Pyroptosis endotypes and malnutrition linked to mortality in older adults with community-acquired pneumonia

This retrospective cohort study examined 282 older adults (aged ≥75 years) hospitalized for community-acquired pneumonia. The analysis focused on pyroptosis activation patterns categorized as hyper-pyroptotic, intermediate-pyroptotic, and hypo-pyroptotic endotypes, alongside nutritional status measured by the MNA-SF. These biomarkers were compared against the Pneumonia Severity Index to evaluate their utility in predicting outcomes.

Main results indicated a strong association between pyroptosis endotypes and mortality. Among patients with a hyper-pyroptotic endotype, 28-day all-cause mortality was 57.5% (n=73). In contrast, mortality was 10.2% (n=128) for those with an intermediate-pyroptotic endotype and 1.2% (n=81) for those with a hypo-pyroptotic endotype. Additionally, malnutrition prevalence was notably high in the hyper-pyroptotic group, affecting 48.2% of patients. Biological markers also varied significantly; the median IL-6 level in the hyper-pyroptotic group was 98.4 pg/mL. Risk escalated sharply when GSDMD levels exceeded 3.5 ng/mL.

The study developed an integrated prognostic model that achieved an AUC of 0.898 (95% CI: 0.847–0.943). This performance surpassed the Pneumonia Severity Index, which yielded an AUC of 0.793. The research highlighted nonlinear biomarker-mortality relationships and distinct biological endotypes. No adverse events, serious adverse events, discontinuations, or tolerability issues were reported, as safety data were not applicable to this observational biomarker analysis.

Key limitations include the retrospective design and the lack of reported certainty regarding causality. The findings suggest that pyroptosis patterns may refine risk stratification in this vulnerable population. However, clinical application requires cautious interpretation given the observational nature of the data and the absence of reported funding conflicts or specific practice relevance details.