Pulmonologist and medical researcher Dr Yoshiaki Minakata and his colleagues at the National Hospital Organization Wakayama Hospital in Wakayama, Japan, try to improve the outlook for patients with chronic obstructive pulmonary disease by examining the relationship between that serious lung condition and physical activity.

The Breath of Life That Most of Us Take for Granted

When a baby takes its first breath – often a sudden cry – it’s the sign of new life. In fact, in many countries a baby isn’t legally born until it takes the first breath. Then, at the end of life, a person’s final breath signals the crossing over into the so-called ‘great beyond’, that place we go after our Earthly race is finished. But between those two bookends – life and death – we experience an estimated 680,000,000 breaths if we live to be 80 years old. Of course, the number may be higher for some, lower for others, depending on how long you live or how often you exercise. A question to think about, though: do you notice those breaths as you go about your everyday existence? Do you worry that you may not be breathing fast enough or getting enough air into your lungs? People with chronic obstructive pulmonary disease certainly do worry about these things. They can live their everyday lives in fear of not getting enough air.

Chronic obstructive pulmonary disease (COPD) is the current medical term for a condition that includes diseases with older names – chronic bronchitis and emphysema. COPD results in the inability to properly push air out of the lungs when exhaling – thus, obstructive disease – thereby resulting in insufficient air flowing back into the lungs upon inhaling. Inflammation of the bronchial tree causes thickening of the air passages and production of mucus in chronic bronchitis. Inflammatory damage of the air cells in the lungs – the alveoli, where oxygen exchange takes place – causes these cells to disintegrate and form large, useless pockets in emphysema. In either case, the lungs cannot deflate properly to allow a new breath. The lungs simply don’t exhale enough air initially to be able to enough to draw in enough fresh air with each subsequent breath. The patient suffering from COPD classically suffers from dyspnea – shortness of breath – where normal individuals simply breathe comfortably. This is where Dr Minakata as a pulmonologist strives to treat patients with COPD and make their lives more comfortable. However, as a scientist, Dr Minakata wants more than that – he wants to find out the whys and wherefores of the illness and find ways to treat it scientifically.

A Disease That Leaves the Whole World Breathless

COPD is a worldwide disease, affecting rich and poor, rural and city dwellers. According to the American College of Physicians, in the United States COPD affects more than 5% of the adult population and is the third leading cause of death. The economic costs of COPD in the United States were 50 billion USD in 2010, and the total direct cost of medical care is almost 30 billion USD annually. In the UK, 1.2 million people are living with diagnosed COPD, according to the British Lung Foundation. This makes COPD the second most common lung disease in the UK, after asthma. Around 2% of the whole population, and 4.5% of all people aged over 40, live with the diagnosis of COPD. Importantly, an aging population implies an increasing risk of COPD.

In Japan, Dr Minakata’s country, COPD is not as prevalent as in the US or the UK. According to the World Health Organisation, the latest estimates from 2004 indicated 64 million people worldwide with COPD and 3 million deaths per year due to the illness.

‘It may be that improvement of physical activity could improve the prognosis of COPD and might elongate the healthy life expectancy’

WHO calculates that COPD will become the third leading cause of death in the world by the year 2020. However, while the US has an age-standardised mortality rate from COPD of 248.2 per million population and the UK has a rate of 210.7 per million, Japan has a rate of 40.9 per million. However, Dr Minakata worries that in Japan ‘there are many COPD patients who need or will need treatment, since 8 to 10% of the population over 40 years of age have COPD.’

According to the WHO, the causes for COPD vary depending upon the geographic area. In high- and middle-income countries, tobacco smoke is the biggest risk factor. We all know smoking is bad for your health. However, in low-income countries exposure to indoor air pollution, such as the use of fuels for cooking and heating, is the prime cause of COPD.

Since almost three billion people throughout the world use coal or other biomass fuel as their main energy source, indoor air pollution is actually responsible for a greater fraction of COPD risk than smoking or outdoor air pollution. Biomass fuels used for cooking by women are the source for the high rate of COPD among non-smoking women in areas of the Middle East, Africa and Asia. Indoor air pollution due to the burning of wood and other biomass fuels is estimated to kill two million women and children each year. But in either case – be it cigarette smoke or indoor cooking smoke – the longer an individual is exposed to the smoke or fumes, the higher the risk of COPD. So that risk obviously rises as the person gets older and older, spending more years in contact with cigarette smoke or village fires or other sources of lung irritation. This is what concerns Dr Minakata about his patients in Japan. The population is getting older and COPD is on the rise. The question is, what to do about it?

How Do You Exercise If You Can’t Breathe?

Everyone knows – if they talk to their primary care doctor or other healthcare provider – that exercise treats lots of diseases or at least covers some of our unhealthier sins, like over-eating. Indeed, Dr Minakata the pulmonologist has medical training and experience that tells him ‘improved physical activity might improve the conditions or the prognosis of comorbid diseases, because physical activity is the third risk factor of death for lifestyle-related diseases in Japan.’ But what about patients with COPD who can’t even catch their breath at rest, much less during exercise? How are they to get the benefits of exercise? And even more, will exercise help their COPD like it might help, say, their diabetes or hypertension? Those are questions that Dr Minakata the scientist is trying to answer. He wants to know whether exercise can help COPD, not to mention how COPD patients can exercise in spite of their breathing difficulties. Because, according to Dr Minakata: ‘It may be that improvement of physical activity could improve the prognosis of COPD and might elongate the healthy life expectancy.’

First, Dr Minakata and his associates are quite cognisant of the fact that patients with COPD do not exercise as much as patients without COPD. In a paper published in the journal Rehabilitative Nursing, Dr Minakata and his colleagues studied the activity and walking pattern of patients with COPD and compared them to control subjects. The average walking velocity – as well as time spent sitting, standing, and lying – and the numbers of steps per day were measured in nine people with COPD and eight healthy control subjects. The walking speed in individuals with COPD was the same as the control subjects, but the people with COPD walked a lot less than the control subjects. They concluded that the walking speed of people with COPD tended to minimise their energy cost per distance. In other words, presumably because they couldn’t catch their breath well, COPD patients tried to walk as little as they could to conserve oxygen, or at least minimise the increase in oxygen demand. This underscored the need to maintain walking velocity in any exercise prescription for individuals with COPD so they can benefit from exercise just like any other patient with medical problems. COPD patients can’t let their breathing issues interfere with their doctor’s prescription for exercise. The obvious question, though, is how does one exercise if you can’t catch your breath? Dr Minakata believes that problem can be addressed by judicious use of drugs to open the respiratory passages to allow COPD patients to exercise properly.

One of the standard treatments for people with COPD, especially when they have sudden exacerbations of their problems, is bronchodilator therapy. Bronchodilator medications open up the respiratory passages that are closed or obstructed by COPD and allow easier breathing. Used with or without steroids – to treat the underlying inflammatory process – bronchodilators are a mainstay of COPD treatment.

The positive effects of using bronchodilators on the ‘exercise capacity’ – the maximum potential of a patient for physical exertion – of COPD sufferers have already been reported by many researchers. However, the effects of bronchodilators on patients’ ‘physical activity’ – the level of usual daily activity but not the maximum potential – have been much less clear. Furthermore, the relationship between improving patients’ potential exercise capacity and their actual daily physical activity has been found to be surprisingly weak. Thus, it was believed that behavioural changes along with optimisation of therapy would be necessary to improve daily physical activity, representing a big challenge in the field of COPD therapy. As Dr Minakata explains: ‘The improvement of “exercise capacity” is relatively easy, but the improvement of “physical activity” is difficult, because not only pulmonary function but also other physical or psychogenic conditions or circumstances can affect a patient’s physical activity.’

Dr Minakata, however, was hopeful that bronchodilators might be able to improve physical activity in COPD patients. To explore this relationship, he carried out a study, published in the International Journal of COPD, investigating bronchodilator use in people with COPD during their daily activities. Remarkably, he found that bronchodilator medication actually improved physical activity in patients with COPD, especially at a relatively high intensity of activity if medication was administered based on measures of airflow limitation and breathlessness. This improvement was seen mostly in the patients with better baseline lung volume – patients with initially poor lung function didn’t respond as well. But the results were encouraging. Patients with COPD – especially those with early disease – can look forward to getting their physical activity by using bronchodilator medication. This is a great benefit, seeing as how lack of exercise is related to poor health. Dr Minakata’s COPD patients don’t have to sit on the side at the health club any more.

Where Do We Look Next?

For the foreseeable future, Dr Minakata and his research associates will continue their quest to unravel the questions of physical activity and COPD. They want to better understand the relationship between COPD and the person’s daily physical activities. For example, they recently published a report in the International Journal of COPD looking at the differences in physical activity in patients with COPD of differing degrees of severity. They found, not surprisingly, that worse degrees of dyspnea predicted lower levels of physical activity in those patients. Getting those patients to exercise more is a prime goal of future research.

As a scientist, Dr Minakata wants to investigate interventions that could improve physical activity in COPD patients at the molecular level. It’s nice to know what works clinically and what doesn’t. But for the big picture, understanding the mechanisms of the improvement on a cellular and biochemical level will allow a more informed discussion of possibilities for clinical and laboratory research. The aim is the same, though. We would all like COPD patients to breathe easier, both while they exercise and while they are at rest. Ideally Dr Minakata wants everyone to breathe as freely and effortlessly as they did when they took that first cry on their mother’s tummy the day they were born.

Dr Yoshiaki Minakata received his MD from Wakayama Medical University in Wakayama, Japan, in 1986 and did a residency in general medicine at the Third Department of Internal Medicine of the Wakayama Medical University and pulmonary medicine at the Department of Respiratory Disease there. From 1986 to 1989 Dr Minakata was a member of the clinical staff in the Internal Medicine at the Saiseikai Wakayama Hospital, during which time he did medical research at Wakayama Medical University. He received his PhD in 1994 and did a stint as research scientist from 1995 to 1997 at Hotel Dieu de la Montreal in Quebec, Canada. In 1997, Dr Minakata returned to Wakayama Medical University as an assistant teacher, and in 2004, he became associate professor. Since 2014, he is Director of Hospital in the National Hospital Organization Wakayama Hospital.

Dr Minakata’s research interests include the pathophysiology and treatment of chronic obstructive pulmonary disease, especially the role of physical activity and exercise in improving the outcome in patients with COPD. He has authored or co-authored over 90 articles published in peer-reviewed journals and other professional proceedings and is authorised by the Japanese Societies of Internal Medicine, Thoracic Diseases and Bronchology, as well as the Japan Primary Care Association.

CONTACT

T: (+81) 738 22 3256
E: minakaty@wakayama2.hosp.go.jp

KEY COLLABORATORS

Kazuto Matsunaga, Yamaguchi University
Masakazu Ichinose, Tohoku University
Hisatoshi Sugiura, Tohoku University
Akira Koarai, Tohoku University
Atsushi Hayata, Wakayama Medical University

FUNDING

Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research

REFERENCES

A Hayata, Y Minakata, K Matsunaga, M Nakanishi, N Yamamoto, Differences in physical activity according to mMRC grade in patients with COPD, Int. J. Chron. Obstruct. Pulmon. Dis., 2016, 11, 2203–2208.

Y Sakamoto, K Sakamoto, Y Minakata, S Shiba, T Nakamura, M Ichinose, F Tajima, Walking Pattern in COPD Patients, Rehabil. Nurs., 2016, 41, 211–217.

Y Minakata, Y Morishita, T Ichikawa, K Akamatsu, T Hirano, M Nakanishi, K Matsunaga, M Ichinose, Effects of pharmacologic treatment based on airflow limitation and breathlessness on daily physical activity in patients with chronic obstructive pulmonary disease, Int. J. Chron. Obstruct. Pulmon. Dis., 2015, 10, 1275–1282.

Y Minakata, A Sugino, M Kanda, T Ichikawa, K Akamatsu, A Koarai, T Hirano, M Nakanishi, H Sugiura, K Matsunaga, M Ichinose, Reduced level of physical activity in Japanese patients with chronic obstructive pulmonary disease, Respiratory investigation, 2014, 52, 41–48.

K Sugino, Y Minakata, M Kanda, K Akamatsu, A Koarai, T Hirano, H Sugiura, K Matsunaga, M Ichinose, Validation of a compact motion sensor for the measurement of physical activity in patients with chronic obstructive pulmonary disease, Respiration, 2012, 83, 300–307.

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