Objective To investigate the expression and clinical significance of serum long non-coding RNA small nucleolar RNA host gene 16(lncRNA SNHG16)and mothers against decapentaplegic homolog 4(SMAD4)in elderly patients with chronic obstructive pulmonary disease(COPD)and pulmonary infection(PI).Methods A total of 237 elderly COPD patients admitted to the hospital from January 2021 to January 2023 were enrolled in the study.Among them,117 patients with concomitant PI were classified as the concur-rent group,and 120 patients without concomitant PI were classified as the COPD group.Real-time fluores-cence quantitative polymerase chain reaction(qRT-PCR)was applied to detect the expression level of serum lncRNA SNHG16 in two groups.Enzyme linked immunosorbent assay(ELISA)was applied to detect the lev-el of SMAD4 in patients'serum.Simplified clinical pulmonary infection scale(sCPIS)was used to evaluate the degree of PI of patients in the concurrent group.Multivariate Logistic regression was applied to analyze the in-fluencing factors of PI in elderly COPD patients.Correlation between serum lncRNA SNHG16,SMAD4 levels and sCPIS in elderly COPD patients with PI was analyzed by using Spearman correlation analysis.Receiver op-erating characteristic(ROC)curve was applied to analyze the diagnostic value of serum lncRNA SNHG16 and SMAD4 levels in elderly COPD patients with PI.Results The serum relative expression level of lncRNA SNHG16 in the concurrent group was higher than that in the COPD group,but the serum SMAD4 level was lower than that in the COPD group(P<0.05).In addition,the proportions of patients with age≥70 years,smoking history,complicated with diabetes and COPD course≥5 years and the levels of tumor necrosis fac-tor-α(TNF-α),interferon-γ(INF-γ)in the concurrent group were higher than those in the COPD group,and FEV1/FVC and the level of interleukin-10(IL-10)in concurrent group were lower than those in COPD group(P<0.05).Multivariate Logistic analysis showed that age≥70 years old,complicated with diabetes,COPD course≥5 years,high levels of TNF-α,INF-γ and lncRNA SNHG16 were risk factors for elderly patients with COPD complicated with PI(P<0.05),but high FEV1/FVC and high levels of SMAD4 and IL-10 were protective factors(P<0.05).Spearman correlation analysis showed that serum relative expression level of ln-cRNA SNHG16 was positively correlated with sCPIS in COPD patients with PI(r=0.505,P<0.001),while SMAD4 level was negatively correlated with sCPIS(r=-0.550,P<0.001).The area under the curve(AUC)of the combined diagnosis of serum lncRNA SNHG16 and SMAD4 for PI in elderly COPD patients was higher than those of individual diagnosis(Z=2.416,P=0.016;Z=2.375,P=0.018).Conclusion The serum relative expression level of lncRNA SNHG16 increases and SMAD4 level decreases in elderly COPD pa-tients with PI,both are influencing factors for elderly COPD patients complicated with PI,and both are related to the degree of PI in patients,and both have diagnostic value for elderly COPD patients complicated with PI,and the diagnostic efficacy of combined detection is better.