Figures
- FIGURE 1
PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram.
- FIGURE 2
Number of studies, according to year and region, which compared exercise training with exercise training plus “add-on” in the present review.
- FIGURE 3
Forest plot of the effect of “add-on” therapies on 6-min walking distance change (in metres). Effect estimates (mean differences) without coloured shading denote unweighted analyses of data from single studies within intervention groups or subgroups. CPET: cardiopulmonary cycle exercise test; NMES: neuromuscular electrical stimulation; NIV: noninvasive ventilation; NA: not available; ISWT: incremental shuttle walk test. #: random effects model used for meta-analysis; ¶: statistically significant positive effect reported.
Tables
- TABLE 1
Description of studies included in the final screening
First author [ref.] Year Completed n (% of initial) Respiratory rehabilitation programme Exercise test PEDro score Add-on intervention Components of training Exercise training sessions n Additional exercise modalities Benton [9] 2013 19 (100) Single set of resistance training Cy, Tr 16 6MWT 4 Vonbank [10] 2012 24 (100) Strength training Cy 24 CPET 3 Bernard [11] 1999 36 (80) Strength training Cy 36 CPET+ 5 Dourado [12] 2009 24 (73) Strength training Tr, Cal 36 6MWT 4 Phillips [13] 2006 19 (unclear) Strength training Cy, Tr, Cal, PE 13 6MWT 4 Mador [14] 2004 24 (unclear) Strength training Cy, Tr 24 CPET, 6MWT 6 Würtemberger [15] 2001 24 (100) Strength training Cy, PE NR CPET, 6MWT 4 Alexander [16] 2008 20 (75) Strength training Cy, Tr 16 6MWT 3 Holland [17] 2004 38 (100) Upper and lower limb strength Cy, Tr 12 6MWT 7 Subin [18] 2010 17 (100) Upper and lower limb strength Tr 20 6MWT 4 Sívori [19] 1998 28 (65) Upper and lower limb strength Cy 24 CPET, 12MWT 4 Costi [20] 2009 46 (92) Upper and lower limb strength Tr, Cal, St 15 6MWT§ 8 Vivodtzev [21]# 2006 17 (100) NMES Tr, Cal, St 16 6MWT 5 Rooyackers [22] 2003 24 (100) Eccentric cycling Cy, St 50 CPET, 6MWT 4 Gloeckl [23] 2012 72 (88) Whole body vibration Cy, Cal, St, PE, Nut 15 6MWT§,ƒ 6 NIV Johnson [24]¶ 2002 22 (79) Bi-level NIV Tr, PE 12 CPETƒ 4 Toledo [25] 2007 18 (100) Bi-level NIV Tr 36 CPET 3 Reuveny [26]# 2005 19 (79) Bi-level NIV Tr 16 CPET 6 Costes [27] 2003 14 (100) Bi-level NIV Cy 24 CPET, endurance## 4 van’t Hul [28]# 2006 21 (72) Inspiratory support Cy 24 ISWT, endurance 8 Hawkins [29] 2002 19 (66) Proportional assisted ventilation Cy 18 CPET, endurance 5 Bianchi [30] 2002 19 (58) Proportional assisted ventilation Cy, St, PE, Nut 18 CPET, 6MWT 5 Garrod [31] 2000 37 (82) Nocturnal NIV Cy, Tr, St, PE 16 ISWT§,ƒ 6 Duiverman [32]# 2008 62 (86) Nocturnal NIV Cy, Tr, St, IMT, PE, Nut 36, plus 69 nights of NIV 6MWT, endurance, CPET 4 Oxygen Scorsone [33]¶ 2010 30 (100) Supplementary oxygen Cy 24 CPET, enduranceƒ 5 Emtner [34]# 2003 29 (100) Supplementary oxygen Cy, PE 21 CPET, endurance 7 Garrod [35]# 2000 22 (88) Supplementary oxygen Cy, Tr, Cal, PE 18 ISWT 8 Wadell [36]# 2001 20 (100) Supplementary oxygen Tr 24 6MWT 6 Dyer [37]# 2012 47 (85) Supplementary oxygen Tr, St, PE 14 ESWT§,ƒ 6 Rooyackers [38]# 1997 24 (unclear) Supplementary oxygen Cy, Cal, St, PE 50 CPET, 6MWT 5 Bjørgen [39] 2009 12 (79) Supplementary oxygen Cy 24 CPETƒ 3 Ringbaek [40]# 2013 38 (84) Continuous oxygen supplement Cy, Tr, PE 14 ESWTƒ 5 Heliox Johnson [24]¶ 2002 21 (88) Supplementary heliox Tr, PE 12 CPETƒ 4 Eves [41] 2009 31 (82) Supplementary heliox Cy, Tr, Cal, St, PE 16 CPET, enduranceƒ 9 Scorsone [33]¶ 2010 30 (100) Supplementary heliox Cy 24 CPET, enduranceƒ 5 Prescription medications Pasqua [42]# 2010 22 (100) Tiotropium Cy, Tr, Cal, IMT 20 6MWT 3 Ambrosino [43] 2008 120 (68) Tiotropium Tr 24 6MWTƒ 8 Casaburi [44] 2005 91 (84) Tiotropium Tr 24 Endurance§ 6 Creutzberg [45] 2003 63 (100) Anabolic steroids Cy 40 CPET 10 Ferreira [46]# 1998 17 (100) Anabolic steroids Cy, IMT 40 CPET, 6MWT## 7 Miki [47]# 2012 29 (100) Ghrelin Cy, Cal, PE 45 6MWTƒ 9 Burdet [48]# 1997 16 (100) Growth hormone Aero NR 36 CPET, 6MWT## 8 Miki [49]# 2013 20 (100) Ghrelin Cy, Cal, PE 15 CPET¶¶ 9 Hornikx [50] 2012 49 (98) Vitamin D supplement Cy, Tr, St, PE 36 CPET¶¶, 6MWT 8 Blanco [51]# 2013 41 (85) Sildenafil Cy, St 36 CPET, enduranceƒ, 6MWT 8 Satta [52] 1991 20 (unclear) Ubidecarenone Tr NR CPET 6 Valderramas [53] 2009 64 (94) Hypertonic saline Tr, Cal, St 24 6MWTƒ,## 8 Nutrition Laviolette [54] 2010 20 (92) Whey protein Cy, St 24 Endurance 6 Sugawara [55] 2012 26 (83) MEIN (whey protein) Tr, Cal, IMT, PE NR 6MWT 8 Steiner [56] 2003 60 (70) Carbohydrates, protein and fat Tr, Cal, PE 14 ISWTƒ, ESWT 8 Gurgun [57]# 2013 30 (100) Carbohydrates, protein and fat Cy, Tr, St 16 ISWT, 6MWT 4 Broekhuizen [58] 2005 80 (78) Polyunsaturated fat Cy, Tr, PE NR CPET+ 7 Deacon [59] 2008 80 (80) Creatine monohydrate Cy, Tr, St, PE 21 ISWTƒ, ESWT 7 Faager [60] 2006 23 (100) Creatine monohydrate Cy, Cal, St, PE 16 ESWT 5 Fuld [61] 2005 25 (66) Creatine monohydrate Cy, Cal, St, PE 16 CPET, ISWTƒ 7 Menier [62] 2001 60 (100) Branched-chain amino acid Cy, Cal, St 30 CPET 3 Borghi-Silva [63] 2006 16 (unclear) L-carnitine Tr, IMT 18 CPET, 6MWT§ 5 Breathing exercises Magadle [64] 2007 27 (87) Inspiratory muscle training Cy, Tr, St 108 6MWT 7 Mador [65] 2005 29 (76) Inspiratory muscle training Cy, Tr, Cal, PE 24 CPET, 6MWT 5 Larson [66] 1999 28 (unclear) Inspiratory muscle training Cy 80 CPET 5 Berry [67] 1996 16 (94) Inspiratory muscle training Tr, St 36, plus 96 IMT sessions CPET, endurance, 12MWT 5 Wanke [68] 1994 42 (unclear) Inspiratory muscle training Cy 32, plus 56 IMT sessions CPET 4 Weiner [69] 1992 24 (unclear) Inspiratory muscle training Cy, St 72 Endurance, 12MWT§ 5 Dekhuijzen [70]# 1991 40 (100) Inspiratory muscle training Cy, Tr, St 100 CPET, 12MWT 5 Kunikoshita [71] 2006 15 (100) Inspiratory muscle training Tr, Cal 18 CPET 4 Sykes [72] 2005 37 (93) Inspiratory muscle training Cy, St 40 CPET, 6MWT 7 Goldstein [73] 1989 11 (100) Inspiratory muscle training Aero NR Exercise training++ plus 40 IMT sessions Endurance, 6MWT 5 Collins [74] 2008 33 (79) Ventilation feedback Cy, Tr 36 CPET, endurance 5 van Gestel [75] 2012 40 (100) Controlled breathing Cy, St 10 6MWT 6 Other Carrieri-Kohlman [76] 1996 51 (100) Coaching versus monitoring Tr 12 CPET, 6MWT 5 Zanotti [77] 2012 20 (100) Osteopathy Cy, St, PE 20 6MWT 9 Alexander [78] 2012 27 (unclear) Harmonica playing Cy, Tr 16 6MWT 4 de Godoy [79] 2003 30 (100) Psychotherapy Cy, Tr, Cal, St 24 6MWT 5 Sharifabad [80] 2010 63 (100) Written disclosure therapy Cy, Tr, St, PE 24 6MWT 4 Norweg [81]¶ 2005 33 (89) Activity training/lectures Tr, Cal 15, plus ∼1 h·week−1 6MWT 3 Deering [82] 2011 41 (100) Acupuncture Tr 14 ISWT 6 NIV: noninvasive ventilation; Cy: cycling; Tr: treadmill; 6MWT: 6-min walk test; CPET: cardiopulmonary exercise testing; Cal: calisthenics; PE: psychological or educational support; NR: not reported; 12MWT: 12-min walk test; St: strengthening; NMES: neuromuscular electrical stimulation; Nut: nutritional support; endurance: cycle endurance test; ISWT: incremental shuttle walk test; IMT: inspiratory muscle training; ESWT: endurance shuttle walk test; Aero NR: no aerobic training details reported. #: exemplar studies of patient-centred care; ¶: study included two appropriate interventions; +: statistically significant effect favouring intervention for peak work rate outcome; §: statistically significant effect favouring intervention; ƒ: outcomes with adequate statistical power, according to original publication; ##: statistically significant effect favouring control; ¶¶: statistically significant effect favouring intervention for peak oxygen uptake outcome; ++: training duration of 4 weeks, frequency not reported. Bold indicates statistically significant effects.
- TABLE 2
Overview of methodological quality (PEDro score) of included studies
First author [ref.] PEDro criteria 1# 2 3 4 5 6 7 8 9 10 11 Total Additional exercise modalities Benton [9] + + + + + 4 Vonbank [10] + + + 3 Bernard [11] + + + + + + 5 Dourado [12] + + + + + 4 Phillips [13] + + + + + 4 Mador [14] + + + + + + + 6 Würtemberger [15] + + + + + 4 Alexander [16] + + + 3 Holland [17] + + + + + + + + 7 Subin [18] + + + + + 4 Sívori [19] + + + + + 4 Costi [20] + + + + + + + + + 8 Vivodtzev [21]¶ + + + + + + 5 Rooyackers [22] + + + + 4 Gloeckl [23] + + + + + + 6 NIV Johnson [24]§ + + + + + 4 Toledo [25] + + + + 3 Reuveny [26]¶ + + + + + + 6 Costes [27] + + + + 4 van ’t Hul [28]¶ + + + + + + + + 8 Hawkins [29] + + + + + + 5 Bianchi [30] + + + + + + 5 Garrod [31] + + + + + + + 6 Duiverman [32]¶ + + + + + 4 Oxygen Scorsone [33]§ + + + + + 5 Emtner [34]¶ + + + + + + + 7 Garrod [35]¶ + + + + + + + + + 8 Wadell [36]¶ + + + + + + + 6 Dyer [37]¶ + + + + + + + 6 Rooyackers [38]¶ + + + + + + 5 Bjørgen [39] + + + + 3 Ringbaek [40]¶ + + + + + + 5 Heliox Johnson [24]§ + + + + + 4 Eves [41] + + + + + + + + + + 9 Scorsone [33]§ + + + + + 5 Prescription medications Pasqua [42]¶ + + + + 3 Ambrosino [43] + + + + + + + + + 8 Casaburi [44] + + + + + + + 6 Creutzberg [45] + + + + + + + + + + + 10 Ferreira [46]¶ + + + + + + + + 7 Miki [47]¶ + + + + + + + + + + 9 Burdet [48]¶ + + + + + + + + + 8 Miki [49]¶ + + + + + + + + + + 9 Hornikx [50] + + + + + + + + + 8 Blanco [51]¶ + + + + + + + + + 8 Satta [52] + + + + + + 6 Valderramas [53] + + + + + + + + + 8 Nutrition Laviolette [54] + + + + + + + 6 Sugawara [55] + + + + + + + + + 8 Steiner [56] + + + + + + + + + 8 Gurgun [57]¶ + + + + + 4 Broekhuizen [58] + + + + + + + + 7 Deacon [59] + + + + + + + + 7 Faager [60] + + + + + + 5 Fuld [61] + + + + + + + 7 Menier [62] + + + 3 Borghi-Silva [63] + + + + + 5 Breathing exercises Magadle [64] + + + + + + + 7 Mador [65] + + + + + + 5 Larson [66] + + + + + + 5 Berry [67] + + + + + + 5 Wanke [68] + + + + 4 Weiner [69] + + + + + 5 Dekhuijzen [70]¶ + + + + + + 5 Kunikoshita [71] + + + + 4 Sykes [72] + + + + + + + + 7 Goldstein [73] + + + + + 5 Collins [74] + + + + + 5 van Gestel [75] + + + + + + + 6 Other Carrieri-Kohlman [76] + + + + + + 5 Zanotti [77] + + + + + + + + + + 9 Alexander [78] + + + + + 4 de Godoy [79] + + + + + + 5 Sharifabad [80] + + + + + 4 Norweg [81]§ + + + + 3 Deering [82] + + + + + + + 6 1: eligibility criteria specified; 2: randomisation; 3: concealed allocation; 4: groups similar at baseline; 5: blinding of subjects; 6: blinding of therapists; 7: blinding of assessors; 8: at least one key outcome with >85% of initially allocated subjects; 9: intention-to-treat analysis; 10: between-group statistical comparison; 11: study provides both point measures and measures of variability for at least one key outcome; NIV: noninvasive ventilation; +: criteria decision rule satisfied. #: item does not contribute to overall score; ¶: exemplar studies of patient-centred care; §: study included two appropriate interventions.
- TABLE 3
Summary of treatment effect estimates, weighted according to outcome
V′O2peak L·min−1 Peak work rate W Cycle endurance min ISWT m ESWT 6MWT m 12MWT m Additional exercise training LL strength 0.10 (−0.08–0.29); N2=32i versus 28c 3.64 (−4.95–12.30); N4=54i versus 54c 2.50 (−20.63–25.64); N6=62i versus 68c UL/LL strength 0.00 (−0.18–0.16); N1=14i versus 14c 23.36 (−4.59–51.32)#; N3=54i versus 47c 4.78 (−122.43–131.99); N1=14i versus 14c Other 0.10 (−0.31–0.51); N1=12i versus 12c −2.00 (−44.24–42.24); N1=12i versus 12c 24.43 (0.13–48.74); N3=57i versus 56c NIV 0.08 (−0.08–0.24); N3=25i versus 26c −0.03 (−7.55–7.50); N4=35i versus 36c 0.61 (−5.23–6.46)#; N3=27i versus 25c 23.71 (2.65–44.77); N2=27i versus 31c −17.35 (−48.39–13.70); N2=39i versus 42c Oxygen −0.11 (−0.29–0.07); N3=36i versus 32c −1.38 (−5.47–2.72); N3=36i versus 32c 4.70 (−1.96–11.36); N1=14i versus 15c 233.38 (−245.24–712.0) m#; N2=40i versus 45c −37.0 (−98.61–24.61); N1=12i versus 12c Heliox 0.02 (−0.04–0.08); N2=26i versus 20c 4.61 (−0.50–9.72); N2=26i versus 20c 5.20 (−0.17–10.57); N1=16i versus 15c Prescription medications Tiotropium 5.35 (0.89–9.81); N1=47i versus 44c 7.06 (−15.13–29.26); N2=68i versus 74c Anabolic steroids 0.10 (−0.02–0.23); N1=33i versus 30c 4.00 (−5.28–13.28); N1=33i versus 30c −63.0 (−91.09– −34.91); N1=10i versus 7c Growth hormone 0.05 (0.01–0.09); N2=18i versus 18c −11.00 (−26.48–4.48); N1=8i versus 8c −26.21 (−148.92–96.50)#; N2=22i versus 23c Vitamin D 0.64 (0.07–1.22); N1=25i versus 24c 7.00 (−0.28–14.28); N1=25i versus 24c 29.0 (−7.62–65.62); N1=25i versus 24c Hypertonic saline −190.0 (−247.34– −132.66); N1=30i versus 27c Nutritional supplementation Proteins/fats −0.03 (−0.12–0.06); N1=38i versus 42c 9.00 (4.32–13.68); N1=38i versus 42c 2.86 (−2.00–7.72); N1=10i versus 10c −19.48 (−42.23–3.27); N2=40i versus 50c −0.24 (−1.65–1.17) min; N1=15i versus 15c 8.02 (−31.21–47.26); N2=31i versus 25c Creatine 0.14 (−0.02–0.29); N1=14i versus 11c 4.29 (−9.53–18.11); N1=14i versus 11c −3.62 (−31.75–24.52); N2=52i versus 53c −0.11 (−0.46–0.24) units¶; N3=65i versus 63c Amino acids −0.90 (−14.55–12.75); N1=30i versus 30c 53.00 (24.09–81.91); N1=8i versus 8c Breathing exercises Inspiratory muscle training 0.03 (−0.26–0.31) units¶; N6=97i versus 95c −0.07 (−10.56–10.43); N4=70i versus 69c 12.72 (−16.21–42.26); N4=55i versus 49c 211.45 (−56.66–479.56)#; N3=39i versus 41c Breathing retraining 0.20 (−1.58–1.98); N1=17i versus 16c 8.50 (−4.38–21.38); N1=17i versus 16c −12.58 (−35.93–10.77); N1=20i versus 20c Other −0.28 (−0.83–0.27); N1=24i versus 27c 3.20 (−24.06–30.46); N1=16i versus 25c 10.26 (−21.85–42.38); N6=78i versus 183c Data are presented as mean difference (95% CI), where the mean difference is the change from baseline and a positive effect estimate favours intervention (“add-on” therapies). Data from individual studies may appear more than once across different outcomes (columns). V′O2peak: peak oxygen uptake; ISWT: incremental shuttle walk test; ESWT: endurance shuttle walk test; 6MWT: 6-min walk test; 12MWT: 12-min walk test; LL: lower limb; UL: upper limb; NIV: noninvasive ventilation; Nx: number of participants (x is number of studies); i: intervention group; c: control group. #: random effects model; ¶: standardised mean difference. Bold indicates statistically significant treatment effect.
- TABLE 4
Summary of standardised effect estimates for studies defined as “exemplar” models of patient-centred care
V′O2peak L·min−1 Peak work rate W Cycle endurance min ISWT m ESWT 6MWT m 12MWT m Additional exercise training LL strength UL/LL strength Other 39.00 (−54.57–132.57); N1=9i versus 8c NIV 0.15 (−0.29–0.59) units¶; N2=39i versus 42c 8.00 (−5.53–21.53); N1=9i versus 10c 3.50 (−1.38–8.38); N1=10i versus 11c 17.00 (−5.47–39.47); N1=10i versus 11c 15.00 (−41.69–71.69); N1=30i versus 32c Oxygen −4.52 (−17.07–8.03); N2=26i versus 27c 4.70 (−1.96–11.36); N1=14i versus 15c 233.38 (−245.24–712.0) m#; N2=40i versus 45c −37.0 (−98.61–24.61); N1=12i versus 12c Heliox Prescription medications Tiotropium 4.66 (−69.63–78.95); N1=11i versus 11c Anabolic steroids −0.59 (−1.58–0.40) units¶; N1=10i versus 7c −63.0 (−91.09– −34.91); N1=10i versus 7c Growth hormone 0.05 (0.01–0.09); N2=18i versus 18c −26.21 (−148.92–96.50)#; N2=22i versus 23c Vitamin D Hypertonic saline Nutritional supplementation Proteins/fats −26.00 (−72.28–20.28); N1=15i versus 15c −0.12 (−0.84–0.6) units¶; N1=15i versus 15c −0.70 (−42.16–40.76); N1=15i versus 15c Creatine Amino acids Breathing exercises Inspiratory muscle training −0.06 (−0.19–0.07); N1=20i versus 20c −7.00 (−32.90–18.90); N1=20i versus 20c 69.00 (−154.89–292.89); N1=20i versus 20c Breathing retraining Other Data are presented as mean difference (95% CI), where the mean difference is the change from baseline and a positive effect estimate favours intervention (“add-on” therapies). Data from individual studies may appear more than once across different outcomes (columns). V′O2peak: peak oxygen uptake; ISWT: incremental shuttle walk test; ESWT: endurance shuttle walk test; 6MWT: 6-min walk test; 12MWT: 12-min walk test; LL: lower limb; UL: upper limb; NIV: noninvasive ventilation; Nx: number of participants (x is number of studies); i: intervention group; c: control group. #: random effects model; ¶: standardised mean difference. Bold indicates statistically significant treatment effect.
- TABLE 5
Sensitivity analysis: summary of treatment effect estimates, weighted according to outcome, including studies with PEDro scores >5 only
V′O2peak L·min−1 Peak work rate W Cycle endurance min ISWT m ESWT 6MWT m 12MWT m Additional exercise training LL strength −0.10 (−0.43–0.23); N1=11i versus 13c 9.00 (−14.60–32.60); N1=11i versus 13c −4.60 (−102.05–92.85); N1=11i versus 13c UL/LL strength 30.90 (−10.39–72.20)#; N2=45i versus 39c Other 26.70 (0.94–52.46); N1=36i versus 36c NIV 0.08 (−0.15–0.32); N1=9i versus 10c 8.00 (−5.53–21.53); N1=9i versus 10c 3.50 (−1.38–8.38); N1=10i versus 11c 23.71 (2.65–44.77); N2=27i versus 31c Oxygen −0.04 (−0.26–0.18); N1=14i versus 15c 3.00 (−16.32–22.32); N1=14i versus 15c 4.70 (−1.96–11.36); N1=14i versus 15c 490.00 (237.90–742.10) m; N1=24i versus 23c Heliox 0.02 (−0.04–0.08); N2=16i versus 15c 4.00 (−4.15–12.15); N1=16i versus 15c 5.20 (−0.17–10.57); N1=16i versus 15c Prescription medications Tiotropium 5.35 (0.89–9.81); N1=47i versus 44c 7.30 (−15.96–30.56); N1=57i versus 63c Anabolic steroids 0.10 (−0.02–0.23); N1=33i versus 30c 4.00 (−5.28–13.28); N1=33i versus 30c −63.0 (−91.09– −34.91); N1=10i versus 7c Growth hormone 0.05 (0.01–0.09); N2=18i versus 18c −11.00 (−26.48–4.48); N1=8i versus 8c −26.21 (−148.92–96.50)#; N2=22i versus 23c Vitamin D 0.64 (0.07–1.22); N1=25i versus 24c 7.00 (−0.28–14.28); N1=25i versus 24c 29.0 (−7.62–65.62); N1=25i versus 24c Hypertonic saline −190.0 (−247.34– −132.66); N1=30i versus 27c Nutritional supplementation Proteins/fats −0.03 (−0.12–0.06); N1=38i versus 42c 9.00 (4.32–13.68); N1=38i versus 42c 2.86 (−2.00–7.72); N1=10i versus 10c −17.40 (−43.52–8.72); N1=25i versus 35c 82.70 (−38.59–203.99); N1=16i versus 10c Creatine 0.14 (−0.02–0.29); N1=14i versus 11c 4.29 (−9.53–18.11); N1=14i versus 11c −3.62 (−31.75–24.52); N2=52i versus 53c −0.67 (−2.96–1.63) min; N2=52i versus 53c Amino acids Breathing exercises Inspiratory muscle training 0.48 (−0.17–1.14) units¶; N1=20i versus 17c 29.68 (−9.48–68.84); N2=34i versus 30c Breathing retraining −12.58 (−35.93–10.77); N1=20i versus 20c Other 3.20 (−24.06–30.46); N1=16i versus 25c 64.80 (−12.94–142.54); N1=10i versus 10c Data are presented as mean difference (95% CI), where the mean difference is the change from baseline and a positive effect estimate favours intervention (“add-on” therapies). Data from individual studies may appear more than once across different outcomes (columns). V′O2peak: peak oxygen uptake; ISWT: incremental shuttle walk test; ESWT: endurance shuttle walk test; 6MWT: 6-min walk test; 12MWT: 12-min walk test; LL: lower limb; UL: upper limb; NIV: noninvasive ventilation; Nx: number of participants (x is number of studies); i: intervention group; c: control group. #: random effects model; ¶: standardised mean difference. Bold indicates statistically significant treatment effect.
