Absence of diurnal variability of airway reactivity and hypoxic ventilatory drive in adolescents with stable asthma

Background: Symptoms from asthma are often prominent at night. In adults significant circadian variation has been shown with reduced peak expiratory flow rates and increased bronchial reactivity to methacholine in the early morning hours. Because adolescence is the age group with the greatest increase in asthma-related deaths in the 1980s, we hypothesized that adolescents might be susceptible to circadian variation of airway reactivity. Objective: We sought to measure circadian variation of reactivity to methacholine (PC₂₀) and hypoxic ventilatory drive (HVD), both of which would accentuate asthma that occurs at night and may predispose to death. Methods: Sixteen children with asthma of various severity, aged 9 to 18 years, were studied at 4 PM and again at 4 AM to define circadian variation in FEV₁, PC₂₀, and HVD. Eleven children were studied on a second day 4 to 10 weeks after the first study. Results: There was no systematic variation between 4 PM and 4 AM for FEV₁ (P = .69), PC₂₀ (P = .94), or HVD (P = .47). Six of the 16 children had PC²⁰ values that were greater than 2-fold different between 4 PM and 4 AM; 3 of these were more reactive (requiring less methacholine) at 4 PM, and 3 were more reactive at 4 AM. At the second study, results were similar, with no systematic variation. Diurnal variability for PC²⁰ was not consistent over the 2 study days, and at the second study all children with diurnal variability were more reactive at 4 PM. Conclusion: These data on airway reactivity, HVD, and other measures modulated by cholinergic neural mechanisms do not identify any systematic diurnal variation that would place an adolescent at risk for nighttime problems with asthma.