Lung–Muscle Interaction in ARDS: Implications for Injury, Recovery, and Long‐Term Outcomes

ABSTRACT

Acute respiratory distress syndrome (ARDS) is increasingly recognized as a systemic syndrome in which the consequences of lung injury extend beyond the respiratory system. Among its extra‐pulmonary manifestations, skeletal muscle dysfunction has emerged as a major determinant of short‐ and long‐term outcomes. Accumulating evidence supports a bidirectional lung–muscle interaction in ARDS, involving both peripheral and respiratory muscles. The injured lung may promote muscle atrophy, weakness, contractile dysfunction, and impaired regeneration through multiple upstream drivers, including systemic inflammation, altered gas exchange, respiratory support strategies, immobilization, and pharmacologic exposures. These factors converge on downstream intramuscular pathways such as enhanced proteolysis, impaired protein synthesis, and mitochondrial dysfunction. In turn, skeletal muscle dysfunction may adversely affect the respiratory system through direct mechanical effects of respiratory muscle weakness or excessive inspiratory effort, as well as through indirect systemic mechanisms involving inflammatory and endocrine signaling. Thus, skeletal muscle should be viewed not only as a target of ARDS‐related insults, but also as a biologically active organ that may influence injury propagation, recovery, and long‐term functional outcomes. In this review, we examine the physiological basis of lung–muscle communication and discuss how these interactions become dysregulated in ARDS and acute lung injury. A better understanding of this integrated lung–muscle axis may help redefine supportive care in ARDS and design strategies aimed at preserving both pulmonary and muscular function.