Terfenadine modifies airway narrowing induced by the inhalation of nonisotonic aerosols in subjects with asthma.
A change in osmolarity of the respiratory tract is a potent stimulus for provoking an attack of asthma. The mechanism for this is thought to be the release of histamine and other mediators from airway mast cells. We studied the effect of a potent and selective H1 receptor antagonist on the airway response to nonisotonic aerosols (NIA) in 12 asthmatic subjects 19 to 57 yr of age. Terfenadine (T) (180 mg) or its placebo (P) was given 150 min before challenge with NIA. The FEV1 was measured before and after the inhalation of aerosols of isotonic (0.9%), hypertonic (1.8, 3.6, 4.5, and 5.4%), and hypotonic NaCl (0.6, 0.3, and 0%) aerosols. Each concentration of aerosol was inhaled for 3 min, and each day the concentration was increased or decreased until a 20% fall in FEV1 was recorded. Terfenadine caused a significant reduction in airway narrowing as assessed by (1) the percent fall in FEV1 (hypertonic mean +/- 1 SD P, 26.1 +/- 9.5 versus T, 15.6 +/- 14, p = 0.025; hypotonic P, 29.8 +/- 13.1 versus T, 16.6 +/- 13.1, p less than 0.02); (2) the lowest FEV1 percent predicted (%FEV1) (hypertonic P, 61 +/- 13 versus T, 76 +/- 16, p less than 0.005; hypotonic P, 56 +/- 10 versus T, 78 +/- 14, p less than 0.001) documented at the dose common to both placebo and terfenadine test days; (3) the difference in %FEV1 before and after challenge (hypertonic, p less than 0.034; hypotonic, p less than 0.035).(ABSTRACT TRUNCATED AT 250 WORDS)
Finney
M J
MJ
Department of Pharmacology, University of Sydney, New South Wales, Australia.
Anderson
S D
SD
Black
J L
JL
D000328:Adult; D000336:Aerosols; D001249:Asthma / Q000139:chemically induced / Q000503:physiopathology*; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D007038:Hypotonic Solutions / Q000009:adverse effects*; D008297:Male; D009994:Osmolar Concentration; D012462:Saline Solution, Hypertonic / Q000009:adverse effects*; D016593:Terfenadine
D000336:Aerosols; D001559:Benzhydryl Compounds; D006634:Histamine H1 Antagonists; D007038:Hypotonic Solutions; D012462:Saline Solution, Hypertonic; D016593:Terfenadine