Perinatal and maternal risk factors for autism spectrum disorders in New South Wales, Australia.

BACKGROUND: This study was commenced in 1999 with the aim of examining risk factors for autism using established population-based data for comparison. METHODS: Cases were ascertained using active surveillance and compared with birth data. RESULTS: Four risk factors were found to be significantly associated with autism using binary logistic regression analysis; being male [adjusted odds ratio (OR) 4.7, 95% confidence interval (CI) 3.2-7.0], being born prematurely (adjusted OR 2.2, 95% CI 1.5-3.5), having maternal age >/=35 years (adjusted OR 1.7, 95% CI 1.2-2.4) and having a mother born outside Australia (adjusted OR 1.4, 95% CI 1.0-1.9). For analysis completed for pregnancies, rather than live births, multiple birth was also a significant risk factor for one or more children of the pregnancy to be affected by autism (adjusted OR 2.5, 95% CI 1.1-5.5). There was a statistically significant trend towards increasing risk with increasing risk factor 'dose' for gestational age (P = 0.019), multiple birth (P = 0.016) and maternal age (P < 0.001). For mother's country of birth the group with the highest risk were children of mother's born in south-east or north-east Asia. There was a non-significant trend towards a higher proportion of children with developmental disability having risk factors. CONCLUSION: Replication of risk factors from previous studies and a significant risk factor 'dose' effect add to growing evidence that maternal and perinatal factors are low magnitude risk factors for autism. The association between developmental disability and autism risk factors warrants further examination.

Role of acetyl salicylic acid and sodium metabisulfite in chronic childhood asthma.

The role of a commonly ingested food additive, the preservative sodium metabisulfite (MBS), and aspirin (ASA), in chronic asthma has been studied in 29 children. After 1 week on a strict elimination diet, all 29 children were challenged, in a single-blind fashion, in the pulmonary function laboratory on three consecutive days with placebo, MBS (capsule form and solution), and ASA. Children with a positive response to MBS were prescribed a diet that excluded foods containing MBS. Patients with a positive response to ASA were prescribed a diet excluding medications containing aspirin and natural salicylates. After 3 months on these restricted diets, the children were reassessed to determine whether there had been any therapeutic response. There was a 66% (19/29) incidence of positive challenge (greater than 20% decrease in forced expiratory volume in one second) with MBS and a 21% (6/29) incidence of positive challenge with ASA. None of the children reacted to MBS in capsule form (maximum dose = 100 mg), but 19/29 reacted to MBS in solution with 30 mL of 0.5% citric acid. After 3 months on the restricted diet, four of 19 children on the MBS-free diet and one of six on the salicylate-free diet had objective signs of improvement, namely, reduction in asthma medications and/or improvement in lung function. Unfortunately, compliance with the restrictive diet during this 3-month period was poor, particularly with the ASA-sensitive children.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchial reactivity in cystic fibrosis.

There is considerable dispute regarding the prevalence of asthma in patients with cystic fibrosis (CF). We studied 50 patients with CF and compared their responsiveness to inhaled histamine with that of asthmatic children. The incidence of positive responses to inhaled histamine was 24% in the patients with CF and more than 90% in the asthmatic patients. We found no correlation, in the patients with CF, between the histamine response and several indexes of atopy (clinical allergic disease and positive allergen skin tests). Positive responders to histamine were not evenly distributed over the disease spectrum of CF. Instead, positive responses occurred only in those patients whose prechallenge pulmonary function was abnormal. We conclude that the heightened bronchial reactivity in patients with CF reflects the severity of their underlying lung disease rather than the presence of coexistent asthma.

Mucoid Pseudomonas aeruginosa is a marker of poor survival in cystic fibrosis.

The aim of this study was to assess the prognostic significance of mucoid and non-mucoid isolates of Pseudomonas aeruginosa (muPs and non-muPs) from the sputa of patients with cystic fibrosis (CF). Eighty-one children with CF who coughed up sputum daily were recruited and followed over 12 months with frequent sputum cultures. At the end of this observation period they were classified to one of three age-matched groups. In 50 mPs was isolated on one or more occasions; 19 grew non-muPs but not muPs, and 12 grew no isolates of Ps aeruginosa. These 81 children and adolescents were followed for a further 8 years or until they died. Twenty-one (42%) of the muPs patients died compared with two (11%) of the non-muPs and one (8%) of the no Ps patients (P less than 0.01). Stepwise regression indicated that forced expiratory volume in 1 second (FEV1) had the main predictive effect but that age, Shwachman score and muPs also had a predictive effect. Identification of mucoid forms of Ps aeruginosa is an unfavorable prognostic factor but the isolation of non-mucoid strains does not appear to be any more important than the isolation of other common respiratory pathogens.

The cost of childhood asthma to Australian families.

There have been no estimates of the actual cost of asthma care to Australian families. Previous estimates have been of the total cost to the community and have relied upon data collected by government departments and agencies. It was the aim of this investigation to estimate the cost of childhood asthma from the parents perspective in Australian families. A total of 238 asthmatic children aged 8-12 years were identified through prevalence studies of asthma in Sydney and Belmont, N.S.W. Children were selected if they had wheezed in the previous 12 months, had used asthma medicines or had airway hyperresponsiveness when tested. The study sample had a wide range of asthma severity. Data were collected retrospectively and prospectively. Parents completed a questionnaire which asked about health insurance and special asthma equipment costs in the previous 12 months. Every 2 weeks for a total of 3 months between February and June parents completed further questionnaires which assessed costs incurred because of their child's asthma, together with time spent obtaining treatment. Items included doctor consultations and tests, alternative practitioner consultations and tests, medications and alternative therapies purchased, hospital and ambulance use, and the cost of childcare as a consequence of asthma. We collected two or more months of prospective data from a total of 193 children. The mean annual cost of asthma to the family was A$212.48 per asthmatic child and 13.4 hr were spent obtaining treatment. For the group of children who had not visited a doctor in the previous year, the mean annual cost was A$85.60 and 13.1 hr were spent obtaining treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Randomized controlled study of in-hospital exercise training programs in children with cystic fibrosis.

The aim of this study was to compare aerobic and resistance training in children with cystic fibrosis (CF) admitted to hospital with an intercurrent pulmonary infection with a control group. The subjects were randomized into three groups on the first day of admission. The fat-free mass (FFM) was calculated, using the skin fold thickness from four sites (biceps, triceps, subscapular, and iliac crest). Pulmonary function tests were performed within 36 hr of admission and repeated on discharge from the hospital, and again at 1 month after discharge. All subjects performed an incremental treadmill exercise test, using a modified Bruce protocol. Lower limb strength was measured using a Cybex dynamometer. An assessment of quality of life was made using the Quality of Well Being Scale, as previously reported. Activity levels were measured using a 7-day activity diary, and subjects also wore an accelerometer on their hips. There were no significant differences between the three groups in terms of disease severity, and length of stay in hospital. Subjects in all three groups received intravenous antibiotics and nutritional supplementation as determined by the physician. Children randomized to the aerobic training group participated in aerobic activities for five sessions, each of 30-min duration, a week. The children randomized to the resistance training group exercised both upper and lower limbs against a graded resistance machine. Subjects in the control group received standard chest physiotherapy. Our study demonstrated that children who received aerobic training had significantly better peak aerobic capacity, activity levels, and quality of life than children who received the resistance training program. Children who received resistance training had better weight gain (total mass, as well as fat-free mass), lung function, and leg strength than children who received aerobic training. A combination of aerobic and resistance training may be the best training program, and future studies to assess optimal training programs for CF patients are indicated.

The economic aspects of drug delivery in asthma.

The need for cost-effective asthma therapy is driven by the high prevalence of asthma as well as the high cost of both medical care and lost productivity through illness. Limited healthcare resources demand proven therapies that maintain sustained disease control. Optimal disease control is the essence of cost effectiveness, but this in turn is dependent on correct drug selection and appropriate drug delivery. Successful treatment depends on delivery of medication to the site of action in the airways. Although there is a substantial number of aerosol delivery systems available, there is considerable confusion as to the most suitable method in different clinical settings, and across different age groups. Optimal drug delivery can be achieved without adding substantially to the overall cost of therapy. Both drugs and delivery systems need to be individualised to the needs of the patients. The early introduction of oral corticosteroids for acute exacerbations has resulted in reduced hospitalisation and shortened illness, providing substantial cost savings. A reduction in the reliance on nebuliser therapy in both the acute and chronic setting will further optimise therapy and reduce costs. We have reviewed the current literature to determine the most cost-effective methods of drug delivery in asthma.

The cost of asthma: can it be reduced?

Asthma is a major public health problem in developed countries, where it consumes a large and increasing share of scarce health resources. Ideally, medical management should be both optimal in terms of improving the patient's quality of life, and cost-effective for society. At present, there is very little information relating to costs and economic efficiency of current asthma management. Although the true total cost of asthma is unknown, current estimates suggest it is high. The main value of recent total cost estimates is that they identify the most expensive areas of asthma costs, and ideally, formal cost-effectiveness analyses should be concentrated on these areas. Asthma is still under- or inappropriately diagnosed, and undertreated. Several national and international consensus plans for the optimal management of asthma in children and adults have been published. If these inadequacies in asthma management were corrected, using current treatment recommendations, the overall cost of asthma from both the community and patient perspective should fall. The situation requires increased use of preventative medications {sodium cromoglycate (cromolyn sodium) or inhaled corticosteroids}, more widespread use of written crisis plans, more proactive medical consultations (rather than reactive or urgent consultations), further expansion of asthma education programmes, and further education of medical practitioners about the optimum management of both long term asthma and the acute exacerbation of asthma in the patient's home, the doctor's office, the hospital emergency room and the hospital inpatient setting. The increased costs associated with these measures would be more than offset by reduced expenditure on bronchodilator drugs, less widespread use of nebulisers at home and in hospitals, reduced antibiotic usage, reduced need for expensive emergency medical care and particularly reduced utilisation of hospital resources. To ensure that resources are being directed into the most cost-effective areas of asthma care, clinical trials of asthma should include utilisation of healthcare resources as an outcome measure, and estimates of the costs of the treatment under study. In addition, since the intangible cost (quality of life) is one of the most important effects of treatment from the patient's perspective, this should be more widely used as an outcome measure in clinical trials. Ultimately, prevention of asthma is the long term goal. If the hypothesis that sensitisation to house dust mite in early infancy is a major contributor to the subsequent development of asthma, then prevention may require drastic and expensive changes to current housing.

Problems and possibilities in understanding the natural history of asthma.

In early life, asthma symptoms can occur intermittently or may not be severe enough to limit normal activities, which makes it difficult for the clinician to make reliable predictions and administer therapy with some precision. In the case of pediatric asthma, the identification of children who will experience the development of a clinically important illness that will impair their quality of life can be a complex process. The usual methods for describing this information include the prognostic statistics of sensitivity, specificity, likelihood ratio, and positive predictive value. The sensitivity, specificity, and likelihood ratio of various early markers of asthma have been calculated from several cohort studies. (J Allergy Clin Immunol 2000;106:S144-52.)

The significance of nasal eosinophils and mast cells in children with nasal symptoms.

Nasal smears from children with symptoms of nasal obstruction and/or discharge were examined for the presence of eosinophils, mucus-containing cells and mast cells. The presence of more than one eosinophil or any mast cells was significantly associated with atopy as determined by immediate hypersensitivity on skin prick testing. Twelve children with markedly increased numbers of nasal smear mast cells are described. In these children symptoms frequently commenced in the first 6 months of life. Nasal eosinophilia was not noted in any of the cases. Nasal smear mastocytosis was associated with significant perennial symptoms and would be missed if nasal smears are examined only for eosinophilia.