Genetic and genomic medicine across the lung transplant continuum: inherited disease, pharmacogenomics, and molecular surveillance

PURPOSE OF REVIEW: Genetic information is increasingly relevant across the lung transplant continuum. A molecular diagnosis of the recipient's native lung disease can refine candidate evaluation, identify extrapulmonary vulnerability, guide family counseling, and anticipate posttransplant complications. Pharmacogenetic and molecular biomarkers offer opportunities to individualize therapy and allograft surveillance. This review summarizes the clinical utility and limitations of these emerging approaches. RECENT FINDINGS: Recent literature highlights the importance of cystic fibrosis in the era of highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulators, short telomere syndromes and hereditary pulmonary fibrosis, alpha-1 antitrypsin deficiency, primary ciliary dyskinesia, pharmacogenomics, and molecular surveillance. Among these, recognition of short telomere syndromes before transplantation has the clearest implications for multidisciplinary risk assessment and posttransplant management. CYP3A5 can inform initial tacrolimus dosing, but therapeutic drug monitoring remains indispensable; thiopurine methyltransferase and Nudix hydrolase 15 are actionable when azathioprine is used. Donor-derived cell-free DNA is a promising, noninvasive marker of allograft injury and prognosis, yet it is not specific for rejection and cannot independently replace microbiologic assessment, donor-specific antibody testing, bronchoscopy, or biopsy. SUMMARY: Genomic tools are most useful when applied selectively and interpreted within clinical context. A tiered implementation model offers a practical path for incorporating genomic tools, improving patient outcomes while limiting overinterpretation.