What DNA methylation patterns in peripheral blood cells and in lung tissue are associated with:
• Low lung function?
• Personal smoking or exposure to tobacco smoke?
Ovid to search MEDLINE and EMBASE databases
Web of Science platform to search the Web of Science Core Texts.
Screen the references of all included studies to further gather any cited studies that match our inclusion criteria.
For MEDLINE and EMBASE, searches will be based on “Title” and “Abstract”
For Web of Science and Google Scholar searches will be based on “Title”
To make the search as sensitive as possible the “NOT” Boolean operator will not be used.
We will not impose any limits on the search regarding date or language, however, later exclusion based on unavailability of an English Abstract may occur.
Types of study to be included
Epidemiological studies including cross-sectional, case-control studies and cohort.
Randomised control trials may be considered if they include the relevant information but it is predicted that this is unlikely.
In vitro study designs are excluded from selection.
Condition or domain being studied
Chronic obstructive pulmonary disease (COPD) is a progressive, inflammatory disease of the lungs characterised by deficits in lung function measures. DNA methylation is an epigenetic modification of DNA that silences/repressed transcription of the affected gene
Children and adults taking part in epidemiological studies that include measures of lung function, COPD or smoking status, and measures of DNA methylation in peripheral blood cells or lung tissue.
Primary study not related to COPD, low lung function or smoking
DNA methylation not related to peripheral blood cells or to lung tissue
Animal or in vitro study
Abstract not available in English
Not a peer reviewed primary research publication (eg: abstract only)
The exposure is the relative DNA methylation between comparison groups.
COPD vs No COPD, smoker vs non-smoker, low lung function vs good lung function
Within participants who are representative of the general population or in patients who are representative of the population of those with disease.
Difference in DNA methylation patterns (global and locus specific)
If appropriate, a meta-analysis will be performed to estimate the effect size and statistical significance of either global DNA methylation or locus-specific DNA methylation sites.
Relative DNA methylation
Data extraction, (selection and coding)
Two researcher (DJ and MM) to screen identified titles/abstracts
Two researchers (DJ and MM) to read full text, and extract data.
Risk of bias (quality) assessment
The selection of the studies will be undertaken by three review authors independently and any discrepancies will be discussed and resolved.
The risk of bias will also be independently assessed by these authors using available tools as appropriate.
Strategy for data synthesis
The studies will initially be assessed in the form of a narrative review based on the DNA methylation patterns in the differing groups, analysing similarities and differences between them. Where possible, individual data will be used but due to the nature of the study aggregative analysis will be used to assess the overall differences in DNA methylation patterns between groups.
Where possible, a meta-analysis will be used to quantitatively assess the likelihood of a given DNA methylation pattern being associated with the outcomes – however it is predicted that the data extracted from the studies will be heterogeneous - and alternative strategies may be required and developed.
Analysis of subgroups or subsets
Subgroups may include (if sufficient studies available)
1) Peripheral blood cells vs lung tissue
2) Children vs adult
Presentations within organisation and at local conferences.
Presentations within research consortium working in the field (ALEC)
Contact details for further information
Emmanuel Kaye Building
London SW3 6LR
Organisational affiliation of the review
NHLI, Imperial College London
Professor Deborah Jarvis, NHLI Dr Andre Amaral, Mr Matthew Manchin,
Professor John Holloway, University of Southampton
Formal screening of search results against eligibility criteria
Risk of bias (quality) assessment
PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites.