Can a management pathway for chronic cough in children improve clinical outcomes: protocol for a multicentre evaluation.

BACKGROUND: Chronic cough is common and is associated with significant economic and human costs. While cough can be a problematic symptom without serious consequences, it could also reflect a serious underlying illness. Evidence shows that the management of chronic cough in children needs to be improved. Our study tests the hypothesis that the management of chronic cough in children with an evidence-based management pathway is feasible and reliable, and improves clinical outcomes. METHODS/DESIGN: We are conducting a multicentre randomised controlled trial based in respiratory clinics in 5 major Australian cities. Children (n = 250) fulfilling inclusion criteria (new patients with chronic cough) are randomised (allocation concealed) to the standardised clinical management pathway (specialist starts clinical pathway within 2 weeks) or usual care (existing care until review by specialist at 6 weeks). Cough diary, cough-specific quality of life (QOL) and generic QOL are collected at baseline and at 6, 10, 14, 26, and 52 weeks. Children are followed-up for 6 months after diagnosis and cough resolution (with at least monthly contact from study nurses). A random sample from each site will be independently examined to determine adherence to the pathway. Primary outcomes are group differences in QOL and proportion of children that are cough free at week 6. DISCUSSION: The clinical management pathway is based on data from Cochrane Reviews combined with collective clinical experience (250 doctor years). This study will provide additional evidence on the optimal management of chronic cough in children. TRIAL REGISTRATION: ACTRN12607000526471.

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.

Gender differences in habitual activity in children with cystic fibrosis.

AIMS: (1) To compare habitual activity levels in prepubescent and pubescent boys and girls with different degrees of CF lung disease severity and healthy controls. (2) To assess the relation between habitual activity levels and measures of fitness, lung function, nutrition, pancreatic status, and quality of life. METHODS AND RESULTS: A total of 148 children (75 girls and 73 boys) with CF and matched controls were studied. Regardless of disease severity, there were no differences in habitual activity between prepubescent boys and girls with CF. Pubescent boys with CF were significantly more active than girls with the same degree of disease severity. There were no significant differences in habitual activity between prepubescent children with CF and controls. Pubescent children with mild CF were significantly more active than controls, but those with moderate to severe disease were less active than controls. The best correlates with habitual activity levels were anaerobic power, aerobic capacity, and quality of life. In children with moderate to severe disease, nutrition status correlated significantly with activity levels. The impact of pancreatic status on activity levels and other measures of fitness was most apparent in pubescent girls. CONCLUSION: Gender differences in habitual activity were evident only after the onset of puberty. The impact of pancreatic insufficiency on measures of fitness and habitual activity was greatest in pubescent females. The reason for this gender difference may be an interplay of genetic, hormonal, and societal factors and is the focus of a longitudinal study.

Tracheomalacia, timing of symptoms, and thymic enlargement: cause or coincidence?

The authors report a case of severe primary tracheomalacia in a 3-month-old boy. The left lobe of the enlarged thymus was resected at operation to facilitate aortopexy. The authors suggest a possible role for the enlarging thymus contributing to the delayed onset of the symptoms of tracheomalacia, despite the presence of the tracheal lesion from birth.

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 childhood asthma prevention study (CAPS): design and research protocol of a randomized trial for the primary prevention of asthma.

The Childhood Asthma Prevention Study is a randomized controlled trial to measure whether the incidence of atopy and asthma can be reduced by house dust mite allergen reduction, a diet supplemented with omega-3 fatty acids, or a combination of both interventions. Six hundred and sixteen pregnant women whose unborn children were at high risk of developing asthma because of a family history were randomized prenatally. Study groups are as follows: Group A (placebo diet intervention, no house dust mite reduction), Group B (placebo diet intervention, active house dust mite reduction), Group C (active diet intervention, no house dust mite reduction), and Group D (active diet intervention, active house dust mite reduction). The house dust mite reduction intervention comprises use of physical and chemical methods to reduce allergen contact. The dietary intervention comprises use of a daily oil supplement from 6 months or at onset of bottle-feeding, and use of margarine and cooking oils based on sunflower or canola oils to increase omega-3 dietary intake. Data is collected quarterly until the infant is 1 year old and then half yearly until age 5 years. Questionnaires are used to collect respiratory illness history and information about diet and home environment. Dust is collected from the child's bed and bedroom and playroom floors. Blinded assessments are conducted at 18 months, 3 years, and 5 years. Skin prick tests to common allergens, blood tests, and detailed illness, medication use, and vaccination histories are collected. Primary outcomes will be the development of allergic sensitization and the presence and severity of asthma. This study is designed to measure the effectiveness of allergen reduction and dietary supplementation, both separately and in combination, for the primary prevention of atopy and asthma. The results of this study may have important implications for public health policies to reduce the incidence of childhood asthma. Control Clin Trials 2001;22:333-354

Continuing the debate about measuring asthma in population studies.

The reasons for measuring atopy and airway hyperresponsiveness (AHR) and the methods of validating measurements of asthma in population studies continue to be debated. The debate has centred around standards against which to validate asthma measurements but the absence of a "gold standard" makes the criterion validation of measurements difficult. Questionnaires will always be useful but cannot be validated against a doctor diagnosis because of self-selection and recall biases. In practice, measurements should be selected on the merits of what they measure rather than being regarded as validated or non-validated alternatives. The measurement of AHR is invaluable because it is reliable, not influenced by variations in symptom perception or diagnostic trends, and is closely related to the underlying mechanisms of asthma. The value of AHR lies in its high specificity (rate of true negatives) and low sensitivity (rate of false positives) against asthma symptoms which gives additional information about symptomatic subjects. Atopy is also a useful test and, in quantifying its association with asthma, we should not place any currency on ecological evidence. Atopy is a strong risk factor for asthma in the presence of regionally specific allergens and ecological analyses that ignore these effects are diversionary rather than productive. For preventing asthma, we need to identify the group at greatest risk of developing it, measure the risk factors with precision, and develop interventions that are effective in changing environmental exposures and homogeneous outcomes. This is the only approach that has the potential to lead to significant public health benefits.

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.)

Epidemiology of invasive pneumococcal disease in urban New South Wales, 1997-1999.

OBJECTIVES: To describe the serotypes, incidence and morbidity of invasive pneumococcal disease in urban New South Wales. DESIGN: Prospective laboratory surveillance. SETTING: Microbiology laboratories and hospitals in the Sydney, Hunter and Illawarra Statistical Divisions of NSW, June 1997 to May 1999. RESULTS: 1270 cases were identified in two years. Incidence of disease was highest in those aged < 2 years (96.4 per 100,000; 95% CI, 83.7-107.9) and > or = 85 years (100.1 per 100,000; 95% CI, 81.8-121.3). Incidence of disease increased significantly from the age of 60 years, compared with low rates in those aged 5-59 years. Underlying diseases predisposing to pneumococcal infection increased with age, from 4% (< 2 years) to 60% (> or = 65 years). A seven-valent conjugate vaccine would have covered 84.8% of serotypes in those aged 0-14 years, falling to 69% in those > or = 15 years. Penicillin resistance was significantly higher in the < 5 years group (19.0%) than in older people (14.6%). CONCLUSIONS: Incidence of invasive pneumococcal disease was higher in this study using active surveillance than in previous Australian studies. An effective sevenvalent conjugate pneumococcal vaccine could prevent more than 80% of cases in children aged < 5 years.

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.

Outcome evaluation of early discharge of asthmatic children from hospital: a randomized control trial.

The objective of our study was to compare the safety and efficacy of discharging asthmatic children from hospital on three versus four hourly nebulized salbutamol. The setting was a tertiary referral paediatric hospital in Sydney, NSW, Australia. The design was a randomized controlled parallel group study. All children admitted to hospital with acute asthma and who were over 18 months of age were eligible to enter the study. Patients were excluded if they had non-English speaking parents, no telephone, or chronic cardiac or neurological disease. Children were treated according to standard asthma management but were randomly allocated to be discharged on three or four hourly nebulized salbutamol. Patients were surveyed using a telephone questionnaire 1 to 2 weeks after discharge. The primary outcome measure was re-presentation to the Emergency Department (ED) within 7 days. Other outcomes included readmission to hospital, re-presentation to the local doctor, parental satisfaction and length of hospital stay. A total of 63 children were enrolled in the study (32 in the three hourly group and 31 in the four hourly group). There were no re-presentations to the ED or hospital readmissions within 1 to 2 weeks in either group. However, re-presentations to the local doctor were common, 71.8% in the three hourly and 74.1% in the four hourly groups, respectively. These were predominantly for routine review. The mean (+/- SD) hospital length of stay was not significantly different between the three and four hourly groups, 48.94 (+/- 20.61) and 54.88 (+/- 32.59) hours, respectively (P = 0.672). Parents felt the timing of discharge was 'too early' in five (15.6%) of three hourly and five (16.1%) of four hourly patients. Three (9.7%) of the four hourly but none of the three hourly patients felt they were sent home 'later than necessary'. Five (15.1%) of the three hourly and three (9.7%) of the four hourly group parents did not feel comfortable looking after their child at home immediately after discharge. None of these differences were statistically significant. Discharge of asthmatic children from hospital on three hourly nebulized salbutamol is as safe and effective as on four hourly. Parents are generally very satisfied with timing of discharge, irrespective of frequency of nebulization. Earlier discharge benefits both the child and their family, and improves hospital bed utilization.

Is asthma documentation improved by computer-facilitated data entry?

The documentation of acute asthma in written medical records was compared with data entered into a Computer-Assisted Triage System (CATS) in 104 children who presented to the emergency department and subsequently admitted to the Royal Alexandra Hospital for Children, Sydney. A total of 65 items in 5 categories were analysed and satisfactory documentation was defined as the recording of a specific item in more than 80% of records (written or electronic). Satisfactory documentation was observed for all 6 items in visit details and 9 out of 10 items in triage details for both recording systems. Nursing observations were better documented in the medical record than in CATS (87 vs 25%; kappa = 0.63). Documentation of medical details was also worse in CATS (75 vs 25%; kappa = 0.24) and the documentation of asthma severity was poor in both systems (31 vs 0%; kappa = 0.31). Attempts to improve asthma documentation through the development of a computerized medical record have highlighted further barriers to documentation.

A review of open biopsy for mediastinal masses.

OBJECTIVE: To review the recent experience with biopsied mediastinal lesions in children and to assess the impact of recent advances in imaging and surgical techniques on diagnosis. METHODOLOGY: The clinical and radiological features of 55 patients who had mediastinal biopsies at The Royal Alexandra Hospital For Children (RAHC) over 15 years were reviewed. RESULTS: Fifty-five patients presented to RAHC between 1978 and 1993 with lesions of the mediastinum requiring biopsy of that site. Thirty-one of the 55 (56%) lesions were malignant. Neurogenic tumours were the most common (40%). In order of frequency the following lesions were found: neuroblastoma (15), teratoma (eight), non-Hodgkin's lymphoma (NHL; eight), enteric cyst/duplication (five), ganglioneuroma (five), bronchogenic cyst (three), ganglioneuroblastoma (two), lymphangioma (two), abscess (two), Hodgkin's lymphoma (HL; two), oesophageal granuloma (one), Langerhan's cell histiocytosis (one), congenital fibromatosis (one). Eighty-two per cent of neurogenic tumours were located in the posterior mediastinum, while 75% of teratomas and 100% lymphoid tumours were located anteriorly. Symptoms were generally unhelpful in establishing a specific diagnosis and in 27% of cases the lesions were discovered incidentally. Physical signs, such as thoracic inlet obstruction and neurological findings, were helpful clinically in localizing lesions within the mediastinum. Chest radiography enabled lesions to be subdivided within the mediastinum. This localization, in combination with the age at presentation, predicted the tissue diagnosis. Computerized tomography (CT) and magnetic resonance imaging (MRI) further defined the lesion and demonstrated involvement of adjacent structures. Histology, however, was essential to distinguish benign from malignant lesions. CONCLUSIONS: The clinical presentation of mediastinal masses is often non-specific or incidental. Despite recent advances in imaging technology and biopsy techniques, full histological examination is required to exclude malignancy.

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.

Accuracy of asthma treatment in schoolchildren in NSW, Australia.

Insufficient use of anti-inflammatory drugs, such as inhaled corticosteroids and cromoglycate, may contribute to the disease burden associated with asthma. Conversely, aggressive treatment of mild disease may result in avoidable costs and/or adverse drug effects. The aim of this study was to determine the relationship between asthma severity and inhaled corticosteroid/cromoglycate use in a large (n=4,909) random sample of children, aged 8-11 yrs, in NSW, Australia. Asthma and its treatment were assessed by questionnaire responses. Asthma, defined as diagnosis plus current wheeze, was present in 901 children (18% of the sample), of whom 225 (5%) had moderate asthma, defined as asthma plus additional symptoms (sleep disturbance), utilization (hospital, casualty), or disability (reduced activity, school absence). Use of inhaled corticosteroid/cromoglycate was reported by 636 children (13% of the sample). Determinants of use included: asthma diagnosis, current wheeze, and troublesome dry nocturnal cough. There was also a strong relationship between anti-inflammatory treatment and a multicomponent asthma severity score constructed for each child. Inhaled corticosteroids and/or cromoglycate were used by 56% of the children with asthma (24% daily) and by 76% of children with moderate asthma (42% daily). Undertreatment, defined as less than daily inhaled corticosteroids/cromoglycate in moderate asthma, was identified in 130 children (14% of those with asthma or 3% of the sample). Conversely, apparently aggressive treatment, defined as inhaled corticosteroid/cromoglycate use in children with persistent minimal symptoms (asthma severity score of less than 3) was identified in 101 children (2% of the sample). Although there were significant differences between regions in the choice of anti-inflammatory drugs and in the prevalence both of undertreatment and apparently aggressive treatment, there was no clear relationship to regional utilization of emergency and hospital services for asthma. Nevertheless, the frequency of undertreatment suggests an opportunity to reduce asthma morbidity by more consistent application of current therapeutic guidelines.

Measuring health outcome in paediatrics: development of the RAHC measure of function.

OBJECTIVE: To develop a genetic measure of health outcome (the RAHC Measure of Function) for paediatric health services. METHODOLOGY: The RAHC Measure of Function (MOF) was modified from the Child Global Assessment Scale. The utility and reliability of the MOF was then tested by inter-clinician agreement on case scenarios, by inter-clinician agreement in outpatients, by parent-clinician agreement in outpatients and by responsiveness to change in acute admissions. RESULTS: The inter-clinician agreement on MOF ratings for case scenarios was moderately good, with an overall kappa of 0.42; P < 0.0001. Clinicians at respiratory and child psychiatry clinics nominated the same or adjacent MOF category to describe 100% (95% CI: 71.5-100) and 90% (95% CI: 68.3-98.8%) of 11 and 20 cases assessed, respectively. Parents nominated the same or adjacent MOF category as the attending clinician for 89.7% (95% CI: 72.7-97.8) and 82.9% (95% CI: 67.9-92.9) of 29 and 41 children in the same two clinics. Twenty-eight inpatient children had an MOF assessed on admission and discharge, and the median MOF score improved from 50.5 to 79 points (z = 4.53; P < 0.0001). CONCLUSIONS: The MOF is easy to use and provides a valuable description of health outcome that parents are able to understand. The MOF is moderately reliable, is likely to be sufficiently reliable to compare groups of paediatric patients and is responsive to change.

Prevalence and severity of childhood asthma and allergic sensitisation in seven climatic regions of New South Wales.

OBJECTIVE: To compare the prevalence and severity of asthma and of allergic sensitisation in children in different regions. We hypothesised that regions with different standardised hospital admission rates would have different prevalences of childhood asthma and that diverse climates would result in a range of sensitisations to different allergens. DESIGN AND SETTING: We studied large random population samples of children in seven regions in New South Wales (NSW) in 1991-1993. Hospitalisation rates were obtained from NSW Department of Health data. PARTICIPANTS: 6394 children aged 8-11 years. OUTCOME MEASURES: History of respiratory symptoms by self-administered questionnaire; airway hyperresponsiveness by histamine inhalation test; and sensitisation to allergens by skin-prick tests. RESULTS: Children in all regions had a high prevalence of recent wheeze (22%-27%), of diagnosed asthma (24%-38%) and of use of asthma medications (22%-30%), but no region was consistently higher or lower for all measurements. The prevalence of current asthma in children living in three coastal regions (where sensitisation to house-dust mites was high) and in the far west (where sensitisation to alternaria was high) was 12%-13%, which was significantly higher than the prevalence of 7%-10% in children living in three inland regions (where sensitisation to these allergens was lower) (P < 0.01). CONCLUSIONS: We found significant variations in the prevalence and severity of childhood asthma in NSW. The prevalence of hospitalisations, diagnosed asthma, recent symptoms and medication use may relate to different regional diagnostic patterns, whereas current asthma prevalence may relate to different levels of allergic sensitisation.