Natural History of Airway Hyperresponsiveness and Its Association With Asthma Traits

The natural history of airway hyperresponsiveness (AHR) from childhood to adulthood and its association with asthma status are poorly understood. We aim to define the natural history of AHR in relation to asthma characteristics such as symptoms, atopy and lung function to improve our understanding of the changes in AHR with asthma pathophysiology during adolescence.

Methacholine bronchial challenge test (BCT) was undertaken in the Isle of Wight whole population birth cohort at 10 years (n = 783), 18 years (n = 585) and 26 years (n = 86). Data on wheeze, lung function, and atopy were collected at each time point. Definite AHR was defined as methacholine concentration provoking a 20% decrease in Forced Expiratory Volume in 1 s (PC₂₀) at < 4 mg/mL.

AHR prevalence was 21.6% (169/783) at 10 years and 5% (29/585) at 18 years of age (p < 0.01). In 406 participants, where methacholine BCT was performed at both 10 and 18 years, 80.9% of those with AHR at age 10 became negative at 18 years. At a population level, AHR trajectory was in the opposite direction to that of asthma (14.7% at age 10 to 17.6% at age 18; p = 0.004), atopy (26.9% at age 10 to 41.5% at age 18; p < 0.001) and airway obstruction (FEV₁/FVC ratio of 0.88 at age 10 to 0.87 at age 18; p < 0.001). AHR prevalence remained stable between the ages of 18 and 26 years.

The natural history of AHR is characterised by a marked decrease in prevalence during adolescence, in contrast to asthma and other asthma characteristics. Age should be considered when interpreting AHR as an asthma defining trait.