Collagen biomarkers and subclinical interstitial lung disease: The Multi-Ethnic Study of Atherosclerosis

Purnema Madahar, Daniel A. Duprez, Anna J. Podolanczuk, Elana J. Bernstein, Steven M. Kawut, Ganesh Raghu, R. Graham Barr, Myron D. Gross, David R. Jacobs, David J. Lederer

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Background: Lung fibrosis is attributed to derangements in extracellular matrix remodeling, a process driven by collagen turnover. We examined the association of two collagen biomarkers, carboxy-terminal telopeptide of collagen type I (ICTP) and amino-terminal propeptide of type III procollagen (PIIINP), with subclinical interstitial lung disease (ILD) in adults. Methods: We performed a cross-sectional analysis of 3244 participants age 45–84 years in the Multi-Ethnic Study of Atherosclerosis. Serum ICTP and PIIINP levels were measured at baseline by radioimmunoassay. Subclinical ILD was defined as high attenuation areas (HAA) in the lung fields on baseline cardiac CT scans. Interstitial lung abnormalities (ILA) were measured in 1082 full-lung CT scans at 9.5 years median follow-up. We used generalized linear models to examine the associations of collagen biomarkers with HAA and ILA. Results: Median (IQR) for ICTP was 3.2 μg/L (2.6–3.9 μg/L) and for PIIINP was 5.3 μg/L (4.5–6.2 μg/L). In fully adjusted models, each SD increment in ICTP was associated with a 1.3% increment in HAA (95% CI 0.2–2.4%, p = 0.02) and each SD increment in PIIINP was associated with a 0.96% increment in HAA (95% CI 0.06–1.9%, p = 0.04). There was no association between ICTP or PIIINP and ILA. There was no evidence of effect modification by gender, race, smoking status or eGFR. Conclusions: Higher levels of collagen biomarkers are associated with greater HAA independent of gender, race and smoking status. This suggests that extracellular matrix remodeling may accompany subclinical ILD prior to the onset of clinically evident disease.

Original languageEnglish (US)
Pages (from-to)108-114
Number of pages7
JournalRespiratory Medicine
StatePublished - Jul 2018

Bibliographical note

Funding Information:
DJL has received consulting fees from Genentech/Roche, Boehringer-Ingelheim, Gilead, Pharmakea, Veracyte, Patara Pharmaceuticals, Degge Group and the France Foundation related to IPF; Columbia University has received funding for clinical trials in IPF from Boehringer-Ingelheim, Gilead, Bayer, Global Blood Therapeutics and Fibrogen; Columbia University has received funding from the Pulmonary Fibrosis Foundation for DJL's consulting services; DJL has received fees for serving as a Deputy Editor for the Annals of the American Thoracic Society and as a Statistical Editor for Thorax. SMK reports grants from NIH during the conduct of the study and non-financial support from the ATS. He has received personal fees from the European Respiratory Journal for serving on an editorial board. The University of Pennsylvania has received grants from Actelion, United Therapeutics, Gilead, Lung Biotech and Bayer for CME courses.

Funding Information:
This research was supported 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 National Heart, Lung, and Blood Institute , by grants R01-HL-103676 , K24-HL-131937 , R01-HL-077612 , R01-HL-093081 , RC1-HL100543 , and R01 HL098382 from the National Heart, Lung, and Blood Institute , and by grants UL1-TR-000040 and UL1-TR-001079 from NCRR / NCATS . The investigators were also supported by the Pulmonary Fibrosis Foundation , the Rheumatology Research Foundation Scientist Development Award and the Rocco Guinta Research Fund.


  • Collagen biomarkers
  • Extracellular matrix
  • Lung fibrosis
  • Subclinical interstitial lung disease

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