Association between serum tumor necrosis factor-alpha levels and rheumatoid arthritis-associated interstitial lung disease: a cross-sectional study.
Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is one of the most severe extra-articular complications of rheumatoid arthritis (RA). Although tumor necrosis factor-α (TNF-α) plays a central role in RA pathogenesis, its relationship with RA-ILD remains uncertain. This study aimed to investigate the association between serum TNF-α levels and RA-ILD, with a focus on sex-stratified patterns.
We performed a cross-sectional study that initially included 1,191 consecutive RA inpatients at Xingtai People's Hospital between March 2022 and December 2024. Clinical and laboratory data were extracted from electronic medical records. RA-ILD was diagnosed using high-resolution computed tomography, with subtypes classified by consensus. Multivariable logistic regression and generalized additive models were used to assess the association of TNF-α with RA-ILD. Serum TNF-α was natural log-transformed (ln) to improve linearity and reduce the influence of extreme values.
After exclusions, 790 patients were included in the final analysis, of whom 149 (18.86%) had RA-ILD, with a higher prevalence in males than in females (30.68% vs 15.47%). In sex-stratified analyses, after adjusting for age, disease duration, rheumatoid factor, and anti-citrullinated protein antibody in both sexes, and additionally adjusting for smoking in males, serum TNF-α was associated with RA-ILD in females (highest vs lowest tertile: OR = 1.96, 95% CI: 1.10 - 3.48; P for trend < 0.01). This association followed a nonlinear pattern, with an exploratory inflection point above which elevated TNF-α showed a positive association with increased odds of RA-ILD. In males, no statistically significant association was observed across all models. However, the formal sex ×ln(TNF-α) interaction term was not statistically significant (P = 0.08).
In sex-stratified analyses, serum TNF-α was associated with RA-ILD in females, exhibiting a nonlinear relationship with a potential inflection point; no statistically significant association was observed in males. However, as the interaction testing did not confirm a statistically significant sex difference, these findings are exploratory and warrant further prospective validation in larger cohorts.
We performed a cross-sectional study that initially included 1,191 consecutive RA inpatients at Xingtai People's Hospital between March 2022 and December 2024. Clinical and laboratory data were extracted from electronic medical records. RA-ILD was diagnosed using high-resolution computed tomography, with subtypes classified by consensus. Multivariable logistic regression and generalized additive models were used to assess the association of TNF-α with RA-ILD. Serum TNF-α was natural log-transformed (ln) to improve linearity and reduce the influence of extreme values.
After exclusions, 790 patients were included in the final analysis, of whom 149 (18.86%) had RA-ILD, with a higher prevalence in males than in females (30.68% vs 15.47%). In sex-stratified analyses, after adjusting for age, disease duration, rheumatoid factor, and anti-citrullinated protein antibody in both sexes, and additionally adjusting for smoking in males, serum TNF-α was associated with RA-ILD in females (highest vs lowest tertile: OR = 1.96, 95% CI: 1.10 - 3.48; P for trend < 0.01). This association followed a nonlinear pattern, with an exploratory inflection point above which elevated TNF-α showed a positive association with increased odds of RA-ILD. In males, no statistically significant association was observed across all models. However, the formal sex ×ln(TNF-α) interaction term was not statistically significant (P = 0.08).
In sex-stratified analyses, serum TNF-α was associated with RA-ILD in females, exhibiting a nonlinear relationship with a potential inflection point; no statistically significant association was observed in males. However, as the interaction testing did not confirm a statistically significant sex difference, these findings are exploratory and warrant further prospective validation in larger cohorts.
Authors
Li Li, Leng Leng, Han Han, Zhang Zhang, Shang Shang, Zhang Zhang, Liu Liu, Qiao Qiao
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