Respiratory disease

To the Editor: The approach of spring, together with high winter rainfall in and around Melbourne,1 heralds another severe pollen season, raising the risk of allergic rhinitis and asthma in pollen-sensitive individuals. It is therefore timely to report an epidemic of “thunderstorm asthma” that occurred in Melbourne during spring 2010. Thunderstorm asthma is the phenomenon of a sudden increase in acute asthma exacerbations temporally related to a thunderstorm.2 Previous epidemics in 1987 and 1989 saw up to 10-fold increases in asthma presentations to emergency departments across Melbourne over 24-hour periods.3 Those commonly affected are young adults with a history of seasonal allergic rhinitis but not necessarily asthma, and people with a previous diagnosis of asthma, many of whom do not use preventer medication.4 Rye-grass pollen is believed to be the major causative allergen in Melbourne thunderstorm epidemics.2 In Melbourne, this common springtime aeroallergen is generally filtered out by the nose due to its relatively large 20-micron diameter, causing allergic rhinitis in sensitised individuals. When exposed to moisture, such as in a developing storm cloud, osmotic stress can lead rye-grass pollen to rupture into submicronic particles that are respirable to the lower airways.2 Thunderstorms have outflow winds which concentrate these particles at ground level,4 resulting in epidemics of asthma in exposed, pollen-sensitive individuals. We analysed pollen counts and numbers of asthma presentations at the emergency department of Austin Health (a tertiary hospital servicing north-eastern Melbourne) in the days before and after the thunderstorm of 25 November 2010 (Box). There was a clear spike in asthma presentations immediately after the storm, similar in magnitude to previous epidemics.3 Although we report the experience of one institution only, this was a city-wide event that caused considerable media interest and implementation of the ambulance disaster response plan due to the large number of emergency calls received.5 Pollen counts were in the extreme range (> 100 grains/m3) during some of the days before the thunderstorm, but they were only moderate on the day of the storm (Box). Therefore, while pollen counts can be used as a guide for atopic individuals, they are not the only indicator of an allergenic environment. We propose that additional warnings of elevated risk of asthma exacerbations in pollen-allergic individuals should be made when springtime and summertime thunderstorms follow several days of high or extreme pollen counts. Individuals with seasonal asthma should use preventer medication, at least during spring, and should have an asthma management plan. Patients with allergic rhinitis should be warned of the possibility of new-onset thunderstorm asthma and advised to seek assistance rapidly if asthma symptoms manifest. Allergen immunotherapy may be administered in carefully selected individuals to prevent springtime symptoms and assessment of such patients by an allergy physician is recommended. Daily pollen counts in Melbourne and Austin Health emergency department presentations for acute asthma before and after a thunderstorm in Spring 2010* * Pollen count data were provided by Ed Newbegin, School of Botany, University of Melbourne.

Megan L Howden · Christine F McDonald · Michael F Sutherland

Position statement from the Thoracic Society of Australia and New Zealand, Australian Society for Microbiology, Australasian Society for Infectious Diseases and Public Health Association of Australia Many high-income countries with a low incidence of tuberculosis (TB) are confronting the complicated issue of the cross-border movement of people with TB from neighbouring low-income countries with a high burden of TB. Well documented examples where this is an issue include the United States–Mexico border and Scandinavian countries adjacent to Russia and the Baltic States.1,2 In Australia, we face similar dilemmas, not only with Papua New Guinea (PNG) nationals crossing into the Torres Strait Protected Zone, but also with fisherpersons illegally entering our territory, temporary residents on short-term work visas and students attending tertiary education institutions. Cross-border communicable diseases present a complex mix of clinical, public health, humanitarian, ethical, political and financial issues for governments and health care providers. Fortunately, international organisations have provided guiding principles that should underpin a country’s response to cross-border TB cases. For example, the World Health Organization (WHO) has published ethical guidelines for care of patients with TB and control of the disease.3 This document states that: . . . all governments have a fundamental obligation to provide universal access to high-quality TB diagnosis and treatment . . . universal access to TB care implies a duty to ensure the quality of that care . . . The international community must provide financial and technical assistance to countries that lack the resources to satisfy this obligation on their own. These ethical guidelines are based on numerous values including equity, solidarity, and common good (as providing effective TB treatment prevents ongoing transmission of disease, and thereby benefits everyone). Similar recommendations are made by two complementary documents, The patient’s charter for tuberculosis care (PCTC) and International standards for tuberculosis care (ISTC).4,5 These principles are also embodied in the final draft of the Australian National TB Strategic Plan (2011–2016), which is expected to be published in early 2012. In view of these international ethical guidelines, the Thoracic Society of Australia and New Zealand (TSANZ), the Australian Society for Microbiology (ASM), the Australasian Society for Infectious Diseases (ASID) and the Public Health Association of Australia (PHAA) believe that Australia’s response to any situation involving cross-border TB cases should be based on the following four principles. All patients with TB who present to health care services within Australia’s borders should have free and equal access to TB care from diagnosis to completion of treatment, irrespective of their legal status or other demographic characteristics as outlined in the PCTC.4 Health professionals dealing with these complex issues must have enough support from the relevant Australian state and federal health agencies to enable them to implement best-practice care, and should be closely engaged in the process of consultation about service delivery. Patients should only be transferred to their home country for ongoing care when the TB service in the responsible Australian state is satisfied that the patient’s ongoing care will be of a suitable standard that meets the ISTC.5 Australia should provide financial and technical support to neighbouring countries where TB is endemic, so that they can develop national TB programs meeting the ISTC standards to which Australia’s TB services can confidently return international patients, who are increasingly mobile. The development of these programs may demand an ongoing investment over many years. The complexity and cost of treating multidrug-resistant tuberculosis (MDR-TB) or TB/HIV co-infection compound the dilemmas in providing cross-border TB care. WHO estimates that the cost of treating a patient with MDR-TB is about 100 times greater than for treating a patient with drug-susceptible TB.6 Poor standards of care of patients with cross-border mobility place nations on both sides of the border at risk of dissemination of untreatable drug-resistant disease. Based on the same values of equity, solidarity and common good, the international ethical guidelines argue that the universal right to receive medical advice and treatment must extend to patients with MDR-TB and/or HIV infection.3,4 The TSANZ, ASM, ASID and PHAA therefore recommend that the above four principles should also apply to cross-border patients with MDR-TB or TB with HIV co-infection. Initial substandard care of patients with drug-susceptible TB is the greatest contributing factor to the development of MDR-TB and extensively drug-resistant TB. MDR-TB in expatriates therefore suggests that the national tuberculosis program in their home country is failing. Hence, health care professionals and governments who propose repatriating patients with MDR-TB must be wary of the level of care that will be available when those patients arrive home. The Green Light Committee, an MDR-TB working group that advises WHO and evaluates applications from countries for access to second-line antituberculosis drugs, has developed a set of criteria for assessing nascent MDR-TB treatment programs in low-income countries.7 These criteria include the level of government commitment and funding, the availability of medical personnel trained and experienced in managing MDR-TB, access to supporting laboratory services that are externally quality controlled, the reliability of second-line drug supplies, and existing strategies to assure patient adherence to treatment regimens. Australian governments and state TB services should use the same criteria when determining whether cross-border patients with MDR-TB can be safely returned to their home country for ongoing care. Although they are ethically justified, the above four principles for the care of cross-border patients with TB may appear financially onerous. Interestingly, modelling has found that increasing United States investment in TB programs in Mexico, Haiti and the Dominican Republic could reduce tuberculosis-related morbidity and mortality among migrants, and produce net cost savings for the US.8 The TSANZ, ASM, ASID and PHAA therefore strongly support the four principles described above for the care of cross-border patients with TB on ethical, clinical and public health grounds (including the protection of Australian citizens), and we believe this approach is economically justified. It is critical that all parties involved in providing care of cross-border patients with TB work together to ensure that the necessary outcomes are achieved.

Paul N Reynolds MD, PhD, FRACP · John D Turnidge MB BS, FRACP, FRCPA · Thomas Gottlieb MB BS, FRACP, FRCPA · Michael J Moore BA, DipEd, MPopHealth

To the Editor: We published a case in the Journal in 2009 titled “Spontaneous chylothorax in a 2-year-old child”.1 Subsequently, it has come to our attention that trauma is likely to have been the cause of the chylothorax. At the time of caring for the child, and submission of our article to the Journal, we had no evidence of this. We had specifically asked for a history of trauma and looked for external signs of injury. The chest x-ray and computed tomography (CT) scan had been reviewed with our radiology staff at the time and we did not detect abnormalities of the vertebrae or paravertebral tissue, and no such abnormalities were detected during surgery. However, the child presented with serious injuries 9 months later and died on arrival at hospital. At autopsy, a CT scan showed a paravertebral haematoma and vertebral injury in the lower thoracic vertebrae where the thoracic duct traverses the diaphragm and ascends on the right side (it was a right-sided chylothorax). On further review of the original chest x-ray and CT scan, it was possible to see that some of these findings were evident at the initial presentation with chylothorax. At the time of submission of our article, we speculated that vomiting could have caused injury to the thoracic duct. We now wish to highlight that apparently spontaneous chylothorax may be due to trauma. In children, non-accidental injury must be considered as a possible cause.2

Manuel E Soto-Martinez · Vanessa Clifford · Tom Clarnette · Sarath Ranganathan · R John Massie

Objective: To assess mortality trends among people with cystic fibrosis (CF) in Australia.Design and setting: We augmented Australian summary data for deaths from CF registered during 1979–2005 with information from Australian transplant centres on lung transplantation among CF patients for 1989–2005 to allow us to follow trends in all “mortality events” (death or lung transplantation).Main outcome measure: Age at death or lung transplantation.Results: Between 1979 and 2005, the mean age at death increased from 12.2 years to 27.9 years for males and from 14.8 years to 25.3 years for females. Overall, female deaths in childhood (0–14 years) occurred at an age-standardised rate of 0.40 per 100 000 (95% CI, 0.34–0.45) during 1979–2005, which exceeded the corresponding rate for males of 0.24 (95% CI, 0.20–0.28) per 100 000. Among 0–14-year-old boys, event rates declined markedly after 1989, but they declined later and more gradually for girls, with the result that the age-standardised rate for girls was 2.38 times that of boys during 1989–2005 (95% CI, 1.69–3.36).Conclusions: The pattern of CF mortality in Australia has changed substantially. Mortality rates continue to be higher for girls than for boys, but death in childhood has become uncommon. Survival has increased since 1979, but females continue to have reduced length of life.

David W Reid BSc, MB ChB · C Leigh Blizzard PhD · Dace M Shugg RN · Ceri Flowers BSc · Catherine Cash BSc · Hugh M Greville MD

Objectives: To describe the demographics, clinical features and outcomes among people with cystic fibrosis (CF) in Australia and to estimate incidence of the disease.Design and setting: Cross-sectional analysis using data from the Australian Cystic Fibrosis Data Registry for 2009.Main outcome measures: Numbers of diagnoses, pulmonary and anthropometric measurements, microbiological culture results, rates of hospitalisation and transplantation, and numbers of medical complications and deaths.Results: In 2009, data were submitted on 2986 people (48% female). Median age was 17.6 years and 49% of people were aged 18 years or over. Seventy-eight people were newly diagnosed. Fourteen people died and 14 people underwent lung transplantation in the year. Lung function and nutrition were relatively normal among children but deteriorated (more rapidly) among adolescents. With increasing age, progressive respiratory disease was apparent, and the frequency of CF-related complications and use of health care resources increased. In all age groups, there was a wide range in severity of lung disease and nutritional status.Conclusions: CF remains a progressive respiratory disease and is associated with multisystem complications. The acceleration in disease severity in adolescence and early adulthood suggests that better treatment at these stages is required to further improve survival.

Scott C Bell MB BS, MD, FRACP · Peter T P Bye MB BS, PhD, FRACP · Peter J Cooper MB ChB, FRACP · A James Martin MB ChB, MRCP, FRACP · Karen O McKay LLB(Hons), PhD · Phillip J Robinson MD, PhD, FRACP · Gerard F Ryan MB BS, FRACP · Geoff C Sims BComm, GradDip(Pop health), GradCertBiostats

Objective: To evaluate the effectiveness of the Practitioner Asthma Communication and Education (PACE) Australia program, an innovative communication and paediatric asthma management program for general practitioners.Design: Randomised controlled trial.Setting: General practices from two regions in metropolitan Sydney.Participants: 150 GPs, who were recruited between 2006 and 2008, and 221 children with asthma in their care.Intervention: GPs in the intervention group participated in two 3-hour workshops, focusing on communication and education strategies to facilitate quality asthma care.Main outcome measures: Patient outcomes included receipt of a written asthma action plan (WAAP), appropriate medication use, parent days away from work, and child days away from school or child care. GP outcomes included frequency of providing a WAAP and patient education, communication and teaching behaviour, and adherence to national asthma guidelines regarding medication use.Results: More patients of GPs in the intervention group reported receipt of a WAAP (difference, 15%; 95% CI, 2% to 28%; adjusted P = 0.046). In the intervention group, children with infrequent intermittent asthma symptoms had lower use of inhaled corticosteroids (difference, 24%; 95% CI, − 43% to − 5%; P = 0.03) and long-acting bronchodilators (difference, 19%; 95% CI, − 34% to − 5%; P = 0.02). GPs in the intervention group were more confident when communicating with patients (difference 22%; 95% CI, 3% to 40%; P = 0.03). A higher proportion of GPs in the intervention group reported providing a WAAP more than 70% of the time (difference, 23%; 95% CI, 11% to 36%; adjusted P = 0.002) and prescribing spacer devices more than 90% of the time (difference, 29%; 95% CI, 16% to 42%; adjusted P = 0.02).Conclusions: The PACE Australia program improved GPs’ asthma management practices and led to improvements in some important patient outcomes.Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12607000067471.

Smita Shah MB ChB, MCH · Susan M Sawyer MB BS, MD, FRACP · Brett G Toelle DipAppSc(Nursing), BA(Psychology), PhD · Craig M Mellis MPH, MD, FRACP · Jennifer K Peat PhD · Marivic Lagleva BSc(Hons) · Timothy P Usherwood MD, FRACGP, FRCP · Christine R Jenkins MB BS, MD

Clinical record A 17-year-old girl presented to her general practitioner with a 1-week history of fever, arthralgia, general malaise and dry cough. She had a history of systemic onset juvenile idiopathic arthritis (SOJIA), diagnosed at age 2 years and treated with aspirin, and had been in remission for 13 years. She was initially treated by her GP with oral roxithromycin, and admitted to hospital 3 days later with worsening of her symptoms. Her admission chest x-ray (Box 1) revealed bilateral perihilar infiltrates. A diagnosis of severe community-acquired pneumonia was made and broad spectrum antibiotics were commenced, including vancomycin, moxifloxacin, and oseltamivir. Despite this treatment, her condition deteriorated. On Day 3 of admission she required endotracheal intubation and circulatory support with noradrenaline 18–50 μg/kg/min, and was admitted to the intensive care unit (ICU). She remained hypotensive, with a mean arterial pressure of 50 mmHg, and with sinus tachycardia of 132 beats/min, and subsequently required renal replacement therapy. She remained febrile for the first 3 days after admission (temperature range 37.5°C–39°C), and her temperature settled to normal after appropriate therapy was initiated. Investigations included a computed tomography scan of her abdomen, which showed hepatosplenomegaly, and liver function tests, which showed elevated conjugated bilirubin (36 mmol/L; reference range [RR], < 4 mmol/L), γ-glutamyl transferase (84 U/L; RR, < 24 U/L), lactate dehydrogenase (3540 U/L; RR, 150–280 U/L), alanine aminotransferase (108 U/L; RR, 10–30 U/L) and aspartate transaminase (388 U/L; RR, < 30 U/L). Other abnormal parameters were her haemoglobin level (93 g/L; RR, 120–160 g/L), platelet count (65 x 109/L; RR, 150–400 109/L), white cell count (2.9 x 109/L; RR, 4.5–13 x 109/L), international normalised ratio (2.1; RR, 0.9–1.2) and fibrinogen level (0.9 g/L; RR, > 2.5 g/L). Elevated inflammatory markers included C-reactive protein (301 mg/L; RR, < 5 mg/L) and serum ferritin (50 500 μg/L; RR, 7–140 μg/L). A transthoracic echocardiogram showed a left ventricular ejection fraction of 60%, a mild reduction in right ventricular contractility, and a right ventricular systolic pressure of 48 mmHg. A full screen for sepsis was performed, including a nasopharyngeal aspirate, bronchoalveolar lavage, blood cultures and serological testing; all were unremarkable. Other immunological tests performed were for Mycoplasma pneumoniae antibodies, Streptococcus pneumoniae urinary antigen, Legionella pneumophila urinary antigen, herpes simplex virus, cytomegalovirus, Epstein–Barr virus (EBV) IgM and IgG, influenza A and B, H1N1 influenza RNA, respiratory syncytial virus, parainfluenza and adenovirus DNA, Q fever (Coxiella burnetti) IgM and IgG, and serological tests for hepatitis, dengue fever IgM and Leptospira IgM, all of which were non-reactive. Urinalysis revealed a white blood cell count of 140 x 106/L (RR, < 10 x 106) and an erythrocyte count of > 500 x 106/L (RR, < 10 x 106/L) with no microbial growth on culture. A bone marrow aspirate with trephine was performed on Day 4 (Day 2 in the ICU), and EBV DNA was detected in the resulting sample using a qualitative DNA test. The patient’s failure to improve, in combination with her past history of SOJIA, hepatosplenomegaly and a very high ferritin level led to a preliminary diagnosis of macrophage activation syndrome (MAS). Immunosuppressive treatment in the form of high-dose methylprednisolone (10 mg/kg daily) and intravenous immunoglobulin (1 g/kg daily) were commenced. Inotrope and ventilatory requirements improved within 24 hours of this treatment. On Day 9 of admission she was extubated, and was discharged home on high-dose steroids 8 days later with no complications. Her bone marrow aspirate histological examination showed haemophagocytosis which confirmed the diagnosis of MAS (Box 2). Macrophage activation syndrome (MAS) is a severe, potentially fatal condition associated with paediatric rheumatic diseases. It is a form of secondary haemophagocytic lymphohistiocytosis (HLH) with uncontrolled activation and proliferation of well differentiated macrophages and T-lymphocytes.1,2 The central pathophysiological abnormality in HLH is cytokine dysfunction, resulting in uncontrolled accumulation of activated T-lymphocytes and activated histiocytes (macrophages) in many organs. High levels of cytokines are found in these patients due to ineffective natural killer cells and T-lymphocytes (a positive feedback loop started by ineffective T-cells, triggering an unopposed release of cytokines that attracts further T-cells).3 Hyperactivated macrophages cause damage in different tissues, and this is thought to be the origin of the high serum ferritin levels characteristic of these conditions. The cause of the macrophage activation is multifactorial. Ineffective cytotoxic immunity is due to underactive natural killer cells and reduced perforin production. Secondary HLH can be precipitated by infection, drugs, malignancy and rheumatic diseases. SOJIA has been linked to polymorphisms in genes controlling production of cytokines, such as tumour necrosis factor. This could in turn be a cause for MAS, leading some authors to postulate that MAS and SOJIA could be part of the same disease.4 Clinical manifestations include fever (91%–100%), hepatomegaly (90%–92.3%), splenomegaly (77%–84%), lymphadenopathy (41%–62%), neurological symptoms (47%) and rash (43%).5,6 The central nervous system is commonly affected,7 and patients may present with agitation, seizures, coma, respiratory failure from adult respiratory distress syndrome, and multiorgan failure.7 MAS has a mortality of up to 22%.8 To our knowledge, this is the only reported case of MAS in a patient nearing adult age and with a long inactive rheumatic disease period. MAS is well described in the paediatric population with SOJIA, and has a median age of 5 years at the time of presentation.9 The mean time between initial diagnosis of SOJIA and presentation with MAS is 4 years.8 Our patient was aged 17 years at the time of presentation with MAS, and had not had symptoms of, nor required treatment for, SOJIA for 13 years. Diagnosis was described by Ravelli and colleagues,7 and is based on clinical findings such as organomegaly and laboratory findings such as hypofibrinogenaemia, thrombocytopenia and elevated serum liver enzymes. A bone marrow aspirate can aid diagnosis in uncertain cases, the pathognomonic feature being the presence of well differentiated macrophages actively phagocytosing haemopoietic cells.8 Infections, medications and malignancies have all been identified as triggers for MAS. EBV DNA was found in the patient’s bone marrow aspirate, and EBV has been identified as one of the more common triggers for MAS.5,7 It is likely that EBV was the trigger for this patient’s MAS. Treatment is based on immunosuppression using steroid therapy. Cyclosporin has been used as the first-line treatment, or used in combination with corticosteroids. Other treatment options include plasma exchanges or intravenous immunoglobulins.10 This patient presented with fever, prominent respiratory failure and cardiovascular collapse. Her initial systemic symptoms and radiological findings suggested severe sepsis, most likely respiratory in origin, her SOJIA had been in remission for over 10 years, and there was no neurological involvement. These factors made clinical suspicion of MAS difficult, but her hepatosplenomegaly and highly raised ferritin levels suggested the diagnosis, which was supported by her laboratory test results (leucopenia, thrombocytopenia, hypofibrinogenaemia and abnormal liver function test results) and bone marrow aspirate histological findings (Box 2). Despite MAS predominantly presenting in a paediatric population with active disease, this case report emphasises the need to exercise diagnostic vigilance in treating young adult patients with multiorgan failure and a distant history of rheumatic disease. Lessons from practice Multiorgan dysfunction and vasodilatory shock may not be of infectious origin. If a patient fails to improve when treated with broad spectrum antimicrobials, alternative diagnoses should be sought. Although macrophage activation syndrome (MAS) primarily affects children with active rheumatic disease close to the time of diagnosis, it may occur in adults after a prolonged disease-free period. Diagnosis of MAS is based on history, clinical examination and laboratory findings. Demonstrating haemophagocytosis in a bone marrow aspirate can aid uncertain diagnosis. 1 Chest x-ray of the 17-year-old patient, taken on admission, showing bilateral perihilar infiltrates 2 Macrophage (long arrow), containing a red blood cell (arrow head), seen in the bone marrow aspirate taken from the 17-year-old patient (May–Grünwald–Giemsa stain x 100)

David Gutierrez MD · Louis Guy MB BS · Veera S Katikireddi MB ChB(Hons), MRCP(UK) · Jason P Butler MMedSci, FRACP, FRCPA · John Gowardman FRACP, FCICM

Cause of chylothorax: In “Spontaneous chylothorax in a 2-year-old child” in the 2 March 2009 issue of the Journal (Med J Aust 2009; 190: 262-264), the cause of chylothorax was unknown, but attributed to strenuous vomiting. Additional information has become available and trauma is now thought to have been the cause. In a child, this raises the possibility of non-accidental injury. Further details are published in this issue of the Journal (See Soto-Martinez et al).

Manuel E Soto-Martinez · Vanessa Clifford · Tom Clarnette · Sarath Ranganathan · R John Massie

Asbestos manufacturers have never warned homeowners of the risks of renovation On the Australian mainland, there have only been two manufacturers of asbestos cement products used in home construction and renovation: James Hardie and Wunderlich, a subsidiary of CSR. Asbestos products were manufactured from the 1920s up until 1984, when Hardies ceased using asbestos in their building products (Wunderlich had been acquired by James Hardie in June 1977). In 1978, James Hardie boasted that their products were in most homes in Australia. The range of asbestos cement building products (once widely known as “fibro”) that were made in Australia include flat and striated walls, eaves and panels; corrugated panels (used primarily for fencing and roofing); flat sheets covered with crushed or artificial brick; flues for gas heaters; thick sheets for flooring or as tile underlay; and sheets covered with coloured or patterned vinyl used in bathrooms and other wet areas. As the country with the highest rate of mesothelioma in the world,1 Australia has lived through two “waves” of asbestos-related disease — the first from the mining of asbestos and the manufacturing of asbestos products, and the second from asbestos use in industry. In this issue of the Journal, Olsen and colleagues clearly reveal that the “third wave” of the asbestos disease epidemic in Australia comprises non-industrial users of asbestos products,2 and a significant contributor to this cohort are the non-professionals who cut and fixed asbestos cement products in home renovation or maintenance and other do-it-yourself activities, or who demolished asbestos cement products during renovations. Family members present during these activities are also part of this cohort. The most alarming feature of this third wave is its potential to continue to grow for many years to come. Neither James Hardie nor CSR have ever taken any steps to systematically warn people who have asbestos products in their homes — including products that contain the highly dangerous Wittenoom blue asbestos used by both manufacturers — of the potential for fatal consequences in 20–40 years if they demolish those products today. We contend that the manufacturers have a legal duty of care to these people (Box). Claims for compensation and damages for people with asbestos disease because a manufacturer breached a duty of care have been pursued for over 25 years. Many of the legal precedents derived from the early claims against CSR by workers at the Wittenoom mine, and against James Hardie by its employees, have been applied in these product-user claims. Most mesothelioma claims are now successfully resolved out of court without a trial. When this does not occur, the claims primarily involve one or two instances of construction or demolition. The major issues of controversy are (i) the claimant’s ability to prove that the manufacturer could, and should, have taken steps that would (before the time of exposure) have drawn the risk to the user’s attention; and (ii) proving, more probably than not, that the exposure in such limited circumstances was a cause of, or made a contribution to, the mesothelioma manifesting many years later. Almost from the first acceptance in 1960 of mesothelioma as a cancer uniquely related to asbestos, it has been recognised that this cancer could be caused by very low exposures.1 The argument is sometimes put that mesothelioma can occur without asbestos exposure at all, or can be caused by exposure to the very low “background” levels present in most urban environments and some non-urban environments. In reality, in an individual mesothelioma case, all cumulative asbestos exposure — “background”, unrecalled or unrecognised exposure, and specifically recalled exposure — must, on biological mechanistic grounds, be considered to be playing a part in causation.3 With acceptable evidence of specific exposure, no matter how slight, a claimant should succeed, as such exposure would add more than a minimal dose to any background exposure. No threshold for asbestos causation of mesothelioma has been demonstrated.4,5 The article by Olsen et al documents an upward trend in mesothelioma cases in home renovators.2 This trend was appearing in reports of the Australian Mesothelioma Register operated by the National Occupational Health and Safety Commission (NOHSC) up to 2001.6 However, until now, it has not been possible to statistically confirm the trend, because of incomplete coverage of the Register from 2001 onwards. This was a consequence of the drastic cutbacks in the scientific capacity of the NOHSC, and over-stringent privacy legislation preventing comparisons with state cancer registries and the collecting of data on exposure history. We hope that the newly reconstituted Australian Mesothelioma Registry collaboration, administered by the New South Wales Cancer Council, and covering all mesothelioma cases in Australia diagnosed after 1 July 2010, will enable continued monitoring across the whole of Australia of this tragic third wave of the mesothelioma epidemic. While the Western Australian Mesothelioma Register study2 and the new Australia-wide initiative will be of small comfort to those who already have or will develop mesothelioma, these initiatives may assist in maintaining an awareness of the risks of exposure during home maintenance, and of other possibly unrecognised exposures, and hasten regulatory and control activities both nationally and internationally. All asbestos use was banned in Australia in 2003, and it is also banned in 56 other countries. (There are a few very limited, technical exceptions to the ban; eg, for military use where no substitute is available.) However, there are a few countries where it is still being used in building products (eg, India, Thailand, Russia, China and Indonesia). Data from Australian registers serve a very important purpose in sending a global warning of the deadly nature of this substance and the need for a complete global ban on any future use.7 The legal duty of care A manufacturer of an asbestos cement building product owes a legal duty of care to users of the product. The duty obliges the manufacturer to take reasonable care that a person is not at risk of suffering a foreseeable injury from using the product. A foreseeable injury is one of which the manufacturer, knowing the way the product is used, and up to date with the literature concerning injury from use of such a product and any potentially dangerous components or ingredients of that product, is, or ought to be, aware. As asbestos cement building products were used in homes, people who used the new product in the construction or renovation of their homes were owed the duty, as will the people who later demolish and remove the product, as both uses should be contemplated by the product manufacturer. The steps required of the manufacturer to discharge this duty — ceasing manufacture, warning, and recall — will be proportionate to the likelihood, and the potential seriousness, of the injury. If a person is injured because of a breach of the duty of care, they are entitled to compensation commensurate with the loss and harm suffered.

John R C Gordon BJuris, LLB · James Leigh MD, FAFOEM, FAFPHM

Objective: To determine trends in incidence of malignant mesothelioma (MM) caused by exposure to asbestos during home maintenance and renovation.Design, setting and participants: Using the Western Australian Mesothelioma Register, we reviewed all cases of MM diagnosed in WA from 1960 to the end of 2008, and determined the primary source of exposure to asbestos. Categories of exposure were collapsed into seven groups: asbestos miners and millers from Wittenoom; all other asbestos workers; residents from Wittenoom; home maintenance/renovators; other people exposed but not through their occupation; and people with unknown asbestos exposure; or no known asbestos exposure. Latency periods and age at diagnosis for each group were calculated and compared.Results: In WA, 1631 people (1408 men, 223 women) were diagnosed with MM between 1960 and 2008. Since 1981, there have been 87 cases (55 in men) of MM attributed to asbestos exposure during home maintenance and renovation, and an increasing trend in such cases, in both men and women. In the last 4 years of the study (2005–2008), home renovators accounted for 8.4% of all men and 35.7% of all women diagnosed with MM. After controlling for sex and both year and age at diagnosis, the latency period for people exposed to asbestos during home renovation was significantly shorter than that for all other exposure groups, but the shorter follow-up and difficulty recalling when exposure first occurred in this group may partly explain this.Conclusions: MM after exposure to asbestos during home renovation is an increasing problem in WA, and these cases seem to have a shorter latency period than other types of exposure. MM cases related to renovation will probably continue to increase because of the many homes that have contained, and still contain, asbestos building products.

Nola J Olsen BAppSc, RGN · Peter J Franklin BSc(Hons), PostGradDipEnvSci, PhD · Alison Reid RGN, MSc, PhD · Nicholas H de Klerk BSc, MSc, PhD · Timothy J Threlfall MB BS, MPH, PhD · Keith Shilkin FRCPA, FCRPath, FHKCPath · Bill Musk FRACP, MSc, MD

Desley and Les Carbon are preparing for a much-anticipated road trip from their home in Perth up the Western Australian coast to Exmouth. “I’ve just purchased a couple of large fishing rods”, says Mr Carbon. “My wife loves fishing but she’s allergic to fish — so if she catches any I’ll eat them!” The couple in their 60s are looking forward to a few weeks of relaxation after what’s been a difficult 18 months. Early last year, Mrs Carbon began experiencing recurrent flu-like symptoms, with a hacking cough and difficulty breathing. Multiple courses of antibiotics did little to relieve the symptoms. Her asthma worsened, and she was diagnosed with pneumonia. She had a litre of fluid drained from her lungs, but continued to experience chest pain. “I saw a specialist and said ‘why do I still have pain, when all the fluid’s gone?’” She had various chest x-rays and a CT scan, but nothing showed up. In April, after a PET scan followed by a biopsy, Mrs Carbon was diagnosed with pleural mesothelioma. “The first question I asked was, ‘How long have I got?’ The doctor said 12 months. But I hope I will get a bit longer than that.” **** Mesothelioma is a rare and fatal cancer of the pleura or peritoneum, almost always caused by exposure to asbestos. As Nola Olsen and colleagues write in this issue of the Journal, asbestos was mined and used widely as a building material for decades in Australia. Until the 1960s, 25% of all new homes used asbestos cement cladding. The legacy of this era is that Australia now has the highest mesothelioma rate in the world.1 Historically, mesothelioma was mainly an occupational cancer, but Mrs Carbon is one of a growing number of people with the disease who were exposed to asbestos at home, particularly during renovations or home maintenance. Olsen and coauthors find that although the number of cases associated with occupational asbestos exposure has plateaued, those related to domestic exposure continue to rise. “Malignant mesothelioma cases associated with home maintenance and renovation have increased markedly over the past 10 years and remain on an upward trend”, they write. This group of mesothelioma cases has been called the “third wave”, and it is not known when this wave will peak. The first wave affected workers involved in mining, milling and manufacturing asbestos products, while the second wave comprised workers who used asbestos products in industry, such as builders and plumbers. Margaret Kent, practice group leader in asbestos litigation at Slater & Gordon lawyers, has been obtaining compensation for people with asbestos diseases for the past 15 years. Like Olsen and colleagues, she has noted a “gradual and very discernible” trend in the nature of asbestos exposure among people seeking compensation for mesothelioma. “The decrease in occupationally exposed people and the increase in non-occupationally exposed people have been very obvious. Once upon a time most people who called us would be occupationally exposed but that’s not the case any more.” Clients have included people who developed mesothelioma after washing the clothes of their husband or father who worked in the asbestos industry, people living near a business that used asbestos, or painters who’ve sanded back asbestos-laced walls. Although most of Slater & Gordon’s clients are over 60 years of age, some are in their 30s and 40s. The youngest that Ms Kent has worked with was only 22 years old and may have been exposed as a toddler. **** As an indication of how ubiquitous asbestos is in Australia, Mrs Carbon has identified six occasions when she may have inhaled asbestos fibres, starting from when she was a young girl watching her uncle build extra bedrooms on to their farmhouse. “I used to help my uncle hold the big asbestos sheets while he was cutting them. We would play with the bits that fell off.” At age 25, and newly married, she lived in a house in Albany, WA. When Cyclone Alby tore the asbestos-laden roof off the house in April 1978, she and her husband lifted the pieces of broken roof to be cleared away. The newlyweds renovated their house, including sanding down the eaves, which also contained asbestos. “We used a steel wire brush, and sometimes we used sandpaper. There was lots of dust going everywhere.” Mrs Carbon knew other people with mesothelioma at the time of her diagnosis, but she was shocked to be diagnosed herself. “I had thought it could be cancer, but I never for one minute thought that it was mesothelioma.” **** Ms Kent from Slater & Gordon says there is still a public perception that mesothelioma is an occupational disease. She says most people exposed to asbestos during home renovation had no idea of the dangers and receive a “particularly bad and huge shock when they discover they have an asbestos-related illness”. She is concerned that there is a lot of misinformation in the community about the nature of asbestos and the potential risks of home renovation. “It worries me. We’re a great renovating country and the estimate is that one in three houses has some asbestos in it. Increasingly, people don’t know what it looks like, and they don’t understand that it’s very hazardous, potentially even in small quantities.” She adds that do-it-yourself TV shows have a role to play in increasing awareness of the risks of home renovation. “If they show pictures of people hacking with sledgehammers into asbestos sheeting, then it’s incredibly irresponsible, but if an explanation of the hazards is given, and some attempt to demonstrate doing it properly — then that could be a good thing.” Ms Kent’s concerns are shared by Unions NSW, which passed a unanimous resolution last month, calling on home renovation TV shows to include on-air warnings about the dangers of asbestos. Network Ten’s TV program The Renovators did not respond to the Journal’s request for a comment. Mrs Carbon agrees that there needs to be greater awareness of the risks of home renovation. “You have to be very careful; it only takes one fibre. You really have to wear masks, but we didn’t. We didn’t know anything about it.” **** Mrs Gladys (Joyce) Hyde, aged 78, was similarly surprised when she was diagnosed with mesothelioma 18 months ago, particularly given that she had never worked with asbestos or handled it during home renovation. Her asbestos exposure was indirect and probably occurred when she was living with her family in south-west Melbourne. They were next door to an agricultural company that conducted substantial building work in the late 1970s and early 80s. No one warned the family of possible risks and she had no idea her health was potentially in danger. “We didn’t think about it at all.” She was admitted to hospital 18 months ago because she was having difficulty breathing. “I could barely get to the bathroom to have a shower, it was that bad.” She ended up having five litres of fluid drained. “When they found the mesothelioma, it was a shock.” Professor Bill Musk, a Perth-based respiratory physician, says patients with mesothelioma typically present to their GP with chest pain or breathlessness. “The GP then does a chest x-ray and finds something on it, particularly pleural effusion.” A cell sample to confirm the diagnosis is usually obtained by aspirating the pleural effusion, but false negative results are common. A closed biopsy, a video-assisted thoracoscopic biopsy, or occasionally an open biopsy, can also confirm the diagnosis of mesothelioma. **** Mesothelioma is an unpredictable disease. Once diagnosed, the median survival is 9 to 12 months, but it is difficult to give an accurate prognosis. “Occasionally, a patient survives 10 to 15 years”, says Professor Musk. And although the cancer is almost always linked to asbestos exposure, it’s impossible to predict who, of those exposed, will develop the cancer. Mr Carbon has luckily not developed the disease, despite having sanded back the same eaves with his wife in Albany in the late 1970s. He also had a career as a ship’s master, which involved putting asbestos lagging on exhaust pipes, and later breaking it off when it became hard and brittle. “It was the most dangerous thing we could do to it, but I’ve never experienced any problems”, he said. Mrs Hyde is also acutely aware of the unpredictability of mesothelioma. “My oncologist said that a man could work with asbestos all of his life and never get it, but his wife could wash his clothes and get it. His view was it’s just the luck of the draw.” **** At the urging of her grandson, Mrs Hyde approached the law firm Slater & Gordon to seek compensation. Slater & Gordon’s defendants have included everyone from asbestos manufacturers, James Hardie and Wunderlich (a subsidiary of CSR), to state and federal government bodies. Legal claims focus on proving that there was a failure to warn of the dangers or of the need to take precautions, or to provide ways of minimising the asbestos dust. “It ranges from failure to put a warning on the product to failing to inform the public of the known dangers”, says Ms Kent. As lawyer John Gordon writes in this issue of the Journal , neither James Hardie nor CSR have ever taken any steps to systematically warn people of the dangers of asbestos products in their homes, or “of the potential for fatal consequences in 20 to 40 years if they demolish those products today”. **** Both Mrs Hyde and Mrs Carbon have had chemotherapy. “I’m waiting for 4 weeks to see if the cancer has shrunk. I’m a bit in limbo at the present”, says Mrs Hyde. A grandmother of 10, she is enjoying time with her family. Twice a week she helps with reading lessons at the school where her daughter works. “That’s been fabulous”, she says. She used to be a keen lawn and tenpin bowler, but the cancer and treatment have tired her out. “I was always reasonably active, and then to get something like this and it mucks everything up. It is hard but I’ve got a good family. You just have to keep on going.” Mr and Mrs Carbon are also pushing on. With the oversized fishing rods packed in their motorhome, they’re taking their minds off the diagnosis for a few weeks. “When I was first told it was mesothelioma I thought, ‘how am I going to get this out of my mind? I was thinking about it all day’”, Mrs Carbon says. Mr Carbon says the couple are only now coming to realise the full impact of the diagnosis. “But we’re boxing on and trying to enjoy life, making the most of every minute.”

Sophie McNamara

Objectives: To compare the clinical diagnosis of chronic obstructive pulmonary disease (COPD) with results of post-bronchodilator spirometry in general practice, and examine practitioner, practice and patient characteristics associated with agreement between clinical and spirometric diagnoses.Design, setting and participants: General practitioners from practices in Sydney identified eligible patients aged 40–80 years seen in the past year and prescribed respiratory medications whom they regarded as having COPD. Between November 2006 and April 2008, we collected information on the GPs and their practices, and demographic information, smoking status, comorbidities, respiratory medicines use, vaccination status, quality of life and spirometry results for participating patients.Main outcome measures: Frequency of COPD diagnosis on spirometry; odds ratios for characteristics associated with agreement between clinical and spirometric diagnoses.Results: 56 GPs from 44 practices participated in the study. Of 1144 eligible patients, 445 were recruited (mean age, 65 years; 49% male). Of these, 257 (57.8%) had post-bronchodilator spirometry consistent with COPD ± asthma, 16 (3.6%) had asthma only, 82 (18.4%) had normal spirometry, and 90 (20.2%) had other spirometric diagnoses. Having a spirometer in the practice was not predictive of agreement between clinical and spirometric diagnoses. Older patient age was significantly associated with correct diagnosis, while higher numbers of comorbidities were associated with misdiagnosis.Conclusions: A substantial proportion of patients clinically identified as having COPD in general practice do not have the condition according to spirometric criteria, with inaccurate diagnosis more common in patients with comorbidities. Policy and practice change is needed to support the use of spirometry in primary care.

Nicholas A Zwar MB BS, PhD, FRACGP · Guy B Marks MB BS, PhD, FRACP · Oshana Hermiz MB BS · Sandy Middleton PhD · Elizabeth J Comino BVS, PhD · Iqbal Hasan MB BS · Sanjyot Vagholkar MB BS, MPH · Stephen F Wilson MB BS, PhD, FAFRM

To the Editor: Animal and human studies confirm the view that colonisation by non-typeable Haemophilus influenzae (NTHi) of airways already damaged by inhaled toxins initiates a second major pathway of damage in chronic obstructive pulmonary disease (COPD). This provides a framework for novel and effective management strategies for this condition, which has previously been considered to be a self-induced disease of elderly people for which nothing can be done.1 Acute exacerbations of COPD are recognised as critical determinants of acute and long-term outcomes. They represent a shift within the bronchus of the balance between two pressures — colonising NTHi and protective recruitment of phagocytic cells — that favours the bacteria and results in an inappropriate and excessive inflammatory response. A novel oral vaccine that reduces acute exacerbations in COPD is currently undergoing an advanced clinical trial in 21 centres across Australia. Oral immunotherapy with enteric-coated inactivated NTHi enhances the efficiency of mucosal immune protection (Box). In a rodent model, specific T cells, derived from stimulation of Peyer’s patches by orally administered NTHi, enhanced clearance of bacteria from the bronchus by recruiting and activating phagocytes.2 In mice co-infected with NTHi and influenza virus, oral administration of NTHi abrogated the increase in levels of both bacteria and virus, suggesting NTHi is a final common pathway for both viral and bacterial infections.2 In humans who smoke, seasonal increase in circulating specific T cells was significantly augmented after oral immunotherapy with NTHi, blocking access of inhaled NTHi into peripheral airways.3 These data support a mechanism whereby NTHi increases physiological protection based on aspiration of bronchus content into the gut. Qualitative2-4 and quantitative2,3 sputum analysis showed that protection was correlated with a reduction of all pathogens and a significant 3-log fall in NTHi, as expected from specific activation of a non-specific clearance mechanism (phagocytosis). In COPD, T cell-recruited neutrophils within sputum undergo a phenotypic change characterised by longevity and enhanced phagocytosis, maintained by autocrine loops.2 Early clinical trials4 of oral immunotherapy showed reductions in the frequency and severity of exacerbations, with consistent decreases in antibiotic usage of more than 50%. A potent and well characterised NTHi isolate with broad cross-protection in screening assays has now been developed for use as the vaccine HI-164OV (unpublished data). Phase II clinical studies of the vaccine have shown it is safe and effective3 and resulted in significant reductions in exacerbations treated with systemic corticosteroids (63%) and hospital admissions (90%)5 among patients with severe COPD taking best-practice treatment. Phase IIb trials are now underway. Evidence of IgE antibody to NTHi in both COPD and treatment-resistant asthma predicts broader clinical value for oral therapy with HI-164OV, through its capacity to prevent inhaled bacteria (allergens) penetrating into small airways.3 Enhancement of mucosal immune protection by oral immunotherapy with enteric-coated inactivated non-typeable Haemophilus influenzae1 Aspiration of bronchus content (including bacteria) into the gut (1) stimulates Peyer’s patches (3) to release T lymphocytes that “home” to the bronchus (4). T lymphocytes — directly or indirectly — secrete cytokines and chemokines that augment recruitment and activation of phagocytes (5). Phagocytes reduce the colonising load of bacteria in the damaged bronchus mucosa. Ingestion of inactivated non-typeable Haemophilus influenzae (2), as a vaccine, augments this protective loop.

Robert L Clancy · Margaret Dunkley

To the Editor: Grills eloquently informs readers on the dangers of the Easter bunny and chocolate, and reminds us that Easter eggs may pose a choking hazard.1 It is worth noting that the foil used to wrap Easter eggs also poses a health risk. This was demonstrated in the case of a 20-year-old woman who presented to hospital with respiratory distress after inhaling foil wrapping from an Easter egg.2 The foil wrapper had been pushed inside the woman’s salbutamol inhaler by her 2-year-old son and subsequently occluded her left lower lobe bronchus after she used her inhaler.

Mark Naunton

To the Editor: A recent study of adult bodyweights recorded in 199 countries showed an increase in mean body mass index (BMI) of 0.4 kg/m2 per decade between 1980 and 2008.1 The increase in Australia was even greater: 0.9 kg/m2 for men and 1.2 kg/m2 for women.1 This increase in BMI, sometimes referred to as an “obesity epidemic”, has also been reported in coronial cases in South Australia, with the percentage of morbidly obese individuals (BMI > 40 kg/m2) undergoing autopsy rising from 1.3% to 4.8% between 1986 and 2006.2 While attention is often focused on complications of obesity such as diabetes mellitus, hypertension and cardiac disease, there is also a link to pulmonary thromboembolism (PTE). A recent prospective forensic autopsy series found that 24 of 32 cases of fatal PTE were in individuals who were overweight or obese.3 To examine this association further, we performed two analyses. First, we recorded the numbers of sudden deaths subject to coronial autopsies in SA from 2000 to 2009 (inclusive) where the cause of death was PTE. These were divided into two periods (2000–2004 and 2005–2009) and expressed as the percentage of the total number of coronial autopsies. Second, we analysed all deaths due to PTE that were the subject of coronial autopsies in SA in 2008 (the most recent year for which complete autopsy data were available at the time that the study was initiated). Age, sex and BMI were recorded, and the group was compared with an age- and sex-matched control group taken from other coronial autopsy cases. Despite considerable yearly fluctuations, the death rate due to PTE showed a small increase over time (Box). The rate of deaths due to PTE per total number of autopsies increased from 3.59% (198/5521) in 2000–2004 to 3.71% (239/6442) in 2005–2009. In 2008, there were 44 individuals (21 men, 23 women) with PTE as cause of death. The age range of this group and the 44 matching controls was 27–93 years (mean, 67 years). The mean BMI for individuals dying of PTE (29.6 kg/m2; range, 19.0–51.8 kg/m2) was significantly higher than for the controls (25.9 kg/m2; range, 17.7–44.6 kg/m2) (Student t test, P < 0.05). If PTE is conclusively found to be associated with BMI, there may be significant effects on hospital diagnostic services, coronial forensic investigation units and public expenditure in the future. Coronial cases in South Australia where death was due to pulmonary thromboembolism, 2000–2009

Roger W Byard · Hannah Rosenfeld

The Thoracic Society of Australia and New Zealand has updated its guidelines on corticosteroid use in childhood asthma The understanding of childhood asthma has increased substantially since the publication of the Thoracic Society of Australia and New Zealand (TSANZ) position statement The role of corticosteroids in the management of childhood asthma in 2002.1 In particular, recognition of the need for separate asthma management guidelines for children aged 5 years or younger has increased,2 and considerably more clinical research evidence on the role of asthma medications in children has become available. The 2010 revision of the TSANZ position statement provides updated recommendations on the roles of inhaled corticosteroids, oral corticosteroids, leukotriene receptor antagonists and combination medications (inhaled corticosteroids plus long-acting β-agonists) in childhood asthma management based on recently published evidence.3 The role of leukotriene receptor antagonists in the management of childhood asthma has also been addressed in detail in a recent National Asthma Council Australia information paper.4 The National Asthma Council Australia provides a comprehensive overview of the role of preventive treatment in childhood asthma in its Asthma management handbook 2006.5 It advocates a stepwise approach to drug therapy that is based on asthma severity. If control is not achieved using initial preventer therapy, it is important to review the diagnosis of asthma — particularly in children aged 5 years or younger — as many children with recurrent cough are mislabelled as having asthma6 and different wheezing phenotypes require different treatment approaches.2 Before escalating the level of preventer therapy, it is also essential to check the child’s inhaler technique and adherence to treatment. Step-down treatment (“back titration”) is advocated once control has been achieved and sustained for at least 3 months. Two placebo-controlled studies of montelukast have established the efficacy and safety of this medication and form the basis of its current Pharmaceutical Benefits Scheme listing for children with frequent intermittent or mild persistent asthma.3,4 Compared with placebo, regular montelukast therapy produces a modest reduction in exacerbation risk in children with viral-induced wheezing.3,4 An additional benefit of montelukast therapy is its proven efficacy for protecting against exercise-induced bronchoconstriction,3,4 being more effective than long-acting β-agonists without development of the tolerance seen with long-acting β-agonists.3 This information led to the current Pharmaceutical Benefits Scheme listing of montelukast for children aged 6–14 years who have ongoing activity-related asthma despite inhaled corticosteroid treatment. The effectiveness of prophylactic inhaled corticosteroids in persistent childhood asthma is well established.3 In contrast, regular inhaled corticosteroid treatment for intermittent, viral-induced wheezing does not reduce rates of hospitalisation, use of oral corticosteroids, or frequency and duration of acute episodes.3 Systemic effects of inhaled corticosteroids in children are well documented; they include impaired linear growth, adrenal suppression, and effects on bone mineralisation.3 Although the clinical significance of these adverse effects is uncertain, factors such as individual susceptibility, severity of asthma, age, pubertal status, total dose, and dose delivery may affect risk of systemic toxicity. Although it is common to add a long-acting β-agonist to inhaled corticosteroids (as a single combination inhaler) there are few paediatric studies examining this practice, and these suggest that, while the combination improves lung function, it does not reduce exacerbation risk — in fact, it may increase it.3 These recent studies support the current National Asthma Council recommendations of reserving the addition of long-acting β-agonists for children with asthma that is not adequately controlled by 200–250 μg/day fluticasone propionate or equivalent doses of other inhaled corticosteroids,3 and highlight the potential role of montelukast as an alternative add-on therapy. The use of long-acting β-agonists is not, however, recommended for children aged 5 years or younger.2,3 Our recommendations for preventer treatment in childhood asthma are summarised in the Box. Children with infrequent intermittent asthma require no preventer therapy. Current evidence suggests that non-steroidal preventers should be trialled first in children with frequent intermittent or mild persistent asthma, while inhaled corticosteroids are indicated as first-line preventer treatment in children with moderate–severe persistent asthma. Long-acting β-agonists or montelukast are add-on options in children with persistent symptoms despite adequate inhaled corticosteroid treatment. In terms of acute asthma management, oral corticosteroids improve outcomes in children presenting to hospital with acute asthma, but the efficacy of oral corticosteroids for children aged 5 years or younger with acute, mild–moderate, viral-induced wheezing has been questioned.3 Based on current evidence, we recommend oral corticosteroids be reserved for children with moderate–severe acute asthma exacerbation and children with an incomplete response to β-agonists. However, in children aged 5 years or younger (particularly those with intermittent, viral-induced wheezing) the use of oral corticosteroids should be limited to those with severe wheeze who require hospital admission; an initial dose of 2 mg/kg prednisolone (maximum 60 mg) is recommended, followed by daily doses of 1 mg/kg if required. Although a 3-day course is generally sufficient, a more prolonged course may be indicated in severe cases. There is some evidence for the benefit of intermittent inhaled corticosteroids and leukotriene receptor antagonists in acute asthma, but oral corticosteroids remain the treatment of choice — particularly for more severe episodes, because of ease of administration, low cost and greater proven efficacy in severe acute asthma. The need for recurrent systemic corticosteroid therapy requires reassessment of the child’s interval therapy, particularly in cases of persistent asthma, and specialist referral. Preventer therapy for children who have frequent intermittent or persistent asthma symptoms* FP = fluticasone propionate. BDP–HFA = beclomethasone dipropionate – hydrofluoroalkane. BUD = budesonide. CIC = ciclesonide. * Modified from the Asthma management handbook 2006 with permission from the National Asthma Council Australia.5 † Long-acting β-agonists not recommended for children aged 5 years or younger.

Peter P Van Asperen MB BS, MD, FRACP · Craig M Mellis MPH, MD, FRACP · Peter D Sly MD, DSc, FRACP · Colin F Robertson MSc, MD, FRACP

Unsatisfactory outcomes in medicine are too common. There are multiple causes, one of which is medical errors. In our society the response to medical error is typically legal, rather than investigative and remedial. This should be deplored by both the profession and the public. The clash between the legal and medical systems rarely leads to a decrease in the likelihood of future error. Rather, a defensive approach is fostered that encourages concealment of error and the attribution of blame. This balkanises the parties and makes solutions more difficult to find. The legal response to error and harm is reflective not only of our culture and history but also of the need for patients to ascertain information about the error and receive a financial remedy if loss has occurred. Given that this is the setting in which we find ourselves, the availability of the defence of “peer professional practice” (that an action is not negligent if the professional acts in a way that is widely accepted by his or her peers) gives some comfort. Mahar and Burke, in this issue of the Journal, draw attention to some important limitations of this defence (→ What is the value of professional opinion? The current medicolegal application of the “peer professional practice defence” in Australia). They point out that the defence is not a substitute for the need to properly warn patients of the material risks involved in a procedure. They also demonstrate that the requirement to practise according to widely accepted professional standards implies the need to be abreast of contemporary clinical practice. Surely this is the purpose of continuing professional education. Consequently, there is no justification for the practice of purely “defensive” medicine. Mahar and Burke’s article also highlights a negative interaction between the legal and medical cultures. In a recent case that relied on the peer professional practice defence, the testimony of one of the expert witnesses was discounted because, when forming his opinion, he consulted a colleague about her views on the case, which led the court to doubt the witness’s standing as an expert. In contrast, the medical view is that consultation in the face of doubt is protective of the patient and not a sign of weakness. As a doctor, the legalistic approach of the court in this regard reinforces the perception that the law is an ass, that it will never be understandable or reasonable, and that the solution to medical errors will never lie in the legal sphere. As a profession, this mandates that we make the study and minimisation of medical error and unfavourable outcomes our own. It is time to responsibly admit and embrace error and empower ourselves to grow. While “the truth will set you free”,* US President James Garfield was probably closer to the reality of the process when he supposedly added, “but first it will make you miserable”. * John 8: 32.

Annette G Katelaris MB BS, MPH, FRACGP

A 66-year-old woman presented to the emergency department with sudden-onset, severe thoracic back pain associated with dyspnoea and diaphoresis after consuming lunch. She was otherwise well, and her only medical history of note was gastro-oesophageal reflux disease. Examination showed a large right-sided pneumothorax, which was confirmed by chest x-ray. A pleural catheter was inserted, which resolved the pneumothorax, but the patient’s pain continued. A computed tomography scan showed a 2.7 cm transverse, linear foreign body in the patient’s oesophagus at the level of the aortic arch (Figure, arrow). This had caused perforation, pneumothorax, pneumomediastinum and pneumopericardium. The chicken bone was removed surgically, and the patient made an uneventful recovery.

Philippa J Bunting

Objective: To describe the epidemiology of adult patients hospitalised with influenza or pneumonia during a pandemic season in a sentinel network in Australia.Design, participants and setting: Prospective case series of adult hospital admissions to eight acute care general public hospitals (Influenza Complications Alert Network [Flu CAN] sentinel hospitals) in six Australian jurisdictions, 1 July to 4 December 2009.Main outcome measures: Demographic, clinical and outcome measures in patients admitted with laboratory-confirmed pandemic (H1N1) 2009 influenza in the sentinel hospitals compared with data from national notifications and intensive care unit (ICU) surveillance; admissions for influenza and pneumonia over time in each jurisdiction.Results: During 190 hospital-weeks of observation, there were 538 influenza admissions. Of these, 465 patients (86.4%) had the pandemic strain, representing 9.3% of total admissions with pandemic (H1N1) 2009 influenza (n = 4992) recorded nationally in 2009. Of these patients, 250/465 (53.8%) were women, 67/453 (14.8%) were Indigenous, and the median age was 46 years (interquartile range, 29–58 years). Comorbidities were present in 354/464 patients (76.3%), and 40 were pregnant (30.3% of women aged 15–49 years). FluCAN reported that 102 patients (21.9%) were admitted to ICUs, and of patients admitted to hospital, 26 (5.6%) died. FluCAN results were very similar to national notification data and published ICU admissions data. Of those who were followed to 30 days after discharge, 30 (6.5%) were readmitted. Of 1468 patients hospitalised with pneumonia, 718 (48.9%) were tested for influenza and 163 (11.1%) were co-infected with the pandemic strain.Conclusions: Sentinel surveillance systems can provide important and reliable information in a timely fashion and can monitor changes in severity of influenza during a pandemic season.

Paul M Kelly MB BS, PhD, FAFPHM · Tom Kotsimbos MD, FRACP · Anna Reynolds BSc, PhD · Richard Wood-Baker DM, FRACP · Bob Hancox MD, FRACP · Simon G A Brown MB BS, PhD, FACEM · Mark Holmes MB BS, MD, FRACP · Graham Simpson MD, FRCP, FRACP · Simon Bowler MB BS(Hons), FRACP · Grant Waterer PhD, FRACP, FCCP · Louis B Irving MB BS, FRACGP, FRACP · Christine Jenkins MD, FRACP · Phillip J Thompson MD, FRACP · Allen C Cheng FRACP, MPH, PhD

To the Editor: We view with concern the listed minimum investigations for chronic suppurative lung disease and bronchiectasis in children and adults recommended in the position statement from the Thoracic Society of Australia and New Zealand and the Australian Lung Foundation, published in the Journal.1 We do not agree with the inclusion of measurement of IgG subclasses in the list. Interpretation of IgG subclasses is fraught with difficulties.2 It is unclear whether the isolated finding of low levels of one or more IgG subclasses is a risk factor for developing severe recurrent bacterial infections. Individuals with complete absence of IgG subclasses due to gene deletions may remain entirely asymptomatic, and the finding of a low or absent response to specific bacterial protein and/or polysaccharide is more closely associated with propensity to infection. In addition, the lack of reproducibility of IgG subclass assays and lack of well standardised age-specific reference ranges hinder interpretation of results. Of major concern is the lack of evidence to provide clear guidance on the efficacy of immunoglobulin replacement therapy in IgG subclass deficiency. In general, the finding of isolated IgG subclass deficiency is not sufficient grounds for commencement of immunoglobulin therapy and is not recommended as an indication for intravenous immunoglobulin therapy in the current Australian guidelines.2 We urge the authors to reconsider the inclusion of IgG subclasses in the list of minimum investigations for chronic suppurative lung disease and bronchiectasis.

David S Gillis · D Sean Riminton

In reply: We thank Gillis and Riminton for their comments highlighting the inclusion of IgG subclasses in the list of suggested investigations when reviewing a patient with chronic suppurative lung disease or bronchiectasis. We agree that a finding of one or more low IgG subclasses in isolation is not an indication for immunoglobulin therapy and that interpretation of serum IgG subclass concentrations is difficult. Indeed, this was debated at length by the position statement authors. However, after considerable discussion, we decided that measurement of IgG subclasses should be included. Although the data are weak, it is an important area of possible aetiology, and there are varying opinions regarding associations with impaired adaptive immunity.1-3 As with some other investigations, an abnormal test result in the context of a child or adult with suppurative lung disease would lead to discussion with an appropriate subspecialist for advice on interpretation and/or further evaluation. Space limitations in the Journal version of our position statement did not permit us to elaborate further.4 In the full document available online,5 we stated that: The benefits of performing IgG subclasses in isolation are particularly controversial as the role of a reduction of a subclass is likely over-diagnosed.[88-91] If IgG subclass is low, assessment of response to vaccinations is advocated.

Anne B Chang

In the absence of evidence of infection with the hepatitis C virus (HCV), detecting the immunological disorder of mixed cryoglobulinaemia is a challenge. Only after extensive investigation did we suspect that our patient’s recurrent acute dyspnoea, lower limb paraesthesia and renal impairment with active urinary sediment were attributable to the rare phenomenon of non-HCV-related mixed essential cryoglobulinaemia — our suspicion was confirmed by significant serum levels of cryoglobulins. (MJA 2010; 194: 142-144) Clinical recordIn October 2008, an 84-year-old man with increasing dyspnoea on exertion for 1 week was referred for hospital admission by his general practitioner. His medical history included rheumatic heart disease leading to aortic valve replacement (AVR) in 1973. In 2001, he underwent a redo AVR, a mitral valve replacement (non-mechanical) and coronary artery bypass grafting. He then required implantation of a permanent cardiac pacemaker for complete heart block. He had chronic kidney disease (Stage 3) of unknown cause and mild, well controlled asthma. He was a lifelong non-smoker and occasionally drank alcohol. At presentation, he was afebrile and haemodynamically stable, with a respiratory rate of 20 breaths per minute and oximetry of 95 per cent on room air. There were no signs of fluid overload or peripheral stigmata of infective endocarditis. Chest auscultation revealed bibasal crackles, and loud first and second heart sounds in keeping with previous valve surgery. Mild stasis eczema was the only notable skin lesion. He reported experiencing, for the past few months, lower limb paraesthesia and sicca-like symptoms. His daily medications included perindopril 2.5 mg, digoxin 125 μg, frusemide 40 mg and warfarin at varying doses. For asthma, he was prescribed a daily inhalation of fluticasone 250 μg, with salmeterol 25 μg, and inhalations of salbutamol 100 μg as needed. Results of blood, urine and sputum tests done at presentation are shown in Box 1; results showed an inflammatory response and renal impairment with active urinary sediment (repeat urinary analysis a week after presentation also revealed active urinary sediment). An electrocardiogram showed no arrhythmias. Chest x-ray at presentation showed air bronchograms at the right lower zone (Box 2). Our patient was admitted and treated for right lower lobe pneumonia with intravenous antibiotics. He was also prescribed high-dose oral steroids, with gradual tapering of doses. A computed tomography scan showed probable right lower chest infection. During the early weeks of his hospitalisation, the patient had further episodes of acute dyspnoea, and repeat chest x-rays showed bilateral migratory opacities (Box 3). Acute episodes of dyspnoea were treated with high-dose oral steroids and intravenous antibiotics; a regular regimen of low-dose steroids was maintained between episodes. During each acute episode, his biochemistry results showed an inflammatory response, with varying elevated serum levels of C-reactive protein (CRP): 243 mg/L; 332 mg/L; 73 mg/L; 16 mg/L; 148 mg/L; and 90 mg/L (reference range [RR], < 5.0 mg/L). With treatment, the CRP level fell to 5.3 mg/L. Repeated blood and urine cultures produced no growth. A transthoracic echocardiogram revealed a normal left ventricular ejection fraction and no regurgitation from the prosthetic valves, and a transoesophageal echocardiogram showed no valvular vegetations. The serum level of B-type natriuretic peptide was 246 ng/L (RR, < 100 ng/L), making acute left ventricle failure unlikely in view of the patient’s renal impairment. No respiratory viruses were detected in nasopharyngeal aspirate. The patient’s serological tests were negative for hepatitis B virus, hepatitis C virus (HCV), HIV, cytomegalovirus, mycoplasma, Chlamydia, Legionella pneumophila, Legionella longbeachae, Brucella, Histoplasma, and Toxoplasma. The result of the QuantiFERON-TB Gold assay (Celeste) was indeterminate. Serum electrophoresis was negative and no Bence–Jones protein was detected in urine. Liver ultrasound showed no evidence of chronic liver disease. Screening for autoimmune discrepancies was significant but inconclusive — test results for serum levels of rheumatoid factor (RF) and antinuclear antibody were positive but other antibody test results were negative or within reference ranges (Box 4). On further investigation (5 weeks after admission), the patient’s serum levels of complement components C3 and C4 were 0.77 g/L (RR, 0.70–1.60 g/L) and < 0.02 g/L (RR, 0.10–0.30 g/L), respectively; repeated test results were C3, 0.74 g/L and C4, < 0.02 g/L. Such a result — low C4 with normal C3 levels — may be due to cryoglobulinaema, C4 null alleles, hereditary angioedema or activation of the classical complement pathway. Types and levels of cryoglobulins found in the patient’s serum were: monoclonal IgM/kappa, 0.4 g/L and polyclonal IgG, 0.1 g/L. HCV RNA was not detected. On the basis of the presence of cryoglobulins in serum and supported by evidence of lung and inflammatory involvement, a diagnosis of mixed essential cryoglobulinaemia (Type II cryoglobulinaemia) was made. The patient was reviewed by an immunologist, who agreed with the diagnosis. To exclude lymphoma, particularly B-cell lymphoma which is the most frequent malignant complication of mixed cryoglobulinaemia, a bone marrow biopsy was done; no significant population of B-cell biomarkers (CD19+/CD20+ cells) was found, nor any other suggestion of lymphoma. Despite the investigative effort, we did not identify a cause for our patient’s cryoglobulinaemia. He gave informed consent for all investigations. DiscussionCryoglobulins are single or mixed immunoglobulins that, in serum and other body fluids, undergo reversible precipitation at low temperatures (below 37°C in serum). According to the Brouet classification, cryoglobulinaemia is grouped into three types based on the composition of the detected cryoglobulins. Type I cryoglobulinaemia, or simple cryoglobulinaemia, is the result of a monoclonal immunoglobulin, which rarely has RF activity and is not known to activate complement in vitro. The cryoglobulins of Types II and III cryoglobulinaemia (mixed cryoglobulinaemia) contain RF, which forms complexes with the “fragment crystallisable” (Fc) portion of polyclonal IgG. The actual RF may be monoclonal immunoglobulin (in Type II cryoglobulinaemia) or polyclonal immunoglobulin (in Type III cryoglobulinaemia). Types II and III cryoglobulinaemia represent 80% of all occurrences of the disease. HCV is associated with most cases of mixed cryoglobulinaemia, with the prevalence of anti-HCV antibodies or HCV RNA ranging from 70% to almost 100%.1 The clinical manifestations of cryoglobulinaemia are generally caused by the inflammatory effects of circulating immune complexes on multiple organs. The criteria for diagnosing mixed cryoglobulinaemia are: detection in serum of mixed cryoglobulins, along with purpura and leukocytoclastic vasculitis; or detection in serum of mixed cryoglobulins, along with peripheral neuropathy, membranoproliferative glomerulonephritis, chronic hepatitis or skin rashes.1 Signs and symptoms that our patient showed fulfilled the latter set of criteria. Although our patient had no skin lesion typical of the disease (and suitable for biopsy), nor evidence of liver disease, he had lower limb paraesthesia and tested positive for renal impairment and active urinary sediment. The success of steroid treatment indicated an inflammatory component to the problem. Furthermore, lung involvement is reported to be quite frequent in mixed essential cryoglobulinaemia,2 and migratory lung lesions have been associated with the disease.3 What is notable about this case is the lack of evidence of HCV infection. To the extent that we are able to establish (two PubMed searches of English-language articles were undertaken), it is the first reported case of mixed essential cryoglobulinaemia with migratory lung lesions and unrelated to HCV infection. 1 Results of patient’s blood, urine and sputum investigations at presentation Test Result Blood Haemoglobin 110 g/dL (RR, 135–180 g/dL) White cell count 9.2 x 109 cells/L (RR, 4.0–11.0 x 109 cells/L) Neutrophils 6.5 x 109 cells/L (RR, 2.0–8.0 x 109 cells/L) Platelets 174 x 109 cells/L (RR, 140–400 x 109 cells/L) C-reactive protein 243 mg/L (RR, < 5.0 mg/L) Sodium 138 mmol/L (RR, 135–145 mmol/L) Potassium 4.8 mmol/L (RR, 3.5–5.1 mmol/L) Urea 13.3 mmol/L (RR, 2.9–8.2 mmol/L) Creatinine 160 μmol/L (RR, 64–108 μmol/L) Cultures (three sets) No growth after 1 week incubation Urine Microscopic analysis Active sediment* Dipstick Moderate blood, 2 + leukocytes, trace protein Culture No growth after 1 week incubation Sputum Culture Normal respiratory flora RR = reference range. * Active urinary sediment is sediment found in a centrifuged urine sample and showing red cells, red cell casts and at times white cells and white cell casts; it indicates active kidney inflammatory disease such as glomerulonephritis, interstitial nephritis or vasculitis. 2 Patient’s chest x-ray at presentation showing air bronchograms at right lower zone (2 October 2008) 3 Patient’s chest x-rays several weeks after presentation showing bilateral migratory opacities (A, 16 November 2008; B, 24 November 2008) 4 Results of patient’s autoimmunity screening tests at presentation and 4 weeks after presentation Test Initial result Result at 4 weeks Rheumatoid factor (RR, < 20 IU/mL) 51 IU/mL < 20 IU/mL Anticyclic citrullinated peptide antibody (anti-CCP) < 6 U/mL — Antinuclear antibody (ANA) (RR, < 40 titre) > 2560 titre 640 (homogenous) titre Anti-double-stranded DNA antibodies negative — Anti-Sjögren’s syndrome A / anti-Sjögren’s syndrome B antibodies (anti SSA/SSB antibodies) negative — Direct Coombs test negative — Antithyroid peroxidise antibodies (RR, < 50 IU/mL) 1 IU/mL — Antithyroglobulin antibodies (RR, < 100 IU/mL) 7 IU/mL — Antitissue transglutaminase antibody (anti-TTG [IgA]) (RR, < 5 U/mL) 0 U/mL — RR = reference range

Muhammad Kashif Nadeem MB BS, MRCP · Mohammed A Khateeb MB BS, FRACP

To the Editor: A patient of mine recently reported that she had had a busy week, with the death and funeral of her sister. The woman had died with lung cancer at the age of 77, after having smoked tobacco for 61 years from the age of 17. On further enquiry, I was informed that the woman had “smoked all day and all night”, at the rate of 60 to 80 cigarettes per day. People could hardly stand to visit her home because “the house was always full of smoke”. Two different brands were used, including packs of 40. She had required oxygen therapy for the past 12 to 18 months and was severely disabled by breathlessness. She would “chain smoke”, with one cigarette behind each ear and one in her mouth. Rather than light them with a match or cigarette lighter, she would light her next cigarette from the butt of the one she was just finishing. At an average of 70 cigarettes every day for 60 years, the total intake amounts to around 1 500 000 cigarettes. At, say, 50c for each cigarette, this equates to a cost of $35 a day or $12 775 for a single year. A principal reason for taking the trouble to offer this anecdote for publication is that this is the greatest number of cigarettes I have ever heard of being smoked by any one person.

C Ross Philpot

Objective: Design, setting and participants: A randomised single-blind controlled trial with a treatment duration of 3 days and a follow-up period of 4 days was conducted at a sauna in Berlin, Germany. Between November 2007 and March 2008 and between September 2008 and April 2009, 157 patients with symptoms of the common cold were randomly assigned to an intervention group (n = 80) and a control group (n = 77).Interventions: Participants in the intervention group inhaled hot dry air within a hot sauna, dressed in a winter coat, whereas participants in the control group inhaled dry air at room temperature within a hot sauna, also dressed in a winter coat.Main outcome measures: Area under the curve (AUC) summarising symptom severity over time (Days 2, 3, 5 and 7), symptom severity scores for individual days, intake of medication for the common cold and general ill feeling.Results: No significant difference between groups was observed for AUC representing symptom severity over time (intervention group mean, 31.2 [SEM, 1.8]; control group mean, 35.1 [SEM, 2.3]; group difference, − 3.9 [95% CI, − 9.7 to 1.9]; P = 0.19). However, significant differences between groups were found for medication use on Day 1 (P = 0.01), symptom severity score on Day 2 (P = 0.04), and participants’ ratings of the effectiveness of the therapy on Day 7 (P = 0.03).Conclusion: Inhaling hot air while in a sauna has no significant impact on overall symptom severity of the common cold.Trial registration: ClinicalTrials.gov identifier NCT00552981.

Daniel Pach MD · Bettina Knöchel CandMed · Rainer Lüdtke MSc · Katja Wruck Documentalist · Stefan N Willich MD, MPH, MBA · Claudia M Witt MD, MBA

Objective: To determine whether changes in 24-hour average background ozone (O3), nitrogen dioxide (NO2), carbon monoxide (CO) and particulates < 10 μm (PM10) increase the risk of hospital emergency department (ED) presentations for asthma among children.Design, setting and subjects: A time-stratified case-crossover method was used to analyse data of 603 children and young adults aged 0–19 years who were resident in a south-west metropolitan area of Perth, Western Australia, and who had presented with asthma at any public ED within Perth between 1 January 2002 and 31 December 2006. Effect sizes were assessed in relation to age group, sex and season of exposure. City-wide background air pollution was estimated from air monitoring network data.Main outcome measures: ED presentation with asthma.Results: Patients 0–4 years with 1-day lagged exposure to NO2 and CO showed the most significant risk of ED presentation for asthma. An interquartile range (IQR) increase in NO2 resulted in an odds ratio (OR) of 1.70 (95% CI, 1.08–2.69). An IQR increase in CO resulted in an OR of 1.40 (95% CI, 1.06–1.84).Conclusions: The effect sizes observed in this study were higher than those of past studies, and indicated that children aged 0–4 years were the most vulnerable to the effects of air pollution. The period of exposure most clinically relevant is the day before ED presentation.

Gavin Pereira MAppStats, BCM, GCResCom · Angus Cook MB ChB, PhD · Annemarie J B M De Vos PhD, MPH, RN · C D’Arcy J Holman MB BS, MPH, PhD