Vaccines for preventing influenza in people with asthma

Christopher J Cates, Brian H Rowe, Christopher J Cates, Brian H Rowe

Abstract

Background: Influenza vaccination is recommended for asthmatic patients in many countries as observational studies have shown that influenza infection can be associated with asthma exacerbations. However, influenza vaccination has the potential to cause wheezing and adversely affect pulmonary function. While an overview concluded that there was no clear benefit of influenza vaccination in patients with asthma, this conclusion was not based on a systematic search of the literature.

Objectives: The objective of this review was to assess the efficacy and safety of influenza vaccination in children and adults with asthma.

Search methods: We searched the Cochrane Airways Group trials register and reviewed reference lists of articles. The latest search was carried out in November 2012.

Selection criteria: We included randomised trials of influenza vaccination in children (over two years of age) and adults with asthma. We excluded studies involving people with chronic obstructive pulmonary disease.

Data collection and analysis: Inclusion criteria and assessment of trial quality were applied by two review authors independently. Data extraction was done by two review authors independently. Study authors were contacted for missing information.

Main results: Nine trials were included in the first published version of this review, and nine further trials have been included in four updates. The included studies cover a wide diversity of people, settings and types of influenza vaccination, and we pooled data from the studies that employed similar vaccines. PROTECTIVE EFFECTS OF INACTIVATED INFLUENZA VACCINE DURING THE INFLUENZA SEASON: A single parallel-group trial, involving 696 children, was able to assess the protective effects of influenza vaccination. There was no significant reduction in the number, duration or severity of influenza-related asthma exacerbations. There was no difference in the forced expiratory volume in one second (FEV) although children who had been vaccinated had better symptom scores during influenza-positive weeks. Two parallel-group trials in adults did not contribute data to these outcomes due to very low levels of confirmed influenza infection. ADVERSE EFFECTS OF INACTIVATED INFLUENZA VACCINE IN THE FIRST TWO WEEKS FOLLOWING VACCINATION: Two cross-over trials involving 1526 adults and 712 children (over three years old) with asthma compared inactivated trivalent split-virus influenza vaccine with a placebo injection. These trials excluded any clinically important increase in asthma exacerbations in the two weeks following influenza vaccination (risk difference 0.014; 95% confidence interval -0.010 to 0.037). However, there was significant heterogeneity between the findings of two trials involving 1104 adults in terms of asthma exacerbations in the first three days after vaccination with split-virus or surface-antigen inactivated vaccines. There was no significant difference in measures of healthcare utilisation, days off school/symptom-free days, mean lung function or medication usage.EFFECTS OF LIVE ATTENUATED (INTRANASAL) INFLUENZA VACCINATION: There were no significant differences found in exacerbations or measures of lung function following live attenuated cold recombinant vaccine versus placebo in two small studies on 17 adults and 48 children. There were no significant differences in asthma exacerbations found for the comparison live attenuated vaccine (intranasal) versus trivalent inactivated vaccine (intramuscular) in one study on 2229 children (over six years of age).

Authors' conclusions: Uncertainty remains about the degree of protection that vaccination affords against asthma exacerbations that are related to influenza infection. Evidence from more recently published randomised trials of inactivated split-virus influenza vaccination indicates that there is no significant increase in asthma exacerbations immediately after vaccination in adults or children over three years of age. We were unable to address concerns regarding possible increased wheezing and hospital admissions in infants given live intranasal vaccination.

Conflict of interest statement

None known. The authors have not represented the producers of these vaccine products. CJC acted in an advisory capacity in the design of one of the studies (Bueving 2003).

Figures

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1
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
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2
Forest plot of comparison: 1 Protection from inactivated influenza vaccine versus placebo, outcome: 1.1 Influenza‐related asthma exacerbations.
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3
Forest plot of comparison: 2 Split virus or surface antigen vaccine versus placebo (adverse events in first two weeks), outcome: 2.1 Asthma exacerbation within two weeks.
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4
Forest plot of comparison: 2 Split virus or surface antigen vaccine versus placebo (adverse events in first two weeks), outcome: 2.2 Asthma exacerbation within three days.
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5
Forest plot of comparison: 2 Split virus or surface antigen vaccine versus placebo (adverse events in first two weeks), outcome: 2.3 Asthma exacerbation within two weeks (subgrouped by previous vaccination status).
1.1. Analysis
1.1. Analysis
Comparison 1 Protection from inactivated influenza vaccine versus placebo, Outcome 1 Influenza‐related asthma exacerbations.
1.2. Analysis
1.2. Analysis
Comparison 1 Protection from inactivated influenza vaccine versus placebo, Outcome 2 Duration of influenza‐related asthma exacerbation (days).
1.3. Analysis
1.3. Analysis
Comparison 1 Protection from inactivated influenza vaccine versus placebo, Outcome 3 Severity of influenza‐related asthma exacerbation (symptom score).
1.4. Analysis
1.4. Analysis
Comparison 1 Protection from inactivated influenza vaccine versus placebo, Outcome 4 Difference in symptom score during influenza positive weeks.
1.5. Analysis
1.5. Analysis
Comparison 1 Protection from inactivated influenza vaccine versus placebo, Outcome 5 Proportion of patients with minimum important difference in total symptom score (influenza‐positive weeks).
1.6. Analysis
1.6. Analysis
Comparison 1 Protection from inactivated influenza vaccine versus placebo, Outcome 6 FEV1 (% predicted) during influenza positive weeks.
2.1. Analysis
2.1. Analysis
Comparison 2 Adverse effects of inactivated influenza vaccine versus placebo, Outcome 1 Asthma exacerbation within 2 weeks.
2.2. Analysis
2.2. Analysis
Comparison 2 Adverse effects of inactivated influenza vaccine versus placebo, Outcome 2 Asthma exacerbation within 3 days.
2.3. Analysis
2.3. Analysis
Comparison 2 Adverse effects of inactivated influenza vaccine versus placebo, Outcome 3 Asthma exacerbation within 2 weeks (subgrouped by previous vaccination status).
2.4. Analysis
2.4. Analysis
Comparison 2 Adverse effects of inactivated influenza vaccine versus placebo, Outcome 4 Hospital admission (0 to 14 days post vaccination).
2.5. Analysis
2.5. Analysis
Comparison 2 Adverse effects of inactivated influenza vaccine versus placebo, Outcome 5 Number of symptom‐free days in 2 weeks after vaccination.
2.6. Analysis
2.6. Analysis
Comparison 2 Adverse effects of inactivated influenza vaccine versus placebo, Outcome 6 ≥ 1 day off school or work.
2.7. Analysis
2.7. Analysis
Comparison 2 Adverse effects of inactivated influenza vaccine versus placebo, Outcome 7 Medical consultation (0 to 14 days after immunisation).
2.8. Analysis
2.8. Analysis
Comparison 2 Adverse effects of inactivated influenza vaccine versus placebo, Outcome 8 Patients at least 15% fall in FEV1 within 5 days.
2.9. Analysis
2.9. Analysis
Comparison 2 Adverse effects of inactivated influenza vaccine versus placebo, Outcome 9 Fall in mean peak flow (% baseline) days 2 to 4.
2.10. Analysis
2.10. Analysis
Comparison 2 Adverse effects of inactivated influenza vaccine versus placebo, Outcome 10 New or increased oral corticosteroid use (0 to 14 days after immunisation).
2.11. Analysis
2.11. Analysis
Comparison 2 Adverse effects of inactivated influenza vaccine versus placebo, Outcome 11 Increased nebuliser usage within 3 days.
2.12. Analysis
2.12. Analysis
Comparison 2 Adverse effects of inactivated influenza vaccine versus placebo, Outcome 12 Increased use of rescue medication following vaccination (days 1 to 3).
3.1. Analysis
3.1. Analysis
Comparison 3 Adverse effects of live attenuated vaccine (intranasal) versus placebo, Outcome 1 Hospital admission for asthma exacerbation.
3.2. Analysis
3.2. Analysis
Comparison 3 Adverse effects of live attenuated vaccine (intranasal) versus placebo, Outcome 2 Asthma exacerbations in the month after vaccination.
3.4. Analysis
3.4. Analysis
Comparison 3 Adverse effects of live attenuated vaccine (intranasal) versus placebo, Outcome 4 Mean FEV1 at 2 to 5 days post vaccination (% predicted).
3.5. Analysis
3.5. Analysis
Comparison 3 Adverse effects of live attenuated vaccine (intranasal) versus placebo, Outcome 5 Number of patients with significant fall in FEV1 (over 12% to 15% or 50 mL) on day 2 to 4.
3.6. Analysis
3.6. Analysis
Comparison 3 Adverse effects of live attenuated vaccine (intranasal) versus placebo, Outcome 6 Fall in mean FEV1 (L) (day 2 to 4).
3.7. Analysis
3.7. Analysis
Comparison 3 Adverse effects of live attenuated vaccine (intranasal) versus placebo, Outcome 7 Number of puffs of beta2‐agonist per day (in month following vaccination).
3.8. Analysis
3.8. Analysis
Comparison 3 Adverse effects of live attenuated vaccine (intranasal) versus placebo, Outcome 8 Morning peak flow of greater than 30% below baseline at least once in the 4 weeks after vaccination.
4.1. Analysis
4.1. Analysis
Comparison 4 Protection from live attenuated vaccine (intranasal) versus trivalent inactivated vaccine (intramuscular), Outcome 1 Difference in incidence of asthma exacerbation over total study period.
4.2. Analysis
4.2. Analysis
Comparison 4 Protection from live attenuated vaccine (intranasal) versus trivalent inactivated vaccine (intramuscular), Outcome 2 Hospitalisations due to respiratory illness.
4.3. Analysis
4.3. Analysis
Comparison 4 Protection from live attenuated vaccine (intranasal) versus trivalent inactivated vaccine (intramuscular), Outcome 3 Days off school or work (incidence rates).
4.4. Analysis
4.4. Analysis
Comparison 4 Protection from live attenuated vaccine (intranasal) versus trivalent inactivated vaccine (intramuscular), Outcome 4 Unscheduled healthcare visits (incidence rates).
4.5. Analysis
4.5. Analysis
Comparison 4 Protection from live attenuated vaccine (intranasal) versus trivalent inactivated vaccine (intramuscular), Outcome 5 Children with serious adverse events.
5.1. Analysis
5.1. Analysis
Comparison 5 Adverse effects of live attenuated vaccine (intranasal) versus trivalent inactivated vaccine (intramuscular), Outcome 1 Subjects reporting wheeze in the first 15 days.
5.2. Analysis
5.2. Analysis
Comparison 5 Adverse effects of live attenuated vaccine (intranasal) versus trivalent inactivated vaccine (intramuscular), Outcome 2 Subjects reporting runny nose or nasal congestion in the first 15 days.
5.3. Analysis
5.3. Analysis
Comparison 5 Adverse effects of live attenuated vaccine (intranasal) versus trivalent inactivated vaccine (intramuscular), Outcome 3 Subjects reporting bronchospasm as an adverse event in first 15 days.
5.4. Analysis
5.4. Analysis
Comparison 5 Adverse effects of live attenuated vaccine (intranasal) versus trivalent inactivated vaccine (intramuscular), Outcome 4 Subjects reporting rhinitis as an adverse event in the first 15 days.

Source: PubMed

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