Mixed Ventilatory Defects in Pulmonary Sarcoidosis: Prevalence and Clinical Features

Chest. 2020 Nov;158(5):2007-2014. doi: 10.1016/j.chest.2020.04.074. Epub 2020 Jun 12.


Background: In cohort studies of pulmonary sarcoidosis, abnormal ventilatory patterns have generally been subdivided into restrictive and obstructive defects. Mixed ventilatory defects have largely been overlooked in pulmonary sarcoidosis, as total lung capacity has seldom been taken into account in historical series.

Research question: This study evaluated the prevalence of mixed disease in pulmonary sarcoidosis and its clinical associations.

Study design and methods: In patients with pulmonary sarcoidosis (N = 1,110), mixed defects were defined according to American Thoracic Society/European Respiratory Society 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. Compared with isolated airflow obstruction, mixed defects were associated with lower diffusing lung capacity for carbon monoxide levels (50.7 ± 16.3 vs 70.8 ± 18.1; P < .0001), a higher prevalence of chest radiographic stage IV disease (63.5% vs 38.3%; P < .0001), and higher mortality (hazard ratio, 2.36; 95% CI, 1.34-4.15; P = .003). These findings were reproduced in all patient subgroup analyses, including patients with a histologic diagnosis, a clinical diagnosis, incident disease, and prevalent disease.

Interpretation: Mixed disease is present in approximately 25% of patients with pulmonary sarcoidosis and airflow obstruction and is associated with lower diffusing lung capacity for carbon monoxide 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.

Keywords: mixed ventilatory defect; pulmonary sarcoidosis; static lung volumes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • England / epidemiology
  • Female
  • Forced Expiratory Volume / physiology*
  • Humans
  • Lung / physiopathology*
  • Male
  • Middle Aged
  • Prevalence
  • Pulmonary Diffusing Capacity / physiology*
  • Retrospective Studies
  • Sarcoidosis, Pulmonary / epidemiology
  • Sarcoidosis, Pulmonary / physiopathology*
  • Spirometry