Gharib Arya R, Jensen Paul N, Psaty Bruce M, Hoofnagle Andrew N, Siscovick David, Gharib Sina A, Sitlani Colleen M, Sotoodehnia Nona, Lemaitre Rozenn N
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
Departments of Medicine, Epidemiology, and Health Systems and Population Health, University of Washington, Seattle, WA, USA.
ERJ Open Res. 2023 Apr 3;9(2). doi: 10.1183/23120541.00346-2022. eCollection 2023 Mar.
COPD is the third leading cause of death in the United States. Sphingolipids, structural membrane constituents that play a role in cellular stress and apoptosis signalling, may be involved in lung function.
In the Cardiovascular Health Study, a prospective cohort of older adults, we cross-sectionally examined the association of plasma levels of 17 sphingolipid species with lung function and COPD. Multivariable linear regression and logistic regression were used to evaluate associations of sphingolipid concentrations with forced expiratory volume in 1 s (FEV) and odds of COPD, respectively.
Of the 17 sphingolipids evaluated, ceramide-18 (Cer-18) and sphingomyelin-18 (SM-18) were associated with lower FEV values (-0.061 L per two-fold higher Cer-18, p=0.001; -0.092 L per two-fold higher SM-18, p=0.002) after correction for multiple testing. Several other associations were significant at a 0.05 level, but did not reach statistical significance after correction for multiple testing. Specifically, Cer-18 and SM-18 were associated with higher odds of COPD (odds ratio per two-fold higher Cer-18 1.29, p=0.03 and SM-18 1.73, p=0.008). Additionally, Cer-16 and SM-16 were associated with lower FEV values, and Cer-14, SM-14 and SM-16 with a higher odds of COPD.
In this large cross-sectional study, specific ceramides and sphingomyelins were associated with reduced lung function in a population-based study. Future studies are needed to examine whether these biomarkers are associated with longitudinal change in FEV within individuals or with incident COPD.
慢性阻塞性肺疾病(COPD)是美国第三大死因。鞘脂作为细胞膜的结构成分,在细胞应激和凋亡信号传导中发挥作用,可能与肺功能有关。
在心血管健康研究中,这是一项针对老年人的前瞻性队列研究,我们对17种鞘脂类物质的血浆水平与肺功能及COPD之间的关联进行了横断面研究。采用多变量线性回归和逻辑回归分别评估鞘脂浓度与1秒用力呼气量(FEV)及COPD患病几率之间的关联。
在评估的17种鞘脂中,经多重检验校正后,神经酰胺-18(Cer-18)和鞘磷脂-18(SM-18)与较低的FEV值相关(Cer-18每增加两倍,FEV降低0.061升,p = 0.001;SM-18每增加两倍,FEV降低0.092升,p = 0.002)。其他几种关联在0.05水平上具有显著性,但经多重检验校正后未达到统计学显著性。具体而言,Cer-18和SM-18与较高的COPD患病几率相关(Cer-18每增加两倍,比值比为1.29,p = 0.03;SM-18每增加两倍,比值比为1.73,p = 0.008)。此外,神经酰胺-16(Cer-16)和鞘磷脂-16(SM-16)与较低的FEV值相关,神经酰胺-14(Cer-14)、鞘磷脂-14(SM-14)和SM-16与较高的COPD患病几率相关。
在这项大型横断面研究中,在基于人群的研究中,特定的神经酰胺和鞘磷脂与肺功能降低有关。未来需要开展研究,以检验这些生物标志物是否与个体FEV的纵向变化或新发COPD相关。