Protocol

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Mar 1, 2015 - key traffic-related air pollutants when road traffic is specified as their ... Stage 3. HK will screen the references lists of all eligible studies to ...

Protocol Study: Childhood exposure to traffic-related air pollution and the onset of asthma Date: 02/02/2015 Authors: Haneen Khreis, Charlotte Kelly, James Tate and Roger Parslow

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Table of Contents Table of Contents ................................................................................................................................ 1 Background ......................................................................................................................................... 2 Research question ............................................................................................................................... 3 Search strategy .................................................................................................................................... 3 Removing duplicates and extracting titles and abstracts..................................................................... 3 Eligibility criteria ................................................................................................................................ 3 Review strategy ................................................................................................................................... 4 

Stage 1..................................................................................................................................... 4



Stage 2..................................................................................................................................... 4



Stage 3..................................................................................................................................... 4

Quality assessment .............................................................................................................................. 4 Data extraction .................................................................................................................................... 5 Data synthesis ..................................................................................................................................... 5 Dissemination ..................................................................................................................................... 5 References ........................................................................................................................................... 6

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Background Asthma is a chronic inflammatory disorder of the airways affecting some 300 million people worldwide (Masoli et al. 2004).Over the latter part of the 20th century, asthma prevalence has steadily increased in most industrialized countries (Anandan et al. 2010, Woolcock and Peat 1997, Asher et al. 2006, Koenig 1999), making it the most common chronic illness of childhood (Gasana et al. 2012, Gaffin and Phipatanakul 2014). Whilst hereditary factors are highly important in the prognosis of asthma, these rapid rises in prevalence outstrip the pace of genomic variation (Gaffin et al. 2014). As recent increases in prevalence remain unexplained by genetic factors alone, exposure to modern environmental factors, independently and jointly with genetics, are thought to be responsible (Clark et al. 2010, Cookson 2004). In recent years, the number of epidemiological studies investigating a range of environmental exposures which may modify the risks of developing asthma has grown substantially. As such, the association between exposure to ambient air pollution, a ubiquitous environmental exposure of present times, and the initial development of asthma is now a subject of active enquiry. The common wisdom about air pollution and asthma was that air pollution, especially nitrogen dioxide (NO2), particulate matter (PM) and ozone (O3), can exacerbate pre-existing asthma across a variety of outcomes such as increasing rates of hospitalizations, symptoms reporting, and medication used (Schildcrout et al. 2006, Schwartz et al. 1993, Gauderman et al. 2002, Sunyer et al. 1997, Lierl and Hornung 2003, Lipsett et al. 1997, Von Klot et al. 2002, Slaughter et al. 2003, Handzel 2000). The role of exposure to ambient air pollution, however, in the initial development of childhood asthma, remains unclear, and the general consensus was that air pollution cannot cause the onset of this disease (Eder et al. 2006, Committee on the Medical Effects of Air Pollutants 1995, Anderson 1997, Koenig 1999). Moreover, studies undertaken within some well-established and wellcharacterized cohorts such as the Southern California’s Children's Health Study demonstrated that the incidence of asthma is generally not higher in communities with higher regional air pollution (McConnell 2013). In recent years, research has shifted its focus from investigating the correlations between regional air pollution, such as that found in the vicinity of stationary sources, and asthma onset to investigating the correlations between local air pollution, such as that found in the vicinity of traffic, and asthma onset. Traffic-related air pollution is a mixture certainly different in nature and composition than regional air pollution. Findings from previous studies exploring the associations between childhood exposures to trafficrelated air pollution and the onset of asthma remain inconsistent and even conflicting. Whilst some studies have demonstrated that exposure to different traffic-related pollutants and residing in proximity to busy roads increase the likelihood of developing asthma in children (Brauer et al. 2002, Clark et al. 2010, Committee on the Medical Effects of Air Pollutants 2010, Gehring et al. 2010, Hwang et al. 2005, Gruzieva et al. 2013), other studies have disagreed and showed that this effect is absent (Committee on the Medical Effects of Air Pollutants 1995, Lindgren et al. 2013, Sahsuvaroglu et al. 2009). Furthermore, despite acknowledging that it is implausible that air pollution would be “protecting” against the onset of asthma, protective effects have been previously identified (Hwang et al. 2005, Lindgren et al. 2013, Gruzieva et al. 2013, Oftedal et al. 2009). Because of such inconsistent and contradictory findings, and the fact that the mechanisms underlying air pollution toxicity are as yet not well-characterized, the question of whether there is a causal 2

association between exposure to traffic-related air pollution and the onset of asthma remains unresolved. With childhood asthma currently reaching epidemic proportions in many regions, being a condition which profoundly affects the quality of life for a large number of the population, and with air pollution being a modifiable environmental factor, understanding these associations is a priority. This systematic review attempts to clarify these associations. The key objective of this review is to identify, synthesise and evaluate the international empirical evidence available on the association between children's exposure to traffic-related air pollution and their risks of developing asthma.

Research question Does children’s exposure to traffic-related air pollution increase their risks of developing asthma?

Search strategy EMBASE, MEDLINE, and Transport Database were searched for relevant studies using key words on 13th August 2014. No restriction on language, study type, or publication period was placed on the searches. In each of the three databases, four searches were performed using the following key words combinations:    

‘Child*’ AND ‘air pollution’ AND ‘asthma’ … (search 1) ‘Child*’ AND ‘air quality’ AND ‘asthma’ … (search 2) ‘Child*’ AND ‘vehicle emissions’ AND ‘asthma’ … (search 3) ‘Child*’ AND ‘ultrafine particles’ AND ‘asthma’ … (search 4)

The term child* identified the population of interest, and picked up child and other relevant terms such as childhood and children. The terms air pollution, air quality, vehicle emissions and ultrafine particles identified the exposure(s) of interest, and the term air pollution picked up traffic-related air pollution. The pollutant ultrafine particles (UFPs) was specifically given its own search term as toxicological studies emphasize its high biologic potency in inducing relevant adverse health effects (Li et al. 2003, Oberdörster and Utell 2002, Health Effects Institute 2013), and as no study investigating its effect on childhood asthma was found in a previous literature review undertaken on identify studies the same topic. Finally, as the aim of this review is to which specifically define asthma and investigate the risks of its initial development as the primary outcome of interest, only the term asthma was used to identify the outcome of interest.

Removing duplicates and extracting titles and abstracts After running the four searches in each database, the returned results were combined using OR in a fifth search so as to exclude duplicates across the same database. This process identified 2,118 references from EMBASE, 1,654 references from MEDLINE, and 12 references from the Transport Database. All 3,784 references were selected and exported to EndNote. The EndNote ‘Find Duplicates’ function was used and identified 1,649 duplicate/ triplet references. The automatically highlighted duplicate/ triplet copy was deleted (849 references), and the remaining duplicates were then located and removed manually (316 references). 2,619 unique references remained.

Eligibility criteria The eligibility criteria which will be used to shortlist the collected references at each stage of the review are as follows: 3

- Include human studies only (exclude experimental studies) - Include observational studies only (exclude reviews, government reports, letters to editors etc.) - Include studies which specifically investigate asthma’s development risks in childhood only (exclude studies which investigate asthma’s development risks in adulthood, investigate the risks of other outcomes such as the exacerbations, the prevalence or the severity of asthma in childhood and studies which investigate other endpoints in isolation such as wheeze or related asthma symptoms) - Include studies which specifically investigate exposure to traffic-related air pollution or any of the key traffic-related air pollutants when road traffic is specified as their source of origin. Key trafficrelated air pollutants include nitrogen dioxide, particulate matter, polycyclic aromatic hydrocarbons and ultra-fine particles (exclude studies which investigate exposure to air pollution originating from other sources such as industrial and indoor combustion sources) - Include studies which investigate children’s exposure to traffic-related air pollution only (exclude studies which investigate maternal or in-utero exposure) - Include studies which report a measure of association and its confidence interval precision for the association between exposure to traffic-related air pollution and the onset of asthma (exclude studies which don’t report any or report other outcome measures)

Review strategy Stage 1 HK will perform title and abstract reading for all 2,619 titles and abstracts identified from the database searches. CK will independently perform title and abstract reading for 10% randomly selected titles and abstracts. The titles and abstracts reading will identify studies which address/ potentially address the review’s question, to be full-text read in stage 2.

Stage 2 HK will obtain full papers of studies identified from stage 1. HK will perform full-text reading to shortlist collected studies, and a record of decisions made for each article will be kept. JT will independently perform full-text reading for 10% randomly selected studies. The full-text reading will identify studies which meet all eligibility criteria.

Stage 3 HK will screen the references lists of all eligible studies to identify any additional relevant studies or reviews for further screening. The lists of references for three relevant reviews which were identified previously (Braback and Forsberg 2009, Gasana et al. 2012, Wong and Leung 2005), will also be screened.

Quality assessment HK will assess the quality of the eligible studies using the ‘Critical Appraisal Skills Programme’ (CASP) checklists. The CASP checklists consist of 12 or 11 questions that need to be considered when appraising cohort or case-control studies, respectively. These questions relate to the focus of the study, the appropriateness of the recruitment procedure, possible misclassification bias when measuring the exposure and the outcome, the confounding factors considered and accounted for in the analysis, the follow-up completion and length, the precision of the risk estimates, and the overall implications and transferability of the results (Critical Appraisal Skills Programme 2014). HK and JT will then assess the strengths and weaknesses of the exposure assessment methods used in the included studies.

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Data extraction HK will perform the data extraction for all eligible studies. CK will independently perform data extraction for 10% randomly selected studies. The following data fields will be extracted from each eligible study: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28.

Country and city of origin Study’s design Parent study’s design where applicable Recruitment details Sample size Participants age group Participants’ gender split where available Participants’ ethnicity where available Definition used for asthma Procedure used to identify the onset of asthma Categorization of asthma where available Co-morbidities or secondary outcomes assessed Details of follow-up where applicable Exposure assessment method used Traffic-related pollutants studied where applicable Surrogates of exposure to traffic-related air pollution where applicable Details of exposure models used where applicable Quantitative measures of the exposure models’ performance where applicable Exposure time windows investigated Exposure place investigated Confounders selection Risk factors mentioned or found Statistical methods used Key findings Outcome measures and their confidence interval precision Limitations as reported by the authors Details of any sensitivity analysis undertaken And any additional notes

Data synthesis Data extracted from the eligible studies will be tabulated and categorized by themes. A descriptive summary will be constructed. A meta-analysis will be explored and undertaken, if meaningful.

Dissemination On completion, it is planned to submit the review for publication. The review will also form part of HK's PhD thesis.

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