. 2022 Aug 9;2022(8):CD002768. doi: 10.1002/14651858.CD002768.pub5

Summary of findings 1. Physical activity compared with no physical activity for cystic fibrosis.

Physical activity compared with no physical activity for cystic fibrosis
Patient or population: adults and children with cystic fibrosis Settings: at home or in hospital Intervention: physical activity Comparison: no physical activity (usual care)
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Usual care	Physical activity
Exercise capacity: change in VO₂ peak (mL/min per kg bodyweight) Active intervention: > 6 months	VO₂ peak was 1.60 mL/min per kg bodyweight higher in the physical activity group than in the control group (0.16 mL/min per kg bodyweight higher to 3.05 mL/min per kg bodyweight higher).		—	348 (6)	⊕⊕⊕⊝ Moderate^a,b	P = 0.005 Sensitivity analysis which removed 1 small outlying study did not alter the results. Other time points: Active intervention ≤ 6 months 8 studies reported the effect of physical activity for periods of up to and including 6 months (MD 2.10 mL/min per kg bodyweight, 95% CI 0.06 to 4.13; n = 323; P = 0.04). There was a high level of heterogeneity in the results. Follow‐up (no active intervention) This was reported by 3 out of 9 studies. VO₂ peak was higher in the physical activity versus control groups (MD 3.27 mL/min per kg bodyweight, 95% CI 1.37 to 5.18; n = 125; P < 0.001).
FEV₁ % predicted (change from baseline) Active intervention: > 6 months	The mean change in FEV₁ % predicted was 2.41% higher in the physical activity group than in the control group (0.49% lower to 5.31% higher).		—	367 (6)	⊕⊕⊝⊝ Low^a,c	P = 0.1 Sensitivity analysis which removed 1 small outlying study with wide CIs changed the effect slightly towards a beneficial effect of physical activity (MD 1.71 % predicted, 95% CI 0.15 to 3.26; P = 0.02). Other time points: Active intervention ≤ 6 months 8 studies found no difference between the physical activity group and control group (MD 1.30 % predicted, 95% CI ‒3.01 to 5.61; n = 356; P = 0.56). Follow‐up (no active intervention) 3/9 studies reported this outcome and found no difference between groups (MD 5.68 % predicted, 95% CI ‒1.88 to 13.23; n = 128; P = 0.14).
HRQoL: change in CFQ‐R physical functioning domain score Active intervention: > 6 months	The mean change in CFQ‐R score was 2.19 points higher in the physical activity group than in the control group (3.42 points lower to 7.80 points higher).		—	247 (4)	⊕⊕⊝⊝ Low^d	P = 0.44 Other time points: Active intervention ≤ 6 months 6 studies reported that there was no difference in HRQoL CFQ‐R scores between groups (MD 4.67, 95% CI ‒2.55 to 11.90; n = 217; P = 0.21). Follow‐up (no active intervention) No studies reported CFQ‐R after a period off training.
HRQoL: change in CFQ‐R respiratory symptoms domain score Active intervention: > 6 months	The mean change in CFQ‐R score was 0.05 points lower in the physical activity group than in the control group (3.61 points lower to 3.51 points higher).		—	251 (4)	⊕⊕⊝⊝ Low^d	P = 0.98 Other time points: Active intervention ≤ 6 months 5 studies reported that there was no difference in HRQoL CFQ‐R scores between groups (MD ‒1.87, 95% CI ‒5.66 to 1.92; n = 212; P = 0.33). Follow‐up (no active intervention) No studies reported CFQ‐R after a period off training.
Pulmonary exacerbations: number of exacerbations occurring in the study period Active intervention: 12 months	There was no difference in the number of pulmonary exacerbations between the physical activity and control group. The incidence rate ratio was 1.28 (95% CI 0.85 to 1.94).		—	117 (1)	⊕⊕⊕⊕ High	P = 0.24 There was also no difference in the time to first exacerbation between the groups, HR 1.34 (95% CI 0.65 to 2.80). Other time points: Active intervention ≤ 6 months 1 study reported no difference in the number of exacerbations between groups at the 6‐month time point (incidence rate ratio 1.07, 95% CI 0.60 to 1.90), or in the time to first exacerbation (HR 1.34, 95% CI 0.65 to 2.80). Follow‐up (no active intervention) No studies reported this outcome after a period off training.
Diabetic control: change in blood glucose levels at rest, at 60 and 120 minutes after a glucose ingestion (mmol/L) Active intervention: 9 months	There were no differences between the physical activity and control groups with regard to blood glucose. At rest: MD ‒0.16 mmol/L (95% CI ‒0.44 to 0.12) After 60 minutes: MD ‒0.04 mmol/L (95% CI ‒1.11 to 1.03) After 120 minutes: MD ‒0.44 mmol/L (95% CI ‒1.43 to 0.55)		—	91 (1)	⊕⊕⊕⊝ Moderate^e	Participants included for this outcome did not have a diagnosis of CFRD on entry to the study. Other time points: Active intervention ≤ 6 months 1 study (n = 14, including 2 people with CFRD at study entry) assessed HbA1c, plasma glucose and insulin response to an oral glucose tolerance test. There was no difference in HbA1c (MD ‒0.00%, 95% CI ‒0.01 to 0.00). There was no difference in plasma glucose values between groups at any time point apart from at 120 minutes postglucose test when there was a significant difference favouring the exercise group (Beaudoin 2017). Follow‐up (no active intervention) No studies reported this outcome after a period off training.
Adverse events: number of adverse events Active intervention: 12 months	1 study reported no adverse events in either the physical activity or control group during the 12‐month study period (Kriemler 2013). A larger study reported no difference in the number of participants experiencing an adverse event or serious adverse event related to the intervention between the physical activity and no physical activity group (adverse events: OR 6.22, 95% CI 0.72 to 53.40; serious adverse events: OR 0.95, 95% CI 0.06 to 15.54) (Hebestreit 2022).		—	156 (2)	⊕⊕⊝⊝ Low^f,g	Other time points: Active intervention ≤ 6 months 2 studies reported adverse events: in the first study there was muscle stiffness (common after active video games) and in the second study there was an ankle injury in the physical activity group and haemoptysis in 1 participant in the control group. 1 further study reported no adverse events during the 6‐week intervention period. Follow‐up (no active intervention) In 1 study it was not clear if the earlier reported muscle stiffness continued in the follow‐up period. The study that reported no adverse events in the 6‐week intervention period, also observed no adverse events in the follow‐up period.
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% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; CFQ‐R: Cystic Fibrosis Questionnaire – Revised; CFRD: cystic fibrosis‐related diabetes; FEV₁: forced expiratory volume in 1 second; HbA1c: glycated haemoglobin; HR: hazard ratio; HRQoL: health‐related quality of life; MD: mean difference; n: number of participants; OR: odds ratio; VO₂ peak: peak oxygen uptake.
GRADE Working Group grades of evidence High certainty: further research is very unlikely to change our confidence in the estimate of effect. Moderate certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low certainty: 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 certainty: we are very uncertain about the estimate.

^aDowngraded once due to high or unclear risk of bias across many of the domains for the included studies. Two studies contributing data to this outcome were at high risk of bias due to concerns around randomisation and allocation concealment. ^bThere was moderate heterogeneity in the results, but this was due to an outlying study (Kriemler 2013). When this study was removed from the analysis, the result remained significant and therefore we did not downgrade the certainty of evidence due to inconsistency. The outlying study included small numbers and had wide CIs around the effect. ^cThere was moderate heterogeneity in the results due to a small outlying study with wide CIs (Kriemler 2013); downgraded once. ^dDowngraded twice due to risk of bias across several domains in the studies included in this analysis. There were particular concerns around randomisation and allocation concealment in three of the four included studies. ^eDowngraded once due to imprecision caused by a small number of participants. ^fDowngraded once due to risk of bias in one of the two included studies for this outcome. ^gDowngraded once for imprecision (low event rates and wide CIs).