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Review
. 2018 Jun 26;6(6):CD002733.
doi: 10.1002/14651858.CD002733.pub3.

Influenza Vaccine for Chronic Obstructive Pulmonary Disease (COPD)

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Free PMC article
Review

Influenza Vaccine for Chronic Obstructive Pulmonary Disease (COPD)

Zoe Kopsaftis et al. Cochrane Database Syst Rev. .
Free PMC article

Abstract

Background: Influenza vaccinations are currently recommended in the care of people with COPD, but these recommendations are based largely on evidence from observational studies, with very few randomised controlled trials (RCTs) reported. Influenza infection causes excess morbidity and mortality in people with COPD, but there is also the potential for influenza vaccination to cause adverse effects, or not to be cost effective.

Objectives: To determine whether influenza vaccination in people with COPD reduces respiratory illness, reduces mortality, is associated with excess adverse events, and is cost effective.

Search methods: We searched the Cochrane Airways Trials Register, two clinical trials registries, and reference lists of articles. A number of drug companies we contacted also provided references. The latest search was carried out in December 2017.

Selection criteria: RCTs that compared live or inactivated virus vaccines with placebo, either alone or with another vaccine, in people with COPD.

Data collection and analysis: Two review authors independently extracted data. All entries were double-checked. We contacted study authors and drug companies for missing information. We used standard methods expected by Cochrane.

Main results: We included 11 RCTs with 6750 participants, but only six of these included people with COPD (2469 participants). The others were conducted on elderly and high-risk individuals, some of whom had chronic lung disease. Interventions compared with placebo were inactivated virus injections and live attenuated intranasal virus vaccines. Some studies compared intra-muscular inactivated vaccine and intranasal live attenuated vaccine with intra-muscular inactivated vaccine and intranasal placebo. Studies were conducted in the UK, USA and Thailand.Inactivated vaccine reduced the total number of exacerbations per vaccinated participant compared with those who received placebo (mean difference (MD) -0.37, 95% confidence interval (CI) -0.64 to -0.11; P = 0.006; two RCTs, 180 participants; low quality evidence). This was due to the reduction in 'late' exacerbations, occurring after three or four weeks (MD -0.39, 95% CI -0.61 to -0.18; P = 0.0004; two RCTs, 180 participants; low quality evidence). Both in people with COPD, and in older people (only a minority of whom had COPD), there were significantly more local adverse reactions in people who had received the vaccine, but the effects were generally mild and transient.There was no evidence of an effect of intranasal live attenuated virus when this was added to inactivated intramuscular vaccination.Two studies evaluating mortality for influenza vaccine versus placebo were too small to have detected any effect on mortality. However, a large study (N=2215) noted that there was no difference in mortality when adding live attenuated virus to inactivated virus vaccination, AUTHORS' CONCLUSIONS: It appeared, from the limited number of RCTs we were able to include, all of which were more than a decade old, that inactivated vaccine reduced exacerbations in people with COPD. The size of effect was similar to that seen in large observational studies, and was due to a reduction in exacerbations occurring three or more weeks after vaccination, and due to influenza. There was a mild increase in transient local adverse effects with vaccination, but no evidence of an increase in early exacerbations. Addition of live attenuated virus to the inactivated vaccine was not shown to confer additional benefit.

Conflict of interest statement

Kopsaftis Z: none known

Wood‐Baker R: none known

Poole PJ: none known

Figures

1
1
Study flow diagram for 2018 update
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
1.1
1.1. Analysis
Comparison 1 Inactivated influenza vaccine versus placebo, Outcome 1 Total exacerbations per participant.
1.2
1.2. Analysis
Comparison 1 Inactivated influenza vaccine versus placebo, Outcome 2 Early exacerbations per participant.
1.3
1.3. Analysis
Comparison 1 Inactivated influenza vaccine versus placebo, Outcome 3 Late exacerbations per participant.
1.4
1.4. Analysis
Comparison 1 Inactivated influenza vaccine versus placebo, Outcome 4 Participants with at least one exacerbation or acute respiratory illness.
1.5
1.5. Analysis
Comparison 1 Inactivated influenza vaccine versus placebo, Outcome 5 Participants with early exacerbations.
1.6
1.6. Analysis
Comparison 1 Inactivated influenza vaccine versus placebo, Outcome 6 Participants with late exacerbations.
1.7
1.7. Analysis
Comparison 1 Inactivated influenza vaccine versus placebo, Outcome 7 Hospital admissions.
1.8
1.8. Analysis
Comparison 1 Inactivated influenza vaccine versus placebo, Outcome 8 Mortality (all cause).
1.9
1.9. Analysis
Comparison 1 Inactivated influenza vaccine versus placebo, Outcome 9 Mortality (acute respiratory illness‐related).
1.10
1.10. Analysis
Comparison 1 Inactivated influenza vaccine versus placebo, Outcome 10 Overall change in lung function (FEV¹, L).
1.11
1.11. Analysis
Comparison 1 Inactivated influenza vaccine versus placebo, Outcome 11 Change in early lung function (FEV¹, L).
1.12
1.12. Analysis
Comparison 1 Inactivated influenza vaccine versus placebo, Outcome 12 Systemic adverse effects.
1.13
1.13. Analysis
Comparison 1 Inactivated influenza vaccine versus placebo, Outcome 13 Local effects at injection site.
1.14
1.14. Analysis
Comparison 1 Inactivated influenza vaccine versus placebo, Outcome 14 Participants with early breathlessness.
1.15
1.15. Analysis
Comparison 1 Inactivated influenza vaccine versus placebo, Outcome 15 Participants with early tightness.
1.16
1.16. Analysis
Comparison 1 Inactivated influenza vaccine versus placebo, Outcome 16 Participants with early wheeze.
1.17
1.17. Analysis
Comparison 1 Inactivated influenza vaccine versus placebo, Outcome 17 Participants with early cough.
1.18
1.18. Analysis
Comparison 1 Inactivated influenza vaccine versus placebo, Outcome 18 Acute respiratory illness subsequently documented as influenza‐related.
1.19
1.19. Analysis
Comparison 1 Inactivated influenza vaccine versus placebo, Outcome 19 Early acute respiratory illness (ARI).
1.20
1.20. Analysis
Comparison 1 Inactivated influenza vaccine versus placebo, Outcome 20 Participants with early sputum production.
2.1
2.1. Analysis
Comparison 2 Inactivated + live virus versus inactivated virus + placebo, Outcome 1 Total exacerbations per participant.
2.2
2.2. Analysis
Comparison 2 Inactivated + live virus versus inactivated virus + placebo, Outcome 2 Early exacerbations per participant.
2.3
2.3. Analysis
Comparison 2 Inactivated + live virus versus inactivated virus + placebo, Outcome 3 Late exacerbations per participant.
2.4
2.4. Analysis
Comparison 2 Inactivated + live virus versus inactivated virus + placebo, Outcome 4 Participants with improvement in exacerbations.
2.5
2.5. Analysis
Comparison 2 Inactivated + live virus versus inactivated virus + placebo, Outcome 5 Participants with early improvements.
2.6
2.6. Analysis
Comparison 2 Inactivated + live virus versus inactivated virus + placebo, Outcome 6 Participants with late improvements.
2.7
2.7. Analysis
Comparison 2 Inactivated + live virus versus inactivated virus + placebo, Outcome 7 Mortality.
2.8
2.8. Analysis
Comparison 2 Inactivated + live virus versus inactivated virus + placebo, Outcome 8 Early changes in lung function (% predicted FEV¹).
2.9
2.9. Analysis
Comparison 2 Inactivated + live virus versus inactivated virus + placebo, Outcome 9 Early changes in lung function (FEV¹/FVC %).
2.10
2.10. Analysis
Comparison 2 Inactivated + live virus versus inactivated virus + placebo, Outcome 10 Post immunisation lung function (FEV¹).
2.11
2.11. Analysis
Comparison 2 Inactivated + live virus versus inactivated virus + placebo, Outcome 11 Participants with increased lung function (1 category).
2.12
2.12. Analysis
Comparison 2 Inactivated + live virus versus inactivated virus + placebo, Outcome 12 Participants with decreased lung function.
2.13
2.13. Analysis
Comparison 2 Inactivated + live virus versus inactivated virus + placebo, Outcome 13 FEV¹ at end of study.
2.14
2.14. Analysis
Comparison 2 Inactivated + live virus versus inactivated virus + placebo, Outcome 14 Participants with adverse effects (new upper respiratory tract symptoms).
2.15
2.15. Analysis
Comparison 2 Inactivated + live virus versus inactivated virus + placebo, Outcome 15 Participants with early adverse effects.
2.16
2.16. Analysis
Comparison 2 Inactivated + live virus versus inactivated virus + placebo, Outcome 16 Number of days with early symptoms and signs.
2.17
2.17. Analysis
Comparison 2 Inactivated + live virus versus inactivated virus + placebo, Outcome 17 Number of participants with early adverse effects (by type).
2.18
2.18. Analysis
Comparison 2 Inactivated + live virus versus inactivated virus + placebo, Outcome 18 Participants with late adverse effects.
2.19
2.19. Analysis
Comparison 2 Inactivated + live virus versus inactivated virus + placebo, Outcome 19 Acute respiratory illness subsequently documented as influenza‐related.
2.20
2.20. Analysis
Comparison 2 Inactivated + live virus versus inactivated virus + placebo, Outcome 20 Participants with at least one influenza‐like illness.

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