Bexotegrast Shows Dose-dependent Integrin αβ Receptor Occupancy in Lungs of Participants with Idiopathic Pulmonary Fibrosis: A Phase 2, Open-Label Clinical Trial.

: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disease characterized by dyspnea and loss of lung function. Transforming growth factor-beta (TGF-β) activation mediated by α integrins is central to the pathogenesis of IPF. Bexotegrast (PLN 74809) is an oral, once-daily, dual-selective inhibitor of αβ and αβ integrins under investigation for the treatment of IPF.

Associations of Plasma Omega-3 Fatty Acids With Progression and Survival in Pulmonary Fibrosis.

Background: Preclinical experiments suggest protective effects of omega-3 fatty acids and their metabolites in lung injury and fibrosis. Whether higher intake of omega-3 fatty acids is associated with disease progression and survival in humans with pulmonary fibrosis is unknown.

Research Question: What are the associations of plasma omega-3 fatty acid levels (a validated marker of omega-3 nutritional intake) with disease progression and transplant-free survival in pulmonary fibrosis?

Study Design And Methods: Omega-3 fatty acid levels were measured from plasma samples of patients with clinically diagnosed pulmonary fibrosis from the Pulmonary Fibrosis Foundation Patient Registry (n = 150), University of Virginia (n = 58), and University of Chicago (n = 101) cohorts.

Factors associated with listing for lung transplantation in IPF patients: An analysis of the pulmonary fibrosis foundation registry.

Rationale And Objectives: Lung transplantation is a potentially life-saving treatment option for patients with idiopathic pulmonary fibrosis (IPF); however, not all eligible candidates get referred and listed for transplantation. Amongst IPF patients within the Pulmonary Fibrosis Foundation Patient Registry (PFF-R), we sought to determine the proportion of patients who undergo lung transplant listing and the characteristics associated with transplant listing.

Methods: An analysis of IPF patients with at least six months of follow-up data was performed.

A double-blind, placebo-controlled, randomized withdrawal trial of sarilumab for the treatment of glucocorticoid-dependent sarcoidosis.

Objectives: Effective steroid-sparing therapies for the treatment of sarcoidosis are lacking; IL-6 antagonists may reduce sarcoidosis disease activity. This study assessed the safety and efficacy of the IL-6 receptor antagonist, sarilumab, in subjects with glucocorticoid-dependent sarcoidosis.

Methods: This phase II, double-blind, placebo-controlled, randomized withdrawal trial enrolled 15 subjects with biopsy-proven sarcoidosis at Stanford University from November 2019 to September 2022.

First lung and kidney multi-organ transplant following COVID-19 Infection.

As the world responds to the global crisis of the COVID-19 pandemic an increasing number of patients are experiencing increased morbidity as a result of multi-organ involvement. Of these, a small proportion will progress to end-stage lung disease, become dialysis dependent, or both. Herein, we describe the first reported case of a successful combined lung and kidney transplantation in a patient with COVID-19.

Rituximab Versus Mycophenolate in the Treatment of Recalcitrant Connective Tissue Disease-Associated Interstitial Lung Disease.

Objective: Interstitial lung disease (ILD) is a major cause of morbidity and mortality in connective tissue diseases (CTDs). We aimed to assess the effect of rituximab ± mycophenolate mofetil (MMF) compared with MMF on pulmonary function and prednisone dosage in patients with CTD-related ILD (CTD-ILD).

Methods: This retrospective study included 83 patients from Stanford and Centre Hospitalier de l'Universite de Montreal.

Evaluation of integrin αvβ cystine knot PET tracers to detect cancer and idiopathic pulmonary fibrosis.

Advances in precision molecular imaging promise to transform our ability to detect, diagnose and treat disease. Here, we describe the engineering and validation of a new cystine knot peptide (knottin) that selectively recognizes human integrin αvβ with single-digit nanomolar affinity. We solve its 3D structure by NMR and x-ray crystallography and validate leads with 3 different radiolabels in pre-clinical models of cancer.

Estimated impact of hepatitis C-positive lung donor utilization on US donor lung supply.

The availability of highly effective direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV) infection has led to reports of safely transplanting HCV donor lungs into HCV candidates. However, it remains unclear how the ability to use HCV donor lungs for lung transplant could affect the number of donor lungs available for transplant. Using Scientific Registry of Transplant Recipient data, we identified all deceased organ donors within the United States from March 1, 2015, to February 28, 2018, and stratified by HCV status.

Effect of broader geographic sharing of donor lungs on lung transplant waitlist outcomes.

Background: The United States lung allocation system prioritizes allocation based on medical urgency and benefit but does not address a federal mandate for broader geographic organ sharing. It is unknown whether broader geographic sharing of donor lungs would improve lung transplant waitlist outcomes.

Methods: A discrete event microsimulation model simulated donor lung allocation according to different geographic lung-sharing policies, including the historic local donor service area (DSA)-based policy and hypothetical policies that prioritize candidates to donors within 500-mile or 1,000-mile geographic radii.

Multiple listing in lung transplant candidates: A cohort study.

Lung transplant candidates can be waitlisted at more than one transplant center, a practice known as multiple listing. The factors associated with multiple listing and whether multiple listing modifies waitlist mortality or likelihood of lung transplant is unknown. US lung transplant waitlist candidates were identified as either single or multiple listed using data from the Scientific Registry of Transplant Recipients.

Racial and ethnic disparities in lung transplant listing and waitlist outcomes.

Background: The United States lung transplant registry data demonstrate differences in adult waitlist mortality by race/ethnicity. It is unknown whether these differences persist after risk adjustment or occur secondary to disparities in disease severity at the time of listing.

Methods: Adult lung transplant waitlist candidates between May 4, 2005 and March 5, 2015 were identified and compared by non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic and Asian race/ethnicity.

Mechanical ventilation in idiopathic pulmonary fibrosis: a nationwide analysis of ventilator use, outcomes, and resource burden.

Background: Idiopathic pulmonary fibrosis (IPF) is associated with increased risk of respiratory-related hospitalizations. Studies suggest mechanical ventilation (MV) use in IPF does not improve outcomes and guidelines recommend against its general use. Our objective was to investigate MV use and association with cost and mortality in IPF.

Hospital cost and length of stay in idiopathic pulmonary fibrosis.

Objective: To provide a detailed picture of the economic impact of hospitalization in idiopathic pulmonary fibrosis (IPF) and to identify factors associated with cost and length of stay (LOS).

Methods: In this retrospective cross-sectional study using the Nationwide Inpatient Sample (NIS), this study included hospitalizations for IPF (ICD-9-CM 516.3) with a principal diagnosis of respiratory disease (ICD-9-CM 460-519) from 2009-2011; lung transplant admissions were excluded.

Effect of Transplant Center Volume on Cost and Readmissions in Medicare Lung Transplant Recipients.

Rationale: Although lung transplant recipient survival is better at higher volume centers, the effect of center volume on admission cost and early hospital readmission is unknown.

Objectives: To understand the association between transplant center volume and recipient risk-adjusted transplant admission cost, in-hospital mortality, and early hospital readmission in lung transplant recipients.

Methods: Medicare lung transplant recipients from May 4, 2005 to December 31, 2011 were identified through linkage of transplant registry and Medicare administrative claims.

Increased resource use in lung transplant admissions in the lung allocation score era.

Rationale: In 2005, the lung allocation score (LAS) was implemented to prioritize organ allocation to minimize waiting-list mortality and maximize 1-year survival. It resulted in transplantation of older and sicker patients without changing 1-year survival. Its effect on resource use is unknown.

Predicting survival across chronic interstitial lung disease: the ILD-GAP model.

Background: Risk prediction is challenging in chronic interstitial lung disease (ILD) because of heterogeneity in disease-specific and patient-specific variables. Our objective was to determine whether mortality is accurately predicted in patients with chronic ILD using the GAP model, a clinical prediction model based on sex, age, and lung physiology, that was previously validated in patients with idiopathic pulmonary fibrosis.

Methods: Patients with idiopathic pulmonary fibrosis (n=307), chronic hypersensitivity pneumonitis (n=206), connective tissue disease-associated ILD (n=281), idiopathic nonspecific interstitial pneumonia (n=45), or unclassifiable ILD (n=173) were selected from an ongoing database (N=1,012).

Radiographic fibrosis score predicts survival in hypersensitivity pneumonitis.

Background: It is unknown if the radiographic fibrosis score predicts mortality in persistent hypersensitivity pneumonitis (HP) and if survival is similar to that observed in idiopathic pulmonary fibrosis (IPF) when adjusting for the extent of radiographic fibrosis.

Methods: We reviewed records from 177 patients with HP and 224 patients with IPF whose diagnoses were established by multidisciplinary consensus. Two thoracic radiologists scored high-resolution CT (HRCT) scan lung images.

Prevalence and prognosis of unclassifiable interstitial lung disease.

The aim of this study was to determine the prevalence, characteristics and outcomes of patients with unclassifiable interstitial lung disease (ILD) and to develop a simple method of predicting disease behaviour. Unclassifiable ILD patients were identified from an ongoing longitudinal cohort. Unclassifiable ILD was diagnosed after a multidisciplinary review did not secure a specific ILD diagnosis.