Insights from the INSIGHTS-ILD Registry: real-world heterogeneity in treatment patterns for patients with fibrotic interstitial lung disease.

https://bit.ly/4fXcHpn.

Anti-Ro52 Seropositive Interstitial Lung Disease Is Associated With a Higher Risk of Disease Progression and Mortality.

Background: Identifying biomarkers is vital for interstitial lung disease (ILD) management and prognostication. Although anti-Ro52 antibodies frequently are detected in autoimmune diseases, their significance in ILD remains unclear.

Research Question: What is the prognostic significance of anti-Ro52 antibody positivity in patients with ILD?

Study Design And Methods: This retrospective cohort study used an ILD registry of patients seen at an academic tertiary hospital's ILD clinic between 2015 and 2024.

Anti-Mi-2 positive interstitial lung disease (ILD): A progressive disease comparable to other myositis-ILD.

Background: Evaluation for interstitial lung disease (ILD) often involves sending a myositis panel that includes myositis-associated and myositis-specific antibodies (MAA and MSA respectively) such as anti-Mi-2. Little is known about anti-Mi-2 positive ILD. We sought to determine the typical presentation and prognosis of anti-Mi-2 positive ILD.

Approach to the Evaluation and Management of Interstitial Lung Abnormalities: An Official American Thoracic Society Clinical Statement.

There is growing interest in identifying early stages of interstitial lung disease (ILD) to improve patient outcomes. This document reviews updated evidence on interstitial lung abnormalities (ILAs); provides suggestions for screening, evaluation, and management; proposes criteria for distinguishing ILAs from ILD; and identifies research priorities. A committee of clinical and methodology experts met by video conference to define ILAs and ILD by consensus and voted on 11 prespecified questions after reviewing synthesized evidence from a systematic literature search.

Progressive course of anti-nuclear matrix protein-2 (NXP-2) positive-interstitial lung disease.

Background: Evaluating the etiology of interstitial lung disease (ILD) commonly involves ordering a myositis panel containing myositis-specific antibodies (MSAs), including anti-NXP-2. However, little is known about the presentation of patients with ILD and anti-NXP-2 positivity. We sought to define the course of anti-NXP-2-positive ILD in order to guide prognosis and potential treatment strategies.

Personalized Medicine for Systemic Sclerosis-Associated Interstitial Lung Disease.

Purpose Of The Review: Systemic sclerosis (SSc) is a rare immune-mediated connective tissue disease with high morbidity and mortality. Interstitial lung disease (ILD) is now the leading cause of death for patients with SSc. While several therapeutic agents have been approved for SSc-ILD, opportunities remain for a personalized medicine approach to improve patient outcomes.

Dual αβ and αβ Inhibition over 12 Weeks Reduces Active Type I Collagen Deposition in Individuals with Idiopathic Pulmonary Fibrosis: A Phase 2, Double-Blind, Placebo-controlled Clinical Trial.

Idiopathic pulmonary fibrosis (IPF) is characterized by excessive deposition of type I collagen. Ga-CBP8, a type I collagen positron emission tomography probe, measures collagen accumulation and shows higher collagen deposition in patients with IPF. Bexotegrast (PLN-74809) is an oral, once-daily, dual-selective inhibitor of αβ and αβ integrins under late-stage evaluation for treatment of IPF.

Comorbidities in the idiopathic pulmonary fibrosis and progressive pulmonary fibrosis trial population: a systematic review and meta-analysis.

Background: Comorbidities can affect drug tolerability and health outcomes in patients with fibrotic interstitial lung disease. This systematic review and meta-analysis evaluated the types and prevalence of comorbidities amongst participants in pharmaceutical randomised controlled trials (RCTs) of idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF).

Methods: Ovid Medline, Embase and CENTRAL databases were searched to identify phase II and III pharmaceutical RCTs of IPF or PPF.

Molecular Imaging of Pulmonary Fibrosis.

Fibrosing lung diseases affect over 160,000 individuals in the United States alone and can carry a prognosis that is worse than many cancers. Antifibrotic treatments modify only the rate of fibrosis progression, and more effective therapies are urgently needed. Molecular imaging enables visualization of disease pathogenesis in progress.

A GPVI-platelet-neutrophil-NET axis drives systemic sclerosis.

Systemic sclerosis (SSc) is characterized by progressive fibrosis of skin, lung, and other organs and retains among the highest rates of mortality among autoimmune diseases. We identified activation of circulating neutrophils from patients with diffuse SSc, together with concordant transcriptomic evidence of neutrophil activation in blood, skin, and lungs, and in mice with experimental SSc of skin and lung induced by hypochlorous acid or bleomycin. Neutrophil depletion abrogated experimental SSc, while adoptive transfer of SSc neutrophils induced skin and lung fibrosis in healthy mice, identifying neutrophils as both necessary and sufficient for disease.

Plasma NEDD9 is increased following SARS-CoV-2 infection and associates with indices of pulmonary vascular dysfunction.

Compared to healthy volunteers, participants with post-acute sequelae of SARS-CoV-2 infection (PASC) demonstrated increased plasma levels of the prothrombotic protein NEDD9, which associated inversely with indices of pulmonary vascular function. This suggests persistent pulmonary vascular dysfunction may play a role in the pathobiology of PASC.

Adaptive multi-interventional trial platform to improve patient care for fibrotic interstitial lung diseases.

Background: Fibrotic interstitial lung diseases (fILDs) are a heterogeneous group of lung diseases associated with significant morbidity and mortality. Despite a large increase in the number of clinical trials in the last 10 years, current regulatory-approved management approaches are limited to two therapies that prevent the progression of fibrosis. The drug development pipeline is long and there is an urgent need to accelerate this process.

Prognostic factors associated with mortality in acute exacerbations of idiopathic pulmonary fibrosis: A systematic review and meta-analysis.

Background: Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) increases mortality risk, but which factors increase mortality is unknown. We aimed to perform a prognostic review of factors associated with mortality in patients with IPF.

Study Design: and methods: We searched MEDLINE, EMBASE, and CINAHL for studies that reported on the association between any prognostic factor and AE-IPF.

Pulmonary Fibrosis Stakeholder Summit: A Joint NHLBI, Three Lakes Foundation, and Pulmonary Fibrosis Foundation Workshop Report.

Despite progress in elucidation of disease mechanisms, identification of risk factors, biomarker discovery, and the approval of two medications to slow lung function decline in idiopathic pulmonary fibrosis and one medication to slow lung function decline in progressive pulmonary fibrosis, pulmonary fibrosis remains a disease with a high morbidity and mortality. In recognition of the need to catalyze ongoing advances and collaboration in the field of pulmonary fibrosis, the NHLBI, the Three Lakes Foundation, and the Pulmonary Fibrosis Foundation hosted the Pulmonary Fibrosis Stakeholder Summit on November 8-9, 2022. This workshop was held virtually and was organized into three topic areas: ) novel models and research tools to better study pulmonary fibrosis and uncover new therapies, ) early disease risk factors and methods to improve diagnosis, and ) innovative approaches toward clinical trial design for pulmonary fibrosis.

Noninvasive Quantification of Radiation-Induced Lung Injury Using a Targeted Molecular Imaging Probe.

Purpose: Radiation-induced lung injury (RILI) is a progressive inflammatory process seen after irradiation for lung cancer. The disease can be insidious, often characterized by acute pneumonitis followed by chronic fibrosis with significant associated morbidity. No therapies are approved for RILI, and accurate disease quantification is a major barrier to improved management.

T cell responses to SARS-CoV-2 infection and vaccination are elevated in B cell deficiency and reduce risk of severe COVID-19.

Individuals with primary and pharmacologic B cell deficiencies have high rates of severe disease and mortality from coronavirus disease 2019 (COVID-19), but the immune responses and clinical outcomes after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination have yet to be fully defined. Here, we evaluate the cellular immune responses after both SARS-CoV-2 infection and vaccination in patients receiving the anti-CD20 therapy rituximab (RTX) and those with low B cell counts due to common variable immune deficiency (CVID) disease. Assessment of effector and memory CD4 and CD8 T cell responses to SARS-CoV-2 revealed elevated reactivity and proliferative capacity after both infection and vaccination in B cell-deficient individuals, particularly within the CD8 T cell compartment, in comparison with healthy controls.

Noninvasive Quantification of Radiation-Induced Lung Injury using a Targeted Molecular Imaging Probe.

Rationale: Radiation-induced lung injury (RILI) is a progressive inflammatory process commonly seen following irradiation for lung cancer. The disease can be insidious, often characterized by acute pneumonitis followed by chronic fibrosis with significant associated morbidity. No therapies are approved for RILI, and accurate disease quantification is a major barrier to improved management.

Tocilizumab in Patients with Systemic Sclerosis-associated Interstitial Lung Disease: A Systematic Review and Meta-Analysis.

The American Thoracic Society (ATS) convened an international, multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD). To conduct a systematic review and evaluate the literature to determine the impact of treating patients with SSc-ILD with tocilizumab on prespecified critical and important outcomes determined by the ATS guideline panel. A literature search was conducted across MEDLINE, EMBASE, and Cochrane databases through June 2022 for studies using tocilizumab to treat patients with SSc-ILD.

Nintedanib Therapy Alone and Combined with Mycophenolate in Patients with Systemic Sclerosis-associated Interstitial Lung Disease: Systematic Reviews and Meta-analysis.

The American Thoracic Society convened an international multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD). To conduct a systematic review and evaluate the literature to determine whether patients with SSc-ILD should be treated with nintedanib alone or with the combination of nintedanib plus mycophenolate. Literature searches were conducted across MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases through June 2022 for studies using nintedanib or nintedanib plus mycophenolate to treat patients with SSc-ILD.