Relative versus absolute change in forced vital capacity in idiopathic pulmonary fibrosis

BACKGROUND: Decline in forced vital capacity (FVC) over time reliably predicts mortality in patients with idiopathic pulmonary fibrosis. The use of this measure in clinical practice is recommended by current evidence-based guidelines. It is unknown if the method of calculating decline in FVC (relative vs. absolute change) impacts its frequency or its ability to predict mortality.METHODS: Patients with idiopathic pulmonary fibrosis from two prospective cohorts were included if they had a baseline and 12-month follow-up FVC. A ?10% decline in FVC from baseline was calculated in two ways: a relative decline of 10% (e.g., from 60% predicted to 54% predicted) and an absolute decline of 10% (e.g., from 60% predicted to 50% predicted). The frequency of a ?10% decline in FVC and its ability to predict 2-year transplant-free survival were compared between these two methods. Declines in FVC of ?5% and ?15% were similarly compared. Analyses were performed unadjusted and adjusted for age, gender, use of oxygen, baseline FVC and baseline diffusion capacity for carbon monoxide.RESULTS: The frequency of any given FVC decline was significantly greater using the relative change in FVC method. For ?10% decline, both methods predicted 2-year transplant-free survival with similar accuracy, and remained significant predictors after adjusting for baseline characteristics. The absolute change method appeared more predictive for ?5% decline.CONCLUSIONS: Using the relative change in FVC maximises the chance of identifying a ?10% decline in FVC without sacrificing prognostic accuracy. This may not hold true for ?5% decline in FVC. These findings have important implications for clinical practice and the design of clinical trials.<br/

Diagnosis and Detection of Sarcoidosis An Official American Thoracic Society Clinical Practice Guideline

Background: The diagnosis of sarcoidosis is not standardized but is based on three major criteria: a compatible clinical presentation, finding nonnecrotizing granulomatous inflammation in one or more tissue samples, and the exclusion of alternative causes of granulomatous disease. There are no universally accepted measures to determine if each diagnostic criterion has been satisfied; therefore, the diagnosis of sarcoidosis is never fully secure.Methods: Systematic reviews and, when appropriate, meta-analyses were performed to summarize the best available evidence. The evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation approach and then discussed by a multidisciplinary panel. Recommendations for or against various diagnostic tests were formulated and graded after the expert panel weighed desirable and undesirable consequences, certainty of estimates, feasibility, and acceptability.Results: The clinical presentation, histopathology, and exclusion of alternative diagnoses were summarized. On the basis of the available evidence, the expert committee made 1 strong recommendation for baseline serum calcium testing, 13 conditional recommendations, and 1 best practice statement. All evidence was very low quality.Conclusions: The panel used systematic reviews of the evidence to inform clinical recommendations in favor of or against various diagnostic tests in patients with suspected or known sarcoidosis. The evidence and recommendations should be revisited as new evidence becomes available

IFN-γproducing t-helper 17.1 cells are increased in sarcoidosis and are more prevalent than t-helper type 1 cells

Rationale: Pulmonary sarcoidosis is classically defined by T-helper (Th) cell type 1 inflammation (e.g., IFN-γ production by CD4(+) effector T cells). Recently, IL-17A–secreting cells have been found in lung lavage, invoking Th17 immunity in sarcoidosis. Studies also identified IL-17A–secreting cells that expressed IFN-γ, but their abundance as a percentage of total CD4(+) cells was either low or undetermined. Objectives: Based on evidence that Th17 cells can be polarized to Th17.1 cells to produce only IFN-γ, our goal was to determine whether Th17.1 cells are a prominent source of IFN-γ in sarcoidosis. Methods: We developed a single-cell approach to define and isolate major Th-cell subsets using combinations of chemokine receptors and fluorescence-activated cell sorting. We subsequently confirmed the accuracy of subset enrichment by measuring cytokine production. Measurements and Main Results: Discrimination between Th17 and Th17.1 cells revealed very high percentages of Th17.1 cells in lung lavage in sarcoidosis compared with controls in two separate cohorts. No differences in Th17 or Th1 lavage cells were found compared with controls. Lung lavage Th17.1-cell percentages were also higher than Th1-cell percentages, and approximately 60% of Th17.1-enriched cells produced only IFN-γ. Conclusions: Combined use of surface markers and functional assays to study CD4(+) T cells in sarcoidosis revealed a marked expansion of Th17.1 cells that only produce IFN-γ. These results suggest that Th17.1 cells could be misclassified as Th1 cells and may be the predominant producer of IFN-γ in pulmonary sarcoidosis, challenging the Th1 paradigm of pathogenesis