Pulmonary airway challenge has become an accepted method for assessment of airway reactivity. These assessments focus almost exclusively on measurements of resistance to airflow. However, spontaneous bronchoconstriction in asthma is associated not only with increased resistance to airflow, but also with marked changes in ventilation/perfusion relationships. Whether similar changes occur during induced bronchoconstriction has not been previously reported in detail, to our knowledge, although the clinical relevance is obvious. The present study was therefore undertaken to examine the effects of histamine-induced bronchoconstriction on pulmonary ventilation/perfusion relationships in asthmatic patients. fully
Methods Nine asthmatic subjects, five male and four female (mean age± SD = 25±4.4 years) were studied; written informed consent was obtained from each subject. Subjects were selected on the basis of a history of asthma, with no exacerbations of asthma during the previous three months, and with a resting FEV, greater than 80 percent of the predicted value. None of the subjects was concurrently taking any medication at the time of the study. The study was performed on two separate days on each subject. On the first day, the airways response to histamine was assessed; on the second day, the full study was performed with assessment of pulmonary gas exchange in response to histamine inhalation. At the initial study, spirometric evaluation was performed at baseline and at 5-min intervals for 30 min following histamine inhalation.
A rolling seal spirometer (Ohio Medical Products, model 840) and X-Y plotter (Hewlett-Packard, model 7041M) were used to perform spirometry by standard techniques. Immediately following each spirometric measurement, pulmonary resistance (Rint) was measured by the interrupter technique (see below). The lung volume at FRC was measured at baseline and at time intervals similar to the FEV,, following histamine inhalation. FRC was measured in a constant volume body plethysmograph (Collins, Inc) by the technique of Dubois et al. Following baseline measurements, histamine in graded concentrations was inhaled by the subject; the technique has been described in detail previously.,<UI The total dose of histamine required to achieve an approximately 20 percent decrease in FEV,, and the corresponding change in Rint in each subject, was noted. In the majority of subjects, the FEV, returned to baseline at 25 min following histamine inhalation.