and aggravate sleep disturbances. In addition to usual clinical assessment, the presence and impact of anxiety and depression may be reliably predicted with several validated questionnaires. Referral to a support groupPatients who receive education and psychosocial support show greater improvements in more aspects of health-related quality of life than those who receive education with no ongoing support.105 One way to provide such education and support is through patient support groups. Support groups aim to empower patients with COPD to take a more active role in the management of their healthcare, and thus reduce the psychosocial impact of their disease. Although no direct evaluation of support groups has been published, the likely benefits are summarised in Box 12. 12: Patient support groups Typical support group activities Regular meetings Expert guest speakers on COPD topics Telephone calls, hospital and home visits Receive and distribute lung health education information Special seminars and patient programs Social outings Rehabilitation assistance and maintenance of exercise Social enjoyment Benefits of support groups Reinforce and clarify information learnt from health professionals Provide access to new information on lung health Share experiences in a caring environment Empower patients to be more actively involved in their healthcare through self-management techniques Participate in social activities and exercise programs Encourage patients to think more positively about their lung disease Help carers understand lung disease COPD = chronic obstructive pulmonary disease. End-of-life issuesTerminally ill patients with COPD are usually elderly and have already experienced one or more decades of increasingly frustrating functional restriction. Their course is likely to have been punctuated by hospital admissions. They often have several comorbidities and are frequently dependent on the care of others. Determining prognosis in end-stage COPD is difficult, although guides to shortened survival include an FEV1 < 25% predicted, weight loss (body mass index below 18), respiratory failure (Paco2 > 50mmHg, or 6.7 kPa), and right heart failure. The major ethical issues are deciding whether to offer invasive or non-invasive ventilatory support, or, alternatively, to withhold, limit or withdraw such support. These decisions are often complex, but, as in other areas of medicine, they are ultimately constrained by the standard ethical principles of respect for patient autonomy, and ensuring that good and not harm is achieved. Most patients with end-stage COPD wish to participate in end-of-life management decisions and would prefer to do so in a non-acute setting. In some states the patient's wishes can be given legal force through the use of an enduring power of attorney or advance health directive. Although difficult for the health professional and potentially distressing for the patient, a frank discussion about these often unspoken issues can be beneficial. Opioids and many anxiolytics depress ventilatory drive and are contraindicated in most patients with COPD. When palliation is warranted, however, their use could be considered. X: Manage eXacerbations Home management — COPD acute exacerbation plan — Initial assessment of severity — Optimise treatment — Refer appropriately — Controlled oxygen delivery — Non-invasive positive pressure ventilation — Invasive ventilation (intubation) — Clearance of secretions — Monitor and review — Discharge planning — Support after discharge — Clinical review and follow-up Acute exacerbations of COPD often require hospital admission for treatment of respiratory failure. Hospital mortality for such patients is about 10%, reaching 40% at one year after discharge, and higher for patients aged over 65 years.14,150,151 In one study of more than 1000 patients admitted to several hospitals with an acute exacerbation of severe COPD, about 50% were admitted with a respiratory infection, 25% with congestive cardiac failure, and 30% with no known cause for the exacerbation.14 A study of 173 patients with COPD reported an average of 1.3 (range, 0–9.6) exacerbations annually. In patients with COPD the normally sterile lower airway is frequently colonised by Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. While the number of organisms may increase during exacerbations of COPD, the role of bacterial infection is controversial.152-160 Exacerbations can also be caused by viral infection and by non-infectious causes, such as left ventricular failure, pulmonary embolus, and possibly other factors, such as air pollution.161 Chest trauma and inappropriate use of sedatives can lead to sputum retention and hypoventilation. Early diagnosis and treatment may prevent admission 108,148 [evidence level C] Early diagnosis and prompt management of exacerbations of COPD may prevent progressive functional deterioration and reduce hospital admissions.108,148 Education of the patient, carers, other support people and family may aid in the early detection of exacerbations. A self-management plan developed in conjunction with the patient's GP and specialist to indicate how to step-up treatment may be useful (see examples at http://www.lungnet.com.au/copd.html). This plan might indicate which medications to take, including antibiotics and oral glucocorticoids. The plan should also require patients to contact their GPs or community nurses to allow rapid assessment (see section D, page S25). Home managementMultidisciplinary care may assist home management 108,148,162,163 [evidence level B] The shortage of hospital beds, especially in winter, has prompted interest in home care for management of COPD exacerbations, with involvement of multidisciplinary teams assisting GPs. Economic studies of such programs have shown mixed results.108,148,162,163 COPD acute exacerbation planInitial assessment of severityAssessment of severity of the exacerbation includes a medical history, examination, spirometry and, in severe cases (FEV1 < 40% predicted), blood gas measurements, chest x-rays and electrocardiography. Patients should be provided with and bring a summary of their medical problems and treatment (eg, a personal health record). If available, results of previous stable lung function tests and arterial blood gas measurements are invaluable for comparison. Spirometry: Unless confused or comatose, even the sickest of patients can perform an FEV1 manoeuvre. An FEV1 less than 1.0 L (or < 40% predicted) is usually indicative of a severe exacerbation in patients with moderate COPD. For patients with stable levels below these values (ie, severe COPD), the most important signs of a severe exacerbation will be worsening hypoxaemia, acute respiratory acidosis (carbon dioxide retention), or both. Arterial blood gases: Arterial blood gas levels should be measured if the FEV1 is less than 1.0 L or less than 40% predicted, or if there are signs of respiratory failure or cor pulmonale. Values obtained while breathing room air are the most useful for assessing ventilation–perfusion inequality. A Pao2 less than 60 mmHg (8 kPa) indicates respiratory failure, while a Paco2 greater than 45 mmHg indicates ventilatory failure. Chest x-ray and electrocardiogram: These help to identify alternative diagnoses and complications, such as pulmonary oedema, pneumothorax, pneumonia, empyema, arrhythmias, myocardial ischaemia and others. Optimise treatmentAn acute exacerbation of COPD may involve an increase in airflow limitation, excess sputum production, airway inflammation, infection, hypoxia, hypercarbia and acidosis. Treatment is directed at each of these problems. Bronchodilators: Inhaled β-agonist (eg, salbutamol, 400–800 μg; terbutaline, 500–100 μg) and anticholinergic agent (ipratropium, 80 μg) can be given by pressurised metered dose inhaler and spacer, or by jet nebulisation (salubutamol, 2.5–5 mg; terbutaline, 5 mg; ipratropium, 500 μg). The dose interval is titrated to the response and can range from hourly to six-hourly. Glucocorticoids: Oral glucocorticoids hasten resolution and reduce the likelihood of relapse. Up to two weeks' therapy with prednisolone (40–50 mg daily) is adequate. Longer courses add no further benefit and have a higher risk of side effects. Antibiotics: Antibiotics are given for purulent sputum to cover for typical and atypical organisms. Controlled oxygen therapy: This is indicated in patients with hypoxia, with the aim of improving oxygen saturation to over 90% (Pao2 > 50 mmHg, or 6.7 kPa). Use nasal prongs at 0.5–2.0 L/minute or a venturi mask at 24% or 28%. Minimise excessive oxygen administration, which can worsen hypercapnia. Ventilatory assistance: This is indicated for increasing hypercapnia and acidosis. Non-invasive positive pressure ventilation by means of a mask is the preferred method. Inhaled bronchodilators are effective treatments for acute exacerbations6,141,142,164-166 [evidence level A] In exacerbations of COPD, the immediate bronchodilator effect is small, but may result in significant improvement in clinical symptoms in patients with severe obstruction. Studies of acute airflow limitation in asthma indicate that β-agonists are as effectively delivered by metered dose inhaler and spacer as by nebuliser. This may be applicable to patients with COPD. An adequate dose should be used. The dose equivalent to 5 mg of salbutamol delivered by nebuliser is 8–10 puffs of 100 μg salbutamol by metered dose inhaler and spacer. Airflow in the nebuliser should be 6 L per minute or higher to achieve an aerosol. Avoid using high-flow oxygen, which may worsen carbon dioxide retention. High doses of β-agonists may induce hypokalaemia and predispose to cardiac arrhythmias. Few studies have examined the use of ipratropium bromide in acute exacerbations of COPD.165,166 One study which compared the effectiveness of ipratropium bromide with a β-agonist showed that each drug produced a small but significant improvement in pulmonary function.165 Inhaled ipratropium bromide also produced a small but significant increase in Pao2 (average, 6 mmHg, or 0.8 kPa) within 30 minutes of its delivery. Hospital management of a severe exacerbation usually includes nebulised β-agonist bronchodilator (eg, salbutamol, terbutaline), given continuously in extremely unwell patients and intermittently in others. This will usually be delivered by means of high flow air. An anticholinergic agent (ipratropium bromide) may be delivered together with the nebulised β-agonist in patients with severe exacerbations (triage categories 1 and 2) or when response to β-agonists alone is poor. Nebulised medications can also be administered through the assisted ventilation circuit if required.166 The mode of delivery should be changed to a metered dose inhaler with a spacer device or a dry powder inhaler within 24 hours of the initial dose of nebulised bronchodilator, unless the patient remains severely ill.167,168 The use of oral theophylline and IV aminophylline in the management of acute exacerbations of COPD has diminished because of their potential for toxicity169-173 [evidence level A]. The routine use of aminophylline is not recommended for acute exacerbations [evidence level D]. Exacerbations with clinical signs of infection (increased volume and change in colour of sputum and/or fever, leukocytosis) benefit from antibiotic therapy 138,139,174-176 [evidence level B] Bacterial infection may have either a primary or secondary role in about 50% of exacerbations of COPD.152,155,160,175 Haemophilus influenzae, Streptococcous pneumoniae and Moraxella catarrhalis are most commonly involved.152,154,159 Mycoplasma pneumoniae and Chlamydia pneumoniae are seen relatively frequently.152,158 As lung function deteriorates (FEV1 < 35%), Pseudomonas aeruginosa and Staphylococcus aureus are often encountered.152,154,160 A meta-analysis174 examining the use of oral antibiotics in patients with exacerbations of COPD showed a small but significant clinical and symptomatic benefit. The greatest improvement was seen in patients who had been hospitalised rather than ambulatory. Therapeutic guidelines: antibiotic177 recommend the use of oral agents such as doxycycline or amoxycillin (alternatively, erythromycin or roxithromycin). If patients do not respond, or if resistant organisms are suspected, amoxycillin–clavulanate should be prescribed. If pneumonia, pseudomonas or staphylococci is suspected, appropriate antibiotics should be used. Typically, a course of treatment should be over seven to 10 days. A response is usually seen within three to five days, and a change of antibiotic should be considered if the response is unsatisfactory. If parenteral administration was commenced, oral treatment should be substituted within 72 hours. Radiologically proven pneumonia in patients with COPD, especially in those who have been frequently hospitalised, may not be restricted to the above organisms. Gram-negative organisms, Legionella spp. and even anaerobic organisms may be responsible. Initial empiric antibiotic therapy should be tailored according to clinical and radiographic criteria. Systemic glucocorticoids reduce the severity of and shorten recovery from acute exacerbations178-180 [evidence level A] A recent randomised controlled trial of systemic glucocorticoids for acute exacerbations of COPD showed a moderate improvement in clinical outcomes.179 Maximum improvement was gained within two weeks of therapy, and prolonging the course of treatment thereafter did not result in further benefit. An important side effect was hyperglycaemia, often sufficiently severe to warrant treatment. Blood glucose levels should be monitored. Oral or parenteral glucocorticoids are recommended for treating acute exacerbations of COPD [evidence level A]. The optimal dose has not been established, but 30–50 mg prednisolone daily is sufficient for most patients. If intravenous therapy was commenced, this should be changed to oral therapy within 48 hours. The continued use of inhaled corticosteroids and the administration technique should be reviewed. At discharge, therapy with oral prednisolone (25–37.5 mg daily) may be continued for a total of seven to 14 days and then ceased. Tapering of glucocorticoid therapy is not necessary after short-term administration. However, patients who have taken glucocorticoids for more than three consecutive weeks may have adrenal suppression,179,180 and their glucocorticoid therapy should not be ceased abruptly. Patients on long-term oral steroid therapy (≥ 7.5 mg prednisolone daily for more than 6 months) are at risk of developing osteoporosis. Prevention and treatment of steroid-induced osteoporosis should be considered. Refer appropriatelyThe risk of death from exacerbations of COPD increases with acute carbon dioxide retention (respiratory acidosis), the presence of significant comorbid conditions (eg, ischaemic heart disease) and complications (eg, pneumonia and empyema). Depending on the nature and severity of the exacerbation, the patient may require urgent specialist review, hospital assessment or admission to a high-dependency or intensive care facility for ventilatory support and appropriate monitoring (see Boxes 13 and 14). 13: Indications for hospitalisation of patients with chronic obstructive pulmonary disease Marked increase in intensity of symptoms Patient has acute exacerbation characterised by increased dyspnoea, cough or sputum production, plus one or more of the following: Inadequate response to ambulatory management Inability to walk between rooms when previously mobile Inability to eat or sleep because of dyspnoea Cannot manage at home even with home-care resources High risk comorbidity condition — pulmonary (eg, pneumonia) or non-pulmonary Altered mental status suggestive of hypercapnia Worsening hypoxaemia or cor pulmonale Newly occurring arrhythmia 14: Indications for increased respiratory support or intensive care unit admission Severe dyspnoea that responds inadequately to initial emergency therapy Confusion, lethargy or evidence of hypoventilation Persistent or worsening hypoxaemia despite supplemental oxygen, worsening hypercapnia (Paco2 > 70 mmHg), or severe or worsening respiratory acidosis (blood pH < 7.3) Assisted mechanical ventilation is required. Controlled oxygen deliveryControlled oxygen delivery (28%, or 0.5–2.0 L/min) is indicated for hypoxaemia 181 [evidence level C] Correction of hypoxaemia to achieve a Pao2 of at least 55 mmHg (7.3 kPa) and an oxygen saturation of 88%–92% is the immediate priority.6 Where there is evidence of acute respiratory acidosis (or a rise in Paco2), together with signs of increasing respiratory fatigue and/or obtunded conscious state, assisted ventilation should be considered. Early non-invasive positive pressure ventilation (NIPPV) may reduce the need for endotracheal intubation (see below for more detail). Administering oxygen at an inspired oxygen concentration (fraction of inspired oxygen; Fio2) of 24%–28% by means of a venturi mask is usually sufficient to improve oxygenation in most patients. Nasal cannulas, although more comfortable, deliver a variable concentration of oxygen, but a flow of 0.5–2.0 L per minute is usually sufficient. Gas flow provided through Hudson-type masks is inadequate when patients are tachypnoeic, so these should not be used. Careful monitoring with oximetry and, where hypercapnia is a potential concern, arterial blood gas measurement is required. There is no benefit in trying to obtain Spo2 levels over 92%. High flow oxygen should be avoided, as it is rarely necessary and may lead to hypoventilation and worsening respiratory acidosis. Patients should be weaned off supplementary oxygen as soon as possible, with none for 24–48 hours before discharge, unless home oxygen is prescribed. Non-invasive positive pressure ventilationNon-invasive positive pressure ventilation is effective for acute hypercapnic ventilatory failure85,182-196 [evidence level A] Ventilatory support with intermittent positive pressure ventilation (IPPV) should be considered in patients with rising Paco2 levels who are unable to ventilate adequately (ie, acute or acute-on-chronic respiratory acidosis).182-186 This can be achieved non-invasively (by means of a face mask, NIPPV) or invasively through an endotracheal tube.187,188 NIPPV is an effective and safe means of treatment of ventilatory failure. Its use allows preservation of cough, physiological air warming and humidification, and normal swallowing, feeding and speech. Early intervention with NIPPV is suggested when the respiratory rate is less than 30 per minute and blood pH is less than 7.35. An improvement in respiratory rate and pH usually occurs within one hour of starting NIPPV.182-186 Failure to respond or further deterioration would indicate a need to consider intensive care unit admission (Box 14). Applying non-invasive ventilation in addition to conventional therapy reduces the need for intubation and its potential complications. NIPPV results in more rapid improvements in respiratory rate, dyspnoea score and blood gas abnormalities than conventional therapy alone. Some studies have also shown an improvement in survival and a reduced length of stay in hospital.85,182-196 Invasive ventilation (intubation)NIPPV is contraindicated in patients who are unable to protect their airways, are not spontaneously breathing or who have severe facial injury or burns.188 Relative contraindications (situations where NIPPV may be less effective) include life-threatening refractory hypoxaemia (Pao2 < 60 mmHg, or 8 kPa on 100% inspired oxygen), bronchiectasis with copious secretions, severe pneumonia, and haemodynamic instability. These patients may require intubation. Patients who need mechanical ventilation have an inpatient mortality of 17%–30%.189 The patient's wishes regarding intubation and resuscitation should ideally be documented before an admission for management of respiratory failure. Patients who require ventilatory support during exacerbations of COPD may have impaired control of breathing or apnoeas during sleep, even when well. Therefore, performing a diagnostic sleep study when the patient's condition is stable should be considered. Narcotic analgesics and sedatives should be avoided, as these may worsen ventilatory failure and hasten the need for positive pressure ventilation. Clearance of secretionsPatients who regularly expectorate or those with tenacious sputum may benefit from forced expiratory techniques. If patients produce more than 25 mL sputum per day, or if mucus plugging with lobar atelectasis is present, physiotherapy incorporating the use of postural drainage and associated techniques such as percussion and vibration may help.117,139 Monitor and reviewThe aim is to relieve hypoxaemia and obtain improvement in clinical signs and symptoms. Clinical examination: Reduction in wheeze, accessory muscle use, respiratory rate, distress. Gas exchange: Arterial blood gas levels and/or pulse oximetry levels should be monitored until the patient's condition is stable (Spo2 88%–92%). Respiratory function testing: FEV1 should be recorded in all patients after recovery from an acute exacerbation. Discharge planning: Discharge planning should be commenced within 24–48 hours of admission. Discharge planningInvolving the patient's general practitioner in a case conference and developing a care plan may facilitate early discharge147-149,163 [evidence level C] Discharge planning involves the patient, external lay and professional carers, the multidisciplinary hospital and community team and the patient's regular GP. It should commence on admission and be documented within 24–48 hours. Appropriate patient education and attention to preventive management are likely to reduce the frequency of further acute exacerbations. Assessment of social supports and domestic arrangements are critical in discharge planning. A discharge pack, which includes general information about COPD, advice on medication use and written instructions on use of inhalation and oxygen devices, if appropriate, as well as a plan for management of worsening symptoms, should be provided. The GP (and respiratory outreach program, if available) should be notified during the patient's admission. A case conference involving the multidisciplinary team and GP may assist successful transition to the community. Medicare Benefits Schedule Enhanced Primary Care item numbers may be claimed for "participation in a case conference" and "contribution to a care plan" (see Section D, page S25). Before discharge, referral to a comprehensive pulmonary rehabilitation program should be considered. 15: Criteria for discharge Suggested criteria for a patient's readiness for discharge include: The patient should be in a clinically stable condition and have had no parenteral therapy for 24 hours Inhaled bronchodilators are required less than four-hourly Oxygen delivery has ceased for 24 hours (unless home oxygen is indicated) If previously able, the patient is ambulating safely and independently, and performing activities of daily living The patient is able to eat and sleep without significant episodes of dyspnoea The patient or caregiver understands and is able to administer medications Follow-up and home care arrangements (eg, home oxygen, home-care, Meals on Wheels, community nurse, allied health, GP, specialist) have been completed Support after dischargeFollow-up at home after discharge from hospital may extend the continuum-of-care process begun within the acute environment, although evidence supporting benefit from this practice is still being evaluated. Telephone follow-up may be a way of systematically extending support to patients and increasing their coping strategies at home, but the outcomes of this intervention have not been studied systematically. Clinical review and follow-upThere are no randomised clinical trials that have addressed the best method for follow-up.197 It is recommended that the first review after a hospital admission should be by the GP and within seven days of discharge (Box 16). A decision about the requirement for specialist review should be made at the time of discharge. Follow-up care allows further discussion of self-management plans and future monitoring.197 16: Follow-up – initial and subsequent Assessment of the patient's coping ability and strategies Measurement of FEV1 and performance status Reassessment of medication adherence and techniques with inhalation devices Review of vaccination status (influenza and pneumococcal) Assessment for long-term oxygen therapy (may require reference to specialist facility) Consideration of referral for pulmonary rehabilitation Assessment of risk of osteoporosis and management Smoking cessation — counsel and/or refer Assess nutritional status (frequent small meals reduce dyspnoea)

David K McKenzie PhD, FRACP · Peter A Frith MB BS, FRACP

To the Editor: In the abstract of his article on asthma prevention with dietary manipulation,1 Mellis states that "we know" that the major modifiable dietary environmental risk factors for childhood asthma are not having been breastfed and low intake of omega-3 fatty acids. In his discussion of the evidence, Mellis suggests that breastfeeding may be protective and, importantly, acknowledges the controversy. He further states (in the abstract) that observational studies have shown a reduction in childhood asthma in children who eat fish regularly (that is, have a high intake of omega-3 fatty acids), similar to those who were exclusively breastfed for three months. However, he provides no references for these observational studies, and nor does he discuss any specific evidence in support of including omega-3 fatty acids for reducing childhood asthma. While there are some suggestions of such an association, the evidence is extremely limited compared with the extensive literature on the potential for the protective effect of breastfeeding. Further, there are substantial methodological issues associated with the few studies that do exist, not the least of which is the measurement of the relevant dietary parameters. Australian studies have suggested a protective influence of at least two fish meals per week on bronchial hyperresponsiveness in 7–11-year olds2 and of eating oily fish3 on the prevalence of childhood asthma. However, neither of these studies had the capacity to measure omega-3 fatty acid nor fish intake in a valid way. These limitations were acknowledged by the authors of the studies, and have been noted by others;4 they need to be included in any discussion of a putative protective effect. It should also be noted that the biological plausibility of such an association has been challenged.4 There are many valid reasons for promoting the consumption of omega-3 fatty acids, but shouldn't we wait for the outcome of the randomised clinical trial currently under way before accepting the statement that "we know" that a low intake of these fatty acids increases the risk of childhood asthma?

Jill L Sherriff

In reply: Sherriff is correct in pointing out that the studies showing protection from bronchial asthma (and bronchial hyperresponsiveness) are based on consumption of fish meals rather than a direct measure of omega-3 fatty acid intake. This protection has been observed consistently in cross-sectional studies of New South Wales primary school children. Thus, the level of evidence is at best Level III, albeit using a proxy for omega-3 fatty acid intake. Results of a randomised-controlled trial of omega-3 fatty acid supplementation currently under way in western Sydney are now in the public arena at 18-month follow-up.1,2 At this early stage, it is uncertain who has genuine asthma rather than other wheezing syndromes. Nevertheless, the group who received omega-3 fatty acid supplementation have differences in rates of wheeze compared with those not supplemented.1,2 For example, the rate of "ever" having had wheeze was 52.6% in the controls versus 42.8% in the supplemented group (absolute risk reduction, 9.8%; number need to treat, about 10). In the table of recommendations in my article,3 I carefully pointed out that supplementing infants with omega-3 fatty acid is something to "consider" rather than strongly recommending it. It should also be noted the level of evidence is low (Level III). Stronger recommendations will depend on the long-term results of randomised trials, such as the western Sydney trial.1,2 In summary, at this stage the only strong dietary recommendations which can be made are: not to use strict elimination diets during pregnancy (Level I evidence); and to consider using lactobacillus probiotic supplements. The evidence for lactobacillus is Level II (from a single randomised controlled trial), although the protection shown is for atopy rather than asthma. Clearly, the children in the lactobacillus study will need further follow-up, and the trial will need to be repeated in other populations. All of this highlights the need for better-quality studies in the area of primary prevention of asthma, based on dietary factors during pregnancy or early infancy.

Craig M Mellis

Three children presented with adrenal crises, manifested by vomiting and hypoglycaemia, after protracted courses of high-dose inhaled corticosteroids for asthma. Significant dose reduction was possible in all three without loss of asthma control, emphasising the importance of back-titration to minimise dose. Parents of children taking high doses of inhaled corticosteroids should be alerted to the clinical features of adrenal insufficiency. If suspected, prompt medical assessment should be arranged, including serum glucose and cortisol measurement. The effectiveness of prophylactic inhaled corticosteroids (ICS) in childhood asthma is well established1 and these drugs are recommended as a safe, first-line preventive therapy.2-4 Dose-dependent biochemical adrenal suppression with ICS has been well documented,3-5 although, until recently, reports of frank adrenal insufficiency in children have been rare.6-9 We present the first documented Australian report of three children who presented with adrenal crises while being treated with ICS for asthma. Each had a history of an intercurrent illness during which they were unable to mount a stress-response rise in cortisol level. Clinical recordsPatient 1Presentation: A seven-year-old boy presented with hypoglycaemia associated with vomiting, abdominal pain and drowsiness preceded by two days of fever, rhinorrhoea and fatigue. He had had a previous episode of hyponatraemia and vomiting, but his blood glucose level was not documented at the time. Although he had been noted to have a cushingoid appearance in the past, he was normal on physical examination, his height and weight were on the 3rd percentile, and his growth velocity was normal. He was found to be hypoglycaemic and hyponatraemic, with a low serum cortisol level (Box 1). A short Synacthen test confirmed adrenal insufficiency (Box 2). Asthma history: The patient had a history of "poorly controlled" asthma, but his wheeze was minimal and not associated with increased work of breathing. He undertook normal physical activity and was rarely absent from school. Spirometry findings in the past had been normal. Medications: He was taking fluticasone propionate (1500 μg daily), nebulised budesonide (1000 μg daily till three weeks before presentation), salmeterol (50 μg twice daily), nebulised salbutamol (5 mg four times daily) and ipratropium (250 μg four times daily) and montelukast (5 mg daily). From the age of two years his ICS doses had been progressively increased and had been at these levels for 10 months before this presentation. He had received frequent doses of oral prednisolone from the age of four years, but had had none for the past eight months. Treatment and clinical course: Immediate treatment included a glucose bolus, fluid replacement and hydrocortisone. Ongoing treatment involved giving regular hydrocortisone while reducing the dose of ICS, with no deterioration of asthma control. Four months after his presentation he was taking 500 μg fluticasone daily and being weaned off hydrocortisone. Patient 2Presentation: A four-year-old boy was referred for investigation of two episodes of hypoglycaemia associated with vomiting and lethargy. There was a third episode of vomiting and lethargy; his blood glucose level was normal on this occasion (his mother had treated him with glucose before presentation at hospital). The patient was normal on physical examination, with height and weight between the 10th and 25th percentiles and with normal growth velocity. He was not cushingoid in appearance and had no abnormal pigmentation. Results of available baseline investigations during the hypoglycaemic episodes are shown in Box 1. A short Synacthen test confirmed secondary adrenal insufficiency (Box 2). Asthma history: The patient had had a history of episodic cough and wheeze since the age of four months, but had good exercise tolerance and minimal nocturnal symptoms between episodes. Past spirometry findings were normal. He had started taking ICS at 18 months of age, with progressively increasing doses in an attempt to control acute episodes. Medications: His medications were 1–2 puffs of 250 μg fluticasone propionate with 25 μg salmeterol (Seretide 250/25; Allen & Hanburys) twice daily (giving a daily fluticasone dose of 500–1000 μg), and salbutamol and ipratropium as required. He had never previously required oral steroids. Treatment and clinical course: With each hypoglycaemic episode he was treated with intravenous fluids, with good clinical response, but on one occasion he also received a short course of prednisolone for a "mild exacerbation of asthma". With the normoglycaemic episode he was treated with intravenous fluids and hydrocortisone for two days. After adrenal insufficiency was confirmed (Box 2), therapy with replacement hydrocortisone was commenced and he was weaned from his ICS dose. He currently takes 100 μg fluticasone and 4 mg montelukast daily, with no significant symptoms. He takes hydrocortisone as needed in times of stress, such as during infections. The patient was also subsequently found to have normal spirometry results, even during acute episodes of asthma. Patient 3Presentation: A 10-year-old boy presented after a hypoglycaemic seizure preceded by 24 hours of vomiting. He was normal on physical examination. His height was on the 90th percentile, weight between the 25th and 50th percentiles, and his growth velocity was normal. He was not of cushingoid appearance and had no abnormal pigmentation. He was found to have hypoglycaemia (Box 1), and hyponatraemia was also detected, but was possibly dilutional, as it was collected from the same intravenous cannula through which the dextrose bolus was given. A short Synacthen test confirmed secondary adrenal insufficiency (Box 2). Asthma history: The patient had a history of frequent episodic wheeze and breathlessness during early childhood, and had been admitted to a rural intensive care unit for asthma exacerbation at the age of five years. Past spirometry findings had been normal. He had been taking his current ICS dose for the previous two years, despite having no acute episodes of asthma or interval symptoms. Medications: He was taking Seretide 500/50 twice daily (giving 1000 μg fluticasone propionate daily) and salbutamol as needed. Treatment and clinical course: Therapy with replacement hydrocortisone was begun while the ICS dose was gradually decreased to two puffs of Seretide 50/25 twice daily (giving 200 μg fluticasone daily); hydrocortisone therapy was continued for four months and is now taken as stress cover for intercurrent illness. DiscussionOur case series further highlights the potential for the systemic activity of ICS to manifest as an acute adrenal crisis. These children, as well as patients in previously reported cases,6-9 all had biochemical evidence of adrenal insufficiency in the absence of other causes (normal long-chain fatty acids, excluding adrenoleukodystrophy, and normal adrenal antibodies, excluding autoimmune adrenalitis [Box 2]). The vomiting associated with hypoglycaemia seen in the three children has been previously described,6-9 as have seizures7-9 seen in our Patient 3. The hyponatraemia found in two of our patients is an unexpected feature, but mild hyponatraemia with normokalaemia has been documented in secondary adrenal insufficiency and postulated to be the result of inappropriate vasopressin secretion10 or subnormal aldosterone secretion in response to severe sodium restriction.11 Hydrocortisone has some mineralocorticoid action, and its use as sole replacement therapy was sufficient to restore electrolyte balance in these instances. While growth suppression was noted in one case series,6 and has been reported in association with asymptomatic adrenal suppression,12,13 it was not a feature in our patients, or in other reports.7,8 This suggests that adrenal suppression may manifest differently, perhaps related to differing patient susceptibility, or dose or duration of ICS use. Our patients and most children in previous reports6-9,12,13 were taking high doses of fluticasone. This may reflect current prescribing habits. While fluticasone may be more likely to cause severe adrenal suppression owing to its higher potency compared with other ICSs,7-9,12,13 all ICS medications have been shown to produce dose-dependent adrenal suppression in children.3-5 The low doses used in some reported cases6 again suggest varying patient susceptibility. Screening for asymptomatic adrenal insufficiency in children receiving high doses of ICS is problematic, particularly as abnormal results do not accurately predict clinically meaningful adrenal-axis suppression.4 Clinical indicators of systemic effects, such as poor growth or cushingoid features, were not seen in our patients or in previously reported cases.6-9 Results of tests such as 24-hour urinary free cortisol excretion and random serum or salivary cortisol levels are often indeterminate.14 Early-morning levels of serum or salivary cortisol which are at the high end of the normal range reassure that there is no serious adrenal suppression, but lower levels can be indeterminate.15 "Gold standard" tests, such as insulin-induced hypoglycaemia or metyrapone suppression, carry significant risks and are difficult to justify in this situation. The standard dose (250 μg) short Synacthen test is generally reliable, but may give false normal results in some instances where central hypothalamic–pituitary–adrenal-axis suppression predominates. The low-dose (0.5 μg/1.73 m2) short synacthen test has been proposed as being less prone to such errors,14 but abnormal test results do not always have clinical significance. A more pragmatic approach would be to warn the parents of children taking high dose ICS of the potential for adrenal suppression so that they seek medical advice during an intercurrent illness associated with unexpected lethargy, vomiting, abdominal pains or seizures. Such "non-respiratory" presentations warrant urgent assessment and tests for baseline blood glucose level (for hypoglycaemia) and serum cortisol level (which may be inappropriately low). Prompt recognition and treatment with hydrocortisone and intravenous fluids containing glucose may be life saving in the event of an adrenal crisis. In less acute presentations, suspected adrenal suppression warrants referral for endocrine assessment and adrenal testing, although there is considerable debate as to the best method for doing this.16,17 If significant adrenal suppression is evident by either a low cortisol level at the time of hypoglycaemia or an extremely low response to cortisol stimulation, then maintenance hydrocortisone should be used in the short term to facilitate safe weaning of the child from ICS. However, it is important to remember that some degree of adrenal suppression and risk of adrenal crisis may persist in such children if any steroid therapy continues, or for up to 12 months after steroid therapy is ceased. Two other important messages arise out of these case reports. Firstly, it is important to ensure that ICS therapy is appropriate for the child. The United Kingdom national survey indicated that around 20% of patients presenting with adrenal crisis were later shown not to have asthma.9 Other areas where ICS have no proven benefit are children presenting with recurrent cough18 or episodic viral wheeze.19 Secondly, in children with asthma receiving ICS therapy, it is important to minimise the dose by "back-titration" or by adding long-acting β-agonists (or both), as highlighted in recent guidelines.2,3 All our patients were taking more than 500 μg per day of fluticasone, which is currently the upper limit of the recommended dose for children.2 Further, significant dose reduction was possible without loss of asthma control, suggesting that these children were being overtreated. This report also serves to reinforce the recent guideline recommendation for specialist referral for children requiring high doses of ICS.2,3 1: Baseline investigations Daily dose of fluticasone propionate Blood glucose level (normal, > 3.5 mmol/L) Sodium level (normal, 135–145 mmol/L) Urinary sodium concentration (normal, < 20 mmol/L) Patient 1 1500 μg 1.3 mmol/L 130 mmol/L* 88 mmol/L Patient 2 (two episodes) 500–1000 μg 2.2 mmol/L < 1.2 mmol/L Not available 135 mmol/L Not available Not available Patient 3 1000 μg < 1.0 mmol/L 126 mmol/L† Not available * Specimen collected before glucose bolus. † Specimen collected after glucose bolus. 2: Adrenal investigations Stimulated cortisol level (normal, > 600 nmol/L) Adrenocorticotropic hormone level (normal, 2–10 pmol/L) Adrenal antibodies (normal, negative) Very long chain fatty acids (normal, negative) Patient 1 108 nmol/L* Not available Negative Negative Patient 2 44 nmol/L† < 1 pmol/L Negative Negative Patient 3 129 nmol/L† < 1 pmol/L Negative Negative * At time of presentation with hypoglycaemia (blood glucose level, 1.3 mmol/L). † During short Synacthen test (60 minutes after an injection of 250 μg Synacthen).

Joseph S Macdessi MB BS, DCH · Peter P van Asperen MD, FRACP · Tabitha L Randell MB ChB, MRCP, MRCPCH · Kim C Donaghue MB BS, PhD, FRACP · Geoffrey R Ambler MD, FRACP · Craig M Mellis MD, MPH, FRACP

Objective: To define the evidence for doses of inhaled corticosteroids in asthma and describe this in clinically meaningful, evidence-based terms.Data source: Cochrane Database of Systematic Reviews.Study selection and data extraction: We identified systematic reviews of randomised controlled trials of dosing of inhaled corticosteroids in asthma. Data on efficacy and safety of different doses were extracted from meta-analyses and summarised as the number needed to treat (NNT) and number needed to harm (NNH).Data synthesis: Inhaled corticosteroids were highly efficacious, with a relatively flat dose–response curve. Three patients needed to be treated with fluticasone 100 μg daily to prevent worsening asthma (NNT 3), and for fluticasone 1000 μg the NNT was 2.1 patients. The dose–response curve for side effects was steep. For a dose of fluticasone 100 μg, oral candidiasis developed in one of every 90 subjects treated (NNH 90). In contrast, the NNH for fluticasone 1000 μg and 2000 μg daily were 23 and 6, respectively.Conclusion: Level 1 evidence supports the use of low-dose inhaled corticosteroids in asthma. Clinicians should review doses of inhaled corticosteroids used for treating patients with asthma.

Heather Powell RN, MMedSci (ClinEpid) · Peter G Gibson MB BS, FRACP

To the Editor: Our recent study of patients' priorities for asthma care1,2 provides additional evidence supporting the concerns of Wilson and Robertson in their editorial questioning the possible overuse of inhaled corticosteroids.3 We have reported a qualitative study of 62 individuals who presented to an emergency department at either a central city, suburban or rural hospital, in which we explored individuals' perceptions about their asthma, its care and the impact of asthma on their lives.1,2 We also asked participants to complete a questionnaire on the use of medications and sought to amplify this information by further probing the use of medications in our qualitative data collection. Of the 82% of participants in our study currently using inhaled corticosteroid medication (51), 30% (16) were taking 1000 μg of fluticasone or equivalent daily and another 19% (10) were taking more than 1500 μg or equivalent. Current product information for fluticasone suggests a maximum dose of 1000 μg twice daily, whereas National Asthma Council (NACA) guidelines recommend that 500 μg fluticasone or equivalent daily may be the upper limit of useful effect.4,5 We also asked patients how long their medication lasted. Eleven (18%) stated that inhaled corticosteroid devices lasted three weeks or less. Use above recommended doses did not only occur for inhaled corticosteroids, but also for symptom controller medications. Twenty-four (35%) of the 31 (50%) patients receiving this medication reported that a device lasted three weeks or less, indicating use above usual recommended doses. Most patients in our study voiced concerns about the cost of asthma and drug side effects; some adjusted their medication use to manage these issues.1 In such individuals, high use or overuse of preventive and controller medication would increase both costs and side effects, partly explaining these patients' concerns. Doctors may be overprescribing inhaled corticosteroid medication because there is a discrepancy between dosages recorded in published drug information and newer recommendations for optimal inhaled corticosteroid dose.4,5 Our findings show that, in some patients, the risks associated with the use of inhaled corticosteroids are likely to be compounded by using them at higher doses than those recommended. Doctors need to be aware of this in managing patients with asthma who have severe symptoms, in whom overuse, rather than underuse, is likely to be a problem.

Dianne P Goeman · Susan M Sawyer · Michael J Abramson · Kay Stewart · Francis C K Thien · Rosalie A Aroni · Jo A Douglass