THE SEVERITY OF BREATHLESSNESS DURING CHALLENGES WITH INHALED METHACHOLINE AND HYPERTONIC SALINE IN ATOPIC ASTHMATIC SUBJECTS - THE RELATIONSHIP WITH DEEP BREATH-INDUCED BRONCHODILATION

The severity of breathlessness at given degrees of airway obstruction varies between patients with asthma. It has been postulated that the s ymptoms during bronchoconstriction are determined in part by involveme nt of airway inflammation. We compared the severity of breathlessness at various degrees of acute airway obstruction between a direct stimul us of airway smooth muscle, methacholine, and an indirectly acting sti mulus, hypertonic saline. Twelve atopic asthmatic adults (mean +/- SD; age 25.3 +/- 3.4 yr; baseline FEV(1) 91.2 +/- 10.4 %pred; PC20 1.0 mg /ml methacholine +/- 1.7 doubling dose) entered a methacholine and a h ypertonic saline period in random order. In each period doubling doses of either methacholine (0.03 to 256 mg/ml) or hypertonic saline (0.9 to 14.4% NaCl) were inhaled on two occasions 7 d apart, using standard ized tidal breathing methods. The response was obtained by FEV(1) and, in order to assess volume history effects on airway caliber, by the r atio of flows obtained from volume history standardized maximal and pa rtial expiratory how-volume curves (M/P ratio). Breathlessness was mea sured by a visual analogue scale (VAS), which ranged from 0 (none) to 100% (most severe experienced). The subjects were blinded to the respo nse in lung function. The changes from baseline in VAS scores at inter vals of 5% fall in FEV(1) (Delta VAS) and the changes in M/P ratios (D elta M/P ratio) were calculated by linear interpolation. The results w ere analyzed by MANOVA. There were no differences in baseline FEV(1) o r baseline VAS scores between the methacholine and hypertonic saline p eriods (p > 0.40). At all revels of airway obstruction Delta VAS was g reater for hypertonic saline than for methacholine, and the mean diffe rence at 10% fall in FEV(1) (95% confidence interval [Cl]) was 5.7% (1 .5 to 9.9%). Delta M/P ratios were lower for hypertonic saline than fo r methacholine (mean difference at 10% fall in FEV(1) (95% Cl): 0.40 ( 0.03 to 0.77). There was a negative relation between the changes in De lta VAS and Delta M/P ratio during methacholine and hypertonic saline inhalation (r = 0.73, p < 0.02). We conclude that the severity of brea thlessness in patients with asthma at the same reduction in FEV(1) is greater in response to inhaled hypertonic saline compared with methach oline. This difference in breathlessness is related to the decreased b ronchodilator effect of a deep breath. These results suggest that brea thlessness in patients with asthma depends on the involvement and perc eption of inflammatory mechanisms within the airway wall.