Determinants of airway hyperresponsiveness in mild asthma

Background: Patients with mild asthma may have coexisting severe airway hyperresponsiveness (AHR), although the reasons for this are uncertain.Objective: To evaluate the factors that determine AHR in mild asthma.Methods: We performed a retrospective database evaluation of two groups of patients with mild asthma with forced expiratory volume in 1 second (FEV1) of 80% or more than predicted. Group A (n = 92; mean inhaled corticosteroid dose, 491 mug) had moderate-to-severe AHR to methacholine (provocative dose causing a 20% decrease in FEV, [methacholine PD20], less than or equal to100 mug), whereas group B (n = 92; mean inhaled corticosteroid dose, 509 mug) had borderline AHR (methacholine PD20, greater than or equal to800 mug). Both groups were matched for age, sex, inhaled corticosteroid use, and FEV1.Results: From our database, we found 361 patients with an FEV, of 80% or more than predicted of whom 123 (34%) had a methacholine PD20 of 100 mug or less and 138 (38%) had a methacholine PD20 of 800 mug or more. The methacholine PD20 geometric means (geometric SE) of groups A and B were 25 mug (3 mug) and 5,392 mug (295 mug), respectively. Despite matched mean values for FEV,, compared with group B, group A had a lower predicted forced expiratory flow between 25% and 75% (71% vs 81%, P = 0.007). A greater proportion of group A compared with group B patients were sensitized to house-dust mite (76% vs 54%, P = 0.002). No significant differences were found between groups in terms of presence of rhinitis and sensitization to other individual aeroallergens.Conclusions: Increased sensitization to house-dust mite and reduced small airway caliber were associated with moderate-to-severe AHR in mild asthma. Skin prick testing to common aeroallergens, especially house-dust mite, should be a routine part in the evaluation of asthmatic patients, including those patients with mild disease.