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.

Measuring changes in logarithmic data, with special reference to bronchial responsiveness.

Bronchial provocation tests with agents such as histamine and methacholine are commonly used in clinical and epidemiological studies of respiratory illness because bronchial hyperresponsiveness is a non-specific abnormality of the airways which is characteristic of asthma. However, measurements of bronchial responsiveness are log-normally distributed. As a result, special considerations need to be given to reporting within-subject changes in these measurements in longitudinal studies as, for example, in clinical trials or in any study in which a before-and-after experimental design is used. In these types of experiments, changes in bronchial responsiveness should not be simply expressed in the units of the measurement, such as dose of provoking agent, but must be expressed in units based on a logarithmic scale. The appropriate log-based units for measuring within-subject changes are doubling dose, fold difference or percent change. This paper explains the methods for calculating changes in these units in a statistically correct manner. All three units represent different ways of expressing the same change on a logarithmic scale. However, 'doubling dose' is only appropriate when it relates directly to the method of administering the provoking agent in doubling concentrations and 'fold difference' or 'percent change' are both appropriate for expressing any log-based changes. The methods for calculating changes in these units also apply to calculations of repeatability within test methods and to calculations of comparability and agreement between test methods. The methods are described solely for reporting changes in units of bronchial responsiveness but are applicable to other log-normally distributed measurements.

Factors that affect normal lung function in white Australian adults.

STUDY OBJECTIVE: To classify abnormal lung function in epidemiologic studies, we first calculated "normal" values using data from Australian white adults. We then examined the effects of airway hyperresponsiveness (AHR), respiratory symptoms, current and past asthma, and current smoking on spirometric function. METHODS: A large random sample of 1,527 adults aged 18 to 73 years was studied. We measured respiratory symptoms and smoking history by questionnaire and AHR by histamine inhalation test. RESULTS: Data from 729 "normal" subjects (asymptomatic nonsmokers without AHR) were used to obtain regression models for FVC, FEV1, peak expiratory flow rate, and forced expiratory flow between 25% and 75% of FVC. The R2 values were 0.76, 0.74, 0.58, and 0.29, respectively. The presence of AHR reduced FVC by 0.1 L and FEV1 by 0.2 L, on average. Subjects with asthma-related symptoms had a mean reduction in FVC of 0.1 L for both genders and in FEV1 of 0.08 L for women and 0.2 L for men. Current asthma reduced FVC by 0.3 L, on average, and FEV1 by 0.5 L for women and 0.6 L for men. The FEV1 was reduced by 0.002 L per cigarette smoked daily. CONCLUSION: Recent symptoms, AHR, and current smoking were all important predictors of reduced lung function.

Measuring persistent cough in children in epidemiological studies: development of a questionnaire and assessment of prevalence in two countries.

STUDY OBJECTIVE: Cough is a common symptom in children that is frequently encountered in general practice. However, most of the information on the prevalence of persistent cough has come from studies that use different, often ambiguous, definitions for persistent cough. It is therefore important that a validated questionnaire to accurately measure persistent cough is developed and is appropriate for use in different age groups of children and in different cultures. Such a questionnaire is essential for accurately measuring the prevalence of persistent cough and the factors associated with its occurrence. DESIGN: A parent-administered respiratory questionnaire was developed and administered twice during a 3-week interval pilot study to test repeatability. The questionnaire was then administered to a randomly selected cross-section of Australian children aged 5 to 7 years old and 8 to 11 years old (N = 511 and N = 654, respectively), and to 566 Nigerian children aged 8 to 11 years old. RESULTS: The new questionnaire was reliable, with most of the questions having a kappa value of above 0.6. The prevalence of persistent cough was similar in younger and older Australian children, but significantly less in Nigerian children (p < 0.001). Also, persistent cough was more prevalent in children of high rather than low socioeconomic status among older Australian children (p = 0.04). CONCLUSIONS: The newly developed questionnaire will be an important tool in epidemiological studies for measuring the prevalence, morbidity, and risk factors of persistent cough in childhood. Although our findings showed that persistent cough does not occur more frequently in younger than in older Australian children, it is more frequent in Australian than in Nigerian children.

Reliability of a respiratory history questionnaire and effect of mode of administration on classification of asthma in children.

Because there is no consensus definition of asthma for epidemiology, we have examined the reliability of a questionnaire and the effect of its mode of administration on classification of asthma in children. A symptom history questionnaire was parent self-administered and then readministered within three months by a nurse. The questions of diagnosed asthma, cumulative wheeze, and recent wheeze (wheeze in the previous 12 months) were more repeatable than questions of night cough, but 7 percent of children changed diagnosed asthma category, 13 percent changed cumulative wheeze category, and 9 percent changed recent wheeze category at second questionnaire. Because the numbers who changed from symptom positive to negative roughly equalled the changes from negative to positive, prevalence estimates were not affected. Methods of measuring asthma with greater precision are urgently needed. Because of reporting bias, epidemiologic information collected by current questionnaires should be treated with some caution.

Questionnaire items that predict asthma and other respiratory conditions in adults.

The International Union Against Tuberculosis and Lung Disease questionnaire is widely used in epidemiologic studies of adult asthma. We examined whether the symptom questions could be classified into groups that represent different "syndromes," and whether some questions are better for predicting asthma than others. We analyzed questionnaire data from a population sample of 1,527 adults aged 18 to 55 years using factor analyses to classify the 17 respiratory symptom questions into four different groups that we termed asthma, cough, breathlessness, and urgent medical visit. The urgent medical visit was a subset of asthma. These four "syndromes" had good validity when measured against airway responsiveness to histamine, atopy to common allergens, lung function, smoking status, and body mass index. Questions that predicted asthma syndrome were those that asked about wheeze at rest or following exercise, asthma attack, chest tightness, and shortness of breath at rest. Questions about cough identified a different group of subjects who apparently did not have asthma. Questions of breathlessness did not aggregate with "asthma" or with "cough syndrome." The identification of particular questions that measure different respiratory conditions is important for epidemiologic studies when short questionnaires or more precise definitions are required.

Prevalence of bronchial hyperresponsiveness in children: the relationship between asthma and skin reactivity to allergens in two communities.

A coastal population mainly reactive to house dust mite was compared with an inland population mainly reactive to other allergens to investigate whether exposure to house dust mite plays a part in initiating childhood asthma. Respiratory symptoms, asthma, bronchial hyperresponsiveness, hay fever and atopy were all more common in the dry inland area than in the humid coastal area. In both areas 38% of children were atopic. Coastal children had more skin reactivity to house dust mites and inland children were more reactive to grass pollen extracts. The findings suggest that the clinical presentation of asthma may be related more to the total burden of aeroallergens than to exposure to a particular allergen.

Effect of passive smoking, asthma, and respiratory infection on lung function in Australian children.

We have calculated normal standards for lung function of Australian children and have estimated the effects on lung function of passive smoking, current asthma, past asthma, and a current respiratory infection. Three cross-sectional samples of children in school years 3-5 (aged 8-11 years) were studied. The 2765 children were from two rural regions of NSW and from the city of Sydney. Details of passive smoking and respiratory illness were collected by a questionnaire sent to parents. Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), peak expiratory flow rate (PEFR), and forced mid-expiratory flow rate (FEF25-75%) were used as measures of lung function. Airway responsiveness was assessed by histamine inhalation test. Data from 1278 "normal" children were used in regression analysis to calculate prediction models for lung function. Passive smoking was associated with reduced FEV1, PEFR, and FEF25-75%. Children with current asthma had reduced FEV1 and FEF25-75% and children with past asthma had reduced FEF25-75%. Children with a current respiratory infection had reduced FVC, FEV1, PEFR, and FEF25-75%. The effects of these deficits on the future lung function of these children is not known but is likely to be important.

Meta-analysis on the association between environmental tobacco smoke (ETS) exposure and the prevalence of lower respiratory tract infection in early childhood.

The aim of this study was to obtain quantitative information from published data on the association between environmental tobacco smoke (ETS) exposure and the prevalence of serious lower respiratory tract infections (LRTI) in infancy and early childhood. We identified 21 relevant publications on the relation between ETS and the prevalence of serious LRTI by reviewing reference lists in relevant reports and by conducting manual and computer searches (Medline database; Dissertation abstracts index of Xerox University Microfilms) of published reports between 1966 and 1995. Thirteen studies were included in a quantitative overview using random effects modeling to derive pooled odds ratios. Sensitivity analyses were conducted to test the decision rules used in extracting odds ratio data. The results of community and hospital studies are broadly consistent and show that the child of a parent who smokes is at approximately twice the risk of having a serious respiratory tract infection in early life that requires hospitalization. This association was pronounced in children younger than age two and diminished after the age of two. The combined odds ratio for hospitalization for lower respiratory tract infections in infancy or early childhood is 1.93 (95% CI 1.66-2.25); the combined odds ratio of prevalence of serious LRTI at age less than 2 years, between 0 and 6 years, and between 3 and 6 years were 1.71 (95% CI 1.33-2.20); 1.57 (1.28-1.91), and 1.25 (0.88-1.78), respectively. There was no evidence of heterogeneity across the studies in these combined odds ratios. We conclude that this meta-analysis provides strong evidence that exposure to ETS causes adverse respiratory health outcomes such as either a serious LRTI or hospitalization for LRTI. New public health campaigns are urgently needed to discourage smoking in the presence of young children.

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)

Daycare attendance before the age of two protects against atopy in preschool age children.

Early attendance at daycare has been shown to protect against atopy, as defined by a positive skin prick test. One proposed hypothesis for this association is that early exposure to other children protects against atopy by facilitating the spread of infections among children. An alternative hypothesis is that children attending daycare centers have less atopy due to lower levels of exposure to indoor allergens. Our aim was to determine whether attendance at daycare before age 2 years protects against atopy in Australian preschool age children and to test the two alternative hypotheses, as well as a number of potential confounding factors. We conducted a cross-sectional study of children aged 3-5 years living in one humid coastal city (Lismore, n = 286) and one dry, inland city (Wagga Wagga, n = 364) in New South Wales, Australia, in 1995. Atopy was assessed by skin prick tests to six common allergens. Daycare attendance and other possible risk factors for atopy were measured by a parent-completed questionnaire. Children who attended daycare before age 2 years had a reduced risk of atopy at 3-5 years. The greatest effect was seen in children who attended a daycare center (odds ratio (OR), 0.26; 95% CI, 0.14-0.50) rather than family daycare (OR, 0.66; 95% CI, 0.41-1.04). The results of this study do not support either of the proposed hypotheses, nor can the effect be explained by any of the other potential confounders measured. Further work is needed to determine the exposure that is responsible for the protective effect of daycare attendance on atopy.

Use of a paper disposable cup as a spacer is effective for the first-aid management of asthma.

OBJECTIVE: There are many settings in which a spacer device is not available for the administration of bronchodilator. Therefore, we tested whether a paper disposable cup is as effective as a commercially produced spacer to administer bronchodilator. METHODOLOGY: Randomised controlled trial. 50 subjects aged 16-50 years who had wheeze and a greater than 10% decrease in FEV1 after histamine inhalation test (HIT). Subjects were randomised to either the 150 ml paper disposable cup group (CUP) or the commercially produced spacer group (SPACER). Twenty minutes after 400 microg salbutamol was administered FEV1 was measured. The recovery index measured post-bronchodilator FEV1 as a percentage of baseline FEV1. Also, analysis of covariance tested whether recovery of FEV1 was related to the magnitude of the fall following the HIT. RESULTS: There were no statistically significant differences between CUP and SPACER groups in any characteristics. There was no difference for the recovery index (t48=1.14, P=0.26). Regression analyses showed that the relation between the magnitude of the fall in FEV1 during the HIT and the percent recovery was not different between the CUP and SPACER groups (t=-1.2, P<0.23). CONCLUSIONS: A paper disposable cup was effective for the reversal of mild to moderate bronchoconstriction. Therefore, a paper disposable cup can be used for the first-aid management of asthma when there is concern about cross-infection and a commercially produced spacer is not available.

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.

Growth and feeding practices of Vietnamese infants in Australia.

OBJECTIVE: To investigate the growth and feeding practices in first-generation Vietnamese infants living in Australia. DESIGN: Cohort study. SETTING: The study was conducted between 1999 and 2002 in Sydney. SUBJECTS: A total of 239 Vietnamese women were recruited randomly from antenatal clinics, and of these 210 were initially seen. During the first year, 20 cases (9.5%) were lost to follow-up. Data were collected at 0.5, 2, 4, 6, 9 and 12 months. RESULTS: Vietnamese infants were significantly longer and heavier than reference data (both P<0.0001). The Vietnamese infants had a significant decline in weight growth with age compared with reference data (P<0.001). The Vietnamese infants had marginally higher s.d. score for ideal weight for length than reference data (P=0.044). There was a significant decline in ideal weight for length with age compared with reference data (P=0.0065). Both parents were significantly shorter (mean s.d. height scores: -1.5+/-0.8 (mother) and -1.8+/-0.8 (father)) than reference data (P<0.001). The incidence of breast feeding was 79%, but half of the breast feeding women had stopped breast feeding by 3 months. A total of 162 (79.8%) infants were given infant formula within the first week, of whom 131 (80.1%) were fed infant formula within the first 24 h after birth. CONCLUSIONS: Vietnamese infants in this study had growth comparable with reference data despite their parents being shorter than reference data. Breast feeding duration was short with infant formula being introduced early.

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.)

Prevalence of asthma in adults in Busselton, Western Australia.

OBJECTIVE: To estimate whether the prevalence of asthma in adults increased over a nine year interval. DESIGN: Serial cross sectional studies of the population with a protocol that included both subjective and objective measurements. SETTING: Busselton, Western Australia. SUBJECTS: A random sample of 553 subjects aged 18-55 years in 1981, and of 1028 subjects aged 18-55 years in 1990. MAIN OUTCOME MEASURES: Respiratory symptoms measured by self administered questionnaire, bronchial responsiveness measured by bronchial challenge with histamine, and allergy measured by skin prick tests. RESULTS: Symptoms with increased prevalence were those with significant association with allergy in this population. Recent wheeze increased from 17.5% to 28.8% (p < 0.001) and diagnosed asthma increased from 9.0% to 16.3% (p < 0.001). The increase was greatest in subjects less than 30 years old. The prevalence of shortness of breath coming on at rest and of hay fever also increased significantly, but the prevalence of shortness of breath on exertion, chronic cough, bronchial hyperresponsiveness, current asthma (defined as recent wheeze plus bronchial hyperresponsiveness), and allergy did not increase. The severity of bronchial responsiveness did not change significantly in any symptom group. CONCLUSIONS: Young adults showed a significant increase in reporting of symptoms related to allergy but not in the prevalence of current asthma. The increase in symptoms may be due to increased awareness of asthma in this community, to changed treatment patterns, or to increased exposures to allergens.

Changing prevalence of asthma in Australian children.

OBJECTIVE: To investigate whether prevalence of asthma in children increased in 10 years. DESIGN: Serial cross sectional studies of two populations of children by means of standard protocol. SETTING: Two towns in New South Wales: Belmont (coastal and humid) and Wagga Wagga (inland and dry). SUBJECTS: Children aged 8-10 years: 718 in Belmont and 769 in Wagga Wagga in 1982; 873 in Belmont and 795 in Wagga Wagga in 1992. MAIN OUTCOME MEASURES: History of respiratory illness recorded by parents in self administered questionnaire; airway hyperresponsiveness by histamine inhalation test; atopy by skin prick tests; counts of house dust mites in domestic dust. RESULTS: Prevalence of wheeze in previous 12 months increased in Belmont, from 10.4% (75/718) in 1982 to 27.6% (240/873) in 1992 (P < 0.001), and in Wagga Wagga, from 15.5% (119/769) to 23.1% (183/795) (P < 0.001). The prevalence of airway hyperresponsiveness increased twofold in Belmont to 19.8% (173/873) (P < 0.001) and 1.4-fold in Wagga Wagga to 18.1% (P < 0.05). The prevalence of airway hyperresponsiveness increased mainly in atopic children only, but the prevalence of atopy was unchanged (about 28.5% in Belmont and about 32.5% in Wagga Wagga). Numbers of house dust mites increased 5.5-fold in Belmont and 4.5-fold in Wagga Wagga. CONCLUSIONS: We suggest that exposure to higher allergen levels has increased airway abnormalities in atopic children or that mechanisms that protected airways of earlier generations of children have been altered by new environmental factors.

Effect of peer led programme for asthma education in adolescents: cluster randomised controlled trial.

OBJECTIVE: To determine the effect of a peer led programme for asthma education on quality of life and related morbidity in adolescents with asthma. DESIGN: Cluster randomised controlled trial. SETTING: Six high schools in rural Australia. PARTICIPANTS: 272 students with recent wheeze, recruited from a cohort of 1515 students from two school years (mean age 12.5 and 15.5 years); 251 (92.3%) completed the study. INTERVENTION: A structured education programme for peers comprising three steps (the "Triple A Program"). MAIN OUTCOME MEASURES: Quality of life, school absenteeism, asthma attacks, and lung function. RESULTS: When adjusted for year and sex, mean total quality of life scores showed significant improvement in the intervention than control group. Clinically important improvement in quality of life (>0.5 units) occurred in 25% of students with asthma in the intervention group compared with 12% in the control group (P=0.01). The number needed to treat was 8 (95% confidence interval 4.5 to 35.7). The effect of the intervention was greatest in students in year 10 and in females. Significant improvements occurred in the activities domain (41% v 28%) and in the emotions domain (39% v 19%) in males in the intervention group. School absenteeism significantly decreased in the intervention group only. Asthma attacks at school increased in the control group only. CONCLUSION: The triple A programme leads to a clinically relevant improvement in quality of life and related morbidity in students with asthma. Wider dissemination of this programme in schools could play an important part in reducing the burden of asthma in adolescents.