Exercise and physical activity for asthma management: The European Academy of Allergy and Clinical Immunology perspective

Asthma is a complex heterogeneous disease characterized by bronchial hyperresponsiveness (BHR), airway inflammation and variable symptoms such as cough, wheeze and dyspnoea. It is currently the most common respiratory condition worldwide, affecting approximately 350 million people, and remains a major source of economic and societal burden.1 In the past, short-acting beta-2-agonists (SABA) have formed the mainstay of pharmacological reliever therapy; however, in response to increasing concern regarding the potential consequences of SABA therapy in isolation (i.e. heightened risk of severe exacerbation and mortality), the Global Initiative for Asthma (GINA) published revised guidelines in April 2019, to include inhaled corticosteroid (ICS) therapy across all treatment levels.2 Specifically, asthma management strategies now focus on pharmacological intervention (i.e. symptom-driven, low dose ICS + long-acting beta-2-agonist) with a stepwise approach to treatment escalation.2 Yet, while this approach is effective in the majority of cases, disease control remains suboptimal across all asthma severities3 and the adverse side effects associated with long-term ICS and/or oral corticosteroids (e.g. osteoporosis) can be significant.4 Furthermore, poor adherence to asthma medication is a longstanding issue, and a high proportion of individuals with severe or difficult-to-treat disease are considered therapy resistant. While emerging biologicals represent a significant step forward for the management of severe disease, indications vary and there is inequity in access across the globe.5 It is therefore important that scalable and cost-effective adjunct therapies are identified to improve clinical care and patient-reported outcomes moving forward. Physical activity is defined as ‘any bodily movement produced by the contraction of skeletal muscle that increases energy expenditure above a basal level’. In contrast, exercise refers to a sub-type of physical activity, that consists of planned, structured and repetitive movement designed to improve or maintain fitness (i.e. ability to participate in sport or undertake specific occupational or daily activities).6 The health benefits of exercise and physical activity have been recognized for some time; however, over the past decade, it has become increasingly apparent that physical inactivity (i.e. failing to meet current physical activity recommendations) is an independent risk factor associated with the onset and progression of several non-communicable diseases (e.g. cancers, diabetes and cardiovascular disease, etc.). Accordingly, the ability to lead an active lifestyle is now considered a key requirement for health maintenance.7 The reasons underpinning sedentary behaviour are complex and include physiological, psychological, social, cultural, environmental and/or economic factors.8 However, for people with asthma, exercise is one of the most common symptom triggers (i.e. many also experience exercise-induced bronchoconstriction9) and thus dyspnoea on exertion has the potential to impact an individual's exercise tolerance or desire to undertake physical activity. In support of this concept, recent systematic reviews have shed light on the fact that individuals with asthma typically engage in lower levels of habitual physical activity in comparison to healthy counterparts, and that sedentary behaviour is closely related to adverse clinical and health-related outcomes.10, 11 On the other hand, elite level athletes engaging in regular high-intensity exercise (i.e. training volume exceeding 10–15 h per week), particularly those exposed to noxious environmental stimuli (e.g. choline derivatives in swimmers), are thought to be heightened risk of developing asthma-related issues over the course of their sporting careers.12-14 In the context of asthma management, regular exercise and physical activity is thought to possess disease modifying potential by modulating inflammatory and immune responses.15, 16 Although specific mechanisms have yet to be fully elucidated, animal studies (primarily using ovalbumin-sensitized mice as a model of allergic asthma) indicate that moderate intensity aerobic exercise decreases leukocyte infiltration, cytokine production (notably, IL-4, IL-5, IL-13), BHR and structural airway remodelling. However, in humans, mechanistic studies evaluating the role of exercise and physical activity remain limited, with the majority of prior work focussing on clinically relevant outcome measures such as symptom scores, health status, quality of life, lung function, body mass index and functional capacity.15 While some studies have reported that aerobic exercise decreases BHR and systemic inflammation in adults with moderate and severe asthma,17 a recent meta-analysis of randomized controlled trials in an adult population concluded that although exercise has the potential to improve asthma control and lung function, biomarkers of airway inflammation (i.e. fractional exhaled nitric oxide and/or sputum eosinophilia) remain unchanged.18 It is also unclear in the obese asthma phenotype whether exercise directly modulates asthma-related inflammation, or inflammation driven by adiposity.11 It is therefore apparent that current evidence concerning the role of exercise and physical activity for asthma management remains somewhat equivocal. Indeed, while regular physical activity is endorsed in the current GINA report,2 there is a lack of evidence-based recommendations concerning the specific frequency, intensity, duration (i.e. dose–response relationship) or type of activity to undertake according to disease severity or sub-type. This is an important consideration, on the basis that asthma encompasses several clinical phenotypes and endotypes, that is, Type-2 high versus Type-2 low asthma (with significant heterogeneity in disease patterns according to sex and age-onset) that respond differently to specific treatment interventions. In the era of personalized and precision medicine, it is therefore important that further research is conducted in this area to inform and stratify asthma-specific exercise and physical activity-based recommendations. In this respect, it is also important moving forward that clinicians and healthcare professionals receive appropriate training or have access to evidence-based educational resources to permit tailored exercise prescription during routine asthma review. Furthermore, exploring patient barriers and enablers to exercise and physical activity engagement in order to design and implement effective behaviour change interventions to elicit long-term lifestyle modification remains a key priority. This is particularly relevant for paediatric cohorts given the strong association between exercise engagement in early life and physical activity status across the lifespan. To address the aforementioned gaps in scientific knowledge and facilitate future research to improve the lives of people living with asthma, the European Academy of Allergy and Clinical Immunology (EAACI) have therefore assembled an expert panel under its Research and Outreach Committee (ROC). The immediate, medium- and long-term aims of this initiative are to: Establish an international collaborative research network encompassing a multidisciplinary group of experts (including allergists, pulmonologists, respiratory healthcare professionals, clinical immunologists, exercise physiologists and behaviour change scientists) and patient representatives to provide a platform to identify unmet need and exchange ideas for future research. Launch a European survey to qualitatively explore patients', parents and healthcare providers knowledge, experience, perceptions and opinions of exercise and physical activity in the context of asthma management. Develop a research informed practically focussed EAACI position paper detailing exercise and physical activity recommendations (informed according to current best available evidence and expert opinion) and online supplementary patient- and clinician-focussed educational resources. Identify relevant funding opportunities and formulate competitive grant applications to conduct robust multicentre basic, clinical and translational research with established protocols and endpoints. OJP drafted the first version of this manuscript with critical revision and important intellectual content from SDG, RG, CJ, MO, NGP, MB. The authors wish to thank the EAACI Research and Outreach Committee for supporting this initiative. OJP, SDG, RG, CJ, MO, MB have no conflict of interest in respect to the submitted work. NGP has been a speaker and/or advisory board member for Abbott, Abbvie, ALK, Asit Biotech, AstraZeneca, Biomay, Boehringer Ingelheim, GSK, HAL, Faes Farma, Medscape, Menarini, MSD, Novartis, Nutricia, OM Pharma, Regeneron, Sanofi, Takeda, Viatris.