Detection of rheumatoid arthritis-interstitial lung disease is enhanced by serum biomarkers

Tracy J. Doyle, Avignat S. Patel, Hiroto Hatabu, Mizuki Nishino, Guodong Wu, Juan C. Osorio, Maria F. Golzarri, Andres Traslosheros, Sarah G. Chu, Michelle L. Frits, Christine K. Iannaccone, Diane Koontz, Carl Fuhrman, Michael E. Weinblatt, Souheil Y. El-Chemaly, George R. Washko, Gary M. Hunninghake, Augustine M K Choi, Paul F. Dellaripa, Chester V. OddisNancy A. Shadick, Dana Ascherman, Ivan O. Rosas

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Rationale: Interstitial lung disease (ILD), a leading cause of morbidity and mortality in rheumatoid arthritis (RA), is highly prevalent, yet RA-ILD is underrecognized. Objectives: To identify clinical risk factors, autoantibodies, and biomarkers associated with the presence of RA-ILD. Methods: Subjects enrolled in Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS) and American College of Rheumatology (ACR) cohorts were evaluated for ILD. Regression models were used to assess the association between variables of interest and RA-ILD. Receiver operating characteristic curves were generated in BRASS to determine if a combination of clinical risk factors and autoantibodies can identify RA-ILD and if the addition of investigational biomarkers is informative. This combinatorial signature was subsequently tested in ACR. Measurements and Main Results: A total of 113 BRASS subjects with clinically indicated chest computed tomography scans (41% with a spectrum of clinically evident and subclinical RA-ILD) and 76 ACR subjects with research or clinical scans (51% with a spectrum of RA-ILD) were selected. A combination of age, sex, smoking, rheumatoid factor, and anticyclic citrullinated peptide antibodies was strongly associated with RA-ILD (areas under the curve, 0.88 for BRASS and 0.89 for ACR). Importantly, a combinatorial signature including matrix metalloproteinase 7, pulmonary and activation-regulated chemokine, and surfactant protein D significantly increased the areas under the curve to 0.97 (P = 0.002, BRASS) and 1.00 (P = 0.016, ACR). Similar trends were seen for both clinically evident and subclinical RA-ILD. Conclusions: Clinical risk factors and autoantibodies are strongly associated with the presence of clinically evident and subclinical RA-ILD on computed tomography scan in two independent RA cohorts. A biomarker signature composed of matrix metalloproteinase 7, pulmonary and activation-regulated chemokine, and surfactant protein D significantly strengthens this association. These findings may facilitate identification of RA-ILD at an earlier stage, potentially leading to decreased morbidity and mortality.

Original languageEnglish (US)
Pages (from-to)1403-1412
Number of pages10
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume191
Issue number12
DOIs
StatePublished - Jun 15 2015

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Interstitial Lung Diseases
Rheumatoid Arthritis
Biomarkers
Serum
Rheumatology
Pulmonary Surfactant-Associated Protein D
Matrix Metalloproteinase 7
Autoantibodies
Chemokines
Area Under Curve
Tomography
Morbidity
Lung
Mortality
Rheumatoid Factor
ROC Curve

Keywords

  • Biomarkers
  • Interstitial lung disease
  • Rheumatoid arthritis
  • Risk prediction
  • Subclinical

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Detection of rheumatoid arthritis-interstitial lung disease is enhanced by serum biomarkers. / Doyle, Tracy J.; Patel, Avignat S.; Hatabu, Hiroto; Nishino, Mizuki; Wu, Guodong; Osorio, Juan C.; Golzarri, Maria F.; Traslosheros, Andres; Chu, Sarah G.; Frits, Michelle L.; Iannaccone, Christine K.; Koontz, Diane; Fuhrman, Carl; Weinblatt, Michael E.; El-Chemaly, Souheil Y.; Washko, George R.; Hunninghake, Gary M.; Choi, Augustine M K; Dellaripa, Paul F.; Oddis, Chester V.; Shadick, Nancy A.; Ascherman, Dana; Rosas, Ivan O.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 191, No. 12, 15.06.2015, p. 1403-1412.

Research output: Contribution to journalArticle

Doyle, TJ, Patel, AS, Hatabu, H, Nishino, M, Wu, G, Osorio, JC, Golzarri, MF, Traslosheros, A, Chu, SG, Frits, ML, Iannaccone, CK, Koontz, D, Fuhrman, C, Weinblatt, ME, El-Chemaly, SY, Washko, GR, Hunninghake, GM, Choi, AMK, Dellaripa, PF, Oddis, CV, Shadick, NA, Ascherman, D & Rosas, IO 2015, 'Detection of rheumatoid arthritis-interstitial lung disease is enhanced by serum biomarkers', American Journal of Respiratory and Critical Care Medicine, vol. 191, no. 12, pp. 1403-1412. https://doi.org/10.1164/rccm.201411-1950OC
Doyle, Tracy J. ; Patel, Avignat S. ; Hatabu, Hiroto ; Nishino, Mizuki ; Wu, Guodong ; Osorio, Juan C. ; Golzarri, Maria F. ; Traslosheros, Andres ; Chu, Sarah G. ; Frits, Michelle L. ; Iannaccone, Christine K. ; Koontz, Diane ; Fuhrman, Carl ; Weinblatt, Michael E. ; El-Chemaly, Souheil Y. ; Washko, George R. ; Hunninghake, Gary M. ; Choi, Augustine M K ; Dellaripa, Paul F. ; Oddis, Chester V. ; Shadick, Nancy A. ; Ascherman, Dana ; Rosas, Ivan O. / Detection of rheumatoid arthritis-interstitial lung disease is enhanced by serum biomarkers. In: American Journal of Respiratory and Critical Care Medicine. 2015 ; Vol. 191, No. 12. pp. 1403-1412.
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title = "Detection of rheumatoid arthritis-interstitial lung disease is enhanced by serum biomarkers",
abstract = "Rationale: Interstitial lung disease (ILD), a leading cause of morbidity and mortality in rheumatoid arthritis (RA), is highly prevalent, yet RA-ILD is underrecognized. Objectives: To identify clinical risk factors, autoantibodies, and biomarkers associated with the presence of RA-ILD. Methods: Subjects enrolled in Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS) and American College of Rheumatology (ACR) cohorts were evaluated for ILD. Regression models were used to assess the association between variables of interest and RA-ILD. Receiver operating characteristic curves were generated in BRASS to determine if a combination of clinical risk factors and autoantibodies can identify RA-ILD and if the addition of investigational biomarkers is informative. This combinatorial signature was subsequently tested in ACR. Measurements and Main Results: A total of 113 BRASS subjects with clinically indicated chest computed tomography scans (41{\%} with a spectrum of clinically evident and subclinical RA-ILD) and 76 ACR subjects with research or clinical scans (51{\%} with a spectrum of RA-ILD) were selected. A combination of age, sex, smoking, rheumatoid factor, and anticyclic citrullinated peptide antibodies was strongly associated with RA-ILD (areas under the curve, 0.88 for BRASS and 0.89 for ACR). Importantly, a combinatorial signature including matrix metalloproteinase 7, pulmonary and activation-regulated chemokine, and surfactant protein D significantly increased the areas under the curve to 0.97 (P = 0.002, BRASS) and 1.00 (P = 0.016, ACR). Similar trends were seen for both clinically evident and subclinical RA-ILD. Conclusions: Clinical risk factors and autoantibodies are strongly associated with the presence of clinically evident and subclinical RA-ILD on computed tomography scan in two independent RA cohorts. A biomarker signature composed of matrix metalloproteinase 7, pulmonary and activation-regulated chemokine, and surfactant protein D significantly strengthens this association. These findings may facilitate identification of RA-ILD at an earlier stage, potentially leading to decreased morbidity and mortality.",
keywords = "Biomarkers, Interstitial lung disease, Rheumatoid arthritis, Risk prediction, Subclinical",
author = "Doyle, {Tracy J.} and Patel, {Avignat S.} and Hiroto Hatabu and Mizuki Nishino and Guodong Wu and Osorio, {Juan C.} and Golzarri, {Maria F.} and Andres Traslosheros and Chu, {Sarah G.} and Frits, {Michelle L.} and Iannaccone, {Christine K.} and Diane Koontz and Carl Fuhrman and Weinblatt, {Michael E.} and El-Chemaly, {Souheil Y.} and Washko, {George R.} and Hunninghake, {Gary M.} and Choi, {Augustine M K} and Dellaripa, {Paul F.} and Oddis, {Chester V.} and Shadick, {Nancy A.} and Dana Ascherman and Rosas, {Ivan O.}",
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T1 - Detection of rheumatoid arthritis-interstitial lung disease is enhanced by serum biomarkers

AU - Doyle, Tracy J.

AU - Patel, Avignat S.

AU - Hatabu, Hiroto

AU - Nishino, Mizuki

AU - Wu, Guodong

AU - Osorio, Juan C.

AU - Golzarri, Maria F.

AU - Traslosheros, Andres

AU - Chu, Sarah G.

AU - Frits, Michelle L.

AU - Iannaccone, Christine K.

AU - Koontz, Diane

AU - Fuhrman, Carl

AU - Weinblatt, Michael E.

AU - El-Chemaly, Souheil Y.

AU - Washko, George R.

AU - Hunninghake, Gary M.

AU - Choi, Augustine M K

AU - Dellaripa, Paul F.

AU - Oddis, Chester V.

AU - Shadick, Nancy A.

AU - Ascherman, Dana

AU - Rosas, Ivan O.

PY - 2015/6/15

Y1 - 2015/6/15

N2 - Rationale: Interstitial lung disease (ILD), a leading cause of morbidity and mortality in rheumatoid arthritis (RA), is highly prevalent, yet RA-ILD is underrecognized. Objectives: To identify clinical risk factors, autoantibodies, and biomarkers associated with the presence of RA-ILD. Methods: Subjects enrolled in Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS) and American College of Rheumatology (ACR) cohorts were evaluated for ILD. Regression models were used to assess the association between variables of interest and RA-ILD. Receiver operating characteristic curves were generated in BRASS to determine if a combination of clinical risk factors and autoantibodies can identify RA-ILD and if the addition of investigational biomarkers is informative. This combinatorial signature was subsequently tested in ACR. Measurements and Main Results: A total of 113 BRASS subjects with clinically indicated chest computed tomography scans (41% with a spectrum of clinically evident and subclinical RA-ILD) and 76 ACR subjects with research or clinical scans (51% with a spectrum of RA-ILD) were selected. A combination of age, sex, smoking, rheumatoid factor, and anticyclic citrullinated peptide antibodies was strongly associated with RA-ILD (areas under the curve, 0.88 for BRASS and 0.89 for ACR). Importantly, a combinatorial signature including matrix metalloproteinase 7, pulmonary and activation-regulated chemokine, and surfactant protein D significantly increased the areas under the curve to 0.97 (P = 0.002, BRASS) and 1.00 (P = 0.016, ACR). Similar trends were seen for both clinically evident and subclinical RA-ILD. Conclusions: Clinical risk factors and autoantibodies are strongly associated with the presence of clinically evident and subclinical RA-ILD on computed tomography scan in two independent RA cohorts. A biomarker signature composed of matrix metalloproteinase 7, pulmonary and activation-regulated chemokine, and surfactant protein D significantly strengthens this association. These findings may facilitate identification of RA-ILD at an earlier stage, potentially leading to decreased morbidity and mortality.

AB - Rationale: Interstitial lung disease (ILD), a leading cause of morbidity and mortality in rheumatoid arthritis (RA), is highly prevalent, yet RA-ILD is underrecognized. Objectives: To identify clinical risk factors, autoantibodies, and biomarkers associated with the presence of RA-ILD. Methods: Subjects enrolled in Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS) and American College of Rheumatology (ACR) cohorts were evaluated for ILD. Regression models were used to assess the association between variables of interest and RA-ILD. Receiver operating characteristic curves were generated in BRASS to determine if a combination of clinical risk factors and autoantibodies can identify RA-ILD and if the addition of investigational biomarkers is informative. This combinatorial signature was subsequently tested in ACR. Measurements and Main Results: A total of 113 BRASS subjects with clinically indicated chest computed tomography scans (41% with a spectrum of clinically evident and subclinical RA-ILD) and 76 ACR subjects with research or clinical scans (51% with a spectrum of RA-ILD) were selected. A combination of age, sex, smoking, rheumatoid factor, and anticyclic citrullinated peptide antibodies was strongly associated with RA-ILD (areas under the curve, 0.88 for BRASS and 0.89 for ACR). Importantly, a combinatorial signature including matrix metalloproteinase 7, pulmonary and activation-regulated chemokine, and surfactant protein D significantly increased the areas under the curve to 0.97 (P = 0.002, BRASS) and 1.00 (P = 0.016, ACR). Similar trends were seen for both clinically evident and subclinical RA-ILD. Conclusions: Clinical risk factors and autoantibodies are strongly associated with the presence of clinically evident and subclinical RA-ILD on computed tomography scan in two independent RA cohorts. A biomarker signature composed of matrix metalloproteinase 7, pulmonary and activation-regulated chemokine, and surfactant protein D significantly strengthens this association. These findings may facilitate identification of RA-ILD at an earlier stage, potentially leading to decreased morbidity and mortality.

KW - Biomarkers

KW - Interstitial lung disease

KW - Rheumatoid arthritis

KW - Risk prediction

KW - Subclinical

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