title: A cross sectional analysis of the role of the antimicrobial peptide cathelicidin in lung function impairment within the ALIVE cohort.
abstract: BACKGROUND
  Vitamin D deficiency is associated with reduced lung function. Cathelicidin, an antimicrobial peptide regulated by vitamin D, plays a role within the innate immune system. The association of cathelicidin with lung function decrement and respiratory infection is undefined. We determined the independent relationship of cathelicidin with lung function.
  
  
  METHODS
  In a cross-sectional analysis of 650 participants in an urban observational cohort with high smoking prevalence, plasma 25(OH)-vitamin D and cathelicidin levels were measured from stored samples obtained within 6 months of spirometry study visits. Multivariable linear regression was used to determine the independent association between low cathelicidin (defined as the lowest quartile of the cohort) and absolute forced expiratory volume in 1 second (FEV1).
  
  
  RESULTS
  The mean age of the cohort was 49 years; 91% were black, 35% female and 41% HIV-infected. Participants with low cathelicidin had a 183 mL lower FEV1 compared to higher cathelicidin (p = 0.009); this relationship was maintained (115 ml lower; p = 0.035) after adjusting for demographics, BMI, and smoking. Neither HIV serostatus, heavy smoking history, nor 25(OH)-vitamin D levels were associated with cathelicidin levels. Participants with low cathelicidin had a greater prevalence of prior bacterial pneumonia (21% versus 14%; p = 0.047). Inclusion of pneumonia in adjusted models did not substantially reduce the FEV1 decrement observed with low cathelicidin (104 mL lower FEV1; p = 0.05). Lung function decrements associated with low cathelicidin were greatest among individuals with lower 25(OH)-vitamin D levels.
  
  
  CONCLUSIONS
  In a cohort at risk for airflow obstruction, low cathelicidin was independently associated with lower FEV1. These clinical data support a mechanistic link between 25(OH)-vitamin D deficiency and lung function impairment, independent of pneumonia risk.
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Allison A
authors.initials: AA
authors.lastname: Lambert
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Johns Hopkins University, Baltimore, Maryland, United States of America; Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Kirk
authors.affiliation: Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Jacquie
authors.initials: J
authors.lastname: Astemborski
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Enid R
authors.initials: ER
authors.lastname: Neptune
authors.affiliation: Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Shruti H
authors.initials: SH
authors.lastname: Mehta
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wise
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: M Bradley
authors.initials: MB
authors.lastname: Drummond
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D023181:Antimicrobial Cationic Peptides / Q000097:blood; D054804:Cathelicidins; D003430:Cross-Sectional Studies; D005541:Forced Expiratory Volume; D015658:HIV Infections / Q000097:blood / Q000503:physiopathology; D008168:Lung / Q000503:physiopathology; D012907:Smoking / Q000097:blood / Q000503:physiopathology; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000503:physiopathology
chemical_list: C104450:25-hydroxyvitamin D; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D014807:Vitamin D
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