Elsevier

The Lancet

Volume 372, Issue 9643, 20–26 September 2008, Pages 1058-1064
The Lancet

Articles
Wheezing and bronchial hyper-responsiveness in early childhood as predictors of newly diagnosed asthma in early adulthood: a longitudinal birth-cohort study

https://doi.org/10.1016/S0140-6736(08)61447-6Get rights and content

Summary

Background

Incidence of asthma increases during early adulthood. We aimed to estimate the contributions of sex and early life factors to asthma diagnosed in young adults.

Methods

1246 healthy newborn babies were enrolled in the Tucson Children's Respiratory Study. Parental characteristics, early-life wheezing phenotypes, airway function, and bronchial hyper-responsiveness to cold dry air and sensitisation to Alternaria alternata were determined before age 6 years. Physician-diagnosed asthma, both chronic and newly diagnosed, and airway function were recorded at age 22 years.

Findings

Of 1246 babies enrolled, 849 had follow-up data at 22 years. Average incidence of asthma at age 16–22 years was 12·6 per thousand person-years. 49 (27%) of all 181 cases of active asthma at 22 years were newly diagnosed, of which 35 (71%) were women. Asthma remittance by 22 years was higher in men than in women (multinomial odds ratio [M-OR] 2·0, 95% CI 1·2–3·2, p=0·008). Age at diagnosis was linearly associated with the ratio of forced expiratory volume at 1 s to forced vital capacity at age 22 years. Factors independently associated with chronic asthma at 22 years included onset at 6 years (7·4, 3·9–14·0) and persistent wheezing (14·0, 6·8–28·0) in early life, sensitisation to A alternata (3·6, 2·1–6·4), low airway function at age 6 years (2·1, 1·1–3·9), and bronchial hyper-responsiveness at 6 years (4·5, 1·9–10·0). Bronchial hyper-responsiveness (6·9, 2·3–21·0), low airway function at 6 years (2·8, 1·1–6·9), and late-onset (4·6, 1·7–12·0) and persistent wheezing (4·0, 1·2–14·0) predicted newly diagnosed asthma at age 22 years.

Interpretation

Asthma with onset in early adulthood has its origins in early childhood.

Funding

National Heart Lung and Blood Institute.

Introduction

Several lines of evidence indicate that most people diagnosed with asthma in the first two decades of life had recurrent episodes of wheezing in early childhood,1 suggesting that the disease process might have started years before diagnosis. Prospective data from the 1958 British cohort2 indicated an upsurge in incident cases of asthma and wheezing in early adulthood. This second wave of newly diagnosed disease has not been extensively studied but constitutes a high proportion of asthma in young adults and contributes to respiratory morbidity in this age group, especially in women.3 Whether factors in early life contribute to the risk of this second wave of asthma, as they do for asthma developing during the school years, is unknown. Strachan and co-workers2 reported that pre-existing allergic rhinitis was an important risk factor for new-onset asthma in early adult life; Guerra and colleagues4 confirmed this finding and suggested that allergy-related factors might play a part. Whether respiratory events and changes in airway and immune reactivity before age 6 years affect the incidence and prevalence of asthma in early adulthood needs to be assessed.

Children who have lower respiratory tract illnesses in early life are at increased risk of wheezing and asthma.5, 6 In a longitudinal study of unselected children,1 we showed that those who are wheezing at age 6 years are at increased risk of subsequent asthma up to the age of 16 years, whereas those with transient early wheezing (ie, those who wheeze with lower respiratory tract illnesses but do not report wheezing at age 6 years) are not. What the relation is between these early wheezing phenotypes and new-onset asthma in early adulthood is unknown.

Bronchial hyper-responsiveness, a central characteristic of asthma irrespective of age at onset,7 is an abnormal bronchoconstrictive response to various stimuli. We previously showed in this same longitudinal cohort that non-asthmatic children with bronchial hyper-responsiveness at age 6 years were at increased risk of asthma by 11 years, but the association was not independent of allergic sensitisation and mild wheezing at 6 years.8

We aimed to determine whether potential risk factors for asthma measured during the preschool years predict prevalence, incidence, and remission of physician-diagnosed asthma and asthma-like symptoms in early adulthood.

Section snippets

Study design

Healthy infants were enrolled at birth in the Tucson Children's Respiratory Study in Tucson, AZ, USA, between 1980 and 1984.9 Parents were contacted shortly after their children were born and completed a questionnaire describing their ethnicity, history of physician-diagnosed asthma, years of education, and current smoking habits. Informed consent was obtained from the parents for their children, or by the enrollees themselves if appropriate, and the Institutional Review Board of the University

Results

1246 children were enrolled. 858 had data at 22 years; mean age at final data collection was 21·7 years (SD 1·2)—735 collected at 22 years, 77 at 18 years, and 46 at 24 years. Of these 858, 835 completed questionnaires at 2 (mean age 1·6 years, SD 0·3), 769 at 3 (2·9, 0·5), 840 at 6 (6·2, 0·9), 727 at 8 (8·6, 0·7), 831 at 11 (10·9, 0·6), 646 at 13 (13·5, 0·6), and 712 at 16 (16·6, 0·6) years. Individuals who had information for asthma and respiratory symptoms at age 22 years were more likely to

Discussion

In over 70% of people with current asthma and 63% of those with newly diagnosed asthma at age 22 years, episodes of wheezing had happened in the first 3 years of life or were reported by parents at age 6 years (table 4). Cold-air bronchial hyper-responsiveness (but not sensitisation to Alternaria) at age 6 years, late-onset and persistent wheezing by 6 years, and female sex, were independent predictors of incident physician-diagnosed asthma at 22 years. Moreover, cold-air bronchial

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