Predictive value of childhood airway hyper-responsiveness to indirect stimuli: 10-year longitudinal study

Airway hyper-responsiveness (AHR) is a common feature in asthma. The use of AHR in predicting active asthma or the persistence of AHR in childhood is poorly understood. By analyzing longitudinal connections including different measures of AHR, lung function, and inflammation markers, we sought to identify the best available method for predicting persistence of AHR and identification of later active asthma.

We tested 105 asthmatic children aged 3-7 years with fractional exhaled nitric oxide (FeNO), impulse oscillometry (IOS), and AHR evaluated by indirect methods (hypertonic saline and exercise challenge). Ten years later, 64 children participated in the follow-up visit and were tested with FeNO, IOS, spirometry, and methacholine challenge. At both study visits, blood samples were collected, and a questionnaire was completed.

Asthma was in remission in 66% of patients at adolescence. AHR measured by hypertonic saline challenge at preschool age was associated with asthma symptoms (OR 10.2; 95% CI 2.8, 37.3) but not with AHR estimated with methacholine challenge 10 years later. AHR measured by exercise challenge was not associated with AHR or recent asthma symptoms in adolescence. Preschool eosinophilia continued until adolescence in 87% of patients but was not associated with AHR or subjective signs of asthma 10 years later. Wheezy preschoolers with atopy had a higher risk for AHR in adolescence (OR 4.1; 95% CI 1.0, 16.2).

Results from hypertonic saline challenge are associated with persistent asthma symptoms even after a decade. AHR measured by indirect methods at preschool age did not predict AHR in adolescence.