Effects of physical exercise on aerobic capacity and quality of life in patients diagnosed with asthma: A systematic review and meta-analysis

Daniel Gallardo-Gómez, et al. 342 Arch Med Deporte 2022;39(6):342-352 Revisión Summary Introduction: Nowadays, asthma is a disabling disease with no cure, and the development of effective non-pharmacological treatments which can alleviate side effects of drugs and pathological symptoms is urgent. Some studies have shown that physical exercise may have beneficial effects in patients with asthma, but results were controversial and inconsistent. More evidence is needed to ensure exercise as possible effective treatment in people with asthma. Objectives: To examine the effects of physical exercise on aerobic capacity and quality of life in patients with asthma. Also, we analyze the possible moderation effects of the selected covariates. As a final aim, we verified if a correlation exists between benefits on aerobic capacity and those obtained on quality of life. Material and method: We followed the PRISMA statement to search for randomized controlled trials that used physical exercise as intervention to improve aerobic capacity or quality of life in patients diagnosed with asthma. After data extraction, we conducted a random-effects meta-analysis model with moderation analysis. Then, we inspected the correlation between both outcomes through a multivariate approach. Finally, we performed some additional analyses: methodological quality analysis through the PEDro scale, publication bias analysis through funnel asymmetry tests and funnel plot visualization, and sensitivity analyses by outliers and influential cases detection. Results: Physical exercise had positive effects on aerobic capacity and quality of life. None of the covariates showed a significant moderation effect. We found a positive correlation between the effects of exercise on aerobic capacity and those caused on their quality of life. Conclusions: Our meta-analysis reports information that supports the use of physical exercise as part of the management and treatment of asthma. However, more specific studies are needed to find optimal type and dose of physical activity for those patients. Key words: Physical exercise. Aerobic capacity. Quality of life. Asthma. Meta-analysis. Recibido: 14/07/2021 Aceptado: 08/09/2021 Effects of physical exercise on aerobic capacity and quality of life in patients diagnosed with asthma: A systematic review and meta-analysis Daniel Gallardo Gómez, Francisco Álvarez Barbosa Departamento de Educación Física y Deporte. Universidad de Sevilla. Sevilla. Departamento de Actividad Física y Deporte. Epidemiology of Physical Activity and Fitness Across the Lifespan Research Group EPAFit. Efectos del ejercicio físico en la capacidad aeróbica y la calidad de vida en pacientes diagnosticados con asma: revisión sistemática y meta-análisis Correspondencia: Daniel Gallardo-Gómez E-mail: [email protected] doi: 10.18176/archmeddeporte.00113 Premio SEMED a la Investigación 2021 Resumen Introducción: Actualmente, el asma es una enfermedad incapacitante sin cura, y urge el desarrollo de tratamientos no farmacológicos eficaces que puedan aliviar los efectos secundarios de los fármacos y los síntomas patológicos. Algunos estudios han demostrado que el ejercicio físico puede tener efectos beneficiosos en pacientes con asma, pero los resultados fueron controvertidos e inconsistentes. Se necesita más evidencia para garantizar que el ejercicio sea un posible tratamiento eficaz en personas con asma. Objetivos: Examinar los efectos del ejercicio físico sobre la capacidad aeróbica y la calidad de vida en pacientes con asma. Además, analizamos los posibles efectos de moderación de las covariables seleccionadas. Como objetivo final, verificamos si existe una correlación entre los beneficios en la capacidad aeróbica y los obtenidos sobre la calidad de vida. Material y método: Seguimos la declaración PRISMA para buscar ensayos controlados aleatorios que utilizaran el ejercicio físico como intervención para mejorar la capacidad aeróbica o la calidad de vida en pacientes con diagnóstico de asma. Después de la extracción de datos, realizamos un modelo de meta-análisis de efectos aleatorios con análisis de moderación. Luego, inspeccionamos la correlación entre ambos resultados a través de un enfoque multivariado. Finalmente, realizamos algunos análisis adicionales: análisis de calidad metodológica a través de la escala PEDro, análisis de sesgos de publicación a través de pruebas de asimetría de embudo y visualización de gráficos de embudo, y análisis de sensibilidad mediante la detección de ‘outliers’ y de casos influyentes. Resultados: El ejercicio físico tuvo efectos beneficiosos en la capacidad aeróbica y en la calidad de vida. Ninguna de las covariables presentó un efecto moderador significativo. Encontramos una correlación positiva entre los efectos del ejercicio sobre la capacidad aeróbica y los provocados en la calidad de vida. Conclusiones: Nuestro meta-análisis presenta información que respalda el uso del ejercicio físico como parte del manejo y tratamiento del asma. Sin embargo, se necesitan estudios más específicos para encontrar qué tipo y qué dosis de actividad física son los óptimos para estos pacientes. Palabras clave: Ejercicio físico. Capacidad aeróbica. Calidad de vida. Asma. Meta-análisis. Effects of physical exercise on aerobic capacity and quality of life in patients diagnosed with asthma: A systematic review and meta-analysis 343 Arch Med Deporte 2022;39(6):342-352 Introduction Asthma is a major non-communicable disease whose symptoms (i.e., any combination of cough, wheeze, shortness of breath and chest tightness) affect an estimated 300 million people1, causing approximately 500,000 deaths1. Also, asthma is the most common chronic disease among children1, which increases a) the global impact of this disease on vital outcomes (e.g., aerobic capacity, quality of life, or activities of daily-living)2 and b) the urgency to discover new possible treatments and refine those that currently exist3. Although there is no definitive treatment for asthma3, existing evidence shows that the most effective pharmacological treatments against the symptoms of the disease seem to be strategies with combined inhaled corticosteroids and long-acting β agonists4. Nonetheless, drug treatment has associated side effects such as weight gain or stress5, which is detrimental to the quality of life of these patients. Scientific literature shows that physical exercise could be an effective non-pharmacological intervention to reduce these side effects and cope the symptoms of the disease6, such as the inflammation of the small airways7. Several meta-analyses6,8–10 showed a possible preventive effect of exercise on asthma development6, and positive effects on asthma control8,9, aerobic capacity10, lung function9, and quality of life10. However, the current evidence is scarce, low-quality, and imprecise11. A point we must consider is that most of the meta-analyses that have inspected the effects of exercise in asthmatic patients only focused on aerobic exercises (e.g., swimming, walking, leisure biking and hiking)6,9, being a knowledge gap the potential effects on quality of life and asthma control of other types of physical exercise such as multicomponent or strength. We also found discrepancy on the results (e.g., positive effects10 vs. null12 on quality of life), which combined with some methodological concerns (e.g., unexplained high levels of heterogeneity, differences in the age groups studied, or a clear definition of the analyzed variable), makes the information about physical exercise effects on asthmatic patients inconsistent11. Everything points that this lack of robustness may hamper the application of physical exercise as an effective non-pharmacological treatment to manage asthma symptoms. Therefore, we analyzed the effects of physical exercise on aerobic capacity (i.e., the maximum oxygen consumption during physical activity) and quality of life, both clinically important outcomes in patients suffering from asthma. We also examined the possible interactions between covariates selected for their evidence in the literature6 and the effects on the study outcomes. Finally, we inspected the correlation between aerobic capacity and quality of life to detect potential associations between the effects caused in this target population. Material and method This systematic review with meta-analysis was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement13. Search strategy Guided by the PICOS framework, we performed a systematic search in the databases PubMed (MEDLINE), Scopus, Web of Science and SportDiscus from inception to April 2021. The search strategy was based on combining all terms related to the same cluster (e.g., participants or interventions) with OR and finally to combine all clusters with AND. Terms related to the search were “asthma patients”, “exercise”, “physical therapy”, “aerobic capacity”, “quality of life” and “randomized controlled trial”. Study selection We searched for and included: (1) Randomized controlled trials in which (2) aerobic capacity or quality of life were studied in (3) patients who were five years old or older diagnosed with asthma14 (4) that received an intervention based on aerobic or multicomponent physical exercises as the main element of the intervention (5) compared with non-exercise treatments or another exercise intervention. As an exclusion criterion, we determined that interventions that consisted in physical exercise plus another healthy lifestyle intervention (e.g., diet) and patients diagnosed with an obstructive pulmonary disease other than asthma were excluded. Data extraction All data corresponding to trial patients’ characteristics (e.g., sample size, age, sex), descriptive statistics (i.e., pre- and post-sample size, means, standard deviations of experimental and control groups) and outcome description were extracted into a self-made data extraction spreadsheet in Excel. If information was missing, the corresponding author was requested to supply the information or data for inclusion in the analyses. Data synthesis As we anticipated considerable between-study heterogeneity, a random-effects meta-analysis model was used to pool effect sizes, which were calculated as standardized mean differences (SMD; Hedges’ g15). The restricted maximum likelihood estimator16 was used to calculate the heterogeneity variance tau2. We used Knapp-Hartung adjustments17 to calculate the confidence interval (CI) around the pooled effect. We also estimated the prediction intervals (PI) as accurate measures. Then, we conducted a moderation analysis to find possible interaction effects between the pooled effects and the selected covariates (i.e., age, type of exercise, and duration of the intervention) identified by existing evidence6. Lastly, assuming a moderate correlation coefficient of 0.4118, we estimated the correlation between pooled effects using a multivariate approach to find potential associations between aerobic capacity and quality of life in these patients. All analyses were performed in R statistical software (version 4.0.3)19. We used the ‘esc’ package20 to calculate the effect sizes (Hedges’ g), the ‘dmetar’ package21 contains utility functions to facilitate the conduction of a random-effects meta-analysis model, and the ‘meta’ package22 to evaluate biases in meta-analysis (i.e., outliers detection, influential cases analysis, and publication bias). Daniel Gallardo-Gómez, et al. 344 Arch Med Deporte 2022;39(6):342-352 Additional analyses Methodological quality The score extracted from the Physiotherapy Evidence Database was used to evaluate the methodological quality of each trial and avoid the risk of bias23. When the score of an article was not shown in the PEDro website, reviewers agreed on a rating of this study following the criteria stipulated by the PEDro scale. Total PEDro scores of 0–3 are considered ‘poor’, 4–5 ‘fair’, 6–8 ‘good’, and 9-10 ‘excellent’. However, for trials evaluating complex interventions (e.g., exercise) a total PEDro score of 8/10 is optimal24. Publication bias We used the visualization of the standard errors corresponding to each study and its effect size through a funnel plot per outcome. To quantify this possible asymmetry, we used the significance of the Eggers’ test25. To support these results, we conducted the same analysis under Pustejovsky-Rodges approach26, an option to conduct Eggers’ test with the corrected standard error formula recommended for studies that used SMD as effect size26. Sensitivity analyses To analyze the between-study heterogeneity, we inspected the studies with an extreme effect size (i.e., outliers) and those which heavily pushed the pooled effect of our analysis into one direction (i.e., influential cases). Furthermore, to support the influential cases analysis, we conducted a leave-one-out meta-analysis model27, which reported the individual contribution to the pooled effect of a specific outcome and to heterogeneity levels (i.e., I2). After removing the studies detected as outliers or influential cases, we conducted new meta-analytical models and plotted their corresponding forest plots to visualize models’ comparison. Results Included studies We identified 1,963 registers through the initial searches. After screening citations by title and abstract, we considered 87 possible eligible studies for inclusion. After removing duplicates and applying the selection criteria, 17 studies8,28-43 (1,329 patients; 29 effect sizes) were selected for inclusion in this meta-analysis (Figure 1). The year of publication ranged from 2001 to 2020. A total of 627 (47.18%) of patients were women. The average age was 25.58±18.34 years old (range of 10 - 68.2). The average body mass index (BMI) was 23.11±3.54. The interventions had an average duration of 10.64±3.92 weeks. The interventions used in the included studies were aerobic exercises (n = 16) and multicomponent exercises (n = 13). All studies’ characteristics referring to the intervention and control groups details, evaluation tools and main results are presented in Table 1. Meta-analysis Our results showed that exercise had positive effects on aerobic capacity in patients diagnosed with asthma (k = 15; Hedges’ g = 0.73; 95% CI [0.16, 1.28]; p = 0.01). Also, significant effects were found for exercise on the quality of life of these patients (k = 14; Hedges’ g = 0.69; 95% CI [0.26, 1.11]; p < 0.01). Forest plots are illustrated in Figure 2. None of the analyzed covariates showed a significant moderation effect. For aerobic capacity, the between-study heterogeneity variance was estimated at tau2 = 0.78 (95% CI: 0.37 - 2.43), with an I2 value of 84% (95% CI: 75 - 90%). For quality of life, the between-study heterogeneity variance was estimated at tau2 = 0.28 (95% CI: 0.11 - 1.51), with an I2 value of 69% (95% CI: 45 - 82%). The prediction intervals ranged from g = –1.25 to 2.71 in aerobic capacity, and from g = –0.56 to 1.93 in quality of life, indicating that negative intervention effects cannot be ruled out for future studies. Correlation between aerobic capacity and quality of life We found a positive moderate correlation (r = 0.59) between aerobic capacity and quality of life, indicating that positive effects on aerobic capacity may cause positive effects on quality of life. The pooled effects and the association between outcomes are illustrated in Figure 3. Figure 1. PRISMA flowchart of study selection. Included IdentificationScreeningEligibility Records after duplicated removed (n = 1,138) Records screened (n = 1,138) Full-text articles assessed for eligibility (n = 87) Studies included in qualitative synthesis (n = 17) Studies included in quantitative synthesis (n = 17) Duplicates excluded (n = 825) Records excluded (n = 1,051) Full-text articles excluded, with reasons (n = 709) No RCT (n = 7) No asthma diagnosis (n=13) Exercise as main intervention (n=39) Outcomes of interest (n=11) Records identified through database searching (n = 1,963) Additional records identified through other sources (n = 0) Effects of physical exercise on aerobic capacity and quality of life in patients diagnosed with asthma: A systematic review and meta-analysis 345 Arch Med Deporte 2022;39(6):342-352 Study Participants Age (average) BMI Protocol duration Intervention parameters Control parameters Evaluation tools Main results Abdelbasset, 2018 38 (23 females) 10 21.8 10 weeks 3 sessions/ week 40 min/session Intensity: 50-70% HRmax Type: Walking Conventional treatment VO2max 6-MWT PAQLQ 10 weeks of physical exercise had beneficial effects on pulmonary functions, aerobic capacity, and quality of life in children with asthma Andrade, 2014 33 (12 females) 10 19.8 6 weeks 3 sessions/ week ~40 min/ session Intensity: 70-80% HRmax Type: Treadmill Usual care 6-MWT PAQLQ An improvement was found in functional capacity, maximal respiratory pressure, quality of life and asthmarelated symptoms Basaran, 2006 62 (22 females) 10.4 18.3 8 weeks 3 sessions/ week 60 min/session Intensity: NA Type: Calisthenics + submaximal basketball training Home respiratory exercises 6-MWT PAQLQ 8-weeks of regular submaximal exercise has benefitial effects on quality of life and exercise capacity in asthmatic children Coelho, 2018 37 (32 females) 46 28.6 12 weeks 5 sessions/ week 30 min/session Intensity: moderate Type: Walking Usual care 6-MWT AQLQ Participants of the intervention group increased their exercise capacity and their daily steps Dogra, 2011 36 (22 females) 34.1 24.7 24 weeks 3-5 sessions/ week NA min/ session Intensity: 70-85% HR max Type: outdoor jogging, treadmill, recumbent, or upright cycling, and ellitical or rowing machines Usual care VO2max Mini-AQLQ A structured exercise intervention can improve asthma control Fanelli, 2007 38 (NA females) 10.5 18.1 16 weeks 2 sessions/ week 90 min/session Intensity: 70% RM Type: Cycling and/ or treadmill and endurance exercises Educational program VO2max PAQLQ Supervised exercise training might be associated with benefitial effects on disease control and quality of life in children França-Pinto, 2015 43 (34 females) 42 26.4 12 weeks 2 sessions/ week 30 min/session Intensity: Vigorous (anaerobic threshold) Type: Yoga breathing exercises + treadmill Yoga breathing exercises + sham intervention VO2max AQLQ Adding exercise as an adjunct therapy to pharmacological treatment could improve the main features of ast Jaakkola, 2019 89 (70 females) 39.7 24.9 24 weeks 3 sessions/ week ~30 min/ session Intensity: NA Type: Aerobic exercise + muscle training Usual care VO2max Regular exercise improves asthma control Mendes, 2010 101 (79 females) 39.3 24.8 12 weeks 2 sessions/ week 30 min/session Intensity: 60-70% VO2max Type: Yoga breathing exercises + aerobic exercises Educational program VO2max AQLQ Aerobic training can play an important role in the clinical management of patients with persistent asthma Moreira, 2008 31 (14 females) 12.7 20.4 12 weeks 2 sessions/ week 50 min/session Intensity: submaximal. Type: Aerobic exercises + strength training + balance adn coordination exercises Usual care AQLQ There is no reason to discourage asthmatic children with controlled disease to exercise Refaat, 2015 68 (37 females) 37.1 22.5 6 weeks 3 sessions/ week 30 min/session Intensity: 60-80% HRmax Type: Cycling, step ups, wall squats and upper limb endurrance exercises Usual care AQLQ Physical training can improve quality of life and pulmonary function in patients with moderate and severe bronchial asthma Table 1. Characteristics of the included studies. (continúa) Daniel Gallardo-Gómez, et al. 346 Arch Med Deporte 2022;39(6):342-352 Study Participants Age (average) BMI Protocol duration Intervention parameters Control parameters Evaluation tools Main results Sanz-Santia- go, 2020 53 (29 females) 11.5 NA 12 weeks 3 sessions/ week 60 min/session Intensity: moderate. Type: Cycling + resistance exercises Usual care VO2max PAQLQ Combined exercise training improved cardiorespiratory fitness and muscle strength in children Shaw, 2011 44 (32 females) 21.9 27.1 8 weeks 3 sessions/ week 30 min/session Intensity: 60% HRmax Type: Walking and/or jogging Usual care VO2max Aerobic exercise plus diaphragmatic inspiratory resistive breathing might be useful as an adjunct therapy in asthmatic patients Turner, 2011 35 (19 females) 67.8 27.7 6 weeks 3 sessions/ week 80-90 min/ session Intensity: 80% of the average walking speed + Borg scale Type: Walking + cycling + endurance exercises Usual care 6-MWT AQLQ Supervised exercise training improves symptoms and quality of life in these patients Van Veldhsen, 2001 47 (13 females) 10.6 18.5 12 weeks 2 sessions/ week 60 min/session Intensity: NA. Type: Fitness training + different physical activities Usual care VO2max Physical exercise program not only enhanced physical fitness, but also improved coping behavior with asthma Wang, 2009 30 (10 females) 10 20 6 weeks 3 sessions/ week ~50 min /session Intensity: 65% HR peak Type: Swimming Usual care VO2max Swimming may be an effective non-pharmacological intervention for the children or adolescent with asthma Weisgerber, 2008 45 (24 females) 10.3 23 9 weeks 3 sessions/ week 30 min/session Intensity: High (8-10 METs) Type: Swimming Golf intervention VO2max AQLQ Results suggest a potentially benefitial role for moderate to vigorous physical activity in childhood asthma HRmax: Maximal Heart Rate; 6-MWT: 6-Minutes Walking Test; PAQLQ: Pediatric Asthma Quality of Life Questionnaire; AQLQ: Asthma Quality of Life Questionnaire. Table 2. PEDro scale scores of the included studies. Study Eligibility Random Concealed Baseline Blinded Blinded Blinded Adequate Intention Between Point Overall criteria* allocation allocation compasubjects therapists assessors follow to-treat group estimates rison -up analysis compa- and rison variability Abdelbasset, 2018 Yes Yes Yes Yes No No Yes Yes No Yes Yes 7 Andrade, 2014 Yes Yes Yes Yes No No No No Yes Yes Yes 6 Basaran, 2006 No Yes No Yes No No No Yes No Yes Yes 5 Coelho, 2018 Yes Yes Yes Yes No No No Yes Yes Yes Yes 7 Dogra, 2011 Yes Yes Yes Yes No No No No No Yes Yes 5 Fanelli, 2007 Yes Yes No Yes No No Yes No No Yes Yes 5 França-Pinto, 2015 Yes Yes Yes Yes No No No No No Yes Yes 5 Jaakkola, 2019 Yes Yes No Yes No No No No No Yes Yes 4 Mendes, 2010 Yes Yes No Yes No No No Yes No Yes Yes 5 Moreira, 2008 Yes Yes Yes Yes No No No Yes Yes Yes Yes 7 Refaat, 2015 Yes Yes No Yes No No No No No Yes Yes 4 Sanz-Santiago, 2020 No Yes Yes Yes No No No No Yes Yes Yes 6 Shaw, 2011 No Yes Yes Yes No No No Yes No Yes Yes 6 Turner, 2011 No Yes No Yes No No No Yes No Yes Yes 5 Van Veldhoven, 2001 Yes Yes No Yes No No No Yes No Yes Yes 5 Wang, 2009 No Yes No Yes No No No Yes No Yes Yes 5 Weisgerber, 2008 Yes Yes No Yes No No No No No No No 2 *Invalid criterion for final score. Effects of physical exercise on aerobic capacity and quality of life in patients diagnosed with asthma: A systematic review and meta-analysis 347 Arch Med Deporte 2022;39(6):342-352 Methodological quality of included studies We found that 6 studies31,35,38,41–43 presented a good methodological quality, 10 studies8,28–30,33,34,36,37,39,40 obtained a fair methodological quality score and only 1 study32 presented a poor methodological quality. In summary, we can determine the methodological quality of our study as fair-good. All scores of the included studies are presented in Table 2. Publication bias analysis Eggers’ test does not indicate the presence of funnel asymmetry (Table 3). After performing sensitivity analysis with the Pustejovsky- Rodges approach, our results also did not show the presence of funnel asymmetry, which indicates data consistency. To visualize the funnel symmetry, the funnel plots of both outcomes are illustrated in Figure 4. Figure 2. Effect sizes for exercise on study outcomes. Studies are ordered according to their effect sizes. A) Aerobic capacity; B) Quality of life. A B Daniel Gallardo-Gómez, et al. 348 Arch Med Deporte 2022;39(6):342-352 Figure 3. Effect sizes and confidence ellipses of both outcomes. The diamonds near the axes are the estimates of the effect size of our variables and the black arrows represent their 95% CI. The diamond in the center is the combined effect for both variables. The red ellipse represents the 95% CI ellipse of our combined effect size. The black ellipse is 95% PI for all effects of all studies under a random-effects model. Each point represents a study and the dashed line its 95% CI. Effect sizes and their Confidence Ellipses Quality of life -1.0 -0.5 -0.0 0.5 1.0 3 1.5 2.0 0 1 Aerobic capacity 2 Figure 4. Contour-Enhanced Funnel Plots. Aerobic capacity Quality of life Standardised Mean Difference Standardised Mean Difference Standard Error 1.0 0.0 1.50.50.0-0.5 0.3 0.2 0.1 Standard Error 00.0 0.35 0.05 0.10 0.15 0.20 0.25 0.30 Effects of physical exercise on aerobic capacity and quality of life in patients diagnosed with asthma: A systematic review and meta-analysis 349 Arch Med Deporte 2022;39(6):342-352 Figure 5. Leave-One-Out Meta-Analysis to identify the individual contribution to the heterogeneity and effect size. A) Aerobic capacity; B) Quality of life. A B Daniel Gallardo-Gómez, et al. 350 Arch Med Deporte 2022;39(6):342-352 Sensitivity analysis Observing the variance in effect sizes and heterogeneity through leave-one-out meta-analysis method, we detected 3 studies30,38,41 for aerobic capacity outcome and 2 studies30,38 for quality of life outcome that could have influenced the pooled effects. The individual contributions to the effect size and heterogeneity are illustrated in Figure 5. Removing the observed influential studies, the pooled effects of both outcomes decreased, but we obtained a significant reduction in the heterogeneity level and more accurate confidence and prediction intervals, suggesting significant positive effects of physical exercise on quality of life of these patients. All data referred to sensitivity analysis appeared in Table 4. Discussion To our knowledge, our meta-analysis, with a final representation of 1,329 patients with asthma (17 studies; 29 effect sizes), was the firstever in reporting a significant correlation between aerobic capacity and quality of life effects in patients diagnosed with asthma. Furthermore, we found significant positive effects of physical exercise on aerobic capacity and quality of life in these patients. A point we must consider is that prediction intervals of both outcomes included zero in our main analyses. However, when we removed the influential studies, we obtained clear improvements on aerobic capacity and quality of life (i.e., prediction intervals did not include zero), a significant decrease in the heterogeneity levels, and more accurate intervals (i.e., confidence and prediction). In contrast, we also observed an effect size shrinking in that process. Lastly, we found a moderate positive correlation between both outcomes, suggesting that beneficial effects on quality of life may have been caused by benefits on aerobic capacity. The results obtained in our meta-analysis are in line with other reviews6,8–10, supporting the beneficial effects of exercise in asthmatic patients. Asthma is an inflammatory disease, and exercise and/or physical activity can play an important role in controlling its symptoms: improving the aerobic capacity of these patients may provide a reduction in exercise-induced bronchoconstriction (i.e., airway muscles contraction)44, which is the main cause of the notorious sedentary behavior of people diagnosed with asthma45, and a better physical exercise tolerance46. Hence, these benefits could be reflected on the overall quality of life of people with asthma, since the greater impact on any asthma symptom, the better their quality of life47, which may partially explain the found correlation between both outcomes. This research adds consistent evidence on the usefulness of physical exercise in the management and treatment of asthma. Considering our data and the current evidence48, we hypothesize that physical exercise could improve some pathologies which share symptoms with asthma disease such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), from common symptoms (e.g., cough) to severe ones (e.g., difficulty breathing, shortness of breath, or loss of movement), taken in account all pathology symptoms, the context, and patient status. However, in order to transfer this knowledge to clinical practice, we need to fill in the existing gaps in the literature about the optimal type and dose for these patients49. International organizations recommend keeping a healthy and active life, encouraging people with asthma to engage in regular physical activity49, at least 30 minutes of moderately intense physical activity or structured physical exercise every day49, resulting in global recommendations, not specifications. In order to establish optimal physical exercise for these people, there is limited evidence which suggests that aquatic activities (e.g., swimming) are more beneficial by reducing the airborne particles exposure47, and that moderate-vigorous intensity activities could result in greater benefits47. This information scarcity could explain that we do not detect moderation effects differentiating by type of physical exercise (i.e., aerobic vs. multicomponent), although significant interactions could be hidden by lack of available data. In this point, we can identify several key strengths to our study. Our meta-analysis is the first one that has been able to explain part of the benefits caused on quality of life by aerobic capacity improvements. Sensitivity analyses allow us to explain large amounts of heterogeneity given in the main analyses. Included studies presented a fair-good methodological quality. Additional analysis did not show the presence of publication bias. Conversely, we also detected some limitations. We have only focused on exercise, but future meta-analyses should include different types of physical activities (e.g., body-mind or aquatic activities). Table 3. Publication bias analysis results. Method Intercept 95% CI t-value p Egger –3.49 –7.10 – 0.12 –1.896 0.0904 Pustejovsky-Rodges –1.28 –4.12 – 3.13 0.95 0.366 Outcome Analysis Hedges’ g 95% CI p 95% PI I2 95% CI Aerobic capacity Main Analysis 0.73 0.16 - 1.28 0.01 –1.25 - 2.71 84% 75 - 90 Infl. Cases Removed 0.30 0.06 - 0.54 0.002 –0.31 - 0.91 43%* 13 - 72 Quality of life Main Analysis 0.69 0.26 - 1.11 0.004 –0.56 - 1.93 69% 45 - 82 Infl. Cases Removed 0.51 0.27 - 0.74 < 0.001 0.03 - 0.98* 28%* 0 - 64 1Removed as outliers: Abdelbasset, 2018; Andrade, 2014; Franelli, 2007 2Removed as outliers: Andrade, 2014; Franelli, 2007 *Significanrt changes between models Table 4. Sensitivity analysis results