Importance of inspiratory flow rate in the cough response to citric acid inhalation in normal subjects

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Abstract
1. The cough response to inhalation of citric acid is produced mainly by irritation of the larynx and trachea. Variations in the inspiratory flow rate might lead to changes in deposition of the drug, and consequently in the cough threshold. 2. We have studied the effect of three different inspiratory flow rates in 11 normal, non-smoking subjects (nine males, aged 23-39 years), who inhaled nebulized citric acid (2.5-640 mg/l). The test finished when a cough was produced at each inhalation (cough threshold) or the maximum concentration was reached. 3. The inspiratory flow rate was limited with a fixed resistance and displayed on a screen so that the subjects could reach a constant inspiratory flow rate of 50, 100 and 150 1/min with a submaximal inspiratory effort. 4. The mean (SD) inspiratory flow rates achieved were 51.4 (5.3), 86.2 (16.6) and 134.4 (22.9) 1/min. Baseline forced expiratory volume in 1 s and functional vital capacity were not different on the 3 study days. 5. The cough threshold (geometric mean and 95% confidence intervals) was 21 (9-54) mg/l at an inspiratory flow rate of 50 1/min and 43 (13-141) mg/l at 150 1/min (P < 0.05). The amount of drug tolerated by the subjects before the cough threshold was achieved was 5.2 (2.0-13.8) mg at an inspiratory flow rate of 50 1/min and 11.6 (3.4-39.8) mg at 150 1/min (P < 0.05). The number of coughs per inhalation was 1.6 (1.1-2.0) at an inspiratory flow rate of 50 1/min and 1.1 (0.7-1.5) at 150 1/min (P < 0.05). 6. We conclude that lower inspiratory flow rates were associated with a greater cough stimulus in the citric acid challenge procedure used in this study. This may be related to increased laryngeal deposition. The inspiratory flow rate is a variable which should be controlled in the performance of cough challenges with citric acid.