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Plasma sphingolipids, lung function and COPD: the Cardiovascular Health Study
Arya R Gharib1, Paul N Jensen1, Bruce M Psaty1,2
1Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
Insights
Specific sphingolipids, such as ceramides and sphingomyelins, are linked to reduced lung function and increased COPD risk in older adults. Further research is needed to confirm these findings and explore their impact on disease progression.
Area of Science:
- Biochemistry
- Pulmonology
- Gerontology
Background:
- Chronic Obstructive Pulmonary Disease (COPD) is a major cause of mortality in the US.
- Sphingolipids, crucial for cell membranes, are implicated in cellular stress and apoptosis, suggesting a role in lung health.
Purpose of the Study:
- To investigate the association between plasma sphingolipid levels and lung function.
- To examine the relationship between sphingolipid profiles and the prevalence of COPD in older adults.
Main Methods:
- Utilized data from the Cardiovascular Health Study, a prospective cohort of older adults.
- Employed multivariable linear and logistic regression to analyze 17 sphingolipid species against forced expiratory volume in 1-second (FEV1) and COPD odds.
Main Results:
- Elevated levels of ceramide-18 (Cer-18) and sphingomyelin-18 (SM-18) were significantly associated with lower FEV1.
- Cer-18 and SM-18 were also linked to increased odds of COPD, with odds ratios of 1.29 and 1.73, respectively.
- Other sphingolipids like Cer-16, SM-16, Cer-14, and SM-14 showed associations with lung function and COPD, though some did not meet stringent statistical significance after multiple testing corrections.
Conclusions:
- Specific ceramides and sphingomyelins correlate with diminished lung function in a population-based sample of older adults.
- These sphingolipids may serve as potential biomarkers for COPD.
- Further longitudinal studies are warranted to explore the predictive value of these sphingolipids for FEV1 decline and COPD incidence.
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.
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