From multi-omics candidates to a biochemical pathway for the Macklin effect

A narrative review of candidate genetic and multi-omics determinants in Macklin effect development could help organize scattered biomarkers into pathway-level hypotheses. The central distinction is whether candidates converge on a process such as alveolar barrier injury, extracellular matrix failure, or dysregulated tissue repair, rather than merely tracking the severity of acute respiratory distress syndrome.

The review would be most informative if it maps each candidate to a defined biochemical step and separates upstream susceptibility from downstream injury markers. Concordance across genomic, transcriptomic, proteomic, and metabolomic layers could then identify pathway modules worth testing prospectively, while inconsistent direction across layers would limit mechanistic interpretation.