LACK OF INTERACTION OF HYPERPNEA WITH METHACHOLINE AND HISTAMINE IN ASTHMA

1. The thermal precipitants of asthma (exercise and hyperventilation) appear to have a unique pathogenesis that does not alter bronchial res ponsiveness. In the present work, we tested whether hyperpnoea interac ts with other constrictor stimuli. 2. To provide data on this issue, w e exposed 17 subjects with asthma to isocapnic hyperventilation of fri gid air (HV), methacholine (METH) and histamine (HIS) alone and in com bination. 3. With HV (mean ventilation =55.6+/-7.7 litres/min), METH ( 2.20+/-0.7 mmol/l) and HIS (10.35 +/- 5.04 mmol/l) alone, the decremen ts in forced expiratory volume in 1 s (FEV1) from baseline were 27.4 /- 3.4, 27.4 +/- 3.8 and 32.4 +/- 3% respectively (n = 9). Giving the agonists simultaneously did not produce additive effects (Delta FEV1 H V + METH = 32.8 +/- 3.6%; HV + HIS = 28.7 +/- 5.1%). None of the indiv idual or combined responses was significantly different from each othe r. Changing the sequence of the experiments and giving METH at the hei ght of the HV-induced bronchial narrowing, instead of during hyperpnoe a, did not alter the findings (n = 8). The maximum fall in FEV1 after both bronchoconstrictors in this experiment (Delta FEV1 = 32.3 +/- 4.3 %) was not significantly different from either alone (HV = 22.8 +/- 1. 0%; METH = 27.3 +/- 1.9%). When METH and HIS were administered togethe r, however (n = 5), a positive interaction ensued (METH = 1.53 +/- 0.5 6 mmol/l, Delta FEV1 = 15.6 +/- 4.6%; HIS = 4.77 +/- 2.07 mmol/l, Delt a FEV1 = 18.8 +/- 3.1%; METH + HIS Delta FEV1 = 33.4 +/- 5.2%; P < 0.0 01 compared with the individual effects). 4. These results indicate th at HV does not interact with stimuli that directly or indirectly modul ate airway calibre. It is unclear if this effect represents protection conferred from increased bronchial blood flow or derives from differe nces in effector mechanisms between the thermal and pharmacological ag onists.