Diaphragm-Directed Strategies for Prolonged Air Leak Prevention After Lung Resection: A Narrative Review of the Residual Pleural Space Paradigm.

Background/Objectives: Prolonged air leak (PAL) remains one of the most common and costly complications after lung resection. A growing body of evidence implicates the residual pleural space (RPS) as a central pathogenetic link between recognized risk factors and persistence of the alveolopleural fistula. This review synthesizes evidence on RPS pathogenesis and compares six interventions that reduce RPS by acting on the diaphragm for PAL prevention. Methods: A narrative literature search was performed in PubMed, Google Scholar, Web of Science, eLibrary.ru, and China National Knowledge Infrastructure (CNKI), covering clinical and experimental studies, systematic reviews, and classic physiological work relevant to intrapleural pressure (IPP), RPS, and diaphragmatic control. Results: RPS and PAL are reciprocally linked, and major, upper-lobe, and right-sided resection independently predict both. RPS is accompanied by excess negative IPP, reduced lung compliance, and disproportionate wall stress at the resection margin. Six methods for reducing RPS volume through diaphragmatic control are described. Conclusions: RPS is the mechanistic link connecting established PAL risk factors to fistula persistence. Among the six methods, chemical denervation with botulinum toxin type A (BTX-A) is, in principle, the only method combining full reversibility, dose-dependent control, and no need for dedicated equipment. However, this conclusion rests on a single pilot animal study in a lower-lobectomy model, and translating it to upper-lobe, low-reserve patients, who carry the greatest PAL burden, requires dedicated dose-ranging and safety work before a clinical trial can be considered.