Freitas et al. BMC Pulmonary Medicine (2015) 15:124 DOI 10.1186/s12890-015-0111-2 STUDY PROTOCOL Open Access The effects of exercise training in a weight loss lifestyle intervention on asthma control, quality of life and psychosocial symptoms in adult obese asthmatics: protocol of a randomized controlled trial Patricia D. Freitas1, Palmira G. Ferreira1, Analuci da Silva2, Sonia Trecco3, Rafael Stelmach4, Alberto Cukier4, Regina Carvalho-Pinto4, João Marcos Salge4, Frederico LA Fernandes4, Marcio C. Mancini5, Milton A. Martins5 and Celso RF Carvalho1,5* Abstract Background: Asthma and obesity are public health problems with increasing prevalence worldwide. Clinical and epidemiologic studies have demonstrated that obese asthmatics have worse clinical control and health related quality of life (HRQL) despite an optimized medical treatment. Bariatric surgery is successful to weight-loss and improves asthma control; however, the benefits of nonsurgical interventions remain unknown. Methods/Design: This is a randomized controlled trial with 2-arms parallel. Fifty-five moderate or severe asthmatics with grade II obesity (BMI ≥ 35 kg/m2) under optimized medication will be randomly assigned into either weight-loss program + sham (WL + S group) or weight-loss program + exercise (WL + E group). The weight loss program will be the same for both groups including nutrition and psychological therapies (every 15 days, total of 6 sessions, 60 min each). Exercise program will include aerobic and resistance muscle training while sham treatment will include a breathing and stretching program (both programs twice a week, 3 months, 60 min each session). The primary outcome variable will be asthma clinical control. Secondary outcomes include HRQL, levels of depression and anxiety, lung function, daily life physical activity, body composition, maximal aerobic capacity, strength muscle and sleep disorders. Potential mechanism (changes in lung mechanical and airway/systemic inflammation) will also be examined to explain the benefits in both groups. Discussion: This study will bring a significant contribution to the literature evaluating the effects of exercise conditioning in a weight loss intervention in obese asthmatics as well as will evaluate possible involved mechanisms. Trial registration: NCT02188940 Keywords: Asthma, Obesity, Weight loss, Exercise training, Asthma control * Correspondence: [email protected] 1Department of Physical Therapy, University of São Paulo, Av. Dr. Arnaldo 455, Rm 1210, São Paulo, SP 01246-903, Brazil 5Department of Medicine, School of medicine, University of São Paulo, Brazil, Av. Dr. Arnaldo 455 – room 1210, Sao Paulo, SP 01246-903, Brazil Full list of author information is available at the end of the article © 2015 Freitas et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Freitas et al. BMC Pulmonary Medicine (2015) 15:124 Page 2 of 11 Background the only to include physical activity as an adjuvant treat- Asthma is a chronic respiratory disease characterized by ment; the authors observed that the patients who par- episodes of reversible airway obstruction, chronic airway ticipated in physical activity did not experience inflammation and airway hyperresponsiveness. Its symp- additional benefits in terms of weight loss and im- toms include wheezing, shortness of breath, chest tight- provements in clinical control, although this finding ness and cough, which may resolve either spontaneously may have overlooked the levels of physical activity in or with the administration of an appropriate treatment which these patients participated at baseline. There- [1]. Asthma affects approximately 300 million people fore, the Cochrane review study did not find any worldwide and is expected to affect an additional 100 studies using a comprehensive approach to lifestyle million people by 2025 [1, 2]. The dramatic increase in intervention focused on diet, physical activity and be- the prevalence of asthma over the past few decades has haviour self-management as recommended by the occurred in conjunction with an increase in the preva- most recently published guidelines [17]. lence of obesity [3, 4], a finding suggestive of a possible Recent evidence suggests that improving physical fit- relationship between the two conditions. Obesity is char- ness among patients with asthma is important because it acterized by excess fat accumulation in the body as a re- improves airway hyperreactivity [23], psychosocial fac- sult of a complex interaction among genetics, dietary tors [24], and health related quality of life [25], and also caloric intake and energy expenditure and is often diag- reduces the need for corticoid administration [23, 26]. nosed in adults with a BMI ≥ 30.0 kg/m2 [5]. Obesity Moreover, recent studies have also demonstrated the also affects a large number of individuals, as more than anti-inflammatory effects of exercise training in pa- 200 million men and nearly 300 million women are tients with asthma [27, 28]; these results are consist- obese. The prevalence of obesity is highest in WHO ent with those of studies utilizing animal asthma Regions of America (27 % of obesity) and lowest in the models [29–31]. Additionally, improvements in physical WHO Regions for South East Asia (5 % of obesity) [6]. fitness also effect the immune system in obese subjects by Many cross-sectional epidemiologic studies have demon- decreasing the activity of pro-inflammatory mediators strated a relationship between asthma and obesity [7–9]. [Interleukin (IL-6), monocyte chemotactic protein-1 Obesity is a major risk factor for asthma, as over- (MCP-1), C-reactive protein (CRP), IL-8 and tumour weight and obese subjects are 38 % and 92 % more necrosis factor (TNF-α)] and increasing the levels of anti- likely to develop asthma, respectively, than patients inflammatory markers and mediators (adiponectin and IL- with normal weights [10]. Additionally, obesity results 10) [32–34]. Therefore, exercise not only plays a role in in the development of a difficult-to-control asthma lifestyle interventions intended to facilitate weight loss in phenotype in which patients experience worse clinical asthma but is also an intervention in and of itself. control, poorer quality of life, reduced lung function, As previously discussed, asthma and obesity are clin- poor responses to corticosteroids and more psycho- ical conditions characterized by chronic inflammation; social symptoms [11–14]. As obesity is a risk factor the effects of exercise have been evaluated in the setting for the development of asthma, Global Initiative for of each condition but not in the setting of both diseases asthma (GINA) 2014 [1] recommends weight loss for together. Our hypothesis is that exercise training ampli- all obese asthmatics. fies weight loss and exerts both anti-inflammatory and Some interventions have been considered for weight immunoregulatory effects, resulting in improved clinical loss in obese asthmatic patients and bariatric surgery has control and quality of life, as well as improved psycho- been suggested as a means of improving asthma control, social symptoms and sleep disorders among obese asth- lung function and decreased medication usage [15, 16]. matic patients. The objective is to assess the effects of However, the most recent guidelines pertaining to the exercise training in a weight-loss program on asthma management of obesity recommend utilizing a compre- control, quality of life and psychosocial symptoms in hensive approach to weight-loss intervention focused on obese patients with stable asthma. diet, physical activity and behaviour self-management as a first-line therapy [17]. A recent Cochrane review found only 4 randomized Methods controlled trials (RCTs) pertaining to weight loss in the Study design setting of asthma [18] via nonsurgical intervention. Two This is a prospective and randomized open-label con- trials used meal replacement with a very low calorie diet trolled trial with 2 arms and blinded assessments. Both [19, 20], and Dias-Junior et al. [21] combined a low cal- groups will receive similar educational and weight loss orie diet with anti-obesity drugs (orlistat and subtra- interventions (composed of both nutritional and psycho- mine). Each of these studies observed positive effects logical therapies), but only one group will perform exer- following weight loss. The study by Scott et al. [22] was cise training. The study design is depicted in Fig. 1. Freitas et al. BMC Pulmonary Medicine (2015) 15:124 Page 3 of 11 Fig. 1 Study flow chart. After being included in the study, the patients will be evaluated during 3 non-consecutives visits. Each of the groups will receive the same education program and will participate in the same weight loss program* (composed of nutrition and psychological therapy); however, only one of the groups will participate in exercise training, as the remaining group will perform a sham intervention (breathing and stretching exercises). The groups will performed 24 intervention session,