Plasma Cathelicidin is Independently Associated with Reduced Lung Function in COPD: Analysis of the Subpopulations and Intermediate Outcome Measures in COPD Study Cohort
The antimicrobial peptide cathelicidin, also known in humans as LL-37, is a defensin secreted by immune and airway epithelial cells. Deficiencies in this peptide may contribute to adverse pulmonary outcomes in chronic obstructive pulmonary disease (COPD). Using clinical and biological samples from t...
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| Published in | Chronic obstructive pulmonary diseases Vol. 7; no. 4; pp. 370 - 381 |
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| Main Authors | , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
COPD Foundation Inc
01.01.2020
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| Subjects | |
| Online Access | Get full text |
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| Summary: | The antimicrobial peptide cathelicidin, also known in humans as LL-37, is a defensin secreted by immune and airway epithelial cells. Deficiencies in this peptide may contribute to adverse pulmonary outcomes in chronic obstructive pulmonary disease (COPD).
Using clinical and biological samples from the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS), we assessed the associations of plasma cathelicidin levels with cross-sectional and longitudinal COPD outcomes.
A total of 1609 SPIROMICS participants with COPD and available plasma samples were analyzed. Cathelicidin was modeled dichotomously (lowest quartile [< 50 ng/ml] versus highest 75% [≥ 50 ng/ml]) and continuously per 10 ng/ml. Fixed-effect multilevel regression analyses were used to assess associations between cathelicidin and cross-sectional as well as longitudinal lung function. The associations between cathelicidin and participant-reported retrospective and prospective COPD exacerbations were assessed via logistic regression.
Cathelicidin < 50 ng/ml (N=383) was associated with female sex, black race, and lower body mass index (BMI).At baseline,cathelicidin < 50 ng/ml was independently associated with 3.55% lower % predicted forced expiratory volume in 1 second (FEV
)(95% confidence interval [CI] -6.22% to -0.88% predicted;
=0.01), while every 10 ng/ml lower cathelicidin was independently associated with 0.65% lower % predicted FEV
(95% CI -1.01% to -0.28% predicted;
< 0.001). No independent associations with longitudinal lung function decline or participant-reported COPD exacerbations were observed.
Reduced cathelicidin is associated with lower lung function at baseline. Plasma cathelicidin may potentially identify COPD patients at increased risk for more severe lung disease. |
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| Bibliography: | The authors thank the SPIROMICS participants and participating physicians, investigators and staff for making this research possible. More information about the study and how to access SPIROMICS data is at www.spiromics.org. We would like to acknowledge the following current and former investigators of the SPIROMICS sites and reading centers: Neil E. Alexis, PhD; Wayne H. Anderson, PhD; R. Graham Barr, MD, DrPH; Eugene R. Bleecker, MD; Richard C. Boucher, MD; Russell P. Bowler, MD, PhD; Elizabeth E. Carretta, MPH; Stephanie A. Christenson, MD; Alejandro P. Comellas, MD; Christopher B. Cooper, MD, PhD; David J. Couper, PhD; Gerard J. Criner, MD; Ronald G. Crystal, MD; Jeffrey L. Curtis, MD; Claire M. Doerschuk, MD; Mark T. Dransfield, MD; Christine M. Freeman, PhD; MeiLan K. Han, MD, MS; Nadia N. Hansel, MD, MPH; Annette T. Hastie, PhD; Eric A. Hoffman, PhD; Robert J. Kaner, MD; Richard E. Kanner, MD; Eric C. Kleerup, MD; Jerry A. Krishnan, MD, PhD; Lisa M. LaVange, PhD; Stephen C. Lazarus, MD; Fernando J. Martinez, MD, MS; Deborah A. Meyers, PhD; John D. Newell, Jr., MD; Elizabeth C. Oelsner, MD, MPH; Wanda K. O’Neal, PhD; Robert Paine, III, MD; Nirupama Putcha, MD, MHS; Stephen I. Rennard, MD; Donald P. Tashkin, MD; Mary Beth Scholand, MD; J. Michael Wells, MD; Robert A. Wise, MD; and Prescott G. Woodruff, MD, MPH. The project officers from the Lung Division of the National Heart, Lung, and Blood Institute were Lisa Postow, PhD, and Thomas Croxton, PhD, MD. RMB is supported through grants from the National Institutes of Health. APC receives grants from the National Institutes of Health and receives consulting fees from VIDA. JMW receives grants from the National Institutes of Health. GJC receives grants from the National Institutes of Health and receives consulting fees from Novartis, AstraZeneca, Respironics, MedImmune, Actelion, Forest, and Pearl. REK receives contracts and grants from the National Institutes of Health. RP receives grants from the National Institutes of Health and research monies from the COPD Foundation. SAC receives grants from the National Institutes of Health and consulting fees from GlaxoSmithKline, Amgen, Glenmark, Sunovion, Genetech and MedImmune. CBC receives grants from the National Institutes of Health and contracts from the National Institutes of Health Foundation. IZB has consulting fees from Amgen, Theravance, GE Healthcare, AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim and Verona Pharma. JAK receives grants from the National Institutes of Health and the Patient-Centered Outcomes Research Institute and consulting fees from Inogen. MKH receives grants from the National Institutes of Health. JLC receives grants from the National Institutes of Health. NNH receives grants from the National Institutes of Health and the COPD Foundation and has contracts from AstraZeneca, Boehringer Ingelheim and Mylan. RAW receives consulting fees from AstraZeneca, Boehringer Ingelheim, Contrafect, Pulmonx, Roche, Spiration and Sunovion. MBD receives grants from the National Institutes of Health. ASC, DJC, SPP, and WWL have nothing to declare. Author Contributions: RMB, ASC, MBD conceptualized the study. ASC and RMB performed data analysis. RMB and MBD drafted the original manuscript. All coauthors were involved in collection of data, interpretation of of data, and critical review and revision of this manuscript. |
| ISSN: | 2372-952X 2372-952X |
| DOI: | 10.15326/jcopdf.7.4.2020.0142 |