Chest
Volume 134, Issue 3, September 2008, Pages 552-558
Journal home page for Chest

Original Research
Asthma
Exercise-Induced Asthma May Be Associated With Diminished Sweat Secretion Rates in Humans

https://doi.org/10.1378/chest.08-0366Get rights and content

Background

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.

Methods

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.

Results

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).

Conclusion

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.

Section snippets

Materials and Methods

These studies were approved by our institutional review board, and all volunteers gave written informed consent. We recruited 56 subjects who had been referred to our medical center for the evaluation of signs and symptoms suggestive of new-onset, exercise-induced asthma. Subjects were otherwise healthy, young, male and female US Navy and Marine Corps personnel between 18 and 32 years of age. This evaluation included the measurement of bronchiolar reactivity to methacholine. No patients were

Results

Fifty-six otherwise healthy subjects with signs and symptoms suggestive of exercise-induced bronchospasm volunteered for this study. Twenty-two subjects were classified as having a positive MCT result using standard clinical criteria4, 13 (ie, they had at least a 20% fall in their FEV1 over baseline measurements following methacholine challenge), and 34 subjects had a minimal response, if any, to methacholine challenge. As shown in Figure 1, there were wide-ranging differences in the

Discussion

It has been shown that targeted disruption of the gene encoding Aqp5 results in mice with decreased osmotically dependent water movement into, and out of, alveoli, but the loss of Aqp5 did not modify hydrostatically driven lung edema or active alveolar fluid reabsorption. Furthermore, lower airway humidification, as determined by the moisture content of the expired air, was reduced by only 3 to 4% in mice that lacked both Aqp5 and Aqp1.10, 11 On the basis of these two reports,10, 11 one would

Acknowledgment

We thank Justin Clark, MD, from the University of Michigan, for providing the measurements of sweat sodium concentrations. Also, the following individuals from the Naval Medical Center San Diego contributed to our work: Ryan Woodman for drawing our graphs; Debra James, Waine Macallister, and Suzana Hazeldon for the editorial assistance; and Robert Riffenburgh, PhD, for statistical analyses. Dr. Lockette has had full access to all of the data in the study and takes responsibility for the

References (31)

  • MD Lee et al.

    Human Aquaporin-5 gene: molecular characterization and chromosomal localization

    J Biol Chem

    (1996)
  • SD Anderson et al.

    Sensitivity to heat and water loss at rest and during exercise in asthmatic patients

    Eur J Respir Dis

    (1982)
  • A Bundgaarad et al.

    Influence of temperature and relative humidity of inhaled gas on exercise-induced asthma

    Eur J Respir Dis

    (1982)
  • KW Rundell et al.

    Exercise-induced bronchospasm in the elite athlete

    Sports Med

    (2002)
  • S Nielson et al.

    Aquaporins in complex tissues: iI Subcellular distribution in respiratory and glandular tissues of the rat

    Am J Physiol

    (1997)
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    The comments expressed represent the personal opinions of the authors and they do not necessarily reflect the views of the Department of the Navy or the Department of Defense.

    The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

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