Treatable traits in interstitial lung disease: towards precision medicine

BACKGROUND: Currently available pharmacotherapies for interstitial lung disease (ILD) are limited to systemic glucocorticoids, steroid-sparing immunosuppressive medications and antifibrotic medications. Each of these treatments target major components of ILD biology. OBJECTIVE: This review presents the relevant evidence to the pharmacological management of ILD that is based on a treatable traits approach. We further highlight major knowledge gaps that should be the focus of future research that moves patient care toward a more precision-medicine approach. SUMMARY OF REVIEW: The previous treatment paradigm for the pharmacotherapy of ILD is based on the integration of several clinical, laboratory, radiological and pathological features to an underlying biology that is more likely to respond to a given medication strategy. Patients with more acute presentations and suggestion of significant inflammation are typically treated with systemic glucocorticoid therapy, with the route and initial dose decided primarily based on the severity of disease. Patients with ILD who have chronic disease with suggestion of inflammatory features are typically treated with long-term steroid-sparing immunosuppression. Patients with ILD who have chronic disease with progressive fibrotic features are typically treated with antifibrotic medication. Emerging therapies include nerandomilast, a phosphodiesterase 4B inhibitor with antifibrotic and immunomodulatory effects that has recently been approved in the USA. A major goal is future integration of molecular endotypes to support a transition towards precision-based management of ILD. CONCLUSIONS: Pharmacotherapy of ILD has previously focused on a morphology-based treatable traits approach that uses various clinical, laboratory, radiological and pathological clues to suggest a preferred treatment. We describe this approach and highlight specific questions that need to be addressed in future studies as we move toward a precision-based approach to patient management.