© 2003 American Thoracic Society
Airway Narrowing in AthletesA Different Kettle of Fish?Harvard Medical School Brigham & Women's Hospital Boston, Massachusetts Over the past 30 years there has been considerable interest in the therapeutic potential of fish oils for various inflammatory conditions such as rheumatoid arthritis, inflammatory bowel diseases, and asthma. Omega-3 polyunsaturated fatty acids, such as eicosapentaenioc acid and docosahexaenoic acid in fish oils, compete with arachidonic acid as substrates for the formation of inflammatory mediators, such as leukotrienes and prostaglandins (1). Moreover, they appear to have additional antiphlogistic effects mediated through direct action on neutrophil and monocyte production of mediators, chemotactic responses, and production of cytokines (1, 2). Considering the role of leukotrienes, prostaglandins, and cell–cytokine interactions in maintaining airway inflammation and narrowing in asthma, the potential therapeutic effect of a diet rich in fish oil in ameliorating asthma has been examined repeatedly. Taken together, these studies show no consistent improvement in FEV1, asthma symptoms, medication use, or bronchial hyperresponsiveness in patients taking high doses of fish oils (3). In this issue of the Journal (pp. 1181–1189), Mickleborough and coworkers present a study on fish oil supplementation and its effect on exercise-induced airway narrowing in a category of patients that has not been studied previously—elite athletes (4). They studied the effect of a 3-week course of polyunsaturated fatty acids on exercise-induced airway narrowing in 10 elite athletes with, and another 10 elite athletes without, exercise-induced airway narrowing. The fish oil diet had no effect on baseline pulmonary function. Surprisingly, in the group of elite athletes who had a history of exercise-induced airway narrowing, the fish oil diet reduced the fall in FEV1 at 15 minutes post-exercise by almost 80%. Further, there was a greater than 20% reduction in bronchodilator use (apparently exercise related) in these subjects. These data stand in marked distinction to those reported by Arm and colleagues. In the latter study of 12 subjects with asthma and 8 controls, there was no effect of a fish oil diet on exercise challenges (5). The striking disparity between the current study and the study of Arm and coworkers raises interesting questions as to the biology of exercise-induced airway narrowing in "asthmatics" versus airway narrowing in elite athletes. In the current study, subjects had a history of shortness of breath and intermittent wheezing following exercise which was relieved by inhaled bronchodilator therapy, but subjects were specifically excluded if they had "a physician diagnosis of asthma." Most studies of exercise-induced narrowing are performed in patients who do have a diagnosis of asthma. Is it possible that the mechanism of exercise-induced narrowing in elite athletes differs from the mechanism in patients with asthma? Studies of exercise-induced airway narrowing in asthma suggest that the effect is unrelated to the cardiovascular effects of exercise per se, but rather to the effects of hyperventilation of ambient air. Exercise-induced airway narrowing does not occur when subjects breathe warm, moist air (6). Hyperventilation of ambient air appears to produce narrowing by several mechanisms. A significant stimulus to narrowing is an increase in osmolarity of airway surface liquid, which results from water loss by evaporation and the conditioning of large volumes of air during intense exercise (7). Further, heat loss that occurs with hyperventilation is followed by airway re-warming and edema, which also contributes to airway narrowing (8). In this regard, eucapnic–hyperpnea with cold air (physically also dry air, because water content is decreased at low temperature) and hyperosmolar aerosols have been used as surrogates for exercise-induced airway narrowing (9). In asthma, the airway narrowing that occurs after exercise, or surrogate challenges, has been associated with release and/or synthesis of eicosanoids (leukotrienes, prostaglandins), histamine, neuropeptides, and cytokines (10, 11). Such mediator release occurs in the context of the underlying airway inflammation in asthma and produces exaggerated airway narrowing. Did the same mechanisms operate in the airway narrowing experienced by the elite athletes of Mickleborough and coworkers when they exercised to exhaustion? Several types of evidence suggest that the airway narrowing in elite athletes may differ from that in patients with asthma after exercise. Almost half of patients with asthma experience a significant decrease in exercise-induced bronchospasm when treated with inhaled corticosteroids, but such a response does not occur in elite athletes (12). Eighty to 90 percent of patients with asthma who have a positive methacholine challenge experience exercise-induced bronchospasm (13). In contrast, Holzer and coworkers studied 50 elite summer athletes and showed that only 9 out of 42 athletes with respiratory complaints had a positive methacholine challenge as compared with 25 of the 42 subjects with a positive response to eucapnic-hyperventilation (14). Further, while asthmatic inflammation is associated with eosinophils, hyperpnea seems to be associated with a neutrophilic inflammation that can be induced in non-asthmatics (15). Biopsy specimens of elite skiers, without a diagnosis of asthma, showed neutrophil counts more than twofold greater than in patients with asthma and less than one-fourth the eosinophil counts (16). Additionally, some investigators have suggested that the degree of hyperpnea in elite athletes may overwhelm the ability to rehumidify the expired air, resulting in significant dehydration of the airway mucosa in the small airways. These investigators hypothesize that this effect in the small airways may result in airway edema and mucus that might amplify small amounts of physiologic airway narrowing (7). The positive findings of Mickleborough and coworkers with fish oil in elite athletes, in the face of previous negative findings in patients with asthma, reinforce the suggestion that airway narrowing in elite athletes may occur by different mechanisms than it does in patients with asthma who have pre-existing inflammation. Should elite athletes who experience respiratory symptoms with extreme exercise "dope up" with fish oils? Several caveats need to be considered. First, the current study was done in a small group of patients and such results require reproduction. More importantly, while the effects on airflow were impressive, the improvement in performance was not. These patients were exercised to exhaustion and there was no change in the amount of time to exhaustion when patients ingested fish oil (personal communication from the authors). Thus, while exercise-induced airway narrowing in elite athletes may represent a different phenomenon than exercise-induced bronchospasm in patients with asthma, use of a fish oil diet to prevent such episodes does not appear to be helpful in "garden variety" asthma, and may still be a little "fishy" even for elite athletes. FOOTNOTES Conflict of Interest Statement: J.S. and E.I. have no declared conflict of interest. REFERENCES
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