Plasma sphingolipids, lung function and COPD: the Cardiovascular Health Study

Arya R Gharib; Paul N Jensen; Bruce M Psaty; Andrew N Hoofnagle; David Siscovick; Sina A Gharib; Colleen M Sitlani; Nona Sotoodehnia; Rozenn N Lemaitre

doi:10.1183/23120541.00346-2022

Plasma sphingolipids, lung function and COPD: the Cardiovascular Health Study

ERJ Open Res. 2023 Apr 3;9(2):00346-2022. doi: 10.1183/23120541.00346-2022. eCollection 2023 Mar.

Authors

Arya R Gharib¹, Paul N Jensen¹, Bruce M Psaty^{1

2}, Andrew N Hoofnagle³, David Siscovick⁴, Sina A Gharib^{1

5}, Colleen M Sitlani¹, Nona Sotoodehnia^{1

6}, Rozenn N Lemaitre¹

Affiliations

¹ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
² Departments of Medicine, Epidemiology, and Health Systems and Population Health, University of Washington, Seattle, WA, USA.
³ Department of Laboratory Medicine, University of Washington, Seattle, WA, USA.
⁴ New York Academy of Medicine, New York, NY, USA.
⁵ Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA, USA.
⁶ Division of Cardiology, Department of Medicine, University of Washington, Seattle, WA, USA.

Abstract

Rationale: 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.

Methods: 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 (FEV₁) and odds of COPD, respectively.

Results: Of the 17 sphingolipids evaluated, ceramide-18 (Cer-18) and sphingomyelin-18 (SM-18) were associated with lower FEV₁ 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 FEV₁ values, and Cer-14, SM-14 and SM-16 with a higher odds of COPD.

Conclusion: 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 FEV₁ within individuals or with incident COPD.

Abstract

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