Asthma diagnosis and treatment
Influence of early life exposures on incidence and remission of asthma throughout life

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Abstract

Background

Knowledge of the effects of early environmental and congenital factors on the natural history of asthma may provide important clues to the pathogenesis of asthma.

Objective

We assessed associations between potential, early determinants and the incidence and remission of asthma throughout life, and tested whether the strength and direction of these associations varied in childhood, adolescence, and adulthood.

Methods

The data pertaining to the individual asthma history of 18,156 subjects, age 0 to 44 years, who attended the clinical stage of the European Community Respiratory Health Survey were analyzed retrospectively by life-event methods. Onset of asthma was defined as age at the first attack, and asthmatic patients were considered to be in remission if they had not been under treatment or had an attack of asthma in the past 24 months. Onset and remission were evaluated in 3 time windows: <10, 10 to 20, and ≥20 years of age. The associations of asthma with early determinants were estimated by hazard ratios (HRs).

Results

A family history of asthma or allergy was associated with a higher risk of developing asthma (HR, 1.89; 95% CI, 1.67-2.13) and a lower chance of remission (HR, 0.79; 95% CI, 0.64-0.99) throughout life. No matter what one's genetic predisposition was, early, acute respiratory infections were associated with an increased lifelong risk of asthma onset (pooled HR, 3.19; 95% CI, 2.75-3.69), whereas early contact with older children, which is a marker of prolonged, intermittent exposure to infectious agents, conferred permanent protection against asthma (HR, 0.84; 95% CI, 0.74-0.96) and increased the chance of remission in childhood asthma (HR, 1.50; 95% CI, 1.10-2.04). Pet ownership had a protective effect only in childhood (HR, 0.78; 95% CI, 0.74-0.96), whereas maternal smoking did not show a significant association with asthma. Female sex was negatively associated with the onset of asthma in childhood (HR, 0.62; 95% CI, 0.52-0.75) and positively in adulthood (HR, 2.01; 95% CI, 1.61-2.51). The pattern of associations was similar in sensitized (positive assay to specific IgE) and nonsensitized asthmatic patients.

Conclusion

Genetic predisposition and exposure to infectious agents are major early determinants that influence a subsequent history of asthma. The length and type of exposure to infectious agents seem able either to promote or to suppress an anti-inflammatory process, unrelated to IgE, which can partially interfere with an acquired predisposition for asthma.

Section snippets

Study design

The data presented in this study were collected within the framework of the ECRHS between 1991 and 1993. ECRHS is an international, cross-sectional, 2-stage study on the prevalence, determinants, and management of asthma and has been fully described previously.10 The study involved several centers in different countries; centers were defined by pre-existing administrative boundaries and had a population of at least 150,000 inhabitants. In each center, a random sample of at least 1500 men and

Results

A total of 1558 of 18,156 valid responders (8.6%) reported lifelong asthma. The main characteristics and distribution of studied determinants are given in Table I.

The crude lifelong incidence of asthma was 2.61/1000/y in males and 2.72/1000/y in females (P = .45; Table II); incidence decreased in males as age increased, whereas it remained stable in females. The rate of remission was higher in male patients than in female patients (34% vs 27%; P = .004); in both sexes, the percentage of remittent

Discussion

In recent years, there has been a great epidemiologic effort devoted to the study of environmental factors early in life and their importance to subsequent asthma and allergy. However, until now, only 1 recently published article investigated prospectively the natural history of asthma in a random sample of subjects from age 9 years to age 26 years, suggesting that outcomes in adult asthma may be determined primarily in early childhood.14

The novelty of our approach is that it considers the

Acknowledgements

We thank the ECRHS Co-ordinating Centre (London), the Project Management Group, and the Study Group for their assistance (for a list of principal participants in ECRHS, see the Journal's Online Repository at www.mosby.com/jaci).

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    Supplementary data associated with this article can be found at doi:10.1016/j.jaci.2004.01.780.

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