An integrated clinicoradiological staging system for pulmonary sarcoidosis: a case-cohort study

Background Mortality in pulmonary sarcoidosis is highly variable and a reliable prognostic algorithm for disease staging and for guiding management decisions is needed. The objective of this study is to derive and test a staging system for determining prognosis in pulmonary sarcoidosis. Methods We identified the prognostic value of high-resolution computed tomography (HRCT) patterns and pulmonary function tests, inducting the composite physiological index (CPI) in patients with pulmonary sarcoidosis. We integrated prognostic physiological and HRCT variables to form a clinical staging algorithm predictive of mortality in a test cohort. The staging system was externally validated in a separate cohort by the same methods of discrimination used in the primary analysis and tested for clinical applicability by four test observers. Findings The test cohort included 251 patients with pulmonary sarcoidosis in the study referred to the Sarcoidosis clinic at the Royal Brompton Hospital, UK, between Jan 1, 2000, and June 30, 2010. The CPI was the strongest predictor of mortality (HR 1.04, 95% CI 1.02-1.06, p<0.0001) in the test cohort. An optimal CPI threshold of 40 units was identified (HR 4.24, 2.84-6.33, p<0.0001). The CPI40, main pulmonary artery diameter to ascending aorta diameter ratio (MPAD/AAD), and an extent of fibrosis threshold of 20% were combined to form a staging algorithm. When assessed in the validation cohort (n=252), this staging system was strikingly more predictive of mortality than any individual variable alone (HR 5.89, 2.68-10. 08, p<0.0001). The staging system was successfully applied to the test and validation cohorts combined, by two radiologists and two physicians. Interpretation A clear prognostic separation of patients with pulmonary sarcoidosis is provided by a simple staging system integrating the CPI and two HRCT variables.