Susan S. Jacobs

Rationale: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disease characterized by dyspnea and loss of lung function. Transforming growth factor-β (TGF-β) activation mediated by αv integrins is central to the pathogenesis of IPF. Bexotegrast (PLN-74809) is an oral, once-daily, dual-selective inhibitor of αvβ6 and αvβ1 integrins under investigation for the treatment of IPF. Positron emission tomography (PET) using an αvβ6-specific PET tracer could confirm target engagement of bexotegrast in the lungs of participants with IPF. Objectives: This Phase 2 study evaluated αvβ6 receptor occupancy in the lung as assessed by changes from baseline in αvβ6 PET tracer uptake, after single-dose administration of bexotegrast to participants with IPF. Methods: In this open-label, single-center study, adults with IPF received up to two single doses of bexotegrast, ranging from 60 to 320 mg with or without background IPF therapy (pirfenidone or nintedanib). At baseline and approximately 4 hours after each orally administered bexotegrast dose, a 60-minute dynamic PET–computed tomography scan was conducted after administration of an αvβ6-specific PET probe ([18F]FP-R01-MG-F2). αvβ6 receptor occupancy by bexotegrast was estimated from the changes in PET tracer uptake after bexotegrast administration. Pharmacokinetics, safety, and tolerability of bexotegrast were also assessed. Results: Eight participants completed the study. Total and unbound plasma bexotegrast concentrations increased in a dose-dependent manner, and regional PET volume of distribution values decreased in a dose- and concentration-dependent manner. The data for volume of distribution fit a simple saturation model, producing an unbound bexotegrast half maximal effective concentration estimate of 3.32 ng/ml. Estimated maximum receptor occupancy was 35%, 53%, 71%, 88%, and 92% after single 60-, 80-, 120-, 240-, and 320-mg doses of bexotegrast, respectively. No treatment-emergent adverse events related to bexotegrast were reported. Conclusions: Dose and concentration-dependent αvβ6 receptor occupancy by bexotegrast was observed by PET imaging, supporting once-daily 160- to 320-mg dosing to evaluate efficacy in clinical trials of IPF. Clinical trial registered with www.clinicaltrials.gov (NCT04072315).

Background: Evidence-based guidelines are needed for effective delivery of home oxygen therapy to appropriate patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). Methods: The multidisciplinary panel created six research questions using a modified Delphi approach. A systematic review of the literature was completed, and the Grading of Recommendations Assessment, Development and Evaluation approach was used to formulate clinical recommendations. Recommendations: The panel found varying quality and availability of evidence and made the following judgments: 1) strong recommendations for long-term oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe chronic resting hypoxemia, 2) a conditional recommendation against long-term oxygen use in patients with COPD with moderate chronic resting hypoxemia, 3) conditional recommendations for ambulatory oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe exertional hypoxemia, 4) a conditional recommendation for ambulatory liquid-oxygen use in patients who are mobile outside the home and require >3 L/min of continuous-flow oxygen during exertion (very-low-quality evidence), and 5) a recommendation that patients and their caregivers receive education on oxygen equipment and safety (best-practice statement). Conclusions: These guidelines provide the basis for evidence-based use of home oxygen therapy in adults with COPD or ILD but also highlight the need for additional research to guide clinical practice.

More than 1.5 million adults in the United States use supplemental oxygen for a variety of respiratory disorders to improve their quality of life and prolong survival. This document describes recommendations from a multidisciplinary workshop convened at the ATS International Conference in 2017 with the goal of optimizing home oxygen therapy for adults. Ideal supplemental oxygen therapy is patient-specific, provided by a qualified clinician, includes an individualized prescription and therapeutic education program, and offers oxygen systems that are safe, promote mobility, and treat hypoxemia. Recently, patients and clinicians report a growing number of problems with home oxygen in the United States. Oxygen users experience significant functional, mechanical, and financial problems and a lack of education related to their oxygen equipment—problems that impact their quality of life. Health care providers report a lack of readily accessible resources needed to prescribe oxygen systems correctly and efficiently. Patients with certain lung diseases are affected more than others because of physically unmanageable or inadequate portable systems. Analysis is needed to quantify the unintended impact that the Centers for Medicare and Medicaid Services Competitive Bidding Program has had on patients receiving supplemental oxygen from durable medical equipment providers. Studies using effectiveness and implementation research designs are needed to develop and evaluate new models for patient education, identify effective ways for stakeholders to interface, determine the economic benefit of having respiratory therapists perform in-home education and follow-up testing, and collaborate with technology companies to improve portable oxygen devices. Generation of additional evidence of the benefit of supplemental oxygen across the spectrum of advanced lung diseases and the development of clinical practice guidelines should both be prioritized.