Lambert Allison A, Kirk Gregory D, Astemborski Jacquie, Neptune Enid R, Mehta Shruti H, Wise Robert A, Drummond M Bradley
Department of Medicine, Division of Pulmonary and Critical Care, Johns Hopkins University, Baltimore, Maryland, United States of America.
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.
PLoS One. 2014 Apr 17;9(4):e95099. doi: 10.1371/journal.pone.0095099. eCollection 2014.
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.
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).
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.
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.
维生素D缺乏与肺功能下降有关。抗菌肽cathelicidin受维生素D调节，在先天免疫系统中发挥作用。cathelicidin与肺功能下降和呼吸道感染之间的关联尚不清楚。我们确定了cathelicidin与肺功能之间的独立关系。
在一项对吸烟率高的城市观察队列中的650名参与者进行的横断面分析中，从肺活量测定研究访视的6个月内采集的储存样本中测量血浆25(OH)-维生素D和cathelicidin水平。采用多变量线性回归来确定低水平cathelicidin（定义为队列中最低四分位数）与一秒用力呼气容积（FEV1）之间的独立关联。
该队列的平均年龄为49岁；91%为黑人，35%为女性，41%感染了艾滋病毒。与cathelicidin水平较高的参与者相比，cathelicidin水平较低的参与者FEV1低183毫升（p = 0.009）；在调整了人口统计学、体重指数和吸烟因素后，这种关系依然存在（低115毫升；p = 0.035）。艾滋病毒血清状态、重度吸烟史和25(OH)-维生素D水平均与cathelicidin水平无关。cathelicidin水平较低的参与者既往细菌性肺炎的患病率更高（21%对14%；p = 0.047）。在调整模型中纳入肺炎因素并没有显著降低观察到的cathelicidin水平较低时的FEV1下降幅度（FEV1低104毫升；p = 0.05）。在25(OH)-维生素D水平较低的个体中，与低水平cathelicidin相关的肺功能下降最为明显。
在有气流阻塞风险的队列中，低水平cathelicidin与较低的FEV1独立相关。这些临床数据支持了25(OH)-维生素D缺乏与肺功能损害之间的机制联系，且独立于肺炎风险。
