Respiratory disease

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

Objective: To evaluate whether systematic asthma care involving a register-recall system, postcard prompts for review, and education for general practitioners and staff in Australian general practice improves the quality of care and health outcomes for adult patients with moderate to severe asthma.Design and setting: Cluster randomised controlled trial in 40 general practices in urban and rural South Australia and New South Wales over the 2 years 2004 and 2005; practices were randomly allocated to the intervention or control group.Participants: 565 adult patients of these randomly allocated practices who had doctor-diagnosed moderate to severe asthma and were taking inhaled corticosteroids.Main outcome measures: Clinical asthma indicators, quality of care, acceptability of the intervention to patients, quality of life, and asthma self-management skills at baseline, 6 months and 12 months.Results: Although 46% of patients in the intervention group practices responded to the postcard prompts, only 32% actually attended for their asthma review. At 12 months, there was a statistically significant difference in provision of written asthma action plans (rate ratio, 1.9; 95% CI, 1.0–3.5; P = 0.04) for intervention group patients compared with control group patients; there was no significant difference in other indicators.Conclusion: We found little objective evidence of improvement in patient management and outcomes resulting from a systematic model of asthma care.Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12605000091606

Christine H Holton GDAcc, GDPH, CPA · Justin J Beilby MD, MPH, FRACGP · Mark F Harris MB BS, MD, FRACGP · Clare E Harper BSc(Hons), MMedSci(Human Nutr) · Judith G Proudfoot GradDipSpEd, MA(Psych), PhD · Emmae N Ramsay BSc(Ma · Richard E Ruffin MD, FRACP, AM

Consensus recommendations for managing chronic suppurative lung disease (CSLD) and bronchiectasis, based on systematic reviews, were developed for Australian and New Zealand children and adults during a multidisciplinary workshop. The diagnosis of bronchiectasis requires a high-resolution computed tomography scan of the chest. People with symptoms of bronchiectasis, but non-diagnostic scans, have CSLD, which may progress to radiological bronchiectasis. CSLD/bronchiectasis is suspected when chronic wet cough persists beyond 8 weeks. Initial assessment requires specialist expertise. Specialist referral is also required for children who have either two or more episodes of chronic (> 4 weeks) wet cough per year that respond to antibiotics, or chest radiographic abnormalities persisting for at least 6 weeks after appropriate therapy. Intensive treatment seeks to improve symptom control, reduce frequency of acute pulmonary exacerbations, preserve lung function, and maintain a good quality of life. Antibiotic selection for acute infective episodes is based on results of lower airway culture, local antibiotic susceptibility patterns, clinical severity and patient tolerance. Patients whose condition does not respond promptly or adequately to oral antibiotics are hospitalised for more intensive treatments, including intravenous antibiotics. Ongoing treatment requires regular and coordinated primary health care and specialist review, including monitoring for complications and comorbidities. Chest physiotherapy and regular exercise should be encouraged, nutrition optimised, environmental pollutants (including tobacco smoke) avoided, and vaccines administered according to national immunisation schedules. Individualised long-term use of oral or nebulised antibiotics, corticosteroids, bronchodilators and mucoactive agents may provide a benefit, but are not recommended routinely.

Anne B Chang MPHTM, PhD, FRACP · Scott C Bell MB BS, MD, FRACP · Cass A Byrnes MB ChB, MD, FRACP · Keith Grimwood MB ChB, MD, FRACP · Peter W Holmes MB BS, FCCP, FRACP · Paul T King MB BS, FRACP, PhD · John Kolbe MB BS, FRACP · Louis I Landau MB BS, MD, FRACP · Graeme P Maguire MB BS, FRACP, PhD · Malcolm I McDonald MB BS, FRCPA, PhD · David W Reid MB ChB, MRCP, FRACP · Francis C Thien MB BS, MD, FRACP · Paul J Torzillo MB BS, FRACP, FJFICM

Objective: To document trends in subject demographics, anthropometry and sleep disorder severity over 21 years of diagnostic sleep studies.Design, participants and setting: A retrospective observational study of consecutive subjects undergoing initial diagnostic polysomnography for investigation of possible sleep disorders in a university-affiliated tertiary public metropolitan hospital in the Hunter New England region of New South Wales between 1987 and 2007.Main outcome measures: Body weight, body mass index (BMI) and severity of sleep-related breathing disorders (apnoea-hypopnoea index [AHI]).Results: Between 1987 and 2007, 14 648 new diagnostic sleep studies were performed. The median age of subjects (51 years; interquartile range, 41–61 years) did not change over time and the proportion of women increased from 20% to 39%. Median body weight increased from 89 kg to 99 kg for men (11%) and from 73 kg to 85 kg for women (16%), equating to a yearly increase in median BMI of 0.15 kg/m2 for men and 0.14 kg/m2 for women. The proportion of subjects who were morbidly obese (BMI ≥ 40) increased from 3% in 1987 to 16% in 2007. Median AHI progressively increased from 1992–1995 to 2004–2007 (from 6.5 events/h to 14.3 events/h; P < 0.001), indicating increasing disease severity. Over the same period, for every unit increase in BMI, AHI increased by 5.5 events/h for men and by 2.8 events/h for women. About 80% of the observed variance in AHI over this period was attributable to variance in BMI.Conclusion: There is a continuing trend towards increasing body weight and BMI in people undergoing diagnostic sleep studies. Our data do not support the hypothesis that increased accessibility to diagnostic services and increased awareness of sleep disorders are resulting in a decline in disease severity. These findings are consistent with the premise that worsening severity in sleep-disordered breathing is primarily attributable to increasing obesity.

Jeffrey J Pretto DHlthSc, BAppSc, CRFS · Stephen G Gyulay GradDipClinEpid · Michael J Hensley MB BS, PhD, FRACP

Objective: To determine whether spirometry with regular medical review improves the quality of life or other health outcomes among patients with asthma or chronic obstructive pulmonary disease (COPD) managed in general practice.Design, setting and participants: Cluster randomised controlled trial conducted in 31 general practices in Melbourne during 2007–2008. Practices recruited 305 adult patients who had been prescribed inhaled medication in the preceding 6 months.Intervention: Practices were randomly assigned to one of three groups: Group A patients received 3-monthly spirometry performed by a respiratory scientist with results returned to the practice and regular medical review; Group B patients received spirometry only before and after the trial; and Group C patients received usual care.Main outcome measures: Quality of life, assessed with the 36-item Short Form (SF-36) Australian (English) Version 2 questionnaire at baseline and 3, 6, 9 and 12 months. Secondary outcomes were assessed with the European Community Respiratory Health Survey at baseline and 12 months.Results: The trial was completed by 253 participants: 79 in Group A, 104 in Group B, and 70 in Group C. Median age was 58 years (range, 18–70 years), and 167 participants (66%) were women. There were no significant changes in SF-36 Physical and Mental Component Summary scores from baseline to 12 months, or significant differences between groups on either scale or any subscale of the SF-36. There were also no significant differences in respiratory symptoms, asthma attacks, written asthma action plans, days lost from usual activities or health care utilisation.Conclusion: Three-monthly spirometry and regular medical reviews by general practitioners are not associated with any significant improvement in quality of life or other health outcomes for patients with asthma and/or COPD.Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12606000378527.

Michael J Abramson MB BS, PhD, FRACP · Rosa L Schattner BEc, MPH · Nabil D Sulaiman MB ChB, FFPHM, PhD · Kate E Birch BSc(Hons) · Pam P Simpson BSc(Hons) · Eleonora A Del Colle BAppSc · Rosalie A Aroni BA(Hons), PhD · Rory Wolfe BSc, PhD · Francis C K Thien MB BS, FRACP, MD

Laboratory-confirmed influenza is a nationally notifiable disease in Australia. According to notification data, Queensland has experienced more severe influenza seasons than other states and territories. However, this method ignores available denominator data: the number of laboratory tests performed. We propose that negative results of laboratory tests for influenza should be made notifiable, alongside laboratory-confirmed disease, and used to calculate the proportion of positive test results in real-time. Using data from the public health pathology services of three Australian states — Queensland Health laboratories, the Victorian Infectious Diseases Reference Laboratory and Western Australia’s PathWest — for 2004 to 2008, we show that incorporating laboratory-negative test data into national surveillance data would add to and improve our understanding of influenza epidemiology.

Stephen B Lambert MB BS, MAppEpid, PhD · Cassandra E Faux MSc(ClinMicro) · Kristina A Grant BSc · Simon H Williams BSc(Hons) · Cheryl Bletchly BSc(Hons), GradCertHlthMgt, PhD · Michael G Catton MB BS, FRCPA · David W Smith MB BS, FRCPA, FACTM · Heath A Kelly MB BS, MPH

To the Editor: We describe here some of the difficulties in managing and investigating outbreaks of viral respiratory infection in aged care facilities (ACFs) in the context of an influenza pandemic. This adds to the previous report on logistics in a hospital setting.1 On 12 June 2009, NSW Health received a call from a surveillance officer in a remote town regarding a possible pandemic (H1N1) 2009 influenza outbreak in an ACF. On 9 June, a 77-year-old female resident had become unwell, without specific symptoms of influenza-like illness. From 7 to 10 June, nine of the other 27 residents developed influenza-like illness. On 10 June, nasal swabs were taken from the 10 unwell residents by the local general practitioner for influenza nucleic acid testing (NAT). On 12 June, the index case tested positive for pandemic influenza, while the other residents tested negative. Due to concern that there might be a pandemic influenza outbreak in the facility, the index case and the nine residents with influenza-like illness were given oseltamivir (75 mg twice a day for 5 days) from 13 June; the other 18 residents and the 27 staff were given oseltamivir prophylaxis (75 mg daily for 10 days). A formal outbreak investigation and further laboratory testing (NAT, serological testing) revealed a dual outbreak dominated by rhinovirus (10 cases), with two cases of pandemic influenza and one case of untyped influenza A. All 28 residents and 26 of the 27 staff had received seasonal influenza vaccine in early 2009. This outbreak illustrates that more than one respiratory virus may co-circulate in ACFs during winter outbreaks of respiratory infection. We followed Department of Health and Ageing policy guidelines for oseltamivir use in ACFs2 and the facility was closed to visitors from 12 to 18 June. However, as all residents had received seasonal influenza vaccination, and given that older people are generally at lower risk of pandemic (H1N1) 2009 influenza,3 we could have had a higher threshold for oseltamivir use. The total estimated cost of treatment and prophylaxis was $2750 (55 residents and staff at $50/person) for oseltamivir alone. Co-infection with respiratory viruses may be more common than thought in ACFs; a recent Canadian study found two and three different pathogens in 15% and 4% of respiratory infection outbreaks, respectively, from a total of 83 outbreaks (of which 91% occurred in long-term care facilities).4 If many ACF outbreaks have more than one respiratory virus involved, laboratory investigations should take a multiplex approach that covers common respiratory viruses. As many patients as practical (at least five) should be swabbed and tested to guide treatment, prophylaxis and other investigations. Community influenza surveillance should ideally include information on sensitivity to oseltamivir, and on other circulating respiratory viruses.

Gulam Khandaker · Bridget Doyle · Dominic E Dwyer · Robert Booy

To the Editor: Treatment of critically ill pregnant women is challenging, and information on medication use during pregnancy is scant. We describe the case of a pregnant woman who required extracorporeal membrane oxygenation (ECMO), prolonged sedation and paralysis to treat acute respiratory distress syndrome secondary to pandemic (H1N1) 2009 influenza. A 34-year-old pregnant woman (G2P1) at 21 weeks’ gestation presented to a metropolitan hospital with level 1 intensive care unit facilities. She had known Grade 2 placenta praevia, a 5-day history of influenza-like symptoms, and no history of asthma, chronic disease or recent travel. On examination, she was severely hypoxic (PaO2, 27 mmHg on 15 L/min O2), conscious, tachypnoeic and speaking in single words. A chest x-ray showed extensive bilateral infiltrates (Box). She needed urgent endotracheal intubation but remained hypoxic despite maximal intensive mechanical ventilation. The patient was transferred to St Vincent’s Hospital, Sydney, where venovenous ECMO was commenced on arrival. Her oxygenation status improved and remained satisfactory. Mechanical ventilation was reduced (tidal volume, < 6 mL/kg; peak pressure, < 30 cm H2O) to avoid ventilator-induced lung injury. The patient required very high doses of morphine, fentanyl, midazolam, propofol, dexmedetomidine, cisatracurium and heparin during ventilation and ECMO. In addition, empirical treatment with oseltamivir (150 mg twice a day, Days 1–8), azithromycin and ceftriaxone was started on admission, before a bronchoalveolar lavage specimen tested positive for influenza A and pandemic influenza. Furthermore, a multiresistant Escherichia coli caused ventilator-associated pneumonia, which was treated with meropenem (1 g three times a day, Days 17–30). ECMO was discontinued on Day 19, when lung function had improved. No other organ failure developed. On Day 21, a tracheostomy was performed for severe weakness and weaning failure. The patient was weaned from the ventilator on Day 35 and was discharged home 2 weeks later, after making a full recovery. She gave birth by caesarean section at 35 weeks’ gestation. The baby was in good health and the patient recovered well — both left hospital 3 days after the birth. Information on the use of medication in pregnant women who require intensive care is limited, especially the use of neuraminidase inhibitors.1 We found little evidence on the safety of long-term use of neuromuscular blockers and sedation in pregnancy, with or without ECMO.2 Most literature on this topic describes short-term use of neuromuscular blockers and sedation. Dexmedetomidine has a short postmarketing history, and has therefore had limited use. Data from Australia and New Zealand indicate that 9% of patients admitted to an intensive care unit with pandemic influenza are pregnant. An estimated inhospital mortality rate of more than 16% in this population indicates the severity of the infection.3,4 Single-organ lung failure is a common feature of complicated pandemic influenza, and venovenous ECMO should be considered in these circumstances.2,4,5 Our case demonstrates that ECMO and the drugs necessary for its use can be used during pregnancy in a patient with influenza-associated acute respiratory distress syndrome, and that survival of the patient and fetus is possible. Chest x-ray of a pregnant woman with influenza-associated acute respiratory distress syndrome showing extensive bilateral infiltrates

Susan A Welch · Leone N Snowden · Hergen Buscher

Objective: To assess the outcomes of an education intervention for childhood asthma conducted by Australian Indigenous health care workers (IHCWs).Design and setting: Randomised controlled trial in a primary health care setting on Thursday Island and Horn Island, and in Bamaga, Torres Strait region of northern Australia, April 2005 to March 2007.Participants: 88 children, aged 1–17 years, with asthma diagnosed by a respiratory physician (intervention group, 35; control group, 53; 98% Indigenous children).Interventions: Children were randomly allocated to: (i) three additional asthma education sessions with a trained IHCW, or (ii) no additional asthma education. Both groups were re-assessed at 12 months.Main outcome measures: Primary endpoint: number of unscheduled visits to hospital or a doctor caused by asthma exacerbation. Secondary outcomes: measures of quality of life (QoL) and functional severity index; asthma knowledge and understanding of asthma action plans (AAPs); and school days missed because of wheezing.Results: The groups were comparable at baseline (except for asthma severity, which was adjusted for in the analysis). There were no significant differences in the primary outcome (number of unscheduled medical visits for asthma). School children in the intervention group missed fewer school days because of wheezing (100% < 7 days v 21% of those in the control group missed 7–14 days). Significantly more carers in the intervention group could answer questions about asthma medication, knew where their AAP was kept (84% v 56%), and were able to describe the plan (67% v 40%). In both the intervention and control groups (before-and-after comparison), there was a significantly reduced frequency of asthma exacerbations, as well as an improved QoL score and functional severity index, with no significant differences between the groups.Conclusions: A community-based asthma education program conducted by trained IHCWs improves some important asthma outcomes in Indigenous children with asthma.Trial registration: Australian Clinical Trials Registry ACTRN012605000718640.

Patricia C Valery MD, MPH, PhD · Ian B Masters MB BS, FRACP, PhD · Brett Taylor MEd, GradDipExSpSc, BEd(Hons) · Yancy Laifoo IndigCommMgntDev · Peter K O’Rourke BSc(Hons), BA(Hons), PhD · Anne B Chang FRACP, MPHTM, PhD

To the Editor: The recent article by Davis and colleagues reported that the SMART-COP score underestimates the severity of pneumonia in tropical northern Australia, but can be improved by using locally relevant additions.1 The authors’ revised scoring system, SMARTACOP, increased the score for an albumin level < 35 g/L and added Aboriginal or Torres Strait Islander status as a variable. While these additions are useful, the reason for adding ethnicity was not fully clarified. A factor overlooked was low serum 25-hydroxyvitamin D [25(OH)D] levels among dark-skinned Australians.2 Smoking, identified as a marginally insignificant risk factor,1 is also associated with lower serum 25(OH)D levels.3 Vitamin D enhances the innate immune system through induction by 1,25-dihydroxyvitamin D of cathelicidin and defensins, which combat several types of bacterial and viral infections including upper respiratory tract infections.4 In the 1918–1919 influenza pandemic in the United States, many deaths were due to pneumonia that occurred as a complication of influenza infection. An ecological study found that indices for levels of vitamin D production from solar ultraviolet-B irradiance explained 50% of the variance in pandemic case-fatality rates among 12 communities.5 The mechanisms proposed for the beneficial effect of vitamin D were reduced proinflammatory cytokine production, which would reduce damage to the epithelial lining of the lungs, and induction of cathelicidin and defensins to fight the secondary bacterial pneumonia infection. If sera are available for those included in the Australian SMART-COP study,1 they could be analysed for 25(OH)D levels to test this hypothesis.

William B Grant

In reply: We thank Grant for his interest in our study on pneumonia severity assessment in tropical Australia. Our revised scoring system included increased weighting for hypoalbuminaemia, as well as adding a point for Indigenous status, because these two factors had the strongest association with the need for intensive respiratory or vasopressor support on univariate analysis.1 Unlike vitamin D status, these and the other factors included in the scoring system are readily available measures that can be used in the clinical setting to rapidly predict the need for intensive support. The scoring system was not intended to identify underlying aetiology or risk factors for severe pneumonia. For example, Indigenous status is likely to be a surrogate measure for undiagnosed comorbidities, lack of access to health care, and socioeconomic disadvantage. We agree that vitamin D is important in immune function and that the levels of insufficiency that result in impaired resistance to infection are not well defined.2 Most data on vitamin D deficiency in dark-skinned populations in Australia come from temperate areas,3,4 and the reference offered by Grant to support the concern about vitamin D deficiency does not cite any data from Australian populations north of southern Queensland.5 Further studies are needed on the prevalence of vitamin D deficiency in Indigenous Australians in tropical areas, and the additional contribution of vitamin D deficiency independent of known risk factors of severity and outcome.

Joshua S Davis · Allen C Cheng · Bart J Currie · Nicholas M Anstey

To the Editor: The recent article by Chang and colleagues concluded that “the clinical course and outcomes of pandemic (H1N1) 2009 influenza virus are comparable to those of the current circulating seasonal influenza”, and that: “The high number of hospital admissions reflects a high incidence of disease in the community rather than an enhanced virulence of the novel pandemic influenza virus”.1 We are concerned that these assertions underemphasise the true severity of the influenza pandemic, and have led to inappropriate reporting in the media.2 The single-centre series reported by Chang et al had a small sample size and was almost certainly underpowered to detect important differences. It is also likely that some of the five untypeable patients who were categorised in the seasonal influenza group had had false-negative test results for pandemic (H1N1) 2009 influenza. Despite the small numbers, this study suggested that patients with pandemic (H1N1) 2009 influenza were younger and less immunocompromised than those with seasonal influenza; both of these characteristics of the patients affected may indicate that the pandemic virus is a more virulent strain. However, regardless of whether its virulence was greater, our significant concern is that our community will underestimate the real burden of the pandemic, which was substantial in Australia and New Zealand during the recent winter. In recent publications, we described more than 700 people admitted to intensive care units (ICUs) throughout these two countries with pandemic (H1N1) 2009 influenza.3,4 These were often young and previously healthy people, and many were pregnant women.3 Two-thirds needed mechanical ventilation for influenza-induced respiratory failure,3 and a smaller but substantial number developed rapidly progressive acute respiratory distress syndrome and required extracorporeal membrane oxygenation (ECMO),4 the most extreme life support available. This is not the normal pattern of influenza in Australasia. In comparison to a normal winter, ICU admissions for viral pneumonitis increased 15-fold,3 and the use of ECMO for acute lung injury increased 17-fold.4 Patients infected with pandemic (H1N1) 2009 influenza required prolonged stays in both the ICU and hospital and, despite optimal care, more than 100 died. ICU bed occupancy by patients with pandemic (H1N1) 2009 influenza ran as high as 19%3 in a system that normally runs close to maximal occupancy. There is a real risk that the pandemic will affect Australia again next winter or earlier, and we feel the Australasian medical community should not be misled into believing that the pandemic (H1N1) 2009 influenza virus is not virulent and has not been responsible for significant mortality and morbidity in a population not normally affected.

Andrew R Davies · Steven A Webb · Ian M Seppelt · Rinaldo Bellomo

In reply: Our study found that both subtypes of influenza caused substantial morbidity and mortality, but that there was no difference in outcomes between patients infected with seasonal and pandemic (H1N1) 2009 influenza.1 The large numbers of cases of pandemic (H1N1) 2009 infection, and especially those requiring intensive care unit (ICU) management, is not disputed — 37 537 cases, 655 ICU admissions and 191 deaths in Australia had been reported as of 18 December 2009.2 However, this is not a function of enhanced virulence of the pandemic strain, but rather a function of vast numbers of infected individuals in a naïve population. The article by the Australian and New Zealand Intensive Care study investigators supports our conclusions, as they found no difference in outcome between pandemic (H1N1) 2009 and seasonal influenza.3 As specimens were tested in “real time”, RNA degradation is unlikely to have resulted in incorrect categorisation. The real impact of influenza has probably been under-reported before this pandemic, as virological testing of respiratory specimens has not been routine. Influenza per se is a significant disease, and thus appropriate planning, including resource allocation for ICU management and routine virological testing of respiratory specimens should be undertaken.

Iain B Gosbell · Sebastiaan J van Hal · Peter M Spencer · Ya-Shu Chang · Peter W Collett

To the Editor: Chang and colleagues suggest that the clinical course and outcomes of patients infected with pandemic (H1N1) 2009 influenza virus are comparable to those with seasonal influenza infection, and that increased hospital and intensive care unit (ICU) admissions with influenza reflected a higher incidence of disease in the community rather than enhanced virulence of the pandemic influenza virus.1 However, this conclusion was based on an analysis of data from a single hospital, which did not examine whether the community incidence of influenza was increased or whether infection with pandemic (H1N1) 2009 influenza increased the risk of admission to a hospital or ICU compared to infection with seasonal influenza. Seasonal influenza co-circulated with the pandemic influenza strain during the recent influenza epidemic in New South Wales.2 We used the results of influenza tests (excluding rapid antigen tests) performed at eight major NSW public laboratory services to estimate the risk of admission to an ICU with pandemic (H1N1) 2009 influenza compared with seasonal influenza A infection. These public laboratories confirmed 95% of people admitted to hospital with pandemic (H1N1) 2009 influenza, and 84% of all laboratory-confirmed pandemic influenza cases in NSW. For the weeks ending 5 June to 2 October 2009, 38 060 specimens were tested for respiratory viruses, of which 7602 were positive on polymerase chain reaction for influenza A. Of these, 4172 (55%) were identified as pandemic (H1N1) 2009 influenza. During the same period, we collected data on all patients admitted to an ICU with influenza A infection.3 In total, 274 patients with influenza A were admitted to NSW ICUs — 229 with pandemic (H1N1) 2009 influenza, 38 with seasonal influenza A and seven with unsubtyped influenza A infection. Excluding the seven unsubtyped influenza A cases, we calculated a relative risk of 4.9 (95% CI, 3.5–7.0) for admission to ICU with pandemic (H1N1) 2009 influenza compared with seasonal influenza A infection. A sensitivity analysis assigning the unsubtyped influenza A cases admitted to ICUs to either pandemic (H1N1) 2009 influenza or seasonal influenza A produced no significant change in our findings, with a relative risk of admission to ICU with pandemic influenza compared with seasonal influenza A infection of 5.1 (95% CI, 3.6–7.1) and 4.2 (95% CI, 3.1–5.7), respectively. Although we attempted to collect data on all patients admitted to an ICU with influenza A infection, repeated testing for pandemic (H1N1) 2009 influenza in ICU patients may have resulted in identification of pandemic (H1N1) 2009 influenza in a greater proportion of ICU patients than community patients. However, our results suggest there was a significantly increased risk of admission to an ICU with pandemic (H1N1) 2009 influenza infection compared with other seasonal influenza A strains circulating in NSW. Given the potential for a subsequent pandemic wave, this provides support for maximising rates of community vaccination with a pandemic-specific vaccine.

Craig B Dalton · Michelle A Cretikos · David N Durrheim · Ian M Seppelt · William D Rawlinson · Dominic E Dwyer

To the Editor: Kelly showed that the pandemic (H1N1) 2009 influenza epidemic experience in Victoria was similar, overall, to a moderately severe influenza season.1 As with seasonal influenza, 0–4 year olds had the highest hospital admission rates,2,3 with those in the first year of life most likely to be admitted to intensive care units (ICUs). “Swine flu” did have differences to seasonal flu, with “younger” people having disproportionally more serious illness.2,3 However, these younger groups were not necessarily what most would regard as young. Eighty per cent or more of deaths associated with pandemic (H1N1) 2009 influenza were among those aged over 35 years, and most had identifiable risk factors.2,3 The peak 5-year age group for ICU admissions was 50–54 years.2 Those aged over 65 years seemed relatively protected — presumably because most had pre-existing immunity resulting from infection with H1N1-type viruses circulating since 1918. Pre-existing immunity was also not uncommon in others. In 18–65-year-olds, 30% had protective antibody levels to pandemic (H1N1) 2009 influenza before vaccination.4 Using data from New South Wales, we can ascertain the severity of pandemic (H1N1) 2009 influenza in different age groups.2 In NSW last winter, 1214 people were hospitalised, 225 were admitted to ICUs and 48 died with pandemic (H1N1) 2009 influenza (17.2, 3.2 and 0.7 per 100 000 population, respectively). Pregnant women had a 10 times higher risk of death (1.4 per 100 000) than other women of their age. For the overall population aged under 40, the death rate was 0.4 per 100 000, with most having identifiable risk factors. Thus, the death rate for those aged under 40 years, but with no known risk factors, was about one per million people. Most of the mortality predictions for this epidemic have been consistently wrong and exaggerated. Some were suggesting 10 000 deaths in NSW alone.5 These, and other predictions of second and third killer waves, have generated needless fear and inappropriate responses.6 Many experts and even health departments were postulating that more than 20% of the population would become infected, with an associated case fatality rate of 1% or more. That translates to a population mortality rate of 200 per 100 000 people, which is 300 times higher than what actually occurred. We need to learn from our recent experience so we can better plan and act in the future. Analysis such as that performed by Kelly is essential if we do not want to repeat the mistakes we made during this pandemic, caused by a virus of relatively low virulence.

Peter J Collignon

Cough is a common and distressing symptom that results in significant health care costs from medical consultations and medication use. Cough is a reflex activity with elements of voluntary control that forms part of the somatosensory system involving visceral sensation, a reflex motor response and associated behavioural responses. At the initial assessment for chronic cough, the clinician should elicit any alarm symptoms that might indicate a serious underlying disease and identify whether there is a specific disease present that is associated with chronic cough. If the examination, chest x-ray and spirometry are normal, the most common diagnoses in ADULTS are asthma, rhinitis or gastro-oesophageal reflux disease (GORD). The most common diagnoses in CHILDREN are asthma and protracted bronchitis. Management of chronic cough involves addressing the common issues of environmental exposures and patient or parental concerns, then instituting specific therapy. In ADULTS, conditions that are associated with removable causes or respond well to specific treatment include protracted bacterial bronchitis, angiotensin-converting enzyme inhibitor use, asthma, GORD, obstructive sleep apnoea and eosinophilic bronchitis. In CHILDREN, diagnoses that are associated with removable causes or respond well to treatment are exposure to environmental tobacco smoke, protracted bronchitis, asthma, motor tic, habit and psychogenic cough. In ADULTS, refractory cough that persists after therapy is managed by empirical inhaled corticosteroid therapy and speech pathology techniques.

Peter G Gibson MB BS, FRACP · Anne B Chang FRACP, MPHTM, PhD · Nicholas J Glasgow FRACGP, MD, FAChPM · Peter W Holmes MB BS, FCCP, FRACP · Peter Katelaris MB BS, MD, FRACP · Andrew S Kemp MB BS, FRACP, PhD · Louis I Landau AO, MD, FRACP · Stuart Mazzone PhD · Peter Newcombe DipT, BEd, PhD · Peter Van Asperen MB BS, MD, FRACP · Anne E Vertigan BAppSc(SpPath), MBA, PhD

Pandemic (H1N1) 2009 influenza has generated many controversies in Australia around case definitions, laboratory diagnosis, case management, medical logistics and travel restrictions. Our experience as clinical advisers in the Victorian Department of Human Services Emergency Operations Centre suggests the following: Case definitions may change frequently, and will tend to become more clinically specific over time. Early in a pandemic, laboratory diagnosis plays a critical role in case finding and pathogen identification. Later in the pandemic, standardised case management applied to well crafted case definitions should reduce reliance on the diagnostic laboratory in clinical management. The diagnostic laboratory will remain critical to monitoring disease surveillance, pathogen virulence, and drug susceptibility. Medical logistics will continue to challenge pandemic managers as the health sector struggles to do the most good for the greatest number of people. Travel restrictions remain scientifically controversial public health recommendations. Issues of scalability (escalation and de-escalation of the response) relating to virus lethality need to be resolved in current pandemic planning.

David A Bradt MD, FACEM, FAFPHM · Joseph Epstein FRACS, BA(Hons), FACEM

Objective: To compare the patient characteristics, clinical features and outcomes of adult patients hospitalised with pandemic (H1N1) 2009 influenza and seasonal influenza.Design and setting: Retrospective medical record review of all patients admitted to Liverpool Hospital, Sydney, with laboratory-confirmed influenza from the initiation of the “PROTECT” phase of the pandemic response on 17 June until the end of our study period on 31 July 2009.Main outcome measures: Severity of illness; requirement for admission to the intensive care unit (ICU) and/or invasive ventilation; mortality.Results: Sixty-four adults were admitted to Liverpool Hospital with influenza, 48 with pandemic (H1N1) 2009 influenza and 16 with seasonal influenza. Thirteen patients were admitted to the ICU. Seven required invasive ventilation, with 2 patients requiring ongoing extracorporeal membrane oxygenation (ECMO). Five patients died (mortality rate, 8%) with two deaths occurring after the study period. Patients with pandemic (H1N1) 2009 influenza were younger and less likely to be immunocompromised than patients with seasonal influenza. However, the clinical features of pandemic (H1N1) 2009 influenza and seasonal influenza were similar.Conclusions: Our findings show that the clinical course and outcomes of pandemic (H1N1) 2009 influenza virus are comparable to those of the current circulating seasonal influenza in Sydney. The high number of hospital admissions reflects a high incidence of disease in the community rather than an enhanced virulence of the novel pandemic influenza virus.

Ya-Shu Chang MB ChB · Sebastiaan J van Hal MB ChB, FRACP, FRCPA · Peter M Spencer MB BS · Iain B Gosbell MD, FRACP, FRCPA · Peter W Collett MB BS, PhD, FRACP

To the Editor: We describe two liver transplant patients who presented with unexplained dyspnoea and were subsequently found to have unilateral right diaphragmatic palsy, an uncommon complication of orthotopic liver transplantation.1-3 Both transplant recipients were male. One, aged 64 years, had a liver transplant in 2005 for hepatitis C-related chronic liver disease. The other, aged 66 years, had a liver transplant in 2004 for end-stage alcoholic liver cirrhosis. Both patients had presented with exertional dyspnoea several weeks after transplantation. Both were reformed smokers with no prior respiratory symptoms or established respiratory or cardiac condition. Preoperative pulmonary function tests had been essentially normal in both patients (Box 1). Chest x-rays of both patients during the postoperative convalescence period showed unilateral elevation of the right hemidiaphragm compared with the immediate pre-transplant images. (Images for Patient 1 are shown in Box 2.) Fluoroscopic study (the “sniff test”) and a computed tomography scan of the chest confirmed the presence of right hemidiaphragmatic palsy in both patients. Follow-up chest x-rays and pulmonary function tests over 2 years showed no significant improvement. In both patients, the postoperative clinical course over these 2 years was characterised by recurrent hospital admissions with hypoxaemia and intercurrent respiratory tract infections, some requiring supplemental oxygen therapy, non-invasive positive pressure ventilation and invasive ventilation in the intensive care unit. Currently, one of these patients is well, apart from dyspnoea on moderate exertion. The other patient died from a cause unrelated to his diaphragmatic palsy. Unilateral diaphragmatic palsy following liver transplantation is thought to be related to traumatic crush injury to the right phrenic nerve from a clamp placed on the inferior vena cava (IVC) during surgery.1 The proximity of the phrenic nerve to the IVC renders it very vulnerable to this type of injury from side-to-side cross-clamping of the suprahepatic IVC.1,2 In 2008, we modified our technique to avoid cross-clamping of the IVC by performing cavocavostomy, a type of “piggyback” technique that involves “side-biting” (partial clamping) of the retrohepatic IVC away from the diaphragm.4 Unilateral diaphragmatic palsy can reduce exercise tolerance5 and may place additional mechanical stress on ventilation, which could exacerbate hypoxaemia if these patients develop intercurrent pulmonary infections. Reporting on a series of patients with phrenic nerve injury after liver transplantation, McAlister and colleagues1 found right hemidiaphragmatic palsy in 38% of patients after transplantation, but most of the patients recovered their diaphragmatic function within 9 months. In contrast, our patients did not show any signs of recovery for over 2 years, indicating that loss of diaphragmatic function after liver transplantation may be longstanding or permanent. 1 Comparison of pulmonary function tests before and after orthotopic liver transplantation* Patient 1 Patient 2 Pulmonary function test Before transplant After transplant Difference Before transplant After transplant Difference FEV1 (% of predicted) 2.72 L (80%) 1.73 L (51%) – 29% 2.78 L (85%) 1.40 L (47%) – 38% FVC (% of predicted) 3.79 L (87%) 2.41 L (56%) – 31% 3.83 L (92%) 2.17 L (57%) – 35% FEV1/FVC 0.72 0.72 0.73 0.65 TLC (% of predicted) 5.81 L (87%) 4.28 L (62%) – 25% 7.09 L (110%) 5.18 L (86%) – 24% FEV1 = forced expiratory volume in 1 second. FVC = forced vital capacity. TLC = total lung capacity. * Tests were performed while the patients were in a clinically stable condition. 2 Erect chest x-rays before and after orthotopic liver transplantation, Patient 1 A: In 2005, before liver transplant. B: In 2006, 6 months after liver transplant. Note marked elevation of the right hemidiaphragm and presence of bilateral calcified pleural plaques.

H S Subhash · John W C Chen · Libby John · Jeffery J Bowden · Dimitar Sajkov · Peter Frith

Objectives: To determine the rate of prescription of and government expenditure for domiciliary oxygen therapy (DOT) in Australia, and to identify interstate differences in rates, costs and service provision.Design: Retrospective observational study.Participants and setting: Government departments and health services (state and federal) that funded DOT in Australia in the 2004–05 financial year (including the Department of Veterans’ Affairs [DVA] and the Department of Health and Ageing [DoHA]).Main outcome measures: Prescription rates, cost of DOT in 2004–05, and services provided in each jurisdiction.Results: In 2005, 20 127 patients were using DOT, giving a national prevalence of 100 prescriptions per 100 000 population. The total cost was about $31 million. State governments, the DVA and the DoHA funded 13 899 (69%), 4084 (20%) and 2144 (11%) patients, respectively. Prescription rates varied threefold between the states, ranging from 44 (Northern Territory) to 133 (Tasmania) per 100 000 population. Cost per patient per year varied fourfold between the DVA and the DoHA. All jurisdictions funded oxygen according to the clinical criteria of the Thoracic Society of Australia and New Zealand, but considerable variability in service provision was identified.Conclusion: DOT prescription rates and costs vary considerably between jurisdictions. An urgently needed national DOT register would enable the current variability to be understood and allow service planning and benchmarking of clinical outcomes.

John G Serginson RN, BN, MCN · Ian A Yang MB BS(Hons), PhD, FRACP · John G Armstrong MB BS, PhD, FRACP · David M Cooper MB BS, MSc, FRACP · Anthony M Matthiesson MB BS, FRACP · Stephen C Morrison MB BChir, PhD, FRACP · Judy M Gair MHSc · Barbara Cooper MB BS, FRACMA, FRACGP · Paul V Zimmerman MB BS, MD, FRACP

To the Editor: Bronchiolitis, most often associated with respiratory syncytial virus (RSV), is a major cause of hospitalisation in young children. Those with chronic lung and congenital heart disease (the latter affecting about 192 births annually in Western Australia) are at particularly high risk.2 Immunoprophylaxis with the RSV monoclonal antibody palivizumab is effective in reducing severe RSV-related hospitalisations, and monthly immunoprophylaxis is recommended in high-risk children.2,3 Monthly immunoprophylaxis is costly; therefore, the most cost-effective schedule follows the times of peak RSV activity4 — usually the winter months, May to October. Using the Western Australian Data Linkage System,5 we investigated the seasonality of bronchiolitis hospitalisations (International Classification of Diseases-10 code J21) from 1996 to 2005 as a proxy for RSV-related illness. Data specifically for RSV-related illness were considered unreliable because some children may not have been tested for RSV, test results may not have been documented on hospital discharge notes, or RSV immunofluorescence tests may have given false negative results. Furthermore, RSV codes (B97.4, J12.1, J20.5, J21.0) were not used by hospitals in WA until July 1999. We identified 11 988 hospitalisations for bronchiolitis throughout WA among 245 249 births. Most bronchiolitis admissions (81%) were in children younger than 12 months. In the Perth metropolitan region, there was a clear winter seasonal pattern, with hospitalisations peaking in July. However, in the Kimberley region in northern WA, there was a sustained bimodal seasonality, with a peak in April and second peak in August (Box). Moreover, only 51.5% (469) of bronchiolitis admissions in the Kimberley and 61.5% (444) in the Pilbara–Gascoyne (located in mid-north WA) occurred between May and October, as opposed to 84.3% (6354) in the metropolitan region. These data support an earlier implementation and longer dosing schedule with palivizumab for high-risk children in the Kimberley and Pilbara–Gascoyne than for those in Perth. Our study has some limitations. Not all bronchiolitis hospitalisations may be caused by RSV. However, when we investigated only those hospitalisations with a specific RSV code, the monthly distribution showed a similar pattern. Additionally, timing of RSV activity, and therefore bronchiolitis, may vary from year to year. Although the numbers were too small to allow separate analysis by calendar year, bronchiolitis hospitalisations in the Kimberley showed extended seasons in 8 of the 10 years. Our findings support the need for each jurisdiction to know its seasonal pattern of bronchiolitis and RSV hospitalisations, and to implement recommended palivizumab schedules accordingly. Such use of extended prophylactic regimens may well require its cost-effectiveness to be reconsidered. Our analysis highlights the relevance of population-based data linkage studies to clinical care policy. Monthly distribution of bronchiolitis hospitalisations by region of child’s birth, 1996–2005

Hannah C Moore · Anthony D Keil · Peter C Richmond · Deborah Lehmann