Elena G. Belousova

Risk factors for onset and remission of atopy, wheeze, and airway hyperresponsiveness

Background: Although many children with asthma may have a remission as they grow and other children who did not have asthma may develop asthma in adult life, knowledge about the factors that influence the onset and prognosis of asthma during adolescence and young adulthood is very limited. Methods: A cohort of 8–10 year old children (n=718) living in Belmont, New South Wales, Australia were surveyed six times at 2 yearly intervals from 1982 to 1992, and then again 5 years later in 1997. From this cohort, 498 subjects had between three and seven assessments and were included in the analysis. Atopy, airway hyperresponsiveness (AHR), and wheeze in the last 12 months were measured at each survey. Late onset, remission, and persistence were defined based on characteristics at the initial survey and the changes in characteristics at the follow up surveys. Results: The proportion of subjects with late onset atopy (13.7%) and wheeze (12.4%) was greater than the proportion with remission of atopy (3.2%) and wheeze (5.6%). Having atopy at age 8–12 years (OR 2.8, 95% CI 1.5 to 5.1) and having a parental history of asthma (OR 2.0, 95% CI 1.02 to 4.13) were significant risk factors for the onset of wheeze. Having AHR at age 8–12 years was a significant risk factor for the persistence of wheeze (OR 4.3, 95% CI 1.3 to 15.0). Female sex (OR 1.9, 95% CI 1.01 to 3.60) was a significant risk factor for late onset AHR whereas male sex (OR 1.9, 95% CI 1.1 to 2.8) was a significant risk factor for late onset atopy. Conclusions: The onset of AHR is uncommon during adolescence, but the risk of acquiring atopy and recent wheeze for the first time continues during this period. Atopy, particularly present at the age of 8–10 years, predicts the subsequent onset of wheeze.

Double blind randomised controlled trial of two different breathing techniques in the management of asthma

Background: Previous studies have shown that breathing techniques reduce short acting β2 agonist use and improve quality of life (QoL) in asthma. The primary aim of this double blind study was to compare the effects of breathing exercises focusing on shallow nasal breathing with those of non-specific upper body exercises on asthma symptoms, QoL, other measures of disease control, and inhaled corticosteroid (ICS) dose. This study also assessed the effect of peak flow monitoring on outcomes in patients using breathing techniques. Methods: After a 2 week run in period, 57 subjects were randomised to one of two breathing techniques learned from instructional videos. During the following 30 weeks subjects practised their exercises twice daily and as needed for relief of symptoms. After week 16, two successive ICS downtitration steps were attempted. The primary outcome variables were QoL score and daily symptom score at week 12. Results: Overall there were no clinically important differences between the groups in primary or secondary outcomes at weeks 12 or 28. The QoL score remained unchanged (0.7 at baseline v 0.5 at week 28, p = 0.11 both groups combined), as did lung function and airway responsiveness. However, across both groups, reliever use decreased by 86% (p<0.0001) and ICS dose was reduced by 50% (p<0.0001; p>0.10 between groups). Peak flow monitoring did not have a detrimental effect on asthma outcomes. Conclusion: Breathing techniques may be useful in the management of patients with mild asthma symptoms who use a reliever frequently, but there is no evidence to favour shallow nasal breathing over non-specific upper body exercises.

Pregnancy and Birth Outcomes in Families with Asthma

Studies of maternal asthma in pregnancy have shown an increased risk of adverse neonatal and maternal outcomes such as preeclampsia, hypertension, cesarean delivery, prematurity, low birth weight, and perinatal/neonatal mortality. However, results are not consistent between studies. We studied the association between maternal asthma and various adverse neonatal and maternal outcomes and explored whether there is any evidence that pregnancy exacerbates maternal asthma. The data were collected as part of the Childhood Asthma Prevention Study. Pregnant women with asthma or women whose partners or other children had current symptoms of asthma were recruited at six Sydney hospitals. All women recruited were post 36 weeks gestation and were living within 30 km of the study recruitment center. Information about family history of asthma was collected using a questionnaire at 36 weeks gestation and subsequent information about antenatal and perinatal events was obtained from hospital records. Data from 611 pregnant women were available for analysis, 340 of whom had asthma. Hypertension was significantly more common in asthmatics than in nonasthmatics [OR = 2.16 (1.02–4.6), p<0.043]. The prevalence of gestational diabetes, labor complications, delivery complications, and adverse neonatal outcomes did not differ significantly between the groups. We also found that the course of maternal asthma usually remains unchanged during pregnancy, but that more severe asthma is likely to get worse. We have confirmed previous observations that women with asthma are at increased risk of hypertension in pregnancy, which is consistent with studies that show that pregnant asthmatic women have a slightly increased risk of preeclampsia. However, we did not find evidence of an increased risk of adverse perinatal outcomes.

Family patterns of asthma, atopy and airway hyperresponsiveness: an epidemiological study.

The patterns of inheritance of asthma have largely been explored using data of symptom history collected by questionnaires which are subject to bias and which may therefore distort the measured relationship.

Maternal cigarette smoking is associated with reduced high-density lipoprotein cholesterol in healthy 8-year-old children

AIMS Smoking in pregnancy is common. Its effects on lipoprotein levels and arterial structure in childhood are not well characterized. We aimed to determine the effects of maternal smoking in pregnancy on lipoprotein levels and arterial wall thickness in healthy pre-pubertal children. METHODS AND RESULTS A community-based longitudinal study with prospective ascertainment of exposure to smoking in pregnancy and environmental tobacco smoke (ETS) since birth and then lipoprotein and arterial measurements at age 8 years. In 616 newborn infants (gestation >36 weeks and birth weight >2.5 kg) data were collected prospectively by questionnaire on smoking in pregnancy and ETS exposure in childhood. At age 8-years, 405 of the children had measurements of lipoproteins, blood pressure (BP) and carotid intima-media thickness. Children born to mothers who smoked in pregnancy had lower HDL cholesterol [1.32 vs. 1.50 mmol/L, 95% confidence interval (CI) for difference -0.28 to -0.08, P = 0.0005], higher triglycerides (1.36 vs. 1.20 mmol/L, 95% CI for ratio 1.01-1.30, P = 0.04) and higher systolic BP (102.1 vs. 99.9 mmHg, 95% CI for difference 0.6-3.8, P = 0.006). After adjustment for maternal passive smoking, post-natal ETS exposure, gender, breast feeding duration, physical inactivity, and adiposity, smoking in pregnancy remained significantly associated with lower HDL cholesterol (difference = -0.22 mmol/L, 95% CI -0.36 to -0.08, P = 0.003) but not with higher systolic BP. Neither smoking in pregnancy nor post-natal ETS exposure was associated with alterations of carotid artery wall thickness. CONCLUSION Smoking in pregnancy is independently associated with significantly lower HDL cholesterol in healthy 8-year-old children.

Respiratory health effects of exposure to low-NOx unflued gas heaters in the classroom: a double-blind, cluster-randomized, crossover study.

Background There are long-standing concerns about adverse effects of gas appliances on respiratory health. However, the potential adverse effect of low-NOx (nitrogen oxide) unflued gas heaters on children’s health has not been assessed. Objectives Our goal was to compare the respiratory health effects and air quality consequences of exposure to low-NOx unflued gas heaters with exposure to non–indoor-air-emitting flued gas heaters in school classrooms. Methods We conducted a double-blind, cluster-randomized, crossover study in 400 primary school students attending 22 schools in New South Wales, Australia. Children measured their lung function and recorded symptoms and medication use twice daily. Nitrogen dioxide (NO2) and formaldehyde concentrations were measured in classrooms using passive diffusion badges. Results NO2 concentrations were, on average, 1.8 times higher [95% confidence interval (CI), 1.6–2.1] and formaldehyde concentrations were, on average, 9.4 ppb higher (95% CI, 5.7–13.1) during exposure to unflued gas versus flued gas heaters. Exposure to the unflued gas heaters was associated with increased cough reported in the evening [odds ratio (OR) = 1.16; 95% CI, 1.01–1.34] and wheeze reported in the morning (OR = 1.38; 95% CI, 1.04–1.83). The association with wheeze was greater in atopic subjects. There was no evidence of an adverse effect on lung function. Conclusions We conclude that classroom exposure to low-NOx unflued gas heaters causes increased respiratory symptoms, particularly in atopic children, but is not associated with significant decrements in lung function. It is important to seek alternative sources of heating that do not have adverse effects on health.

Questionnaire Responses That Predict Airway Response to Hypertonic Saline

Background: Airway hyperresponsiveness to hypertonic saline (HS) is associated with airway inflammation. We investigated if responsiveness to HS was predicted by asthma symptoms in the last 3 months. Objectives: To investigate if responsiveness to HS can be estimated by questionnaire items investigating asthma symptoms of the last 3 months. Methods: Six hundred and four patients with physician-diagnosed asthma being assessed for asthma severity were studied. Bronchial provocation with 4.5% saline was performed, and a questionnaire was administered. The response to 4.5% saline was reported as the provoking dose to cause a 15% fall in the forced expiratory volume in 1 s FEV1 (PD15) and the response-dose ratio (RDR). Results: Based on the GINA guidelines, asthma severity was intermittent in 497 patients, mild in 107 patients, moderate in 3 patients and severe in 1 patient. A PD15 to 4.5% saline was recorded in 234 of the 604. Questions on self-recognition of asthma, dust as a trigger, food as a trigger, and frequency of bronchodilator use were significant predictors for a PD15, and currently taking steroids decreased the likelihood of a positive response to 4.5% saline. Using a multiple-linear regression model, a difference in the RDR could be calculated between those who answered positively compared with the reference group, who answered negatively. This difference could be used as a guide for predicting abnormal reactivity. An increase in RDR in response to 4.5% saline, compared with the reference group, was demonstrated in the presence of self-recognition of asthma severity, dust and cats as a trigger or use of bronchodilator during sleep hours. Conclusions: Because of the high positive predictive value of HS for identifying patients with asthma it might be that the need for bronchodilator use at night not only predicts airway hyperresponsiveness to HS, it also could reflect the severity of asthma.

Weighted Road Density and Allergic Disease in Children at High Risk of Developing Asthma

Background Evidence for an association between traffic-related air pollution and allergic disease is inconsistent, possibly because the adverse effects may be limited to susceptible subgroups and these have not been identified. This study examined children in the Childhood Asthma Prevention Study (CAPS), potentially susceptible to air pollution effects because of a family history of asthma. Methods We examined cross-sectional associations at age eight years between road density within 75 m and 50 m of home address weighted by road type (traffic density), as a proxy for traffic-related air pollution, on the following allergic and respiratory outcomes: skin prick tests (SPTs), total and specific serum IgE, pre- and post-bronchodilator lung function, airway hyperresponsiveness, exhaled NO, and reported asthma and rhinitis. Results Weighted road density was positively associated with allergic sensitisation and allergic rhinitis. Adjusted relative risk (RR) for house dust mite (HDM) positive SPT was 1.25 (95% CI: 1.06–1.48), for detectable house dust mite-specific IgE was 1.19 (95% CI: 1.01–1.41) and for allergic rhinitis was 1.30 (95% CI: 1.03–1.63) per 100 m local road or 33.3 m motorway within 50 m of home. Associations were also seen with small decrements of peak and mid-expiratory flows and increased risk of asthma, current wheeze and rhinitis in atopic children. Conclusion Associations between road density and allergic disease were found in a potentially susceptible subgroup of children at high risk of developing atopy and asthma.

Lung Function Is Associated with Arterial Stiffness in Children

Background In older adults, an independent association exists between impaired lung function and cardiovascular disease. This interaction might be related to the effects of aging and/or smoking. In order to explore possible childhood antecedents to this association, we hypothesized that decreased lung function and vascular stiffness might be related, in early life. Objective To determine the relationship between lung function and carotid augmentation index (AIx), a measure of vascular stiffness, in 8-year old children. Methods Data on brachial blood pressure, lung function (FEV1, FVC, FEV1/FVC, obtained by spirometry) and carotid AIx75 (AIx standardised to an arbitrary heart rate of 75 beats per minute, obtained by applanation tonometry) was available in 249 community-based 8-year old children. These healthy children had been subjects in a randomised controlled trial of two interventions (omega-3 fatty acid supplementation and house-dust mite avoidance) to prevent asthma. Smoking in pregnancy and childhood environmental tobacco smoke (ETS) exposure was prospectively collected by questionnaire. The association between lung function and carotid AIx75 was assessed in multivariate models that included sex, height, smoking status during pregnancy, ETS exposure and randomisation groups (house dust mite avoidance and dietary intervention) as covariates. Results In the fully adjusted models, Carotid AIx75 was independently associated with FEV1 (standardised β = −0.17,b = −6.72, partial R2 = .02, p = 0.03), FVC (standardised β = −0.29, b = −9.31, partial R2 = 0.04, p<0.001) and FEV1/FVC (standardised β = .13, b = 18.4, partial R2 = 0.02, p = 0.04). Conclusion Lower lung volumes are associated with increased vascular stiffness at an early age. The interaction between lung function and vascular stiffness may thus represent more than just age-related alterations in both the pulmonary and vascular systems.

Measuring peak flow enhances adherence to monitoring in asthma

Peak expiratory flow (PEF) monitoring is recommended in the management of moderate to severe asthma,1 and PEF outcome variables are used in many clinical trials. However, adherence with PEF monitoring is poor, and this is often attributed to the burden of measurement and recording. This analysis examined whether adherence with symptom monitoring was impaired by asking patients also to record PEF measurements. Data were obtained from a randomised double blind study of breathing techniques in adults with poorly controlled asthma. Full details of the clinical trial are reported elsewhere.2 Subjects were non-smokers aged 19–80 years, using reliever as-needed ⩾4 times/week and taking inhaled corticosteroids ⩾200 μg/day. Figure 1 shows the study design, with between-visit intervals of 2 or 6 weeks. Throughout the study, 57 subjects used electronic diary spirometers (AM2, Erich Jaeger GmbH, Hoechberg, Germany) twice daily to answer questions about symptom frequency/intensity and treatment. There were three “PEF periods” during which subjects also measured spirometry twice daily. PEF was displayed after each of three manoeuvres followed by the highest PEF. …