Hyperosmolarity as the stimulus to asthma induced by hyperventilation?

Hyperosmolarity of the epithelial fluid of the large airways caused by evaporative water loss (wloss) has been proposed as the stimulus to exercise-induced asthma. The aim of this study was to compare the wloss during hyperpnea with a theoretical wloss from a known hypertonic stimulus in order to determine whether comparable volumes of wloss will induce the same response. Since wloss also occurs during isocapnic hyperventilation (ISH), we decided to compare the airway response to ISH with the response obtained after inhaling 4.5% NaCl aerosol. Changes in FEV1 were measured in 17 subjects with asthma in response to increasing rates of ventilation (ISH) and increasing doses of 4.5% NaCl aerosol. For ISH, wloss was calculated at 29 mg/L of expired air and for 4.5% NaCl, at 4.0 ml/l ml of aerosol inhaled, as this is the volume of water that will bring the periciliary fluid to normal tonicity. Two dose-response curves were drawn for each subject. These curves were similar both in position (PD20) and in shape (i.e., the slope of the curve as estimated by the ratio of wloss for maximum recorded percent fall in FEV1 [PDmax] to PD20). There was no significant difference in the PD20 (ISH, 10.3 ml, 95% confidence limits 7.5 and 13.9; 4.5% NaCl, 12.3 ml, 95% confidence limits 8.9 and 17.1) or between the ratio of log PDmax:log PD20 (ISH, 1.19 +/- 1 SD, 0.14; 4.5% NaCl, 1.17 +/- 1 SD, 1.17; p = not significant). These findings support the concept that airway hyperosmolarity may be the mechanism for ISH and exercise-induced asthma.