Associations of D-dimer with computed tomographic lung abnormalities, serum biomarkers of lung injury, and forced vital capacity MESA lung study

John S. Kim, Michaela R. Anderson, Elana J. Bernstein, Elizabeth C. Oelsner, Ganesh Raghu, Imre Noth, Michael Y. Tsai, Mary Salvatore, John H.M. Austin, Eric A. Hoffman, R. Graham Barr, Anna J. Podolanczuk

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 languageEnglish (US)
Pages (from-to)1839-1848
Number of pages10
JournalAnnals of the American Thoracic Society
Volume18
Issue number11
DOIs
StatePublished - 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

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