LAUSR

BACKGROUND In cohort studies of pulmonary sarcoidosis, abnormal ventilatory patterns have generally been sub-divided into restrictive and obstructive defects. Mixed ventilatory defects have been largely overlooked in pulmonary sarcoidosis as total lung capacity (TLC) has seldom been taken into account in historical series. RESEARCH QUESTION We evaluated the prevalence of mixed disease in pulmonary sarcoidosis and its clinical associations. STUDY DESIGN and Methods: In patients with pulmonary sarcoidosis (n=1110), mixed defects were defined using ATS/ERS criteria. Clinical data, pulmonary function variables and vital status were abstracted from clinical records. Chest radiographs were evaluated independently by two experienced radiologists. RESULTS The prevalence of a mixed ventilatory defect was 10.4% in the whole cohort, rising to 25.9% in patients with airflow obstruction. When compared to isolated airflow obstruction, mixed defects were associated with lower DLco levels (50.7 ± 16.3 versus 70.8 ± 18.1, p<0.0001), a higher prevalence of chest radiographic stage IV disease (63.5% versus 38.3%, p<0.0001), and higher mortality (HR 2.36; 95% CI 1.34, 4.15; p=0.003). These findings were reproduced in all patient sub-group analyses, including patients with a histologic diagnosis, a clinical diagnosis, incident disease and prevalent disease. INTERPRETATION Mixed disease is present in approximately 25% of pulmonary sarcoidosis patients with airflow obstruction and is associated with lower DLco levels, a higher prevalence of stage IV disease and higher mortality than seen in a pure obstructive defect. These observations identify a distinct phenotype associated with a mixed ventilatory defect, justifying future studies of its clinical and pathogenetic significance.