The Therapeutic Pipeline: Future Treatments and Precision Medicine

Objective: rare interstitial lung diseases (ILDs) represent a heterogeneous group of disorders characterized by various pathogenic mechanisms, clinical presentations, prognoses, and therapeutic challenges. Among these, acid sphingomyelinase deficiency (ASMD), pulmonary alveolar proteinosis (PAP), and pulmonary Langerhans cell histiocytosis (PLCH) exemplify rare pulmonary diseases driven by distinct biological mechanisms, including lysosomal dysfunction, impaired surfactant homeostasis, and activation of the mitogen-activated protein kinases (MAPK) pathways. Recent advancements in molecular biology, genomics, and translational research boosted the development of precision medicine strategies and disease-specific therapies for these conditions. Study design: this narrative review was conducted in accordance with the SANRA guidelines. A thorough literature search of the PubMed/MEDLINE, Embase, and Scopus databases was performed from January 2000 to June 2026. Results: significant progress has been made in treating all three diseases. In ASMD, enzyme replacement therapy with olipudase alfa has greatly improved visceral and lung symptoms, while research in gene therapy, gene editing, and metabolic treatments is ongoing. For PAP, inhaled granulocyte–macrophage colony-stimulating factor (GM-CSF) is now the primary disease-specific treatment, now supported by phase III trial evidence for inhaled molgramostim, complemented by potential therapies such as immunomodulation, macrophage transplantation, and gene-based strategies. In PLCH, the discovery of recurrent MAPK pathway variants has supported the use of genotype-targeted treatments with BRAF and MEK inhibitors. Under these conditions, advances in molecular diagnostics, circulating biomarkers, quantitative HRCT, radiomics, and artificial intelligence (AI) are poised to enhance diagnosis, patient stratification, prognosis, and treatment decisions. Conclusions: ASMD, PAP and PLCH are entering into an era of precision medicine, in which disease-specific molecular mechanisms play an increasing role in guiding diagnosis and treatment. Ongoing integration of genomics, biomarkers, advanced imaging, AI, and targeted therapies could revolutionise the management of conditions such as ASMD, PAP, and PLCH, leading to better long-term patient outcomes.