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Meta-Analysis
. 2014 Mar 5;16(2):R61.
doi: 10.1186/ar4498.

Cigarette Smoking and Risk of Rheumatoid Arthritis: A Dose-Response Meta-Analysis

Free PMC article
Meta-Analysis

Cigarette Smoking and Risk of Rheumatoid Arthritis: A Dose-Response Meta-Analysis

Daniela Di Giuseppe et al. Arthritis Res Ther. .
Free PMC article

Abstract

Introduction: Although previous studies found that cigarette smoking is associated with risk of rheumatoid arthritis (RA), the dose-response relationship remains unclear. This meta-analysis quantitatively summarizes accumulated evidence regarding the association of lifelong exposure to cigarette smoking assessed as pack-years with the risk of RA.

Methods: Relevant studies were identified by a search of MEDLINE and EMBASE from 1966 to October 2013, with no restrictions. Reference lists from retrieved articles were also reviewed. Studies that reported relative risks (RR) or odds ratio (OR) estimates with 95% confidence intervals (CIs) for the association between pack-years of cigarette smoking and rheumatoid arthritis were included in a dose-response random-effects meta-regression analysis.

Results: We included 3 prospective cohorts and 7 case-control studies in the meta-analysis. They included a total of 4,552 RA cases. There was no indication of heterogeneity (Pheterogeneity = 0.32) and publication bias did not affect the results. Compared to never smokers, the risk of developing RA increased by 26% (RR = 1.26, 95% CI 1.14 to 1.39) among those who smoked 1 to 10 pack-years and doubled among those with more than 20 pack-years (RR for 21 to 30 pack years = 1.94, 95% CI 1.65 to 2.27). The risk of RA was not increasing further for higher exposure levels (RR for >40 pack-years = 2.07, 95% CI 1.15 to 3.73). The risk of RA was statistically significantly higher among rheumatoid factor (RF)-positive RA cases (RR = 2.47, 95% CI 2.02 to 3.02) compared to RF-negative (RR = 1.58, 95% CI 1.15 to 2.18) when comparing the highest versus lowest category of pack-years for the individual studies.

Conclusions: Lifelong cigarette smoking was positively associated with the risk of RA even among smokers with a low lifelong exposure. The risk of RA did not further increase with an exposure higher than 20 pack-years.

Figures

Figure 1
Figure 1
Flow chart of selection of studies for inclusion in the meta-analysis.
Figure 2
Figure 2
Non-linear dose-response relationship between pack-years of cigarettes smoking and relative risk of RA. Relative risk (solid line) and 95% confidence interval (long dashed lines) from the restricted cubic splines model. The short dashed line represents the RR from the linear model. Estimates reported in the table are based on median value of each category.
Figure 3
Figure 3
Forest plot of relative risk estimates for rheumatoid arthritis risk associated with pack-years of cigarette smoking (highest vs. lowest category). CI indicates confidence intervals; RR indicates relative risk. The size of each square is proportional to the study’s weight (inverse variance). *Test for heterogeneity: cohort studies, P = 0.96, I2 = 0.0%; case-control studies, P = 0.19, I2 = 28.7%, overall studies, P = 0.32, I2 = 12.7%.

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