TY - JOUR
T1 - Telomere length and genetic variant associations with interstitial lung disease progression and survival
AU - Newton, Chad A.
AU - Oldham, Justin M.
AU - Ley, Brett
AU - Anand, Vikram
AU - Adegunsoye, Ayodeji
AU - Liu, Gabrielle
AU - Batra, Kiran
AU - Torrealba, Jose
AU - Kozlitina, Julia
AU - Glazer, Craig
AU - Strek, Mary E.
AU - Wolters, Paul J.
AU - Noth, Imre
AU - Garcia, Christine Kim
N1 - Funding Information:
Support statement: The authors acknowledge funding support provided by the National Institutes of Health (awards R01 HL09309 (C.K. Garcia), KL2TR001103 (C.A. Newton), K23HL13890 ( J.M. Oldham), KL2TR001870 (B. Ley) and R01 HL130796 (I. Noth)). Funding information for this article has been deposited with the Crossref Funder Registry.
Funding Information:
Conflict of interest: C.A. Newton reports grants from the National Institutes of Health (KL2TR001103), during the conduct of the study. J.M. Oldham reports grants from the National Heart, Lung, and Blood Institute (NHLBI), and personal fees from Genentech and Boehringer Ingelheim, outside the submitted work. B. Ley has nothing to disclose. V. Anand has nothing to disclose. A. Adegunsoye reports speaking fees and honoraria for advisory boards with Boehringer Ingelheim related to idiopathic pulmonary fibrosis (IPF) within the last 12 months. G. Liu has nothing to disclose. K. Batra has nothing to disclose. J. Torrealba reports personal fees for expert panel work from Roche–Ventana and AbbVie, outside the submitted work. J. Kozlitina has nothing to disclose. C. Glazer is a member of a speaker bureau for Genentech. There is no discussion of therapy in this paper. M.E. Strek reports grants and personal fees for advisory board work and speaker fees from Boehringer Ingelheim, and grants from Genentech-Roche, Gilead and MedImmune, outside the submitted work. P.J. Wolters reports grants from Medimmune and Genentech, and personal fees from Roche and Boehringer Ingelheim, outside the submitted work. I. Noth reports personal fees for consultancy from Boehringer Ingelheim, Genentech, Sanofi Aventis and Global Blood Therapeutics, outside the submitted work, and has a patent pending on TOLLIP and IPF pharmacogenomics. C.K. Garcia reports grants from the National Institutes of Health (R01 HL09309) during the conduct of the study and was previously a member of the advisory board for Pliant Therapeutics.
Publisher Copyright:
Copyright © ERS 2019
PY - 2019/4/1
Y1 - 2019/4/1
N2 - Leukocyte telomere length (LTL), MUC5B rs35705950 and TOLLIP rs5743890 have been associated with idiopathic pulmonary fibrosis (IPF). In this observational cohort study, we assessed the associations between these genomic markers and outcomes of survival and rate of disease progression in patients with interstitial pneumonia with autoimmune features (IPAF, n=250) and connective tissue disease-associated interstitial lung disease (CTD-ILD, n=248). IPF (n=499) was used as a comparator. The LTL of IPAF and CTD-ILD patients (mean age-adjusted log-transformed T/S of −0.05±0.29 and −0.04±0.25, respectively) is longer than that of IPF patients (−0.17±0.32). For IPAF patients, LTL <10th percentile is associated with faster lung function decline compared to LTL ≥10th percentile (−6.43% per year versus −0.86% per year; p<0.0001) and worse transplant-free survival (hazard ratio 2.97, 95% CI 1.70-5.20; p=0.00014). The MUC5B rs35705950 minor allele frequency (MAF) is greater for IPAF patients (23.2, 95% CI 18.8-28.2; p<0.0001) than controls and is associated with worse transplant-free IPAF survival (hazard ratio 1.92, 95% CI 1.18-3.13; p=0.0091). Rheumatoid arthritis (RA)-associated ILD (RA-ILD) has a shorter LTL than non-RA CTD-ILD (−0.14±0.27 versus −0.01±0.23; p=0.00055) and higher MUC5B MAF (34.6, 95% CI 24.4-46.3 versus 14.1, 95% CI 9.8-20.0; p=0.00025). Neither LTL nor MUC5B are associated with transplant-free CTD-ILD survival. LTL and MUC5B MAF have different associations with lung function progression and survival for IPAF and CTD-ILD.
AB - Leukocyte telomere length (LTL), MUC5B rs35705950 and TOLLIP rs5743890 have been associated with idiopathic pulmonary fibrosis (IPF). In this observational cohort study, we assessed the associations between these genomic markers and outcomes of survival and rate of disease progression in patients with interstitial pneumonia with autoimmune features (IPAF, n=250) and connective tissue disease-associated interstitial lung disease (CTD-ILD, n=248). IPF (n=499) was used as a comparator. The LTL of IPAF and CTD-ILD patients (mean age-adjusted log-transformed T/S of −0.05±0.29 and −0.04±0.25, respectively) is longer than that of IPF patients (−0.17±0.32). For IPAF patients, LTL <10th percentile is associated with faster lung function decline compared to LTL ≥10th percentile (−6.43% per year versus −0.86% per year; p<0.0001) and worse transplant-free survival (hazard ratio 2.97, 95% CI 1.70-5.20; p=0.00014). The MUC5B rs35705950 minor allele frequency (MAF) is greater for IPAF patients (23.2, 95% CI 18.8-28.2; p<0.0001) than controls and is associated with worse transplant-free IPAF survival (hazard ratio 1.92, 95% CI 1.18-3.13; p=0.0091). Rheumatoid arthritis (RA)-associated ILD (RA-ILD) has a shorter LTL than non-RA CTD-ILD (−0.14±0.27 versus −0.01±0.23; p=0.00055) and higher MUC5B MAF (34.6, 95% CI 24.4-46.3 versus 14.1, 95% CI 9.8-20.0; p=0.00025). Neither LTL nor MUC5B are associated with transplant-free CTD-ILD survival. LTL and MUC5B MAF have different associations with lung function progression and survival for IPAF and CTD-ILD.
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U2 - 10.1183/13993003.01641-2018
DO - 10.1183/13993003.01641-2018
M3 - Article
C2 - 30635297
AN - SCOPUS:85062701792
SN - 0903-1936
VL - 53
JO - Scandinavian Journal of Respiratory Diseases
JF - Scandinavian Journal of Respiratory Diseases
IS - 4
M1 - 1801641
ER -