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Hypersensitivity pneumonitis (HP) is a heterogeneous interstitial lung disease (ILD) that may be difficult to confidently diagnose. Recently, the 2020 ATS/JRS/ALAT HP diagnostic guidelines were published, yet data validating their performance in real-life settings are scarce. We aimed to assess the diagnostic performance of the HP guidelines compared to the gold-standard multidisciplinary discussion (MDD). For this purpose, we included consecutive ILD patients that underwent diagnostic bronchoscopy between 2017 and 2020 in three large medical centers. Four diagnostic factors (antigen exposure history, chest computed tomography pattern, bronchoalveolar lavage lymphocyte count, and histology results) were used to assign guidelines-based HP diagnostic confidence levels for each patient. A sensitivity analysis was performed, with MDD diagnosis as the reference standard. Overall, 213 ILD patients were included, 45 (21%) with an MDD diagnosis of HP. The guidelines' moderate (≥70%) confidence threshold produced optimal performance with 73% sensitivity for HP, 89% specificity, and a J-index of 0.62. The area under the receiver operating characteristic curve (AUC) for a correct guidelines-based diagnosis was 0.86. The guidelines had better performance for non-fibrotic than fibrotic HP (AUC 0.92 vs. 0.82). All diagnostic factors, except bronchoalveolar lavage lymphocyte count, were independent predictors for MDD diagnosis of HP in a multivariate analysis. In conclusion, the HP guidelines exhibited a good diagnostic performance compared to MDD diagnosis in real-life setting. [ABSTRACT FROM AUTHOR]

Rationale: Disease activity in idiopathic pulmonary fibrosis (IPF) remains highly variable, poorly understood, and difficult to predict. Objectives: To identify a predictor using short-term longitudinal changes in gene expression that forecasts future FVC decline and to characterize involved pathways and cell types. Methods: Seventy-four patients from COMET (Correlating Outcomes with Biochemical Markers to Estimate Time-Progression in IPF) cohort were dichotomized as progressors (≥10% FVC decline) or stable. Blood gene-expression changes within individuals were calculated between baseline and 4 months and regressed with future FVC status, allowing determination of expression variations, sample size, and statistical power. Pathway analyses were conducted to predict downstream effects and identify new targets. An FVC predictor for progression was constructed in COMET and validated using independent cohorts. Peripheral blood mononuclear single-cell RNA-sequencing data from healthy control subjects were used as references to characterize cell type compositions from bulk peripheral blood mononuclear RNA-sequencing data that were associated with FVC decline. Measurements and Main Results: The longitudinal model reduced gene-expression variations within stable and progressor groups, resulting in increased statistical power when compared with a cross-sectional model. The FVC predictor for progression anticipated patients with future FVC decline with 78% sensitivity and 86% specificity across independent IPF cohorts. Pattern recognition receptor pathways and mTOR pathways were downregulated and upregulated, respectively. Cellular deconvolution using single-cell RNA-sequencing data identified natural killer cells as significantly correlated with progression. Conclusions: Serial transcriptomic change predicts future FVC decline. An analysis of cell types involved in the progressor signature supports the novel involvement of natural killer cells in IPF progression. [ABSTRACT FROM AUTHOR]

T cell-B cell interaction is the key immune response to protect the host from severe viral infection. However, how T cells support B cells to exert protective humoral immunity in humans is not well understood. Here, we use COVID-19 as a model of acute viral infections and analyze CD4 + T cell subsets associated with plasmablast expansion and clinical outcome. Peripheral helper T cells (Tph cells; denoted as PD-1 high CXCR5 - CD4 + T cells) are significantly increased, as are plasmablasts. Tph cells exhibit "B cell help" signatures and induce plasmablast differentiation in vitro. Interestingly, expanded plasmablasts show increased CXCR3 expression, which is positively correlated with higher frequency of activated Tph cells and better clinical outcome. Mechanistically, Tph cells help B cell differentiation and produce more interferon γ (IFNγ), which induces CXCR3 expression on plasmablasts. These results elucidate a role for Tph cells in regulating protective B cell response during acute viral infection., Competing Interests: Declaration of interests D.A.H. has received research funding from Bristol-Myers Squibb, Novartis, Sanofi, and Genentech. He has been a consultant for Bayer Pharmaceuticals, Bristol Myers Squibb, Compass Therapeutics, EMD Serono, Genentech, Juno Therapeutics, Novartis Pharmaceuticals, Proclara Biosciences, Sage Therapeutics, and Sanofi Genzyme. Further information regarding funding is available at https://openpaymentsdata.cms.gov/physician/166753/general-payments. N.K. reports personal fees from Boehringer Ingelheim, Third Rock, Pliant, Samumed, NuMedii, Indalo, Theravance, LifeMax, Three Lake Partners, and RohBar in the last 36 months and Equity in Pliant. N.K. is also a recipient of a grant from Veracyte and non-financial support from Miragen. In addition, N.K. has patents on New Therapies in Pulmonary Fibrosis and ARDS (unlicensed) and Peripheral Blood Gene Expression as biomarkers in IPF (licensed to biotech), all outside the submitted work. S.H.K. receives consulting fees from Northrop Grumman. K.B.H. receives consulting fees from Prellis Biologics., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Physicians are often insufficiently trained in bedside teaching and mentoring skills., Objectives: To develop, implement and assess a simulation-based training program designed to improve clinical teaching among physicians., Methods: We developed a one-day tutor training program based on six simulated scenarios with video-based debriefing. The program's efficacy was assessed using questionnaires completed by the participating physicians and their students. Main outcome measures were self-perceived teaching skills at baseline, after participation in the program, and following completion of the tutor role. Secondary outcome measures were the students' perceptions regarding their tutor skills., Results: Thirty-two physicians (mean age 35.5 years, 56% females) participated in the program. Self-assessment questionnaires indicated statistically significant improvement following the program in 13 of 20 measures of teaching skills. Additional improvement was observed upon completion of the tutor role, leading to significant improvement in 19 of the .20 measures. Questionnaires completed by their students indicated higher scores in all parameters as compared to a matched control group of tutors who did not participate in the program, though not statistically significant. Most participants stated that the program enhanced their teaching skills (88%), they implement program-acquired skills when teaching students (79%), and they would recommend it to their peers (100%). Satisfaction was similar among participants with and without previous teaching experience., Conclusions: A novel one-day simulation-based tutor training program was developed and implemented with encouraging results regarding its potential to improve clinical teaching and mentoring skills.