Joint Association of Systemic Immune-inflammation Index and Phenotypic Age Acceleration with Chronic Respiratory Disease: a Cross-sectional Study

Overview

Journal BMC Public Health

Publisher Biomed Central

Date 2025 Jan 17

PMID 39825391

Authors

Yuan Zhan

Ruonan Yang

Jie Feng

Genlong Bai

Xiangyun Shi

Jiaheng Zhang

Jingbo Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Chronic respiratory diseases (CRD) represents a series of lung disorders and is posing a global health burden. Systemic inflammation and phenotypic ageing have been respectively reported to associate with certain CRD. However, little is known about the co-exposures and mutual associations of inflammation and ageing with CRD. Here, we aim to systematically elucidate the joint and mutual mediating associations of systemic immune-inflammation index (SII) and phenotypic age acceleration (PhenoAgeAccel) with CRD based on data from National Health and Nutrition Examination Survey (NHANES).

Methods: Data for this study was obtained from NHANES 2007-2010 and 2015-2018. The single and combined associations of SII and PhenoAgeAccel with CRD were analyzed using multivariable logistic regression models. The dose-response relationship between exposures and outcomes was determined by restricted cubic splines (RCS) regression. Subgroup and mediation analyses were further conducted.

Results: Totally, 15,075 participants were enrolled in this study including 3,587 CRD patients. Compare with controls, CRD patients tended to be older, females and present higher SII and PhenoAgeAccel values. Single-index analysis indicated that either SII or PhenoAgeAccel demonstrated a significantly positive association with CRD via logistic regressions and RCS curves. Furthermore, the joint-indexes analysis revealed that compared to individuals with lower SII and PhenoAgeAccel, those with higher SII and PhenoAgeAccel exhibited remarkably stronger associations with CRD (adjusted OR [aOR], 1.56; 95% CI, 1.31-1.85; P < 0.001), chronic obstructive pulmonary disease (aOR, 1.56; 95% CI, 1.22-2.00; P = 0.001) and asthma (aOR, 1.40; 95% CI, 1.16-1.70; P = 0.001), which were predominant among those aged above 40 years, females and smokers. Eventually, mediation analyses suggested the mutual mediating effects of SII and PhenoAgeAccel on CRD and PhenoAgeAccel mediated SII resulting in CRD more significantly.

Conclusion: This study confirmed the coexposure effect and mutual mediation between SII and PhenoAgeAccel on CRD. We recommend that the joint assessment may conduce to the accurate identification for populations susceptible to CRD and early prevention of chronic respiratory diseases.

References

Kuo P, Schrack J, Shardell M, Levine M, Moore A, An Y . A roadmap to build a phenotypic metric of ageing: insights from the Baltimore Longitudinal Study of Aging. J Intern Med. 2020; 287(4):373-394. PMC: 7670826. DOI: 10.1111/joim.13024. View

Levine M, Lu A, Quach A, Chen B, Assimes T, Bandinelli S . An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY). 2018; 10(4):573-591. PMC: 5940111. DOI: 10.18632/aging.101414. View

Jousilahti P, Salomaa V, Hakala K, Rasi V, Vahtera E, Palosuo T . The association of sensitive systemic inflammation markers with bronchial asthma. Ann Allergy Asthma Immunol. 2002; 89(4):381-5. DOI: 10.1016/S1081-1206(10)62039-X. View

Fallahzadeh A, Tehrani Y, Sheikhy A, Ghamari S, Mohammadi E, Moghaddam S . The burden of chronic respiratory disease and attributable risk factors in North Africa and Middle East: findings from global burden of disease study (GBD) 2019. Respir Res. 2022; 23(1):268. PMC: 9521864. DOI: 10.1186/s12931-022-02187-3. View

Desquilbet L, Mariotti F . Dose-response analyses using restricted cubic spline functions in public health research. Stat Med. 2010; 29(9):1037-57. DOI: 10.1002/sim.3841. View

Kuo C, Pilling L, Liu Z, Atkins J, Levine M . Genetic associations for two biological age measures point to distinct aging phenotypes. Aging Cell. 2021; 20(6):e13376. PMC: 8208797. DOI: 10.1111/acel.13376. View

Lee H, Park H . Role of mTOR in the Development of Asthma in Mice With Cigarette Smoke-Induced Cellular Senescence. J Gerontol A Biol Sci Med Sci. 2021; 77(3):433-442. PMC: 8893251. DOI: 10.1093/gerona/glab303. View

Andujar P, Courbon D, Bizard E, Marcos E, Adnot S, Boyer L . Smoking, telomere length and lung function decline: a longitudinal population-based study. Thorax. 2017; 73(3):283-285. DOI: 10.1136/thoraxjnl-2017-210294. View

Li X, Li C, Zhang W, Wang Y, Qian P, Huang H . Inflammation and aging: signaling pathways and intervention therapies. Signal Transduct Target Ther. 2023; 8(1):239. PMC: 10248351. DOI: 10.1038/s41392-023-01502-8. View

10.

Franceschi C, Garagnani P, Parini P, Giuliani C, Santoro A . Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol. 2018; 14(10):576-590. DOI: 10.1038/s41574-018-0059-4. View

11.

Mou Y, Cao W, Wang R, Liu X, Yang X, Zhu J . The causality between C-reactive protein and asthma: a two-sample Mendelian randomization analysis. Postgrad Med J. 2024; 100(1186):555-561. DOI: 10.1093/postmj/qgae019. View

12.

Xu Y, Yan Z, Li K, Liu L . The association between systemic immune-inflammation index and chronic obstructive pulmonary disease in adults aged 40 years and above in the United States: a cross-sectional study based on the NHANES 2013-2020. Front Med (Lausanne). 2023; 10:1270368. PMC: 10704483. DOI: 10.3389/fmed.2023.1270368. View

13.

Singh A, Schurman S, Bektas A, Kaileh M, Roy R, Wilson 3rd D . Aging and Inflammation. Cold Spring Harb Perspect Med. 2023; 14(6). PMC: 11146314. DOI: 10.1101/cshperspect.a041197. View

14.

. Prevalence and attributable health burden of chronic respiratory diseases, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Respir Med. 2020; 8(6):585-596. PMC: 7284317. DOI: 10.1016/S2213-2600(20)30105-3. View

15.

Coppe J, Desprez P, Krtolica A, Campisi J . The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol. 2010; 5:99-118. PMC: 4166495. DOI: 10.1146/annurev-pathol-121808-102144. View

16.

Radzikowska U, Golebski K . Sex hormones and asthma: The role of estrogen in asthma development and severity. Allergy. 2022; 78(3):620-622. DOI: 10.1111/all.15548. View

17.

Reeves J, Kooner J, Zhang W . Accelerated ageing is associated with increased COVID-19 severity and differences across ethnic groups may exist. Front Public Health. 2022; 10:1034227. PMC: 9792858. DOI: 10.3389/fpubh.2022.1034227. View

18.

Liu Z, Kuo P, Horvath S, Crimmins E, Ferrucci L, Levine M . A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV: A cohort study. PLoS Med. 2019; 15(12):e1002718. PMC: 6312200. DOI: 10.1371/journal.pmed.1002718. View

19.

Yin X, Zhang Y, Zou J, Yang J . Association of the systemic immune-inflammation index with all-cause and cardiovascular mortality in individuals with rheumatoid arthritis. Sci Rep. 2024; 14(1):15129. PMC: 11219888. DOI: 10.1038/s41598-024-66152-4. View

20.

Parikh P, Wicher S, Khandalavala K, Pabelick C, Britt Jr R, Prakash Y . Cellular senescence in the lung across the age spectrum. Am J Physiol Lung Cell Mol Physiol. 2019; 316(5):L826-L842. PMC: 6589594. DOI: 10.1152/ajplung.00424.2018. View