Cigarette smoking and the occurrence of influenza – Systematic review
Introduction
Influenza is an acute viral respiratory tract infection affecting all ages and associated with a significant morbidity and mortality. It affects 10–20% of patients annually in developed countries.1 The illness ranges from a mild self-limiting disease to a severe illness requiring hospitalisation. In the UK during an average influenza season, 1.3% and 0.1% of seniors aged 75 years or over consult their GP for an episode for respiratory illness attributable to influenza A and B respectively.2 In hospital, Influenza accounts for an estimated 10% of the attributed respiratory admissions and deaths.3 The primary mode of prevention in many countries is annual influenza vaccination targeting primarily selected populations considered at risk of complications or severe disease.4, 5
Figures from the Office of National Statistics suggest that in the UK an estimated 15.8% of the adult population were current tobacco smokers in 2016.6 Smokers have a significantly increased risk of chronic respiratory disease and acute respiratory infections.7 Cigarette smoke produces structural changes in the respiratory tract, disrupting respiratory immune defences. These changes include peri-bronchiolar inflammation and fibrosis, increased mucosal permeability, impairment of the mucociliary clearance, changes in pathogen adherence and disruption of the respiratory epithelium.8 Cigarette smoking is also associated with a variety of alterations in cellular and humoral immune system function which may predispose to infection.9
The association of tobacco smoking with influenza infection is not well established and currently, active smoking alone without associated co-morbidities does not identify an individual into a high-risk group requiring influenza vaccination. The aim of this systematic review was to summarise and quantify the risk of influenza infection in tobacco smokers compared to non-smokers.
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Search strategy and inclusion criteria
In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement, we systematically searched online databases (MEDLINE, EMBASE, CINAHL, LILACS and Web of Science) using Medical Subject Headings to identify published and unpublished studies on the association between smoking and influenza from database inception to 7 November 2017. No restrictions on published language or date range were applied. We included randomised control trials (RCTs), cohort and
Results
We identified 2579 references for screening of which 102 studies were assessed for full text eligibility. The main reasons for study exclusion were irrelevance (n = 37) and incorrect outcome (n = 22). Of the final eleven studies, six were cohort studies,11, 12, 13, 14, 15, 16 four were case control studies17, 18, 19, 20 and one was a RCT21 – see Fig. 1. One study was subsequently excluded as it focussed on risk factors for Influenza A(H7N9), a predominantly avian influenza rarely causing
Discussion
Our main finding is that current smokers have an increased risk of developing influenza compared to non-smokers. This association was much stronger in all of the studies where influenza infection was confirmed microbiologically rather than based on a clinical diagnosis of an ILI.
Experimental data in animal models and in human cell culture suggest that tobacco smoke components can inhibit antiviral pathways and increase susceptibility to influenza via mechanisms involving oxidant stress but that
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
None.
Funding
This work was supported by the Medical Research Council [grant number MR/K023195/1}; the UK Centre for Tobacco and Alcohol Studies (http://www.ukctas.net); and the British Heart Foundation, Cancer Research UK, the Economic and Social Research Council, and the National Institute of Health Research, under the auspices of the UK Clinical Research Collaboration.
WSL's institution has received unrestricted investigator-initiated research funding from Pfizer for an unrelated study in which he is the
Role of the funder/sponsor
The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
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