Collagen biomarkers and subclinical interstitial lung disease: The Multi-Ethnic Study of Atherosclerosis. (July 2018)

• Record Type: Journal Article
• Authors: Madahar, Purnema; Duprez, Daniel A.; Podolanczuk, Anna J.; Bernstein, Elana J.; Kawut, Steven M.; Raghu, Ganesh; Barr, R. Graham; Gross, Myron D.; Jacobs, David R.; Lederer, David J.
• Is Part Of: Respiratory medicine. Volume 140(2018)
• Page Start: 108
• Page End: 114
• Publication Date: 2018-07
• Subjects: Subclinical interstitial lung disease -- Collagen biomarkers -- Extracellular matrix -- Lung fibrosis; Chest -- Diseases -- Periodicals; Chest -- Diseases -- Great Britain -- Periodicals; Respiratory organs -- Diseases -- Periodicals; Respiratory Tract Diseases -- Periodicals; Appareil respiratoire -- Maladies -- Périodiques; Thorax -- Maladies -- Périodiques; Appareil respiratoire -- Maladies -- Traitement -- Périodiques; Electronic journals; 616.2
• DOI: 10.1016/j.rmed.2018.06.001
• Languages: English
• ISSNs: 0954-6111

Abstract

Abstract: 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. Highlights: High attenuation areas (HAA) on CT scan are a validated marker of subclinical interstitial lung disease. HAA is associated with collagen biomarkers. Collagen activity may be present early in subclinical lung injury prior to clinically relevant symptoms.