Developing better drugs for pulmonary sarcoidosis: determining indications for treatment and endpoints to assess therapy based on patient and clinician concerns [version 1; peer review: 3 approved]

Abstract

Pulmonary sarcoidosis involves the deposition of granulomas within the lung. These granulomas may affect lung function and lead to pulmonary symptoms, pulmonary dysfunction, functional impairment, and worsening of quality of life. Corticosteroids are generally highly effective in resolving the granulomatous inflammation of sarcoidosis. However, despite the effectiveness of corticosteroids, many corticosteroid-responsive patients continue to experience significant problems because of the development of fibrosis from previously active or active smoldering granulomatous inflammation, inflammatory effects from sarcoidosis unrelated to granuloma deposition in lung tissue (parasarcoidosis syndromes), and the development of significant corticosteroid-related side effects. For these reasons, the decision to treat pulmonary sarcoidosis and endpoints to measure meaningful outcomes may extend beyond considerations of pulmonary granulomatous inflammation alone. In this article, we propose a conceptual framework to describe the mechanisms by which pulmonary sarcoidosis significantly impacts patients. This conceptual framework suggests that indications for the treatment of pulmonary sarcoidosis and endpoints to assess treatment depend on the specific mechanisms that are causing functional or quality-of-life impairment (or both) in patients with pulmonary sarcoidosis. We believe that these concepts are important to clinicians treating pulmonary sarcoidosis and to clinical researchers designing pulmonary sarcoidosis trials.