BREATHLESSNESS DURING ACUTE BRONCHOCONSTRICTION IN ASTHMA - PATHOPHYSIOLOGIC MECHANISMS

The purpose of this study was to examine potential contributing factor s to breathlessness during bronchoconstriction, in particular, to eval uate the role of lung hyperinflation. We also wished to elucidate qual itative aspects of the unpleasant sensory experience and to identify f actors that contribute to intersubject variability in subjective and o bjective assessments of airflow obstruction. We studied sensory-mechan ical interrelationships during and after induced bronchoconstriction i n 21 subjects with mild stable asthma. Breathlessness (Borg scale), sp irometry, and inspiratory capacity (IC) were measured after each dose during methacholine bronchoprovocation to a maximal change (Delta) in FEV(1) of 50%. Breathing pattern, specific airway resistance (SRaw), p lethysmographic thoracic gas volume, and maximal inspiratory mouth pre ssure (MIP) were recorded at baseline, at maximal response, and at ful l symptom recovery. End-expiratory lung volume (EELV) was derived from IC. Borg increased from 0.4 +/- 0.1 (very, very slight) at baseline t o 5.0 +/- 0.5 (severe) at maximal bronchoconstriction (mean +/- SEM, p < 0.001). FEV(1) fell significantly (p < 0.001) to 48% predicted at m aximal response. Of the 21 subjects, 19 reported increased inspiratory rather than expiratory difficulty and predominantly described sensati ons of reduced inspiratory capacity and unrewarded inspiratory effort. Stepwise multiple regression analysis using Delta Borg (outcome varia ble) versus changes in spirometry, SRaw, IC, and breathing pattern com ponents, selected Delta IC as the principal contributing factor: Delta Borg = 0.09(Delta IC,%fall); n = 193, r = 0.86, p < 0.001. Delta IC c ontinued to contribute significantly (p < 0.001) to the variance in Bo rg ratings after accounting for Delta FEV(1), and it was the strongest predictor of symptom recovery (p < 0.05). In a subgroup of seven subj ects in whom esophageal pressure (Pes) measurements were available, st rong statistical interrelationships (p < 0.01) were found between Borg ratings, Delta EELV(%TLC), and Pes(%Plmax)/VT(%TLC), an index of neur omechanical uncoupling of the ventilatory pump. In conclusion, breathl essness during bronchoconstriction encompasses qualitatively discrete perceptions of heightened inspiratory difficulty. Lung hyperinflation contributes importantly to acute breathlessness in asthma, and variati on in its extent partly accounts for intersubject variability in breat hlessness for a given level of bronchoconstriction.