Daily Ards Research Analysis

INTRODUCTION: PaO OBJECTIVES: To evaluate the clinical utility of the PFP ratio in prognosticating mortality and its impact on reclassification of ARDS severity as compared to the traditional PF ratio. MATERIALS AND METHODS: This systematic review and meta-analysis (SRMA) was performed following PRISMA guidelines and registered in PROSPERO (CRD420251110685). A search for relevant studies from inception to July 2025 was performed, and the studies on adults with ARDS receiving invasive mechanical ventilation (IMV) and those that reported PFP ratio and mortality outcomes were included. Summary receiver operating characteristic (sROC) model was used to evaluate the prognostic accuracy, while the reclassification of ARDS severity using PFP vs PF ratio was descriptively analyzed. RESULTS: A total of five studies with 4,454 patients were included for meta-analysis. The pooled sensitivity and specificity of the PFP ratio for prognosticating mortality were 0.55 [95% confidence interval (CI): 0.41-0.67] and 0.90 (95% CI: 0.80-0.96), respectively. The area under the sROC was 0.84 (95% CI: 0.80-0.85), inferring good discriminant ability. For reclassification of ARDS severity based on PFP ratio, a total of four studies were included, and 30-71.9% of patients were reclassified, showing significant bidirectional shifts. CONCLUSION: Positive end-expiratory pressure incorporation to the PF ratio improves the prognostic ability and leads to meaningful reclassification of ARDS severity. HOW TO CITE THIS ARTICLE: Prabhu V, Chaudhuri S, Rao S, Todur P. Clinical Utility of Positive End-expiratory Pressure-incorporated PaO

BACKGROUND: Non-invasive ventilation (NIV) is used for an increasing range of clinical conditions at various levels of care, including intensive care units (ICUs), and has been shown to carry a lower risk of nosocomial pneumonia (NP) compared with invasive mechanical ventilation (IMV). OBJECTIVES: To assess the incidence of NP and clinical outcomes (intubation rates and mortality) in patients receiving NIV as initial support. METHODS: A systematic search of PubMed, Embase and Scopus for relevant research articles published in English was conducted up to 6 February 2025. Eligible studies included adult patients who received NIV for any respiratory condition and reported the incidence of NP. NP was defined as any new-onset pneumonia occurring at any point during the clinical course and ≥48 hours after initiating NIV. Furthermore, a subset of patients in whom NP was attributed solely to NIV support was defined as NIV-associated pneumonia (NIVAP). Two reviewers independently conducted database searches, data extraction and risk-of-bias assessment. A subgroup analysis was performed based on the indication for NIV, country and study design to identify heterogeneity. RESULTS: We incorporated 30 studies, including 36 049 patients receiving NIV. Of these, 29 studies reported the incidence of NP, while only 22 reported the incidence of NIVAP. Overall, the incidence of NP was 6% (95% confidence interval (CI) 4 - 8; I2=89.4%), and the pooled incidence of NIVAP was 3% (95% CI 2 - 4; I²=32.9%). The rate of intubation was 28% (95% CI 22 - 35; I²=89.3%), and overall mortality was 18% (95% CI 15 - 23; I²=99.0%) among patients receiving NIV. CONCLUSION: NP, including NIVAP, remains a significant complication in patients receiving NIV. Our findings underscore the need for standardised diagnostic criteria for NP in patients receiving NIV. CONTRIBUTION OF THE STUDY: This systematic review and meta-analysis provide robust pooled estimates of nosocomial pneumonia (NP) (6%; 95% CI: 4-8) and NIV-associated pneumonia (NIVAP) (3%; 95% CI: 2-4) among patients receiving non-invasive ventilation (NIV), addressing an important gap in the literature. It shows that the risk of pneumonia persists despite avoidance of intubation, challenging the prevailing assumption that NIV substantially mitigates infection risk. It also reveals significant variability in NP incidence across study designs, geographic regions, and patient subgroups-particularly a higher risk in patients with acute respiratory distress syndrome (ARDS)-highlighting the importance of context-specific risk assessment. Importantly, it underscores the lack of standardised definitions and diagnostic criteria for NP and NIVAP, which likely contributes to under-recognition and heterogeneity in reported outcomes. Collectively, these findings emphasise the need for improved surveillance, uniform diagnostic frameworks, and targeted preventive strategies for pneumonia in patients receiving NIV, extending beyond the traditional focus on invasive mechanical ventilation.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are traditionally understood as hyperinflammatory syndromes characterized by cytokine excess, neutrophil infiltration, and disruption of the alveolar-capillary barrier. However, this framework does not fully explain why some injured lungs undergo effective resolution whereas others progress toward persistent inflammation, defective epithelial regeneration, and long-term pulmonary dysfunction. Increasing evidence suggests that ALI is better conceptualized as a disorder of dysregulated tissue-centered innate immune circuits rather than a simple consequence of uncontrolled inflammation. Among the key cellular regulators of these circuits, macrophages and innate lymphoid cells (ILCs), especially ILC2s, play central and complementary roles. Macrophages function as early sentinels, inflammatory amplifiers, efferocytic cleaners, and reparative coordinators, with their impact determined by lineage origin, temporal state transitions, and niche-dependent plasticity. ILCs, in parallel, translate epithelial alarm signals into tissue-adaptive responses and contribute to barrier protection, homeostatic restoration, and modulation of macrophage function. Importantly, macrophages, ILCs, and epithelial cells form an interdependent communication network that governs the balance between inflammatory escalation and successful repair. When this network becomes disrupted, the injured lung shifts from coordinated recovery to failed repair. In this review, we discuss macrophage heterogeneity and plasticity in ALI, epithelial-macrophage and macrophage-ILC crosstalk, mechanisms of inflammatory resolution and repair failure, and emerging therapeutic opportunities aimed at restoring innate immune circuit competence in the injured lung.