Mortality Outcomes and ACE Inhibitor Use in Patients with Idiopathic Pulmonary Fibrosis.

Background: ACE inhibitors (ACEi) are widely used antihypertensive agents with proven cardioprotective effects. Previous mechanistic and clinical studies have suggested ACEi therapy may slow disease progression and reduce mortality in idiopathic pulmonary fibrosis (IPF).

Research Question: Does ACEi use associate with reduced all-cause in a real-world population of IPF patients, and if so, is the association also present in COPD patients?

Study Design And Methods: A retrospective analysis was conducted using electronic health records from the Clinical Practice Research Datalink (CPRD) GOLD database (2019), linked with HES Admitted Patient Care and ONS death registration data.

Distinct Morphological Types of Small Airway Obstructions in Smokers with Emphysema and End-Stage COPD.

Rationale: The precise nature of small airway obstructions in COPD remains poorly understood, especially at early disease stages.

Objectives: This study aimed to characterize small airway obstructions and numbers up to the terminal bronchioles (TB) in smokers with limited emphysema and end-stage COPD. We hypothesized that obstruction subtypes would differ in morphology, nature and number from early to end-stage COPD.

Stratifying GAP Stages by MUC5B rs35705950 T-Allele Carriage Refines Survival Prediction in IPF.

The genetic contribution to idiopathic pulmonary fibrosis (IPF) has become increasingly evident, enabling its translation into clinical practice. MUC5B rs35705950 has emerged as a promising prognostic biomarker. The gender-age-physiology (GAP)-model is regularly used for IPF survival prediction.

Alveolar epithelial cell plasticity and injury memory in human pulmonary fibrosis.

Acute and repetitive lung epithelial injury can lead to irreversible and even progressive pulmonary fibrosis; Idiopathic pulmonary fibrosis (IPF) is a fatal disease and quintessential example of this phenomenon. The composition of epithelial cells in human pulmonary fibrosis - irrespective of disease etiology - is marked by the presence of Aberrant Basaloid cells: an abnormal cell phenotype with pro-fibrotic and senescent features, localized to the surface of fibrotic lesions. Despite their relevance to human pulmonary fibrosis, the exotic molecular profile of Aberrant Basaloid cells has obscured their etiology, preventing insights into how or why these cells emerge with fibrosis.

A deep generative model for deciphering cellular dynamics and in silico drug discovery in complex diseases.

Human diseases are characterized by intricate cellular dynamics. Single-cell transcriptomics provides critical insights, yet a persistent gap remains in computational tools for detailed disease progression analysis and targeted in silico drug interventions. Here we introduce UNAGI, a deep generative neural network tailored to analyse time-series single-cell transcriptomic data.

Pulmonary arteriole narrowing in end-stage cystic fibrosis lungs occurs with and without small airway disease.

Background: Pulmonary hypertension (PH) is an important, life-limiting co-morbidity in cystic fibrosis (CF), where multiple mechanisms such as hypoxia, inflammation and primary CF-transmembrane regulator (CFTR) dysfunction may affect vascular integrity. We aimed to characterize the structural impact of vascular wall changes in the pulmonary microcirculation, to uncover the potential need for therapeutic strategies targeting vascular disease.

Methods: End-stage inflated CF (n=6), and control (n=4) lungs were processed to lung cores (2.

Effect of Admilparant, a Lysophosphatidic Acid Receptor 1 Antagonist, on Disease Progression in Pulmonary Fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) are chronic fibrosing interstitial lung diseases associated with irreversible loss of lung function and early mortality. Admilparant (BMS-986278) is an oral lysophosphatidic acid receptor 1 antagonist under development for treatment of IPF and PPF.

Research Question: How does admilparant affect time to disease progression in patients with IPF or PPF?

Study Design And Methods: In a phase 2, randomized, double-anonymized, placebo-controlled study, parallel cohorts of patients with IPF or PPF were randomized separately 1:1:1 to receive 30 mg admilparant, 60 mg admilparant, or placebo twice daily for 26 weeks; background antifibrotics were allowed.

Computational fluid dynamics of small airway disease in chronic obstructive pulmonary disease.

Background: Small airways (<2 mm diameter) are major sites of airflow obstruction in chronic obstructive pulmonary disease (COPD). This study aimed to quantify the impact of small airway disease, characterized by narrowing, occlusion, and obliteration, on airflow parameters in smokers and end-stage patients with COPDs.

Methods: We performed computational fluid dynamics (CFD) simulations of inspiratory airflow in three lung groups: control non-used donor lungs (no smoking/emphysema history), non-used donor lungs with a smoking history and emphysema, and explanted end-stage COPD lungs.

Interleukin 6 inhibition in refractory antisynthetase syndrome: case-based literature review.

Introduction: Antisynthetase syndrome (ASyS) is a rare idiopathic inflammatory myopathy (IIM), characterised by the presence of anti-aminoacyl tRNA synthetase antibodies. Significant clinical heterogeneity often results in delayed or missed diagnoses. While corticosteroids are the primary treatment for ASyS, immunosuppressants are frequently added as steroid-sparing agents.

Person-centred health outcomes in the routine care for people with progressive pulmonary fibrosis: the COCOS-IPF project's European survey on healthcare professionals' views and practices.

Background: Idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) are interstitial lung diseases (ILD) that carry a high burden and mortality. IPF/PPF experts and patients call for standardized care, outcome harmonization and holistic management in these complex and devastating diseases, with a focus on person-centeredness. In this cross-sectional international survey study, we aimed to gather information on the person-centred health outcomes European healthcare professionals (HCPs) already use or deem important for use in routine care for IPF/PPF.

Lung ultrasound outperforms symptom-based screening to detect interstitial lung disease associated with rheumatoid arthritis.

Objectives: Interstitial lung disease associated with rheumatoid arthritis (RA-ILD) is linked to high mortality. Currently, effective screening tools are lacking. We assessed the role of symptoms and lung ultrasound (LUS) as potential screening tools.

Epigenetic age acceleration in idiopathic pulmonary fibrosis revealed by DNA methylation clocks.

In this research, we delve into the association between epigenetic aging and idiopathic pulmonary fibrosis (IPF), a debilitating lung disease that progresses over time. Utilizing the Illumina MethylationEPIC array, we assessed DNA methylation levels in donated human lung tissue from patients with IPF, categorizing the disease into mild, moderate, and severe stages based on clinical assessments. We used seven epigenetic clocks to determine age acceleration, which is the discrepancy between biological (epigenetic) and chronological age.

Diagnosis, screening, and follow-up of patients with familial interstitial lung disease: Results from an international survey.

Background: Advances in the field of genetics of interstitial lung diseases (ILDs) have led to the recent consensus statements made by expert groups. International standards for genetic testing in ILD have not yet been established. We aimed to examine current real-world strategies employed by pulmonologists working with familial ILD.

Identifying outcome domains to establish a core outcome set for progressive pulmonary fibrosis: a scoping review.

Introduction: People with idiopathic pulmonary fibrosis (IPF) and other forms of progressive pulmonary fibrosis (PPF) have a high symptom burden and a poor health-related quality of life (HRQoL). Despite efforts to offer specialised treatment, clinical care for these patients remains suboptimal and several nonmedical needs remain unaddressed. Developing a core outcome set (COS) can help to identify a minimum set of agreed-upon outcomes that should be measured and acted-upon in clinical care.

Continued Treatment with Nintedanib in Patients with Progressive Pulmonary Fibrosis: Data from INBUILD-ON.

Purpose: In the INBUILD trial in patients with progressive pulmonary fibrosis (PPF), nintedanib slowed the decline in forced vital capacity (FVC) versus placebo, with a safety profile characterised mainly by gastrointestinal events. INBUILD-ON, the open-label extension of INBUILD, assessed the safety of nintedanib during longer-term treatment. Data on FVC were collected.

Airway Remodeling in Cystic Fibrosis Is Heterogeneous.

Cystic fibrosis (CF) is characterized by bronchiectasis on imaging, while functionally evolving toward obstructive impairment. Despite its assumed importance in CF, small airway remodeling and its relation to bronchiectasis remains poorly understood. The aim of our study was to explore both large and small airway disease morphometrically, by using detailed imaging techniques, such as high-resolution computed tomography (HRCT) and micro-computed tomography (μCT), and histological analysis in advanced CF.

Predicting lung aging using scRNA-Seq data.

Age prediction based on single cell RNA-Sequencing data (scRNA-Seq) can provide information for patients' susceptibility to various diseases and conditions. In addition, such analysis can be used to identify aging related genes and pathways. To enable age prediction based on scRNA-Seq data, we developed PolyEN, a new regression model which learns continuous representation for expression over time.

Bexotegrast in people with idiopathic pulmonary fibrosis (IPF): a plain language summary of publication of the INTEGRIS-IPF study.

This plain language summary shares results from a clinical study called INTEGRIS-IPF that was published in the in 2024. This study looked at a medicine called (beck-so-teh-grast) as a possible treatment for (i-dee-uh-pa-thick pul-muh-ner-ee fie-bro-sis; IPF). is an investigational medicine, which means that it is being studied and has not yet been approved by the US Food and Drug Administration (FDA), for people with IPF to take as a treatment.

Bexotegrast in Patients with Idiopathic Pulmonary Fibrosis: The INTEGRIS-IPF Clinical Trial.

Idiopathic pulmonary fibrosis (IPF) is a rare and progressive disease that causes progressive cough, exertional dyspnea, impaired quality of life, and death. Bexotegrast (PLN-74809) is an oral, once-daily, investigational drug in development for the treatment of IPF. This Phase-2a multicenter, clinical trial randomized participants with IPF to receive, orally and once daily, bexotegrast at 40 mg, 80 mg, 160 mg, or 320 mg, or placebo, with or without background IPF therapy (pirfenidone or nintedanib), in an approximately 3:1 ratio in each bexotegrast dose cohort, for at least 12 weeks.

ERS International Congress 2023: highlights from the Interstitial Lung Diseases Assembly.

This article summarises a selection of scientific highlights in the field of interstitial lung diseases (ILDs) presented at the International Congress of the European Respiratory Society in 2023. Translational and clinical studies focused on the whole spectrum of ILDs, from (ultra)rare ILDs to sarcoidosis, ILDs associated with connective tissue disease and idiopathic pulmonary fibrosis. The main topics of the 2023 Congress presentations were improving the diagnostic process of ILDs, better prediction of disease course and investigation of novel treatment options.

Physical activity coaching in patients with interstitial lung diseases: A randomized controlled trial.

Objectives: Physical activity is reduced in patients with interstitial lung disease (ILD) and physical inactivity is related to poor health outcomes. We investigated the effect of a telecoaching intervention to improve physical activity in patients with ILD.

Methods: Eighty patients with ILD were randomized into the intervention or control group.