Key Point

Intensive exercise, nutritional intervention, and dietary supplementation may have anti-inflammatory effects that benefit COPD patients.

LONDON—For some time now it has been recognized that inflammation is an important pathologic feature of asthma, and now a similar trend is happening with COPD. After reviewing the literature, British investigators have suggested that COPD may be a disease of low-grade systemic inflammation as well as of chronic airway obstruction.¹

“This topic has not received much attention in the literature, but there is now increasing evidence that inflammatory markers are also raised in COPD patients,” lead investigator Rachel Garrod, PhD, told Pulmonary Reviews. Dr. Garrod is a Reader in Physiotherapy at St. George’s/Kingston University of London.

There is especially keen interest in the role of cytokines as possible causes of inflammation in COPD. In particular, C-reactive protein (CRP) has drawn much of the attention because of its ability to predict cardiovascular mortality (an important cause of death in COPD) and because of its statistical associations with exercise tolerance, health status, and COPD severity. Preliminary data have shown that among COPD patients stratified by Medical Research Council Dyspnea Score, the perception of breathlessness was greater among those with higher CRP levels.²

Research involving the measurement of CRP levels in athletes training for a marathon may have implications for COPD management, Dr. Garrod and colleagues noted. They cited a study by Mattusch et al,3 which showed that after nine months of training, CRP was significantly reduced from baseline in 10 of the 12 athletes studied. In addition, among the training effects was increased aerobic capacity, as demonstrated by treadmill testing. By contrast, the CRP levels of 10 controls who were not in training were unchanged from baseline at nine months.

Clues that regular intensive exercise may be beneficial to COPD patients come from the HERITAGE Family study,⁴ Dr. Garrod and colleagues contended. In that study, 652 sedentary healthy men and women, stratified according to baseline CRP levels, participated in a 20-week standardized exercise training program. At study’s end, CRP levels were significantly reduced from baseline among participants whose initial values were high (ie, > 3 mg/L).

Prolonged physical training reduces the inflammatory response associated with acute bouts of exercise. In one study, plasma interleukin-6 (IL-6) levels below 2 pg/mL were seen in a group of highly trained cyclists; in a separate study, a cohort of recreational cyclists (who presumably were much less conditioned) dem­onstrated postexercise IL-6 levels of about 25 pg/mL. Research also has shown IL-6 to enhance feelings of fatigue in healthy athletes.⁵ In COPD patients, high IL-6 is associated with increased dyspnea. Dr. Garrod and colleagues hypothesize that in COPD, raised IL-6 during activity may contribute to perceptions of fatigue, particularly in muscle-depleted patients. “Future studies investigating immunological changes in COPD will need to clearly characterize patients, not only in terms of severity of airflow obstruction but also in terms of routine activity [and fat-free mass],” they said.

It also may be possible to minimize IL-6 in COPD patients with dietary carbohydrates. Carbohydrate intake during prolonged exercise and a high-carbohydrate diet in general both appear to optimize plasma IL-6 response to exercise, Dr. Garrod explained. Such a diet could be a nonpharmacologic form of anti-inflammatory therapy for COPD patients, she suggested.

Physicians should be careful about recommending antioxidant supplements for COPD patients, because the effect of such supplements on the IL-6 response to exercise is uncertain, cautioned Dr. Garrod. Some data indicate that there is no effect in healthy persons, while others have shown a proinflammatory effect.

However, there is compelling preliminary evidence that omega-3 polyunsaturated fatty acids (n-3 PUFAs) may have anti-inflammatory properties in COPD. For example, significant decreases in the sputum tumor necrosis factor α (TNF-α) and IL-8 levels of COPD patients were observed after two years of n-3 PUFA supplementation, compared with a similar period of n-6 PUFA supplementation.⁶ Notably, improved exercise capacity has been reported in COPD patients who took PUFA supplements, but the improvement could not be attributed to reduced systemic levels of CRP, IL-6, or TNF-α.

A priority of future studies should be to confirm the anti-inflammatory effect of physical training in COPD, stressed Dr. Garrod. “As yet, there is no strong evidence that this is occurring in COPD patients, but data from studies in healthy subjects make further investigation worthwhile,” she asserted. “It would also be interesting to see if there is any benefit from adding anti-inflammatory medications to the pulmonary rehabilitation regimens of COPD patients.”

—Timothy Begany

Reference
1. Garrod R, Ansley P, Canavan J, Jewell A. Exercise and the inflammatory response in chronic obstructive pulmonary disease (COPD): does training confer anti-inflammatory properties in COPD? Med Hypotheses. 2007;68:291-298.
2. Garrod R, Marshall J, Fredericks S, et al. CRP as a marker of impairment and disability in chronic obstructive pulmonary disease (COPD). Proc Am Thoracic Soc. 2005;2: A639.
3. Mattusch R, Dufaux B, Heine O, et al. Reduction of the plasma concentration of C-reactive protein following nine months of endurance training. Int J Sports Med. 2000;21: 21-24.
4. Lakka TA, Lakka HM, Rankinen T, et al. Effect of exercise training on plasma levels of C-reactive protein in healthy adults: the HERITAGE Family Study. Eur Heart J. 2005;26: 2018-2025.
5. Robson-Ansley PJ, de Milander L, Collins M, Noakes TD. Acute interleukin-6 administration impairs athletic performance in healthy, trained male runners. Can J Appl Physiol. 2004;29:411-418.
6. Matsuyama W, Mitsuyama H, Watanabe M, et al. Effects of omega-3 polyunsaturated fatty acids on inflammatory markers in COPD. Chest. 2005;128:3817-3827.

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