Craig Mellis

Changing prevalence of asthma in Australian children.

Abstract 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 fators.

Importance of house dust mite and Alternaria allergens in childhood asthma: an epidemiological study in two climatic regions of Australia

The relation of house dust mite allergen levels to asthma and allergy was examined in two population samples of children aged 8–11 years in northern New South Wales. We studied 805 children in Lismore (a hot, humid, coastal region) and 770 in Moree/ Narrabri (a hot, dry inland region). Respiratory symptoms were measured by questionnaire, bronchial hyperresponsiveness (BHR) by histamine inhalation test, and allergy by skin‐prick tests. Current asthma was defined as the presence of both wheeze in last 12 months and BHR. Der p I levels were measured in dust from the bed and floors in the homes of 57 randomly selected children in the coastal region and of 74 inland children. Der p I levels were significantly higher by the coast (83.0 vs 11.2 μg/g, P < 0.001). House dust mite sensitivity was of similar prevalence in both regions (28.6 vs 26.4%, n.s.) but Alternaria sensitivity was higher inland (4.0 vs 15.2%P < 0.001). Bronchial responsiveness was more severe in coastal children sensitized to house dust mites and in inland children who were sensitized to Alternaria. The adjusted odds ratios for current asthma in children sensitized to house dust mites were 21.3 (95% CI 10.5, 43.2) by the coast and 2.7 (95% CI 1.3, 5.4) inland, and in children sensitized to Alternaria were 3.4 (95% CI 1.3, 9.1) in the coastal region and 5.6 (95% CI 3.1, 10.1 inland. These studies suggest that high house dust mite allergen levels in a humid, subtropical region act to significantly increase bronchial responsiveness in sensitized children, and that Alternaria allergens have a similar but less potent action in a dry, rural region.

An exercise challenge protocol for epidemiological studies of asthma in children: comparison with histamine challenge

We investigated whether an exercise challenge protocol is suitable for measuring bronchial responsiveness in epidemiological studies of asthma in children, and determined its comparability with histamine challenge. The exercise challenge was 6 minutes of outdoor, free-range running at 85-90% of maximum heart rate, measured by heart rate monitor. Nose clips were worn. Distance run was measured to estimate oxygen consumption. Water content of the inspired air was < 10 mg H2O.l-1. Histamine challenge was by the rapid method. We used questionnaires to measure respiratory symptoms and skin prick tests to measure atopy. A total of 96 children aged 8-11 years were studied. Bronchial hyperresponsiveness (BHR) to exercise challenge was defined as a fall in forced expiratory volume in one second (FEV1) of 13% of greater. Eleven children had a positive response to exercise challenge and 11 to histamine challenge but 12 responded to one challenge and not to the other. The correlation coefficient between the two tests was 0.65 (p = 0.0001). Exercise challenge thus proved to be a practical epidemiological tool for objective measurements of bronchial responsiveness in children. In this sample, some children responded to one challenge and not to the other which suggests that the two challenges identify different abnormalities of the airways.

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 homogenous outcomes. This is the only approach that has the potential to lead to significant public health benefits.

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 childs 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

Effect of omega‐3 fatty acid concentrations in plasma on symptoms of asthma at 18 months of age

The objective of this study was to assess the relation between observed levels of omega‐3 fatty acids in plasma and symptoms of asthma and atopy in children at 18 months of age. A total of 616 women at risk of having a child who would develop asthma because of a family history were recruited from the antenatal clinics of six hospitals in Sydney, Australia. Families were randomized to either active omega‐3 supplemented or control group. The active group received a daily tuna fish oil supplement and omega‐3‐rich margarines and cooking oils and the control group received a placebo supplement with polyunsaturated margarines and cooking oils. When the children were 18 months of age an assessment of symptoms was carried out by a research nurse blinded to treatment group allocation. Atopy was measured by skin prick tests, blood was collected to determine serum immunoglobulin E (IgE), and plasma fatty acid concentrations. A total of 376 children (61.0% of total recruited) completed an assessment at 18 months and had blood taken to determine plasma fatty acid concentrations. Omega‐3 fatty acid levels were expressed in quintiles of exposure ‘as treated’ without reference to treatment group allocation. Wheeze ever, doctor visits for wheeze, bronchodilator use and nocturnal coughing were significantly reduced in children in the higher exposure quintiles. Serum IgE was reduced in the highest quintile but not significantly so. There was no difference in diagnosed asthma or atopy between the exposure quintiles. Although wheeze at this age may not be a good indicator of asthma in later childhood, it is encouraging that some symptoms have been reduced in children with high omega‐3 fatty acid concentrations in plasma.

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.

Medical students as peer tutors: a systematic review

BackgroundWhile Peer Assisted Learning (PAL) has long occurred informally in medical education, in the past ten years, there has been increasing international interest in formally organised PAL, with many benefits for both the students and institutions. We conducted a systematic review of the literature to establish why and how PAL has been implemented, focussing on the recruitment and training process for peer tutors, the benefits for peer tutors, and the competency of peer tutors.MethodA literature search was conducted in three electronic databases. Selection of titles and abstracts were made based on pre-determined eligibility criteria. We utilized the ‘AMEE Peer assisted learning: a planning and implementation framework: AMEE Guide no. 30’ to assist us in establishing the review aims in a systematic review of the literature between 2002 and 2012. Six key questions were developed and used in our analysis of particular aspects of PAL programs within medical degree programs.ResultsWe found nineteen articles that satisfied our inclusion criteria. The PAL activities fell into three broad categories of teacher training, peer teaching and peer assessment. Variability was found in the reporting of tutor recruitment and training processes, tutor outcomes, and tutor competencies.ConclusionResults from this review suggest that there are many perceived learning benefits for student tutors. However, there were mixed results regarding the accuracy of peer assessment and feedback, and no substantial evidence to conclude that participation as a peer tutor improves one’s own examination performance. Further research into PAL in medicine is required if we are to better understand the relative impact and benefits for student tutors.

A Multicenter Study on Chronic Cough in Children Burden and Etiologies Based on a Standardized Management Pathway

BACKGROUND While the burden of chronic cough in children has been documented, etiologic factors across multiple settings and age have not been described. In children with chronic cough, we aimed (1) to evaluate the burden and etiologies using a standard management pathway in various settings, and (2) to determine the influence of age and setting on disease burden and etiologies and etiology on disease burden. We hypothesized that the etiology, but not the burden, of chronic cough in children is dependent on the clinical setting and age. METHODS From five major hospitals and three rural-remote clinics, 346 children (mean age 4.5 years) newly referred with chronic cough (> 4 weeks) were prospectively managed in accordance with an evidence-based cough algorithm. We used a priori definitions, timeframes, and validated outcome measures (parent-proxy cough-specific quality of life [PC-QOL], a generic QOL [pediatric quality of life (PedsQL)], and cough diary). RESULTS The burden of chronic cough (PC-QOL, cough duration) significantly differed between settings (P = .014, 0.021, respectively), but was not influenced by age or etiology. PC-QOL and PedsQL did not correlate with age. The frequency of etiologies was significantly different in dissimilar settings (P = .0001); 17.6% of children had a serious underlying diagnosis (bronchiectasis, aspiration, cystic fibrosis). Except for protracted bacterial bronchitis, the frequency of other common diagnoses (asthma, bronchiectasis, resolved without specific-diagnosis) was similar across age categories. CONCLUSIONS The high burden of cough is independent of children’s age and etiology but dependent on clinical setting. Irrespective of setting and age, children with chronic cough should be carefully evaluated and child-specific evidence-based algorithms used.

Quality of life of survivors of pediatric intensive care.

Objective Measuring outcome in pediatric intensive care is necessary to equate the high cost of treatment with benefits to the patient. Although mortality rates and morbidity are relatively insensitive measures of the benefits of treatment, quality of life measurement gives insight into the long-term outcomes. The aim of this study was to investigate the long-term quality of life outcome of children admitted to a pediatric intensive care unit. Design Prospective survey. Setting A 13-bed pediatric intensive care unit in a university-affiliated, tertiary referral children’s hospital. Patients Patients were 432 children discharged from the pediatric intensive care unit between May 1992 and April 1994. Interventions Quality of life was measured by using the Royal Alexandra Hospital for Children Measure of Function. The scale has two components, the first part completed by the clinician after parent interview and the second part completed separately by the parent. Measurements and Main Results Parents of 432 children were contacted between 3 and 24 months after discharge. Twenty-seven children (6.3%) had died after discharge from the pediatric intensive care unit; 59.3% (256) had scores indicating a normal quality of life, and 32.4% (140) had a fair quality of life with ongoing health, social, or cognitive problems requiring some intervention. Two percent of survivors (nine children) had scores indicating a poor quality of life as they had continued to experience significant or disabling health problems requiring hospitalization or the equivalent. Predictors of poor quality of life included presence of comorbidities, increased length of stay, and a diagnostic category of malignancy. Diagnostic categories of respiratory, trauma, and cardiac dysfunction were associated with a better outcome. Conclusions Our results indicate that the long-term outcome in terms of quality of life after admission to a pediatric intensive care unit is good or normal for the majority of surviving children. Those children with a poor outcome are likely to have significant comorbidities or a diagnosis of malignancy.