Archimedes

Is there any evidence for influenza vaccination in children with asthma?

Report by Will Carroll, Derby Children's Hospital, Uttoxeter Road, Derby DE22 3NE, UK; will.carroll@nhs.net

Richard Burkimsher, University of Nottingham, Medical School Nottingham, Nottingham NG7 2UH, UK

A 12 year old boy presents for a routine asthma follow‐up appointment during the autumn. He takes 200 μg per day of inhaled budesonide and uses his salbutamol 3–4 times per week. His mother asks if the flu vaccine will make it less likely that he will have an asthma exacerbation over the winter.

Structured clinical question

In children with asthma [patient] does influenza vaccination [intervention] reduce the number of asthma exacerbations associated with influenza [outcome]?

Search strategy and outcome

Primary sources: Medline 1966–April week 3 2006 using the OVID interface: {exp Infant/ or exp Child/ or exp Adolescent/ or exp Child, Preschool/} AND {exp Influenza Vaccines/ or {exp Vaccination/ and exp Influenza, Human/}} AND {exp Asthma/}.

PubMed and EMBASE: No further relevant articles were found.

Secondary sources: The references of relevant papers found by this method revealed one further relevant paper which was included in the analysis (Kramarz et al¹).

Search outcome

117 papers were found of which four were relevant (see table 1).

Commentary

Current Department of Health guidance suggests that influenza vaccination should be offered to all children with “asthma requiring continuous or repeated use of inhaled or systemic steroids or with previous exacerbations requiring hospital admission”.⁵ This type of “umbrella advice” therefore extends to many children with mild and/or well‐controlled asthma. It is not unusual to be asked by parents of children with asthma whether influenza vaccine is necessary. Historically, rates of influenza vaccine uptake amongst children with asthma are known to be low (25% of eligible children).⁶ One of the key barriers to influenza vaccination is lack of physician endorsement of national recommendations⁷ with many doctors remaining ambivalent about the need for influenza vaccination in children with mild or moderate asthma. This view seems to be supported by the lack of convincing benefit shown in the published literature.

Table 1 Evidence for the use of influenza vaccine in children with asthma.

Citation	Patient group	Study type (level of evidence)	Outcomes	Key results	Study weaknesses
Kramarz	Children with asthma	Retrospective	No. of asthma exacerbations	Adjusted rate ratio	Traditional cohort analysis
et al	aged 1–6 years:	cohort study	(hospitalisation or	(vaccinated/comparison)	shows increased risk of asthma
(2000)1	22 231 in 1993–94	(level 2b)	emergency department visit)		exacerbation in vaccinated
	38 669 in 1994–95		Traditional cohort analysis:		children (p = 0.0001 for
	70 753 in 1995–96		1993–94	2.2 (95% CI 1.8 to 2.6)	each cohort)
			1994–95	1.5 (95% CI 1.3 to 1.7)
			1995–96	1.4 (95% CI 1.2 to 1.5)
			Self‐control analysis:
			1993–94	0.78 (95% CI 0.55 to 1.10, p = 0.15)
			1994–95	0.59 (95% CI 0.43 to 0.81, p = 0.001)
			1995–96	0.65 (95% CI 0.52 to 0.80, p = 0.0001)
Smits	349 children	Retrospective	Attack rate of acute	26.1% in non‐vaccinated children	Outcome measure was rate of
et al	with asthma	cohort study	respiratory disease	vs 21.5% in vaccinated children	acute respiratory disease and
(2002)2	aged 0–12 years	(level 2b)	Crude odds ratio* of acute	The protective effect was limited	influenza infection was not
			respiratory disease (all)	to children under 6 years of age	documented
			Crude odds ratio* of acute	0.78 (95% CI 0.57 to 1.2, p = 0.17)	Those who were vaccinated
			respiratory disease (<6 years)	0.52 (95% CI 0.29 to 0.93, p = 0.018)	attended primary care more
					frequently
Christy	800 children aged	Retrospective	Odds of hospitalisation	1.9 (95% CI 0.9 to 3.9, p = 0.10)	Numbers presented in paper
et al	1–19 years	cohort study	Odds of a clinic visit	2.9 (95% CI 2.0 to 4.1, p<0.001)	not internally consistent
(2004)3	randomly selected	(level 2b)	Odds of an emergency	2.0 (95% CI 1.2 to 3.1, p = 0.01)	Those in abstract differ to those
	from a population of		department visit for		in results. Authors conclude
	1400 enrolled in		diagnoses of asthma and		that vaccination may have
	two large paediatric		pneumonia		been a marker for “bad
	teaching practices				asthma” or increased
	in Rochester, New				clinical contact
	York
Bueving	696 children	Randomised	Odds ratio of asthma	More in vaccine group	Primary end‐point failed to
et al	with asthma	double‐blind	exacerbation with	Crude OR 1.33 (95% CI 0.69 to 2.57,	demonstrate a benefit of
(2004)4	aged 6–18 years	placebo	virologically proven	p = 0.39)	vaccination (in fact showed
		controlled	influenza infection	Adjusted OR 1.31 (95% CI 0.59 to 2.09,	trend towards harm). Small
		trial		p = 0.44)	number of asthma
		(level 1b)	Duration of exacerbations	2.0 days shorter in vaccine group	exacerbations in each group
				(95% CI −4.9 to 0.9, p = 0.19)	with virologically proven
					influenza infection

We identified only one randomised placebo controlled trial of influenza vaccination in children with asthma.⁴ The primary endpoint of this study was the number of influenza‐attributable asthma exacerbations during the study period. The authors found that the vaccine did not significantly reduce the number of exacerbations. In fact, in this study there were more asthma exacerbations in the vaccine group, but this was not statistically significant. A secondary analysis suggested that the duration of exacerbations may be longer in unvaccinated children, but again this difference failed to reach statistical significance.

Clinical bottom line

• National guidelines continue to recommend influenza vaccination for all children with asthma receiving inhaled corticosteroids. (Grade D)

• On the basis of the published evidence, there are few data to suggest a benefit of influenza vaccination in children with asthma. (Grade B)

• The need for vaccination in children with asthma should be assessed on a case‐by‐case basis. Younger children may be more likely to benefit from vaccination. (Grade B)

Two out of the three cohort studies show an increased number of exacerbations in children who received the influenza vaccine,^1–3 but as inclusion was not randomised these studies may be subject to considerable bias. Hence children with more severe asthma may be more likely to attend primary care and to be vaccinated. Although no study shows convincing evidence of benefit overall, Smits et al demonstrated statistically significant beneficial effects in children under 6 years of age (crude odds ratio of acute respiratory disease 0.52 (95% CI 0.29 to 0.93, p = 0.018)).² Thus young children may be more likely to benefit from vaccination.