Methacholine responsiveness increases after ultrasonically nebulized water but not after ultrasonically nebulized hypertonic saline in patients with asthma

Airway obstruction can be induced in patients with asthma by the inhalation of ultrasonically nebulized aerosols of nonisotonic solutions. It is the change in osmolarity of the periciliary fluid that is believed to be the stimulus for bronchoconstriction. However, it is not known whether hyperosmolar and hypo-osmolar aerosols induce asthma via the same mechanism. We have previously reported that patients with asthma have a reduction in the dose of provoking agent that induces a 20% fall in FEV1 (PD20) for methacholine after challenge with nebulized water. To determine whether hyperosmolar aerosols also increase sensitivity to methacholine, we studied 13 subjects with asthma on 3 days. On day 1, the PD20 to methacholine was determined. On day 2, a challenge with nebulized 4.5% saline was followed by a challenge with methacholine 40 to 60 minutes later. On day 3, a challenge with nebulized water was followed by a methacholine challenge. Sensitivity to methacholine was significantly increased after water (p less than 0.02) but not after 4.5% saline. Furthermore, there was no relationship between the PD20 to water and to 4.5% saline. When the Spearman's correlation coefficient was used to compare sensitivity to the challenges, there was a significant relationship between the PD20 to 4.5% saline and methacholine (p less than 0.01) but not between the PD20 to water and methacholine. These results suggest that the mechanism of asthma induced by hyperosmolar and hypo-osmolar solutions is different.