: 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. Positron emission tomography (PET) using an αβ-specific PET tracer could confirm target engagement of bexotegrast in the lungs of participants with IPF. : This Phase 2 study (NCT04072315) evaluated αβ receptor occupancy in the lung, as assessed by changes from baseline in αβ PET tracer uptake, following single dose administration of bexotegrast to participants with IPF. : In this open-label, single-center, single-arm study, adults with IPF received up to 2 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/CT scan was conducted following administration of an αβ-specific PET probe ([F]FP-R1-MG-F2). αβ receptor occupancy by bexotegrast was estimated from the changes in PET tracer uptake following bexotegrast. Pharmacokinetics, safety, and tolerability of bexotegrast were also assessed. : Eight participants completed the study. Total and unbound plasma bexotegrast concentrations increased in a dose-dependent manner, and regional PET volume of distribution (V) values decreased in a dose- and concentration-dependent manner. The V data fit a simple saturation model, producing an unbound bexotegrast EC estimate of 3.32 ng/mL. Estimated maximum receptor occupancy was 35%, 53%, 71%, 88%, and 92% following single 60, 80, 120, 240, and 320-mg doses of bexotegrast, respectively. No treatment-emergent adverse events related to bexotegrast were reported. : Dose- and concentration-dependent αβ 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. Trial registration number: NCT04072315 Primary source of funding: Pliant Therapeutics, Inc. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

In patients with obstructive sleep apnea (OSA) treated with continuous positive airway pressure (CPAP), the apnea hypopnea index (AHI) measured CPAP may be decreased relative to baseline AHI preceding CPAP treatment. Semi-invasive "endo-phenotyping" sleep studies attribute this fall in AHI primarily to improved ventilatory control stability. Phenotyping Using Polysomnography (PUP) attempts to reproduce these studies using routine polysomnography (PSG). To determine whether changes in AHI following CPAP associate primarily with changes in PUP-estimated ventilatory control stability (loop gain, LG) or with changes in other PUP-estimated pathophysiologic mechanisms. PUP analyses were performed on existing PSGs in research participants who underwent baseline PSG, 4.4±2.2 months CPAP therapy, and CPAP withdrawal with repeat PSG on night 2 of withdrawal. Pre-CPAP PUP-estimated LG, arousal threshold (ArTH), and upper airway collapsibility (Vpassive) and compensation (Vcomp) were compared to corresponding values during CPAP withdrawal. Mixed effects models were constructed to determine which PUP estimate best explained changes in AHI. PSG data were available for 35 participants (age 47±10.8 years; 12 female; BMI 38.5±8.6 kg/m, AHI3A 58.8±33.1 events/hr, 9 mild/moderate OSA, 26 severe OSA). Following CPAP, AHI decreased, but the change was not statistically significant. However, a significant decrease was observed in those with severe OSA (pre-CPAP 68.2 [32.6-86.3] versus CPAP withdrawal 49.0 [36.1-74.4] events/hr). Across all participants, changes in PUP estimates did not exceed test-retest agreement limits. For those with severe OSA, decrease in LG (0.86 [0.61-1.13] pre-CPAP versus 0.71 [0.61-0.99] on CPAP withdrawal) and increase in Vpassive (64.8 [5.4-88.4] %Veupnea pre-CPAP versus 76.4 [20.7-92.7] %Veupnea on CPAP withdrawal) exceeded test-retest agreement limits. Increased Vpassive, decreased LG, and decreased ArTH were predictors of decreased AHI in mixed effects models. Vpassive had the greatest estimated effect on AHI. After accounting for Vpassive, additional estimates did not improve model performance. However, Vpassive and LG were correlated, and post hoc analyses suggest these estimates may be influenced by both upper airway collapsibility and ventilatory control. According to PUP physiologic estimates, decreases in AHI following several months of CPAP therapy are primarily attributable to improved upper airway collapsibility.

Rationale Pleural infection is associated with significant mortality and its management is complex. Little attention has been given to care process metrics such as management delays, pleural drainage practices, and adequacy of intrapleural therapy administration despite their potential impact on outcomes. Audits revealed gaps in those care processes in our institution. Objectives To assess the impact of quality improvement initiatives on pleural effusion management in adults. Methods We performed a retrospective comparison of patients treated with intrapleural therapy for pleural infection at the McGill University Health Centre before (April 2013-April 2016, N=109) and after interventions (June 2020-June 2021, N=44). Interventions included a pleural drainage policy and order set, an intrapleural therapy protocol and pre-printed order, implementation of intrapleural therapy administration by nurses, local pleural infection guideline development, and an online learning module for physicians. Major outcomes (length of stay, mortality, surgical treatment) and care process metrics (management delays, pleural drainage practices, intrapleural therapy administration) were compared between the two periods. Results After implementation of the interventions, in-hospital mortality and length of stay were unchanged, but surgical management went from 14% to 0% (p=0,01). Delays in drain insertion and intrapleural therapy initiation were not significantly different. Insertion of drains smaller than 12Fr decreased from 51% to 7% (p<0,001). Drain blockage decreased from 20% to 2% (p=0,004). Additional drain insertions went from 62% to 48% (p=0,12). After interventions, 70% of intrapleural therapy doses were given by nurses, the intrapleural therapy protocol was more often adequately followed, less doses were missed, and less extended therapy was prescribed. Complications related to drain insertion and intrapleural therapy were similar between the two periods. Conclusions Following the implementation of multifaceted quality improvement interventions for pleural infection including involvement of nurses in pleural drain flushing and intrapleural therapy, improvements were observed in intrapleural therapy administration, chest drainage practices, and need for surgery. However, length of stay, mortality, and management delays were unchanged.

Patients with obesity hypoventilation syndrome (OHS) have high risk of hospitalization, which might be decreased by home mechanical ventilation (HMV).

The prevalence of obstructive sleep apnea (OSA) is on the rise, driven by various factors including more sensitive diagnostic criteria, increased awareness, enhanced technology through at-home testing enabling easy and cost-effective diagnosis, and a growing incidence of comorbid conditions such as obesity. Treating symptomatic patients with OSA syndrome to enhance quality of life remains a cornerstone approach. However, there is a lack of consensus regarding treatment to improve cardiovascular disease (CVD) outcomes, particularly in light of overall negative results from several randomized controlled trials (RCT) indicating no benefit of positive airway pressure (PAP) therapy on primary and secondary CVD events. These RCTs were limited by suboptimal PAP adherence, use of composite CVD outcomes, and limited diversity and generalizability to Sleep Clinic patients. As such, this workshop assembled clinical experts, as well as researchers in basic and translational science, epidemiology, clinical trials, and population health to discuss the current state, and future research directions to guide personalized therapeutic strategies and future research directions in OSA. There was overall consensus among workshop participants that OSA represents a heterogeneous disease with variable endotypes and phenotypes, and heterogeneous responses to treatment. Future research should prioritize employing multi-modal therapeutic approaches within innovative and adaptive trial designs, focusing on specific subgroups of OSA patients hypothesized to benefit from a CVD perspective. Future work should also be inclusive of diverse populations and consider the life-course of OSA to better comprehend treatment strategies that can address the disproportionate impact of OSA on racially minoritized groups. Further, a more holistic approach to sleep must be adopted to include broader assessments of symptoms, sleep duration, and comorbid sleep and circadian disorders. Finally, it is imperative to establish a sleep research consortium dedicated to collecting raw data and biospecimens categorized by OSA subtypes. This will facilitate mechanistic determinations, foster collaborative research, and help bolster the pipeline of early-career researchers.

Extreme heat exposure is a well-known cause of mortality among older adults. However, the impacts of exposure on respiratory morbidity across US cities and population subgroups is not well understood.

While exposure to air pollution is a known risk factor for adverse pulmonary outcomes, its impact in individuals with idiopathic pulmonary fibrosis (IPF) is less well understood.

Acetazolamide, eszopiclone, and venlafaxine may target different underlying mechanisms of obstructive sleep apnea (OSA) and individually may partially improve OSA severity in select patients. We tested whether acetazolamide+eszopiclone (DualRx) improves OSA severity. We further explored whether addition of venlafaxine (TripleRx) improves OSA in patients who do not fully respond to DualRx.

Equivocal interstitial lung abnormality (ILA) involves less than 5% of any lung zone or presents unilaterally without satisfying the diagnostic criteria for ILA; however, the prevalence and prognosis of equivocal ILA are unknown.

Numerous studies indicate that preserved ratio impaired spirometry (PRISm) is associated with adverse clinical outcomes. However, the impact of PRISm severity, particularly about FVC, on mortality risk remains unclear.

Epidemiologic studies on asthmatics and data suggest a protective role of T2 inflammation in SARS-CoV-2 infection.

Mouth air leak is a major cause of low adherence to nasal CPAP in patients with obstructive sleep apnea (OSA). However, CPAP reports do not distinguish mouth from mask leak. We hypothesized that mouth air leak is terminated abruptly by an arousal from sleep and mouth closing that can be detected by CPAP leak waveform analysis.

Individuals with chronic obstructive pulmonary disease (COPD) in rural areas experience inequitable access to care.

There is a paucity of data, and no consensus, about the composition of interdisciplinary teams of healthcare worker (HCW) that provide care in intensive care units (ICU).

Accurate prognostic awareness (PA) and knowledge of the disease are critical for decision-making regarding treatment options, advance care planning, and end-of-life care. However, they have not been investigated in patients with interstitial lung disease (ILD).

In the United States (U.S.), ambulatory oxygen is recommended for patients with idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) who experience symptomatic exertional hypoxemia. Ambulatory oxygen need is often determined by submaximal hall walk testing; however, this may fail to accurately characterize exertional hypoxemia in some patients.