Repeated exposure of asthmatic airways to inhaled adenosine 5'-monophosphate attenuates bronchoconstriction provoked by exercise.
Inhaled adenosine 5'-monophosphate (AMP) induces bronchoconstriction in subjects with asthma, probably caused by histamine release from airway mast cells, and repeated AMP bronchial challenge leads to attenuation of the bronchoconstrictor response. Since exercise-induced bronchoconstriction may be mediated by hypertonic mast cell degranulation, we postulated that repeated AMP bronchial challenge should reduce the response to subsequent exercise challenge. Eight atopic subjects with asthma took part in an unblinded, randomized trial. On the control study day, a treadmill exercise test previously demonstrated to induce a greater than 20% fall in FEV1 was performed. On the AMP study day, three AMP dose-response bronchial challenges were performed at 1-hour intervals. Each AMP challenge was continued until either a provocative concentration causing a 20% fall in FEV1 had been achieved (PC20) and the PC20 was calculated, or the maximum concentration of AMP (400 mg/ml) had been administered. After recovery of the FEV1 from AMP challenge, a treadmill exercise test identical to the test on the control study day was performed. On the AMP study day, the geometric mean PC20 was 15.3 (7.9 to 29.5) mg/ml for the first test, and 28.2 (10.7 to 77.4) mg/ml for the third test (not significant). On the control study day, the mean maximum percentage fall in FEV1 after exercise was 28.0% +/- 2.7%, whereas on the AMP study day, it was reduced to 13.0% +/- 4.3% (p less than 0.01). A significant correlation was found between the change in responsiveness to AMP induced by repeated challenge and the attenuation of the subsequent exercise response (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Immunopharmacology Group, Southampton General Hospital, England.
J P
JP
Finnerty
R
R
Polosa
S T
ST
Holgate
D000241:Adenosine / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000494:pharmacology* / Q000627:therapeutic use; D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D001250:Asthma, Exercise-Induced / Q000188:drug therapy*; D016084:Bronchoconstriction / Q000187:drug effects*; D005260:Female; D005541:Forced Expiratory Volume; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D008297:Male
D000249:Adenosine Monophosphate; D006632:Histamine; D000241:Adenosine