Novel insights in fibrotic pulmonary sarcoidosis

Abstract

Purpose of reviewIn chronic pulmonary sarcoidosis, the transition from the inflammatory to the fibrotic stage of the lungs occurs in about 10--20% of cases, eventually causing end-stage fibrotic disease. To date, pathogenetic mechanisms and clinical management remain challenging; thus, we highlight the recent evidence in pulmonary fibrotic processes, clinical signs for an early detection and the potential role of the current investigated antifibrotic agents and promising targeted therapies. Recent findingsRecent findings of relevant key cellular pathways can be considered as a glimmer of light in the complexity of sarcoidosis. In some patients, granulomas persist and serve as a nidus for fibrosis growth, sustained by several fibrosis-stimulating cytokines. Preclinical studies have detected profibrotic, antifibrotic and pleiotropic T cells as promoters of fibrosis. Epigenetics, genetics and transcriptomics research can lead to new target therapies. Antifibrotic drug nintedanib has shown a positive effect on non-idiopathic pulmonary fibrosis fibrotic lung diseases including fibrotic sarcoidosis; other antifibrotic drugs are under investigation. SummaryPulmonary fibrosis strongly impacts the outcome of sarcoidosis, and a better understanding of the underlying pathogenic mechanisms can facilitate the development of novel treatments, improving clinical care and life expectancy of these patients. The greatest challenge is to investigate effective antifibrotic therapies once fibrosis develops. The role of these findings in fibrotic sarcoidosis can be translated into other interstitial lung diseases characterized by the coexistence of inflammatory and fibrotic processes.

Phenotypes of Sarcoidosis-Associated Pulmonary Hypertension—A Challenging Mystery

“…In about one-third of the cases, the inflammation becomes chronic. Subsequently, about 20% of patients with persistent inflammation develop lung fibrosis [32]. Based on chest X-ray appearance, five stages of intrathoracic sarcoidosis are distinguished, as presented in Table 2 [33].…”