British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease

Online appendix 2b Bronchiectasis evidence tables

Author(s):
Date:
Question: Long term Mac rolide c ompared to standard for Exac erbation Rate
Setting:
Bibliography:
Certainty assessment № of patients Effect
Certainty Importance
№ of Risk of Other Long term Relative Absolute
Study design Inconsistency Indirectness Imprecision standard
studies bias considerations Macrolide (95% CI) (95% CI)

Exacerbations, (Liu et al 2014) (follow up: mean 6 months; assessed with: Time to first exacerbations (days))

1 1 randomised serious a not serious serious b

serious c,d,e none 22 21 - median 151 ⨁◯◯◯ IMPORTANT
trials days to 1st
VERY LOW
exacerbation
lower
(0 to 0 )

Exacerbation rate, (Serisier et al 2013) (follow up: mean 12 months; assessed with: Exacerbations per patient per year)

1 2 randomised serious f not serious not serious not serious none 59 58 - mean 0.68 ⨁⨁⨁◯ IMPORTANT
trials exacerbations
MODERATE
per patient per
year lower
(0 to 0 )

Exacerbation incidence, (Serisier et al 2013) (assessed with: Incidence rate ratio)

1 2 randomised serious f not serious not serious not serious none 59 58 - mean 0.57 ⨁⨁⨁◯ IMPORTANT
trials Incidence rate
MODERATE
ratio higher
(0.42 higher to
0.77 higher)

Exacerbation rate, (Wong et al 2012) (follow up: 6 months; assessed with: Rate ratio)

1 3 randomised not serious g not serious not serious none 71 70 - Rate Ratio 0.38 ⨁⨁⨁◯ IMPORTANT
trials serious higher
MODERATE
(0.26 higher to
0.54 higher)

Exacerbation rate 6 months post treatment, (Wong et al 2012) (follow up: 12 months; assessed with: Rate Ratio)

1 3 randomised not serious g not serious not serious none 71 70 - Rate Ratio 0.58 ⨁⨁⨁◯ IMPORTANT
trials serious higher
MODERATE
(0.46 higher to
0.74 higher)

Exacerbation, Wong et al 2012 (follow up: 12 months; assessed with: Days to first exacerbation)

1 3 randomised not serious g not serious not serious none 71 70 - median 154 ⨁⨁⨁◯ IMPORTANT
trials serious days to first
MODERATE
exacerbation
more
(0 to 0 )

Exacerbation rate, Altenburg et al 2013 (assessed with: Median difference of exacerbation rate )

1 4 randomised serious h not serious not serious not serious none 43 40 - differenc e of ⨁⨁⨁◯ IMPORTANT
trials median
MODERATE
exac erbation
rate per year 2
exacarbtions
higher
(0 to 0 )

April 2020 1
 British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease
Online appendix 2b Bronchiectasis evidence tables

Exacerbation rate, (Diego 2013) (follow up: 3 months; assessed with: Number in months)

1 5 randomised very not serious not serious serious c none 16 14 - MD 1.1 ⨁◯◯◯ IMPORTANT
trials serious a,i exacerbations
VERY LOW
higher
(0 to 0 )

Exacerbation, (Zhou et al 2014) (follow up: range 8 weeks to 12 months)

4 6 randomised not not serious not serious not serious none 184 178 - OR 0.39 higher ⨁⨁⨁⨁ IMPORTANT
trials serious (0.25 higher to
HIGH
0.63 higher)

Exacerbation, (Fan et al 2015)

5 7 randomised serious a not serious serious j not serious none OR 0.55 1 fewer per ⨁⨁◯◯ IMPORTANT
trials (0.47 to 1,000
LOW
0.64) (from 1 fewer
to 0 fewer)

Exacerbation, (Fan et al 2015) (follow up: range 6 months to 12 months; assessed with: Only in adults double blind trials)

3 7 randomised not not serious not serious not serious none OR 0.55 1 fewer per ⨁⨁⨁⨁ IMPORTANT
trials serious (0.46 to 1,000
HIGH
0.65) (from 1 fewer
to 0 fewer)

Numbers with exacerbations, (Wu et al 2014)

7 8 randomised not not serious not serious not serious none 106/232 147/223 RR 0.70 198 fewer per ⨁⨁⨁⨁ IMPORTANT
trials serious (45.7%) (65.9%) (0.60 to 1,000
HIGH
0.82) (from 264
fewer to 119
fewer)

Exacerbation rate, Wu et al 2014

3 8 randomised not not serious not serious not serious none 118 112 - MD 1.01 ⨁⨁⨁⨁ IMPORTANT
trials serious exacerabations
HIGH
lower
(1.35 lower to
0.67 lower)

Exacerbation rate, Anwar et al 2008

1 9 observational serious k not serious not serious not serious strong 44 - mean 0.4 ⨁⨁◯◯ IMPORTANT
studies assoc iation Exacerbations
LOW
per month
lower
(0 to 0 )

Exacerbation rate, Davies et al 2004

1 10 observational serious a,k not serious not serious not serious strong - mean 0.58 ⨁⨁◯◯ IMPORTANT
studies assoc iation exacarbations
LOW
per month
lower
(0 to 0 )

CI: Confidenc e interval; MD: Mean differenc e; OR: Odds ratio; RR: Risk ratio

Explanations

a. Open Label study

b. Oriental Population
April 2020 2
 British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease
Online appendix 2b Bronchiectasis evidence tables

c . S mall Numbers
d. No c onfidenc e intervals
e. Had all been hospitalised
f. Unc lear baseline exac erbation rates
g. Data for different definition of exac erbation gave a different result
h. Lower exac arbation rate in the treatment group at baseline
i. No Plac ebo
j. Paediatric data inc luded
k. Not blinded

References

1. Liu, J., Zhong, X., He, Z., Wei, L., Zheng, X., Zhang, J., Bai, J., Zhong, W., Zhong, D.. Effec t of low-dose, long-term roxithromyc in on airway inflammation and remodeling of stable nonc ystic fibrosis
bronc hiec tasis. Mediators of Inflammation; 2014.
2. S erisier, D. J., Martin, M. L., Mc Guc kin, M. A., Lourie, R., Chen, A. C., Brain, B., Biga, S ., S c hlebusc h, S ., Dash, P., Bowler, S . D.. Effec t of long-term, low-dose erythromyc in on pulmonary exac erbations
among patients with non-c ystic fibrosis bronc hiec tasis: the BLES S randomiz ed c ontrolled trial. JAMA; 2013.
3. Wong, C., Jayaram, L., Karalus, N., Eaton, T., Tong, C., Hoc key, H., Milne, D., Fergusson, W., Tuffery, C., S exton, P., S torey, L., Ashton, T.. Az ithromyc in for prevention of exac erbations in non-c ystic fibrosis
bronc hiec tasis (EMBRACE): a randomised, double-blind, plac ebo-c ontrolled trial. Lanc et; 2012.
4. Altenburg, J., de Graaff, C. S ., S tienstra, Y., S loos, J. H., van Haren, E. H., Koppers, R. J., van der Werf, T. S ., Boersma, W. G.. Effec t of az ithromyc in maintenanc e treatment on infec tious exac erbations
among patients with non-c ystic fibrosis bronc hiec tasis: the BAT randomiz ed c ontrolled trial. JAMA; 2013.
5. Diego, A. D., Milara, J., Martinez -Moragon, E., Palop, M., Leon, M., Cortijo, J.. Effec ts of long-term az ithromyc in therapy on airway oxidative stress markers in non-c ystic fibrosis bronc hiec tasis.
Respirology; 2013.
6. Zhuo, G. Y., He, Q., Xiang-Lian, L., Ya-Nan, Y., S i-Te, F.. Prolonged treatment with mac rolides in adult patients with non-c ystic fibrosis bronc hiec tasis: meta-analysis of randomiz ed c ontrolled trials.
Pulmonary pharmac ology & therapeutic s; 2014.
7. Fan, L. C., Lu, H. W., Wei, P., Ji, X. B., Liang, S ., Xu, J. F.. Effec ts of long-term use of mac rolides in patients with non-c ystic fibrosis bronc hiec tasis: a meta-analysis of randomiz ed c ontrolled trials. BMC
Infec tious Diseases; 2015.
8. Wu, Q., S hen, W., Cheng, H., Zhou, X.. Long-term mac rolides for non-c ystic fibrosis bronc hiec tasis: a systematic review and meta-analysis. Respirology; 2014.
9. Anwar, G. A., Bourke, S . C., Afolabi, G., Middleton, P., Ward, C., Rutherford, R. M.. Effec ts of long-term low-dose az ithromyc in in patients with non-CF bronc hiec tasis. Respiratory Medic ine; 2008.
10. Davies, G., Wilson, R.. Prophylac tic antibiotic treatment of bronc hiec tasis with az ithromyc in. Thorax; 2004.

April 2020 3
 British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease
Online appendix 2b Bronchiectasis evidence tables

Author(s):
Date:
Question: Long term Mac rolide c ompared to standard c are for QoL
Setting:
Bibliography:
Certainty assessment № of patients Effect
Certainty Importance
№ of Risk of Other Long term standard Relative Absolute
Study design Inconsistency Indirectness Imprecision
studies bias considerations Macrolide care (95% CI) (95% CI)

SGRQ, (Liu et al 2014) (follow up: mean 6 months; Scale from: 0 to 100)

1 1 randomised serious a not serious serious b

serious c,d,e none 22 21 - mean ⨁◯◯◯ IMPORTANT
trials 11.1
VERY LOW
lower
(0 to 0 )

SGRQ, (Serisier et al 2013) (follow up: mean 12 months; Scale from: 0 to 100)

1 2 randomised not serious not serious not serious serious f none 59 58 - median ⨁⨁⨁◯ NOT IMPORTANT
trials 2.9 SGRQ
MODERATE
lower
(7.3 lower
to 1.6
higher)

SGRG, (Wong et al 2012) (follow up: 6 months; Scale from: 0 to 100)

1 3 randomised not serious not serious not serious serious f none 71 70 - MD 3.25 ⨁⨁⨁◯ NOT IMPORTANT
trials SGRQ
MODERATE
lower
(7.21
lower to
0.72
higher)

SGRQ 6 months post treatment, (Wong et al 2012) (follow up: 12 months; Scale from: 0 to 100)

1 3 randomised not serious not serious not serious not serious none 71 70 - 1.82 ⨁⨁⨁⨁ NOT IMPORTANT
trials SGRQ
HIGH
higher
(0.27
lower to
6.32
higher)

SGRQ, (Altenburg et al 2013) (follow up: 12 months; assessed with: SGRQ decrease per 6 months; Scale from: 0 to 100)

1 4 randomised not serious not serious not serious not serious none 43 40 - differenc e ⨁⨁⨁⨁ IMPORTANT
trials in
HIGH
reduc tion
in S GRQ
over 6
months
4.03
SGRQ
lower
(0 to 0 )

SGRQ, Diego 2013 (follow up: 3 months; Scale from: 0 to 100)

April 2020 4
 British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease
Online appendix 2b Bronchiectasis evidence tables

1 5 randomised very not serious not serious serious c none 16 14 - MD 12 ⨁◯◯◯ IMPORTANT
trials serious a,g SGRQ
VERY LOW
lower
(21.6
lower to
2.39
lower)

SGRQ, Zhuo et al 2014 (follow up: range 6 months to 12 months; Scale from: 0 to 100)

3 6 randomised not serious serious h not serious not serious none 173 168 - MD 1.9 ⨁⨁⨁◯ NOT IMPORTANT
trials SGRQ
MODERATE
lower
(7.01
lower to
3.2
higher)

SGRQ, (Fan et al 2015) (Scale from: 0 to 100)

7 randomised not serious serious h not serious serious f none - WMD 5.39 ⨁⨁◯◯ IMPORTANT
trials lower
LOW
(9.88
lower to
0.89
lower)

SGRQ, (Wu et al 2014) (Scale from: 0 to 100)

5 8 randomised not serious serious h not serious serious none - MD 5.39 ⨁⨁◯◯ IMPORTANT
trials SGRQ
LOW
lower
(0.88
lower to
9.89
lower)

5 Point Score, (Davies et al 2004) (assessed with: Cough/Fatigue/Exercise Tolerance/Wheeze/Breathlessness)

1 9 observational very not serious not serious not serious none 5 point sc ore for multiple symptoms inc luding sputum, ⨁◯◯◯ IMPORTANT
studies serious c,g c ough, fatigue, exerc ise, wheez e and breathlessness.
VERY LOW
S tatistic ally signific ant improvement for all.

CI: Confidenc e interval; MD: Mean differenc e

Explanations

a. Open-label
b. Oriental population
c . S mall study
d. No Confidenc e intervals
e. Had all been hospitalised
f. wide c onfidenc e intervals
g. no plac ebo
h. High I2 value

References

1. Liu, J., Zhong, X., He, Z., Wei, L., Zheng, X., Zhang, J., Bai, J., Zhong, W., Zhong, D.. Effec t of low-dose, long-term roxithromyc in on airway inflammation and remodeling of stable nonc ystic fibrosis
bronc hiec tasis. Mediators of Inflammation; 2014.
2. S erisier, D. J., Martin, M. L., Mc Guc kin, M. A., Lourie, R., Chen, A. C., Brain, B., Biga, S ., S c hlebusc h, S ., Dash, P., Bowler, S . D.. Effec t of long-term, low-dose erythromyc in on pulmonary exac erbations
among patients with non-c ystic fibrosis bronc hiec tasis: the BLES S randomiz ed c ontrolled trial. JAMA; 2013.
3. Wong, C., Jayaram, L., Karalus, N., Eaton, T., Tong, C., Hoc key, H., Milne, D., Fergusson, W., Tuffery, C., S exton, P., S torey, L., Ashton, T.. Az ithromyc in for prevention of exac erbations in non-c ystic fibrosis
bronc hiec tasis (EMBRACE): a randomised, double-blind, plac ebo-c ontrolled trial. Lanc et; 2012.
4. Altenburg, J., de Graaff, C. S ., S tienstra, Y., S loos, J. H., van Haren, E. H., Koppers, R. J., van der Werf, T. S ., Boersma, W. G.. Effec t of az ithromyc in maintenanc e treatment on infec tious exac erbations
among patients with non-c ystic fibrosis bronc hiec tasis: the BAT randomiz ed c ontrolled trial. JAMA; 2013.

April 2020 5
 British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease
Online appendix 2b Bronchiectasis evidence tables

5. Diego, A. D., Milara, J., Martinez -Moragon, E., Palop, M., Leon, M., Cortijo, J.. Effec ts of long-term az ithromyc in therapy on airway oxidative stress markers in non-c ystic fibrosis bronc hiec tasis.
Respirology; 2013.
6. Zhuo, G. Y., He, Q., Xiang-Lian, L., Ya-Nan, Y., S i-Te, F.. Prolonged treatment with mac rolides in adult patients with non-c ystic fibrosis bronc hiec tasis: meta-analysis of randomiz ed c ontrolled trials.
Pulmonary pharmac ology & therapeutic s; 2014.
7. Fan, L. C., Lu, H. W., Wei, P., Ji, X. B., Liang, S ., Xu, J. F.. Effec ts of long-term use of mac rolides in patients with non-c ystic fibrosis bronc hiec tasis: a meta-analysis of randomiz ed c ontrolled trials. BMC
Infec tious Diseases; 2015.
8. Wu, Q., S hen, W., Cheng, H., Zhou, X.. Long-term mac rolides for non-c ystic fibrosis bronc hiec tasis: a systematic review and meta-analysis. Respirology; 2014.
9. Davies, G., Wilson, R.. Prophylac tic antibiotic treatment of bronc hiec tasis with az ithromyc in. Thorax; 2004.

April 2020 6
 British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease
Online appendix 2b Bronchiectasis evidence tables

Author(s):
Date:
Question: Long term Mac rolide c ompared to standard c are for drug monitoring/side effec ts/toxic ity
Setting:
Bibliography:
Certainty assessment № of patients Effect
Certainty Importance
№ of Study Risk of Other Long term standard Relative Absolute
Inconsistency Indirectness Imprecision
studies design bias considerations Macrolide care (95% CI) (95% CI)

Nausea, Liu et al 2014 (follow up: mean 6 months; assessed with: Patient reported)

1 1 randomised serious a not serious serious b

serious c,d none 5/22 (22.7%) 0/21 (0.0%) not ⨁◯◯◯ NOT IMPORTANT
trials estimable
VERY LOW

Allergic Response, Liu et al 2014 (follow up: mean 6 months; assessed with: events; Scale from: 0 to infinite)

1 1 randomised serious not serious serious serious none 1 0 - total 1 ⨁◯◯◯ NOT IMPORTANT
trials rash
VERY LOW
more
(0 to 0 )

QTc, Serisier et al 2013 (follow up: 12 months; assessed with: change in QTc)

1 2 randomised not serious not serious not serious serious e none 59 58 - 0 ⨁⨁⨁◯ NOT IMPORTANT
trials (0 to 0 )
MODERATE

Nausea, Serisier et al 2013 (follow up: 12 months)

1 2 randomised not serious not serious not serious not serious none 0/59 (0.0%) 3/58 (5.2%) not ⨁⨁⨁⨁ NOT IMPORTANT
trials estimable
HIGH

GI, Wong et al 2012 (follow up: 12 months)

1 3 randomised not serious not serious not serious serious none 19/71 9/70 (12.9%) not ⨁⨁⨁◯ IMPORTANT
trials (26.8%) estimable
MODERATE

Diarrhoea, Altenburg et al 201 (follow up: 12 months; assessed with: Patient who suffered diarrhoea)

1 4 randomised not serious not serious not serious serious e none 9/43 (20.9%) 1/40 (2.5%) not ⨁⨁⨁◯ IMPORTANT
trials estimable
MODERATE

Rash, ALtenburg et al 201 (follow up: 12 months; assessed with: Patients affected)

1 4 randomised not serious not serious not serious not serious none 8/43 (18.6%) 4/40 (10.0%) not ⨁⨁⨁⨁ NOT IMPORTANT
trials estimable
HIGH

Chest pain, Altenburg et al 2013 (follow up: 12 months; assessed with: patient reported)

1 4 randomised not serious not serious not serious serious e none 1/43 (2.3%) 1/40 (2.5%) not ⨁⨁⨁◯ NOT IMPORTANT
trials estimable
MODERATE

Nausea, Altenburg et al 2013 (follow up: 12 months; assessed with: Patients affected)

1 4 randomised not serious not serious not serious serious none 6/43 (14.0%) 6/40 (15.0%) not ⨁⨁⨁◯ NOT IMPORTANT
trials estimable
MODERATE

Fatigue, Altenberg et al (follow up: 12 months)

April 2020 7
 British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease
Online appendix 2b Bronchiectasis evidence tables

1 4 randomised not serious not serious not serious serious none 1/43 (2.3%) 0/40 (0.0%) not ⨁⨁⨁◯ NOT IMPORTANT
trials estimable
MODERATE

Abdominal pain, Altenburg et al 2013 (follow up: 12 months; assessed with: patients affected)

1 4 randomised not serious not serious not serious not serious none 8/43 (18.6%) 1/40 (2.5%) not ⨁⨁⨁⨁ IMPORTANT
trials estimable
HIGH

Auditory, Altenburg et al 2013 (follow up: 12; assessed with: post-study questionnaire)

1 4 randomised serious f not serious not serious serious e none 5/43 (11.6%) 4/40 (10.0%) not ⨁⨁◯◯ NOT IMPORTANT
trials estimable
LOW

All adverse events, zhou et al 2014 (follow up: range 6 months to 12 months)

3 5 randomised not serious not serious not serious not serious none 94/173 97/168 not ⨁⨁⨁⨁ NOT IMPORTANT
trials (54.3%) (57.7%) estimable
HIGH

Nausea/Vomiting, Zhuo et al 2014 (follow up: range 6 months to 12 months)

3 5 randomised not serious not serious not serious not serious none 15/173 14/168 not ⨁⨁⨁⨁ NOT IMPORTANT
trials (8.7%) (8.3%) estimable
HIGH

Diarrhoea, Zhou et al 2014 (follow up: range 6 months to 12 months)

2 5 randomised not serious not serious not serious not serious none 22/114 5/110 (4.5%) not ⨁⨁⨁⨁ IMPORTANT
trials (19.3%) estimable
HIGH

Abdominal discomfort, Zhou et al 2014 (follow up: range 6 months to 12 months)

2 5 randomised not serious not serious not serious not serious none 13/144 2/110 (1.8%) not ⨁⨁⨁⨁ IMPORTANT
trials (9.0%) estimable
HIGH

Headache, Zhou et al 2014 (follow up: range 6 months to 12 months)

2 5 randomised not serious not serious not serious serious e none 3/114 (2.6%) 5/110 (4.5%) not ⨁⨁⨁◯ NOT IMPORTANT
trials estimable
MODERATE

Rash, Zhou et al 2014 (follow up: range 8 weeks to 12 months)

2 5 randomised not serious not serious not serious serious e none 9/54 (16.7%) 4/50 (8.0%) not ⨁⨁⨁◯ NOT IMPORTANT
trials estimable
MODERATE

Nausea/Vomiting, Fan et al 2015

3 6 randomised not serious not serious not serious not serious none 15/173 14/168 not ⨁⨁⨁⨁ NOT IMPORTANT
trials (8.7%) (8.3%) estimable
HIGH

Diarrhoea, Fan et al 2015

3 6 randomised not serious not serious not serious not serious none 26/126 5/122 (4.1%) OR 5.36 145 ⨁⨁⨁⨁ IMPORTANT
trials (20.6%) (2.06 to more per
HIGH
13.98) 1,000
(from 40
more to
333
more)

Headache, Fan et al 2015

April 2020 8
 British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease
Online appendix 2b Bronchiectasis evidence tables

3 6 randomised not serious not serious not serious serious e none 4/173 (2.3%) 5/168 (3.0%) not ⨁⨁⨁◯ NOT IMPORTANT
trials estimable
MODERATE

Sinusitis, Fan et al 2015

2 6 randomised not serious not serious not serious serious e none 4/130 (3.1%) 4/128 (3.1%) not ⨁⨁⨁◯ NOT IMPORTANT
trials estimable
MODERATE

Rash, Fan et al

2 6 randomised not serious not serious not serious serious e none 9/54 (16.7%) 4/50 (8.0%) OR 2.17 79 more ⨁⨁⨁◯ NOT IMPORTANT
trials (0.66 to 7.99) per
MODERATE
1,000
(from 26
fewer to
330
more)

Adverse events, Wu et al (assessed with: All adverse events)

4 7 randomised not serious not serious not serious not serious none 95/183 97/179 RR 0.96 22 fewer ⨁⨁⨁⨁ NOT IMPORTANT
trials (51.9%) (54.2%) (0.82 to 1.12) per
HIGH
1,000
(from 98
fewer to
65 more)

CI: Confidenc e interval; OR: Odds ratio; RR: Risk ratio

Explanations

a. Open-label
b. Oriental population
c . small study
d. No c onfidenc e intervals
e. small number of events
f. post-study questionnaire

References

1. Liu, J., Zhong, X., He, Z., Wei, L., Zheng, X., Zhang, J., Bai, J., Zhong, W., Zhong, D.. Effec t of low-dose, long-term roxithromyc in on airway inflammation and remodeling of stable nonc ystic fibrosis
bronc hiec tasis. Mediators of Inflammation; 2014.
2. S erisier, D. J., Martin, M. L., Mc Guc kin, M. A., Lourie, R., Chen, A. C., Brain, B., Biga, S ., S c hlebusc h, S ., Dash, P., Bowler, S . D.. Effec t of long-term, low-dose erythromyc in on pulmonary exac erbations
among patients with non-c ystic fibrosis bronc hiec tasis: the BLES S randomiz ed c ontrolled trial. JAMA; 2013.
3. Wong, C., Jayaram, L., Karalus, N., Eaton, T., Tong, C., Hoc key, H., Milne, D., Fergusson, W., Tuffery, C., S exton, P., S torey, L., Ashton, T.. Az ithromyc in for prevention of exac erbations in non-c ystic fibrosis
bronc hiec tasis (EMBRACE): a randomised, double-blind, plac ebo-c ontrolled trial. Lanc et; 2012.
4. Altenburg, J., de Graaff, C. S ., S tienstra, Y., S loos, J. H., van Haren, E. H., Koppers, R. J., van der Werf, T. S ., Boersma, W. G.. Effec t of az ithromyc in maintenanc e treatment on infec tious exac erbations
among patients with non-c ystic fibrosis bronc hiec tasis: the BAT randomiz ed c ontrolled trial. JAMA; 2013.
5. Zhuo, G. Y., He, Q., Xiang-Lian, L., Ya-Nan, Y., S i-Te, F.. Prolonged treatment with mac rolides in adult patients with non-c ystic fibrosis bronc hiec tasis: meta-analysis of randomiz ed c ontrolled trials.
Pulmonary pharmac ology & therapeutic s; 2014.
6. Fan, L. C., Lu, H. W., Wei, P., Ji, X. B., Liang, S ., Xu, J. F.. Effec ts of long-term use of mac rolides in patients with non-c ystic fibrosis bronc hiec tasis: a meta-analysis of randomiz ed c ontrolled trials. BMC
Infec tious Diseases; 2015.
7. Wu, Q., S hen, W., Cheng, H., Zhou, X.. Long-term mac rolides for non-c ystic fibrosis bronc hiec tasis: a systematic review and meta-analysis. Respirology; 2014.

April 2020 9
 British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease
Online appendix 2b Bronchiectasis evidence tables

Author(s):
Date:
Question: Long term mac rolide c ompared to standard c are for exerc ise c apac ity/toleranc e
Setting: Bronc hiec tasis
Bibliography:
Certainty assessment № of patients Effect
Certainty Importance
№ of Study Risk of Other long term standard Relative Absolute
Inconsistency Indirectness Imprecision
studies design bias considerations macrolide care (95% CI) (95% CI)

Activity, Liu et al 2014 (follow up: mean 6; assessed with: SGRQ- Activity; Scale from: 0 to 100)

1 1 randomised serious not serious serious serious none 22 21 - mean ⨁◯◯◯ NOT IMPORTANT
trials 4.4
VERY LOW
SGRQ-
Activity
lower
(0 to 0 )

Exercise capacity, Serisier et al 2013 (assessed with: 6MWT)

1 2 randomised not serious not serious not serious not serious none 59 58 - median ⨁⨁⨁⨁ NOT IMPORTANT
trials 3.55
HIGH
metres
higher
(17.6
lower to
24.7
higher)

Exercise capacity, Wong et al 2012 (follow up: 6 months; assessed with: 6MWT)

1 3 randomised not serious not serious not serious not serious none 71 70 - mean ⨁⨁⨁⨁ NOT IMPORTANT
trials 10.52
HIGH
metres
higher
(26.15
higher to
5.12
lower)

Exercise capacity, Wong et al 2012 (follow up: 12 months; assessed with: 6MWT)

1 3 randomised not serious not serious not serious not serious none 71 70 - 6.48 ⨁⨁⨁⨁ NOT IMPORTANT
trials metres
HIGH
higher
(24.22
higher to
11.28
lower)

Activity, Wong et al 2012 (follow up: 6 months; assessed with: SGRQ- Activity)

1 3 randomised not serious not serious not serious not serious none 71 70 - 1.58 ⨁⨁⨁⨁ NOT IMPORTANT
trials SGRQ-
HIGH
Activity
lower
(7.31
lower to
4.12
higher)

Activity, Wong et al 2012 (follow up: 12 months; assessed with: SGRQ- Activity)

April 2020 10
 British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease
Online appendix 2b Bronchiectasis evidence tables

1 3 randomised not serious not serious not serious not serious none 71 70 - 2.71 ⨁⨁⨁⨁ NOT IMPORTANT
trials SGRQ-
HIGH
Activity
higher
(3.37
lower to
8.79
higher)

Activity, Diego et al 20133 (follow up: 3 months; assessed with: SGRQ-Activity; Scale from: 0 to 100)

1 4 randomised very not serious not serious serious none 16 14 - MD 0.1 ⨁◯◯◯ NOT IMPORTANT
trials serious a,b SGRQ-
VERY LOW
Activity
higher
(0 to 0 )

CI: Confidenc e interval; MD: Mean differenc e

Explanations

a. No plac ebo
b. Open label

References

1. Liu, J., Zhong, X., He, Z., Wei, L., Zheng, X., Zhang, J., Bai, J., Zhong, W., Zhong, D.. Effec t of low-dose, long-term roxithromyc in on airway inflammation and remodeling of stable nonc ystic fibrosis
bronc hiec tasis. Mediators of Inflammation; 2014.
2. S erisier, D. J., Martin, M. L., Mc Guc kin, M. A., Lourie, R., Chen, A. C., Brain, B., Biga, S ., S c hlebusc h, S ., Dash, P., Bowler, S . D.. Effec t of long-term, low-dose erythromyc in on pulmonary exac erbations
among patients with non-c ystic fibrosis bronc hiec tasis: the BLES S randomiz ed c ontrolled trial. JAMA; 2013.
3. Wong, C., Jayaram, L., Karalus, N., Eaton, T., Tong, C., Hoc key, H., Milne, D., Fergusson, W., Tuffery, C., S exton, P., S torey, L., Ashton, T.. Az ithromyc in for prevention of exac erbations in non-c ystic fibrosis
bronc hiec tasis (EMBRACE): a randomised, double-blind, plac ebo-c ontrolled trial. Lanc et; 2012.
4. Diego, A. D., Milara, J., Martinez -Moragon, E., Palop, M., Leon, M., Cortijo, J.. Effec ts of long-term az ithromyc in therapy on airway oxidative stress markers in non-c ystic fibrosis bronc hiec tasis.
Respirology; 2013.

April 2020 11
 British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease
Online appendix 2b Bronchiectasis evidence tables

Author(s):
Date:
Question: Long term Mac rolide c ompared to standard c are for Hospital Admission rate
Setting:
Bibliography:
Certainty assessment № of patients Effect
Certainty Importance
№ of Study Risk of Other Long term standard Relative Absolute
Inconsistency Indirectness Imprecision
studies design bias considerations Macrolide care (95% CI) (95% CI)

Admission rate, Serisier et al 2013

1 1 randomised not serious not serious not serious serious a none 59 58 - mean 0.02 ⨁⨁⨁◯ NOT IMPORTANT
trials Hospital
MODERATE
admissions
per patient
lower
(0 to 0 )

Admissions, Wong et al 2012 (follow up: 12 months; assessed with: Bronchiectasis related admissions)

1 2 randomised not serious not serious not serious serious a none 1/71 (1.4%) 3/70 (4.3%) not ⨁⨁⨁◯ NOT IMPORTANT
trials estimable
MODERATE

Admission rate, Altenburg 2013 (follow up: 12 months; assessed with: admissions to hospital)

1 3 randomised not serious not serious not serious serious a none 1/43 (2.3%) 2/40 (5.0%) not ⨁⨁⨁◯ NOT IMPORTANT
trials estimable
MODERATE

CI: Confidenc e interval

Explanations

a. Wide c onfidenc e intervals

References

1. S erisier, D. J., Martin, M. L., Mc Guc kin, M. A., Lourie, R., Chen, A. C., Brain, B., Biga, S ., S c hlebusc h, S ., Dash, P., Bowler, S . D.. Effec t of long-term, low-dose erythromyc in on pulmonary exac erbations
among patients with non-c ystic fibrosis bronc hiec tasis: the BLES S randomiz ed c ontrolled trial. JAMA; 2013.
2. Wong, C., Jayaram, L., Karalus, N., Eaton, T., Tong, C., Hoc key, H., Milne, D., Fergusson, W., Tuffery, C., S exton, P., S torey, L., Ashton, T.. Az ithromyc in for prevention of exac erbations in non-c ystic fibrosis
bronc hiec tasis (EMBRACE): a randomised, double-blind, plac ebo-c ontrolled trial. Lanc et; 2012.
3. Altenburg, J., de Graaff, C. S ., S tienstra, Y., S loos, J. H., van Haren, E. H., Koppers, R. J., van der Werf, T. S ., Boersma, W. G.. Effec t of az ithromyc in maintenanc e treatment on infec tious exac erbations
among patients with non-c ystic fibrosis bronc hiec tasis: the BAT randomiz ed c ontrolled trial. JAMA; 2013.

April 2020 12
 British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease
Online appendix 2b Bronchiectasis evidence tables

Author(s):
Date:
Question: Long term Mac rolide c ompared to standard c are for Lung func tion
Setting:
Bibliography:
Certainty assessment № of patients Effect
Certainty Importance
№ of Risk of Other Long term standard Relative Absolute
Study design Inconsistency Indirectness Imprecision
studies bias considerations Macrolide care (95% CI) (95% CI)

FEV1, Serisier et al 2013 (follow up: mean 12 months; assessed with: Decline in FEV1%predicted)

1 1 randomised not not serious not serious not serious none 59 58 - mean 2.2 ⨁⨁⨁⨁ IMPORTANT
trials serious %predicted
HIGH
reduction
lower
(0.01 lower
to 4.3
lower)

FEV1, Wong et al 2012 (follow up: 6 months; assessed with: FEV1- Prebronchodilators)

1 2 randomised not not serious not serious not serious none 71 70 - c hange in ⨁⨁⨁⨁ NOT IMPORTANT
trials serious baseline
HIGH
0.04 litres
higher
(0.03 lower
to 0.12
higher)

FEV1, Wong et al 2012 (follow up: 6 months; assessed with: FEV1- Post Bronchodilator)

1 2 randomised not not serious not serious not serious none 71 70 - differenc e ⨁⨁⨁⨁ NOT IMPORTANT
trials serious in c hange
HIGH
from
baseline
0.07 litres
higher
(0.03 lower
to 0.15
higher)

FEV1, Wong et al 2012 (follow up: 12 months; assessed with: FEV1- Pre bronchodilator)

1 2 randomised not not serious not serious not serious none 71 70 - differenc e ⨁⨁⨁⨁ NOT IMPORTANT
trials serious of c hange
HIGH
from
baseline
0.04 litres
higher
(0.02 lower
to 0.11
higher)

FEV1, Wong et al (follow up: 12 months; assessed with: FEV1- postbronchodilator)

1 2 randomised not not serious not serious not serious none 71 70 - differenc e ⨁⨁⨁⨁ NOT IMPORTANT
trials serious in c hange
HIGH
from
baseline
0.07 litres
higher
(0.01 lower
to 0.15
higher)

April 2020 13
 British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease
Online appendix 2b Bronchiectasis evidence tables

FEV1, Altenburg 2013 (follow up: 12 months; assessed with: Rate of change per 3 months)

1 3 randomised not not serious not serious not serious none 43 40 - 1.13 % ⨁⨁⨁⨁ IMPORTANT
trials serious higher
HIGH
(0 to 0 )

FVC, Altenburg et al 2013 (follow up: 12 months; assessed with: Rate of change per 3 months)

1 3 randomised not not serious not serious not serious none 43 40 - 1.63 % ⨁⨁⨁⨁ IMPORTANT
trials serious higher
HIGH
(0 to 0 )

FEV1, Diego 2013 (follow up: 3 months; assessed with: Changes after 3 months)

1 4 randomised very not serious not serious serious c none 16 14 - Mean ⨁◯◯◯ NOT IMPORTANT
trials serious a,b differenc e
VERY LOW
of c hange
of FEV1
0.02 litres
more
(0 to 0 )

FEV1, Fan et al 2015 (assessed with: Changes in FEV1)

4 5 randomised not not serious not serious not serious none 109 105 - WMD 0.02 L ⨁⨁⨁⨁ IMPORTANT
trials serious more
HIGH
(0 to 0.04
more)

FEV1, Fan et al 2015 (assessed with: Change in FEV1% Pred)

3 5 randomised not not serious not serious not serious none 115 110 - WMD 1.52 ⨁⨁⨁⨁ IMPORTANT
trials serious %pred
HIGH
higher
(0.49
higher to
2.56
higher)

FVC, Fan et al 2015 (assessed with: Change in FVC)

3 5 randomised not serious d not serious not serious none 98 95 - WMD 0.05 ⨁⨁⨁◯ NOT IMPORTANT
trials serious litres
MODERATE
higher
(0.03 lower
to 0.13
higher)

FEV1, Wu et al 2014 (assessed with: Change in FEV1)

5 6 randomised serious not serious not serious not serious none - MD 0.02 L ⨁⨁⨁◯ IMPORTANT
trials higher
MODERATE
(0 to 0.04
higher)

FEV1, Anwar et al 2008 (assessed with: FEV1)

1 7 observational serious e not serious not serious not serious none 29 - mean ⨁◯◯◯ IMPORTANT
studies 0.083 litres
VERY LOW
higher
(0 to 0 )

FEV1, Anwar et al 2008 (assessed with: FEV1 %predicted)

April 2020 14
 British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease
Online appendix 2b Bronchiectasis evidence tables

1 7 observational serious e not serious not serious not serious none 29 - mean 3.5 ⨁◯◯◯
studies % higher
VERY LOW
(0 to 0 )

Lung function, Davies et al 2004

1 8 observational serious b not serious not serious not serious none Improvement in all parameters of lung func tion but stats ⨁◯◯◯
studies not desc ribed exc ept for TLCO (p=0.01)
VERY LOW

CI: Confidenc e interval; MD: Mean differenc e

Explanations

a. No Plac ebo
b. Open label
c. S mall study
d. High I2
e. Not blinded

References

1. S erisier, D. J., Martin, M. L., Mc Guc kin, M. A., Lourie, R., Chen, A. C., Brain, B., Biga, S ., S c hlebusc h, S ., Dash, P., Bowler, S . D.. Effec t of long-term, low-dose erythromyc in on pulmonary exac erbations
among patients with non-c ystic fibrosis bronc hiec tasis: the BLES S randomiz ed c ontrolled trial. JAMA; 2013.
2. Wong, C., Jayaram, L., Karalus, N., Eaton, T., Tong, C., Hoc key, H., Milne, D., Fergusson, W., Tuffery, C., S exton, P., S torey, L., Ashton, T.. Az ithromyc in for prevention of exac erbations in non-c ystic fibrosis
bronc hiec tasis (EMBRACE): a randomised, double-blind, plac ebo-c ontrolled trial. Lanc et; 2012.
3. Altenburg, J., de Graaff, C. S ., S tienstra, Y., S loos, J. H., van Haren, E. H., Koppers, R. J., van der Werf, T. S ., Boersma, W. G.. Effec t of az ithromyc in maintenanc e treatment on infec tious exac erbations
among patients with non-c ystic fibrosis bronc hiec tasis: the BAT randomiz ed c ontrolled trial. JAMA; 2013.
4. Diego, A. D., Milara, J., Martinez -Moragon, E., Palop, M., Leon, M., Cortijo, J.. Effec ts of long-term az ithromyc in therapy on airway oxidative stress markers in non-c ystic fibrosis bronc hiec tasis.
Respirology; 2013.
5. Fan, L. C., Lu, H. W., Wei, P., Ji, X. B., Liang, S ., Xu, J. F.. Effec ts of long-term use of mac rolides in patients with non-c ystic fibrosis bronc hiec tasis: a meta-analysis of randomiz ed c ontrolled trials. BMC
Infec tious Diseases; 2015.
6. Wu, Q., S hen, W., Cheng, H., Zhou, X.. Long-term mac rolides for non-c ystic fibrosis bronc hiec tasis: a systematic review and meta-analysis. Respirology; 2014.
7. Anwar, G. A., Bourke, S . C., Afolabi, G., Middleton, P., Ward, C., Rutherford, R. M.. Effec ts of long-term low-dose az ithromyc in in patients with non-CF bronc hiec tasis. Respiratory Medic ine; 2008.
8. Davies, G., Wilson, R.. Prophylac tic antibiotic treatment of bronc hiec tasis with az ithromyc in. Thorax; 2004.

April 2020 15
 British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease
Online appendix 2b Bronchiectasis evidence tables

Author(s):
Date:
Question: Long term Mac rolide c ompared to standard c are for Mic robiologic al resistanc e
Setting:
Bibliography:
Certainty assessment № of patients Effect
Certainty Importance
№ of Risk of Other Long term standard Relative Absolute
Study design Inconsistency Indirectness Imprecision
studies bias considerations Macrolide care (95% CI) (95% CI)

Resistant Streptococci, Serisier et al 2013 (follow up: mean 12 months; assessed with: macrolide resistance oropharyngeal strep)

1 1 randomised not not serious not serious not serious none 59 58 - differenc e ⨁⨁⨁⨁ IMPORTANT
trials serious 25.5
HIGH
%macrolide
resistant
strep more
(0 to 0 )

Resistance, Wong et al 2012 (follow up: 6 months; assessed with: Occurence of resistance)

1 2 randomised very not serious not serious serious b none 2/46 (4.3%) 0/45 (0.0%) not ⨁◯◯◯ NOT IMPORTANT
trials serious a estimable
VERY LOW

Resistance, Altenburg et al 2013 (follow up: 12 months; assessed with: Macrolide resistant pathogens tested)

1 3 randomised serious c not serious not serious not serious none 53/60 29/112 not ⨁⨁⨁◯ IMPORTANT
trials (88.3%) (25.9%) estimable
MODERATE

Resistance, Fan et al 2015

3 4 randomised serious d not serious not serious not serious none OR 16.83 17 fewer ⨁⨁⨁◯ IMPORTANT
trials (7.26 to per 1,000
MODERATE
38.99) (from 39
fewer to 7
fewer)

Resistance, Anwar et al 2008

1 5 observational serious e not serious not serious not serious none not ⨁◯◯◯ NOT IMPORTANT
studies estimable
VERY LOW

CI: Confidenc e interval; OR: Odds ratio

Explanations

a. No planned or c onsistent testing of mac rolide resistanc e

b. Wide c onfidenc e intervals
c. Not c lear whic h samples tested for resistanc e
d. issues from the BAT study whic h is the main data sourc e
e. Not c lear if same number of samples pre and post treatment

References

1. S erisier, D. J., Martin, M. L., Mc Guc kin, M. A., Lourie, R., Chen, A. C., Brain, B., Biga, S ., S c hlebusc h, S ., Dash, P., Bowler, S . D.. Effec t of long-term, low-dose erythromyc in on pulmonary exac erbations
among patients with non-c ystic fibrosis bronc hiec tasis: the BLES S randomiz ed c ontrolled trial. JAMA; 2013.
2. Wong, C., Jayaram, L., Karalus, N., Eaton, T., Tong, C., Hoc key, H., Milne, D., Fergusson, W., Tuffery, C., S exton, P., S torey, L., Ashton, T.. Az ithromyc in for prevention of exac erbations in non-c ystic fibrosis
bronc hiec tasis (EMBRACE): a randomised, double-blind, plac ebo-c ontrolled trial. Lanc et; 2012.
3. Altenburg, J., de Graaff, C. S ., S tienstra, Y., S loos, J. H., van Haren, E. H., Koppers, R. J., van der Werf, T. S ., Boersma, W. G.. Effec t of az ithromyc in maintenanc e treatment on infec tious exac erbations
among patients with non-c ystic fibrosis bronc hiec tasis: the BAT randomiz ed c ontrolled trial. JAMA; 2013.
4. Fan, L. C., Lu, H. W., Wei, P., Ji, X. B., Liang, S ., Xu, J. F.. Effec ts of long-term use of mac rolides in patients with non-c ystic fibrosis bronc hiec tasis: a meta-analysis of randomiz ed c ontrolled trials. BMC
Infec tious Diseases; 2015.
5. Anwar, G. A., Bourke, S . C., Afolabi, G., Middleton, P., Ward, C., Rutherford, R. M.. Effec ts of long-term low-dose az ithromyc in in patients with non-CF bronc hiec tasis. Respiratory Medic ine; 2008.

April 2020 16
 British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease
Online appendix 2b Bronchiectasis evidence tables

Author(s):
Date:
Question: Long term Mac rolide c ompared to standard c are for S putum volume/c olour/c harac ter
Setting:
Bibliography:
Certainty assessment № of patients Effect
Certainty Importance
№ of Risk of Other Long term standard Relative Absolute
Study design Inconsistency Indirectness Imprecision
studies bias considerations Macrolide care (95% CI) (95% CI)

Sputum weight, Serisier et al 2013 (follow up: mean 12 months; assessed with: median 24 hr weight in grams)

1 1 randomised not serious not serious not serious serious a none 59 58 - median ⨁⨁⨁◯ IMPORTANT
trials 4.3
MODERATE
grams
lower
(7.8
lower to
1 lower)

Sputum volume, Diego et al 2013 (follow up: 3 months; assessed with: mls/day)

1 2 randomised very not serious not serious serious d none 16 14 - MD 6.8 ⨁◯◯◯ IMPORTANT
trials serious b,c mls
VERY LOW
lower
(0 to 0 )

Sputum Colour, Diego et al 2013 (follow up: 3 months; assessed with: Scale; Scale from: 0 to 15)

1 2 randomised very not serious not serious serious d none 16 14 - MD 0.1 ⨁◯◯◯ NOT IMPORTANT
trials serious b,c Colour
VERY LOW
Scale
higher
(0 to 0 )

Sputum Volume, Fan et al 2015

4 3 randomised serious b,c

serious e not serious not serious none - MD 7.38 ⨁⨁◯◯ IMPORTANT
trials mls
LOW
lower
(12.9
lower to
1.85
lower)

Sputum Volume, Wu et al 2014

2 4 randomised serious not serious not serious not serious none - MD ⨁⨁⨁◯ IMPORTANT
trials 10.76
MODERATE
mls
lower
(12.7
lower to
8.83
lower)

Sputum volume, Anwar et al 2008 (assessed with: <15mls sputum/daily)

1 5 observational serious f not serious not serious serious g strong assoc iation 18/50 not ⨁◯◯◯ IMPORTANT
studies (36.0%) estimable
VERY LOW

Sputum, Davies et al 2004 (assessed with: 5 point scale)

April 2020 17
 British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease
Online appendix 2b Bronchiectasis evidence tables

1 6 observational serious c not serious not serious not serious none Unvalidated 5 point sc ale suggested improvement in ⨁◯◯◯ IMPORTANT
studies these symptoms
VERY LOW

CI: Confidenc e interval; MD: Mean differenc e

Explanations

a. wide c onfidenc e
b. No plac ebo
c . open label
d. S mall study
e. High i2 value
f. not blinded
g. Imprec ise volume definition

References

1. S erisier, D. J., Martin, M. L., Mc Guc kin, M. A., Lourie, R., Chen, A. C., Brain, B., Biga, S ., S c hlebusc h, S ., Dash, P., Bowler, S . D.. Effec t of long-term, low-dose erythromyc in on pulmonary exac erbations
among patients with non-c ystic fibrosis bronc hiec tasis: the BLES S randomiz ed c ontrolled trial. JAMA; 2013.
2. Diego, A. D., Milara, J., Martinez -Moragon, E., Palop, M., Leon, M., Cortijo, J.. Effec ts of long-term az ithromyc in therapy on airway oxidative stress markers in non-c ystic fibrosis bronc hiec tasis.
Respirology; 2013.
3. Fan, L. C., Lu, H. W., Wei, P., Ji, X. B., Liang, S ., Xu, J. F.. Effec ts of long-term use of mac rolides in patients with non-c ystic fibrosis bronc hiec tasis: a meta-analysis of randomiz ed c ontrolled trials. BMC
Infec tious Diseases; 2015.
4. Wu, Q., S hen, W., Cheng, H., Zhou, X.. Long-term mac rolides for non-c ystic fibrosis bronc hiec tasis: a systematic review and meta-analysis. Respirology; 2014.
5. Anwar, G. A., Bourke, S . C., Afolabi, G., Middleton, P., Ward, C., Rutherford, R. M.. Effec ts of long-term low-dose az ithromyc in in patients with non-CF bronc hiec tasis. Respiratory Medic ine; 2008.
6. Davies, G., Wilson, R.. Prophylac tic antibiotic treatment of bronc hiec tasis with az ithromyc in. Thorax; 2004.

April 2020 18
 British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease
Online appendix 2b Bronchiectasis evidence tables

Author(s):
Date:
Question: Long term mac rolide c ompared to standard c are for S ymptom improvement/S ymptom sc ore
Setting: Bronc hiec tasis
Bibliography:
Certainty assessment № of patients Effect
Certainty Importance
№ of Study Risk of Other long term standard Relative Absolute
Inconsistency Indirectness Imprecision
studies design bias considerations macrolide care (95% CI) (95% CI)

Symptoms, Liu et al 2014 (follow up: 6 months; assessed with: SGRQ-Symptom)

1 1 randomised serious not serious serious serious none 22 21 - mean 4.7 ⨁◯◯◯ IMPORTANT
trials SGRQ-
VERY LOW
Sympt
lower
(0 to 0 )

Symtoms, Serisier et al 2013 (follow up: mean 12 months; assessed with: Leicester Cough Questionnaire)

1 2 randomised not serious not serious not serious not serious none 59 58 - median ⨁⨁⨁⨁ NOT IMPORTANT
trials 0.79 LCQ
HIGH
higher
(0.2 lower
to 1.8
higher)

Symptoms, Serisier et al 2013 (follow up: mean 12 months; assessed with: SGRQ-Symptoms score)

1 2 randomised not serious not serious not serious not serious none 59 58 - median ⨁⨁⨁⨁ NOT IMPORTANT
trials 5.3 SGRQ-
HIGH
Symptoms
lower
(12.6
lower to
2.1
higher)

Symptoms, Wong et al 2012 (follow up: 6 months; assessed with: SGRQ- Symptoms score)

1 3 randomised not serious not serious not serious not serious none 71 70 - 6.7 SGRQ ⨁⨁⨁⨁ IMPORTANT
trials lower
HIGH
(13.37
lower to
0.04
lower)

Symptoms, Wong et al 2012 (follow up: 12 months; assessed with: SGRQ- Symptoms score)

1 3 randomised not serious not serious not serious not serious none 71 70 - 1.82 ⨁⨁⨁⨁ NOT IMPORTANT
trials SGRQ-
HIGH
Symptoms
higher
(0.27
lower to
6.32
higher)

Symptoms, Altenburg et al 2013 (follow up: 12 months; assessed with: LRTI-VAS- decrease per 3 months; Scale from: 0 to 50)

1 4 randomised not serious not serious not serious not serious none 43 40 - 1.05 LRTI- ⨁⨁⨁⨁ IMPORTANT
trials VAS lower
HIGH
(0 to 0 )

Symptoms, Diego et al 2013 (follow up: 3 months; assessed with: Borg; Scale from: 0 to 10)

April 2020 19
 British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease
Online appendix 2b Bronchiectasis evidence tables

1 5 randomised very not serious not serious serious c none 16 14 - MD 0.5 ⨁◯◯◯ IMPORTANT
trials serious a,b Borg
VERY LOW
lower
(0 to 0 )

Symptoms, Diego et al 2013 (follow up: 3 months; assessed with: SGRQ-symptoms)

1 5 randomised very not serious not serious serious c none 16 14 - MD 30 ⨁◯◯◯ IMPORTANT
trials serious a,b SGRQ
VERY LOW
symptoms
lower
(0 to 0 )

Symptoms, Fan et al 2015 (assessed with: SGRQ-Symptom Score)

6 randomised not serious not serious not serious very none - WMD ⨁⨁◯◯ NOT IMPORTANT
trials serious d 13.38
LOW
SGRQ
lower
(30.62
lower to
3.86
higher)

Symptom, Wu et al 2014 (assessed with: Dyspnoea scale)

2 7 randomised serious not serious not serious not serious none - MD 0.31 ⨁⨁⨁◯ IMPORTANT
trials MRC
MODERATE
lower
(0.42
lower to
0.2 lower)

CI: Confidenc e interval; MD: Mean differenc e

Explanations

a. No Plac ebo
b. Open label
c. S mall study
d. large c onfidenc e intervals

References

1. Liu, J., Zhong, X., He, Z., Wei, L., Zheng, X., Zhang, J., Bai, J., Zhong, W., Zhong, D.. Effec t of low-dose, long-term roxithromyc in on airway inflammation and remodeling of stable nonc ystic fibrosis
bronc hiec tasis. Mediators of Inflammation; 2014.
2. S erisier, D. J., Martin, M. L., Mc Guc kin, M. A., Lourie, R., Chen, A. C., Brain, B., Biga, S ., S c hlebusc h, S ., Dash, P., Bowler, S . D.. Effec t of long-term, low-dose erythromyc in on pulmonary exac erbations
among patients with non-c ystic fibrosis bronc hiec tasis: the BLES S randomiz ed c ontrolled trial. JAMA; 2013.
3. Wong, C., Jayaram, L., Karalus, N., Eaton, T., Tong, C., Hoc key, H., Milne, D., Fergusson, W., Tuffery, C., S exton, P., S torey, L., Ashton, T.. Az ithromyc in for prevention of exac erbations in non-c ystic fibrosis
bronc hiec tasis (EMBRACE): a randomised, double-blind, plac ebo-c ontrolled trial. Lanc et; 2012.
4. Altenburg, J., de Graaff, C. S ., S tienstra, Y., S loos, J. H., van Haren, E. H., Koppers, R. J., van der Werf, T. S ., Boersma, W. G.. Effec t of az ithromyc in maintenanc e treatment on infec tious exac erbations
among patients with non-c ystic fibrosis bronc hiec tasis: the BAT randomiz ed c ontrolled trial. JAMA; 2013.
5. Diego, A. D., Milara, J., Martinez -Moragon, E., Palop, M., Leon, M., Cortijo, J.. Effec ts of long-term az ithromyc in therapy on airway oxidative stress markers in non-c ystic fibrosis bronc hiec tasis.
Respirology; 2013.
6. Fan, L. C., Lu, H. W., Wei, P., Ji, X. B., Liang, S ., Xu, J. F.. Effec ts of long-term use of mac rolides in patients with non-c ystic fibrosis bronc hiec tasis: a meta-analysis of randomiz ed c ontrolled trials. BMC
Infec tious Diseases; 2015.
7. Wu, Q., S hen, W., Cheng, H., Zhou, X.. Long-term mac rolides for non-c ystic fibrosis bronc hiec tasis: a systematic review and meta-analysis. Respirology; 2014.

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 British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease
Online appendix 2b Bronchiectasis evidence tables

Author(s):
Date:
Question: Long term Mac rolides c ompared to standard c are to reduce mortality
Setting:
Bibliography:
Certainty assessment № of patients Effect
Certainty Importance
№ of Study Risk of Other Long term standard Relative Absolute
Inconsistency Indirectness Imprecision
studies design bias considerations Macrolides care (95% CI) (95% CI)

Death, Altenburg et al 2013 (follow up: 12 months)

1 1 randomised not serious not serious not serious serious none 0/43 (0.0%) 0/40 (0.0%) not ⨁⨁⨁◯ NOT IMPORTANT
trials estimable
MODERATE

CI: Confidenc e interval

References

1. Altenburg, J., de Graaff, C. S ., S tienstra, Y., S loos, J. H., van Haren, E. H., Koppers, R. J., van der Werf, T. S ., Boersma, W. G.. Effec t of az ithromyc in maintenanc e treatment on infec tious exac erbations
among patients with non-c ystic fibrosis bronc hiec tasis: the BAT randomiz ed c ontrolled trial. JAMA; 2013.

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