Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

Follow-up

Outcome measures and effect size

Comments

Exercise training

Coelho, 2018

Type of study:

RCT

Setting:

Outpatient clinic

Country:

Brazil

Source of funding:

Inclusion criteria:

- 18 to 65 years old

- asthma diagnosis for at least 6 months (Global Initiative for Asthma, 2011)

- were under regular drug therapy with at least moderate doses of inhaled corticosteroids (daily dose above 400 mcg of budesonide equivalent) or with

inhaled corticosteroids plus long-acting beta2-agonists and were clinically stable during the run-in period (21 days)

Exclusion criteria:

- self-report of exercise of any intensity and duration over once a week

- disabling musculoskeletal disease

- cardiopathy

- coronariopathy

- other lung diseases,

- more than 10 pack-years of smoking, illiteracy, pregnancy, and refusal to participate

N total at baseline:

Intervention: 20

Control:17

Important prognostic factors²:

Age ± SD:

I: 45±19 yrs

C: 47±14 yrs

Sex:

I: 10% M

C: 18% M

BMI ± SD:

I: 27,1±6,5 kg/m2

C: 30,3±7,4 kg/m2

ACQ

I: 1,7±1,4

C: 1,8±0,8

Groups comparable at baseline? Yes (no statistically differences, but it is possible that there is a clinical significant difference in BMI)

Describe intervention (treatment/procedure/test):

Unsupervised pedometer-based physical activity program

All participant (intervention and placebo group) attended to an individual standardized educational session with the same physical therapist. The session lasted about one hour and covered important aspects of asthma management and the benefits of exercise on general health and asthma. Moreover, each volunteer was encouraged to start walking at moderate intensity (according to the talk test), at least 5 times per week, for a minimum of 30 minutes. The exercise recommendation included stretching some of the main

ambulatory muscles prior to walking (quadriceps, hamstring, and triceps sural muscles) and using short-acting beta2-agonists

before exercising, if necessary.

Describe control (treatment/procedure/

test):

Length of follow-up:

12 weeks intervention;

Long-term effects were measured after 24-28 weeks.

Loss-to-follow-up:

Intervention:

N=2 (10%)

Reasons: did not attend to reassessment

Control:

N=1 (6%)

Reasons: exacerbation during reassessment

Incomplete outcome data:

Intervention:

N=5 (25%)

Reasons: discontinued intervention (1 angina suspect, 1 back pain crisis, 1 wishes to withdrawal); 2 missed reassessment

Control:

N=2 (12%)

Reasons: discontinued intervention (1 angina suspect); 1 missed reassessment

Outcome measures and effect size (include 95%CI and p-value if available):

Outcome measure 1: ACQ

12 weeks, adjusted difference: -0,3 (-0,8, 0,2).

24-28 weeks, adjusted difference: −0.2 (−0.7 to 0.3)

Outcome measure 2: AQLQ

12 weeks, adjusted difference: 0.3 (−0.3 to 0.9)

24-28 weeks: 0.2 (−0.5 to 0.9)

Outcome measures 3: 6MW

12 weeks, adjusted difference: 21.9 (6.6 to 37.3)

24-28 weeks: 19.6 (−7.4 to 46.5)

Outcome measure 4: Daily steps

12 weeks, adjusted difference: 2488 (803 to 4172)

24-28 weeks: 1367 (−1358 to 4093)

Ook HADS (depressive) meegenomen

Authors conclusions:

The major findings of the present study are that the 12-

week unsupervised pedometer-based physical activity program

resulted in a significant increase in daily steps and in

the distance walked during the 6MWT among adults with

moderate to severe asthma. However, these improvements

were no longer significant 24–28 weeks after randomization.

There were no changes in disease control or in psychological

parameters at any time points.

Franco-Pinto, 2015

Type of study:

RCT

Setting:

Outpatient clinic

Country:

Brazil

Source of funding:

Inclusion criteria:

Outpatients with moderate or severe persistent asthma (GINA, 2005), aged between 20 and 59 years; The patients were managed under optimal medical treatment, monitored by pulmonologists for at least 6 months and considered clinically stable (without exacerbations or changes in medication

for at least 30 days).

Exclusion criteria:

cardiovascular, musculoskeletal or other chronic lung diseases; current participation in a moderate or vigorous exercise programme; and current smokers or ex-smokers.

N total at baseline:

Intervention: 30

Control: 28

Important prognostic factors²:

Age ± SD:

I: 40±11 yrs

C: 44±9 yrs

Sex:

I: 5/22= 23% M

C: 4/21= 19% M

BMI ± SD:

I: 26,5±4,2 kg/m2

C: 26,4±4,3 kg/m2

ACQ:

I: 1,6±0.9

C: 1,4±1,2

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

Aerobic training programme (twice a week, on a treadmill, 35 minutes) + breathing exercises (yoga breathing exercises twice a week, 30 minutes) + educational programme

Describe control (treatment/procedure/test):

educational programme

+ breathing exercises (sham intervention)

Length of follow-up:

12 weeks

Loss-to-follow-up:

Intervention:

N=8 (27%)

Reasons: other health nor related with asthma, work of family problems)

Control:

N=7 (25%)

Reasons: Reasons: other health nor related with asthma, work of family problems)

Incomplete outcome data:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

Outcome measures and effect size (include 95%CI and p-value if available):

Outcome measure 1: ACQ-7

Mean between-group differences:

0.2 (−0.3 to 0.7)

Outcome measure 2: AQLQ

Mean between-group differences:

−0.9 (−1.7 to −0.1)

Outcome measure 3: FEV1

−0.0 (−0.5 to 0.4)

Outcome measure 4: FEV1% predicted

2.5 (−11.5 to 16.5)

Outcome measure 7: bronchial hyperresponsivess

After the intervention, the BHR decreased in the TG (n=18), with an increment in PC20 of 1 dd

(95% CI 0.3 to 1.7 dd), and did not change in the CG (n=19) (0.06 dd; 95% CI −0.6 to 0.7 dd) (p=0.039).

Primary outcome measure: bronchial hyperresponsiveness.

Authors conclusion:

The results of the current study demonstrate that a 12-week

aerobic training programme reduces BHR and serum proinflammatory

cytokines and improves quality of life and asthma exacerbation

in adults with moderate to severe persistent asthma. In

addition, it seems that aerobic training reduces sputum eosinophils

and FeNO in patients with higher inflammation and

improves clinical control in patients with worse asthma control

Refaat, 2015

Type of study:

RCT

Setting: hospital and physiotherapy center

Country:

Kuweit

Source of funding:

Inclusion criteria:

Moderate or severe asthma according to GINA criteria; clinically stable.

Exclusion criteria:

co-existing respiratory, cardiac, or any medical diseases that might impair exercise training. Pregnant patients or planned pregnancy, and patients with smoking history 62 years before

enrolment were also excluded.

N total at baseline:

Intervention: 38

Control: 30

Age ± SD:

I: 35,8±1,7 yrs

C: 38±5,3 yrs

Sex:

I: 44,7% M

C: 46,7% M

BMI ± SD:

I: 23±1,8 kg/m2

C: 22±0,7 kg/m2

Moderate asthma: 48

Severe asthma: 20

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

6-week exercise program + standard medical care

Supervised physical training was performed for three exercise sessions every week for six weeks

at a physiotherapy Centre

Describe control (treatment/procedure/test):

Standard medical care.

They were advised to refrain from any structured exercise

(i.e., maintained their current behavior and usual life activities)

throughout the intervention period

Length of follow-up:

6 weeks exercise; follow-up measurements at 3 months

Loss-to-follow-up:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

Incomplete outcome data:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

Outcome measures and effect size (include 95%CI and p-value if available):

Outcome measure 1: ACQ

Nr

Outcome measure 2: AQLQ

Baseline I: 5.6±2.4

Post-training I: 5.8 ±0.2*

3months I: 6.0±7.3*

* Intragroup difference p<0,05

Baseline C: 5.5± 1.4

Post-training C: 5.6±0.3

3months C: 5.6± 1.8

Outcome measure 3: FEV1

Baseline I: 2.42 ±0.53

After I: 2.78± 0.42, p<0,05

Baseline C: 2.52 ±0.11

Post-training C: 2.51± 0.40, p>0,05

Scores after the intervention differed between groups (p<0,05).

Mendes, 2011

Type of study:

RCT

Setting:

Outpatient clinic

Country:

Brazil

Source of funding:

FAPESP grants 2002/08422-7.

Inclusion criteria:

- moderate of severe persistent asthma

- between 20 and 50 yrs of age.

Patients were under medical treatment for at least 6 months and were considered clinically stable (i.e., no rises or changes in medication for at least 30 d).

Exclusion criteria:

cardiovascular, pulmonary, or musculoskeletal diseases that would impair exercise training

N total at baseline:

Intervention: 34

Control: 34

Some patients participated simultaneously in the study of Mendes, 2010 (n=28)

Important prognostic factors²:

(data only from patients who completed the study)

age (95%IC):

I: 37.9 (25.7-47.3) yrs

C: 36.0 (22.0-47.5) yrs

Sex:

I: 11% M

C: 25% M

BMI (95%CI):

I: 24.5 (19.4-29.2) kg/m2

C: 25.8 (18.2-29) kg/m2

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

Aerobic training program

for 30 min per session twice a week for 3 months in an

indoor treadmill

+ educational program (4h: two classes) + breathing exercise program

Describe control (treatment/procedure/test):

Eduactional program (4h; two classes) + breathing exercise program (0-min session was performed

twice a week for 3 months)

Length of follow-up:

3 months

Loss-to-follow-up:

Intervention:

N=7 (21%)

Reasons: other health, work and family problems

Control:

N=10 (29%)

Reasons= other health, work and family problems

Incomplete outcome data:

Intervention:

N=7 (21%)

Reasons: other health, work and family problems

Control:

N=10 (29%)

Reasons= other health, work and family problems

Outcome measures and effect size (include 95%CI and p-value if available):

Outcome measure 1: ACQ

NR

Outcome measure 2: AQLQ

NR

Outcome measure 3: FEV1 (L)

Baseline I: 2.2 (1.2-3.2)

Post-training I: 2.3 (1.0-3.4)

Baseline C: 2.52 (1.3-3.2)

After C: 2.5 (1.3-3.5)

p=0.71

Outcome measure 4: FEV1% predicted

Baseline I: 85.5 (45.4-112.6)

Post-training I: 84.4 (42.0-114.4)

Baseline C: 79.9 (43.5-107.0)

After C: 79.6 (37.5-106.5)

p=0.89

Outcome measure 5: VO2 max (% predicted)

Baseline C 73.4 (52.5-98.3)

After C: 75.6 (57.6-99.5)

Baseline I: 73.5 (43.6-96.3)

After I: 88.0 (64.9-109.3)

A positive response to

training (improvement in V˙ O2max Q10%) was found in 24 patients (88%) who were considered ‘‘responders.’’

During the 3 months of intervention, the number of visits to the emergency

room (4CG/1TG) and asthma exacerbations (7CG/1TG) was lower in the TG compared with the CG (P G 0.01).

Mendes, 2010

Type of study:

RCT

Setting:

Outpatient clinic

Country:

Brazil

Source of funding:

Fundação de

Amparo à Pesquisa de São Paulo (grants 02/08422-7 and 07/56937-0)

and Conselho Nacional de Pesquisa (grants 480869/04-9)

Inclusion criteria:

- moderate of severe persistent asthma

- between 20 and 50 yrs of age.

Patients were under medical treatment for at least 6 months and were considered clinically stable (i.e., no crises or changes in medication for at least 30 d).

Exclusion criteria:

cardiovascular, pulmonary, or musculoskeletal diseases that would impair exercise training

N total at baseline:

Intervention: 50

Control: 51

Important prognostic factors²:

Age (95%CI):

I: 39.0 (22.0-47.9)

C: 39.5 (23.5-47.0)

Sex:

I: 11 % M

C: 22% M

BMI (95%CI):

I: 25.2 (18.0-29.0

C: 24.5 (20.0-27.3)

Groups comparable at baseline?

Describe intervention (treatment/procedure/test):

Aerobic training program based on VO2 max:

for 30 min per session twice a week for 3 months

+ educational program (4h: two classes)

+ breathing exercise program

Describe control (treatment/procedure/test):

Eduactional program (4h; two classes) + breathing exercise program (0-min session was performed

twice a week for 3 months)

Length of follow-up:

3 months

Loss-to-follow-up:

Intervention:

N=6 (12%)

Reasons: other health, work and family problems

Control:

N=6 (12%)

Reasons= other health, work and family problems

Incomplete outcome data:

Intervention:

N=6 (12%)

Reasons: other health, work and family problems

Control:

N=6 (12%)

Reasons= other health, work and family problems

Outcome measures and effect size (include 95%CI and p-value if available):

Outcome measure 1: ACQ

NR

Outcome measure 2: HRQoL

Baseline I: 61.8 (33.9-84.5)

After I: 39.8 (25.0-63.3) a

Baseline C: 61.3 (36.5-79.1)

After C: 66.0 (34.3-83.0)

P<0.001

Five patients (control

group, n = 4; training group, n = 1) visited the emergency department, and eight (control group, n = 7; training group, n=1) had asthma exacerbations during

the study.

Outcome measure 3: FEV1 (L)

I baseline: 2.3 (1.3-3.2)

I after: 2.3 (1.0-3.4)

C baseline: 2.3 (1.4-3.19)

C after: 2.4 (1.4-3.4)

P=0.49

Outcome measure 4: FEV1% predicted

I baseline: 78.0 (48.0-107.7)

I after: 82.6 (40.0-109.9)

C baseline: 84.0 (53.5-105.3)

C after: 80.0 (49.8-101.9)

P=0.93

Outcome measure 5: VO2 max

N=49/89 (55%).

After the study, only the training group showed an increase in V o 2 max compared with the control group ( P , .001)

without changes in the pulmonary function

( Table 4 ).

Other outcome measures: STAI (State-trait Anxiety Inventory); BDI (depression)

Turner, 2010

Type of study:

RCT

Setting:

Country:

Australia

Source of funding:

Inclusion criteria:

at least 40 years old, had a diagnosis of moderate or severe persistent asthma

with evidence of fixed airflow obstruction following a trial of maximum bronchodilator therapy and a trial of oral corticosteroids of at least 3-week duration.

Exclusion criteria:

evidence of co-existing respiratory

conditions; respiratory tract infection in the previous 4 weeks; current smokers or ex-smokers who ceased within the previous 2 years; smoking history 1 15 pack years; co-morbid conditions

likely to reduce exercise capacity; current participation in 1 30 min/day of moderate or vigorous exercise, and participation in a PRP in the previous 12 months

N total at baseline:

Intervention: 20

Control: 15

Important prognostic factors²:

For example

age ± SD:

I: 63.5±10.8 yrs

C: 71.0±9.7 yrs

Sex:

I: 42% M

C: 47% M

BMI

I: 28.6±5.0 yrs

C: 26.8±7.6 yrs

Groups comparable at baseline?

Describe intervention (treatment/procedure/test):

Exercise program: three exercise classes 980-90 minutes) each week for 6 weeks in the Physiotherapy Department (Sir Charles Gairdner Hospital), supervised by a physiotherapist

Describe control (treatment/procedure/test):

standard

medical care for

Length of follow-up:

Intervention was 6 weeks, follow-up was 3 months

Loss-to-follow-up:

Intervention:

N=1 (%)

Reasons: withdran after baseline assessments due to personal reasons

Control:

N=3 (%) (at 3 months)

Reasons: lost interes, time commitments, medical problems

Incomplete outcome data:

Intervention:

N=1 (5%)

Reasons: withdran after baseline assessments due to personal reasons

Control:

N=3 (20%) (at 3 months)

Reasons: lost interes, time commitments, medical problems

Outcome measures and effect size (include 95%CI and p-value if available):

Outcome measure 1: ACQ

Baseline I: 1,7±0,7

Baseline C: 1,7±1,0

Post-intervention I: 1,5±0,6

Post-intervention C: 1,7±1,0

No significant differences after the intervention or after 3 months.

Outcome measure 2: AQLQ

Change, intervention – placebo (95%CI)

Symptoms: 0.61 (0.26–0.97, p = 0.001)

Activity limitation: 0.43 (0.01–0.84, p = 0.04)

and at the 3-month follow-up

(symptoms, 0.57, 0.18–0.95, p = 0.005, and activity limitation,

0.55, 0.01–1.10, p = 0.04,

Outcome measure: dyspneu

I, baseline: 3.0±1.0

I after: 3.0±2.0

I 3 months: 3.0±1.0

C baseline: 2.5±2.8

C after: 2.5±1.8

C 3 months: 2.0±1.0

Breathing exercises and yoga

Rondinel, 2015

Type of study:

RCT

Setting:

Country: Brazil

Source of funding: The authors have no conflicts of interest to disclose regarding

this article.

Inclusion criteria:

Patients, aged 20-80 years, with severe asthma (inhalation of high doses of steroids (>800 mg per day), who use long-acting beta-2-agonists and FEV1 postbronchodilator (<80%), according to the GINA and Guidelines of the Brazilian Thoracic Association for the Treatment of Asthma), diagnosed 12 months prior to the study.

Exclusion criteria:

history of chest surgery, the presence of another chronic lung disease, infectious lung diseases currently being treated, acute myocardial infarction in the last 6 months, another significant

disease besides asthma, acute severe asthma at the moment of inclusion or recent hospitalisation for more than 24 h in the last 30 d before inclusion, recent acute illness, illiteracy,

smoking (more than five packs per year, or stopped smoking less than 1 year ago), inability to perform spirometry and an inability to attend study visits

N total at baseline:

Intervention: 11

Control: 8

Important prognostic factors²:

Age, medium (range):

I: 57 (37–61)

C: 63 (54–61)

Sex:

I: 25% M

C: 33% M

BMI, medium (range):

I: 28.2 (22.4–35.1)

C: 27.1 (19.9–34.2)

ACQ:

I: 2.2 (1.0,3.6)).

C: 2.1 (0.3,2.4))

Groups comparable at baseline? yes

Describe intervention (treatment/procedure/test):

Incentive spirometry (IS; Spiro-Ball, Leventon, Spain ) and expiratory positive airway pressure (EPAP; Vital Signs, Totowa, USA).

The IS + EPAP group performed breathing exercises at home, twice

daily for 20 min, over a period of 5 weeks.

Describe control (treatment/procedure/test):

Usual care

Length of follow-up:

5 weeks

Loss-to-follow-up:

Intervention:

N=2 (18%)

Reasons: gave up intervention, complications

Control:

N=2 (25%)

Reasons: gave up intervention

Incomplete outcome data:

Intervention:

N=3 (27%)

Reasons; gave up intervention, complications, asthma exacerbation

Control:

N=2 (25%)

Reasons: see above

Outcome measures and effect size (include 95%CI and p-value if available):

Outcome measure 1: ACQ

I: change: -1 (-1.6, 0.6)

C: change: 0.1 (-0.4, 0.8)

P<0.05

Outcome measure 2: AQLQ

I: change: 1 (0.4,2.7)

C: change: 0.3 (-0.1,1.3)

P<0.05

Outcome measure 3: FEV1

No difference

Outcome measure 4: 6MWT

I: 62.5% had clinically significant differences (more than 25 m)

C: 16.6%

P= 0.13).

Shaw, 2011

Type of study:

Single blind RCT

Setting:

Country:

Source of funding:

Inclusion criteria:

Inactive, moderate-persistent asthmatic males and females aged between 18 and 34 years and who met the criteria of moderate-persistent asthma based

on the National Institutes of Health (NIH) guidelines (60-80% of predicted FVC, FEV1 and/or PEF) were included in the study. Furthermore, subjects were nonsmokers, were free from any influenza-like or respiratory infection symptoms 2-3 weeks prior to the evaluations, exhibited daily asthmatic symptoms, exhibited nocturnal asthmatic symptoms more than one night weekly, and had peak flow variability of more than 30%.

Exclusion criteria:

relative and absolute contraindications to exercise (16),

suffered from asthma exacerbations within that last 7 days

prior to the inception into the study, were unable to abstain

from their prescribed asthma medication use 12 h before

each evaluation, and were not weight stable for at least 6 months prior to the study.

N total at baseline:

AE: 22

DR: 22

CE: 22

C: 22

Important prognostic factors²:

Age ± SD:

AE: 21.95±3.87

DR: 21.93±3.95

CE: 22.00±3.95

C: 21.90±3.89

Sex: 64% men

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

Supervised, home-based exercise interventions

Aerobic exercise (AE): walked and/or jogged for

30 min at an intensity of 60% of their individual age-predicted maximum heart rate (HRmax)

Diaphragmatic inspiratory resistive breathing (DR):

diaphragmatic breathing combined with inspiratory resistive breathing in the semirecumbent position with posterior pelvic tilting, knees flexed, and neck extended.

Aerobic exercise combine with diaphragmatic inspiratory resistive breathing (CE)

A combination of

aerobic exercise and diaphragmatic breathing.

Describe control (treatment/procedure/test):

Non-exercise control (NE): subjects were instructed to

maintain their normal daily activities throughout the 8-week

experimental period and were phoned three times weekly to

ensure compliance

Length of follow-up:

8 weeks

Loss-to-follow-up:

N=0 (0%)

Incomplete outcome data:

N=0 (0%)

Outcome measures and effect size (include 95%CI and p-value if available):

Outcome measure 3: FEV1 (L)

AE baseline: 2.72±0.53

AE post-test: 2.97±0.65*

DR baseline: 2.85±0.57

DR post-test: 3.22±0.63*

CE baseline: 2.70±0.67

CE post-test: 3.30±0.70*

C baseline: 2.62±0.53

C post-test: 2.70±0.5n

* statistically significant, p<0.05

Post-hoc analyses showed that CE was more effective than AE, and equally effective as DR. DR and AE were equally effective.

No significant differences in compliance to the exercise

programs were found between the groups, with all subjects

having 100% adherence to their respective exercise interventions.

Note: there were many comparisons made, so risk of chance findings.

McHugh, 2003

Type of study:

Blinded RCT

Setting:

Country: New Zealnd

Source of funding: funded by grants from White Cross Group and

the Tairawhiti Therapeutics and Arts Trust

Inclusion criteria:

Patients between 18 and 70 years old, previously diagnosed with asthma by their GP, and using moderate to high doses of medication for asthma. For the

purposes of this study, asthma was defined as a history of variable difficulty in breathing with wheeze or chest tightness, and improvement after the use of a ß2-agonist. A ‘moderate to high’ dose was defined as at least 1400 mcg of short-acting ß2-agonist weekly (or equivalent long-acting ß2-agonist)

and/or significant use of inhaled steroid medication (1400 mcg of beclomethasone or equivalent per

week). This was measured over the last week of the run-in period.

Exclusion criteria:

experienced a change in inhaled steroid dose or used oral steroids during the four-week run-in period.

N total at baseline:

Intervention: 19

Control: 19

Important prognostic factors²:

Age (range):

I: 48.8 (24-69)

C: 44.0 (18-66)

Sex:

I: 24% M

C: 24% M

Groups comparable at baseline? Yes, except that the BBT group had a significantly lower PEV1-% at the end of the run-in period.

Describe intervention (treatment/procedure/test):

Buyteyko Breathing Technique (BBT), consisting of a series of exercises promoting hypoventilation.

Trial participants underwent training simultaneously in two separate groups. Teaching occurred over

seven days with each session lasting 60–90 minutes.

Describe control (treatment/procedure/test):

Control training consisted of general asthma education and relaxation techniques, as currently used by Gisborne Hospital.

Trial participants underwent training simultaneously in two separate groups. Teaching occurred over

seven days with each session lasting 60–90 minutes.

Length of follow-up:

6 months

Loss-to-follow-up:

Intervention

N=2 (11%)

Reasons: not described

Control:

N=2 (11%)

Reasons: not described

Incomplete outcome data:

Intervention:

N=2 (11%)

Reasons: not described

Control:

N=2 (11%)

Reasons: not described

Outcome measures and effect size (include 95%CI and p-value if available):

Outcome measure 3: FEV1 (%)

Baseline BBT: 70.8±16.3

Baseline control: 82.7±16.2

At baseline significantly different, after 6 months not anymore. No significant change

Outcome measure 4: Steroid reduction (inhaled)

Baseline BBT: 909±881

Baseline Control: 896±502

BBT 3 months: 50% reduction

Control 3 months: 1% increase

P=0.003

Cooper, 2003

Type of study:

RCT

Setting:

Country:

UK

Source of funding:

Inclusion criteria:

Non-smoking, aged 18-70 years with stable asthma; taking an inhaled short acting b2 agonist at least twice a week and regular inhaled corticosteroids with no change in dose in the preceding 4 weeks; pre-bronchodilator forced expiratory volume in 1 second (FEV1) of at least 50% predicted and a 10% increase following 400 mg inhaled

salbutamol; a provocative dose of methacholine causing a 20% fall in FEV1 (PD20) of 10.24 mmol or less; and a mean daily symptom score of one or more during the run in period

Exclusion criteria:

Subjects taking treatment other than sodium cromoglycate (one subject) were excluded.

N total at baseline:

Intervention Buteyko: 30

Intervention PCLE: 30

Control: 30

Important prognostic factors²:

For example

age ± SD:

I:

C:

Sex:

I: % M

C: % M

Groups comparable at baseline?

Describe intervention (treatment/procedure/test):

A. Eucapnic Buteyko technique, taught in five 2-hour sessions. After the instruction, subjects were instructed to do the technique twice a day

B. Cylinder with an expiratory resistance: Pink City Lung Exerciser. One session of training.

Both groups were told only to use B2-agonists for relief of symptoms.

Describe control (treatment/procedure/test):

C. Placebo PCLE device (without valve and with a leak ensured no resistance to breathing).

Length of follow-up:

6 months

Loss-to-follow-up:

Intervention B:

N=7 (%)

Reasons: lack of time/no perceived benefit (n=2); health reasons (n=3); no reason given (n=2)

Intervention PCLE:

N=6 (%)

Reasons: lack of time/no perceived benefit (n=5); health reasons (n=1)

Control:

N=7 (%)

Reasons: lack of time/no perceived benefit (n=6); no reason given (n=1)

Incomplete outcome data:

Intervention B:

N=7 (%)

Intervention PCLE:

N=6 (%)

Control:

N=7 (%)

Outcome measures and effect size (include 95%CI and p-value if available):

Outcome measure 1: ACQ

NR; self-reported symptoms remained relatively stable in the PCLE (–1 (–2 to 0.75) and placebo (medium change 0 (IQR –1 to 1) groups but were reduced in the Buteyko group –3 (–4 to 0) (p=0.003).

Outcome measure 2: AQLQ

A baseline: 0.45 (–0.13 to 1.11)

A 26 weeks: 0.57 (0.07 to 1.10)

B baseline: 0.45 (0.11 to 1.47)

B 26 weeks: 1.03 (0.19 to 1.69)

C baseline: 0.33 (–0.20 to 0.75)

C 26 weeks: 0.61 (–0.11 to 0.95)

P=0,2

Outcome measure 3: FEV (L)

Mean change ± SD

A: 0.06±0.26

B: –0.002±0.14

C 0.001±0.14

P=0,4

Outcome measure 4: FEV1 predicted (%)

NR

Outcome measure 5: steroid reductive

The extent to which

subjects could reduce their inhaled steroid did not differ significantly between groups (p=0.7) (n=60)

Other outcome measures: PD20

There was little change in PD20 from baseline during the study and no significant difference between the groups at 3 and 6 months.

Authors conclusions:

‘In this randomised controlled trial subjects taught the Eucapnic

Buteyko technique had reduced asthma symptoms and

bronchodilator use compared with the other two groups but

there was no difference in bronchial responsiveness or FEV1.

No difference was seen between the PCLE and PCLE placebo

device for any outcome measure.’

Study reference

(first author, publication year)

Describe method of randomisation

Bias due to inadequate concealment of allocation?

(unlikely/likely/unclear)

Bias due to inadequate blinding of participants to treatment allocation?

(unlikely/likely/unclear)

Bias due to inadequate blinding of care providers to treatment allocation?

(unlikely/likely/unclear)

Bias due to inadequate blinding of outcome assessors to treatment allocation?

(unlikely/likely/unclear)

Bias due to selective outcome reporting on basis of the results?

(unlikely/likely/unclear)

Bias due to loss to follow-up?

(unlikely/likely/unclear)

Bias due to violation of

intention to treat analysis?

(unlikely/likely/unclear)

Coelho, 2018

Randomization

was performed through a random number sequence (http://www.

randomizer.org), generated by an independent observer and inserted in sealed opaque envelopes.

Unlikely

Unclear; participants could not be blinded, but there was a well-thought control group

Unclear

Unclear

Unlikely

Unclear; in intervention group higher number of lost to follow-up.

Unlikely

Franco-Pinto, 2015

the eligible patients were randomly

assigned following simple randomisation procedures

(drawing of a sealed opaque envelope containing group code

control group (CG) or training group (TG)) by a researcher not

involved in the study.

Unlikely

Unclear; participants could not be blinded, but there was a well-thought control group

Unlikely (single-blind)

Unlikely (The statistical analysis was blinded to the treatment allocation)

unlikely

High lost-to-follow up rate, but similar between groups

Likely; only per protocol analyses

Refaat, 2015

Not described

Unclear

Likely

Likely

Unclear

unclear

Likely; not reported

Unclear; not described

Mendes, 2011

Patients were randomized by drawing lots into control or

training groups

Unclear

Unclear; participants could not be blinded, but there was a well-thought control group

Likely

Likely

Unlikely

Unlikely, drop-out was high in both groups

Unclear

Mendes, 2010

Patients were randomized (by

drawing lots) into a control group or a training group

Unclear

Unclear; participants could not be blinded, but there was a well-thought control group

Likely

Likely

Unlikely

Unlikely; drop-out rate was equal

Unclear

Turner, 2010

Subjects meeting the above-defined criteria were enrolled in

the trial, stratified by gender and randomised (https://www.randomizer.org/) into an ‘exercise group’ and a ‘control group

Unclear

The investigators were blinded to the subjects’ group

allocation until subjects had completed the run-in period.

Breathing exercises

Rondinel, 2015

Randomisation was performed with a computerised random

number generator (https://www.randomizer.org/).

Unlikely

Likely

Unlikely (The main

investigator, who was unaware of the group allocation of the

subjects, assessed these evaluations)

Unlikely

Unlikely

Unclear; very low numbers included in analyses; drop-out rate was ~25%

Likely; no intention-to-treat analyses available.

Shaw, 2011

Subjects were

matched by age (using years) and gender and randomly assigned using concealed envelopes to one of the following four groups

Unclear

Likely

Likely

Unlikely

Unlikely

Unlikely; no drop-outs

Unlikely

McHugh, 2003

Participants were paired on the basis of severity of asthma. They were then randomised to either Buteyko or control group using a computer-generated list.

Unclear

Unlikely (Trial participants were blinded as to

whether they had been assigned to the treatment or control group)

Likely

Unlikely (Investigators involved in pulmonary

function testing and other outcome assessments were blinded as to treatment assignment as were

investigators who contacted participants during the study to advise re drug dosing)

Unlikely

Unlikely

Likely; no intention-to-treat analyses available

Cooper, 2003

Eligible subjects

were then allocated to one of the three treatment groups using the next available number from computer generated numbers,

randomised in blocks of six, and using sealed envelopes

prepared independently. To ensure sufficient numbers for the

Buteyko sessions, randomisation was skewed towards the

Buteyko group except for the last 12 patients who were

randomised between the two PCLE group

Unclear

Likely

Likely

Unlikely (The assessor was not told which breathing technique subjects were using and subjects were asked not to mention it)

Unlikely

Unlikely

Unlikely

Auteur en jaartal

Redenen van exclusie

Systematische reviews

Cordova-Rivera, 2018

kijkt naar associaties tussen fysieke activiteit en sedentaire tijd met astma-uitkomsten

Vermeulen, 2016

niet-systematisch review, niet de juiste onderzoeksvraag

Yang, 2016

astma breed, wel subgroep analyses naar ernst, maar geen studies beschikbaar voor ernstig astma

Gimeno-Santos, 2015

protocol voor review; nog geen gepubliceerd review beschikbaar

Ruiz, 2015

artikel in het Spaans

Yorke, 2015

Breed review, geen kwantitatieve data waardoor review niet erg bruikbaar is.

British guideline, 2014

astma breed, brede interventies; geen systematische uitwerking van literatuur

Carson, 2014

alleen abstract (voor Cochrane review)

Humphreys, 2013

voldoet niet aan PICO

Pereira, 2014

commentary on other article (wellicht gebruiken voor overwegingen)

Schliehe, 2014

lijkt narrative review/editorial bij COPD en astma

Avallone, 2013

beschrijft associatie tussen astma en fysieke activiteit

Bruurs, 2013

astma breed, geen onderverdeling ernstig astma

Eichenberger, 2013

recenter review beschikbaar

Freitas, 2013

geen ernstig astma (only mild and moderate)

Pakhale, 2013

breed review, veel studies bij kinderen; de enige geschikte studie is elders uitgewerkt

Prem, 2013

I=diafragmatic breathing, 2/3 studies gedaan in mild-moderate, 1/3 onduidelijk

Saguil, 2013

samenvatting van review Chandratilleke, 2012

Silva, 2013

4/5 studies had mild-moderate astma; 1 studie astma breed

Adeniyi, 2012

(evt studies in severe eruit filteren)

Chandratilleke, 2012

nieuwere versie beschikbaar (Carson, 2014) (gebruikt in oude richtlijn)

Dennis, 2012

astma breed

Eijkemans, 2012

alleen observationele studies

Heikkinen, 2012

recenter review beschikbaar; de enige geschikte studie is elders uitgewerkt

Pacheco, 2012

(breed review, relevante artikelen eruit halen)

Bruton, 2011

lijkt narrative review; niet de meest recente

Burgess, 2011

recentere reviews beschikbaar

Eves, 2011

breed review, ook COPD; niet systematisch uitgewerkt

Posadzki, 2011

recenter review beschikbaar

Molassiotis, 2010

breed review, ook COPD; voldoet niet aan PICO

Roberston-Malt, 2010

breed review; recentere reviews beschikbaar

Ernst, 2009

voldoet niet aan PICO

Holloway, 2009

niet de meest recente versie van Cochrane review

Levy, 2008

niet de meest recente versie van Britse richtlijn

Ram, 2009

niet de meest recente versie van Cochrane review

Eneli, 2008

weight loss: verkeerde interventie

Googman, 2008

verkeerde interventie? 1 studie gedaan bij volwassenen (Arandelovic, 2007)

Ernst, 2006

verkeerde interventie

Russia Ministry of Health

Bruton, 2005

narrative review

Hondras, 2005

voldoet niet aan PICO

Ram, 2005

niet de meest recente versie van Cochrane review

Holloway, 2004

niet de meest recente versie van Cochrane review (ook in oude richtlijn opgenomen)

Magnusson, 2004

artikel in het Noors

Barnabe, 2003

gemende groep astma-patienten

Green, 2003

narrative review en niet recent

Ram, 2003

niet de meest recente versie van Cochrane review

Ritz, 2003

niet de meest recente review

Hondras, 2002

niet de meest recente versie van Cochrane review

Huntley, 2002

bij volwassenen en kinderen; geen studies bij volwassenen met severe asthma

Hondras, 2001

niet de meest recente versie van Cochrane review

Carlsen, 2000

niet de meest recente versie van Cochrane review

Dennis, 2000

niet de meest recente versie van Cochrane review

Ernst, 2000

geen studies in ernstig astma

Holloway, 2000

niet de meest recente versie van Cochrane review

Ram, 2000

meest recente review? Studies gedaan in kinderen

RCT’s

Freitas, 2017

Niet de juiste populatie

Good, 2017

adults with exercise-induced bronchoconstriction

Hall, 2017

narrative review

Karpagam, 2017

 Bronchial astma

Schultz, 2017

studieprotocol (wel bij uncontrolled asthma)

Thomas, 2017

Astma breed, niet gelimiteerd tot ernstig astma

Toennesen, 2017

astma breed, niet gelimiteerd tot ernstig astma (wel ACQ>1)

Weatherald, 2017

narrative review

Abd El-Kader, 2016

onduidelijk of het ernstig astma beteft

Agnihotri, 2016

mild-to-moderate persistent asthma

de Araujo, 2016

dierstudie

Del, 2016

commentary on Franco-Pinto, 2015

Majd, 2016

studieprotocol (wel bij severe asthma)

Raghavendra, 2016

ernstig astma werd geexcludeerd

Shei, 2016

narrative review (geeft wel overzicht van studies)

Freitas, 2015

studieprotocol (moderate-severe asthma)

Lingner, 2015

mild-to-severe persistent asthma

Ma, 2015

 I=leefstijlinterventie, niet specifiek fysiotherapie

Meyer, 2015

breed astma (mild-severe); wel interessante I (lange termijn)

Scott, 2015 (Resp)

I=weigth loss intervention ; astma-breed

Scott, 2015

P=Stabiel astma

Evaristo, 2014

protocol voor RCT (bij moderate-severe asthma)

Ritz, 2014

astma breed, niet gelimiteerd tot ernstig astma

Sodhi, 2014

severe werd geexcludeerd

Tahan, 2014

exercise induced asthma in children

Asl Mohammadi, 2013

severe? Artikel in het Arabisch

Bacon, 2013

study protocol

Bruton, 2013

protocol summary of an RCT

lickman-Simon, 2013

lijkt narrative review met zeer brede scope

Mancuso, 2013

mild-to-moderate asthma

Prem, 2013

astma breed, niet gelimiteerd tot ernstig astma

Bidwell, 2012

mild-to-moderate asthma

Boyd, 2012

mild-to-moderate asthma

Laurino, 2012

astma breed, niet gelimiteerd tot ernstig astma (30% wel ernstig)

Mancuso, 2012

mild-to-moderate asthma

Nowobilski, 2012

letter

Patel, 2012

cross-sectionele studie over tevredenheid astmazorg

Singh, 2012

mild to moderate asthma

Dogra, 2011

Astma breed

Grammatopoulou, 2011

mild to moderate asthma

Mahajan, 2011

voldoet niet aan PICO; I=High frequency chest wall oscillation ; niet gelimiteerd tot ernstig astma

Turner, 2011b

mild to moderate

Lemaigre, 2010

Gundling, 2009

commentaar

Kuz'mina, 2009

artikel in het Russisch

Lahmann, 2009

verkeerde P: controlled allergic bronchial asthma due to dust mite allergy

Milanese, 2009

mild-moderate asthma

Shelledy, 2009

Astma breed

Sodhi, 2009

mild-moderate asthma

Thomas, 2009

soort samenvattingsartikel van RCT (zie hieronder)

Thomas, 2009b

astma breed, niet gelimiteerd tot ernstig astma

Cowie, 2008

astma breed

De Vries, 2008

asthma severity level 1-4; niet ernstig astma

Holloway, 2007

astma breed, niet gelimiteerd tot ernstig astma (majority had mild asthma)

Pearson, 2007

editorial

Bruton, 2006

editorial

Slader, 2006

mild and moderate

Farid, 2005

exercise induced asthma

Nathell, 2005

astma breed

Sabina, 2005

mild-to-moderate asthma

De Vries, 2004

artikel in het Duits

Holt, 2004

letter

Kraut, 2004

Artikel in het Duits

McHugh, 2004

reactie op Holt, 2004

Ritz, 2004

narrative review over biofeedback techniques

Steier, 2004

lijkt narrative review

Cegla, 2003

artikel in het Duits

Gellefoss, 2003

lijkt niet aan PICO te voldoen; rol van roken wordt onderzocht

Janson, 2003

mild-to-moderate asthma

Ram, 2003

systematische review; all ages and all level of asthma sevirity; geincludeerde studies waren mild-moderate astma

Thomas, 2003

astma breed

Couturaud, 2002

Stabiel astma

Gallefoss, 2002

artikel in het Noors

Osman, 2002

acute asthma

Perneger, 2002

geen ernstig astma

Ringsberg, 2002

verkeerde P: patients with asthma-like symptoms but negative asthma tests

Weiner, 2002

mild persistent-to-moderate asthma

Weiner, 2002b

mild persistent-to-moderate asthma

Al-Delaimy, 2001

verkeerde P: exercise-induced asthma

Birch, 2001

twijfel, waarschijnlijk alleen abstract voor congres

Carlsen, 2001

verkeerde PICO: astmamedicatie in atleten

Clini, 2001

p=patients with chronic airway obstruction; retrospectieve case-control studie

Cote, 2001

p=acute asthma; astma breed

Eccles, 2001

british guideline uit 2000: oud?

Foglio, 2001

p=chronic airway obstruction

Gallefoss, 2001

mild to moderate asthma

Klein, 2001

Voldoet niet aan PICO

Kuiper, 2001

letter

Loew, 2001

astma breed

Morice, 2001

verkeerde I: role of the asthma nurse in treatment compliance and self-management following hospital admission

Ritz, 2001

niet-systematisch review

Segura-Mendez, 2001

artikel in het Spaans

Van der Palen

astma breed

Walters, 2001

editorial

Alison, 2000

waarschijnlijk ook editorial

Gallefoss, 2000

mild to moderate astma en COPD patienten