Breathlessness during Acute Bronchoconstriction in Asthma: Pathophysiologic Mechanisms

The purpose of this study was to examine potential contributing factors to breathlessness during bronchoconstriction, in particular, to evaluate the role of lung hyperinflation. We also wished to elucidate qualitative aspects of the unpleasant sensory experience and to identify factors that contribute to intersubject variability in subjective and objective assessments of airflow obstruction. We studied sensory-mechanical interrelationships during and after induced bronchoconstriction in 21 subjects with mild stable asthma. Breathlessness (Borg scale), spirometry, and inspiratory capacity (IC) were measured after each dose during methacholine bronchoprovocation to a maximal change (Δ) in FEV1 of 50%. Breathing pattern, specific airway resistance (SRaw), plethysmographic thoracic gas volume, and maximal inspiratory mouth pressure (MIP) were recorded at baseline, at maximal response, and at full symptom recovery. End-expiratory lung volume (EELV) was derived from IC. Borg increased from 0.4 ± 0.1 (very, very slight) at baseline to 5.0 ± 0.5 (severe) at maximal bronchoconstriction (mean ± SEM, p < 0.001). FEV1 fell significantly (p < 0.001) to 48% predicted at maximal response. Of the 21 subjects, 19 reported increased inspiratory rather than expiratory difficulty and predominantly described sensations of reduced inspiratory capacity and unrewarded inspiratory effort. Stepwise multiple regression analysis using ΔBorg (outcome variable) versus changes in spirometry, SRaw, IC, and breathing pattern components, selected ΔIC as the principal contributing factor: ΔBorg = 0.09(ΔIC,%fall); n = 193, r = 0.86, p < 0.001. ΔIC continued to contribute significantly (p < 0.001) to the variance in Borg ratings after accounting for ΔFEV1, and it was the strongest predictor of symptom recovery (p < 0.05). In a subgroup of seven subjects in whom esophageal pressure (Pes) measurements were available, strong statistical interrelationships (p < 0.01) were found between Borg ratings, ΔEELV(%TLC), and Pes(%Pimax)/Vt(%TLC), an index of neuromechanical uncoupling of the ventilatory pump. In conclusion, breathlessness during bronchoconstriction encompasses qualitatively discrete perceptions of heightened inspiratory difficulty. Lung hyperinflation contributes importantly to acute breathlessness in asthma, and variation in its extent partly accounts for intersubject variability in breathlessness for a given level of bronchoconstriction.