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

Abstract

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.

Figure 1

Definitions of asthma at age 22: Inactive asthma is a physician diagnosis of asthma between 2 and 16 years but no current symptoms at age 22, newly diagnosed asthma is first diagnosis and current symptoms at age 22, chronic asthma is a diagnosis between 2 and 16 years and current symptoms at age 22 and no asthma is no diagnosis of asthma through age 22 years.

Figure 2

FEV1/FVC ratio and asthma at age 22 years by age at first asthma diagnosis. FEV1/FVC ratio was adjusted for sex in a linear regression and the standardized residuals from the regression (z-scores) were saved and used as the outcome measure for this figure (a z-score of 1 represents one standard deviation from the group mean of zero). Age at first diagnosis was divided into three groups based on the questionnaire when the diagnosis was first reported: 2-6yrs, 8-11yrs and 13-16yrs. Newly Dx is first diagnosis of asthma and current symptoms at age 22 years, inactive is first diagnosis of asthma between 2 and 16 years with no symptoms at age 22 years, chronic is first diagnosis between 2 and 16 years with active symptoms at age 22 years, the none group never received a diagnosis of asthma during the study period. Age at diagnosis was significantly and linearly related to the FEV1/FVC ratio, p=0.009, among inactive and chronic asthmatics at age 22 years, after adjusting for asthma status and sex.