Inhalation patterns and predominant site of bronchoconstriction in healthy subjects

To determine the relationship between changes in density dependence of maximal expiratory flow and changes in the predominant site of bronchoconstriction, we altered the pattern of inhalation of a methacholine aerosol to achieve deposition either centrally (by short choppy breaths) or peripherally (by slow deep breaths). Partial expiratory flow volume curves on air and on 80% helium-20% oxygen (HeO2) were recorded in six healthy subjects before and after each pattern of methacholine inhalation. We varied concentrations of methacholine and number of inhalations to achieve equivalent degrees of bronchoconstriction as assessed by decreases in maximal flow (Vmax) on air, which fell 27% from control values. Vmax on HeO2 also fell after both inhalation patterns. Density dependence (Vmax on HeO2 divided by Vmax on air) decreased following slow deep breaths of bronchoconstrictor aerosol, and increased following short choppy breaths. In three subjects, inhalation of radiolabeled methacholine aerosol confirmed that the slow deep pattern was associated with a diffuse, more peripheral deposition, whereas the short choppy pattern led to central deposition. We conclude that changes in density dependence reflect the predominant site of obstruction after acute methacholine aerosol challenge in healthy subjects.