Inhalation therapies in interstitial lung diseases

Fibrosing interstitial lung diseases (ILDs), including Idiopathic Pulmonary Fibrosis (IPF) and Progressive Pulmonary Fibrosis (PPF), impose substantial clinical and societal burdens due to irreversible lung function decline, limited therapeutic options, and poor survival. Current oral antifibrotics, while effective in slowing progression, are hampered by severe gastrointestinal side effects and high discontinuation rates, emphasizing the need for better-tolerated treatments.

This review summarizes the therapeutic limitations of existing antifibrotics, emphasizing the challenges posed by systemic exposure. We discuss recent and ongoing clinical trials with inhaled antifibrotics, the associated inhalable formulation challenges and characteristics required to align drug performance with the pathobiology of pulmonary fibrosis. We further outline advances in device technologies and drug delivery strategies for efficient drug deposition to the lungs, together with the emerging preclinical pipeline involving biologics and nanoparticles.

The transition to inhaled antifibrotic therapy represents a promising evolution in ILD management. By achieving high local drug concentrations with markedly reduced systemic exposure, this approach has the potential to improve the limitations of oral antifibrotics. As phase-2 and phase-3 trial results emerge, the clinical success of these therapies will depend on optimized formulation and delivery strategies.