Do influenza vaccines reduce episodes of respiratory illness or death in people with chronic obstructive pulmonary disease (COPD)?
COPD is an umbrella term used to describe progressive lung diseases, including emphysema, chronic bronchitis, and refractory (non-reversible) asthma. The disease is characterized by increasing breathlessness. Despite the almost universal recommendation that people with COPD should receive an annual influenza vaccination, very few randomised controlled trials (studies in which a number of similar people are randomly assigned to two (or more) groups to test a specific drug, treatment or other intervention) have evaluated the effect of this treatment. Influenza vaccines may be produced with an inactivated virus (small particles of the virus wall) or live attenuated virus (reduced power but still alive).
To try to answer our question, we conducted a detailed search for studies from around the world that investigated the use of influenza vaccines for people with COPD.
We included six studies with 2469 participants with COPD, and a further five studies with 4281 older or high risk participants, a proportion of whom had chronic lung disease.
We found some moderate-quality evidence that inactivated influenza vaccine did decrease 'flare ups' of COPD, especially those that are related to the influenza virus itself. The inactivated influenza virus vaccine was given as an injection in the muscle, and was associated with an increase in local side effects (such as pain) at the site of injection, which were short-lived. The inactivated virus vaccine did not cause influenza, or any significant worsening of COPD. Adding a live attenuated virus to the inactivated virus did not add any further protection for the participants.
Quality of the evidence
The evidence was of moderate quality. There have been no new trials since 2004. We conducted the last literature search in December 2017.
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.
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.
To determine whether influenza vaccination in people with COPD reduces respiratory illness, reduces mortality, is associated with excess adverse events, and is cost effective.
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.
RCTs that compared live or inactivated virus vaccines with placebo, either alone or with another vaccine, in people with COPD.
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.
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,