Systemic Immune Response Index Identified as Independent Risk Factor for COPD

The systemic immune response index (SIRI) is an independent risk factor for chronic obstructive pulmonary disease (COPD) that a recent Scientific Reports study found is positively associated with the condition.¹

Although significant progress has been made in understanding COPD, the researchers emphasized the need for further investigation into its underlying mechanisms and effective interventions to improve patient outcomes. They added that while the link between inflammation and COPD is being increasingly recognized, the correlation between the disease and SIRI, a novel marker of inflammation, remains unknown.

“Given how simple it is to get clinical data straight from SIRI, investigating its relationship to COPD is crucial for both diagnosing and treating the disease,” the authors wrote.

The systemic immune response index outperformed other inflammatory markers in predicting chronic obstructive pulmonary disease. | Image Credit: Maks_Lab - stock.adobe.com

To explore this relationship, the researchers conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) on patients with complete lung function between 2007 and 2012. Conducted by the CDC, NHANES provides data on the health and nutritional status of the noninstitutionalized US population.²

They used multifactorial logistic regression analyses to examine the relationship between COPD and various inflammatory markers: SIRI, systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and low-density-lipoprotein to lymphocyte ratio (LLR).¹ Model 1 was unadjusted, model 2 adjusted for age, race, gender, and education, and model 3 adjusted for additional covariates.

Also, a receiver operating characteristic (ROC) curve analysis assessed the diagnostic value of these inflammatory biomarkers, while a smoothed curve fitting analysis explored potential nonlinear associations between COPD and SIRI.

The researchers recruited 5056 participants from NHANES, including 2517 males and 2539 females. The sample consisted of 706 patients with COPD and 4350 participants without COPD.

Model 3, the fully adjusted multivariable logistic regression analysis, showed that SIRI was associated with a high risk of COPD (OR, 1.350; 95% CI, 1.220-1.493). Model 3 also analyzed the inflammatory markers as categorical variables in quartiles. By comparing higher quartiles to quartile 1 (Q1), the researchers assessed whether increasing levels of these inflammatory markers were linked to higher COPD odds.

Consequently, they found that higher quartiles of SIRI (Q3: OR, 1.344; 95% CI, 1.042-1.732; Q4: OR, 1.836; 95% CI, 1.438-2.343) and SII (Q3: OR, 1.288; 95% CI, 1.010-1.642; Q4: OR, 1.486; 95% CI, 1.173-1.883) were significantly associated with increased COPD odds. Similarly, NLR showed a progressive association with COPD across quartiles 2 (OR, 1.313; 95% CI, 1.016-1.698), 3 (OR, 1.611; 95% CI, 1.256-2.067), and 4 (OR, 1.745; 95% CI, 1.370-2.222). However, LLR was only significantly associated with COPD in Q4 (OR, 1.342; 95% CI, 1.060-1.699).

Additionally, the ROC curve analysis found that the area under the curve values for SIRI, LMR, NLR, SII, and LLR were 0.596, 0.583, 0.574, 0.555, and 0.521, respectively, indicating that SIRI outperformed the other inflammatory markers in predicting COPD. After adjusting for all covariates, the smoothed curve fitting showed a linear relationship between SIRI and COPD incidence, with each unit increase in SIRI correlating to a 16% higher COPD risk (OR, 1.166; 95% CI, 1.040-1.307).

Lastly, subgroup analyses indicated that the effect of SIRI on COPD was more pronounced in smokers, especially those who still smoke (OR, 1.58; 95% CI, 1.34-1.86) and in men (OR, 1.62; 95% CI, 1.44-1.83).

The researchers acknowledged their study’s limitations, including that its cross-sectional nature prevented causality between COPD and SIRI from being inferred. Also, the study population consisted solely of people in the US, so the findings may not be generalizable to those in other countries. Despite these limitations, they expressed confidence in their findings and suggested areas for further research.

“To further improve the utility of this marker, it is necessary to confirm the predictive value of SIRI for COPD in future studies with some longitudinal studies and RCTs [randomized controlled trials],” the authors concluded.

References

1. Jia S, Chen Q, Huang W, Wang P, Zeng Y. Relationship between systemic immune response index (SIRI) and COPD: a cross-sectional study based on NHANES 2007-2012. Sci Rep. 2025;15(1):7887. doi:10.1038/s41598-025-90947-8
2. National Health and Nutrition Examination Survey. CDC. Accessed March 21, 2025. https://www.cdc.gov/nchs/nhanes/index.html