A Cross Sectional Analysis of the Role of the Antimicrobial Peptide Cathelicidin in Lung Function Impairment within the ALIVE Cohort

Abstract

BackgroundVitamin 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.MethodsIn 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).ResultsThe 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.ConclusionsIn 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.

Circulating Cathelicidin Concentrations in a Cohort of Healthy Children: Influence of Age, Body Composition, Gender and Vitamin D Status

“…Regardless of vitamin D status, there was no statistically significant difference in cathelicidin concentrations between subjects, consistent with the findings of other recent studies [ 6 , 7 , 12 , 14 , 17 , 20 ]. Varying observations, however, have been made when determining whether a correlation between 25(OH)D and cathelicidin concentrations exists.…”

“…Primarily utilized by monocytes, macrophages, mucosal epithelial cells, and keratinocytes as part of the innate immune system, these cells release cathelicidin along with other cytokines and signal molecules as a first line of defense [ 5 ]. Previous studies have focused on cathelicidin and vitamin D concentrations in patient populations affected by various illnesses or diseases [ 6 ], such as tuberculosis [ 7 ], pneumonia [ 8 ], sepsis [ 9 ], HIV [ 10 – 12 ], and end-stage renal disease hemodialysis [ 13 ], as well as healthy adult populations [ 14 – 19 ]. Additionally, while one study examined the levels of maternal and neonatal vitamin D and cathelicidin concentrations in healthy children at delivery, there is a lack of research to determine correlations between vitamin D status and cathelicidin among healthy children over time [ 20 ], as well as which factors such as age of the child, gender, and body composition may independently impact cathelicidin concentrations.…”

Vitamin D as an adjunctive therapy in asthma. Part 1: A review of potential mechanisms

“…A cross sectional analysis 650 mostly black smokers revealed that participants with low cathelicidin had significantly lower forced expiratomy volume in 1 s compared to higher cathelicidin, a relationship which remained after adjusting for confounders (p ¼ 0.035). Although, 25(OH)D was associated with cathelicidin levels, lung function decrements associated with low cathelicidin were greatest among individuals with lower 25(OH)D levels [138].…”

Vitamin D as an adjunctive therapy in asthma. Part 2: A review of human studies

“…A 20 year, Danish, prospective study with 18,507 subjects demonstrated that lower plasma 25(OH)D levels were associated with both lower lung function and faster decline in lung function (both FVC & FEV 1 ) [1]. Additionally, a crosssectional analysis of 650 mainly black, smokers revealed that there was no relationship between 25(OH)D and cathelicidin levels, but that lung function decrements were associated with low cathelicidin and were greatest among individuals with lower 25(OH)D levels [99].…”