Physical exercise training for cystic fibrosis

Thomas Radtke; Sarah J Nevitt; Helge Hebestreit; Susi Kriemler

doi:10.1002/14651858.CD002768.pub4

. 2017 Nov 1;2017(11):CD002768. doi: 10.1002/14651858.CD002768.pub4

Physical exercise training for cystic fibrosis

Thomas Radtke ^1,^✉, Sarah J Nevitt ², Helge Hebestreit ³, Susi Kriemler ¹

Editor: Cochrane Cystic Fibrosis and Genetic Disorders Group

PMCID: PMC6485991 PMID: 29090734

Abstract

Background

Physical exercise training may form an important part of regular care for people with cystic fibrosis. This is an update of a previously published review.

Objectives

To assess the effects of physical exercise training on exercise capacity by peak oxygen consumption, pulmonary function by forced expiratory volume in one second, health‐related quality of life and further important patient‐relevant outcomes in people with cystic fibrosis.

Search methods

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.

Date of the most recent search: 04 May 2017.

We searched ongoing trials registers (clinicaltrials.gov and the WHO ICTRP). Date of most recent search: 10 August 2017.

Selection criteria

All randomised and quasi‐randomised controlled clinical trials comparing exercise training of any type and a minimum duration of two weeks with conventional care (no training) in people with cystic fibrosis.

Data collection and analysis

Two authors independently selected studies for inclusion, assessed methodological quality and extracted data. The quality of the evidence was assessed using the GRADE system.

Main results

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).

Authors' conclusions

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

Physical training to improve exercise capacity in people with cystic fibrosis

Review question

We reviewed the evidence about whether physical exercise training improves low aerobic fitness, improves health‐related quality of life and slows the decline in lung function in people with cystic fibrosis (CF). This is an update of a previously published review.

Background

CF affects many systems in the body, but mainly the lungs. It causes shortness of breath and limits the amount of exercise people with the condition can tolerate. The progress of lung disease leads to a low ability to exercise and physical inactivity, which in turn affects health and health‐related quality of life. We looked for studies where people with CF of any age did aerobic training (continuous activity at a low to moderate intensity, such as jogging, cycling, swimming or walking) or anaerobic training (weight or resistance training or sprinting at a high intensity for a short duration) or a combination of both compared to no training.

Search date

The evidence is current to: 04 May 2017.

Study characteristics

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).

Key results

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.

Quality of the evidence

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.

Summary of findings

Background

Description of the condition

Cystic fibrosis (CF) is the most common life‐limiting autosomal recessively inherited disease in populations of Northern European descent. The incidence of CF has been estimated as 1 in 3500 live births in the USA (CF Foundation 2009; CF Trust 2010). The prevalence in the European countries varies widely and was recently estimated as 0.840 per 10,000 (Farrell 2008). Although CF is a multisystem disease, the primary cause of death is respiratory failure (CF Trust 2010). Progressive respiratory disease results in an abnormal ventilatory response to exercise in CF, which contributes to dyspnoea (shortness of breath) and is a major limiting factor to exercise tolerance in this population (O'Neill 1987). In addition, a sedentary lifestyle contributes to the progression of physical and functional impairment in CF (Schneiderman 2014). A consequence of this is low aerobic fitness that is associated with reduced life expectancy (Nixon 1992).

Description of the intervention

Physical exercise training is defined as participation in a programme of regular vigorous physical activity designed to improve physical performance, cardiovascular function, muscle strength or any combination of these three (Shephard 1994). There are basically two different types of physical exercise training: aerobic training or anaerobic training, but none can be considered purely 'aerobic' or 'anaerobic' with respect to energy supply. Aerobic training usually involves periods of continuous training (e.g. cycling or running) for a length of time at a target intensity below the anaerobic threshold. Anaerobic training involves training (e.g. weight or resistance training or sprinting) at a high intensity for a short duration above the anaerobic threshold.

How the intervention might work

Physical exercise training has multiple beneficial effects. It contributes to the alleviation of dyspnoea and improves exercise tolerance in people with CF (Cerny 2013). Physical exercise training maintains pulmonary function by improving sputum clearance through a combination of hyperventilation, mechanical vibration, coughing and changes in sputum rheology leading to facilitated and increased sputum expectoration (Dwyer 2011; Dwyer 2017; Hebestreit 2001) and possibly training of respiratory muscles (Houston 2013).

Physical exercise training may also be an important part of the management of diabetes in CF, as exercise improves glycaemic control in type 1 diabetes mellitus by improving insulin sensitivity and reducing systemic inflammation (Galassetti 2013). Regular exercise may delay the onset of osteoporosis by preventing a reduction in bone mineral density (Tejero García 2011). Other postulated benefits of any physical exercise training may be decreased anxiety and depression, enhanced feelings of well‐being and health‐related quality of life (HRQoL) (Hebestreit 2014) and enhanced performance at work, recreational and sport activities (ACSM 2010). It is not clear how many weeks training are required to achieve these benefits or what combination of aerobic and anaerobic training is required. Non‐adherence to prescribed physical training may contribute to worsening signs and symptoms of respiratory disease, more frequent respiratory infections and a reduced ability to perform activities of daily living and thus ultimately have a detrimental effect on the individual's prognosis. Side effects of physical exercise training are extremely rare so that exercise can be considered safe in CF (Ruf 2010).

Why it is important to do this review

This review aims to provide evidence for the inclusion of physical exercise training in regular care for people with CF. This version of the review is an update of previous versions (Bradley 2002; Bradley 2008; Radtke 2015a).

Objectives

To assess the effects of physical exercise training on exercise capacity by peak oxygen consumption (VO₂ peak), pulmonary function by forced expiratory volume at one second (FEV₁), HRQoL and further important patient‐relevant outcomes in people with CF.

Methods

Criteria for considering studies for this review

Types of studies

Randomised controlled trials (RCT) or quasi‐RCTs.

Types of participants

People with CF, of any age, and any degree of disease severity, diagnosed on the basis of clinical criteria and sweat testing or genotype analysis.

Types of interventions

Any type of prescribed physical exercise training delivered to people with CF compared to usual care. Studies which involved pure respiratory muscle training were excluded. In a post hoc change it was stipulated that studies must have a duration of at least two weeks.

Types of outcome measures

Primary outcomes

Exercise capacity (VO₂ peak reported either as L, mL per kg body weight or fat‐free mass or as per cent (%) predicted)
Pulmonary function (FEV₁ reported either as L or % predicted and as absolute values or change from baseline)
HRQoL (measured by generic or disease‐specific instruments, or both using validated instruments or patient reports)

In a post hoc change, the fourth primary outcome 'mortality' was moved to secondary outcomes in line with Cochrane guidance to limit the number of primary outcomes to three.

Secondary outcomes

CF‐related mortality
Muscle strength and anaerobic exercise capacity, measured by muscle force tests (isokinetic or non‐isokinetic tests), a Wingate Anaerobic Test (WaNT) or by a supramaximal sprint test on a cycle ergometer measured by e.g. aerobic capacity as power in absolute values (Watt), adjusted for body weight, fat‐mass; fat‐free mass, or as % predicted), or muscle strength as kg or Nm or anaerobic capacity as peak power, mean power and fatigue index during a WaNT
Additional indices of exercise capacity (such as peak work capacity, peak heart rate, minute ventilation, lactate and functional capacity tests (six‐and 12‐minute walk tests; shuttle tests; three‐minute step test; sit‐to‐stand test); oxygenation; effort and fatigue)
Additional indices of pulmonary function, pulmonary diffusing capacity, ventilation inhomogeneity and respiratory muscle strength (such as forced vital capacity, forced expiratory flows between 25% and 75% of expirated volume, total lung capacity, functional residual capacity, residual volume, pulmonary diffusing capacity for carbon monoxide, pulmonary diffusing capacity for nitric oxide, lung clearance index and maximum inspiratory and expiratory pressures)
Physical activity, measured by self report (diary), validated questionnaires or objectively with pedometers (e.g. number of steps) or accelerometers (counts per min; time spent in different exercise intensities, e.g. light, moderate, vigorous physical activity)
Body composition, measured by weight (kg), body mass index (kg/m² or z scores), skinfolds (mm), bioelectrical impedance analysis or whole body air‐displacement plethysmography or dual‐energy X‐ray absorptiometry (e.g. fat mass, fat‐free mass in kg, % or % predicted)
Acute exacerbations
1. number of exacerbations
2. time to first exacerbation
Antibiotic use (including oral, intravenous or inhaled antibiotics)
Bone health (measured by dual X‐ray energy absorptiometry or peripheral quantitative computed tomography)
Diabetic control, measured by fasting blood glucose levels (mmol/L or mg/dL), insulin levels (mmol/L or mg/dL) or homeostasis model assessment (HOMA) or oral glucose tolerance test (blood glucose in mmol/L or mg/dL)
Compliance with physical exercise training, assessed by questionnaires, (online) diaries, or with exercise monitoring devices such as heart rate monitors
Adverse events related to the exercise intervention or exercise testing as part of intervention

Search methods for identification of studies

There are no restrictions regarding language or publication status.

Electronic searches

Relevant studies were identified from the Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register using the term: exercise.    The Cystic Fibrosis Trials Register is compiled from electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (updated each new issue of the Cochrane Library), weekly searches of MEDLINE, a search of Embase to 1995 and the prospective handsearching of two journals ‐ Pediatric Pulmonology and the Journal of Cystic Fibrosis. Unpublished work is identified by searching through the abstract books of three major cystic fibrosis conferences: the International Cystic Fibrosis Conference; the European Cystic Fibrosis Conference and the North American Cystic Fibrosis Conference. For full details of all searching activities for the register, please see the relevant sections of the Cystic Fibrosis and Genetic Disorders Group website. Date of the most recent search of the Group's Cystic Fibrosis Trials Register: 04 May 2017.

We searched the ongoing trials database clinicaltrials.gov (https://clinicaltrials.gov/) using the terms: "physical activity" AND "cystic fibrosis". A further search was run using the terms "exercise" AND "physical activity" AND "training" AND "cystic fibrosis". Date of most recent search: 01 June 2017.

We also searched the WHO ICTRP (http://apps.who.int/trialsearch/) using the terms: "physical activity and cystic fibrosis". Date of the most recent search: 09 August 2017.

Searching other resources

The reference lists of each RCT and of review articles were searched for additional publications that may contain RCTs. Authors of studies included in this review and other experts in the field were contacted and asked for information on other published and unpublished studies.

Data collection and analysis

Selection of studies

Two authors (for the original review JB, FM; from the 2015 update onwards SK, TR) independently assessed the titles and abstracts of identified citations and selected the studies to be included in the review. They excluded non‐RCTs, those studies involving respiratory muscle training exclusively, those which did not have a programme of exercise training and those that did not meet the inclusion criteria, based on screening the abstracts or full text articles. If disagreement arose on the suitability of a study for inclusion in the review, the authors reached a consensus by discussion. The authors recorded any areas of disagreement. The studies that did not fulfil all of the inclusion criteria were excluded and their details listed with the reason for exclusion. A third review author solved all the discrepancies if disagreement or uncertainty of the two authors persisted.

Data extraction and management

Each author (SK, TR) independently extracted data using standard data acquisition forms containing details about: study design (parallel versus multi‐arm; single‐centre versus multicentre, participants and trial characteristics for baseline equality between groups, details on the number of participants screened for eligibility, randomised, analysed, excluded, lost to follow up and dropped out, method of randomisation and allocation concealment, blinding of personnel and outcome assessors, use of stratification, incomplete outcome data, selective reporting, use of intention‐to‐treat analysis); the detailed intervention (aerobic training versus no training; anaerobic training versus no training and a combination of both versus no training; duration of studies, i.e. short term (less than one month) and long term (more than one month) and whether the study was supervised, partially supervised or not supervised); and outcome measures (continuous and dichotomous). If disagreement arose on the quality of a study, the authors reached a consensus by discussion. If disagreement persisted, they contacted a third author. The authors recorded any areas of disagreement. One author (for the original review JB, from the 2015 update onwards TR) entered the data into the Cochrane software Review Manager (Review Manager 2014) and a second author (from the 2015 update onwards SK) reviewed it. The review authors contacted the authors of the included studies in case of unclear or missing data and information.

Assessment of risk of bias in included studies

For the original review two authors judged the methodological quality of the review (JB, FM). From the 2015 update onwards, two authors (SK, TR) independently assessed the risk of bias for each included study according to the Cochrane risk of bias tool (Higgins 2011). In particular, the authors examined details of the randomisation method with sequence generation, allocation concealment, degree of blinding, inclusion and exclusion criteria, dropouts or withdrawals, intention‐to‐treat and detailed statistical analysis. Authors also examined for selective reporting and any other potential sources of bias. The authors judged the risk of bias as low, unclear or high. Unexplained dropouts or an unequal number of dropouts across treatment groups was considered as a potential risk of bias. Likewise, a lack of important information, e.g. on adverse effects, missing data, statistical methods etc., was also considered as potential risk of bias.

Measures of treatment effect

The authors have currently only been able to report continuous outcome data and have calculated the mean differences (MD) with 95% confidence intervals (CIs) where between‐group differences in the mean change from baseline were recorded. When data on the standard deviation (SD) for an individual group were not available, but instead standard error (SE) of the difference was available they used the available calculator within the Review Manager software (Review Manager 2014). Where possible, the published standard error of the mean (SEM) was used, or alternatively, published CIs were taken to estimate SE. If in future updates of this review, different measurement scales are used for an outcome, e.g. different HRQoL scales, the authors plan to analyse the data using the standardised mean difference (SMD) with 95% CIs.

Also, if in future updates of this review, the authors are able to present data for dichotomous outcomes, e.g. mortality or adverse events, they plan to record the number of participants experiencing an event and the total number of participants by group. They will analyse the data and report the odds ratio (OR) (the odds that an outcome will occur given a particular treatment, compared to the odds of the outcome occurring in the absence of that treatment) with 95% CIs.

Unit of analysis issues

The authors have not included any cross‐over studies in this latest version of the review. If future versions of this review include cross‐over studies and if data are presented in published papers from paired statistical analyses or if available information is available to allow us to adjust for within‐patient correlation using the methods described by Elbourne (Elbourne 2002), we will use the generic inverse variance method for data analysis. If appropriate data are not presented to allow adjustment for within‐patient correlation, we will contact study investigators to request these data. If we are unable to make the necessary adjustments, we will describe data from cross‐over studies narratively in the review.

Dealing with missing data

The review authors contacted the investigators of studies included in this review for further study details and data and 12 investigators responded. The investigators of four studies stated that the requested data were not available (Klijn 2004; Michel 1989; Schneiderman‐Walker 2000; Selvadurai 2002). The investigator of a further study confirmed that the extracted data were correct and that no further data were available (Cerny 1989). The investigators of the Hebestreit study stated that they were in the process of writing up the abstract for publication ‐ the review authors have now included this study in the updated review (Hebestreit 2010). One investigator involved in the Phillips study, currently listed under Studies awaiting classification, confirmed that the study has been completed and the review authors updated the information in the table (Phillips 2008). In both publications by Santana‐Sosa, the means and SEs were reported for all variables; the review authors contacted the investigators for additional data (Santana‐Sosa 2012; Santana‐Sosa 2014). Finally, investigators of six studies provided additional raw data for this review update (Beaudoin 2017; Hebestreit 2010; Kriemler 2013; Rovedder 2014; Santana‐Sosa 2012; Santana‐Sosa 2014).

Assessment of heterogeneity

Due to the low number of included studies and variability of interventions, the authors were unable to combine data for any of the listed outcomes; however, if for future updates of this review the authors are able to combine any data, they will measure heterogeneity between studies using the the Chi² test and the I² statistic (Higgins 2003). The Chi² test measures the deviation of observed effect sizes from the underlying overall effect. A low P value (or a large Chi² statistic relative to its degree of freedom) provides evidence of heterogeneity of intervention effects (variation in effect estimates beyond chance). The authors will use a P value of 0.10, rather than the conventional level of 0.05, to determine statistical significance. The I² statistic, as defined by Higgins (Higgins 2011), measures heterogeneity as a percentage where a value:

• 0% to 40%: might not be important;  • 30% to 60%: may represent moderate heterogeneity;  • 50% to 90%: may represent substantial heterogeneity;  • 75% to 100%: considerable heterogeneity.  The importance of the observed value of I² depends on: (i) magnitude and direction of effects; and (ii) strength of evidence for heterogeneity (e.g. P value from the Chi² test, or a CI for I²).

Assessment of reporting biases

The authors assessed relevant bias and selective reporting by comparing the 'Methods' and 'Results' sections from the included papers and trial registries, if available. They have documented this information in the risk of bias tables and figures. If, for future updates of the review, they are able to include and combine a sufficient number of studies (n = 10), the authors will assess publication bias initially by visual inspection of a funnel plot, although they are aware that an asymmetrical funnel plot is not necessarily due to publication bias.

Data synthesis

The review authors used a fixed‐effect model for all outcome parameters using the Review Manager software (Review Manager 2014). The authors were unable to pool studies due to the low number of available studies, the use of different exercise types and different study durations. For future updates, the authors will use a random‐effects model if substantial or considerable heterogeneity exists. The random‐effects model incorporates any between‐study heterogeneity into a meta‐analysis if the number of studies is sufficient. The authors will select the MD when combining data and use forest plots to compare results across studies.

Subgroup analysis and investigation of heterogeneity

If the authors are able to include a sufficient number of studies (about n = 10) and they observe at least moderate heterogeneity in the pooled analyses, they will undertake subgroup analyses of children versus adults, supervised versus unsupervised training and disease severity.

Sensitivity analysis

If the authors are able to include a sufficient number of studies (n = 10) and in order to investigate whether heterogeneity impacted upon the overall pooled effect estimate, the authors plan to apply random‐effects modelling, and compare this with a fixed‐effect model. They also plan a sensitivity analysis with and without quasi‐randomised studies and based on the quality of the studies. The authors will exclude studies with a high risk of bias from the analysis.

Summary of findings tables and quality of the evidence (GRADE)

In a post hoc change in line with current Cochrane guidance, at the 2017 update we added a summary of findings table for each comparison presented in the review (Table 1; Table 2; Table 3). We selected the following seven outcomes to report (chosen based on relevance to clinicians and consumers):

Summary of findings for the main comparison. Summary of findings ‐ Aerobic training versus no physical training.

Aerobic training compared with no physical training for cystic fibrosis
Patient or population: adults and children with cystic fibrosis Settings: Outpatients Intervention: Aerobic training Comparison: No physical training
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect  (95% CI)	No of participants  (studies)	Quality of the evidence  (GRADE)	Comments
	Assumed risk	Corresponding risk
	No physical training	Aerobic training
Exercise capacity: change in VO₂ peak during maximal exercise (mL/min per kg body weight) Follow‐up: from hospital discharge up to 3 years	Short‐term improvements in exercise tolerance during aerobic training were significantly greater than with no physical training at hospital discharge and 1 month after hospital discharge. One study showed no difference between groups at 3 months and 1 study showed a significant improvement in exercise tolerance following aerobic training at 6 months compared to no physical training. No significant longer‐term differences between groups were observed.		NA	170 (4 studies)	⊕⊝⊝⊝  very low^1,2,3
Pulmonary function: change in FEV₁ (% predicted) Follow‐up: from hospital discharge up to 3 years	There were no short‐term differences between groups at hospital discharge or one month after hospital discharge. Two studies showed a significant improvement in pulmonary function during and following aerobic training at 3 months, 6 months and 18 months post‐training compared to no physical training. However, 1 study showed no significant differences in annual change of pulmonary function between groups were observed over 36 months.		NA	187 (5 studies)	⊕⊕⊝⊝  low^1,2
HRQoL: CFQ Quality of Well‐being Scale and perceived 'positive effects.' Follow‐up: one month after hospital discharge up to three years	No significant differences between the groups were shown according to the CFQ. A significant improvement in HRQoL according to the Quality of Well‐being Scale was observed in the aerobic exercise group compared to the no physical training group at 1 month after hospital discharge, MD 0.10 (95% CI 0.03 to 0.17). Positive effects were reported by 43 out of 49 participants (not reported by treatment group).		NA	143 (3 studies)	⊕⊕⊝⊝  low^1,4
CF‐related mortality Follow‐up: NA	Outcome not reported.				NA
Pulmonary exacerbations: number of hospitalisations and number of days in hospital Follow‐up: up to three years	There were no between‐group differences reported for the mean number of hospitalisations or mean number of days in hospital at year 1, 2 and 3.		NA	65 (1 study)	⊕⊕⊝⊝  low^1,5
Diabetic control Follow‐up:NA	Outcome not reported.				NA
Adverse events Follow‐up: up to two years	One study reported that no adverse effects occurred. In the other study, 1 participant in the aerobic training group injured her ankle and missed 2 days of aerobic training. One participant from the control group developed haemoptysis and withdrew from the study.		NA	71 (2 studies)	⊕⊕⊕⊝  moderate¹
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CFQ: Cystic Fibrosis Questionnaire; CI: confidence interval; FEV₁ : forced expiratory volume in 1 second; HRQoL: health‐related quality of life;MD: mean difference; NA: not applicable; VO₂ peak: peak oxygen consumption.
GRADE Working Group grades of evidence  High quality: further research is very unlikely to change our confidence in the estimate of effect.  Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.  Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.  Very low quality: we are very uncertain about the estimate.

Anaerobic training compared with no physical training for cystic fibrosis
Patient or population: adults and children with cystic fibrosis Settings: outpatients Intervention: anaerobic training Comparison: no physical training
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect  (95% CI)	No of participants  (studies)	Quality of the evidence  (GRADE)	Comments
	Assumed risk	Corresponding risk
	No physical training	Anaerobic training
Exercise capacity: change in VO₂ peak during maximal exercise (mL/min per kg BW) Follow‐up: from hospital discharge up to 3 years	One study showed a significant improvement in exercise capacity following anaerobic training at 6 months compared to no physical training. No significant differences between groups were observed at any other time points.		NA	86 (3 studies)	⊕⊕⊝⊝  low^1,2
Pulmonary function: change in FEV₁ (% predicted) Follow‐up: from hospital discharge up to 3 years	Two studies showed a significant improvement in pulmonary function during and following anaerobic training at hospital discharge, 1 month after discharge, 3 months, 6 months and 18 months post‐training compared to no physical training. The second study showed no significant differences in lung function at any time point.		NA	86 (3 studies)	⊕⊕⊝⊝  low^1,2
HRQoL: Quality of Well‐being Scale or HRQoL scale physical function Follow‐up: up to 2 years	No significant differences between groups were observed according to the Quality of Well‐being Scale or HRQoL scale physical function.		NA	64 (2 studies)	⊕⊕⊝⊝  low^1,3
CF‐related mortality Follow‐up: NA	Outcome not reported.				NA
Pulmonary exacerbations Follow‐up: NA	Outcome not reported.				NA
Diabetic control Follow‐up: NA	Outcome not reported.				NA
Adverse events Follow‐up: 2 years	One study reported that no adverse effects occurred.		NA	22 (1 study)	⊕⊕⊕⊝  moderate¹
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: confidence interval; FEV₁ : forced expiratory volume in 1 second; HRQoL: health‐related quality of life; NA: not applicable; VO₂ peak: peak oxygen consumption.
GRADE Working Group grades of evidence  High quality: further research is very unlikely to change our confidence in the estimate of effect.  Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.  Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.  Very low quality: we are very uncertain about the estimate.

Combined aerobic and anaerobic training compared with no physical training for cystic fibrosis
Patient or population: adults and children with cystic fibrosis Settings: outpatients Intervention: combined aerobic and anaerobic training Comparison: no physical training
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect  (95% CI)	No of participants  (studies)	Quality of the evidence  (GRADE)	Comments
	Assumed risk	Corresponding risk
	No physical training	Combined aerobic and anaerobic training
Exercise capacity: change in VO₂ peak during maximal exercise (mL/min per kg body weight) Follow‐up: 12 weeks to two years	A significantly higher VO₂ peak was found in the combined training compared to the no physical training group after 12 to 18 months in 1 study. No significant difference between groups was found at any other time point.		NA	52 (2 studies)	⊕⊕⊝⊝  low^1,2	Two additional studies recruiting 42 participants showed significant group x time interactions for VO₂ peak; however, these results are not included in this review due to concerns over inconsistencies in the data provided to us by the original trial authors.
Pulmonary function: change in FEV₁ (% predicted) or mL Follow‐up: 12 weeks to two years	No significant differences in pulmonary function were observed between treatment groups at any time point.		NA	103 (3 studies)	⊕⊕⊝⊝  low^1,2
HRQoL: CFQ, Medical Outcomes Study‐36 Item Short‐Form Health Survey, SF‐36 Follow‐up: 12 weeks to 2 years	Two studies showed no significant differences in any HRQoL scale. One study showed a significant improvement in subjective health perception in the combined training group after 3 to 6 months and after 12 to 18 months (but not between 6 and 12 months).		NA	93 (3 studies)	⊕⊝⊝⊝  very low^1,2,3
CF‐related mortality Follow‐up: NA	Outcome not reported.				NA
Pulmonary exacerbations Follow‐up: NA	Outcome not reported.				NA
Diabetic control Follow‐up: 12 weeks	Significant differences in some of the parameters were observed in the no physical training group compared to the combined training group and vice versa. Also no significant differences were observed for some parameters.		NA	14 (1 study)	⊕⊝⊝⊝  very low^1,2,3	The study reported a range of metabolic parameters (HbA1c(%), Glucose AUC, Total Insulin AUC, Insulin Sensitivity Index) Plasma Glucose and Plasma Insulin.
Adverse events Follow‐up: NA	Outcome not reported.				NA
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  AUC: area under the curve; CFQ: Cystic Fibrosis Questionnaire; CI: confidence interval; FEV₁ : forced expiratory volume in 1 second; HRQoL: health‐related quality of life; NA: not applicable; VO₂ peak: peak oxygen consumption.
GRADE Working Group grades of evidence  High quality: further research is very unlikely to change our confidence in the estimate of effect.  Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.  Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.  Very low quality: we are very uncertain about the estimate.

Variable	Group	Pre‐training	Post‐training	Detraining	P value (group x time)	Comments
Age (mean (SE)) years	Intervention	11 (3)	‐	‐	‐
Age (mean (SE)) years	Control	10 (2)	‐	‐	‐
Sex (% boys)	Intervention	55	‐	‐	‐
Sex (% boys)	Control	64	‐	‐	‐
VO₂ peak (mean (95% CI)) ml/min per kg body weight	Intervention	n.a.	3.9 (1.8 to 6.1)	‐3.4 (‐5.7 to 1.7)	0.036	Significantly higher in controls at baseline (P = 0.023). Data were presented in a figure in the original publication.
VO₂ peak (mean (95% CI)) ml/min per kg body weight	Control	n.a.	‐2.2 (‐5.3 to 0.1)	‐0.7 (‐4.4 to 5.9)	0.036
Leg press (mean (95% CI)) kg	Intervention	n.a.	24.9 (14.3 to 34.4)	‐1.0 (‐4.1 to 3.3)	< 0.001	Data are reported in a figure in the original publication. Significantly higher in controls at baseline (P = 0.014).
Leg press (mean (95% CI)) kg	Control	n.a.	n.a.	n.a.	< 0.001
Bench press (mean (95% CI)) kg	Intervention	n.a.	10.5 (7.0 to 14.0)	‐1.2 (‐3.6 to 3.0)	< 0.001	Significantly higher in controls at baseline (P = 0.007). Data presented in a figure in the original publication.
Bench press (mean (95% CI)) kg	Control	n.a.	n.a.	n.a.	< 0.001
Seated row (mean (95% CI)) kg	Intervention	n.a.	12.7 (9.2 to 16.0)	‐0.2 (‐3.6 to 3.2)	< 0.001	Significantly higher in controls at baseline (P = 0.009). Data presented in a figure in the original publication.
Seated row (mean (95% CI)) kg	Control	n.a.	n.a.	n.a.	< 0.001
Oxygen saturation at peak exercise (mean (SE))	Intervention	94.9 (0.9)%	95.6 (0.8)%	94.5 (1.2)%	n.a.
Oxygen saturation at peak exercise (mean (SE))	Control	95.7 (0.5)%	96.4 (0.4)%	96.1 (0.5)%	n.a.
FEV₁ (mean (SE)) litres	Intervention	1.87 (0.24)	1.94 (0.23)	1.90 (0.25)	0.769
FEV₁ (mean (SE)) litres	Control	1.77 (0.17)	1.87 (0.15)	1.79 (0.19)	0.769
FVC (mean (SE)) litres	Intervention	2.41 (0.24)	2.49 (0.25)	2.56 (0.29)	0.920
FVC (mean (SE)) litres	Control	2.29 (0.19)	2.36 (0.20)	2.40 (0.24)	0.920
PI_max (mean (SE)) cm H₂O	Intervention	64.0 (5.5)	69.8 (6.8)	75.2 (6.2)	0.797
PI_max (mean (SE)) cm H₂O	Control	61.5 (6.9)	72.2 (7.2)	76.4 (7.5)	0.797
HRQoL score ‐ children's report (median (range))	Intervention	696 (495 ‐ 741)	719 (550 ‐ 734)	‐	0.257	HRQoL was assessed before and after the intervention. P value for comparison pre versus post‐training.
HRQoL score ‐ children's report (median (range))	Control	649 (578 ‐ 768)	638 (461 ‐ 791)	‐	0.257
HRQoL score ‐ parents' report (median (range))	Intervention	896 (688‐1011)	889 (811 ‐ 973)	‐	0.143	HRQoL was assessed before and after the intervention.
HRQoL score ‐ parents' report (median (range))	Control	911 (842 ‐ 1028)	978 (684 ‐ 1059)	‐	0.143	HRQoL was assessed before and after the intervention.
Weight (mean (SE)) kg	Intervention	39.9 (3.5)	40.5 (3.4)	41.4 (3.4)	0.723
Weight (mean (SE)) kg	Control	34.0 (2.6)	35.1 (2.8)	36.2 (3.0)	0.723
BMI (mean (SE)) kg/m²	Intervention	18.4 (1.0)	18.3 (0.7)	18.5 (0.7)	0.959
BMI (mean (SE)) kg/m²	Control	17.2 (0.8)	17.1 (0.8)	17.4 (0.9)	0.959
Fat‐free mass (mean (SE)) %	Intervention	78.1 (2.7)	79.4 (2.8)	78.8 (2.9)	0.115
Fat‐free mass (mean (SE)) %	Control	81.1 (2.5)	80.9 (2.1)	81.1 (2.2)	0.115
Body fat (mean (SE)) %	Intervention	21.9 (2.7)	20.6 (2.8)	21.2 (2.9)	0.115
Body fat (mean (SE)) %	Control	18.9 (2.5)	19.1 (2.1)	18.9 (2.2)	0.115
Compliance with physical training (mean (SE)) %	Intervention	‐	95.1 (7.4)	‐	‐ ‐	73% of children completed all training sessions.
Compliance with physical training (mean (SE)) %	Control	‐	‐	‐	‐ ‐	73% of children completed all training sessions.
Adverse effects	Intervention	‐	‐	‐	‐	No adverse effects occurred during training or maximal exercise testing.
Adverse effects	Control	‐	‐	‐	‐

Health‐related quality of life	Exercise group (n = 19)	Control group (n = 22)	P value
HRQoL scale ‐ physical (median (interquartile range))	6.1 (‐4 to 8)	2.4 (‐10 to 13)	0.742
HRQoL scale ‐ body image (median (interquartile range))	3.3 (‐11 to 22)	3.0 (‐2 to 11)	0.915
HRQoL scale ‐ digestive (median (interquartile range))	‐1.0 (‐4 to 0)	‐0.5 (0 to 0)	0.953
HRQoL scale ‐ respiratory (median (interquartile range))	3.8 (0 to 11)	‐4.7 (‐1 to 7)	0.925
HRQoL scale ‐ emotional (median (interquartile range))	1.2 (‐6 to 6)	‐4.3 (‐13 to 6)	0.458
HRQoL scale ‐ social (median (interquartile range))	‐1.1 (‐11 to 5)	‐1.7 (‐5 to 11)	0.822
HRQoL scale ‐ food (median (interquartile range))	‐0.3 (‐11 to 6)	‐2.0 (‐11 to 0)	0.913
HRQoL scale ‐ treatment (median (interquartile range))	‐2.0 (‐11 to 0)	‐2.5 (‐11 to 11)	0.850
HRQoL scale ‐ vitality (median (interquartile range))	‐1.2 (‐16 to 8)	2.6 (‐8 to 10)	0.579
HRQoL scale ‐ health (median (interquartile range))	1.7 (‐11 to 16)	‐3.0 (‐11 to 0)	0.382
HRQoL scale ‐ weight (median (interquartile range))	4.6 (0 to 33)	12.1 (0 to 11)	0.410
HRQoL scale ‐ social role (median (interquartile range))	0.8 (‐8 to 8)	1.8 (‐2 to 0)	0.935
SF‐36 ‐ functional capacity (median (interquartile range))	2.8 (‐10 to 15)	2.0 (‐11 to 10)	0.916
SF‐36 ‐ physical aspects (median (interquartile range))	11.8 (‐25 to 50)	6.8 (‐6 to 31)	0.705
SF‐36 ‐ pain (mean (median (interquartile range))	‐7.2 (‐28 to 11)	8.0 (7 to 17)	0.100
SF‐36 ‐ general health (median (interquartile range))	3.7 (‐5 to 10)	‐3.5 (‐11 to 5)	0.197
SF‐36 ‐ vitality (median (interquartile range))	1.2 (‐15 to 20)	7.5 (‐1 to 21)	0.416
SF‐36 ‐ social aspects (median (interquartile range))	15.2 (0 to 33)	21.2 (0 to 66)	0.989
SF‐36 ‐ emotional aspects (median (interquartile range))	4.7 (‐12 to 37)	4.5 (‐12 to 25)	0.914
SF‐36 ‐ mental health (median (interquartile range))	‐0.8 (‐12 to 12)	0.9 (‐9 to 13)	0.752

Date	Event	Description
19 October 2017	New citation required but conclusions have not changed	Despite the inclusion of two new studies our conclusions remain the same.
19 October 2017	New search has been performed	A search of the Cystic Fibrosis and Genetic Disorders Review Group's Cystic Fibrosis Trials Register identified 38 new references which were potentially eligible for inclusion in the review. There was one additional reference to an already included study (Schneiderman‐Walker 2000) and six additional references to five already excluded studies (Amelina 2006; del Corral Nunez‐Flores 2011; Kuys 2011; Lima 2014; Salonini 2015). Six references to two new studies has been included (Beaudoin 2017; Douglas 2015) and seven references to five new studies are listed as 'Awaiting classification' (Housinger 2015; Johnston 2004; Lorenc 2015; Mandrusiak 2011; Oliveira 2010). One study with two references is ongoing (Hebestreit 2016) and a total of 16 references to 13 new studies have been excluded (Bieli 2017; Bongers 2015; Calik‐Kutukcu 2016; Chang 2015; Dwyer 2017; Giacomodonato 2015; Haynes 2016; Kriemler 2016; Ozaydin 2010; Patterson 2004; Shaw 2016; Vallier 2016; Wheatley 2015). A search of clinicaltrials.gov identified 11 additional studies. Five studies were added to 'Awaiting classification' (NCT00609050; NCT00792194; NCT02552043; NCT03100214; NCT03109912), one study was added under ongoing studies (NCT02700243) and five studies were excluded (NCT02277860; NCT02715921; NCT02821130; NCT03117764; NCT02875366). A search of the WHO ICTRN identified three additional studies; one is listed as awaiting classification (ACTRN12617001009303) and two have been added under ongoing studies (Donadio 2017; Gupta 2017). From this update we have stated a minimum duration of the intervention as being at least two weeks.
15 June 2015	New citation required but conclusions have not changed	Two authors from the original review have stepped down at this update and a new team of authors have taken on the review. The title of the review has been changed from 'Physical training for cystic fibrosis' to 'Physical exercise training for cystic fibrosis' as the new team felt this better reflected the content of the review. Despite the inclusion of new studies and data in this update of the review, the conclusions remain the same.
15 June 2015	New search has been performed	A search of the Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Register identified 32 new references which were potentially eligible for inclusion in this review. Three new studies (one reference each) were included (Rovedder 2014; Santana‐Sosa 2012; Santana‐Sosa 2014). Two studies previously listed as excluded have been reassessed and moved to included studies with two new references each (although one paper referred to both studies) (Hebestreit 2010; Kriemler 2013). One study has been moved from 'Awaiting classification' to included studies with an additional two references (Hommerding 2015). One was an additional reference to an already excluded study (Kuys 2011). A total of 14 new studies (20 references) were excluded (Alarie 2012; Amelina 2006; Asher 1982; Balfour 1998; del Corral Nunez‐Flores 2011; Dwyer 2008; Gruet 2012; Lima 2014; Lowman 2012; Petrovic 2013; Rand 2012; Reix 2012; Salonini 2015; Vivodtzev 2013). One study (one reference) has been listed as 'Awaiting classification' until we are able to obtain further information (Almajan 2011).
22 May 2012	Amended	Contact details updated.
7 March 2011	New search has been performed	A total of two new references were identified in a search of the Group's CF Trials Register. One study was excluded as it compared Nintendo Wii exercise training to an existing exercise programme and hence did not meet the inclusion criteria (Kuys 2011). The other study did meet the inclusion criteria but outlined in its abstract that recruitment was ongoing and for this reason it has been listed as an ongoing study; results will be included in the review once the study has been completed (Phillips 2008a). In addition some amendments were made to the Background in order to incorporate updated guidelines and a relevant survey.
19 January 2009	Amended	The fourth primary outcome 'mortality' was moved to Secondary outcomes in line with Cochrane Collaboration guidance to limit the number of primary outcomes to three.
5 January 2009	New search has been performed	A search of the Group's Cystic Fibrosis Trials Register did not identify any references to trials which are potentially eligible for inclusion in this review.
12 November 2008	Amended	Converted to new review format.
14 November 2007	Amended	The generic inverse variance method has been used to analyse data which were previously not able to be presented in the 'Statistical Analysis'.    The 'Synopsis' has been replaced by a new 'Plain Language Summary'.
14 November 2007	New search has been performed	The search identified 11 new references. Of these, two were additional references to already excluded studies (Albinni 2004; Edlund 1986). The remaining nine studies did not fulfill the inclusion criteria; four of these studies which seemed eligible from the title, have been excluded on the basis of trial design and are listed under 'Excluded studies' (Acquino 2006; Balestri 2004; Orenstein 2004; Stanghelle 1998).    The study which was previously listed as 'Awaiting assessment' has been moved to the list of excluded studies after correspondence with the study authors (Hebestreit 2003).
13 November 2007	New citation required and conclusions have changed	Substantive amendment
25 May 2005	New search has been performed	A further article has been included (Klijn 2004). The full paper of the trial by Moorcroft (Moorcroft 2004) has also been included. Following publication of this paper, the details about the published abstracts of this trial, previously listed in the 'Characteristics of included studies' table, under Dodd 1998 and Moorcroft 2000 have been listed under Moorcroft 2004. We contacted authors of trials already included in the review regarding confirmation of data and requests for additional data. Their responses have been included in section detailing the search strategy. One trial has been moved from the 'Studies awaiting assessment' section to the 'Excluded studies' section of the review (Tuzin 1998). One trial has been added to the section 'Studies awaiting assessment' section (Hebestreit 2003). The authors have been contacted and have indicated that this study is in preparation for publication.
31 July 2003	Amended	The presentation of the data in MetaView has been re‐formatted.
31 July 2003	New search has been performed	The full paper of the Selvadurai trial has now been included, previously only the abstract of this trial was included in the review (Selvadurai 2002). A further two trials added to the 'Excluded studies' section of the review (Barry 2001; Kriemler 2001).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change in VO₂ peak during maximal exercise (ml/min per kg BW)	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
1.1 At hospital discharge	1	44	Mean Difference (IV, Fixed, 95% CI)	8.53 [4.85, 12.21]
1.2 At 1 month after discharge	1	44	Mean Difference (IV, Fixed, 95% CI)	4.91 [1.13, 8.69]
1.3 At 3 months	2	59	Mean Difference (IV, Fixed, 95% CI)	2.29 [‐2.71, 7.29]
1.4 At 6 months	1	25	Mean Difference (IV, Fixed, 95% CI)	18.33 [8.95, 27.71]
1.5 At 6 months off training	1	22	Mean Difference (IV, Fixed, 95% CI)	9.51 [‐1.32, 20.34]
1.6 At 18 months off training	1	18	Mean Difference (IV, Fixed, 95% CI)	2.86 [‐9.70, 15.42]
2 Change in FEV₁(% predicted)	4		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
2.1 At hospital discharge	1	44	Mean Difference (IV, Fixed, 95% CI)	2.03 [‐2.31, 6.37]
2.2 At 1 month after discharge	1	44	Mean Difference (IV, Fixed, 95% CI)	1.53 [‐2.93, 5.99]
2.3 At 3 months	2	58	Mean Difference (IV, Fixed, 95% CI)	7.21 [2.49, 11.94]
2.4 At 6 months	1	25	Mean Difference (IV, Fixed, 95% CI)	17.17 [8.59, 25.75]
2.5 At 6 months off training	1	23	Mean Difference (IV, Fixed, 95% CI)	16.92 [6.07, 27.77]
2.6 At 18 months off training	1	20	Mean Difference (IV, Fixed, 95% CI)	12.45 [1.27, 23.63]
2.7 Annual rate of change over 36 months	1	65	Mean Difference (IV, Fixed, 95% CI)	2.01 [‐0.06, 4.08]
3 Change in health‐related quality of life	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
3.1 At 1 month after discharge	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 Change in mean power during WAnT (W per kg BW)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
4.1 At 3 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.2 At 6 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.3 At 6 months off training	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.4 At 18 months off training	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5 Change in strength (Newton metres)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
5.1 At hospital discharge	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.2 At 1 month after discharge	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 Change in peak work capacity during maximal exercise (W per kg BW)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
6.1 At 3 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.2 At 6 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.3 At 6 months off training	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.4 At 18 months off training	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
7 Annual rate of change in peak work capacity during maximal exercise over 36 month (%)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
8 Change in treadmill speed (km/h)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
8.1 At 3 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
9 Change in treadmill exercise time (min)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
9.1 At 3 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
10 Change in heart rate (beats per min)	2		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
10.1 At rest at 3 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
10.2 At maximal exercise at 3 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
10.3 At maximal exercise ‐ annual rate of change over 36 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
11 Change in oxygen saturation (%)	2		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
11.1 During maximal exercise at hospital discharge	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
11.2 During maximal exercise at 3 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
11.3 At rest at 3 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
12 Annual rate of change in peak VE over 36 months (L/min)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
13 Change in FVC (% predicted)	4		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
13.1 At hospital discharge	1	44	Mean Difference (IV, Fixed, 95% CI)	0.06 [‐2.55, 2.67]
13.2 At 3 months	2	58	Mean Difference (IV, Fixed, 95% CI)	4.89 [0.69, 9.08]
13.3 At 6 months	1	25	Mean Difference (IV, Fixed, 95% CI)	12.51 [5.90, 19.12]
13.4 At 1 month after discharge	1	44	Mean Difference (IV, Fixed, 95% CI)	‐0.11 [‐2.64, 2.42]
13.5 At 6 months off training	1	23	Mean Difference (IV, Fixed, 95% CI)	15.09 [6.01, 24.17]
13.6 At 18 months off training	1	20	Mean Difference (IV, Fixed, 95% CI)	9.10 [‐0.94, 19.14]
13.7 Annual rate of change over 36 months	1	65	Mean Difference (IV, Fixed, 95% CI)	2.17 [0.47, 3.87]
14 Change in FEF_25‐75 (% predicted)	2		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
14.1 Annual rate of change	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
14.2 At 3 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
15 Change in RV/TLC (%)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
15.1 At 3 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
15.2 At 6 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
15.3 At 6 months off training	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
15.4 At 18 months off training	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
16 Change in FEV₁/FVC (% predicted)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
16.1 At 3 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
17 Change in total physical activity (counts per min)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
17.1 At 3 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
17.2 At 6 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
17.3 At 6 months off training	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
17.4 At 18 months off training	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
18 Change in moderate‐to‐vigorous physical activity (hours per week)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
18.1 At 3 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
18.2 At 6 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
18.3 At 6 months off training	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
18.4 At 18 months off training	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
19 Change in total physical activity (MJ/day)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
19.1 At hospital discharge	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
20 Change in body weight (kg)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
20.1 At hospital discharge	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
20.2 At 1 month after discharge	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
21 Change in BMI (kg/m²)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
21.1 At 3 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
21.2 At 6 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
21.3 At 6 months off training	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
21.4 At 18 months off training	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
22 Change in BMI z score	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
22.1 At 3 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
23 Change in fat‐free mass (kg)	2		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
23.1 At hospital discharge	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
23.2 At 3 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
23.3 At 6 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
23.4 At 1 month after discharge	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
23.5 At 6 months off training	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
23.6 At 18 months off training	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
24 Change in body fat (%)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
24.1 At 3 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
24.2 At 6 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
24.3 At 6 months off training	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
24.4 At 18 months off training	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
25 Annual rate of change of ideal weight for height (%)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
26 Change in triceps skinfold thickness (mm)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
26.1 At 3 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
27 Change in arm muscle circumference (cm)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
27.1 At 3 months	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]

Outcome or subgroup title	No. of studies	Statistical method	Effect size
1 Change in VO₂ peak during maximal exercise (ml/min per kg BW)	2	Mean Difference (Fixed, 95% CI)	Totals not selected
1.1 At 12 weeks	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 At 3 ‐ 6 months	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
1.3 At 6 months off training	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
1.4 At 12 ‐ 18 months off training	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Change in FEV₁ (% predicted)	3	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.1 At 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 At 3 months	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.3 At 3 ‐ 6 months	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.4 At 6 months off training	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.5 At 12 ‐ 18 months off training	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Annual change in FEV₁ (mL)	1	Mean Difference (Fixed, 95% CI)	Totals not selected
3.1 At 12 months	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
4 Change in subjective health perception (CFQ‐R)	1	Mean Difference (Fixed, 95% CI)	Totals not selected
4.1 At 3 ‐ 6 months	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
4.2 At 6 months off training	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
4.3 At 12 ‐ 18 months off training	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
5 Change in Quality of Life: CFQ‐R	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
5.1 Physical Functioning at 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.2 Vitality at 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.3 Emotional state at 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.4 Eating disturbances at 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.5 Treatment burden at 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.6 Health perception at 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.7 Social limitations at 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.8 Body image at 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.9 Role limitations at 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.10 Weight problems at 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.11 Respiratory symptoms at 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.12 Digestion symptoms at 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 Change in peak power during WAnT (W per kg body weight)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
6.1 At 3 ‐ 6 months	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.2 At 6 months off training	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.3 At 12 ‐ 18 months off training	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
7 Change in mean power during WAnT (W per kg body weight)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
7.1 At 3 ‐ 6 months	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
7.2 At 6 months off training	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
7.3 At 12 ‐ 18 months off training	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
8 Change in muscle strength (all limbs) (1RM test)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
8.1 Right upper limb at 3 months	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.2 Left upper limb at 3 months	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.3 Right lower limb at 3 months	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.4 Left lower limb at 3 months	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
9 Change in muscular strength ‐ leg press (kg; 1 RM test)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
9.1 At 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
10 Change in Muscular Strength ‐ Chest press (kg; 1 RM test)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
10.1 At 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
11 Change in Muscular Strength ‐ Latpull down (kg; 1 RM test)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
11.1 At 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
12 Change in Muscular Strength ‐ Biceps curl (kg; RM test)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
12.1 At 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
13 Change in Muscular Endurance ‐ Number of push ups	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
13.1 At 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
14 Change in Muscular Endurance ‐ Number of sit ups	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
14.1 At 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
15 Change in Muscular Endurance ‐ Flexibility (cm)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
15.1 At 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
16 Change in Muscular Endurance ‐ hand grip strength (kg)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
16.1 At 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
17 Change in peak work capacity during maximal exercise (W per kg BW)	1	Mean Difference (Fixed, 95% CI)	Totals not selected
17.1 At 3 ‐ 6 months	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
17.2 At 6 months off training	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
17.3 At 12 ‐ 18 months off training	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
18 Change in functional exercise capacity	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
18.1 6MWT distance (m) at 3 months	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
18.2 6MWT distance (% predicted) at 3 months	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
19 Change in peak heart rate during 6MWT (beats/min)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
19.1 At 3 months	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
20 Annual change in peak heart rate (beat/min)	1	Mean Difference (Fixed, 95% CI)	Totals not selected
20.1 Constant load bicycle ergometry (at 1 year)	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
20.2 Constant load arm ergometry (at 1 year)	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
21 Annual change in VE (L/min)	1	Mean Difference (Fixed, 95% CI)	Totals not selected
21.1 Constant load bicycle ergometry (at 1 year)	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
21.2 Constant load arm ergometry (at 1 year)	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
22 Change in peak ventilation (VE) during maximal exercise	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
22.1 At 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
23 Annual change in lactate (mmol/l)	1	Mean Difference (Fixed, 95% CI)	Totals not selected
23.1 Constant load bicycle ergometry (at 1 year)	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
23.2 Constant load arm ergometry (at 1 year)	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
24 Change in RR during 6MWT (breaths/min)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
24.1 At 3 months	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
25 Annual change in RR (breaths/min)	1	Mean Difference (Fixed, 95% CI)	Totals not selected
25.1 Constant load bicycle ergometry (at 1 year)	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
25.2 Constant load arm ergometry (at 1 year)	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
26 Annual change in RER	1	Mean Difference (Fixed, 95% CI)	Totals not selected
26.1 Constant load bicycle ergometry (at 1 year)	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
26.2 Constant load arm ergometry (at 1 year)	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
27 Change in oxygen saturation (%)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
27.1 At rest (at 3 months)	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
27.2 During 6MWT (at 3 months)	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
28 Change in Borg breathlessness score	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
28.1 At rest (at 3 months)	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
28.2 During 6MWT (at 3 months)	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
29 Annual change in Borg breathlessness score	1	Mean Difference (Fixed, 95% CI)	Totals not selected
29.1 Constant load bicycle ergometry (at 1 year)	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
29.2 Constant load arm ergometry (at 1 year)	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
30 Change in Borg fatigue score	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
30.1 At rest (at 3 months)	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
30.2 During 6MWT (at 3 months)	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
31 Annual change in Borg muscle effort	1	Mean Difference (Fixed, 95% CI)	Totals not selected
31.1 Constant load bicycle ergometry (at 1 year)	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
31.2 Constant load arm ergometry (at 1 year)	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
32 Change in FVC (% predicted)	3	Mean Difference (Fixed, 95% CI)	Totals not selected
32.1 At 12 weeks	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
32.2 At 3 months	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
32.3 At 3 ‐ 6 months	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
32.4 At 6 months off training	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
32.5 At 12 ‐ 18 months off training	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
33 Annual change in FVC (mL)	1	Mean Difference (Fixed, 95% CI)	Totals not selected
33.1 At 1 year	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
34 Change in RV/TLC (%)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
34.1 At 3 ‐ 6 months	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
34.2 At 6 months off training	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
34.3 At 12 ‐ 18 months off training	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
35 Change in Total Energy Expenditure (k/cal)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
35.1 At 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
36 Change in the Number of Steps	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
36.1 At 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
37 Change in Physical Activity (%)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
37.1 At 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
38 Change in vigorous physical activity (hours per week)	1	Mean Difference (Fixed, 95% CI)	Totals not selected
38.1 At 3 ‐ 6 months	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
38.2 At 6 months off training	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
38.3 At 12 ‐ 18 months off training	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
39 Change in body weight (kg)	2	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
39.1 At 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
39.2 At 3 ‐ 6 months	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
39.3 At 6 months off training	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
39.4 At 12 ‐ 18 months off training	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
40 Change in BMI (kg/m²)	3	Mean Difference (Fixed, 95% CI)	Totals not selected
40.1 At 12 weeks	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
40.2 At 3 ‐ 6 months	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
40.3 Annual change	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
40.4 At 6 months off training	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
40.5 At 12 ‐ 18 months off training	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
41 Change in sum of four skinfolds (mm)	1	Mean Difference (Fixed, 95% CI)	Totals not selected
41.1 At 3‐6 months	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
41.2 At 6 months off training	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
41.3 At 12‐18 months off training	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
42 Change in body fat (%)	2	Mean Difference (Fixed, 95% CI)	Totals not selected
42.1 At 12 weeks	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
42.2 At 3 ‐ 6 months	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
42.3 At 6 months off training	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
42.4 At 12 ‐ 18 months off training	1	Mean Difference (Fixed, 95% CI)	0.0 [0.0, 0.0]
43 Change in fat‐mass (kg)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
43.1 At 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
44 Change in fat‐free mass (kg)	2	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
44.1 At 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
44.2 At 3 ‐ 6 months	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
44.3 At 6 months off training	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
44.4 At 12 ‐ 18 months off training	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
45 Change in metabolic parameters (HbA1c (%))	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
45.1 At 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
46 Change in metabolic parameters (Glucose AUC)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
46.1 At 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
47 Change in metabolic parameters (Total Insulin AUC)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
47.1 At 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
48 Change in metabolic parameters (Insulin Sensitivity Index)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
48.1 At 12 weeks	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
49 Change in Plasma Glucose (mmol/L)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
49.1 After 0 minutes	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
49.2 After 30 minutes	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
49.3 After 60 minutes	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
49.4 After 90 minutes	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
49.5 After 120 minutes	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
50 Change in Plasma Insulin (µU/mL)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
50.1 After 0 minutes	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
50.2 After 30 minutes	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
50.3 After 60 minutes	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
50.4 After 90 minutes	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
50.5 After 120 minutes	1	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]

Methods	Design: single‐centre, open‐label, parallel RCT (the record on clinicaltrials.gov states cross‐over design, but this is not evident from published paper). Inclusion criteria: participants with CF; age > 18 years; sedentary (less than 100 min/week of structured exercise assessed by physical activity questionnaire and phone interview; FEV₁ > 40 % predicted; clinically stable for the last 6 weeks; IGT; CFRD without pharmacological treatment or elevated 1‐h plasma glucose concentration during an oral glucose tolerance test (indeterminate 1‐h glucose concentration of > 11.0 but 2‐h plasma glucose concentration < 7.8 mmol/L^‐1).  Exclusion criteria: current pulmonary exacerbation; use of oral or intravenous corticosteroids; low SaO₂ during exercise; history of haemoptysis in the last 6 weeks.
Participants	14 participants with CF. Group demographics Exercise group (n = 8): mean (range) age 31.9 (24; 41) years. Control groups (n = 6): mean (range) age 35.5 (22; 57) years.
Interventions	12‐week combined aerobic and resistance training study. Exercise group: aerobic and resistance training exercises 3x per week for about 20 ‐ 40 minutes with a day off between the training sessions (in total 36 training sessions). Exercise intensity and volume were progressively increased. Participants recorded their training sessions in a diary. Once every 4 weeks, participants received a supervised training session and a phone call on a weekly basis. Aerobic training consisted of walking, jogging, cycling and elliptic trainer. Training intensity progressively increased throughout the study, starting at 60% of VO₂ peak during the first 4 weeks. Thereafter, intensity was increased to 70% (week 5 ‐ 8) and 80% (week 9 ‐ 12) of VO₂ peak. Resistance training consisted of 5 ‐ 7 exercises for large muscle groups using the own body weight, free weights and elastic bands (goal 8 ‐ 12 repetitions with a weight of 30% ‐ 50% of one repetition maximum). Exercise intensity and volume were progressively increased. Control group: no information was reported in the original publication. Detailed information on control intervention is available on clinicaltrials.gov.
Outcomes	Included in this study were: pulmonary function (FVC, FEV₁); metabolic parameters (HbA1c, plasma glucose area under the curve, insulin sensitivity index, plasma insulin area under the curve (0 ‐ 120 min); exercise capacity measured by a cycle cardiopulmonary exercise test (VO₂ peak and VE at VO₂ peak); muscle strength (leg press, chest press, latpull down, biceps curl) and endurance (push‐up, sit‐up, flexibility, handgrip strength); body composition (bodyweight, BMI, body fat and fat‐free mass); HRQoL and objectively measured physical activity (steps per days; energy expenditure) and assessed by questionnaire. Further, inflammatory markers were measured in this study (e.g., IL‐1; IL‐6; IL‐8; YKL‐40 and CRP‐hs) but inflammatory biomarkers are not outcomes relevant for this review.
Notes	Study registration: The study was registered as cross‐over trial (Clinicaltrials.gov NCT02127957) but results were reported as parallel‐design study. The authors confirmed that they had to stop the study due to recruitment problems. The authors presented only results from the first study phase (12 weeks). Information provided on clinicaltrials.gov "Intervention Model: Crossover Assignment" "Following the visit #6, patients in the control group will be invited to participate in a second study phase to participate in supervised exercise program. This participation will involve an additional 12 weeks of follow‐up, which included the same visit as Group 1 with exercises. In this case, to simplify participation and reduce the volume of blood collected, the final visit (#5) of the project will also be the first visit of exercises phase. This part of study, involves 2 supervised training sessions and 8 follow up phone call. The exercises program will be performed three times per week for about one hour."
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomly assigned open‐label study with two parallel arms. Randomisation was conducted in blocks by gender with a ratio of 2:2. No details given for generation of sequence.
Allocation concealment (selection bias)	Unclear risk	Not discussed.
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Not possible to blind participants to intervention.
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Unclear whether outcome assessors blinded.
Incomplete outcome data (attrition bias)   All outcomes	High risk	At screening,1 participant could not be randomized due to an adverse event during cardiopulmonary exercise testing. There were 3 dropouts *post‐randomisation* (18%). 2 participants dropped out due to a pulmonary exacerbation; group allocation for these 2 participants was not reported. 1 patient was excluded due to non‐compliance with the exercise program, but the criteria for the decision of "non‐compliance" were not reported in the publication. The study was registered as crossover study but results for the second study part were not presented.
Selective reporting (reporting bias)	High risk	Heart rate and SaO₂ were measured during cardiopulmonary exercise testing, but results were not reported. The second study phase was not reported in the original publication.
Other bias	High risk	Sample size Information on sample size and recruitment goals differ between the information provided under Clinicaltrials.gov and the final publication. This study aimed to recruit 24 participants (12 exercise group, 12 control group), see Clinicaltrials.gov, NCT02127957. The recruitment goal was not achieved (N = 18 were recruited but only 17 randomised ), but no information was provided in the final paper. According to the power calculation provided in the original publication, 18 participants (9 per group) were required for the analysis. Finally, 14 participants completed the study so the study is likely to be underpowered. Statistical analyses The authors reported pre‐post within‐group changes and no between‐group differences as would be appropriate for a RCT. We received raw data from the authors and calculated between‐group differences for plasma glucose and plasma insulin values during the oral glucose tolerance test. Our results differ compared to the results reported in the original publication. The initial power analysis, aiming to demonstrate a difference of 1.5 mmol/L in plasma glucose levels 120 minutes after ingestion of the glucose solution after exercise training required a study sample of 18 participants (9 per group). Finally, only 14 participants completed the study that reduces the statistical power to observe a difference between the interventions in the study. Control intervention In the original publication, no information was provided on the control intervention. We noticed discrepancies between the registered (clinicaltrials.gov) and published trial design (cross‐over versus parallel‐group design).

Methods	Design: single‐centre, parallel RCT during hospital admission for acute exacerbation. Inclusion criteria: participants with CF who were admitted to the hospital for treatment of an acute exacerbation. Those who were able to perform a pulmonary function test and provided written informed consent (assumed patient or parental depending on age) were included. Exclusion criteria: not described.
Participants	17 participants with CF.  Group demographics Exercise group (n = 9): mean (SD) age 15.4 (4.9) years. Bronchial hygiene group (n = 8): mean (SD) age 15.9 (4.9) years.
Interventions	Short‐term aerobic study.  Group 1: 2 cycle ergometer sessions and 1 bronchial hygiene session per day during admission: mean (SD) 13 (3) days. Group 2: 3 bronchial hygiene sessions per day during admission: mean (SD) 13 days (2.6 days).
Outcomes	Included in this study were: pulmonary function (FVC, ERV, IC, FEV₁, FEF_25‐75,RV, FRC, TLC, Raw, SGAW, SaO₂, and PFS); exercise performance during cycle ergometry with load increased by 0.3 W/kg every 2 minutes until participant could continue no longer (SaO₂, peak load, EMG activity, peak HR, peak VE to peak load ratio, peak HR to peak load ratio); cough (15 min post treatment session); sputum (wet and dry weight, volume).
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Described as randomised but no details of the method.
Allocation concealment (selection bias)	Unclear risk	Not discussed.
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Not possible to blind participants to intervention. Unclear whether personnel was blinded.
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Unclear whether outcome assessors blinded.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	There were no dropouts.
Selective reporting (reporting bias)	Low risk	All outcomes detailed in methods were reported in results. Data reported for all time points.
Other bias	Unclear risk	Stated the inclusion criteria but not the exclusion criteria. Pulmonary function values FEV₁ and FEF_25‐75 were significantly lower in the control compared to the training group at admission. Clearly described statistical analysis methods.

Methods	Design: single‐centre RCT (INSPIRE‐CF) in the UK; duration 24 months. Powered to show changes in primary outcome measure of FEV₁ z score after 24 months (66 participants needed). Inclusion criteria: not described in abstract. Exclusion criteria: not described in abstract.
Participants	Recruited 71 participants with CF; age 6 to 15.5 years; mean (SD) FEV₁ 89 (16) % predicted. Group demographics Intervention group (n = 37). Control group (n = 34). 67 children completed the study.
Interventions	Intervention group: standard specialist care including weekly exercise training. Control group: standard specialist care without weekly exercise training.
Outcomes	Included in this study were: average and individual exercise training attendance rates (%); reason for non‐attendance to the exercise training programme. At baseline,12 and 24 months the following outcomes were measured: multiple‐breath washout (lung clearance index); spirometry (FEV₁, FVC, FEV₁/FVC (measured in litres and converted to z scores)); growth parameters (height; weight; BMI (measured in cm²; kg; and converted to z scores); cardiopulmonary exercise test (Bruce protocol): at peak and anaerobic threshold (VO₂ peak; work rate (power); V_E/VCO₂; RER; HRmax; SaO₂; 10m modified shuttle walk test (25‐level version) (distance in meters; level achieved); HRmax; SaO₂; Cystic Fibrosis Questionnaire (CFQ UK version). At 6 months only spirometry and the 10 m modified shuttle walk test were repeated.
Notes	INSPIRE‐CF is an 24‐month exercise training study that investigates the effects of an individually tailored and supervised exercise training programme on lung function, exercise capacity and HRQoL for children with CF. This abstract evaluates the participation in the intervention group in the first year of the study (study has been completed, but not yet published in full). Study was powered to show changes after 24 months in primary outcome measure of FEV₁ z score; Required 66 participants.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Described as randomised but no details of the method. Randomised by minimisation to one of the two groups (after baseline testing) by an independent blinded medical statistician using the SiMin software package (Wade 2006).
Allocation concealment (selection bias)	Unclear risk	Not discussed.
Blinding of participants and personnel (performance bias)   All outcomes	Low risk	Not possible to blind participants to intervention. Investigators confirmed that lung function (spirometry and multiple inert gas washout tests), and cycle ergometer cardiopulmonary exercise tests were performed by clinicians who were not made aware of the randomised grouping of the children.
Blinding of outcome assessment (detection bias)   All outcomes	Low risk	Investigators confirmed blinded outcome assessment.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	4 participants dropped out: 1 from the control group at 6 months (social concerns); 3 from the intervention group at 12 months (1 due to moving to a new area and changing hospitals; 2 because they no longer wished to exercise).
Selective reporting (reporting bias)	Unclear risk	This is an abstract so unable to assess if all outcome used in methods were reported in results. Unable to assess if data were reported for all time points.
Other bias	Unclear risk	None identified based on limited information available.

Methods	Design: multicentre parallel RCT; duration 24 months (6‐month intervention and long‐term, open follow‐up period). Inclusion criteria: participants with CF; age > 12 years; FEV₁> 35 % predicted; ability to perform physical activities. Exclusion criteria: non CF‐related chronic diseases and CF‐related conditions posing an increased risk to the participant when exercising. These were specifically oesophageal varicosis, pulmonary bullae, a < 80% drop in arterial oxygen saturation with exercise and signs of pulmonary hypertension on electrocardiogram and/or echocardiogram.
Participants	38 participants with CF. Group demographics Exercise group (n = 23): mean (SD) age 19.5 (6.4) years. Control group (n = 15): mean (SD) age 19.4 (5.3) years.
Interventions	Long‐term partially supervised conditioning programme. Group 1 (intervention): exercise intervention with endurance‐type and strengthening exercises. Participants agreed to increase their vigorous physical activities by a minimum of 3x 60 min per week in the first 6 months of the study. An individual exercise plan was devised for participants; activity counselling was stopped after the first 6 months and participants were encouraged to maintain or further increase their physical activity level. Group 2 (control): participants told to keep their activity level constant during the first 12 months of the study. During the second year (period from 12 ‐ 24 months) they were free to change their activity behaviour.
Outcomes	Included in this study were: VO₂ peak; peak workload; Wingate Anaerobic Test (PP, MP); FVC; FEV₁; RV/TLC; vigorous physical activity; skinfold thickness; body fat; fat‐free mass and HRQoL. Outcomes were measured at baseline and after 3, 6, 12, 18 and 24 months.
Notes	This study is a full text article of the Hebestreit 2003 abstract. The author provided additional raw data for this review were not reported in detail in the original paper (e.g. data for RV/TLC, bodyweight, BMI, body fat and fat‐free mass). The control group in this study is also used in the Kriemler study (Kriemler 2013).
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	40 folded paper tickets were put into a bag with a 3:2 ratio, i.e. 24 tickets for the intervention group and 16 for the control group. Participants drew a ticket at random and the drawn ticket was then destroyed. Principal investigator was aware of the number of lots in the bag.
Allocation concealment (selection bias)	High risk	Participants drew a folded paper ticket from an opaque bag with closed eyes. In case that all lots have been drawn out by 1 study group, allocation concealment would no longer exist.
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Not possible to blind participants to intervention. Unclear whether personnel was blinded.
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Outcome assessors were not blinded with respect to the participants' group allocation for VO₂ peak and skinfold measurements.
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	5 participants dropped out during the first 12 months of the study: 3 gave no reason, 1 joined another study and 1 moved away. At 18 and 24 months, dropout rate was 13% and 26% respectively. Dropouts were balanced between groups. Reasons for drop out were not recorded. Intention‐to‐treat was not performed.
Selective reporting (reporting bias)	Unclear risk	Anaerobic capacity (PP, MP) was only reported for 18 ‐ 24 months follow up (non‐significant) and results for HRQoL are only presented for the scale 'physical functioning'. No effects were observed for all other HRQoL scales.
Other bias	Unclear risk	Financial support (max 200 Euro) was offered for intervention group participants to foster the realisation of the exercise training plan.

Methods	Design: Single‐centre parallel RCT; 3‐month duration Inclusion criteria: participants with CF aged 7 ‐ 20 years; stable disease, no signs of exacerbation of respiratory symptoms in last 15 days. Exclusion criteria: cognitive impairment, non CF‐related bone and muscle abnormalities, heart disease with haemodynamic instability.
Participants	34 participants with CF (20 boys, 14 girls). Group demographics Exercise group (n = 17): mean (SD) age 13.4 (2.8) years. Control group (n = 17): mean (SD) age 12.7 (3.3) years.
Interventions	Aerobic exercise program based on verbal and written guidelines. Exercise group: participants took part in a 3‐month aerobic exercise training program based on verbal and written guidelines. The program included exercises such as jogging, swimming, walking, ball games and stretching exercises. Participants were told to practice the exercises at least twice a week for at least 20 min. No recommendations were provided regarding exercise intensity. Participants received telephone calls every 2 weeks and instructions were provided by one of the authors. Control group: Participants were instructed about aerobic exercises once at baseline according to the CF center routine.
Outcomes	Included in this study were: VO₂ peak; FVC; FEV₁; FEV₁/FVC; FEF_25‐75; HRQoL; self‐reported physical activity; body weight; BMI z score; triceps skinfold thickness; arm muscle circumference; SaO₂ at rest and peak exercise, treadmill time; treadmill speed; peak HR; Borg breathlessness and fatigue.
Notes	The sample size was estimated based on a mean (SD) change of 18.1 (13.8) points in the physical score of the HRQoL questionnaire. The estimated sample size was 15 participants in each group (95% power at a 5% level of significance). 2 more participants were included in each group to account for potential dropouts. Another study from the same group using the same aerobic exercise program was published recently (Schindel 2015). The responsible author of this publication confirmed that the vast majority of included participants were the same as in the Hommerding study (Hommerding 2015). There were only marginal differences in lung function (FEV₁, FVC and FEF_25‐75) compared to the Hommerding study for which reasons we decided not to include lung function data in this review.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants were allocated to the intervention or control group in blocks of 6. A computer‐based program was used for randomisation.
Allocation concealment (selection bias)	Unclear risk	Not discussed.
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Not possible to blind participants to intervention. Unclear whether personnel was blinded.
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Unclear whether outcome assessors blinded.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	No drop outs were reported during the study.
Selective reporting (reporting bias)	Unclear risk	Blood pressure was measured prior to and after cardiopulmonary exercise testing but not reported. HR at rest and SaO₂ at peak exercise were measured but results were not reported at baseline.
Other bias	Unclear risk	No validity criteria for maximal performance during cardiopulmonary exercise testing were reported in the methods. The mean (SD) peak heart rate reached during the exercise test was 157.1 (38.5) beats per min in the training group and 167.7 (20.8) beats per min in the control group, indicative of a submaximal effort. This likely underestimates the true VO₂ peak of the study participants.

Methods	Design: Single‐centre, parallel RCT, 3‐month duration. Inclusion criteria: Participants with CF aged 9 ‐ 18 years; a stable clinical condition (i.e., no need for oral or IV antibiotic treatment in the 3 months prior to testing); the absence of musculoskeletal disorders; and an FEV₁ > 30 % predicted. Exclusion criteria: not specified.
Participants	20 participants with CF (stable disease) completed the study.  Group demographics Group 1 (training) (n = 11): mean (SD) age 13.6 (1.3) years. Group 2 (control) (n = 9): mean (SD) age 14.2 (2.1) years.  3 participants dropped out; 1 withdrew from the training group for practical reasons (training group) and 2 from the control group as they did not complete assessments due to pulmonary exacerbations.
Interventions	Long‐term anaerobic study (12 weeks). Group 1: anaerobic exercise (2 days per week for 30 ‐ 45 min). Group 2: normal daily activities.
Outcomes	Included in this study were: BMI; FEV₁; FVC; FEF_25‐75; RV/TLC; Wingate Anerobic Test (PP, MP); VO₂ peak; peak working capacity; VCO₂; VE; RER; lactate; habitual activity estimation scale; HRQoL; fat‐free mass. Outcomes measured again at 12 weeks follow up.
Notes	To achieve a difference in PP per kg body weight of 10% with an SD of 0.8 W/kg and a statistical power of 80%, it was calculated that 8 participants had to be included in each study group.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Described as randomised, but no details of the method.
Allocation concealment (selection bias)	Low risk	Allocation concealed in opaque envelopes.
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Not possible to blind participants to intervention. The primary researcher was blinded but their role in the study is unclear.
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	The primary researcher was blinded, but it is unclear whether this researcher was responsible for outcome assessment.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Clear description and details about dropouts.  3 participants dropped out: 1 participant from the training group withdrew for practical reasons; 2 from the control group did not complete assessments due to pulmonary exacerbations. Intention‐to‐treat analysis was not performed.
Selective reporting (reporting bias)	Unclear risk	Results for HRQoL are only presented for the scale 'physical functioning' which was significantly higher in the training group after the 12‐week training period. No change in this HRQoL scale was observed in the control group after 12‐weeks. No significant effects were observed for any other HRQoL scales. Data were not reported in detail.
Other bias	Unclear risk	Clearly stated inclusion criteria but exclusion criteria were not reported. Described statistical methods used in analysis.

Methods	Design: multi‐centre, parallel RCT with 3 arms; 24 months (6‐month intervention and long‐term, open follow‐up period). Inclusion criteria: diagnosis of CF; aged 12 years and over; a FEV₁ % predicted ≥ 35%; ability to perform physical activity without harm. Exclusion criteria: non‐CF related chronic diseases and conditions posing an increased risk to the participant when exercising.
Participants	39 participants with CF split into 3 groups. Group demographics Group 1 (aerobic training) (n = 17): mean (95% CI) age 23.8 (21.5 to 26.5) years. Group 2 (strength training) (n = 12): mean (95% CI) age 19.0 (16.0 to 22.0) years. Group 3 (control) (n = 10): mean (95% CI) age 20.3 (17.0 to 23.6) years. A separate control group from a parallel study (Hebestreit 2010) was added due to an unusual deterioration of physical health in the control group in this study (n = 15), mean (95% CI) age 19.5 (16.8 to 22.2) years.
Interventions	Long‐term exercise study. Group 1: participants consented to perform 3 aerobic training sessions per week of 30 ‐ 45 min duration for the first 6 months and received support which was stopped thereafter. Group 2: participants consented to perform 3 strength training sessions per week of 30 ‐ 45 min duration for the first 6 months and received support which was stopped thereafter. Group 3: participants in the control group were told to keep their activity level constant. Free access to a fitness centre for 1 year was offered after the first study year.
Outcomes	Included in this study were: FEV₁; FVC; RV/TLC; VO₂ peak; peak workload; Wingate anaerobic test (PP, MP); physical activity; body fat; fat‐free mass.
Notes	This study is a full text article of the Kriemler 2001 and Hebestreit 2003 abstracts. The control group experienced a deterioration of physical health during the study. In the original paper, a second control group from a German study with similar design and methods (Hebestreit 2010) was used for comparisons.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Participants were randomly assigned by a lot that was drawn from an opaque bag with closed eyes. Investigator was aware of the number of lots in the bag.
Allocation concealment (selection bias)	High risk	Participants drew a lot from an opaque bag with closed eyes. In case that all lots have been drawn out by one study group, allocation concealment would no longer exist.
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Not possible to blind participants to intervention. Unclear whether personnel was blinded.
Blinding of outcome assessment (detection bias)   All outcomes	Low risk	Outcome assessors were blinded for pulmonary function testing (primary outcome FEV₁). Outcome assessors were not involved in supervision and delivery of the intervention.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Clear description and details about excluded participants and drop‐outs. 3 participants were excluded at baseline due to FEV₁ below 35% predicted. 8 participants dropped out at different time points (exacerbation n = 1; non‐compliance n = 2; death n = 2; unclear reasons n = 3). 2 of the participants that dropped out for unclear reasons were in the control group and one was in the aerobic training group. Dropout rate was 21%. Intention‐to‐treat analysis was not performed.
Selective reporting (reporting bias)	Low risk	All outcome detailed in methods were reported in results except HRQoL (secondary outcome) which was mentioned to be reported separately. In the meantime published as Hebestreit et al. BMC Pulm Med. 2014, 27;14:26. HRQoL data were pooled from two intervention studies (Hebestreit 2010; Kriemler 2013) and results were presented for baseline and 6‐month follow up.
Other bias	Unclear risk	Clearly stated inclusion and exclusion criteria and described statistical methods used in analysis. Due to the deterioration of physical health in the control group, the results of this study should be interpreted with caution.

Methods	Design: single‐centre, parallel RCT; 1‐year duration. Inclusion criteria: participants with CF who were willing to participate were recruited from a population of 150 attending the adult CF centre in Manchester at the time of the study. All participants had documented CF on the basis of clinical history plus either an increased sweat chloride or abnormal genetic testing. Exclusion criteria: participation in another clinical trial; pregnancy; transplant listing, or clinical cor pulmonale.
Participants	51 participants with CF were randomised; 42 completed the study.  Group demographics Exercise group (n = 30): mean (SD) age 23.5 (6.4) years. Control group (n = 18): 23.6 (5.5) years.  3 participants dropped out at the start of programme: 1 from training group due to failure to attend on initial assessment; and 2 in the control group were withdrawn due to ill health. A further 6 participants dropped out during the 1‐year period.
Interventions	Long‐term aerobic and anaerobic study over 1 year.  Group 1: unsupervised exercise (based on individual preferences general aerobic exercises for lower body and weight training for upper body) 3 times per week. Group 2: control (continue with usual activities).
Outcomes	Included in this study were: FEV₁; FVC; whole blood lactate; RER; heart rate; Borg breathlessness and muscle effort; VE, RR peak for arm and bicycle ergometry at 55% maximal workload; BMI and weight.
Notes	This study is a full text article of Dodd 1998 and Moorcroft 2000 abstracts.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomised to either active or control groups in a ratio of 3:2. A stratified randomisation in blocks (block size not stated) was used to balance the groups for FEV₁, sputum colonisation by Burkholderia cepacia and gender. No details of method reported.
Allocation concealment (selection bias)	Unclear risk	Not discussed.
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Not possible to blind participants to intervention. Unclear whether personnel was blinded.
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Unclear whether outcome assessors blinded.
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	3 participants dropped out at the start of programme: 1 from training group due to failure to attend on initial assessment; and 2 in the control group were withdrawn due to ill health. A further 6 participants dropped out during the 1‐year period. Reasons for dropout were not clearly reported. After 1 year, overall dropout rate was 18% and balanced among the groups (19% in the intervention and 15% in the control group). Intentition‐to‐treat analysis was not performed. Missing data were treated by omission and only data for those who completed study presented.
Selective reporting (reporting bias)	Low risk	All outcome detailed in methods were reported in results. Data reported for all time points.
Other bias	Low risk	Clearly stated inclusion and exclusion criteria and described method of statistical analysis used.

Methods	Design: single‐centre, parallel RCT; 3‐months home‐based exercise programme. Inclusion criteria: participants diagnosed with CF in accordance with the criteria of the consensus;aged ≥16 years; ≥ 30 days of clinical respiratory disease stability. Exclusion criteria: participants who refused to take part in the study; pregnant ladies; individuals with heart disease, orthopaedic or traumatological problems.
Participants	41 participants with CF. Group demographics Exercise group (n = 22): mean (SD) age 23.8 (8.3) years. Control group (n = 19): mean (SD) age 25.4 (6.9) years. 2 study participants in the exercise group could not be assessed at the 3‐months follow up due to lung transplant assessment.
Interventions	3‐month home‐based exercise programme. Group 1: participants received printed guidance for aerobic and muscle strengthening exercises and were advised to perform the programme on a daily basis. Weekly telephone contacts were performed during the 3‐month period. Group 2: control group participants received standard programme without any specific exercise instructions.
Outcomes	Included in this study were: HRQoL; FEV₁; FVC; walking distance (6MWT); SaO₂ at peak exercise; RR at peak exercise; peak exercise HR; dyspnoea and fatigue scores; upper and lower body muscle strength.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants were randomly allocated in blocks of 6 to the exercise or control group. A computer programme was used to generate randomisation sequence.
Allocation concealment (selection bias)	Unclear risk	Not discussed.
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Not possible to blind participants to intervention. 1 researcher was blinded to the randomisation and intervention and was responsible for database entries.
Blinding of outcome assessment (detection bias)   All outcomes	Low risk	Outcome assessors were blinded.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	2 participants in the exercise group could not be assessed at the 3‐month visit due to submission to the lung transplant programme. Intention‐to‐treat analysis was used and imputations for missing data were performed for these 2 participants.
Selective reporting (reporting bias)	Low risk	All outcome detailed in methods were reported in results. Data reported for all time points.
Other bias	Unclear risk	Clearly stated inclusion and exclusion criteria and described method of statistical analysis used. Baseline between‐group differences existed in BMI which could possibly impact on HRQoL (primary outcome).

Methods	Design: single‐centre, parallel RCT, 3‐year duration. Inclusion criteria: participants with CF aged 7 ‐ 19 years with an FEV₁ > 40% predicted. Exclusion criteria: not specified.
Participants	65 participants with CF; 2 groups similar at baseline. 7 dropouts.  Group demographics Exercise group (n = 30): mean (SD) age 13.4 (3.9 years). Control group (n = 35): mean (SD) age 13.3 (3.6) years.
Interventions	Long‐term aerobic study.  Group 1: minimum of 20 min aerobic activity plus 5 min warm up and cool down 3 times per week. Group 2: maintained regular activity (control).
Outcomes	Included in this study were: FVC; FEV₁; FEF_25‐75; PEFR; TV; VO₂ peak; VCO₂; peak exercise heart rate; peak exercise VE; VE peak/MVV; RER; blood pressure; % of ideal weight for height; compliance and sense of well‐being; feasibility of exercise; hospital stays and number of days in hospital; chest X‐ray; and Schwachman scores.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation sequence.
Allocation concealment (selection bias)	Unclear risk	Not discussed.
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Not possible to blind participants to intervention. Unclear whether personnel blinded.
Blinding of outcome assessment (detection bias)   All outcomes	Low risk	Pulmonary function assessors were blinded to group assignment (primary outcome measure).
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Clear description and details about 7 dropouts were recorded. Intention‐to‐treat analysis was reported to yield similar results for pulmonary function. Results were only reported for 65 participants who completed the 2‐year follow up.
Selective reporting (reporting bias)	Low risk	All outcome detailed in methods were reported in results. Data reported for all time points.
Other bias	Unclear risk	Groups similar at baseline.  Stated the inclusion criteria but not the exclusion criteria.  Described statistical methods used in analysis.

Methods	Design: single‐centre, parallel RCT; hospital admission for recurrent chest infections. Inclusion criteria: children with CF, aged 8 ‐ 16 years who were admitted the the Royal Alexandria Hospital for Children for the treatment of an infectious pulmonary exacerbation. Exclusion criteria: children with known pulmonary hypertension, or who required daytime oxygen prior to the pulmonary exacerbation which led to the hospital admission.
Participants	66 children with CF (28 males, 38 females). No dropouts.  Group demographics Aerobic training group (n = 22): mean (SD) age 13.2 (2.0) years), 9 males and 13 females. Resistance training group (n = 22): mean (SD) age 13.1 (2.1) years, 10 males and 12 females. Control group (n = 22): mean (SD) age 13.2 (2.0) years, 9 male and 1 females.
Interventions	Short‐term aerobic and anaerobic/strength training study during hospital admission (mean duration 18.7 days, range 14 ‐ 36 days).  Group 1: 30 min supervised aerobic exercise training 5 times per week. Group 2: 30 min supervised resistance training 5 times per week. Group 3: no specific training.
Outcomes	Included in this study were: VO₂ peak; peak VE; VCO₂; peak HR; HRQoL; FEV₁; FVC; weight; lower limb strength; and fat‐free mass.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Random allocation in sets of 6. No details given for generation of sequence.
Allocation concealment (selection bias)	Low risk	Concealed information inside opaque envelopes.
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Not possible to blind participants to intervention. Unclear whether personnel blinded.
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Unclear whether outcome assessors blinded.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Stated no dropouts.
Selective reporting (reporting bias)	Unclear risk	Did not report on all secondary outcomes detailed in methods (e.g. VE, VCO₂, RQ) in results. Data reported for all time points.
Other bias	Low risk	Clearly stated inclusion and exclusion criteria.  Described statistical methods used to analyse data.

Study	Reason for exclusion
Alarie 2012	This study compared the acute cardiovascular response in participants playing different active video games. No control group included.
Albinni 2004	This study was designed with the exercise group as the control group, therefore we could not compare data with baseline, no physical exercise training as per our protocol.
Amelina 2006	IMT training and not physical exercise training as per our protocol.
Andreasson 1987	Not a randomised controlled study.
Aquino 2006	This study was designed with the aim of comparing the effectiveness of a single treatment sessions of exercise and PEP on sputum clearance. Participants in this study did not undertake a programme of physical training.
Asher 1982	IMT training and not physical exercise training as per our protocol.
Balestri 2004	This study was designed with the aim of comparing the effectiveness of a single treatment session of exercise and PEP on sputum clearance. Participants in this study did not undertake a programme of physical training.
Balfour 1998	Not a physical exercise training study, comparison of different tests for assessing exercise capacity.
Barry 2001	Not a randomised controlled study.
Bieli 2017	Study of respiratory muscle endurance training, not a physical exercise training study.
Bilton 1992	This study was designed with the aim of comparing the effectiveness of a single treatment session of exercise or physiotherapy or exercise and physiotherapy on sputum clearance and lung function. Participants in this study did not undertake a programme of physical training.
Bongers 2015	Study evaluating the clinical usefulness of the steep ramp test and not a physical training study.
Calik‐Kutukcu 2016	No control group with no physical training.
Chang 2015	Study of methods for evaluating muscle function and not a physical training study.
Chatham 1997	This study involved respiratory muscle training exclusively. This intervention does not constitute physical training as defined within our protocol.
de Jong 1994	Not a randomised controlled study.
del Corral Nunez‐Flores 2011	No control group with no physical training.
Dwyer 2008	Study duration insufficient,
Dwyer 2017	Study duration insufficient,
Edlund 1986	Not a randomised controlled study.
Falk 1988	This study was designed with the aim of comparing the effectiveness of a single treatment session of exercise or positive expiratory pressure on lung function. Participants in this study did not undertake a programme of physical training.
Giacomodonato 2015	Study of respiratory muscle endurance training and not a physical training study.
Gruet 2012	No control group with no physical training.
Haynes 2016	Evaluation of the incremental step test not a study of physical training.
Heijerman 1992	Not a randomised controlled study.
Irons 2012	Not a physical exercise training study, examines effect of a singing program compared to no singing.
Kriemler 2016	Study duration insufficient, only 3 single day interventions on non‐consecutive days of a week.
Kuys 2011	Compares Nintendo Wii exercise training to an existing exercise programme, no control group with no physical training.
Lannefors 1992	This study was designed with the aim of comparing the effectiveness of a single treatment session of exercise and FET or positive expiratory pressure and FET or postural drainage, thoracic expansion exercises and FET on mucous clearance. Participants in this study did not undertake programme of physical training.
Lima 2014	No physical exercise training study, study looks at effect of non‐invasive ventilation on exercise capacity and lung function.
Lowman 2012	No control group with no physical training.
NCT02277860	Not a randomised controlled study, single arm trial of physical exercise,
NCT02715921	Not a randomised controlled study, single arm trial of physical exercise,
NCT02821130	A study of CFTR potentiator therapy and effects on exercise capacity.
NCT02875366	A study of CFTR potentiator therapy and effects on exercise capacity.
NCT03117764	Not a randomised controlled study, study of the effect of antibiotics on muscular strength and not physical training.
Orenstein 1981	Not a randomised controlled study.
Orenstein 2004	Compares aerobic training to upper‐body strength training, no control group with no physical training.
Ozaydin 2010	IMT training and not physical exercise training as per our protocol.
Patterson 2004	Study to evaluate the efficacy of the test of incremental respiratory endurance, not a physical training study.
Petrovic 2013	Not a randomised controlled study.
Rand 2012	Not a physical exercise training study. This study was designed to develop an incremental field exercise test for children with CF.
Reix 2012	Acute study comparing exercise with expiratory breathing manoeuvres to breathing techniques for airway clearance.
Salh 1989	Not a randomised controlled study.
Salonini 2015	A comparison of two exercise interventions (Xbox Kinect versus stationary cycle). No control group with no physical training.
Shaw 2016	No control group with no physical training.
Stanghelle 1998	Not a randomised controlled study.
Tuzin 1998	Not a randomised controlled study.
Vallier 2016	Study to evaluate modified shuttle test and not a study of physical training.
Vivodtzev 2013	This study evaluated neuromuscular electrical stimulation prior to endurance training in people with CF. No control group with no physical training.
Wheatley 2015	Intervention only given on 3 single days, comparison of physical training and albuterol for airway clearance.

Methods	RCT. Parallel design. Duration: 12 weeks.
Participants	Target sample size: 150. Inclusion criteria: confirmed diagnosis of CF, hospital inpatient admission (including hospital in the home) for IV antibiotic therapy for a respiratory cause, informed consent, access to the Internet via computer or mobile device. Exclusion criteria: presence of severe co‐morbidity limiting mobilisation or physical activity participation, previous lung transplantation, pregnancy. Age minimum: 12 Years Age maximum: 24 Years Gender: Both males and females
Interventions	Intervention group: use of the ActivOnline program, via the Internet, as well as usual care. ActivOnline was developed in accordance of the principles of motivational interviewing and has been used to promote physical activity participation in older adults with chronic respiratory disease. Those allocated to the ActivOnline group will be provided with a unique logon and password to access the ActivOnline program and will be asked to record their daily physical activity and exercise using the secure portal. When logging onto ActivOnline they will be prompted to set goals, will record their PA or exercise using a pedometer or other device of their choice and will regularly enter data about that will be displayed graphically so they can see their progress. Control group: usual care. Usual care provides details for an online resource regarding physical activity participation and physical activity targets for children and young adults (www.nhs.uk/Livewell/fitness/Pages/physical‐activity‐guidelines‐for‐young‐people.aspx) as well as activity and exercise guidance, as indicated, as part of their routine clinical care on hospital discharge.
Outcomes	Primary outcome Change in physical activity participation objectively measured via accelerometry Secondary outcomes Change in exercise capacity as measured by the MST  Change in health related quality of life as assessed by the CFQ‐R  Change in HADS  Change in lung function as measured by FEV₁   Change in physical activity participation objectively measured via accelerometry  Change in physical activity participation self reported by the HAES  Change in the CES‐D scale  Change in the PSQI  Number of hospital inpatient days by medical record review  Time to first hospital admission, by medical record review
Notes	Supported by UK CF Trust. Email confirmation from lead investigator (17 August 2017) that trial has been completed and they are currently analysing data. We hope to obtain data for the CF participants once the trial has been published.

PERMALINK

Physical exercise training for cystic fibrosis

Thomas Radtke

Sarah J Nevitt

Helge Hebestreit

Susi Kriemler

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Background

Description of the condition

Description of the intervention

How the intervention might work

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Types of interventions

Types of outcome measures

Primary outcomes

Secondary outcomes

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

Data extraction and management

Assessment of risk of bias in included studies

Measures of treatment effect

Unit of analysis issues

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

Summary of findings tables and quality of the evidence (GRADE)

Summary of findings for the main comparison. Summary of findings ‐ Aerobic training versus no physical training.

Summary of findings 2. Summary of findings ‐ Anaerobic training versus no physical training.

Summary of findings 3. Summary of findings ‐ Combined aerobic and anaerobic training versus no training.

Results

Description of studies

Results of the search

1.

Included studies

Trial characteristics

Participants

Interventions

Outcomes

Excluded studies

Studies awaiting classification

Trial characteristics

Interventions

Outcomes

Ongoing studies

Trial characteristics

Interventions

Outcomes

Risk of bias in included studies

2.

3.

Allocation

Sequence generation

Allocation concealment

Blinding

Blinding of participants and personnel (performance bias)

Blinding of outcome assessment (detection bias)

Incomplete outcome data

Selective reporting

Other potential sources of bias

Description of inclusion or exclusion criteria

1. Exercise capacity by VO₂ peak

2. Pulmonary function (FEV₁)

1. Exercise capacity by VO₂ peak

2. Pulmonary function by FEV₁

Methods	Parallel design RCT. 6‐month intervention.
Participants	38 participants with CF aged 7 ‐ 13 years. No group demographics available. Inclusion criteria: not specified. Exclusion criteria: not specified.
Interventions	Group 1 (n = 19): classical physiotherapy plus sport activities 3 times per week. Group 2 (n = 19): classical physiotherapy alone.
Outcomes	Eligible for inclusion are: FEV_1; FVC; FEF_25‐75; number of hospitalisations; participation at school; and activities of daily living.
Notes	No information were available in the abstract about types of exercises, intensity, frequency and duration of exercise training.

Methods	Design: Modified RCT; motivational incentive‐based walking program for patients hospitalised with pulmonary exacerbation. Series of 2‐week intervals with 1‐week wash‐out periods were created and randomized as either treatment or control.
Participants	29 participants with CF (11 males; 18 females). Group demographics: Intervention group (n = 18) Control group (n = 11) Inclusion criteria: not specified. Exclusion criteria: not specified.
Interventions	Intervention group (n = 18): incentive‐based walking program plus standard care including daily (Monday to Friday) physical therapy. Control group (n = 11): standard care including daily (Monday to Friday) physical therapy.
Outcomes	Included in this study were: 6MWT distance; vital signs; Bruininks‐Oseretsky Test of Motor Proficiency; strengths assessment score and HRQoL (CFQ‐R). Data were collected within 72 hours of hospital admission and within 48 hours of hospital discharge.
Notes

Methods	Design: parallel RCT; 6‐week exercise programme followed by a 16‐week home‐based programme.
Participants	89 participants aged 7 ‐ 11 years old and with different lung conditions: asthma (n = 60), CF (n = 12), a history of chronic neonatal lung disease (n = 17). Group demographics are not available. No information on dropouts. Inclusion criteria: not specified. Exclusion criteria: not specified.
Interventions	6‐week exercise programme with weekly exercise sessions followed by a home‐based programme using behaviour change strategies to promote aerobic exercise. Participants were evaluated at baseline, 7 weeks and 24 weeks. Intervention group: n = 45. Control group: n = 44.
Outcomes	Included in this study were: aerobic fitness (exercise test not specified); vigorous physical activity; self perception of athletic competence and physical appearance.
Notes	We plan to contact the authors to obtain the CF‐specific data.

Methods	Design: parallel RCT; single centre comparative effectiveness trial at the Royal Brompton Hospital, London, UK. Phase 2 study.
Participants	72 participants with CF aged over 6 years from the Royal Brompton Hospital, London. Group demographics are not available. Inclusion criteria: not specified. Exclusion criteria: not specified.
Interventions	Phase 2 study. Group 1: 8x one‐on‐one Tai Chi sessions then given a DVD and a handout to use at home for 9 months and encouraged to practice up to 5 times per week. Group 2: no treatment (standard care) for the first 3 months (this is the control), then 8x online Tai Chi sessions (e.g. via Skype) and given a DVD and a handout to use at home for 6 months and again encouraged to practice up to 5 times per week. The programme was evaluated at baseline and after 3, 6 and 9 months.
Outcomes	Included in this study were: HRQoL; mindfulness, sleep (not specified); medical data (not specified) and respiratory function (not specified); participants' experience; Tai Chi feasibility; perceived health impact and study participation.
Notes	We plan to contact the authors to obtain more information on study design and results.

Methods	Design: parallel RCT, 10 ‐ 14 day inpatient period at a tertiary hospital followed by a 8 ‐ 12 week home‐based program. Blinded assessor.
Participants	31 participants with CF aged 8.5 to 17.6 years and with a mean FEV₁ of 66.74 %. Group demographics Group 1: exercise program (n = 15). Group 2: standard physiotherapy exercise (n = 16). Inclusion criteria: not specified. Exclusion criteria: not specified.
Interventions	Group 1 (n = 15): a novel exercise program including a portable exercise package (FitKit™ ‐ exercise in a bag including instruction cards, exercise equipment and daily exercise log). Group 2 (n = 16): standard physiotherapy exercise practice.
Outcomes	Performance on study measures (scoped within the framework of the International Classification of Functioning, Disability and Health model) ‐ details not reported. Assessment at 3 time points: admission to the inpatient period; at discharge from the 10 ‐ 14 day inpatient period; and at conclusion of the 8 ‐ 12 week home program.
Notes	No data available currently, but will be added when study published in full.

Methods	Design: cross‐over RCT; single blind (outcome assessor); 6 months duration; single‐centre study at Children's Hospital of Pittsburgh, USA.
Participants	Enrolment goal: 38 participants with CF. Inclusion criteria: CF diagnosis; males and females; age 10 ‐ 18 years; reliable pulmonary function test; living at home; able to read; able to ride a stationary bike; able to walk and/pr run on a treadmill. Exclusion criteria: enrolled in another intervention study; participation in structured aerobic exercise for 30 continuous minutes 3 times per week; sibling enrolled in study.
Interventions	Intervention group: home‐based exercise programme at least 3 times per week for 6 months with telephone reinforcement. After the first 6 months, participants receive instructions to maintain their self‐regulated exercise activity for another 6 months without receiving telephone calls. Control group: standard recommendations for exercise activity during the first 6 months. Thereafter, the control group will cross over to the self‐regulated exercise without telephone reinforcement.
Outcomes	Included in this study were: VO₂ peak; peak workload; VO₂ 150 (VO₂ at a heart rate of 150 bpm per minute during an exercise test); FEV₁; sustained phonation time; HRQoL (CF questionnaire and well‐being scale) and exercise experiences of children and parents assessed with interviews.
Notes	A 6‐month program of self‐regulated, home‐based exercise programme with telephone reinforcement on cardiorespiratory fitness, pulmonary function and HRQoL of children with CF, compared to controls. A secondary aim is to exploring the exercise experiences of the children and parents. The principal investigator confirmed that the trial is completed and data are currently being analyzed.

Methods	Design: parallel RCT; open‐label; duration 24 months; partially‐supervised; single‐centre study at University Hospital, Strasbourg, France.
Participants	Enrolment goal: 50 participants with CF. Inclusion criteria: males and females aged 15 ‐ 65 years with CF diagnosed by clinical history and positive genetic or sweat testing; signed informed consent (or by parents for paediatric participants); participant covered by social security; participant has no indication of cardiac issues; stable disease (FEV₁ > 1000 mL); in the case of insulin‐dependent diabetes, it must be stable; participant had been informed of the results of the medical examination; women of childbearing age confirmed not to be pregnant by urine test. Exclusion criteria: participant with unstable diabetes or known cardiac issues; participant on transplant list.
Interventions	Intervention group: partially‐supervised exercise training programme with the aim of exercising 3x per week over 24 months; exercise intensity controlled with heart rate monitors and supported by exercise coaches. Control group: normal daily activities and physiotherapy regimen.
Outcomes	Included in this study were: VO₂ peak; HRQoL (CFQ‐14+ and SF 36).
Notes	The principal investigator of this study responded on our request and confirmed that the study has been closed prematurely due to local organisational and recruitment problems. No publication is planned for this study.

Methods	Design: parallel RCT; duration 6 weeks; open‐label; single‐centre study at Universidad Autonoma de Madrid, Spain.
Participants	Enrolment goal: 41 participants with CF. Inclusion criteria: males and females aged 7‐18 years diagnosed with CF; clinically stable with no exacerbations of the disease in the previous 6 weeks to the inclusion date. Exclusion criteria: clinical evidence of cardiovascular, neuromuscular or osteo‐articular co‐morbidities that limit the participation in exercise programmes; lung transplant candidates and participants that followed any kind of rehabilitation programme 12 months before the study.
Interventions	Intervention group: 30 ‐ 60 min exercise using a Nintendo Wii platform with the game EA SPORTS ACTIVE 2, 5 days/week for 6 weeks. The exercise activities are loaded into each participant's console during the clinical interview and the exercises adjusted according to their age: <12 years and >13 years. The program consists of 6 different workouts (1st and 2nd weeks: legs exercises; 3rd week: upper limb exercises; 4th week: thorax exercises; 5th and 6th weeks: cardio exercises) with gradually increasing intensities reaching the maximum load at the end of the training. Control group: routine clinical management.
Outcomes	Included in this study were: exercise capacity (6MWT; modified shuttle walk test); muscular strength (horizontal jump test, medicine ball throw, handgrip strength); HRQoL using 3 versions of the CFQ‐R (CFQ‐R 6‐11, CFQ‐R 14+, CFQ‐R Parents).
Notes	The aim of this study is to evaluate the efficacy of a long‐term domiciliary exercise program using the Wii video game platform as a training modality in people with CF.

Methods	Design: parallel RCT; outcome assessor (exercise supervisor) blinded; single‐centre study at Hospital de Clínicas de Porto Alegre, Brazil.
Participants	Estimated enrolment: 68 participants with CF. Inclusion criteria: males and females age 16 ‐ 50 years, diagnosed with CF according to consensus criteria and regularly followed up in the Hospital de Clinicas de Porto Alegre Programme for Adolescents and Adults with CF; admitted to hospital (for at least 24 hours) due to exacerbation of lung disease. Exclusion criteria: participants with cardiac, orthopedic or trauma complications that make it impossible to perform the proposed exercises; pregnancy; participants with haemodynamic instability, massive haemoptysis, pneumothorax, and continuous use of non‐invasive ventilation.
Interventions	Intervention group: aerobic and anaerobic exercise 5 times a week during the hospitalisation period, with sessions lasting about an hour, programme beginning within 48 hours of admission. Control group: physiotherapeutic follow‐up (including respiratory physiotherapy, inhalation therapy and techniques for removal of secretions) performed by the physiotherapist of the programme for adults with CF during the hospitalisation period.
Outcomes	Included in this study were: primary outcome: 6MWT distance; secondary outcomes: FEV₁; HRQoL (CFQ‐R); C‐reactive protein; interleukin‐6; interleukin‐8 and tumor necrosis factor.
Notes	This study study aims to evaluate the effects of an early rehabilitation programme based on aerobic training and muscle strength training in adolescent and adult participants with CF hospitalised at Hospital de Clinicas de Porto Alegre for exacerbation of lung disease.

Methods	Design: parallel RCT ("Do More, B'More, Live Fit"), duration 6 months; single‐centre study at Johns Hopkins University, Baltimore, US.
Participants	Enrollment goal: 60 participants with CF. Inclusion criteria: males and females aged 12 ‐ 21 years old with CF and cared for at Johns Hopkins; participants must have a smartphone and/or computer with universal serial bus (USB) to set‐up FitBit Flex. Exclusion criteria: FEV₁ < 40% predicted; individuals already participating in vigorous physical activity (as assessed by the study team) in year‐round organised sports and/or aerobic exercise for longer than 30 minutes more than 5x per weeks may or may not be included in this study at the discretion of the principal investigator and study team.
Interventions	Intervention group: at baseline assessment participants given individualised exercise prescriptions with the aim of achieving 30‐minutes of an endurance‐style exercise (team sports, walking, jump roping, stair climbing or more complex Tabata‐style workouts) 5 times/week for 6 months. At 4‐6 weeks and 8‐10 weeks post‐enrolment, participants attend a follow‐up 30‐minute session which will vary based on initial assessment and previous exercise prescription success, but will include strength training for major muscles groups and/or flexibility exercises with yoga as well as reinforcement of previously learned techniques with additional individualised recommendations. Participants will also receive motivational messages starting 14 days after enrolment via preferred contact method (SMS, telephone call and/or email) every 3‐4 days over the 6‐month study period. Participants also given access to "Do More, B'More, Live Fit" web page which includes spotlighted exercises, instructional exercise photos and videos; also invited to join the "Do More, B'More, Live Fit" Activity Group via the FitBit Dashboard and to friend the study team members and other exercise‐intervention participants in order to take part in FitBit step‐goal challenges. Control group: at baseline assessment, the FitBit daily step goal is set at the manufacturer standard 10,000 steps. At routine clinic visits, baseline and follow‐up assessments (3 and 6 month clinic visits) participants given generic, non‐personalised encouragement and recommendations (if requested by the participant) for physical activity. At the 3‐ and 6‐month visits, exercise is reinforced with generic encouragement, export FitBit data and review any missing data concerning for equipment failure or user error.
Outcomes	Included in this study were: Primary outcomes: LCI (LCI 2.5 and LCI 5.0); daily activity via FitBit step count and daily step count (mean, median and highest daily) recorded through participant FitBit flex. Secondary outcomes: FEV₁ % predicted; self‐reported physical activity (Habitual Activity estimation Scale); HRQoL (CFQ‐R); exercise capacity (modified shuttle walk test); acceptability and feasibility of the programme using semi‐structured interviews.
Notes	This study evaluates the "Do More, B'More, Live Fit", a 6‐month fitness programme designed to optimise exercise habits of participants with CF through structured exercises with personalised coaching, exercise equipment including the FitBit Flex, online support and motivational messages delivered electronically. The intervention incorporates fitness preferences and encompasses endurance, strength and flexibility exercises while adjusting to physical fitness needs. The hypothesis is that intervention participants will have increased and sustained engagement and better health outcomes compared to control group participants.