The clinical and immunologic features of pulmonary fibrosis in sarcoidosis.
Sarcoidosis is a multisystem, granulomatous disease that most often affects the lungs. The clinical course is highly variable; many patients undergo spontaneous remission, but up to a third of patients progresses to a chronic disease course. The development of pulmonary fibrosis (PF) in a subset of patients with chronic disease has a negative impact on morbidity and mortality. While sarcoidosis-associated PF can be progressive, it is often referred to as "burnt out" disease, a designation reflecting inactive granulomatous inflammation. The immune mechanisms of sarcoidosis-associated PF are not well understood. It is not clear if fibrotic processes are active from the onset of sarcoidosis in predisposed individuals, or whether a profibrotic state develops as a response to ongoing inflammation. Transforming growth factor β (TGF-β) is an important profibrotic cytokine, and in sarcoidosis, distinct genotypes of TGF-β have been identified in those with PF. The overall cytokine profile in sarcoidosis-associated PF has not been well characterized, although a transition from a T helper 1 to a T helper 2 signature has been proposed. Macrophages have important regulatory interactions with fibroblasts, and the role of alveolar macrophages in sarcoidosis-associated PF is a compelling target for further study. Elucidating the natural history of sarcoidosis-associated PF will inform our understanding of the fundamental derangements, and will enhance prognostication and the development of therapeutic strategies.
Section of Pulmonary and Critical Care, University of Chicago, Chicago, Ill. karenpatterson100@gmail.com
Karen C
KC
Patterson
Kyle
K
Hogarth
Aliya N
AN
Husain
Anne I
AI
Sperling
Timothy B
TB
Niewold
D016207:Cytokines / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D011859:Radiography; D017565:Sarcoidosis, Pulmonary / Q000150:complications* / Q000276:immunology
D016207:Cytokines