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Summary:To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field. Systemic inflammation is associated with impaired lung function. Studies, most cross-sectional, report a stronger association between systemic inflammation and lung function impairment in men than women. The aim was to evaluate gender differences in the longitudinal association between systemic inflammation and lung function. We used data from randomly chosen residents of Reykjavík, born 1940-54, who were investigated in three stages: Baseline (1973-75; 1983-85) and follow-up (2001-03). The participants (n = 1049, 574 women) had a mean age of 28 ± 6 years at baseline and mean follow-up time of 27 ± 4 years. At each stage lung function (FEV(1) and FVC) and C-reactive protein (CRP) were evaluated. Change in FEV(1) (p = 0.04) and FVC (p = 0.01) was associated with baseline CRP in men but not in women. In the multiple variable analysis, CRP at baseline was associated with a decline in FEV(1) (-3.1 mL/year, 95% CI: -5.1, -0.99) and FVC (-2.5 mL/year, 95% CI: -4.4, -0.65) in men but not in women. Similarly during follow-up, change in CRP, standardised to 1SD, was associated with a decline in FEV(1) (-0.19 mL/year, 95% CI: -0.30, -0.07) and FVC (-0.11 mL/year, 95% CI: -0.22, -0.01)) in men but not in women. This prospective study confirms a stronger association between systemic inflammation and lung function decline in men than in women. This may indicate a gender difference in the mechanisms of lung function decline. Icelandic Research Council 050405011 Landspitali-University Hospital Research Fund