Is air pollution associated with the occurrence of out-of-hospital cardiac arrest?

To identify studies eligible for review, computerized searches of bibliographic databases will be performed (authors TH and TW): MEDLINE (1946 - October 2012); EMBASE (1980– October 2012), CINAHL (1982–October 2012), AustHealth (1997-October 2012) and the Cochrane Library (2004—October 2012). Scopus and Biosis Previews will be searched for additional environmental science literature. Regional electronic bibliographic databases: Chinese Biomedical Literature Database (CBM), CiNii (Japan), KoreaMed (Korea), IndMED (India), LILACS (for Latin America and the Carribean), will also be searched.

Terms will be mapped to the appropriate MeSH/EMTREE subject headings and “exploded”: (1) [“cardiac arrest” OR “heart arrest” OR “sudden cardiac death”] AND [“air pollution” OR “air pollutants” OR “particulate matter” OR “airborne particles” OR “fine particles” OR environmental exposure” OR “soot” OR “elemental carbon” OR “ carbon monoxide” OR “nitrogen dioxide” OR “ozone” OR “sulfur dioxide” OR “ sulphur dioxide”]. Reference lists of relevant review articles and journals will also be hand-searched for relevant papers.

Studies will be included that estimate the association between ambient air pollution levels and OHCA. There will be no restriction by publication date, language or patient age-group.

Studies that examined the relationship of air pollution and the risk of out-of-hospital cardiac arrest, in any study design and in any language will be included.

Animal studies, toxicological studies, summaries, commentaries, case reports and editorials and duplicates are to be excluded.

Articles have to be published in peer-reviewed journals but those published only in abstract form will be excluded. No time limits on journal publication date will be set.

Cardiac arrest refers to the abrupt cessation of cardiac function, commonly due to ventricular fibrillation, electromechanical dissociation, asystole and heart block, with ventricular fibrillation being the most common. Sudden cardiac arrest accounts for more than half of all deaths due to cardiac aetiology in developed countries. Out-of-hospital cardiac arrest (OHCA) is a significant public issue with an estimated incidence in the United States of 95.7 per 100,000 person-years. Survival outcome arising from out-of-hospital cardiac arrest remains poor, with survival to discharge from hospital ranging from 2% in Asia, 6% in North America, 9% in Europe to 11% in Australia. As such, there is an imperative to better understand factors that “trigger” the onset of cardiac arrest.

There is increasing evidence to support the association of ambient air pollution with cardiovascular mortality and morbidity. Exposure to higher than usual levels of air-borne air pollutants over a few hours to several days has been reported to contribute to increased risk of myocardial infarction, arrhythmia, stroke and heart failure in susceptible patients. In particular, the focus has been on fine particulate matter (PM) <2.5 µm in aerodynamic diameter (PM2.5). More recently, ultrafine particles <0.1µm, nitrogen oxides, ozone, elemental carbon, organic carbon and other sources of air pollutants (eg traffic and accidental fires) have also been studied. Much less is known about the association between air pollutants and cardiac arrest.

This systematic review and meta-analysis proposes to review and quantify the associations between air pollutants and the risk of OHCA. The findings can inform primary prevention strategies to reduce the incidence of OHCA attributed to air pollution.

All adults and children including neonates.

Exposure to any airborne pollutant will be examined: particulate matter <=2.5µm, particulate matter <=10µm, nitrogen dioxide, ozone, sulphur dioxide, carbon monoxide will be examined separately.

The controls will vary depending on the study type. For example, in a case-crossover study, the cases are their own controls.

The systematic review will be limited to out-of-hospital cardiac arrest.

Primary outcomes

The risk of out-of-hospital cardiac arrest in subjects exposed to the air pollutants is the primary outcome.

Secondary outcomes

None.

All abstracts and titles will be screened by two independent reviewers (TW and TH) to identify potential studies for the review. Full text articles of studies that meet the study selection criteria will be reviewed for eligibility for the systematic review and meta-analysis. If there is any disagreement, consensus will be sought from a third reviewer (JF).

A standardised checklist will be used to extract data for the assessment of study quality and data synthesis of the observational studies. The data will be collected on a form that will include: study design, study setting, study population, demographic and baseline characteristics, sample sizes, methodology, exposure, exposure levels, effect measurement, control conditions and outcome measurement.

All included studies will be critically appraised by two independent reviewers to assess quality before any synthesis of results occurs. It is anticipated that observational studies (which are more prone to bias as compared to randomised controlled trials) will be included in the review. Two methods will be used to assess study quality. The Cochrane guidelines will be used to assess the study quality for risk of bias, heterogeneity, representativeness of sample selection, exposure ascertainment, baseline differences between study populations, misclassification of subjects, adequate statistical adjustments for socio-demographic differences, co-pollutants and other confounding variables.

A methodological checklist, the Newcastle-Ottawa Scale, will be used to assess quality of non-randomised studies. A ‘star system’ in the Newcastle-Ottawa Scale will be used to judge a study on three broad perspectives:

a) the selection of the study groups;

b) the comparability of the groups; and

c) the ascertainment of the exposure or outcome of interest.

The studies will be graded as poor (1-3 stars), intermediate (4-6 stars) and high (7-9 stars) quality.

Assessment of heterogeneity will be assessed using the Higgins I-squared statistic. Variation between studies will be examined graphically using a forest plot.

Sensitivity analysis will be performed to test the effects of outliers by removing each study sequentially and assessing its impact on the pooled estimates and heterogeneity. Publication bias will be assessed by inspecting a funnel plot.

Study characteristics will be presented in tables and narrative forms, guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Summaries of exposure effects will be reported using risk ratio as a measure of effect size. A meta-analysis using the random effects model will be undertaken with Review Manager (RevMan) using the random effects model. This model is chosen as it is anticipated that significant heterogeneity between studies in terms of population and methods will be observed. If findings show large heterogeneity, stratification will be performed to explore the sources of heterogeneity.

Subgroup analyses will be undertaken for age groups <= 65 years and >65 years, and each pollutant type as defined.

The systematic review will be published in a peer-reviewed journal and at national meetings.

Tiew-Hwa Katherine TENG

Discipline of Emergency Medicine (M516)

R Blk, 2nd floor, QEII Medical Centre

University of Western Australia

Nedlands, WA 6008

katherine.teng@uwa.edu.au

University of Western Australia

www.uwa.edu.au

Dr Tiew-Hwa Katherine TENG, University of Western Australia (Emergency Medicine, SPARHC)
Professor Judith FINN, Monash University (Department of Epidemiology and Preventive Medicine) & University of Western Australia (Emergency Medicine, SPARHC)
Dr Teresa WILLIAMS, University of Western Australia (Emergency Medicine, SPARHC)
Dr Alexandra BREMNER, University of Western Australia (School of Population Health)
Dr Hideo TOHIRA, University of Western Australia (Emergency Medicine, SPARHC)
Dr Peter FRANKLIN, University of Western Australia (School of Population Health)
Professor Andrew TONKIN, Monash University (Department of Epidemiology and Preventive Medicine)
Professor Ian JACOBS, University of Western Australia ( Emergency Medicine, SPARHC) & St John Ambulance (WA).

None

16 October 2012

31 March 2013

None

None known

None

English

Australia

Subject indexing assigned by CRD

Air Pollution; Heart Arrest; Humans

16 October 2012

16 October 2012