Study demonstrates positive effects of physical activity on lung diseases

Aerobic exercise reduces or reverses the inflammation caused by asthma, slows the progression of chronic obstructive pulmonary disease, and protects against infections.

By José Tadeu Arantes  |  Agência FAPESP – Aerobic physical exercise reduces the intensity of inflammation in asthma and the progression of lung damage in chronic obstructive pulmonary disease (COPD). These findings, which are very important for people who suffer from these disorders as well as for the health system in general, have been demonstrated in Brazil for the first time by the Thematic Project “Effects of environment and lifestyle on asthma and chronic obstructive pulmonary disease: studies with experimental animals and people with asthma”, led by Milton de Arruda Martins, Full Professor of General Clinical Medicine at the University of São Paulo’s Medical School (FM-USP) and director of the General Clinical Service of Hospital das Clínicas, FM-USP’s teaching and general hospital. The project was supported by FAPESP.

“We assembled a large group of researchers to conduct both laboratory experiments with animal models and clinical trials in humans,” Martins told Agência FAPESP. “We covered all phases of the exploration of these diseases, from laboratory bench to bedside.”

Asthma is characterized by inflammation of the bronchial tubes, causing the airways to narrow and reducing the flow of air into and out of the lungs. Its causes may be genetic, environmental and/or psychological. It is the most prevalent chronic disease in childhood and one of the most common in adults. The typical asthmatic is a person who feels well and suddenly has an attack triggered by stress, pollution, cigarette smoke, allergenic material or flu, among other factors, presenting with symptoms such as wheezing, coughing, chest tightening and shortness of breath. Many asthmatics have their first attacks in childhood, but adult-onset asthma is also common.

COPD also involves inflammation, but it is generally adult-onset and caused mainly by active tobacco smoking. Examination of the lungs in a patient with COPD shows a combination of emphysema (overinflation or even destruction of the alveoli) and bronchitis (inflammation of the bronchial tubes). Both components are obstructive and cause a reduction in air flow.

Another key difference between the two diseases is progression. Asthma attacks tend not to last very long, whereas in COPD, lung function declines steadily and irreversibly. Both diseases may coexist in the same individual. Some patients were asthmatic in childhood and improved in adolescence, but then they became smokers and developed COPD.

“Our project focused on asthma and COPD in the real world, which means taking into account the effects of tobacco, air pollution and lack of exercise, all of which are part of a person’s lifestyle,” Martins said. “We showed that aerobic exercise attenuates or reverses the inflammation caused by asthma; slows the progression of COPD, even in smokers; and protects the individual against infections.”

The project developed in the shape of four major studies. The starting point for the first study was the finding recorded in the medical literature that lung deterioration is slower in smokers who exercise regularly than in sedentary smokers.

“Our novel contribution in this case consisted of a murine model in which some mice were trained to run for 50 minutes on a treadmill five days a week for two months, while some inhaled cigarette smoke in a special chamber,” Martins said. “We then selected four groups of mice according to the four possible combinations: non-smokers that didn’t exercise, sedentary smokers, smokers that exercised, and non-smokers that exercised.”

The study lasted six months, corresponding to a quarter to a third of a mouse’s lifetime, which is 18 to 24 months. This duration was chosen by analogy with the time a person takes to develop COPD – approximately 20 years of active smoking for an individual with a life expectancy of 70-80 years.

“We found that all the animals exposed to cigarette smoke developed evident pulmonary emphysema, but it was significantly attenuated in smokers that exercised,” Martins said.

The researchers then set out to discover why aerobic exercise protected these mice from further deterioration in lung function. Their conclusion was that it enhanced the body’s capacity to react against oxidizing factors.

The second study, also using an animal model, focused on asthma and exercise, with a similar format to that of the first. Asthma was induced in mice by exposure to aerosolized ovalbumin. Some were trained to perform aerobic exercise. Again, they were divided into four groups combining sedentarism or physical exercise with or without asthma.

“We found that the trained mice developed less intense lung inflammation than the untrained mice,” Martins said. “Moreover, many of the alterations caused by asthma were reversed in the mice that began aerobic training after asthma induction. Thus, the effects of exercise were both preventive and retroactive.”

The third study, led by Celso Fernandes Carvalho, a professor of respiratory physiotherapy at FM-USP and the lead coordinator of the clinical studies performed by the team, focused on the protective effect of aerobic exercise against asthma in humans.

The participants in the third study were volunteers with asthma classified as moderate to severe but with symptoms controlled using inhaled corticosteroids, so that they were not subject to asthma attacks.

Under medical supervision and monitored by coaches and physical therapists, one group completed an aerobic training program on a treadmill, with increases in load and speed according to periodic assessments. The control group also attended the hospital, but instead of aerobic training, they performed only stretching and relaxation exercises.

“A comparison of the two groups showed that the subjects who followed the aerobic training program enjoyed a better quality of life, with fewer attacks and a real improvement in lung inflammation,” Martins said. “To evaluate this inflammation, we used two non-invasive strategies. We measured the amount of nitric oxide exhaled and the amount of eosinophils in induced sputum. Both markers decreased in the asthmatic subjects who followed the aerobic training program, and neither diminished in those who did only stretching and relaxation exercises.”

Better quality of life

This was the first demonstration that aerobic exercise does not just improve the quality of life in asthma, important though that is in itself, Martins noted. It also functions as treatment by reducing the inflammation associated with the disease.

Tests of this kind can evidently be performed only with asthmatics treated with medication to avoid attacks, which would induce a love-hate relationship with exercise.

In a second phase of the same study, 43 volunteers performed a 12-week aerobic training program to assess bronchial hyperresponsiveness, one of the characteristic traits of asthma, based on how they responded to inhalation of bronchoconstrictors and to measure inflammatory mediators in the bloodstream. Both hyperresponsiveness and inflammatory mediators decreased with physical conditioning. At the same time, there was an increase in interleukin 10 (IL-10), an anti-inflammatory agent.

“In other words, we showed that exercise doesn’t only have a positive effect on the lungs. The effects are systemic,” Martins said. “In principle, any aerobic activity can produce them – walking, running, swimming, cycling etc. – provided the exercise reaches a level considered moderate. According to the American College of Sports Medicine, moderate-intensity exercise is reached when you develop a light sweat and your heart rate goes up but you’re not out of breath and can have a normal conversation.”

The effects of exercise are lasting but not permanent. Anyone who performs regular exercise and then stops will return to their previous condition after a few months. For this reason, physical exercise should be practiced frequently, and its intensity should gradually increase.

The fourth study, finally, was conducted with mice in collaboration with researchers at Butantan Institute. It was designed to determine whether physical conditioning is capable of protecting the organism from infections. In this case, some of the mice underwent aerobic training for four weeks, and the rest remained sedentary. They then received a non-lethal intranasal dose of Streptococcus pneumoniae, the bacterium most frequently associated with pneumonia.

“The experiment showed that pneumonia was far less intense in the group of trained animals, in terms of both the inflammatory alterations observed and the number of bacteria isolated from the lungs,” Martins said.

Articles published in international journals by the project team:

Silva RA, Vieira RP, Duarte AC, Lopes FD, Perini A, Mauad T, Martins MA, Carvalho CR. Aerobic training reverses airway inflammation and remodeling in asthma murine model. European Respiratory Journal 35:994-1002, 2010.

Mendes FA, Gonçalves RC, Nunes MP, Saraiva-Romanholo BM, Cukier A, Stelmach R, Jacob-Filho W, Martins MA, Carvalho CR. Effects of aerobic training on psychosocial morbidity and symptoms in asthmatic patients: a randomized clinical trial. Chest 138:331-337, 2010.

Mendes FA, Almeida FM, Cukier A, Stelmach R, Jacob-Filho W, Martins MA, Carvalho CR. Effects of aerobic training on airway inflammation in asthmatic patients. Medicine & Science in Sports & Exercise 43:197-203, 2011.

Toledo AC, Magalhaes RM, Hizume DC, Vieira RP, Biselli PJC, Moriya HT, Mauad T, Lopes FDTQS, Martins MA. Aerobic exercise attenuates pulmonary injury induced by exposure to cigarette smoke. European Respiratory Journal 39:254-264, 2012.

Silva AC, Vieira RP, Nisiyama M, Santos AB, Perini A, Mauad T, Dolhnikoff M, Martins MA, Carvalho CR. Exercise inhibits allergic lung inflammation. International Journal of Sports Medicine 33:402-409, 2012.

Olivo CR, Vieira RP, Arantes-Costa FM, Perini A, Martins MA, Carvalho CRF. Effects of aerobic exercise on chronic allergic airway inflammation and remodeling in guinea pigs. Respiratory Physiology & Neurobiology 182:81-87, 2012.

Olivo CR, Miyaji EN, Oliveira ML, Almeida FM, Lourenço JD, Abreu RM, Arantes PM, Lopes FD, Martins MA. Aerobic exercise attenuates pulmonary inflammation induced by Streptococcus pneumoniae. Journal of Applied Physiology 117:998-1007, 2014.

Silva RA, Almeida FM, Olivo CR, Saraiva-Romanholo BM, Martins MA, Carvalho CR. Airway remodeling is reversed by aerobic training in a murine model of chronic asthma. Scandinavian Journal of Medicine and Science of Sports 25:e258-266, 2015.

França-Pinto A, Mendes FAR, Carvalho-Pinto RM, Agondi RC, Cukier A, Stelmach R, Saraiva-Romanholo BM, Kalil J, Martins MA, Giavina-Bianchi P, Carvalho CRF. Aerobic training decreases bronchial hyperresponsiveness and systemic inflammation in patients with moderate or severe asthma: a randomized controlled trial. Thorax 70:732-729, 2015.