1.The thermal precipitants of asthma (exercise and hyperventilation) appear to have a unique pathogenesis that does not alter bronchial responsiveness. In the present work, we tested whether hyperpnoea interacts with other constrictor stimuli.
2.To provide data on this issue, we exposed 17 subjects with asthma to isocapnic hyperventilation of frigid air (HV), methacholine (METH) and histamine (HIS) alone and in combination.
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 decrements 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 (ΔFEV1 HV+METH = 32.8±3.6%; HV+HIS = 28.7±5.1%). None of the individual or combined responses was significantly different from each other. Changing the sequence of the experiments and giving METH at the height of the HV-induced bronchial narrowing, instead of during hyperpnoea, did not alter the findings (n = 8). The maximum fall in FEV1 after both bronchoconstrictors in this experiment (ΔFEV1 = 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 together, however (n = 5), a positive interaction ensued (METH = 1.53±0.56 ;mmol/l, ΔFEV1 = 15.6±4.6%; HIS = 4.77±2.07 ;mmol/l, ΔFEV1 = 18.8±3.1%; METH+HIS ΔFEV1 = 33.4±5.2%; P< 0.001 compared with the individual effects).
4.These results indicate that HV does not interact with stimuli that directly or indirectly modulate airway calibre. It is unclear if this effect represents protection conferred from increased bronchial blood flow or derives from differences in effector mechanisms between the thermal and pharmacological agonists.
Relation between the bronchial obstructive response to inhaled lipopolysaccharide and bronchial responsiveness to histamine.
