Plasma Cathelicidin is Independently Associated with Reduced Lung Function in COPD: Analysis of the Subpopulations and Intermediate Outcome Measures in COPD Study Cohort.

Abstract

RATRIONALE:

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).

OBJECTIVES:

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.

METHODS:

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.

MEASUREMENTS AND MAIN RESULTS:

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 (FEV1)(95% confidence interval [CI] -6.22% to -0.88% predicted; p=0.01), while every 10 ng/ml lower cathelicidin was independently associated with 0.65% lower % predicted FEV1 (95% CI -1.01% to -0.28% predicted; p< 0.001). No independent associations with longitudinal lung function decline or participant-reported COPD exacerbations were observed.

CONCLUSIONS:

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.

• Authors: Robert M Burkes, Agathe S Ceppe, David J Couper, Alejandro P Comellas, J Michael Wells, Stephen P Peters, Gerard J Criner, Richard E Kanner, Robert Paine 3rd, Stephanie A Christenson, Christopher B Cooper, Igor Z Barjaktarevic, Jerry A Krishnan, Wassim W Labaki, MeiLan K Han, Jeffrey L Curtis, Nadia N Hansel, Robert A Wise, M Bradley Drummond, SPIROMICS collaborators
• Journal: Chronic obstructive pulmonary diseases (Miami, Fla.) (Chronic Obstr Pulm Dis) Vol. 7 Issue 4 Pg. 370-381 (Oct 2020) ISSN: 2372-952X [Print] United States
• PMID: 33108110 (Publication Type: Journal Article)
• Copyright: JCOPDF © 2020.