Publications by authors named "Avraham Unterman"

Background: Interstitial lung disease (ILD) is the main clinical feature of antisynthetase syndrome (ASS). In the absence of randomized controlled trials to guide therapy, treatment strategies are often extrapolated from other diseases, mainly systemic sclerosis (SSc).

Objectives: Our aim was to evaluate the dynamics of ILD severity following immunosuppressive treatment (IST) in ASS compared to SSc.

View Article and Find Full Text PDF

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disorder without curative therapies, underscoring the critical unmet need for identification of novel therapeutics. Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) is a damage-associated molecular pattern protein (DAMP) and Toll-Like Receptor 4 (TLR4) ligand that contributes to the severity of radiation-induced lung fibrosis and NASH-associated hepatic fibrosis. This study investigates eNAMPT as a druggable target in human and preclinical IPF utilizing the eNAMPT-neutralizing ALT-100 monoclonal antibody (mAb).

View Article and Find Full Text PDF

Background: Cardiopulmonary exercise testing (CPET) is used in the evaluation of unexplained dyspnea. However, its interpretation requires expertise that is often not available. We aim to evaluate the utility of ChatGPT (GPT) in interpreting CPET results.

View Article and Find Full Text PDF

COPD exacerbations are a major cause of morbidity and mortality. Although inhaled corticosteroids (ICS) have a role as long-term treatment, their efficacy in exacerbations, particularly as an adjunct to systemic steroids, remains unclear. In this retrospective observational study, we analyzed data from 870 subjects admitted with COPD exacerbations to a tertiary medical center in Israel from January 2018-January 2023.

View Article and Find Full Text PDF

Background: The radiologic criteria of hypersensitivity pneumonitis (HP) guidelines focus on four HP compatible features (HPCF) in high-resolution computed tomography (HRCT): ground glass opacities, mosaic attenuation, air-trapping, and centrilobular nodules. However, evidence to support these criteria are limited.

Methods: Consecutive interstitial lung disease (ILD) patients who underwent HRCT between 2016 and 2021 in three medical centers were included.

View Article and Find Full Text PDF

Purpose: Exacerbations of COPD (ECOPD) significantly impact disease progression and mortality. Visiting a respiratory specialist (RS) in proximity to the exacerbation may lead to prompt treatment and improved outcomes. We aimed to evaluate the association between an RS visit 30-days before admission and exacerbation outcomes.

View Article and Find Full Text PDF

Rationale: The association between immune-cell-specific transcriptomic profiles and Idiopathic Pulmonary Fibrosis (IPF) mortality is unknown.

Objectives: To determine immune-cell-specific transcriptomic profiles associated with IPF mortality.

Methods: We profiled peripheral blood mononuclear cells (PBMC) in 18 participants [University of South Florida: IPF, COVID-19, post-COVID-19 Interstitial Lung Disease (Post-COVID-19 ILD), controls] by single-cell RNA sequencing (scRNA-seq) and identified 16 immune-cell-specific transcriptomic profiles.

View Article and Find Full Text PDF

Background: COPD exacerbations are a major cause of morbidity and mortality. Although inhaled corticosteroids (ICS) have a role as long-term treatment, their efficacy in exacerbations, particularly as an adjunct to systemic steroids, remains unclear.

Methods: In this retrospective observational study, we analyzed data from 870 subjects admitted with COPD exacerbations to a tertiary medical center in Israel from January 2018-January 2023.

View Article and Find Full Text PDF
Article Synopsis
  • Fibrotic hypersensitivity pneumonitis (FHP) is an interstitial lung disease linked to unclear immune reactions, and researchers studied immune cells from various patient groups using single-cell RNA sequencing.
  • The analysis revealed an increase in specific immune cells, including classical monocytes and GZM cytotoxic T cells, in FHP patients compared to controls and those with idiopathic pulmonary fibrosis (IPF).
  • These findings highlight unique immune disturbances in FHP, suggesting potential new biomarkers and treatment strategies based on the distinct inflammatory responses observed in the disease.
View Article and Find Full Text PDF

Background: Implementing standard of care therapy for chronic obstructive pulmonary disease (COPD) has barriers. Hospitalization with an acute exacerbation of COPD (AECOPD) is a major adverse event that could also be an opportunity to improve patients' long-term care.

Objectives: To evaluate which in-hospital interventions during AECOPD are associated with improved 30-day care.

View Article and Find Full Text PDF

Changes in peripheral blood cell populations have been observed, but not detailed, at single-cell resolution in idiopathic pulmonary fibrosis (IPF). We sought to provide an atlas of the changes in the peripheral immune system in stable and progressive IPF. Peripheral blood mononuclear cells (PBMCs) from patients with IPF and control subjects were profiled using 10× chromium 5' single-cell RNA sequencing.

View Article and Find Full Text PDF

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common cause for emergency department (ED) visits. Still, large scale studies that assess the management of AECOPD in the ED are limited. Our aim was to evaluate treatment characteristics of AE-COPD in the ED on a national scale.

View Article and Find Full Text PDF

Hospitalized patients with a high suspicion of pulmonary tuberculosis (HS-PTB) are isolated until a definite diagnosis can be determined. If doubt remains after negative sputum samples, bronchoscopy with bronchoalveolar lavage (BAL) is often sought. Still, evidence of the added value of BAL in this patient population is scarce.

View Article and Find Full Text PDF

Mast-cell expressed membrane protein-1 (MCEMP1) is higher in patients with idiopathic pulmonary fibrosis (IPF) with an increased risk of death. Here we aimed to establish the mechanistic role of MCEMP1 in pulmonary fibrosis. We identified increased MCEMP1 expression in classical monocytes and alveolar macrophages in IPF compared with controls.

View Article and Find Full Text PDF

Background: Impulse oscillometry (IOS) is a noninvasive technique that measures lung physiology independently of patient effort. In the present study, we aimed to investigate the utility of IOS parameters in comparison with pulmonary function testing (PFT) among hospitalized subjects, with emphasis on obstructive and small airway diseases.

Methods: Sixty-one subjects hospitalized either with unexplained dyspnea or for pre-surgery evaluation were included in the study.

View Article and Find Full Text PDF

Background: Mast-Cell Expressed Membrane Protein-1 (MCEMP1) is higher in Idiopathic Pulmonary Fibrosis (IPF) patients with increased risk of death and poor outcomes. Here we seek to establish the mechanistic role of MCEMP1 in pulmonary fibrosis.

Methods: MCEMP1 expression was analyzed by single-cell RNA sequencing, immunofluorescence in Peripheral Blood Mononuclear Cells (PBMC) as well as in lung tissues from IPF patients and controls.

View Article and Find Full Text PDF

Rationale And Objectives: The extent and commonality of peripheral blood immune aberrations in fibrotic interstitial lung diseases are not well characterized. In this study, we aimed to identify common and distinct immune aberrations in patients with idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (FHP) using cutting-edge single-cell profiling technologies.

Methods: Single-cell RNA sequencing was performed on patients and healthy controls' peripheral blood and bronchoalveolar lavage samples using 10X Genomics 5' gene expression and V(D)J profiling.

View Article and Find Full Text PDF

Background: Interstitial lung disease (ILD) evaluation often requires lung biopsy for definite diagnosis. In recent years, transbronchial cryobiopsy (TBCB) emerged as a procedure with higher diagnostic yield than transbronchial forceps biopsy (TBFB), especially for fibrotic ILDs. Nonetheless, studies comparing these modalities in non-fibrotic ILDs and for specific ILD diagnoses are scarce.

View Article and Find Full Text PDF

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).

View Article and Find Full Text PDF
Article Synopsis
  • Symptomatic patients who recovered from acute COVID-19 face significant respiratory challenges and require extensive follow-up care, impacting both their health and healthcare systems.
  • A study of 275 patients showed that a high percentage had impaired lung function and chest abnormalities three months post-infection, indicating potential long-term effects of the virus.
  • Anti-S serological levels emerged as a key indicator, correlating with lung diffusion capacity and previous severity of COVID-19, while other serological markers did not show significant links to health outcomes.
View Article and Find Full Text PDF

Rationale: Changes in peripheral blood cell populations have been observed but not detailed at single-cell resolution in idiopathic pulmonary fibrosis (IPF).

Objectives: To provide an atlas of the changes in the peripheral immune system in stable and progressive IPF.

Methods: Peripheral blood mononuclear cells (PBMCs) from IPF patients and controls were profiled using 10x Chromium 5' single-cell RNA sequencing (scRNA-seq).

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

Background: Patient-reported interstitial lung disease (ILD) questionnaires are commonly used for the evaluation of ILD patients. However, research to test their performance is scarce.

Methods: This study aimed to assess the performance of the Chest Questionnaire in consecutive ILD patients presenting to a tertiary ILD center.

View Article and Find Full Text PDF

Although inhibition of T cell coinhibitory receptors has revolutionized cancer therapy, the mechanisms governing their expression on human T cells have not been elucidated. In the present study, we show that type 1 interferon (IFN-I) regulates coinhibitory receptor expression on human T cells, inducing PD-1/TIM-3/LAG-3 while inhibiting TIGIT expression. High-temporal-resolution mRNA profiling of IFN-I responses established the dynamic regulatory networks uncovering three temporal transcriptional waves.

View Article and Find Full Text PDF

Dysregulated immune responses against the SARS-CoV-2 virus are instrumental in severe COVID-19. However, the immune signatures associated with immunopathology are poorly understood. Here we use multi-omics single-cell analysis to probe the dynamic immune responses in hospitalized patients with stable or progressive course of COVID-19, explore V(D)J repertoires, and assess the cellular effects of tocilizumab.

View Article and Find Full Text PDF