Muscarinic receptor agonists increase water secretion from the acinar cells of respiratory, sweat, salivary, and lacrimal glands. Mice lacking the gene for aqueous water channel aquaporin (Aqp) 5 exhibit methacholine-induced bronchiolar hyperreactivity when compared to normal mice. Individuals with asthma also have enhanced airway responsiveness to methacholine and diminished airway hydration. Because Aqp5 in humans is also expressed in respiratory, sweat, salivary, and lacrimal glands, we hypothesized that those individuals with exercise-induced asthma and excessive bronchiolar reactivity should also have decreased muscarinic receptor-dependent sweat, salivary, and tear gland secretions.
Healthy, athletic subjects who are suspected of having exercise-induced bronchospasm were recruited, and FEV1 values were determined following provocative airway challenges with methacholine. Measurements of pilocarpine-induced sweat secretion were taken in 56 volunteers, and some additional subjects also had timed collections of saliva and tear production.
Subjects manifesting excessive airway reactivity demonstrated by exaggerated methacholine-induced reductions in FEV1 also had diminished values for pilocarpine-induced sweat secretion (n = 56; r = − 0.59; p < 0.0001). The rate of pilocarpine-stimulated sweat secretion in our subjects correlated highly with salivary flow rate (r = 0.69; p < 0.0001) and tearing rate (r = 0.86; p < 0.001).
Hyperhidrosis, sialorrhea, and excessive tearing are traits that may indicate a phenotype that predicts resistance to hyperactive airway diseases such as exercise-induced asthma in humans.