Objective

Whether or not individuals with allergy and asthma experience different patterns of change in the balance of both pro- and anti-inflammatory mediators with acute exercise is not known. We hypothesized that adolescent swimmers with a clinical diagnosis of respiratory allergy would have an exaggerated proinflammatory response to laboratory exercise relative to a no-allergy comparison group.

Methods

Adolescent swimmers (17 with clinical symptoms of respiratory allergy (CSRA) and 17 in comparison group) completed the American Thoracic Society (ATS) exercise challenge on cycle ergometer. Blood was collected at baseline and immediately post-exercise. All study tests were conducted at the Institute for Clinical Translational Science at the University of California, Irvine. Circulating cytokines, growth factors, and adhesion molecules were measured using ELISAs including transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-6, IL-10, P-selectin, and immunoglobulin E (IgE).

Results

There was a trend toward higher resting levels of TNF-α in the CSRA group (P = 0.076). Exercise induced a significant increase in P-selectin and TGF-β1 in both groups. TNF-α increased significantly (17%) in the comparison group (pre = 0.6, post = 0.7 pg/mL), but not in the CSRA group. IL-6 increased significantly in the CSRA group (pre = 0.7, post = 0.8 pg/mL), but not in the comparison group. Circulating levels of IL-4 and IL-10 were not altered immediately post-exercise in either group.

Conclusions

A short bout of intense exercise increased inflammatory growth factors and adhesion molecules, namely TGF-β1 and P-selectin, both of which are known to be involved in allergic airway diseases. Differences in resting IL-6 and TNF-α and exercise alterations in these cytokines may also contribute to allergic disease in adolescent elite swimmers.

Brief high intensity exercise induces peripheral leukocytosis possibly leading to a higher incidence of allergic symptoms in athletes undergoing excessive training. We studied the exercise-induced alternation of circulating Tregs and FoxP3+ Tregs due to acute intense swim exercise in elite swimmers (n = 22, 12 males, age = 15.4 yrs). Twelve had prior or current rhinitis or asthma and 10 had no current or prior allergy or asthma. Circulating Tregs increased significantly (p < .001) following exercise (pre = 133 +/- 11.2, post = 196 +/- 17.6) as did FoxP3+ cells (pre = 44, post = 64 cells/microl). Increases in Tregs and FoxP3+ Tregs occurred to the same extent in both groups of adolescent swimmers.

Rationale

Although exercise-induced bronchoconstriction is more common in adolescents with asthma, it also manifests in healthy individuals without asthma. The steady-state exercise protocol is widely used and recommended by the American Thoracic Society (ATS) as a method to diagnose exercise-induced bronchoconstriction. Airway narrowing in response to exercise is thought to be related to airway wall dehydration secondary to hyperventilation. More rigorous exercise protocols may have a role in detecting exercise-induced bronchoconstriction in those who otherwise have a normal response to steady-state exercise challenge.

Objectives

The objective of this study was to determine the effect of two different exercise protocols--a constant work rate protocol and a progressive ramp protocol--on pulmonary function testing in healthy adolescents. We hypothesized that vigorous exercise protocols would lead to reductions in lung function in healthy adolescents.

Methods

A total of 56 healthy adolescents (mean age, 15.2 ± 3.3 [SD] years) were recruited to perform two exercise protocols: constant work rate exercise test to evaluate for exercise-induced bronchoconstriction (as defined by ATS) and standardized progressive ramp protocol. Pulmonary function abnormalities were defined as a decline from baseline in FEV1 of greater than 10%.

Measurements and main results

Ten participants (17.8%) had a significant drop in FEV1. Among those with abnormal lung function after exercise, three (30%) were after the ATS test only, five (50%) were after the ramp test only, and two (20%) were after both ATS and ramp tests.

Conclusion

Healthy adolescents demonstrate subtle bronchoconstriction after exercise. This exercise-induced bronchoconstriction may be detected in healthy adolescents via constant work rate or the progressive ramp protocol. In a clinical setting, ramp testing warrants consideration in adolescents suspected of having exercise-induced bronchoconstriction and who have normal responses to steady-state exercise testing.

Purpose

Inhaled corticosteroids (ICS) improve symptoms in lung diseases, such as asthma. Initial data suggest that the effects of ICS remain localized in the lung; however, recent studies demonstrate alteration to the peripheral immune system in patients with asthma. We sought to evaluate the effect of ICS on peripheral immune mediators and hypothalamic-pituitary-adrenal axis and their response to exercise in healthy men.

Methods

Eleven healthy males (18-30 yr old) were placed on 2 wk of fluticasone proprionate (440 μg) twice daily. A 30-min bout of exercise was performed on a cycle ergometer at approximately 70% of peak work rate before and after the start of ICS. Blood was sampled before and after exercise. Cytokines and hypothalamic-pituitary-adrenal axis mediators were measured by ELISA, and fluticasone was measured by liquid chromatography/tandem mass spectrometry.

Results

After ICS treatment, cortisol and adrenocorticotropin were decreased, and a blunted exercise response was observed for cortisol, adrenocorticotropin, and growth hormone. Peripheral leukocytes and neutrophils were significantly increased in response to exercise in both the untreated and the ICS-treated conditions and at baseline after ICS treatment. Interleukin-6 was elevated with ICS treatment, but the exercise response was blunted. Circulating median fluticasone levels were 0.15 ng·mL(-1) and were increased to 0.20 ng·mL(-1) in response to exercise.

Conclusions

Exercise revealed deficits in growth hormone production after ICS treatment not identified by static markers. Neutrophils were shown to be surrogate markers of the systemic effect of ICS. Exercise significantly increased circulating levels of fluticasone. Exercise challenge tests can be used to assess the physiological effect of exogenous corticosteroids.

Exhaled nitric oxide (NO) is altered in asthmatic subjects with exercise-induced bronchoconstriction (EIB). However, the physiological interpretation of exhaled NO is limited because of its dependence on exhalation flow and the inability to distinguish completely proximal (large airway) from peripheral (small airway and alveolar) contributions. We estimated flow-independent NO exchange parameters that partition exhaled NO into proximal and peripheral contributions at baseline, postexercise challenge, and postbronchodilator administration in steroid-naive mild-intermittent asthmatic subjects with EIB (24-43 yr old, n = 9) and healthy controls (20-31 yr old, n = 9). The mean +/- SD maximum airway wall flux and airway diffusing capacity were elevated and forced expiratory flow, midexpiratory phase (FEF(25-75)), forced expiratory volume in 1 s (FEV(1)), and FEV(1)/forced vital capacity (FVC) were reduced at baseline in subjects with EIB compared with healthy controls, whereas the steady-state alveolar concentration of NO and FVC were not different. Compared with the response of healthy controls, exercise challenge significantly reduced FEV(1) (-23 +/- 15%), FEF(25-75) (-37 +/- 18%), FVC (-12 +/- 12%), FEV(1)/FVC (-13 +/- 8%), and maximum airway wall flux (-35 +/- 11%) relative to baseline in subjects with EIB, whereas bronchodilator administration only increased FEV(1) (+20 +/- 21%), FEF(25-75) (+56 +/- 41%), and FEV(1)/FVC (+13 +/- 9%). We conclude that mild-intermittent steroid-naive asthmatic subjects with EIB have altered airway NO exchange dynamics at baseline and after exercise challenge but that these changes occur by distinct mechanisms and are not correlated with alterations in spirometry.