Glucocorticoid Treatment in Severe COPD Exacerbations: Biological Rationale, Clinical Effects, and Practical Advice

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD), particularly those requiring hospitalization or intensive care unit (ICU) admission, represent a significant clinical and prognostic burden. Systemic corticosteroids remain a cornerstone of AECOPD management, supporting their role in improving time to recovery, symptom relief, and hospital length of stay. These benefits are primarily attributed to corticosteroids' broad anti-inflammatory and immunomodulatory actions, including the downregulation of pro-inflammatory cytokines such as interleukin (IL)-6, IL-8, and tumor necrosis factor α, as well as the restoration of glucocorticoid receptor function impaired in severe disease. Randomized controlled trials and meta-analyses confirm that short-course, low-to-moderate corticosteroid regimens are as effective as prolonged or higher-dose treatments, minimizing adverse effects such as hyperglycemia and infections. Oral administration is equally effective as intravenous therapy in most hospitalized patients, streamlining care without compromising efficacy. In ICU settings, systemic corticosteroids have been shown to reduce the need for invasive ventilation and shorten ICU stay, although mortality benefits remain inconsistent. Emerging precision medicine approaches highlight the relevance of blood eosinophil counts in predicting corticosteroid responsiveness. Eosinophilic patients experience shorter hospital stays, faster clinical improvement, and fewer treatment failures, suggesting the utility of eosinophil-guided corticosteroid therapy. Conversely, patients with neutrophil-predominant or infectious exacerbations may derive less benefit and face a greater risk of steroid-related complications. This narrative review synthesizes current evidence on the pharmacological, clinical, and biomarker-guided use of corticosteroids in severe AECOPD, emphasizing individualized treatment strategies to optimize therapeutic outcomes. With limitations represented by heterogeneity in study populations, lack of standardized eosinophil thresholds, and sparse data in critically ill or comorbid patients, future directions should include defining optimal corticosteroid regimens, refining eosinophil thresholds, exploring adjunctive therapies, and expanding biomarker-based protocols in ICU populations. Corticosteroid stewardship, guided by inflammatory profiles, represents a critical step toward personalized care in high-risk patients with COPD.