{"id":692,"date":"2025-03-03T21:43:19","date_gmt":"2025-03-03T21:43:19","guid":{"rendered":"https:\/\/perfusfind.com\/ic\/?p=692"},"modified":"2025-03-03T21:43:19","modified_gmt":"2025-03-03T21:43:19","slug":"pathophysiological-mechanisms-of-ards-a-narrative-review-from-molecular-to-organ-level-perspectives","status":"publish","type":"post","link":"https:\/\/perfusfind.com\/ic\/index.php\/2025\/03\/03\/pathophysiological-mechanisms-of-ards-a-narrative-review-from-molecular-to-organ-level-perspectives\/","title":{"rendered":"Pathophysiological mechanisms of ARDS: a narrative review from molecular to organ-level perspectives"},"content":{"rendered":"

Abstract<\/h2>\n
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Background<\/h3>\n

Acute respiratory distress syndrome (ARDS) remains a life-threatening pulmonary condition with persistently high mortality rates despite significant advancements in supportive care. Its complex pathophysiology involves an intricate interplay of molecular and cellular processes, including cytokine storms, oxidative stress, programmed cell death, and disruption of the alveolar-capillary barrier. These mechanisms drive localized lung injury and contribute to systemic inflammatory response syndrome and multiple organ dysfunction syndrome. Unlike prior reviews that primarily focus on isolated mechanisms, this narrative review synthesizes the key pathophysiological processes of ARDS across molecular, cellular, tissue, and organ levels.<\/p>\n

Main body<\/h3>\n

By integrating classical theories with recent research advancements, we provide a comprehensive analysis of how inflammatory mediators, metabolic reprogramming, oxidative stress, and immune dysregulation synergistically drive ARDS onset and progression. Furthermore, we critically evaluate current evidence-based therapeutic strategies, such as lung-protective ventilation and prone positioning, while exploring innovative therapies, including stem cell therapy, gene therapy, and immunotherapy. We emphasize the significance of ARDS subtypes and their inherent heterogeneity in guiding the development of personalized treatment strategies.<\/p>\n

Conclusions<\/h3>\n

This narrative review provides fresh perspectives for future research, ultimately enhancing patient outcomes and optimizing management approaches in ARDS.<\/p>\n<\/div>\n

<\/h3>\n

Key Points<\/h3>\n
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  1. Cytokine Storm and Inflammation in ARDS:<\/strong> ARDS is characterized by a hyperactive immune response leading to excessive cytokine release, including TNF-\u03b1, IL-1\u03b2, and IL-6. These cytokines activate NF-\u03baB and STAT3 pathways, increasing vascular permeability, disrupting the alveolar-capillary barrier, and exacerbating lung injury and hypoxemia.<\/li>\n
  2. Oxidative Stress and Reactive Oxygen\/Nitrogen Species:<\/strong> Oxidative stress results from an imbalance between reactive oxygen species (ROS) and the body\u2019s antioxidant defenses. Excessive ROS damages endothelial and epithelial cells, triggering apoptosis, necrosis, and increased vascular permeability, ultimately worsening pulmonary edema.<\/li>\n
  3. Cell Death Mechanisms in ARDS:<\/strong> Apoptosis, necrosis, and pyroptosis contribute to lung injury. Excessive apoptosis impairs alveolar repair, necrosis releases pro-inflammatory mediators, and pyroptosis amplifies inflammation and tissue damage. Research suggests that inhibiting excessive cell death may improve ARDS outcomes.<\/li>\n
  4. Disruption of Endothelial and Epithelial Barriers:<\/strong> The breakdown of endothelial cells increases vascular permeability, while epithelial cell damage disrupts gas exchange, leading to fluid accumulation and pulmonary edema. Targeting barrier integrity is a key focus for future therapeutic strategies.<\/li>\n
  5. Alveolar-Capillary Barrier Dysfunction and Tissue Remodeling:<\/strong> The loss of alveolar-capillary integrity worsens lung inflammation and fibrosis. While normal tissue remodeling aids recovery, excessive fibrosis results in lung stiffening and impaired function. Future research should focus on balancing tissue repair and fibrosis prevention.<\/li>\n
  6. Systemic Inflammatory Response Syndrome (SIRS) and MODS:<\/strong> Localized pulmonary inflammation can escalate into systemic inflammation, leading to multi-organ dysfunction. ARDS-induced SIRS increases mortality risk through systemic inflammatory mediator dissemination, affecting the heart, kidneys, liver, and brain.<\/li>\n
  7. Current Evidence-Based Therapeutic Strategies:<\/strong> Standard ARDS management includes lung-protective ventilation (low tidal volume), prone positioning, and extracorporeal membrane oxygenation (ECMO). While these strategies improve survival, they fail to address the underlying disease pathology.<\/li>\n
  8. Stem Cell Therapy for ARDS:<\/strong> Mesenchymal stem cells (MSCs) demonstrate immunomodulatory and regenerative properties, showing potential in preclinical ARDS models. However, clinical trials have produced inconsistent results, necessitating further investigation into their therapeutic role.<\/li>\n
  9. Gene Therapy and Immunotherapy:<\/strong> Advances in gene editing (e.g., CRISPR\/Cas9) offer potential for modifying inflammatory pathways in ARDS, while cytokine-targeting therapies, such as IL-6 and TNF-\u03b1 inhibitors, have yielded mixed clinical outcomes.<\/li>\n
  10. Challenges in Translating Novel Therapies into Clinical Practice:<\/strong> The safety, cost, and ethical considerations surrounding emerging therapies pose significant barriers to widespread implementation. Large-scale clinical trials are needed to evaluate their efficacy and feasibility in routine ARDS management.<\/li>\n<\/ol>\n

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