Am. J. Respir. Crit. Care Med., Vol 149, No. 4, Apr 1994, 1012-1019.
Airway effects of local challenge with hypertonic saline in exercise- induced asthma
HK Makker, AF Walls, D Goulding, S Montefort, JJ Varley, M Carroll, PH Howarth and ST Holgate
Immunopharmacology Group, University of Southampton, United Kingdom.
Hypertonicity of airway lining fluid has been suggested as the stimulus for
bronchoconstriction in exercise-induced asthma. We explored the airway
effects of delivering a direct hypertonic stimulus to asthmatic airways via
a fiberoptic bronchoscope, comparing hypertonic saline challenge by direct
instillation with local aerosol delivery. A group of 18 asthmatic subjects
responsive to inhaled hypertonic saline with a history of EIA were studied;
the first 9 subjects received local challenge with hypertonic saline by
direct instillation, and the next 9 subjects were challenged by local
aerosol delivery. A control challenge with isotonic saline by either
instillation or aerosol was performed at a same bronchoscopy. Local
challenge with hypertonic saline by aerosol delivery was found to be more
effective in inducing local bronchoconstriction (8 of 9 subjects) than
instillation (2 of 6 subjects). Paired BAL fluid samples and bronchial
biopsies were obtained in total of 11 and 9 subjects, respectively. Local
challenge with hypertonic saline either by instillation or aerosol produced
no significant change in histamine, tryptase, or PGD2 levels in BAL fluid
or mast cell numbers and degranulation in bronchial biopsies. A significant
correlation was observed between histamine levels in BAL fluid and airway
responsiveness to inhaled hypertonic saline (rs = - 0.59, p < 0.05).
Bronchial biopsies showed evidence of extensive epithelial damage; however,
this was not related to airway responsiveness to inhaled hypertonic saline.