Laboratory Biomarkers Predictive of Respiratory Failure in Hospitalized Patients: A Systematic Review

Abstract

Background:
Respiratory failure is a leading cause of mortality among hospitalized patients, especially during infectious outbreaks such as COVID-19. Early identification of patients at risk is essential to improving outcomes and optimizing resource allocation. Laboratory biomarkers such as interleukin-6 (IL-6), C-reactive protein (CRP), D-dimer, and neutrophil-to-lymphocyte ratio (NLR) have shown promise in predicting respiratory deterioration, but findings across studies remain heterogeneous.
Methods:
We conducted a systematic review following PRISMA guidelines to evaluate the predictive value of laboratory biomarkers for respiratory failure in hospitalized patients. PubMed was searched for studies published between 2000 and 2024. Eligibility criteria included observational or clinical trial studies assessing hospitalized adult patients and reporting on biomarker levels with outcomes related to respiratory failure, including mechanical ventilation or mortality. Study selection, data extraction, and risk of bias assessment (using the QUIPS tool) were performed by two independent reviewers.
Results:
Eight studies were included, comprising five cohort studies and three clinical trials, with sample sizes ranging from 88 to 1,214 patients. IL-6 levels above 80 pg/mL were associated with a significantly increased risk of respiratory failure (OR = 22.0). CRP levels above 100 mg/L and D-dimer levels above 2.0 mg/L were strong predictors of need for mechanical ventilation and in-hospital mortality. NLR >11 was associated with increased ICU length of stay. Studies that combined multiple biomarkers (e.g., IL-6 + CRP) demonstrated improved predictive accuracy (AUC up to 0.88). However, heterogeneity existed in biomarker thresholds and measurement timing.
Conclusions:
IL-6, CRP, D-dimer, and NLR are valuable biomarkers for predicting respiratory failure in hospitalized patients. Combining these markers may enhance clinical risk assessment. Standardized protocols and prospective validation are recommended to improve consistency and applicability.