Control of breathing in chronic obstructive pulmonary disease. The effect of histamine inhalation

In 7 normocapnic and 6 hypercapnic patients with chronic obstructive pulmonary disease (COPD), we confirmed the recently reported observation that hypercapnic and/or hypoxemic patients with COPD breathe with a shorter inspiratory time (TI) and a smaller tidal volume (VT) than normocapnic and/or normoxemic patients with COPD. Both hypercapnic and normocapnic groups were exposed to doubling concentrations of aerosolized histamine, and FEV1 was measured 30 and 90 s after each 2-min exposure. A provocative concentration (PC20) of histamine was defined as that which produced a 20% decrease in FEV1. At PC20, minute ventilation and VT decreased in both groups. The decrease in VT was significantly greater in the normocapnic patients. Inspiratory flow (VT/TI) did not change in either group. Although breathing frequency (f) and inspiratory time (TI) did not change in the hypercapnic group, f increased and TI decreased significantly in the normocapnic patients. The same results were obtained when patients were separated into hypoxemic and "normoxemic" groups. At PC20, therefore, the pattern of breathing of the hypercapnic and/or hypoxemic patients showed only small variations, whereas in the normocapnic and/or "normoxemic" patients, the breathing pattern showed greater changes, becoming similar to that of the hypercapnic and/or hypoxemic patients during control breathing. We speculated, therefore, that activation of histamine-sensitive receptors in the airways could be involved in the pathophysiology of the rapid shallow breathing present at rest in hypercapnic and/or hypoxemic patients with COPD.