Respiratory disease

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

Jill L Sherriff

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

Craig M Mellis

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

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

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

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

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

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

Re: "The effectiveness of coordinated care for people with chronic respiratory disease", by Smith BJ, McElroy HJ, Ruffin RE, Frith PA, Heard AR, Battersby MW, Esterman AJ, Del Fante P and McDonald PJ, published in the 4 November issue of the Journal (Med J Aust 2002; 177: 481–485). The correct credentials and title for Peter A Frith are MB BS, FRACP, Director, Respiratory Medicine, Repatriation General Hospital, Daw Park, SA 5041. The web version of the article was corrected on 18 December 2002.

Brian J Smith MB BS, PhD · Heather J McElroy BSc(Hons) · Richard E Ruffin MD, FRACP · Adrian R Heard MPH, BSocAdmin · Peter A Frith MB BS FRACP · Malcolm W Battersby MB BS, PhD · Adrian J Esterman BSc(Hons), MSc · Peter Del Fante MB BS(Hons), MSc(Public Health) · Peter J McDonald MB BS, FRACP

To the Editor: "Chop-chop" tobacco is illicit tobacco that has been grown and clandestinely distributed by farmers and wholesalers and sold on without government intervention or taxation. There is no quality control over this illicit substance, which may be adulterated or "bulked up". It is sold illegally "under the counter" by weight for rolled cigarettes by unscrupulous tobacconists and grocers. This type of tobacco, which has been roughly chopped up (hence "chop-chop"), is very cheap compared with legally produced manufactured cigarettes. The prevalence of the use of chop-chop in the smoking community is unknown. However, the Australian Taxation Office (ATO) has a keen interest in the distribution of this substance, and estimates that many millions of dollars are lost in revenue from the illegal sale of chop-chop. Arrests and fines initiated by the ATO have so far occurred primarily in Queensland and Victoria. Results of analysis of chop-chop vary from batch to batch, but samples have been shown to contain nicotine (Professor G Starmer, Department of Pharmacology, and Mr B Tattam, Mass Spectrometry Unit, Department of Pharmacy, University of Sydney, personal communication). It may also be fumigated with bleach and may be bulked up to add weight (M Rushton, ATO, personal communication). Although most people smoke it because it is cheap, many have misguided beliefs, for which there is no evidence, that it is "better" than other forms of tobacco. Results of a survey of 44 consecutive patients attending the Smokers' Clinics of the Central Sydney Area Health Service 43% currently using "chop-chop" 84% smoke it because it is cheaper 58% believe it is better for you 74% believe it has no additives 16% believe it has no nicotine 63% know it is not legal A retrospective survey was carried out to assess the prevalence of and attitudes towards illicit tobacco smoking among patients attending the Smokers' Clinics of the Central Sydney Area Health Service (approved by the CSAHS Ethics Committee, June 2002). Patients were routinely asked the type of tobacco they smoked and their beliefs regarding this type of tobacco. The results are shown in the Box. Many of the patients attending the Smokers' Clinics (dedicated exclusively to patients who smoke and have chronic obstructive pulmonary disease [COPD]) smoke this type of illegal tobacco. Several patients volunteered that smoking chop-chop precipitated an acute exacerbation of their COPD. Four patients have recently presented to a hospital emergency department for exacerbation of COPD after smoking chop-chop. Although smokers are loath to volunteer their use of this illegal tobacco, smokers and clinicians should be warned that smoking chop-chop does not constitute a positive health move, is not less harmful, and may be quite dangerous. Quitting smoking altogether is the best health move.

Renee Bittoun

Clinical record In 2001, an outbreak of Bordetella pertussis infection occurred in a hospital special care nursery. The index case, Parent A, had a two- to three-week history of non-productive cough without paroxysms, whooping or vomiting. She was admitted to hospital in labour and gave birth to Baby A on Day 0 in early January 2001. The baby was born four weeks prematurely and remained in the special care nursery for 15 days. The mother spent several hours there each day handling her infant and occasionally assisted with the care of infants in adjoining cots. Serum taken 19 days after she developed cough was negative for Bordetella pertussis IgA and IgM and equivocal for IgG (Figure) by enzyme-linked immunosorbent assay (ELISA). On Day 15, Baby B (in the cot adjacent to Baby A) developed a cough and respiratory distress. Initial investigations did not reveal a cause. A nasopharyngeal aspirate collected on Day 23 was positive for B. pertussis by direct fluorescent antigen testing. On Day 18, a nurse who had cared for Baby A developed a cough. Her serum was positive for B. pertussis IgA on Day 31 by ELISA; she commenced roxithromycin therapy. On Day 31, serum collected from Parent A was positive for B. pertussis IgA. On Day 39, Baby A developed a respiratory illness despite a seven-day prophylactic course of erythromycin. A nasopharyngeal aspirate was positive for B. pertussis by polymerase chain reaction (PCR) on Day 43. Both received erythromycin. On Day 41, a nasopharyngeal aspirate collected during contact tracing from Baby C (in the nursery from Day 0 to 6) grew B. pertussis. She had not received chemoprophylaxis and had a mild cough. She was treated with erythromycin. Contact tracing Contact tracing of infants, parents and staff was undertaken. The incubation period of pertussis is six to 21 days, and is generally less than 10 days.1 The parents of all 19 babies who had been in cots adjoining Baby A were notified, and erythromycin prophylaxis was recommended. Eleven babies received prophylaxis. Parents of other babies in the nursery were contacted and advised to notify the hospital if they or their babies developed a cough over the following 21 days. No further cases were identified. Fifty-three staff with close contact with the cases were screened using direct fluorescent antigen testing of nasopharyngeal aspirates and serum IgA testing. Thirty-three received antibiotic prophylaxis. No staff had illness consistent with acute pertussis or developed infection, as shown by nasopharyngeal and serum IgA tests. There were 10 339 notifications of pertussis in 1999– 2000 in Australia.2 People aged 15 years and over comprised 62% of these notifications.2 Studies indicate that 12% to 32% of cases of prolonged cough (over two weeks' duration) in adolescents and adults are due to B. pertussis.3 Recent articles highlight reasons for the apparent shift in disease burden.3-6 Although adolescents and adults are the primary reservoir of the disease and the main source of infection in infants and unvaccinated children, pertussis often goes unsuspected in these age groups.3,4,7 Pertussis in adults is difficult to detect clinically. Delays and errors in diagnosis occur because the presentation is commonly mild or atypical, and may be asymptomatic.7 This may be a result of immunological recall. As past vaccination or illness does not confer lifelong immunity to pertussis, reinfection is common.8 Detection in adults is further impeded by the poor sensitivity of culture and serological tests,1 particularly if performed several weeks after onset of cough.6 Polymerase chain reaction of nasopharyngeal swabs or aspirates improves detection.6 Deaths from pertussis average one per year in Australia, and almost all involve neonates and unvaccinated infants.2 These groups acquire pertussis in a range of settings, including hospitals;9,10 parents, visitors and healthcare staff are a source of nosocomial outbreaks.7 During the events described here, there was no concurrent epidemic of pertussis in the community (Dr B McCall, Director, Brisbane Southside Public Health Centre, personal communication). Hospitalised infants exposed to pertussis are at high risk of morbidity and mortality, as maternal antibodies provide inadequate protection, while infants less than four weeks old are too young to commence vaccination.11 While erythromycin is the prophylaxis of choice,11 it has been associated with hypertrophic pyloric stenosis in neonates.12 Preventing nosocomial transmissionB. pertussis is spread via mucosal contact with infectious respiratory droplets and secretions.13 We suggest the following standard and transmission-based infection control precautions to protect hospitalised infants: limit access of staff and visitors to nurseries; provide adequate space between open cots (at least one metre); discourage parents from contact with infants other than their own; and perform hand antisepsis before entering the nursery and before and after patient contact. Surgical masks are chiefly designed to protect the wearer from exposure to blood and body fluids; it is suggested that they may also reduce the opportunity for onward transmission of infections spread via large droplets.13 Other important measures include educating staff and visitors to report coughs, diagnosing their aetiology, and providing treatment and prophylaxis. A diagnosis of pertussis can be confirmed by nasopharyngeal aspirate (culture, direct fluorescent antigen testing or PCR) or serological testing (IgA).7 Erythromycin is the treatment and prophylaxis of choice at all ages.11 Targeted booster vaccination of parents and healthcare workers in contact with infants has been recommended, although not universally adopted.3-6 An acellular pertussis vaccine is available for this purpose, but its efficacy and duration of protection remain to be determined.3-5 Australia's pertussis immunisation schedule is restricted to infants and young children.11 Infection control measures are important because of the difficulty in prohibiting all people with coughs from entering hospital nurseries, and the cost implications of vaccinating all adults in contact with infants. Lessons from practice Pertussis should be considered in adults and older children with a cough lasting over two weeks regardless of a past history of pertussis vaccination or infection. If pertussis is suspected, a nasopharyngeal aspirate or swab should be tested by polymerase chain reaction. Serological testing may also be useful when symptoms have been established for longer than two weeks. Adolescents and adults are the primary reservoir of the disease and the main source of infection in infants and unvaccinated children. Hospitalised infants are at high risk for morbidity and mortality from pertussis. Infection control measures are paramount, and targeted vaccination of adults should be considered.

Natalie M Spearing BSN, MBA · Robert L Horvath FRACP · Joseph G McCormack FRCP, MD, FRACP

Objectives: To evaluate the effectiveness of coordinated care for chronic respiratory disease.Design and setting: Community-based geographical control study, in western (intervention) and northern (comparison) metropolitan Adelaide (SA).Participants: 377 adults (223 intervention; 154 comparison) with chronic obstructive pulmonary disease, asthma or other chronic respiratory condition, July 1997 to December 1999.Intervention: Coordinated care (includes care coordinator, care guidelines, service coordinator and care mentor).Main outcome measures: Hospital admissions (any, unplanned and respiratory), functionality (activities of daily living) and quality of life (SF-36 and Dartmouth COOP).Results: At entry to the study, intervention and comparison subjects were dissimilar. The intervention group was 10 years older (P < 0.001), less likely to smoke (P = 0.014), had higher rates of hospitalisation in the previous 12 months (P < 0.001) and had worse self-reported quality of life (SF-36 physical component summary score [P < 0.001] and four of nine COOP domains [P = 0.002–0.013]). After adjustment for relevant baseline characteristics, coordinated care was not associated with any difference in hospitalisation, but was associated with some improvements in quality of life (SF-36 mental component summary score [P = 0.023] and three of nine COOP domains [P = 0.008–0.031]) compared with the comparison group.Conclusions: Coordinated care given to patients with chronic respiratory disease did not affect hospitalisation, but it was associated with an improvement in some quality-of-life measures.

Brian J Smith MB BS, PhD · Heather J McElroy BSc(Hons) · Richard E Ruffin MD, FRACP · Adrian R Heard MPH, BSocAdmin · Peter A Frith MD, FRACP · Malcolm W Battersby MB BS, PhD · Adrian J Esterman BSc(Hons), MSc · Peter Del Fante MB BS(Hons), MSc(Public Health) · Peter J McDonald MB BS, FRACP

To the Editor: Comprehensive care has been shown to improve outcome in asthma management when it has four components — asthma education, self-monitoring, written self-management plans, and regular medical review.1,2 A recent Cochrane Review has explored the role of one of these components — written self-management plans — and concluded that there is "no consistent evidence that written plans produced better patient outcomes".3 Should this cause us to change our management strategies in Australian general practice? Does this mean that our patients are not able to care for their own asthma without our intensive assistance? These findings update a 1998 review of the role of written asthma management plans as part of comprehensive care in 1998: "In five studies which compared subjects who managed their asthma by self-adjustment according to individualised written plan with those whose medications were adjusted by the doctor, lung function data (FEV1 [forced expiratory volume in one second] and PEF [peak expiratory flow]) were significantly higher in the self-managed group."1 In Australian general practice, between 30% and 50% of patients are given a written asthma management plan.4 These plans form part of known beneficial comprehensive asthma care plans, such as the Six-Step Asthma Management Plan5 or the Asthma 3+ Visit Plan.4 The small number of available high quality trials for this most recent review led the authors to say, "Available trials are too small and the results too inconsistent to form any firm conclusions", and suggests that more trials are needed to produce a conclusive result.3 We should be careful not to lose the positive effects of improved chronic disease management in asthma by over-responding to this one review of one component of comprehensive care.

Andrew M Thornett · Jonathan W Newbury · Andre J Duszynski

Comment: A Cochrane systematic review identified the beneficial effects of planned asthma management and education that includes a written action plan.1 These findings have now been adapted for primary care and implemented as the Asthma 3+ Visit Plan. This involves a systematic assessment of asthma symptoms, lung function, and current treatment at each visit. Treatment and management skills are optimised and the patient is given written instructions on how and when to increase treatment when asthma deteriorates (a written action plan). A recent Cochrane review asked whether one can get the same benefits by doing less — by simply supplying a patient with a written action plan.2 The review found that the literature was inconclusive. This doesn't mean that written action plans are not effective; it means that there is not enough evidence to be able to answer the question. The result of "no evidence of effect" is completely different to "evidence of no effect".3,4 This is a crucial distinction, as many systematic reviews find insufficient evidence to be able to assess a treatment. This is a statement about our ignorance rather than a statement about whether a treatment works or not. The review also highlights the need to carefully evaluate the control intervention. For example, the control groups in two studies in the systematic review2 received regular medical review, with assessment of severity and optimisation of inhaled steroid therapy. It is not surprising that these studies found it difficult to identify any additional effect of an action plan. Cochrane systematic reviews conclude with recommendations for clinical practice that highlight effective treatments,1 and with recommendations for research that indicate where more information is needed.2 The review looking at just supplying patients with written action plans2 exemplifies the latter.

Peter G Gibson

To the Editor: The recent article by Johnston et al is an important contribution to the small but growing body of literature on the health effects of particulate matter (PM) pollution derived from bush or forest fire.1 The authors studied an important wood smoke PM exposure in Australia and showed consistent associations between higher concentrations of PM and emergency department presentations for asthma. Most research on the effects of PM has focused on motor-vehicle-derived PM pollution.2,3 However, Johnston et al do not appear to have accounted for serial correlation in their data. Measurements connected in time, such as repeated measurements of the same population, are likely to be correlated and not independent.4 Further, school holidays have been shown to influence hospital admission rates.5 The major Northern Territory school holidays in June and July are in the middle of the study period. Johnston et al adjusted for some important confounders in their analysis (acute respiratory infections and weekdays/weekends).1 However, in time-series data, especially those dealing with asthma, serial correlation, as well as other potentially important confounders such as school holidays and temperature and humidity, should also be assessed. It may be that, even after appropriate adjustments for serial correlation and potential confounders, the rate ratios found by Johnston et al may not alter appreciably. However, it would have been useful for the investigators to have at least discussed any effects that controlling for serial correlation and other potential confounders might have had on their findings.

Bin B Jalaludin · Guy B Marks · Geoffrey G Morgan

In reply: Jalaludin and colleagues query the potential effects that serial correlation and confounding by school holiday time periods may have had on our finding of an association between particulates derived from bushfire smoke and asthma presentations.1 As previously discussed by Schwartz, time series analyses are important to control for serial correlations, particularly those due to the effects of seasonality and weather fluctuations.2 Our study did not cover a number of seasons. It was conducted during one tropical dry season, a period characterised by remarkably stable day-to-day weather conditions.3 For this reason, we believe that the effects of any autocorrelation would have been negligible. It is of interest that the development of statistical methods for analysing time series of count data during the 1990s, and analysis of large studies of particulate pollution using these methods, did not have an important effect on the conclusions reached by earlier studies.4 There is evidence that hospital admissions for asthma fall during school holidays.5 Anecdotal reports of more regional fires suggest that, if anything, particulate concentrations over Darwin might increase at these times. A reanalysis of our data including school holiday periods as a potential confounding factor did not appreciably alter our results in either the continuous (revised incidence rate ratio [IRR],1.26; 95% CI, 1.12–1.41, compared with original IRR, 1.20; 95% CI, 1.09–1.34) or categorical analysis (see Table). Asthma presentations and exposure levels of PM10* (μg/m3) Rate ratio for asthma presentations (95% CI) Same-day PM10 category (μg/m3) Original analysis† Revised analysis‡ < 10 1.0 1.0 10–< 20 0.90 (0.60–1.35) 0.84 (0.43–1.63) 20–< 30 1.11 (0.74–1.69) 1.13 (0.58–2.18) 30–< 40 1.18 (0.72–1.97) 1.21 (0.58–2.50) ≥ 40 2.38 (1.46–3.90) 2.47 (1.21–5.01) * Particles of 10 microns or less in aerodynamic diameter per cubic metre. † Adjusted for influenza-like illness and weekday. ‡ Adjusted for influenza-like illness, weekday and school holiday periods.

Fay H Johnston · Anne Kavanagh · David MJS Bowman · Randall K Scott

Asthma is, quite literally, a household word in Australia, a disease so commonplace that there is a tendency within our community to understate the seriousness of it. But when you have a disease that affects one in four primary-school-aged children, with no known cure, there must be unceasing vigilance in the fight against it. Clearly, we need to know more about asthma and its causes — ...

David Clarke

While we have learnt much of the molecular and immunological basis of childhood asthma and treatment has changed dramatically, the impact on lifestyle, especially in early childhood, has not moved forward as rapidly. This is predominantly due to the difficulty of collecting objective data on the very young. To understand the causes of asthma and improve outcomes, with particular emphasis on primary prevention, it is ...

Craig M Mellis MD, MPH · Louis I Landau MD, FRACP

What we knowWhat we need to know

Louis I Landau MD FRACP

What we knowWhat we need to know

Peter N Le Souëf MD FRACP

What we knowWhat we need to know

Colin F Robertson MD, FRACP

Over the past 20 years, inhaled corticosteroids have become established as cornerstone therapy in the treatment of obstructive pulmonary disorders, ranging from asthma and chronic obstructive pulmonary disease to cystic fibrosis. The appropriate use of inhaled corticosteroids has transformed the management of asthma in children, improving the quality of life of children and their families, improving exercise tolerance, and reducing hospitalisation and mortality rates. Asthma mortality rates in Australia have fallen by more than 50% over the past 12 years, in parallel with our increased use of inhaled corticosteroids and the development of clinical guidelines.1 We have gained confidence in the safety of inhaled steroids at recommended doses, supported by national guidelines and extensive reviews.2 Local side effects, including oropharyngeal candidiasis and laryngeal dysfunction, can usually be controlled with the use of spacer devices. Further, at recommended doses, initial concerns about growth failure and impaired bone mineralisation have not been realised.2 In recent years, with the advent of more potent steroids and more efficient delivery systems, the relative doses commonly used have increased. There have been several reports of serious adverse events resulting from doses of inhaled corticosteroids in excess of those recommended. These include growth failure,3 and suppression of the hypothalamic–pituitary–adrenal axis4-6 — resulting in acute hypoglycaemia, altered consciousness and coma, convulsions7,8 and death.9 While the majority of these effects have been reported at higher doses, some have occurred at a dose within the recommended range, suggesting that individual susceptibility may also be important. These effects are more commonly associated with one potent inhaled corticosteroid, but this is probably a result of over-representation of that drug in the higher dosage range. Comparative studies would suggest that this is a class effect of inhaled corticosteroids.4 Are we overusing inhaled corticosteroids? New evidence-based National Asthma Council guidelines define the need for inhaled corticosteroids in asthma. They recommend an upper limit of 500 μg per day of fluticasone propionate (or equivalent) in children, and 1000 μg per day in adults with severe asthma. In support, a recent meta-analysis, examining the dose response to inhaled corticosteroids in adolescents and young adults, reported that 90% of the maximum benefit was achieved at a daily dose equivalent to 250 μg fluticasone propionate.10 Minimal further improvement resulted from increases up to 600 μg/day. The introduction of long-acting β-agonists at low doses of inhaled corticosteroids can achieve improved asthma control, avoiding the need for higher doses of inhaled corticosteroids. When asthma is not controlled by a dose of inhaled corticosteroids equivalent to 500 μg/day fluticasone propionate and long-acting β-agonists, consideration should be given to issues of adherence to the treatment regimen, inhaler technique or an alternative diagnosis. In the UK survey of adrenal crisis due to inhaled corticosteroids,9 three of the 28 children did not have asthma and, in five, asthma did not account for all the respiratory symptoms. Inhaled steroids have been shown to be ineffective in children with recurrent cough and those with episodic viral-associated wheeze. Clinicians should be alert to the clinical features of hypoadrenalism, particularly when precipitated at a time of metabolic stress, perhaps indicating adrenal crisis. Children taking excessive doses of inhaled corticosteroids (> 500 μg/day fluticasone propionate) should have their hypothalamic–pituitary–adrenal axis assessed, and their parents should be informed of the risks and the potential need for systemic corticosteroid cover during intercurrent illness and surgery. The National Asthma Council recommends the introduction of inhaled corticosteroids (alone or in combination) to gain control of symptoms. On clinical review, there should be a reduction (ie, back-titration) to an appropriate dose to optimise symptom control and reduce the likelihood of adverse effects. By comparison with their United States and European counterparts, Australian prescribers have used higher doses of inhaled corticosteroids, but there is now a clear incentive to reverse this trend. The availability of effective anti-inflammatory therapy, useful and well-publicised guidelines, as well as incentive payments to general practitioners for the treatment of moderate to severe asthma under the 3+ Visit Plan (http://www.health.gov.au/pq/asthma/3plusgp.htm), should pave the way for greater improvements in the management of asthma. The goal of asthma management is to achieve optimal control of asthma symptoms with the lowest effective medication dose, allowing children to enjoy a normal quality of life neither burdened by, nor at risk of, serious adverse events. Inhaled corticosteroids remain the cornerstone of asthma management. Responsible use of inhaled corticosteroids will reinforce confidence in the consumer, whereas irresponsible use will promote steroid phobia — a significant barrier to adherence.

John W Wilson PhD, FRACP · Colin F Robertson MD, FRACP

What we knowWhat we need to know

Karen O McKay LLB, PhD · James C Hogg MD, PhD

What do we know?What do we need to know?

Gary P Anderson PhD

Objectives: To explore the burden of asthma on the lives of people presenting to hospital emergency departments for asthma treatment.Design: A qualitative study. Consenting individuals with asthma who presented to emergency departments were interviewed in-depth, and interviews were taped, transcribed and thematically analysed. Questionnaire data on medication use, respiratory health and asthma knowledge were also collected. Asthma severity was determined from the medical records.Setting: A tertiary teaching hospital and a suburban hospital during March and April 2000, and a rural hospital during July and August 2000.Participants: Sixty-two participants (19 male and 43 female), aged 18–70 years.Results: The burden of asthma was broad, affecting social life, personal relationships, employment and finances. The cost of asthma medication was an issue for nearly two-thirds of participants. Individuals performed their own "cost–benefit analysis" for medication use, weighing up expense, perceived side effects and potential benefits. As a consequence, several participants chose to alter their medication dose, or not to take prescribed medications. For some participants, asthma directly contributed to diminished employment opportunities.Conclusions: To achieve a therapeutic partnership, doctors need to be aware of the substantial social, personal and financial burden of asthma for their patients. They should also recognise that patients' perceptions of treatment cost may compromise treatment adherence.

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

What we knowWhat we need to know

David Isaacs MD, FRACP, FRCPCH · Preeti Joshi PhD, FRACP

What we knowWhat we need to know

Andrew S Kemp PhD, FRACP

What we knowWhat we need to know

Stephen M Stick MD, PhD, FRACP