Robert M Burkes1, Agathe S Ceppe2, David J Couper3, Alejandro P Comellas4, J Michael Wells5, Stephen P Peters6, Gerard J Criner7, Richard E Kanner8, Robert Paine8, Stephanie A Christenson9, Christopher B Cooper10, Igor Z Barjaktarevic10, Jerry A Krishnan11, Wassim W Labaki12, MeiLan K Han12, Jeffrey L Curtis12,13, Nadia N Hansel14, Robert A Wise14, M Bradley Drummond1,2. 1. Division of Pulmonary Diseases and Critical Care Medicine, University of North Carolina, Chapel Hill. 2. Marsico Lung Institute, University of North Carolina, Chapel Hill. 3. Gillings School of Global Public Health, University of North Carolina, Chapel Hill. 4. Division of Pulmonary, Critical Care, and Occupational Medicine, Carver College of Medicine, University of Iowa, Iowa City. 5. Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama, Birmingham. 6. Section of Pulmonary, Critical Care, Allergy, and Immunologic Disease, Wake Forest University, Winston-Salem, North Carolina. 7. Division of Thoracic Medicine and Surgery, Temple University, Philadelphia, Pennsylvania. 8. Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City. 9. Division of Pulmonary Critical Care, Allergy, and Sleep Medicine, University of California, San Francisco. 10. Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California, Los Angeles. 11. Division of Pulmonary, Critical Care, Sleep, and Allergy Medicine, University of Illinois, Chicago. 12. Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor. 13. Medicine Service, VA Ann Arbor Healthcare System, Ann Arbor, Michigan. 14. Division of Pulmonary and Critical Care Medicine, Johns Hopkins University Baltimore, Maryland.
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. JCOPDF
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. JCOPDF
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