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Programas de rehabilitación con ejercicios para la hipertensión pulmonar

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Appendices

Appendix 1. Database search strategies

Cochrane Airways Register of Trials

#1 PULM:MISC1
#2 MeSH DESCRIPTOR Hypertension, Pulmonary Explode All
#3 MeSH DESCRIPTOR Pulmonary Heart Disease
#4 "pulmonary vascular disease":TI,AB
#5 #1 or #2 or #3 or #4
#6 MeSH DESCRIPTOR exercise Explode All
#7 MeSH DESCRIPTOR Exercise Therapy Explode All
#8 MeSH DESCRIPTOR Exercise Tolerance
#9 MeSH DESCRIPTOR Physical Fitness
#10 MeSH DESCRIPTOR Physical Exertion
#11 MeSH DESCRIPTOR Ergometry
#12 MeSH DESCRIPTOR Bicycling
#13 MeSH DESCRIPTOR Weight Lifting
#14 MeSH DESCRIPTOR Muscle Strength
#15 exercis*:TI,AB
#16 conditioning or ergometry or treadmill or endurance or "upper limb" or "lower limb":TI,AB
#17 walk* or swim* or cycle* or cycling or bicycl* or jog*:TI,AB
#18 ((strength* or resistance* or weight*) NEAR3 train*):TI,AB
#19 aerobic*:TI,AB
#20 rehabilitat*:TI,AB
#21 #6 OR #7 OR #8 or #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20
#22 #5 and #21

CENTRAL (CRSO)

#1MESH DESCRIPTOR Hypertension, Pulmonary EXPLODE ALL TREES
#2MESH DESCRIPTOR Pulmonary Heart Disease
#3(pulmonary* NEAR3 hypertens*):TI,AB,KY
#4("pulmonary vascular disease*"):TI,AB,KY
#5#1 OR #2 OR #3 OR #4
#6MESH DESCRIPTOR Exercise EXPLODE ALL TREES
#7MESH DESCRIPTOR EXERCISE THERAPY EXPLODE ALL TREES
#8MESH DESCRIPTOR Exercise Tolerance
#9MESH DESCRIPTOR Physical Fitness
#10MESH DESCRIPTOR Physical Exertion
#11MESH DESCRIPTOR Ergometry EXPLODE ALL TREES
#12MESH DESCRIPTOR Bicycling
#13MESH DESCRIPTOR Weight Lifting
#14MESH DESCRIPTOR Muscle Strength EXPLODE ALL TREES
#15exercis*:TI,AB,KY
#16(conditioning or ergometry or treadmill or endurance or "upper limb" or "lower limb"):TI,AB,KY
#17(walk* or swim* or cycle* or cycling or bicycl* or jog*):TI,AB,KY
#18((strength* or resistance* or weight*) NEAR3 train*):TI,AB,KY
#19aerobic*:TI,AB,KY
#20rehabilitat*:TI,AB,KY
#21#6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20
#22#5 AND #21

MEDLINE (Ovid)

1. exp Hypertension, Pulmonary/

2. Pulmonary Heart Disease/

3. (pulmonary adj3 hypertens$).ti,ab.

4. pulmonary vascular disease.ti,ab.

5. or/1‐4

6. exp Exercise/

7. exp Exercise Therapy/

8. Exercise Tolerance/

9. Physical Fitness/

10. Physical Exertion/

11. exp Ergometry/

12. Bicycling/

13. Weight Lifting/

14. Muscle Strength/

15. exercis$.ti,ab.

16. (conditioning or ergometry or treadmill or endurance or "upper limb" or "lower limb").ti,ab.

17. (walk$ or swim$ or cycle$ or cycling or bicycl$ or jog$).ti,ab.

18. ((strength$ or resistance$ or weight$) adj3 train$).ti,ab.

19. aerobic$.ti,ab.

20. rehabilitat$.ti,ab.

21. or/6‐20

22. 5 and 21

23. (controlled clinical trial or randomized controlled trial).pt.

24. (randomized or randomised).ab,ti.

25. placebo.ab,ti.

26. randomly.ab,ti.

27. trial.ab,ti.

28. groups.ab,ti.

29. or/23‐28

30. Animals/

31. Humans/

32. 30 not (30 and 31)

33. 29 not 32

34. 22 and 33

Embase (Ovid)

1. exp pulmonary hypertension/
2. (pulmonary adj3 hypertens$).ti,ab.
3. pulmonary vascular disease.ti,ab.
4. or/1‐3
5. exp exercise/
6. exp kinesiotherapy/
7. exp ergometry/
8. exp bicycle/
9. exp weight lifting/
10. muscle strength/
11. exercis$.ti,ab.
12. (conditioning or ergometry or treadmill or endurance or "upper limb" or "lower limb").ti,ab.
13. (walk$ or swim$ or cycle$ or cycling or bicycl$ or jog$).ti,ab.
14. ((strength$ or resistance$ or weight$) adj3 train$).ti,ab.
15. aerobic$.ti,ab.
16. rehabilitat$.ti,ab.
17. or/5‐16
18. 4 and 17
19. Randomized Controlled Trial/
20. randomization/
21. controlled clinical trial/
22. Double Blind Procedure/
23. Single Blind Procedure/
24. Crossover Procedure/
25. (clinica$ adj3 trial$).tw.
26. ((singl$ or doubl$ or trebl$ or tripl$) adj3 (mask$ or blind$ or method$)).tw.
27. exp Placebo/
28. placebo$.ti,ab.
29. random$.ti,ab.
30. ((control$ or prospectiv$) adj3 (trial$ or method$ or stud$)).tw.
31. (crossover$ or cross‐over$).ti,ab.
32. or/19‐31
33. exp animals/ or exp invertebrate/ or animal experiment/ or animal model/ or animal tissue/ or animal cell/ or nonhuman/
34. human/ or normal human/ or human cell/
35. 33 and 34
36. 33 not 35
37. 32 not 36
38. 18 and 37

PEDro

Field

Search term

Abstract & Title

pulmonary hypertension

Method

clinical trial

ClinicalTrials.gov

search field

search term

Study type

Interventional

Condition

Pulmonary hypertension

intervention

Exercise

Study flow diagram
Figures and Tables -
Figure 1

Study flow diagram

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
Figures and Tables -
Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies

Risk of bias summary: review authors' judgements about each risk of bias item for each included study
Figures and Tables -
Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study

Forest plot of comparison: 1 Exercise vs control, outcome: 1.1 Exercise capacity: 6MWD
Figures and Tables -
Figure 4

Forest plot of comparison: 1 Exercise vs control, outcome: 1.1 Exercise capacity: 6MWD

Comparison 1 Exercise vs control, Outcome 1 Exercise capacity: 6MWD.
Figures and Tables -
Analysis 1.1

Comparison 1 Exercise vs control, Outcome 1 Exercise capacity: 6MWD.

Comparison 1 Exercise vs control, Outcome 2 Exercise capacity: VO2peak.
Figures and Tables -
Analysis 1.2

Comparison 1 Exercise vs control, Outcome 2 Exercise capacity: VO2peak.

Comparison 1 Exercise vs control, Outcome 3 Exercise capacity: Peak power.
Figures and Tables -
Analysis 1.3

Comparison 1 Exercise vs control, Outcome 3 Exercise capacity: Peak power.

Comparison 1 Exercise vs control, Outcome 4 Exercisecapacity: Anaerobic threshold.
Figures and Tables -
Analysis 1.4

Comparison 1 Exercise vs control, Outcome 4 Exercisecapacity: Anaerobic threshold.

Comparison 1 Exercise vs control, Outcome 5 HRQoL SF36: Physical component score.
Figures and Tables -
Analysis 1.5

Comparison 1 Exercise vs control, Outcome 5 HRQoL SF36: Physical component score.

Comparison 1 Exercise vs control, Outcome 6 HRQoL SF36: Mental component score.
Figures and Tables -
Analysis 1.6

Comparison 1 Exercise vs control, Outcome 6 HRQoL SF36: Mental component score.

Comparison 1 Exercise vs control, Outcome 7 Adverse events.
Figures and Tables -
Analysis 1.7

Comparison 1 Exercise vs control, Outcome 7 Adverse events.

Comparison 1 Exercise vs control, Outcome 8 HRQoL SF36: Physical function.
Figures and Tables -
Analysis 1.8

Comparison 1 Exercise vs control, Outcome 8 HRQoL SF36: Physical function.

Comparison 1 Exercise vs control, Outcome 9 HRQoL SF36: Role physical.
Figures and Tables -
Analysis 1.9

Comparison 1 Exercise vs control, Outcome 9 HRQoL SF36: Role physical.

Comparison 1 Exercise vs control, Outcome 10 HRQoL SF36: Bodily pain.
Figures and Tables -
Analysis 1.10

Comparison 1 Exercise vs control, Outcome 10 HRQoL SF36: Bodily pain.

Comparison 1 Exercise vs control, Outcome 11 HRQoL SF36: General health.
Figures and Tables -
Analysis 1.11

Comparison 1 Exercise vs control, Outcome 11 HRQoL SF36: General health.

Comparison 1 Exercise vs control, Outcome 12 HRQoL SF36: Mental health.
Figures and Tables -
Analysis 1.12

Comparison 1 Exercise vs control, Outcome 12 HRQoL SF36: Mental health.

Comparison 1 Exercise vs control, Outcome 13 HRQoL SF36: Role emotional.
Figures and Tables -
Analysis 1.13

Comparison 1 Exercise vs control, Outcome 13 HRQoL SF36: Role emotional.

Comparison 1 Exercise vs control, Outcome 14 HRQol SF36: Vitality.
Figures and Tables -
Analysis 1.14

Comparison 1 Exercise vs control, Outcome 14 HRQol SF36: Vitality.

Comparison 1 Exercise vs control, Outcome 15 HRQoL SF36: Social function.
Figures and Tables -
Analysis 1.15

Comparison 1 Exercise vs control, Outcome 15 HRQoL SF36: Social function.

Comparison 1 Exercise vs control, Outcome 16 HRQoL: CAMPHOR activities.
Figures and Tables -
Analysis 1.16

Comparison 1 Exercise vs control, Outcome 16 HRQoL: CAMPHOR activities.

Comparison 1 Exercise vs control, Outcome 17 HRQoL: CAMPHOR symptoms.
Figures and Tables -
Analysis 1.17

Comparison 1 Exercise vs control, Outcome 17 HRQoL: CAMPHOR symptoms.

Comparison 1 Exercise vs control, Outcome 18 HRQoL: CAMPHOR QoL.
Figures and Tables -
Analysis 1.18

Comparison 1 Exercise vs control, Outcome 18 HRQoL: CAMPHOR QoL.

Comparison 1 Exercise vs control, Outcome 19 Cardiopulmonary haemodynamics.
Figures and Tables -
Analysis 1.19

Comparison 1 Exercise vs control, Outcome 19 Cardiopulmonary haemodynamics.

Comparison 1 Exercise vs control, Outcome 20 Functional class.
Figures and Tables -
Analysis 1.20

Comparison 1 Exercise vs control, Outcome 20 Functional class.

Comparison 1 Exercise vs control, Outcome 21 B‐type natriuretic peptide.
Figures and Tables -
Analysis 1.21

Comparison 1 Exercise vs control, Outcome 21 B‐type natriuretic peptide.

Comparison 1 Exercise vs control, Outcome 22 Exercise capacity: 6MWD, sensitivity analysis.
Figures and Tables -
Analysis 1.22

Comparison 1 Exercise vs control, Outcome 22 Exercise capacity: 6MWD, sensitivity analysis.

Comparison 1 Exercise vs control, Outcome 23 Exercise capacity: VO2peak, sensitivity analysis.
Figures and Tables -
Analysis 1.23

Comparison 1 Exercise vs control, Outcome 23 Exercise capacity: VO2peak, sensitivity analysis.

Comparison 1 Exercise vs control, Outcome 24 Exercise capacity: Peak power, sensitivity analysis.
Figures and Tables -
Analysis 1.24

Comparison 1 Exercise vs control, Outcome 24 Exercise capacity: Peak power, sensitivity analysis.

Comparison 1 Exercise vs control, Outcome 25 Exercise capacity 6MWD, PAH subgroup only.
Figures and Tables -
Analysis 1.25

Comparison 1 Exercise vs control, Outcome 25 Exercise capacity 6MWD, PAH subgroup only.

Comparison 1 Exercise vs control, Outcome 26 Exercise capacity: VO2peak, PAH subgroup only.
Figures and Tables -
Analysis 1.26

Comparison 1 Exercise vs control, Outcome 26 Exercise capacity: VO2peak, PAH subgroup only.

Comparison 1 Exercise vs control, Outcome 27 Exercise capacity: Peak power, PAH subgroup only.
Figures and Tables -
Analysis 1.27

Comparison 1 Exercise vs control, Outcome 27 Exercise capacity: Peak power, PAH subgroup only.

Comparison 1 Exercise vs control, Outcome 28 Exercise capacity: Anaerobic threshold, PAH subgroup only.
Figures and Tables -
Analysis 1.28

Comparison 1 Exercise vs control, Outcome 28 Exercise capacity: Anaerobic threshold, PAH subgroup only.

Comparison 1 Exercise vs control, Outcome 29 Exercise capacity: 6MWD, subgroup analysis for setting of rehabilitation.
Figures and Tables -
Analysis 1.29

Comparison 1 Exercise vs control, Outcome 29 Exercise capacity: 6MWD, subgroup analysis for setting of rehabilitation.

Summary of findings for the main comparison. Exercise compared to control for pulmonary hypertension

Exercise compared to control for pulmonary hypertension

Patient or population: people with pulmonary hypertension
Settings: inpatient or outpatient rehabilitation, or both
Intervention: exercise training
Comparison: control: people that had usual care and did not undertake exercise training programme

Outcomes

Illustrative comparative effects* (95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Response on control

Treatment effect

Control

Exercise

Change in functional exercise capacity (6MWD)
Distance, metres
Follow‐up median 12 weeks

Median change = 5 m

The mean exercise capacity 6MWD in the intervention groups was 60.12 higher
(30.17 to 90.07 higher)

165
(5 studies)

⊕⊕⊝⊝
low1,2

Subgroup PAH: (2 studies, n = 36), mean 6MWD for intervention group was 33.84 m higher (0.95 to 66.73 higher); these studies used outpatient exercise rehabilitation whilst other studies contributing to meta‐analysis had an inpatient training component

Minimal important difference was 30 metres

Exercise capacity: VO2peak

Oxygen uptake, ml/kg/min
Follow‐up median 13.5 weeks

Median change = ‐0.25 ml/kg/min

The mean VO2peak in the intervention groups was 2.41 ml/kg/min higher
(1.38 to 3.44 higher)

145
(4 studies)

⊕⊕⊝⊝
low1,2

Subgroup PAH (2 studies, n = 36), the mean VO2peak in the intervention groups was 1.28 ml/kg/min higher (‐0.19 to 2.75 higher); these two studies used outpatient exercise rehabilitation whilst other studies contributing to meta‐analysis had an inpatient training component

Exercise capacity: peak power

watts
Follow‐up median 13.5 weeks

Median change = 1 watt

The mean exercise capacity: peak power in the intervention groups was 16.44 W higher
(10.90 to 21.99 higher)

145
(4 studies)

⊕⊕⊝⊝
low1,2

Subgroup PAH (2 studies, n = 36), the mean peak power in the intervention groups was 14.24 watts higher (5.78 to 22.70 higher); these two studies used outpatient exercise rehabilitation whilst other studies contributing to meta‐analysis had an inpatient training component

HRQoL SF‐36: PCS

units

Follow‐up median 11 weeks

Median change = ‐0.49 units

The mean HRQoL SF‐36: PCS in the intervention groups was 4.63 higher (0.80 to 8.47 higher)

33
(2 studies)

⊕⊕⊝⊝
low2,3

Both studies were only PAH

HRQoL SF‐36: MCS

units

Follow‐up median 11 weeks

Median change = ‐0.31 units

The mean HRQoL SF‐36: MCS in the intervention groups was 4.17 higher (0.01 to 8.34 higher)

33
(2 studies)

⊕⊕⊝⊝
low2,3

Both studies were only PAH

*The basis for the response on control is the median control group response across studies

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.

1 Two studies did not report random sequence generation, no studies reported allocation concealment
2 Indirectness: 2 studies did not report number of people assessed to achieve sample size; trial participants may represent a highly selected subgroup of people with PH

3 Imprecision (2 small studies of 33 participants) and neither reported allocation concealment

Figures and Tables -
Summary of findings for the main comparison. Exercise compared to control for pulmonary hypertension
Comparison 1. Exercise vs control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Exercise capacity: 6MWD Show forest plot

5

165

Mean Difference (IV, Random, 95% CI)

60.12 [30.17, 90.07]

2 Exercise capacity: VO2peak Show forest plot

4

145

Mean Difference (IV, Random, 95% CI)

2.41 [1.38, 3.44]

3 Exercise capacity: Peak power Show forest plot

4

145

Mean Difference (IV, Random, 95% CI)

16.44 [10.90, 21.99]

4 Exercisecapacity: Anaerobic threshold Show forest plot

3

66

Std. Mean Difference (IV, Random, 95% CI)

1.05 [0.53, 1.58]

5 HRQoL SF36: Physical component score Show forest plot

2

33

Mean Difference (IV, Random, 95% CI)

4.63 [0.80, 8.47]

6 HRQoL SF36: Mental component score Show forest plot

2

33

Mean Difference (IV, Random, 95% CI)

4.17 [0.01, 8.34]

7 Adverse events Show forest plot

5

165

Risk Difference (M‐H, Random, 95% CI)

0.00 [‐0.04, 0.04]

8 HRQoL SF36: Physical function Show forest plot

4

118

Mean Difference (IV, Random, 95% CI)

6.13 [‐3.73, 16.00]

9 HRQoL SF36: Role physical Show forest plot

4

116

Mean Difference (IV, Random, 95% CI)

21.81 [14.40, 29.23]

10 HRQoL SF36: Bodily pain Show forest plot

3

88

Mean Difference (IV, Random, 95% CI)

5.64 [‐3.09, 14.36]

11 HRQoL SF36: General health Show forest plot

3

84

Mean Difference (IV, Random, 95% CI)

5.76 [‐0.80, 12.32]

12 HRQoL SF36: Mental health Show forest plot

3

87

Mean Difference (IV, Random, 95% CI)

6.21 [‐1.85, 14.27]

13 HRQoL SF36: Role emotional Show forest plot

3

87

Mean Difference (IV, Random, 95% CI)

2.79 [‐7.43, 13.01]

14 HRQol SF36: Vitality Show forest plot

4

115

Mean Difference (IV, Random, 95% CI)

13.47 [7.55, 19.40]

15 HRQoL SF36: Social function Show forest plot

4

118

Mean Difference (IV, Random, 95% CI)

14.01 [9.82, 18.21]

16 HRQoL: CAMPHOR activities Show forest plot

2

33

Mean Difference (IV, Random, 95% CI)

‐1.33 [‐3.56, 0.90]

17 HRQoL: CAMPHOR symptoms Show forest plot

2

36

Mean Difference (IV, Random, 95% CI)

‐3.08 [‐7.78, 1.62]

18 HRQoL: CAMPHOR QoL Show forest plot

2

36

Mean Difference (IV, Random, 95% CI)

‐5.42 [‐8.03, ‐2.81]

19 Cardiopulmonary haemodynamics Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Subtotals only

20 Functional class Show forest plot

2

40

Mean Difference (IV, Random, 95% CI)

‐0.60 [‐0.85, ‐0.35]

21 B‐type natriuretic peptide Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Subtotals only

22 Exercise capacity: 6MWD, sensitivity analysis Show forest plot

4

86

Mean Difference (IV, Random, 95% CI)

67.91 [27.12, 108.69]

23 Exercise capacity: VO2peak, sensitivity analysis Show forest plot

3

66

Mean Difference (IV, Random, 95% CI)

1.94 [0.86, 3.01]

24 Exercise capacity: Peak power, sensitivity analysis Show forest plot

3

66

Mean Difference (IV, Random, 95% CI)

15.27 [8.57, 21.97]

25 Exercise capacity 6MWD, PAH subgroup only Show forest plot

2

36

Mean Difference (IV, Random, 95% CI)

33.84 [0.95, 66.73]

26 Exercise capacity: VO2peak, PAH subgroup only Show forest plot

2

36

Mean Difference (IV, Random, 95% CI)

1.28 [‐0.19, 2.75]

27 Exercise capacity: Peak power, PAH subgroup only Show forest plot

2

36

Mean Difference (IV, Random, 95% CI)

14.24 [5.78, 22.70]

28 Exercise capacity: Anaerobic threshold, PAH subgroup only Show forest plot

2

36

Mean Difference (IV, Random, 95% CI)

41.31 [‐52.05, 134.67]

29 Exercise capacity: 6MWD, subgroup analysis for setting of rehabilitation Show forest plot

5

Mean Difference (IV, Random, 95% CI)

Subtotals only

29.1 Inpatient exercise training

3

129

Mean Difference (IV, Random, 95% CI)

72.79 [28.09, 117.49]

29.2 Outpatient exercise training

2

36

Mean Difference (IV, Random, 95% CI)

33.84 [0.95, 66.73]

Figures and Tables -
Comparison 1. Exercise vs control