Study protocol

Effects of regular exercise on asthma control, physical fitness and quality of life of asthmatics: a study protocol

Original version: 25 January 2011

Trial registration number: ClinicalTrials.gov Identifier: NCT02012400

Principal Investigator: Professor Maritta S. Jaakkola, MD, PhD
Co-PI: Professor Jouni J.K. Jaakkola, MD, DSc, PhD
Center for Environmental and Respiratory Health Research and Medical Research Center, University of Oulu and Oulu University Hospital, Oulu, Finland

Framework for this study

The occurrence of asthma has increased over the past decades in Finland as well as in many other Western countries (1). To address the demands that this presents to the health care, we are developing at the Center for Environmental and Respiratory Health Research (CERH), University of Oulu, a program that evaluates the different stages of a person developing asthma, i.e. healthy person -person at risk –person with early symptoms –diagnosis –person with asthma with good capacity to work and take care of him/herself –increasing loss of capacities and work ability  –person needing hospital or nursing home treatment. In this program we identify questions that need further research, carry out scientific research,  train the health care personnel in our area of responsibility (which is formed of the northern half of Finland) and evaluate the benefits from such interventions.

We have identified self management of asthma as the most urgent question needing further research. The self management guidelines of today have not led to optimal asthma treatment and control of asthma patients. The evidence-base for such guidelines is partly weak and the guidelines are largely based on expert opinion rather than solid research. There are open questions concerning both the use of medications in self management as well as the non-pharmacological part of the asthma management.  We are building up a program to systematically evaluate the existing evidence and then plan and conduct randomized clinical trials related to asthma self management. The trials will be conducted as a collaborative study between our Unit, primary care and occupational health services in Oulu and well as in the future the Kajaani Central Hospital. As the first study question related to self management of asthma we will address the role of regular exercise in asthma management. The model that is developed here will be later applied to address other study questions of asthma self management.

Background

We have conducted a systematic literature review of all clinical trials from 1980 to present that included regular sports program for asthma patients. The search showed that only a small number of mostly small studies (n < 20) without any suitable comparison groups had addressed the effects of regular exercise on asthma (2, 3, 4). Especially there is a need for larger studies with non-exercising group as the reference. A large body of literature has suggested that regular exercise has positive effects on physical fitness and quality of life, but there is a need for more clinical studies on the role of regular exercise for asthmatics (5). Therefore exercise has not yet been a generally used part of the self-management program of asthmatics. This research aims at filling the gap on knowledge of the effects of regular exercise on the disease control and fitness of asthmatics.

Objectives

Our general objective is to gain a better understanding on the effects of regular exercise on asthmatics. Our specific objectives are to investigate the effects of regular exercising on the asthma control, and the physical fitness and quality of life of asthma patients.

Methods

Recruitment

We aim to recruit 200 adult asthma patients from the Municipality of Oulu area. The recruitment takes place in Community Health Care Centers, Occupational Health Care Units and the Oulu University Hospital during the spring and autumn 2011. The patients fulfilling the inclusion criteria are asked to give their informed consent and will then undergo a 4-week run-in phase, during which their suitability and motivation to participate in the study will be assessed.

Inclusion and exclusion criteria

To be included in the study, the person

  • has to be from 16 to 65 years old
  • has to have the diagnosis of asthma made by a physician, or
  • has to have the reimbursement right for asthma medication from the National Social Insurance Institution (code 203), or,
  • in the case of newly diagnosed asthma, has to fulfill the diagnostic criteria for asthma as outlined in the Finnish Guidelines for Asthma Management (6).

Only mild and moderate asthmatics will be included in this study, so those with severe asthma will be excluded. The exclusion criteria for severe asthma applied here include:

  • FEV1 < 60% of predicted in spirometry
  • PEF variability >30% at least 2 times during a 1-week monitoring period
  • use of short-acting bronchodilating medication at least four times daily
  • permanent daily oral steroid treatment

In addition, those who exercise regularly at baseline (before the intervention) at least three times per week will be excluded.

Intervention

The current asthma control of the patient is measured with spirometry as well as one week PEF-follow-up and 4 weeks of filling out a diary on asthma symptoms and activity limitations due to asthma. The patients are interviewed in detail and asked to fill out an extensive questionnaire on respiratory symptoms, Asthma control test (ACT), co-morbidities, health care use in the previous six months, and lifestyle and other factors, such as smoking, that may influence asthma control. The physical condition at the starting point is measured using spiroergometric test, muscle strength testing and 6 minute step test.

Patients assessed as being eligible for the study after the 4 –week run-in period are randomized to either the exercising group or the reference (“control”) group. The exercise group is given a 24-week individualized sports program, including aerobic exercise, muscle training and stretching. They are instructed to carry out aerobic exercise at least three times a week for at least 30 minutes. They will be given individualized advice on the different forms of aerobic exercising. In addition they are instructed to perform muscle exercises to strengthen abdominal, back, upper body and thigh muscles twice a week and to stretch twice a week.

All patients are asked to observe their asthma symptoms and activity limitations daily and to mark these in their diary along with duration, intensity and form of exercising on daily basis. They are also asked to perform PEF-measurements twice a day for one-week period every four weeks.

At the end of the 24-week period, the baseline measurements, including spiroergometry, muscle strength testing, 6-minute step test and questionnaire will be repeated. After this period the control group will receive their individualized sports program.

The participants will be invited to an information session for groups (including 5-10 subjects) at the beginning. This session gives basic information on asthma self-management and information on the study. The intervention group will be motivated to carry out regular exercise by giving them individual advice on exercise suitable for them and the participants are asked to return their PEF and symptom diary on monthly basis and they will be contacted by phone on regular basis.

Assessment of outcomes: asthma control, physical fitness and quality of life

Asthma control will be assessed by:

a) one-week twice a day PEF monitoring every 4 weeks,

b) daily asthma symptoms and activity limitations observation and marking in the diary,

c) questionnaire on symptoms, including Asthma control test (ACT), and health care and medication use at the baseline and after 24 weeks, and

d) spirometry measurements at the baseline and after the 24-week period.

The main outcome will be change in asthma control, which will be assessed according to the principles given in GINA (7) guidelines. The exact operational definition will be developed in the pilot study.

Physical fitness is assessed by spiroergometry test and muscle strength testing at the beginning and in the end of the 24-week study period. In addition, a 6-minute step test is carried out three times during the study.

The quality of life is assessed by St. George's Respiratory Questionnaire (SGRQ) at the beginning, at the midpoint and at the end of the exercise intervention.

Assessment of other variables affecting asthma control

Other lifestyle and environmental factors possibly influencing asthma control are taken into account by asking about these in the questionnaire that will be filled-out at the beginning and end of the exercise intervention. The questions include information on smoking, weight, and home and workplace environment. The randomization should make sure that these other factors will be distributed evenly in the intervention and exercise group, but in the secondary analyses the other factors can also be controlled for by multivariate statistical analyses. Block randomization will be considered after seeing data on the distribution of the main determinants of asthma balance.

The patients are also instructed to mark down in the diary in case they have changes in their asthma medication or catch a flue during the study period. The asthma medication that the patient will use during the study period will be prescribed to them by their own GP or occupational physician and will not be changed as part of this study. We will just record the medication and make sure that the patient has both a medication treating the inflammation of the airways as well as a short-acting bronchodilating medication. In case the asthma symptoms get worse, the patients are instructed to contact their own physician and inform us of any changes in their medication. Any adverse effects related to medications will be reported according to the local guidelines.

Data analysis

The primary analysis involves a simple comparison of the proportion of patients whose asthma control has improved between the intervention and reference groups. Further, the mean changes in the primary outcome variables (occurrence of symptom-free days, PEF variability, FEV1, ACT score) will be compared between the intervention and reference groups. If the randomization will result in imbalanced groups, the differences will be adjusted by using multifactorial regression analyses. Sub group analyses will be conducted according to age, sex and smoking.

Sample size calculation

We calculated that 100 study subjects are needed in the intervention group and in the control group. If there is spontaneous improvement in asthma control in 20% among the control group asthmatics, this sample size would be able to detect a 20% effect, i.e. improvement of asthma control in 40% among the intervention group asthmatics with the power of 0.88 and the p-level 0.05. If the spontaneous improvement among the controls is 30%, a 20% effect in the intervention group will be detected with the power of 0.83.

In the analyses with intraindividual continuous variables such as PEF variability or FEV1 forming the outcome, the proposed sample size will detect small differences between group means of intraindividual change with high power.

Publication plan

The results will be published in international peer-reviewed journals.

Significance of the study

Exercise is proven to have several health benefits in general and is already used in the treatment of many illnesses. Despite the fact that regular exercise is suggested to have positive health impacts on asthmatics as well, regular exercise is still not a part of the national asthma self management programs. This is probably because of the lack of the evidence-based data. This study intends to fill in the gap on knowledge in this area and enable making regular exercise a part of the asthma self management.

In addition, this study will develop a model that can be later applied to address other study questions of asthma self management, e.g. questions related to asthma medication and other lifestyle and environmental factors.

Ethical considerations

Only patients with mild to moderate asthma are recruited in the study. Patients are excluded if they have any severe comorbidity (such as severe heart diseases, severe musculo-skeletal disorders, dementia etc.) or are having severe asthma symptoms when exercising. Also the control group will receive the same individualized sports program after the 24-week intervention period. This study protocol has been approved by the Ethical Committee of the Northern Ostrobothnia Health Care District.

Research team

Professor Maritta S. Jaakkola, MD, PhD (University of Helsinki, Respiratory Medicine), is the Director of Respiratory Research at the Center for Environmental and Respiratory Health Research (CERH) at the University of Oulu. She is the Professor of Respiratory Medicine at the University of Oulu leading the Respiratory Medicine Unit at the Institute of Clinical Medicine and the Chief Physician of Respiratory Medicine at the Oulu University Hospital. Prof. Maritta Jaakkola is a specialist in pulmonary medicine and a respiratory epidemiologist. She has studied the effects of lifestyle and environmental factors on respiratory diseases and lung function, especially on asthma and COPD. For example, she was PI of the Finnish case-control study of adult asthma, which is an internationally recognised, large population-based study. This study has produced a series of publications advancing the knowledge of the aetiology of asthma. She is the Chair-Elect of the Program Committee of Occupational and Environmental Assembly at the American Thoracic Society and serves as an editorial board member of Journal of Respiratory and Critical Care Medicine. As the Principle Investigator of this project she will oversee and provide expertise in respiratory medicine and epidemiology in all parts of the study.

Professor Jouni J.K. Jaakkola, MD (Helsinki), DSc (University of Helsinki, Public Health), PhD (McGill, Epidemiology & Biostatistics), is the Director of Environmental Health Research at the Center for Environmental and Respiratory Health Research (CERH) at the University of Oulu. He is the Dean for Research of the Faculty of Medicine at the University of Oulu, as well as the Professor of Public Health at the Institute of Health Sciences of the University of Oulu. He also has an appointment as Professor of Occupational and Environmental Medicine at the Institute of Occupational and Environmental Medicine, University of Birmingham, UK. Prof. Jouni Jaakkola has a wide experience of studies on lifestyle, environmental and occupational determinants of respiratory health. His special interest lies in asthma. He served as Associate Director of the Johns Hopkins University Center for Childhood Asthma and Urban Environment 1998-2000 and has directed and participated in several projects in Finland, Norway, Russia, Taiwan and USA focusing on asthma. He has conducted several controlled intervention trials and his research training at McGill University included courses in clinical trials. He serves as an associate editor of American Journal of Epidemiology, a leading journal in epidemiology. He has published over 140 articles in peer-reviewed scientific journals. As the Co-PI of this project he will oversee and provide expertise in study design and analytical methods.

Sirpa Heikkinen, BSc (Oulu) is a medical student in her third year. In addition she has studied basic studies in exercise medicine. She has experience in fitness testing and advising and instructing exercise programs. This project will form her PhD thesis. She has also studied English in Brighton, UK.

Katri Wallin, RN is an experienced nurse. She will work in recruiting patients into this study and enter and organize the data.

Timetable

The pilot study with 5 asthma patients to test our methods will be carried out in February 2011, after which we will start the recruitment into the main study. This is anticipated to take place between March and December 2011. The post-intervention assessment will then take place between September 2011- June 2012. Data analysis and reporting will take place in 2012-2014.

References

  1. Eder W, Ege M, von Mutius E. The asthma epidemic. New England Journal of Medicine 2006; 355: 226-235.
  2. Mendes F, Goncalves R, Nunes M et al. Effects or aerobic training on psychosocial morbidity and symptoms in patients with asthma: a randomized clinical trial. Chest 2010; 138; 331-337.
  3. Dogra S, Jamnik V, Baker J. Self-directed exercise improves perceived measures of health in adults with partly controlled asthma. Journal of Asthma 2010; 47: 972-977.
  4. Hallstrand T, Bates P. Schoene R. Aerobic conditioning in mild asthma decreases the hyperpnea of exercise and improves exercise and ventilatory capacity. Chest 2000; 118: 460-469.
  5. Ram F, Robinson S, Black PN, Picot J. Physical training in asthma.
  6. Astma Käypä hoito suositus (updated 2006). www.kaypahoito.fi
  7. Global Initiative For Asthma. Global strategy for asthma management and prevention. Updated 2009. www.ginasthma.com

Oulu, January 25th 2011

Maritta S. Jaakkola
Principal Investigator
Professor and Chief Physician of Respiratory Medicine
Respiratory Medicine Unit
Institute of Clinical Medicine
University of Oulu
P.O.Box 5000
90014 Oulu
Finland

and Oulu University Hospital
e-mail: maritta.jaakkola (a) oulu.fi

Last updated: 29.1.2018