Elsevier

The Lancet

Volume 368, Issue 9537, 26 August–1 September 2006, Pages 763-770
The Lancet

Articles
Perennial allergen sensitisation early in life and chronic asthma in children: a birth cohort study

https://doi.org/10.1016/S0140-6736(06)69286-6Get rights and content

Summary

Background

Reduced lung function is a feature of chronic asthma, which becomes apparent at school age. Unknown factors between birth and school age determine the progressive loss of pulmonary function in children with persistent asthma. We investigated the role of allergic sensitisation and allergen exposure early in life.

Methods

The German Multicentre Allergy Study followed 1314 children from birth to 13 years of age. We regularly interviewed parents about their child's asthma and measured IgE levels. Allergen exposure was assessed at age 6 months, 18 months, and at 3, 4, and 5 years; lung function was assessed at 7, 10, and 13 years; post-bronchodilator response at 10 and 13 years; and a bronchial histamine challenge was done at 7 years.

Results

90% of children with wheeze but no atopy lost their symptoms at school age and retained normal lung function at puberty. By contrast, sensitisation to perennial allergens (eg, house dust mite, cat and dog hair) developing in the first 3 years of life was associated with a loss of lung function at school age. Concomitant exposure to high levels of perennial allergens early in life aggravated this process: forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio was 87·4 (SD 7·4) for those sensitised and with high exposure compared with 92·6 (6·0) for those not sensitised, p<0·0001; and maximal expiratory flow at 50% (MEF50) 86·4 (25·1) for sensitised and with high exposure compared with 101·5 (23·2; p=0·0031) for those not sensitised. Such exposure also enhanced the development of airway hyper-responsiveness in sensitised children with wheeze. Sensitisation and exposure later in life had much weaker effects and sensitisation to seasonal allergens did not play a part.

Interpretation

The chronic course of asthma characterised by airway hyper-responsiveness and impairment of lung function at school age is determined by continuing allergic airway inflammation beginning in the first 3 years of life. However, children with a non-atopic wheezing phenotype lose their symptoms over school age and retain normal lung function at puberty.

Introduction

Morbidity from chronic asthma is very high in the western world. The estimated costs for the management of childhood asthma in the European Union are €3000 million.1 Chronic asthma is characterised by repeated attacks of airway obstruction and intermittent symptoms of increased airway responsiveness to triggering factors such as exercise, allergen exposure, and viral infections. Airway inflammation and airway remodelling have been suggested as underlying mechanisms of this condition. Reduced lung function is a feature of asthma, and asthma management guidelines aim to achieve near-normal lung function in affected patients.2

In prospective studies of children at risk of asthma from birth onwards, a fall in pre-bronchodilator lung function becomes apparent around school age.3 No further progression of lung function impairment up to adolescence and adult age has been identified.3, 4, 5 Lung function in asthmatic people is subnormal but develops at the same rate as in asymptomatic individuals. Unknown factors between birth and school age determine the progressive loss of pulmonary function in children with asthma.

We investigated the role of allergic sensitisation and allergen exposure early in life for the course of asthma and the development of lung function from birth to school age and puberty in the prospective German Multicentre Allergy Study (MAS).

Section snippets

Patients

The MAS, a birth cohort, recruited 1314 healthy mature infants born in 1990 in five German cities. A detailed description of the sampling scheme and the study participants is given elsewhere.6 499 newborns with risk factors for atopy (raised cord blood IgE [≥0·9 kU/L] or at least two atopic family members, or both) and 815 newborns with none of these risk factors were included in the cohort. All children were followed-up at ages 1, 3, 6, 12, 18, and 24 months and from then on yearly within 4

Results

Of the 1314 enrolled children, 971 (73·9%) and 759 (57·8%) had information on wheezing at school age (5–7 years) and at age 13 years, respectively. Participation rates for blood sampling at the respective time points were slightly lower. To assess potential participation bias we analysed the number of attended follow-ups per child—ie, we tested whether some children participated in more follow-ups than other children based on data collected at birth. Of the 1314 children included in the MAS at

Discussion

Children with repeated wheeze over the first 5 years of life who do not develop atopic sensitisation lose their symptoms during school age and retain normal lung function at puberty. By contrast, children with repeated wheeze in the first 5 years who also become sensitised to perennial allergens are prone to a chronic course of asthma characterised by more severe symptoms, presence of airway hyper-responsiveness, and decrements in baseline and post-bronchodilator lung function. Increased

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