Publications

To determine whether cough and bronchoconstriction result from alterations in the osmolarity or alterations in the ion concentration of inhaled aerosols and to determine if the specific ions in the aerosol are important, we had 9 subjects with mild asthma inhale various solutions while we recorded cough and measured specific airway resistance. To evaluate the effects of altering osmolarity and ion concentration separately, we administered aerosols of hypo-osmolar distilled water (0 mosm), iso-osmolar sodium chloride (308 mosm), iso-osmolar dextrose in water (308 mosm), hyperosmolar sodium chloride (1,232 mosm), and a hyperosmolar solution of dextrose and sodium chloride (1,232 mosm). To evaluate cough without bronchoconstriction, we had the subjects inhale metaproterenol before inhaling the same aerosols. To determine whether the absence of a specific ion was important in causing cough or bronchoconstriction, we had the subjects inhale iso-osmolar solutions of sodium bromide, sodium gluconate, and lysine monohydrochloride. We found that alteration in osmolarity away from iso-osmolarity of inhaled aerosols is a stimulus for bronchoconstriction in subjects with mild asthma. Absence of ions in the presence of iso-osmolarity is not a stimulus for bronchoconstriction, but the absence of a permeant anion is a stimulus for cough. Thus, we found that the responses of cough and bronchoconstriction to inhaled aerosols can be separated.

To assess the reproducibility and individual variability of ECG treadmill exercise test results, we evaluated 23 patients with coronary artery disease and stable exertional angina by means of two control exercise tests performed on different days within a 1 week period. In addition, each control test was followed on the same day by a single dose of placebo or active agent determined in a randomized double-blind manner and the exercise test was repeated. When the mean exercise test results from the control tests on days 1 and 2 were compared, there was a significant increase in exercise duration to angina (7.4 +/- 3.2 to 9.0 +/- 3.3 minutes, p less than 0.05), ST segment depression (7.8 +/- 3.9 to 9.6 +/- 3.6 minutes, p less than 0.01), and maximal exercise (9.7 +/- 3.7 to 11.0 +/- 4.1 minutes, p less than 0.01). In addition, when the mean exercise results on the control test were compared to those on the postplacebo test on the same day, similar increases in exercise duration were observed at each end point (p less than 0.01). Individual differences of more than 2 minutes in exercise duration between the two control tests and between the control and postplacebo tests in time to angina, ST segment depression, and maximal exercise were frequent (26% to 33% of patients). However, the mean rate-pressure products on the two control tests performed on days 1 and 2 and on the control and postplacebo tests performed on the same day did not differ at angina, ST segment depression, and maximal exercise.(ABSTRACT TRUNCATED AT 250 WORDS)