Association of bronchoalveolar lavage fluid caspase-4 with inflammatory responses in pediatric acute respiratory distress syndrome.
In a retrospective pediatric ARDS cohort, bronchoalveolar lavage fluid caspase-4 did not differ by infectious etiology or versus controls but correlated with local inflammatory cytokines, D-dimer, and modestly with oxygenation-related measures.
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In a retrospective pediatric ARDS cohort, bronchoalveolar lavage fluid caspase-4 did not differ by infectious etiology or versus controls but correlated with local inflammatory cytokines, D-dimer, and modestly with oxygenation-related measures.
Research significance
The evidence supports BALF caspase-4 as a candidate marker of pulmonary inflammatory intensity, while any hypothesis that caspase-4 inhibition could reduce inflammation or improve ARDS outcomes—including in pediatric oncology patients—remains untested inference.
Source abstract
BACKGROUND: Acute respiratory distress syndrome (ARDS) remains a major cause of morbidity in critically ill children. Although dysregulated inflammation is central to ARDS pathogenesis, the contribution of upstream inflammatory signaling pathways, particularly caspase-4-mediated responses, has not been fully characterized in pediatric populations. This study aimed to investigate bronchoalveolar lavage fluid (BALF) levels of caspase-4 and related inflammatory mediators in children with ARDS and to examine their associations with inflammatory responses and disease severity. METHODS: This retrospective study included children aged 1 month to 14 years with ARDS. After applying predefined inclusion and exclusion criteria, 28 patients with ARDS were enrolled and classified as Gram-negative bacterial infection-associated ARDS (n=14) or virus-associated ARDS (n=14), along with a separate non-infectious control group (n=17). BALF samples were collected during clinically indicated bronchoscopy. Levels of caspase-4, interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured using enzyme-linked immunosorbent assay (ELISA). Correlation analyses were performed to assess associations between caspase-4 levels, cytokines, and clinical severity indicators. RESULTS: BALF levels of caspase-4, IL-1β, IL-6, and TNF-α did not differ significantly among the three groups. However, caspase-4 levels were positively correlated with IL-1β (r=0.641, P<0.001), IL-6 (r=0.668, P<0.001), and TNF-α (r=0.375, P=0.038). Caspase-4 was also positively associated with D-dimer levels (r=0.433, P=0.031) and showed a modest association with oxygenation index-related measures. Conventional inflammatory markers did not demonstrate consistent associations with disease severity. CONCLUSIONS: BALF caspase-4 levels are closely associated with local inflammatory activity in pediatric ARDS (PARDS). Although no significant differences were observed among etiological groups, the correlations between caspase-4 and inflammatory cytokines suggest that caspase-4 may reflect the intensity of pulmonary inflammation rather than pathogen-specific mechanisms. These findings support its potential value as a biomarker for disease assessment in PARDS.