Antonio Campanella

Background Eosinopenia has been reported as a marker of severity in infections, but its prognostic value in patients with severe community-acquired pneumonia (CAP) admitted to the intensive care unit (ICU) is unclear. Methods We retrospectively analyzed 496 patients with severe CAP admitted to the ICU, stratified by presence of eosinopenia at admission. Clinical characteristics, laboratory data, microbiological etiology, treatment, and outcomes were compared. Multivariable Cox regression identified independent predictors of 30-day mortality. Predictive performance of eosinophil counts, severity scores (CRB-65, CURB-65, PSI), and a modified CURB-65 incorporating eosinopenia (CURB-65Eos) were assessed. Results Eosinopenia was detected in 33% of patients. There were no differences in age and comorbidities between eosinopenic and non eosinopenic patients. Compared to non-eosinopenic patients, these patients had lower leukocyte, neutrophil, and lymphocyte counts and more frequent viral or polymicrobial infections. They more often required invasive mechanical ventilation (58% vs. 45%, p = 0.009) and developed pleural effusions (30% vs. 19%, p = 0.008). In-hospital and 30-day mortality were higher in the eosinopenia group (21% vs. 13%, p = 0.036; 20% vs. 12%, p = 0.022). Eosinopenia independently predicted 30-day mortality (HR 1.98; 95% CI 1.23–3.16; p = 0.005). Eosinophil counts alone had poor predictive accuracy (AUC 0.562), while established severity scores performed moderately. CURB-65Eos showed a numerical but nonsignificant improvement over CURB-65. Conclusions Eosinopenia is common in patients with severe CAP admitted to the ICU and is strongly associated with increased severity and mortality independent of age and comorbidities. It may serve as simple and inexpensive biomarker for the early identification of high-risk patients and could help guide more intensive therapeutic interventions.

Acute respiratory distress syndrome (ARDS) remains a heterogeneous and a major challenge disease process despite five decades of study. Emerging translational data delineate three overlapping phases: exudative, proliferative, and fibroproliferative, each driven by distinct immune–mechanical pathways and potentially modifiable by glucocorticosteroids (GC) modulation. Contemporary clinical randomized trials and meta-analyses indicate that early (≤72 hours) administration of systemic GCs at receptor-saturating doses (e.g., dexamethasone from 20 to 10 mg/day, or methylprednisolone 1–2 mg/kg/day) accelerates resolution of pulmonary edema, shortens mechanical ventilation duration, and improves intensive care survival, while prolonged tapering regimens are required once fibroproliferation is established. Conversely, delayed initiation (>14 days), viral pneumonitis with high viral load, recent surgical anastomosis, or uncontrolled fungal coinfection constitute “red flags” in which GCs might increase mortality. Latent-class analyses—a statistical modeling approach in which multivariable data are reduced to indirectly observed (latent) variables—identified two (hyper- and hypoinflammatory) ARDS phenotypes that likely might respond differentially to GC exposure, although we lack validation studies. Therefore, it seems that biomarker-guided precision therapy is poised to replace the historical one-size-fits-all approach. This narrative review integrates epidemiology, pathobiology, pharmacology, and clinical evidence to provide a phase-specific, phenotype-directed framework for GC use in ARDS and outlines future research priorities aimed at harmonizing molecular endotyping with dose, timing, and tapering strategies.