Lou I. Landau

Association between breast feeding and asthma in 6 year old children: findings of a prospective birth cohort study

Abstract Objectives: To investigate the association between the duration of exclusive breast feeding and the development of asthma related outcomes in children at age 6 years. Design: Prospective cohort study. Setting: Western Australia. Subjects: 2187 children ascertained through antenatal clinics at the major tertiary obstetric hospital in Perth and followed to age 6 years. Main outcome measures: Unconditional logistic regression to model the association between duration of exclusive breast feeding and outcomes related to asthma or atopy at 6 years of age, allowing for several important confounders: sex, gestational age, smoking in the household, and early childcare. Results: After adjustment for confounders, the introduction of milk other than breast milk before 4 months of age was a significant risk factor for all asthma and atopy related outcomes in children aged 6 years: asthma diagnosed by a doctor (odds ratio 1.25, 95% confidence interval 1.02 to 1.52); wheeze three or more times since 1 year of age (1.41, 1.14 to 1.76); wheeze in the past year (1.31, 1.05 to 1.64); sleep disturbance due to wheeze within the past year (1.42, 1.07 to 1.89); age when doctor diagnosed asthma (hazard ratio 1.22, 1.03 to 1.43); age at first wheeze (1.36, 1.17 to 1.59); and positive skin prick test reaction to at least one common aeroallergen (1.30, 1.04 to 1.61). Conclusion: A significant reduction in the risk of childhood asthma at age 6 years occurs if exclusive breast feeding is continued for at least the 4 months after birth. These findings are important for our understanding of the cause of childhood asthma and suggest that public health interventions to optimise breast feeding may help to reduce the community burden of childhood asthma and its associated traits. Key messages Asthma is the leading cause of admission to hospital in Australian children and its prevalence is increasing Whether breast feeding protects against asthma or atopy, or both, is controversial Asthma is a complex disease, and the relative risks between breast feeding and asthma or atopy are unlikely to be large; this suggests the need for investigation in a large prospective birth cohort with timely assessment of atopic outcomes and all relevant exposures Exclusive breast feeding for at least 4 months is associated with a significant reduction in the risk of asthma and atopy at age 6 years and with a significant delay in the age at onset of wheezing and asthma being diagnosed by a doctor Public health interventions to promote an increased duration of exclusive breast feeding may help to reduce the morbidity and prevalence of childhood asthma and atop

Breast feeding and respiratory morbidity in infancy: a birth cohort study

Aim: To examine the relation between the duration of breast feeding and morbidity as a result of respiratory illness and infection in the first year of life. Methods: Prospective birth cohort study of 2602 live born children ascertained through antenatal clinics at the major tertiary obstetric hospital in Perth, Western Australia. Main outcome measures were hospital, doctor, or clinic visits, and hospital admissions for respiratory illness and infection in the first year of life. Main exposure measures were the duration of predominant breast feeding (defined as the age other milk was introduced) and partial (any) breast feeding (defined as the age breast feeding was stopped). Main confounders were gender, gestational age less than 37 weeks, smoking in pregnancy, older siblings, maternal education, and maternal age. Results: Hospital, doctor, or clinic visits for four or more upper respiratory tract infections were significantly greater if predominant breast feeding was stopped before 2 months or partial breast feeding was stopped before 6 months. Predominant breast feeding for less than six months was associated with an increased risk for two or more hospital, doctor, or clinic visits and hospital admission for wheezing lower respiratory illness. Breast feeding for less than eight months was associated with a significantly increased risk for two or more hospital, doctor, or clinic visits or hospital admissions because of wheezing lower respiratory illnesses. Conclusions: Predominant breast feeding for at least six months and partial breast feeding for up to one year may reduce the prevalence and subsequent morbidity of respiratory illness and infection in infancy.

Effect of salbutamol on oxygen saturation in bronchiolitis.

Inhaled sympathomimetic agents are often used in bronchiolitis with little objective evidence of benefit. The arterial oxygen saturation (SaO2) reflects the adequacy of ventilation-perfusion balance. The aim of the current study was to determine the effect of inhaled salbutamol on SaO2. In a randomised, double blind study, 21 infants, admitted with bronchiolitis positive for respiratory syncytial virus, had continuous SaO2 measurements made before and after nebulised salbutamol or placebo. SaO2 was recorded over 30 minutes for a baseline, then during the 10 minutes of first nebulisation with either salbutamol or saline, then over 30 minutes after nebulisation, the 10 minutes of second nebulisation with the alternate regime, and another 30 minutes after this second nebulisation. Desaturation occurred after salbutamol and saline nebulisation. The fall in SaO2 with salbutamol was seen whether infants received it as the first or second nebulisation. The fall in SaO2 after saline was seen when given first, but not when given after salbutamol. The decrease in SaO2 was greater and more prolonged with salbutamol than with saline. Routine nebulised aerosol sympathomimetic treatment during acute bronchiolitis cannot be recommended.

Reduced lung function both before bronchiolitis and at 11 years

Background and Aims: We have previously shown an association between reduced premorbid lung function (V‘maxFRC) and bronchiolitis. We hypothesised that individuals with bronchiolitis will go on to have reduced lung function and increased respiratory symptoms in childhood. Methods: V‘maxFRC was measured at 1 month of age; individuals with bronchiolitis were prospectively identified. Annual symptom questionnaires were completed from 3 to 6 years. At 11 years of age, children underwent an assessment including questionnaire, lung function, airway response to histamine (AR), and skin prick testing. Results: Eighteen individuals with bronchiolitis were ascertained from 253 cohort members. Children with bronchiolitis had increased viral induced wheeze at 3 (OR 5.8, 95% CI 1.4 to 25.2; n = 103) and 5 years (OR 5.3, 95% CI 1.1 to 25.5; n = 101). At 11 years of age, 194 children were assessed including 16 with past bronchiolitis. These 16 individuals had reduced mean z scores for % V‘maxFRC compared with other children (−0.56 and 0.06 respectively) and mean z scores for % FEF25–75 at 11 years (−0.53 and 0.06 respectively). At 11 years, FEV1, FVC PEF, AR, atopy, wheeze, and diagnosed asthma were not different between groups. Conclusions: Reduced lung function is present before and after bronchiolitis; the level of reduction is comparable. The mechanism for wheeze and reduced lung function after bronchiolitis appears to be related to premorbid lung function and not bronchiolitis per se.

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.

Associations between postnatal weight gain, change in postnatal pulmonary function, formula feeding and early asthma

Background: A study was undertaken to examine factors that might influence lung function during infancy and to test the hypothesis that change in weight during infancy is negatively associated with change in lung function. Methods: Weight, length and maximal flow at functional residual capacity (V′maxFRC) were measured at ages 1 and 12 months. V′maxFRC was adjusted for length. Asthma symptoms and age at introduction of formula feeds were identified from questionnaires. Groups were dichotomised by V′maxFRC at 1 month and change in V′maxFRC. Results: 154 infants were assessed at ages 1 and 12 months. The change in V′maxFRC was inversely associated with change in weight (r = −0.18, r2 = 0.13, p<0.001). The group with lower V′maxFRC at 1 month and reduced change in V′maxFRC over infancy had the greatest weight gain (p = 0.003) and increased risk for asthma symptoms by 3 years (p = 0.017) but not afterwards. Exclusive breast feeding to 6 months was associated with a mean reduction in weight gain at age 12 months in comparison with earlier introduction of formula milk (mean difference 0.65 kg, p = 0.001), and was also associated with reduced asthma symptoms at 3 years (odds ratio 0.44, p = 0.043) but not at 6 or 11 years of age. Conclusions: Weight gain in infancy is inversely associated with change in lung function during infancy. Postnatal weight gain may be indirectly associated with early transient asthma symptoms via an influence on lung growth during infancy, and this is potentially modifiable by breast feeding. These associations could be relevant to the clinically recognised syndrome of the “fat happy wheezer”.

β2 adrenoceptor Arg16Gly polymorphism, airway responsiveness, lung function and asthma in infants and children

Background We have previously reported a relationship between increased airway responsiveness (AR) in infancy and reduced childhood lung function.

Intrasubject variability of pulmonary function testing in healthy children.

The intrasubject variability of repeat pulmonary function testing was examined in 20 healthy children aged 10 to 16 years. The children were tested a maximum of 11 times over a period of two months. The tests examined were spirometry, maximum expiratory flow-volume curves, body plethysmograph determination of lung volumes, and single breath nitrogen washout. The time of day or the length of the re-test interval, up to a period of two months, did not significantly affect the variability. Standard deviation was used when comparing the variability of measurements with the same units and coefficient of variation was used when comparing measurements of different units. The vital capacity measured by spirometry was the least variable measurement. Functional residual capacity, residual volume and total lung capacity were equally reproducible but as a group were more variable than vital capacity. There was no significant difference between the variability of the following measurements: forced expired flow from 25 to 75% of the vital capacity, flows at 70%, 50% and 40% total lung capacity, and flows at 50% vital capacity. Flows at 25% vital capacity were significantly less variable than other measurements of flow. The variability of forced expired volume in one second was examined and the use of this measurement in determining significant bronchial hyper-reactivity was assessed.

Prenatal ultrasound biometry related to subsequent blood pressure in childhood

Study objective: To relate measures of fetal growth/size other than birth weight with subsequent blood pressure measured on the same individuals within the context of the “fetal origins of adult disease”. Design: A prospective cohort study in which measurements of fetal dimensions obtained by serial ultrasound imaging between 18 and 38 weeks gestation were analysed with reference to systolic blood pressure measurements on the offspring at age 6 years. Setting: Perth, Western Australia. Participants: A subgroup of 707 eligible mother-fetus pairs from a cohort of 2876 pregnant women and their offspring. The number of mother-fetus pairs varied at each gestational age and by measurement of fetal dimension. Subsequent blood pressure recordings were obtained on approximately 300 of the offspring at age 6 years. Main results: The findings confirmed the inverse association between birth weight and systolic blood pressure at age 6. There was, also, an inverse relation between fetal femur length and systolic blood pressure at age 6, adjusted for current height. Furthermore, an inverse association was demonstrated between a statistically derived measure of fetal growth (conditional z score) between 18 and 38 weeks gestation and later systolic blood pressure at age 6. The effect sizes for all three relations were in the order of 1–2 mm Hg per standard deviation change. Conclusion: The mechanisms underpinning the “fetal origins” hypothesis may be operative early in pregnancy and may be reflected in the length of the fetal femur in early to mid-pregnancy.

Cross sectional and longitudinal association of the secretoglobin 1A1 gene A38G polymorphism with asthma phenotype in the Perth Infant Asthma Follow-up cohort

Background Associations between Clara cell secretory protein gene variants (SCGB1A1, also known as CC16, CC10, CCSP and uteroglobin) and the asthma phenotype have been found in five out of eight studies world‐wide. No study has investigated the contribution of SCGB1A1 polymorphisms to the development and/or persistence of the asthma phenotype in a birth cohort followed over time.