Small airway involvement in the late allergic response in asthma

Background: Allergy and asthma are closely linked. Inhalation of allergen induces an early allergic response (EAR) within the airways of allergic asthmatic subjects, which is followed by a late allergic response (LAR) in approximately 50% of the subjects. The LAR is defined as a drop in forced expiratory volume in 1 second (FEV₁) from baseline usually occurring 4-8 hours after exposure and is believed to affect small airways. However, FEV₁ is insensitive to changes in small airway physiology. Objective: Our aim was to investigate and compare the pathophysiological processes in large and small airways during the EAR and the LAR and to characterize subjects with both an EAR and a LAR (dual responders) versus those with an EAR only (single responders). Methods: Thirty-four subjects with allergic asthma underwent an inhaled allergen challenge. Lung physiology was assessed by spirometry, impulse oscillometry (IOS), body plethysmography, inert gas washout, single breath methane dilution carbon monoxide diffusion and exhaled breath temperature (EBT), at baseline and repeatedly for 23 hours post-allergen challenge. Results: Peripheral airway resistance, air trapping and ventilation heterogeneity were significantly increased in dual responders (n = 15) compared to single responders (n = 19) 6-8 hours post-challenge. Parameters of peripheral airway resistance and ventilation heterogeneity, measured with IOS and inert gas washout, respectively, correlated at baseline and during the allergic airway response in all subjects. Conclusion: The LAR involves increased resistance and ventilation defects within the peripheral airways. Alternative definitions of the LAR including small airways pathophysiology could be considered. Clinical relevance: Small airway dysfunction during the LAR suggests that dual responders may have more extensive airway pathology and underscores the relevance of small airways assessment in asthma.