Abstract
Rationale: The coagulation cascade may play a role in the pathogenesis of interstitial lung disease through increased production of thrombin and fibrin deposition. Whether circulating coagulation cascade factors are linked to lung inflammation and scarring among community-dwelling adults is unknown. Objectives: To test the hypothesis that higher baseline D-dimer concentrations are associated with markers of early lung injury and scarring. Methods: Using the MESA (Multi-Ethnic Study of Atherosclerosis) cohort (n = 6,814), we examined associations of baseline D-dimer concentrations with high attenuation areas from examination 1 (2000–2002; n = 6,184) and interstitial lung abnormalities from examination 5 computed tomographic (CT) scans (2010–2012; n = 2,227), and serum MMP-7 (matrix metalloproteinase-7) and SP-A (surfactant protein-A) from examination 1 (n = 1,098). We examined longitudinal change in forced vital capacity (FVC) from examinations 3–6 (2004–2018, n = 3,562). We used linear logistic regression and linear mixed models to examine associations and adjust for potential confounders. Results: The mean (standard deviation) age of the cohort was 62 (10) years, and the D-dimer concentration was 0.35 (0.69) ug/ml. For every 10% increase in D-dimer concentration, there was an increase in high attenuation area percentage of 0.27 (95% confidence interval (CI), 0.08–0.47) after adjustment for covariates. Associations were stronger among those older than 65 years (P values for interaction, 0.001). A 10% increase in D-dimer concentration was associated with an odds ratio of 1.05 for interstitial lung abnormalities (95% CI, 0.99–1.11). Higher D-dimer concentrations were associated with higher serum MMP-7 and a faster decline in FVC. D-dimer was not associated with SP-A. Conclusions: Higher D-dimer concentrations were associated with a greater burden of lung parenchymal abnormalities detected on CT scan, MMP-7, and FVC decline among community-dwelling adults.
Original language | English (US) |
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Pages (from-to) | 1839-1848 |
Number of pages | 10 |
Journal | Annals of the American Thoracic Society |
Volume | 18 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2021 |
Bibliographical note
Funding Information:Supported by the Pulmonary Fibrosis Foundation Scholars Award and grant K23-HL-150301 from the National Heart Lung Blood Institute (NHLBI) (J.S.K.). M.R.A. was supported by grant K23-HL-150280, and Dr. Podolanczuk was supported by grant K23-HL-140199 from the NHLBI. E.J.B. was supported by grant K23-AR-075112 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The MESA (Multi-Ethnic Study of Atherosclerosis) Lung Study was supported by grants R01-HL077612, RC1-HL100543, and R01-HL093081 from the NHLBI. The MESA Lung Fibrosis Study was funded by grant R01-HL-103676 from the NHLBI. MESA was funded by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the NHLBI, U.S. National Institutes of Health (NIH). MESA was also funded by National Center for Advancing Translational Sciences (NIH) grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420.
Publisher Copyright:
© 2021 by the American Thoracic Society
Keywords
- Coagulation cascade
- D-dimer
- Interstitial lung disease
- Lung function
- Smoking