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Running to catch your breath

Light and moderate physical activity has an anti-inflammatory effect that reduces asthma symptoms

MIGUEL BOYAYANIn the Pan-American Games this year, Brazilian swimmer Rebeca Gusmão, winner of the 50 m Freestyle gold medal, left the swimming pool staggering after finishing the 4 x 100 relay. By pushing herself beyond her limits she had an asthma attack and needed to be helped to the first aid post where she used an inhaler to get her breath back. It was swimming, however, that has helped Rebeca suffer less from symptoms of the disease. When she was six years old she began swimming on the recommendation of many doctors: aerobic exercise can improve the patient’s quality of life. This tip goes against common sense, which says that asthma and physical exercise do not mix. It is quite common, for example, for schools to give a waiver from physical education classes to their asthmatic pupils, to avoid any crises of shortness of breath. Now a team of researchers from São Paulo has thrown a spanner in the works as far as this belief is concerned, by showing that the effect of physical activity on the disease is far more beneficial than one might imagine. Doing light and moderate exercise can reduce the pulmonary inflammation that is typical of the disease.

“Many studies have shown that physical activity may worsen asthma, but what we saw was the other side of this story. If the asthma sufferers take medication and the disease is under control, moderate exercise may help them”, explains general practitioner Milton de Arruda Martins, from the Medical School of the University of São Paulo, one of the multidisciplinary study group’s leaders. If they are physically unfit (or in extreme situations, as occurred with Rebeca), asthmatic people who risk going for a run may fall ill due to so-called bronchial hyper-response to effort. The patient’s airways close causing shortness of breath, a cough and wheezing.

Researchers worked with mice, but also with children and adults, and they observed signs of a reduction in the inflammation after training involving exercises in all of them. In animals, a biopsy on the lungs showed this, whereas in humans the assessment was indirect, relying on clinical tests.

In children, says physiotherapist Celso Carvalho, another study leader, one of the first indications that physical fitness was producing favorable results was the observation that the closing of the airways, common after unsuitable physical activity, began to decrease. “Before starting the training, 17 of the 21 children that took part in the study had such a reaction to exercise. At the end of the training (half hour of physical exercise, twice a week, on a treadmill or exercise bike), only four reacted in this way”, he says.

Reduced symptoms
Another sign of improvement was witnessed by child pneumologist Ana Lúcia Cabral, who monitored the clinical state of the 38 children involved in the research. All were taking medication and the disease was under control, but only 21 were doing the training. The others, which comprised the control group, continued going to the Darcy Vargas Children’s Hospital in the south of São Paulo, where the work was carried out, but did no exercise.

“While we were doing the study Ana Lúcia continued with her normal monitoring without knowing if the child was from the group doing exercises or not. She went on treating them in accordance with their symptoms, and unknowingly reduced the medication of the children that were having training”, says Carvalho. “The need for less medication shows that they were truly better.” The results were published at the beginning of this year in the journal Medicine and Science in Sports and Exercise.

Both Martins and Carvalho warn that if the asthma sufferer is not properly medicated, physical activity may cause the condition to deteriorate. They believe that the health benefits observed in the children, and subsequently in adults, occur not only as a result of improved quality of life due to exercise, but also because of the direct action of physical activity on lung inflammation.

By having them inhale an allergen, researchers induced pulmonary inflammation, similar to asthma, in mice. The animals were then put to train in what Martins calls the “mouse gym” – a treadmill on which they did light and moderate exercise five times a week for an hour, the equivalent for humans of walking and running. After four weeks of exercise, the mice’s lungs were analyzed to see what had happened. One of the indicators examined was the presence of eosinophils, an inflammatory cell characteristic of asthma. Under normal conditions this cell occurs in very small quantities in the lungs, but in asthmatics it appears in great quantities. When comparing the lungs of asthmatic animals that had exercised with those taken from the sedentary animals the scientists found that in the former the quantity of eosinophils was smaller.

The researchers also measured the quantity of interleukins secreted by the TH2 lymphocytes, immune system cells involved in asthma. The TH2s produce interleukins 4 and 5, whose function is to summon the eosinophils in the blood stream into the lungs. Once again, they saw that in asthmatic animals there was a smaller quantity of these interleukins when compared with asthmatics that did no physical activity.

“From the study of animals we can assume that physical exercise inhibits the action of the TH2 cells and the production of interleukins 4 and 5. Furthermore, it increases interleukin 10, which has an anti-inflammatory effect. We have shown some of the details about how this mechanism works, but a lot of pieces of the jigsaw are missing”, Martins comments.

Fit lungs
Finally the team also found that another frequent characteristic of asthma was also reduced after physical activity in mice. This is the so-called lung remodeling. With the passing of time the airways of asthmatics undergo structural changes – the quantity of smooth muscle and collagen increases, for example. But in the exercised animals this deformation was reduced. These results have already been approved for publication in the American Journal of Respiratory and Critical Care Medicine.

“Until we began this work, the majority of the reviews of other studies on asthma would say that physical training was good for asthma sufferers because it improved physical fitness and therefore they would be able to deal with the attacks, despite its having no effect on the asthma itself. What’s new about our work is the effect on the inflammation”, explains Martins. It is more complicated to discover this effect in humans because it is not worth resorting to invasive procedures, such as a pulmonary biopsy. Therefore, indirect indicators must be found. Among children from whom the first information was collected, the improvement was measured based on their clinical behavior, but with adults the team used more specific techniques.

Forty two stable patients being treated at the Asthma Help and Research Center (Napa) of São Paulo’s Clínicas Hospital, coordinated by pneumologist Alberto Cukier, were selected. Half of the group exercised for 30 minutes, twice a week, for three months. At the end the team collected the sputum from those taking part and measured the cells expelled from the lungs. Once more they noted a smaller quantity of eosinophils. In comparison with the patients who did no exercise the drop was nearly 50%. “On average, every two days an untrained adult, even one taking medication, has one day of asthma symptoms, whether a cough, irritation, wheezing or shortness of breath. After the physical exercise program, the symptoms only appear once every five days”, comments Carvalho. This is further evidence that physical activity directly helps asthmatic people. “This is probably related to the inflammation mechanism, although this has not been proven.”

Another indicator used was an evaluation of the levels of the gas nitric oxide exhaled, which normally appears in high concentrations in the air exhaled by asthmatics and that is produced by inflammatory cells that reach the lungs. This indicator also posted a drop of 40% to 50% after physical activity. “These figures suggest that one should encourage asthma sufferers to do some kind of aerobic physical activity”, says Martins. This is not a treatment for asthma, however. “It’s just an ancillary treatment. Asthma has to continue being treated in the recommended way, with bronchodilators and/or anti-inflammatory drugs.”

The next step for the HC/USP team will be to observe whether physical activity has similar effects on other pulmonary diseases, particularly chronic obstructive pulmonary disease, also known as “smoker’s cough”. Many smokers, as Martins remembers, go to their doctor asking for an alternative to the problem other than simply stopping smoking. So the researchers are going to test if exercise can reduce the lesion caused by smoke in the lungs. “Perhaps it won’t reduce the inflammation, as happens with asthma; at least not after the disease has already set in”, comments Carvalho. But perhaps exercise has a preventive role to play.

The Project
1. Pulmonary inflammation mechanisms in asthma; Modality: Research Grant – Thematic; Coordinator: Milton Martins – FM/USP; Investment: R$ 854,112.17 (FAPESP).
2. Effect of aerobic physical training exercise on asthma; Modality: Research Grant – Regular; Coordinator: Celso Carvalho – FM/USP; Investment: R$ 93,264.37 (FAPESP).