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 journalArticle

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.

Original languageEnglish (US)
Pages (from-to)108-114
Number of pages7
JournalRespiratory Medicine
Volume140
DOIs
StatePublished - Jul 1 2018

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Interstitial Lung Diseases
Atherosclerosis
Collagen
Biomarkers
Lung
Extracellular Matrix
Smoking
Collagen Type III
Collagen Type I
Radioimmunoassay
Linear Models
Fibrosis
Cross-Sectional Studies
procollagen Type III-N-terminal peptide
Serum

Keywords

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

PubMed: MeSH publication types

  • Journal Article
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Cite this

Madahar, P., Duprez, D. A., Podolanczuk, A. J., Bernstein, E. J., Kawut, S. M., Raghu, G., ... Lederer, D. J. (2018). Collagen biomarkers and subclinical interstitial lung disease: The Multi-Ethnic Study of Atherosclerosis. Respiratory Medicine, 140, 108-114. https://doi.org/10.1016/j.rmed.2018.06.001

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

In: Respiratory Medicine, Vol. 140, 01.07.2018, p. 108-114.

Research output: Contribution to journalArticle

Madahar, P, Duprez, DA, Podolanczuk, AJ, Bernstein, EJ, Kawut, SM, Raghu, G, Barr, RG, Gross, MD, Jacobs, DR & Lederer, DJ 2018, 'Collagen biomarkers and subclinical interstitial lung disease: The Multi-Ethnic Study of Atherosclerosis', Respiratory Medicine, vol. 140, pp. 108-114. https://doi.org/10.1016/j.rmed.2018.06.001
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. / Collagen biomarkers and subclinical interstitial lung disease : The Multi-Ethnic Study of Atherosclerosis. In: Respiratory Medicine. 2018 ; Vol. 140. pp. 108-114.
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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.",
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T2 - The Multi-Ethnic Study of Atherosclerosis

AU - Madahar, Purnema

AU - Duprez, Daniel A.

AU - Podolanczuk, Anna J.

AU - Bernstein, Elana J.

AU - Kawut, Steven M.

AU - Raghu, Ganesh

AU - Barr, R. Graham

AU - Gross, Myron D.

AU - Jacobs, David R.

AU - Lederer, David J.

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N2 - 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.

AB - 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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KW - Extracellular matrix

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KW - Subclinical interstitial lung disease

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