Inhaled Nitric Oxide in Fibrotic Lung Disease: A Randomized, Double-Blind, Placebo-controlled Trial.

Inhaled nitric oxide (iNO) has been shown to result in benefits in moderate to vigorous physical activity (MVPA) in patients with fibrotic interstitial lung disease (f-ILD) receiving supplemental oxygen in two independent trials. This phase III randomized, double-blind, placebo-controlled study sought to validate the benefit of ambulatory iNO in patients with f-ILD requiring supplemental oxygen. Patients with f-ILD receiving supplemental long-term oxygen were randomized in a 1:1 fashion to iNO at 45 μg/kg ideal body weight per hour or placebo for 16 weeks.

Inflammation unites diverse acute and chronic diseases.

Background: Inflammation and immunity contribute pivotally to diverse acute and chronic diseases. Inflammatory pathways have become increasingly targets for therapy. Yet, despite substantial similarity in mechanisms and pathways, the scientific, medical, pharma and biotechnology sectors have generally focused programs finely on a single disease entity or organ system.

Genetics and Genomics of Pulmonary Fibrosis: Charting the Molecular Landscape and Shaping Precision Medicine.

Recent genetic and genomic advancements have elucidated the complex etiology of idiopathic pulmonary fibrosis (IPF) and other progressive fibrotic interstitial lung diseases (ILDs), emphasizing the contribution of heritable factors. This state-of-the-art review synthesizes evidence on significant genetic contributors to pulmonary fibrosis (PF), including rare genetic variants and common SNPs. The promoter variant is unusual, a common SNP that markedly elevates the risk of early and established PF.

Meaningful Endpoints for Idiopathic Pulmonary Fibrosis (IPF) Clinical Trials: Emphasis on 'Feels, Functions, Survives'. Report of a Collaborative Discussion in a Symposium with Direct Engagement from Representatives of Patients, Investigators, the National Institutes of Health, a Patient Advocacy Organization, and a Regulatory Agency.

Idiopathic pulmonary fibrosis (IPF) carries significant mortality and unpredictable progression, with limited therapeutic options. Designing trials with patient-meaningful endpoints, enhancing the reliability and interpretability of results, and streamlining the regulatory approval process are of critical importance to advancing clinical care in IPF. A landmark in-person symposium in June 2023 assembled 43 participants from the US and internationally, including patients with IPF, investigators, and regulatory representatives, to discuss the immediate future of IPF clinical trial endpoints.

Efficacy and Safety of Pirfenidone in Advanced Versus Non-Advanced Idiopathic Pulmonary Fibrosis: Post-Hoc Analysis of Six Clinical Studies.

Introduction: In the European Union (EU), the indication for the antifibrotic pirfenidone prior to April 2023 did not include patients with advanced idiopathic pulmonary fibrosis (IPF). This analysis compared the efficacy and safety of pirfenidone in advanced IPF versus non-advanced IPF.

Methods: Data were included from the following studies of pirfenidone: ASCEND (NCT01366209); CAPACITY (004 [NCT00287716] and 006 [NCT00287729]); RECAP (NCT00662038; advanced IPF defined as percent predicted forced vital capacity [%FVC] < 50% and/or percent predicted carbon monoxide diffusing capacity [%DLco] < 35% at baseline); PASSPORT (NCT02699879; advanced IPF defined as baseline %FVC < 50%); and SP-IPF (NCT02951429; patients with advanced IPF [defined as %DLco ≤ 40% at screening] at risk of group 3 pulmonary hypertension).

Arizona Surge Line: An emergent statewide COVID-19 transfer service with equity as an outcome.

Introduction: The Arizona Surge Line was an emergent initiative during the COVID-19 pandemic to facilitate COVID-19 patient transfers and load-level hospitals on a statewide level. It was designed and implemented by the Arizona Department of Health Services in preparation for the first hospital surge due to COVID-19, recognizing the disproportionate impact that hospital surge would have on rural and tribal populations.

Methods: We analyzed the Arizona Surge Line transfer data for the state's first two COVID-19 surges (4/16/2020-3/6/2021).

Idiopathic Pulmonary Fibrosis Is Associated with Common Genetic Variants and Limited Rare Variants.

Idiopathic pulmonary fibrosis (IPF) is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to nongenetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF.

Machine learning in radiology: the new frontier in interstitial lung diseases.

Challenges for the effective management of interstitial lung diseases (ILDs) include difficulties with the early detection of disease, accurate prognostication with baseline data, and accurate and precise response to therapy. The purpose of this Review is to describe the clinical and research gaps in the diagnosis and prognosis of ILD, and how machine learning can be applied to image biomarker research to close these gaps. Machine-learning algorithms can identify ILD in at-risk populations, predict the extent of lung fibrosis, correlate radiological abnormalities with lung function decline, and be used as endpoints in treatment trials, exemplifying how this technology can be used in care for people with ILD.

Sex and Gender in Lung Diseases and Sleep Disorders: A State-of-the-Art Review: Part 2.

There is now ample evidence that differences in sex and gender contribute to the incidence, susceptibility, presentation, diagnosis, and clinical course of many lung diseases. Some conditions are more prevalent in women, such as pulmonary arterial hypertension and sarcoidosis. Some life stages-such as pregnancy-are unique to women and can affect the onset and course of lung disease.

Sex and Gender in Lung Disease and Sleep Disorders: A State-of-the-Art Review.

The terms sex and gender often are used interchangeably, but have specific meaning when it comes to their effects on lung disease. Ample evidence is now available that sex and gender affect the incidence, susceptibility, presentation, diagnosis, and severity of many lung diseases. Some conditions are more prevalent in women, such as asthma.

Sex and gender in interstitial lung diseases.

Sex and gender differences influence key domains of research, lung health, healthcare access and healthcare delivery. In interstitial lung diseases (ILDs), mouse models of pulmonary fibrosis are clearly influenced by sex hormones. Additionally, short telomeres, a biomarker of telomere regulation gene mutations, are impacted by sex, while heritability unexplained by genetic variation may be attributable to gendered environmental factors that drive epigenetic control.

A Phase-2 Exploratory Randomized Controlled Trial of INOpulse in Patients with Fibrotic Interstitial Lung Disease Requiring Oxygen.

Patients with fibrotic interstitial lung disease often progress to the point of requiring supplemental oxygen. This is invariably accompanied by an impaired quality of life and limitations on activities of daily living. This study aimed to assess the improvement in physical activity in patients with interstitial lung disease requiring supplemental oxygen treated with pulsed inhaled nitric oxide via INOpulse (Bellerophon Therapeutics).

Efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis who are elderly or have comorbidities.

Background: Idiopathic pulmonary fibrosis (IPF) predominantly affects individuals aged > 60 years who have several comorbidities. Nintedanib is an approved treatment for IPF, which reduces the rate of decline in forced vital capacity (FVC). We assessed the efficacy and safety of nintedanib in patients with IPF who were elderly and who had multiple comorbidities.

Stem Cell Therapy for COPD: Hope and Exploitation.

COPD is a chronic inflammatory and destructive disease characterized by progressive decline in lung function that can accelerate with aging. Preclinical studies suggest that mesenchymal stem cells (MSCs) may provide a therapeutic option for this incurable disease because of their antiinflammatory, reparative, and immunomodulatory properties. To date, clinical trials using MSCs demonstrate safety in patients with COPD.

Corrigendum: Antifibrotics in COVID-19 Lung Disease: Let Us Stay Focused.

[This corrects the article DOI: 10.3389/fmed.2020.

Altered pulmonary blood volume distribution as a biomarker for predicting outcomes in COVID-19 disease.

Introduction: Evidence suggests that vascular inflammation and thrombosis may be important drivers of poor clinical outcomes in patients with COVID-19. We hypothesised that a significant decrease in the percentage of blood volume in vessels with a cross-sectional area between 1.25 and 5 mm relative to the total pulmonary blood volume (BV5%) on chest computed tomography (CT) in COVID-19 patients is predictive of adverse clinical outcomes.

Umbilical cord mesenchymal stem cells for COVID-19 acute respiratory distress syndrome: A double-blind, phase 1/2a, randomized controlled trial.

Acute respiratory distress syndrome (ARDS) in COVID-19 is associated with high mortality. Mesenchymal stem cells are known to exert immunomodulatory and anti-inflammatory effects and could yield beneficial effects in COVID-19 ARDS. The objective of this study was to determine safety and explore efficacy of umbilical cord mesenchymal stem cell (UC-MSC) infusions in subjects with COVID-19 ARDS.

Antifibrotics in COVID-19 Lung Disease: Let Us Stay Focused.

After decades of research, two therapies for chronic fibrotic lung disease are now approved by the FDA, with dozens more anti-fibrotic therapies in the pipeline. A great deal of enthusiasm has been generated for the use of these drugs, which are by no means curative but clearly have a favorable impact on lung function decline over time. Amidst a flurry of newly developed and repurposed drugs to treat the coronavirus disease 2019 (COVID-19) and its accompanying acute respiratory distress syndrome (ARDS), few have emerged as effective.