Abstract: Of the 83 studies identified, 15 studies which included 487 participants, met the inclusion criteria. The numbers in each study ranged from nine up to 72 participants; two studies were in adults, seven were in children and adolescents and six studies included all age ranges. Four studies of hospitalised participants lasted less than one month and 11 studies were outpatient-based, lasting between two months and three years. The studies included participants with a wide range of disease severity and employed differing levels of supervision with a mixture of types of training. There was also wide variation in the quality of the included studies. This systematic review shows very low- to low-quality evidence from both short- and long-term studies that in people with cystic fibrosis aerobic or anaerobic physical exercise training (or a combination of both) has a positive effect on aerobic exercise capacity, pulmonary function and health-related quality of life. No study reported on mortality; two studies reported on adverse events (moderate-quality evidence); one of each study reported on pulmonary exacerbations (low-quality evidence) and diabetic control (very low-quality evidence). Although improvements were not consistent between studies and ranged from no effects to clearly positive effects, the most consistent effects of the heterogeneous exercise training modalities and durations were found for maximal aerobic exercise capacity (in four out of seven studies) with unclear effects on forced expiratory volume in one second (in two out of 11 studies) and health-related quality of life (in two out of seven studies). Evidence about the efficacy of physical exercise training in cystic fibrosis from 15 small studies with low to moderate methodological quality is limited. Exercise training is already part of regular outpatient care offered to most people with cystic fibrosis, and since there is some evidence for beneficial effects on aerobic fitness and no negative side effects exist, there is no reason to actively discourage this. The benefits from including physical exercise training in an individual's regular care may be influenced by the type and duration of the training programme. High-quality randomised controlled trials are needed to comprehensively assess the benefits of exercise programmes in people with cystic fibrosis and the relative benefits of the addition of aerobic versus anaerobic versus a combination of both types of physical exercise training to the care of people with cystic fibrosis.

Plain-language summary: This review includes 15 studies with a total of 487 people with CF; the numbers in each study ranged from just nine people up to 72 people in the largest study. Two studies were in adults, seven were in children and adolescents and six studies included all age ranges. Four studies lasted less than one month and took place while the participants were in hospital; 11 studies were outpatient-based and lasted from two months up to three years. The studies included people with a wide range of severity of CF lung disease. There were differing levels of supervision in the studies and a mixture of types of training. The outcome most often reported in the studies was the change in lung function; other commonly reported outcomes included peak oxygen consumption, health-related quality of life, change in muscle strength and change in body composition (e.g. muscle and fat). Due to different study designs (type of exercise training, duration, etc.), we could not combine results from different studies. The short-term studies did not show differences between treatments. The longer studies showed that physical exercise training can improve aerobic capacity, there were some improvements in lung function and health-related quality of life, but these were not consistent across all studies. No study reported the number of deaths; two studies reported on side effects; one study reported on pulmonary exacerbations and another on diabetic control. We included a number of small studies and thought the quality of these studies was moderate at best (only for side effects). Overall, there was only low- to very low-quality evidence that aerobic or anaerobic physical exercise training (or a combination of both) has a positive effect on aerobic exercise capacity, pulmonary function and health-related quality of life in people with CF. In four of the studies the participant characteristics at the start of the studies were different between groups, despite being put into the different treatment groups at random. It is not possible for people not to know which treatment group they are in when comparing exercise training to no exercise. However, we do not think the fact that people knew which treatment they were receiving would affect the results for lung function as long as the assessments were done properly. In contrast, there may be bias when the people assessing an individual's cardiopulmonary fitness are not blinded to which group the volunteer is in. In less than half of the included studies, the investigators tried to prevent the outcome assessors from knowing which groups the participants were in; and in only one study was the lead researcher blinded. The studies did not routinely measure health-related quality of life and where it was measured, different measurement tools were used. Selective reporting of results maybe an issue, especially as most of the included studies were not listed in trial registries, which give advance details of the outcomes being measured. We are uncertain about the effects and further better quality studies will likely change these findings.