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Acute respiratory distress syndrome; ARDS; Pathophysiology; Diagnosis; Treatment; Ventilator management; Lung injury; Critical care

Introduction

Acute Respiratory Distress Syndrome (ARDS) is a life-threatening condition characterized by acute hypoxemic respiratory failure, bilateral pulmonary infiltrates, and decreased lung compliance. First described in the late 1960s, ARDS continues to challenge clinicians worldwide due to its complex pathophysiology and variable clinical course. Despite advances in supportive care and ventilation strategies, ARDS remains associated with high morbidity and mortality rates. This article provides a comprehensive overview of ARDS, encompassing its epidemiology, etiology, pathogenesis, clinical features, diagnostic criteria, and therapeutic interventions [1].

ARDS affects individuals of all ages and can arise from various predisposing factors, including pneumonia, sepsis, trauma, and aspiration. Epidemiological studies have reported an annual incidence of ARDS ranging from 13 to 59 cases per 100,000 populations, with higher rates observed in critically ill patients admitted to intensive care units (ICUs). Despite advancements in critical care medicine, the mortality rate associated with ARDS remains substantial, ranging from 35% to 46% [2].

The pathogenesis of ARDS involves a complex interplay of inflammatory mediators, endothelial dysfunction, alveolar epithelial injury, and dysregulated immune responses. Inflammatory cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), play a pivotal role in initiating and perpetuating the inflammatory cascade within the lungs. Endothelial and epithelial injury disrupts the alveolar-capillary barrier, leading to protein-rich pulmonary edema, impaired gas exchange, and alveolar collapse. Moreover, dysregulated immune responses contribute to ongoing lung injury and perpetuate systemic inflammation, further exacerbating organ dysfunction [3, 4].

ARDS typically presents with acute onset dyspnea, tachypnea, and hypoxemia refractory to supplemental oxygen therapy. Physical examination may reveal diffuse crackles, diminished breath sounds, and signs of respiratory distress. Laboratory investigations often demonstrate leukocytosis, elevated inflammatory markers, and metabolic acidosis. Chest radiography and computed tomography (CT) imaging reveal diffuse bilateral infiltrates consistent with non-cardiogenic pulmonary edema. The diagnosis of ARDS is established based on the Berlin criteria, which include the presence of acute hypoxemia (PaO2/FiO2 ratio ≤ 300 mmHg) with bilateral pulmonary infiltrates on chest imaging, not fully explained by cardiac failure or fluid overload. ARDS is further classified into mild, moderate, and severe categories based on the degree of hypoxemia [5, 6].

The management of ARDS involves a multifaceted approach aimed at addressing underlying causes, optimizing supportive care, and mitigating ventilator-induced lung injury. Lung-protective ventilation strategies, including low tidal volume ventilation and positive end-expiratory pressure (PEEP) titration, are cornerstone interventions in ARDS management. Adjunctive therapies such as prone positioning, neuromuscular blockade, and extracorporeal membrane oxygenation (ECMO) may be employed in severe cases refractory to conventional measures. Pharmacological interventions targeting inflammation, coagulation, and epithelial repair have shown promise in preclinical studies but have yet to demonstrate consistent clinical efficacy [7].

Recent research has unveiled promising avenues for the treatment of ARDS, with a focus on novel pharmacological agents, immunomodulatory therapies, and regenerative medicine approaches. Mesenchymal stem cell (MSC) therapy has garnered significant attention for its potential to attenuate lung inflammation, enhance tissue repair, and restore alveolar epithelial integrity. Preclinical studies have demonstrated the beneficial effects of MSC administration in experimental models of ARDS, leading to reduced pulmonary edema, improved oxygenation, and enhanced lung function. Clinical trials evaluating the safety and efficacy of MSC therapy in ARDS patients have shown encouraging results, with preliminary data suggesting improved clinical outcomes and reduced mortality rates [8].

In addition to cell-based therapies, immunomodulatory agents targeting specific inflammatory pathways have emerged as promising candidates for ARDS treatment. Janus kinase (JAK) inhibitors, such as baricitinib and tofacitinib, have shown efficacy in modulating cytokine signaling and attenuating lung inflammation in preclinical models of ARDS [9]. Clinical trials investigating the use of JAK inhibitors in COVID-19-associated ARDS have demonstrated potential benefits in reducing disease severity and improving oxygenation. Similarly, monoclonal antibodies targeting pro-inflammatory cytokines, such as interleukin-6 (IL-6) and interleukin-1 (IL-1), have shown promise in mitigating the hyper inflammatory response associated with ARDS, although further research is needed to elucidate their optimal dosing regimens and clinical efficacy [10].

Regenerative medicine approaches, including lung tissue engineering and gene therapy, offer innovative strategies for repairing damaged lung tissue and restoring respiratory function in ARDS patients. Bioengineered scaffolds seeded with patient-derived cells hold the potential to regenerate functional lung tissue and promote alveolar repair in ARDS-induced lung injury [11]. Gene therapy techniques, such as CRISPR/Cas9-mediated genome editing, offer precision-targeted approaches for modulating gene expression and correcting genetic abnormalities underlying ARDS pathogenesis. While these regenerative medicine approaches are still in the early stages of development, ongoing research holds promise for translating these therapies into clinical applications for ARDS patients in the future [12].

Despite the promising advances in ARDS research and therapy, several challenges remain in the quest to improve outcomes for affected patients. Heterogeneity in ARDS etiology, clinical presentation, and treatment response underscores the need for personalized medicine approaches tailored to individual patient phenotypes. Biomarker discovery and validation are critical for identifying high-risk patients, predicting disease progression, and guiding targeted therapeutic interventions. Integration of genomic, transcriptomic, and proteomic data may facilitate the development of precision medicine strategies for optimizing ARDS management and improving patient outcomes [13].

Furthermore, the long-term sequelae of ARDS, including pulmonary fibrosis, cognitive impairment, and physical deconditioning, pose significant challenges for survivors and highlight the importance of comprehensive rehabilitation and supportive care services. Multidisciplinary collaboration between critical care specialists, pulmonologists, immunologists, and regenerative medicine experts is essential for advancing our understanding of ARDS pathogenesis and developing innovative therapeutic interventions [14].

Conclusion

In conclusion, ARDS represents a complex syndrome with diverse etiologies, variable clinical manifestations, and significant morbidity and mortality. While significant progress has been made in elucidating its pathophysiology and refining therapeutic strategies, ARDS remains a formidable challenge in critical care medicine. Ongoing research efforts focused on unraveling the underlying mechanisms of ARDS, identifying novel therapeutic targets, and translating innovative therapies into clinical practice offer hope for improving outcomes and reducing the burden of this devastating condition.

Acknowledgement

None

Conflict of Interest

None

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