Purnema Madahar1, Daniel A Duprez2, Anna J Podolanczuk1, Elana J Bernstein1, Steven M Kawut3, Ganesh Raghu4, R Graham Barr5, Myron D Gross6, David R Jacobs7, David J Lederer8. 1. Department of Medicine, Columbia University Irving Medical Center, 161 Fort Washington Avenue, New York, NY, 10032, USA. 2. Department of Medicine, University of Minnesota, 420 Delaware St SE, Minneapolis, MN, 55455, USA. 3. Department of Medicine and the Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, 423 Guardian Drive, Philadelphia, PA, 19104, USA. 4. Department of Medicine, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA. 5. Department of Medicine, Columbia University Irving Medical Center, 161 Fort Washington Avenue, New York, NY, 10032, USA; Department of Epidemiology, Columbia University Irving Medical Center, 161 Fort Washington Avenue, New York, NY, 10032, USA. 6. Department of Laboratory Medicine and Pathology, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA. 7. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA. 8. Department of Medicine, Columbia University Irving Medical Center, 161 Fort Washington Avenue, New York, NY, 10032, USA; Department of Epidemiology, Columbia University Irving Medical Center, 161 Fort Washington Avenue, New York, NY, 10032, USA. Electronic address: davidlederer@columbia.edu.
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.
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.
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