Fibrinogen is a promising biomarker for chronic obstructive pulmonary disease: evidence from a meta-analysis

Abstract Backgrounds: Some studies have reported association of circulating fibrinogen with the risk of chronic obstructive pulmonary disease (COPD), and the results are conflicting. To yield more information, we aimed to test the hypothesis that circulating fibrinogen is a promising biomarker for COPD by a meta-analysis. Methods: Data extraction and quality assessment were independently completed by two authors. Effect-size estimates are expressed as weighted mean difference (WMD) with 95% confidence interval (95% CI). Results: Forty-five articles involving 5586/18604 COPD patients/controls were incorporated. Overall analyses revealed significantly higher concentrations of circulating fibrinogen in COPD patients than in controls (WMD: 84.67 mg/dl; 95% CI: 64.24–105.10). Subgroup analyses by COPD course showed that the degree of increased circulating fibrinogen in patients with acute exacerbations of COPD (AECOPD) relative to controls (WMD: 182.59 mg/dl; 95% CI: 115.93–249.25) tripled when compared in patients with stable COPD (WMD: 56.12 mg/dl; 95% CI: 34.56–77.67). By COPD severity, there was a graded increase in fibrinogen with the increased severity of COPD relative to controls (Global Initiative for Obstructive Lung Disease (GOLD) I, II, III, and IV: WMD: 13.91, 29.19, 56.81, and 197.42 mg/dl; 95% CI: 7.70–20.11, 17.43–40.94, 39.20–74.41, and −7.88 to 402.73, respectively). There was a low probability of publication bias. Conclusion: Our findings indicate a graded, concentration-dependent, significant relation between higher circulating fibrinogen and more severity of COPD.


TITLE Page
Title 1 Identify the report as a systematic review, meta-analysis, or both. 1

Structured summary
2 Provide a structured summary including, as applicable: background; objectives; data sources; study eligibility criteria, participants, and interventions; study appraisal and synthesis methods; results; limitations; conclusions and implications of key findings; systematic review registration number.

INTRODUCTION
Rationale 3 Describe the rationale for the review in the context of what is already known.

4-5
Objectives 4 Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS).

Protocol and registration
5 Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number.

5
Eligibility criteria 6 Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale.

6
Information sources 7 Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.

5
Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.

5
Study selection 9 State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the metaanalysis).
6 Data collection process 10 Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators.

6
Data items 11 List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made. 6

Risk of bias in individual studies
12 Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis.

6-7
Synthesis of results 14 Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I 2 ) for each meta-analysis.

7
Risk of bias across studies 15 Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies).

RESULTS
Study selection 17 Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.

8
Study characteristics 18 For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations.

8-9
Risk of bias within studies 19 Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12).

9
Results of individual studies 20 For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot.

9-10
Synthesis of results 21 Present results of each meta-analysis done, including confidence intervals and measures of consistency.

9-10
Risk of bias across studies 22 Present results of any assessment of risk of bias across studies (see Item 15).

Summary of evidence
24 Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers).

11-12
Limitations 25 Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias).

13
Conclusions 26 Provide a general interpretation of the results in the context of other evidence, and implications for future research.

FUNDING
Funding 27 Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review.