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.

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.

An adjudication algorithm for respiratory-related hospitalisation in idiopathic pulmonary fibrosis.

Background: There is no standard definition of respiratory-related hospitalisation, a common end-point in idiopathic pulmonary fibrosis (IPF) clinical trials. As diverse aetiologies and complicating comorbidities can present similarly, external adjudication is sometimes employed to achieve standardisation of these events.

Methods: An algorithm for respiratory-related hospitalisation was developed through a literature review of IPF clinical trials with respiratory-related hospitalisation as an end-point.

Sfrp1 inhibits lung fibroblast invasion during transition to injury-induced myofibroblasts.

Background: Fibroblast-to-myofibroblast conversion is a major driver of tissue remodelling in organ fibrosis. Distinct lineages of fibroblasts support homeostatic tissue niche functions, yet their specific activation states and phenotypic trajectories during injury and repair have remained unclear.

Methods: We combined spatial transcriptomics, multiplexed immunostainings, longitudinal single-cell RNA-sequencing and genetic lineage tracing to study fibroblast fates during mouse lung regeneration.

Unagi: 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 sequencing 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 analyze time-series single-cell transcriptomic data.

Clinical course of suspected familial and sporadic idiopathic pulmonary fibrosis: Data from the PROOF-Next registry.

Background And Objective: Real-life data on suspected familial fibrosis, defined as the occurrence of the disease in a patient younger than 50 and/or having at least one relative affected by pulmonary fibrosis remain scarce.

Methods: The Belgian and Luxembourg IPF registry (PROOF-Next) is a multicentric prospective longitudinal and observational study set in Belgium and Luxembourg. We compared characteristics and clinical course of patients with suspected familial pulmonary fibrosis (FPF) and sporadic IPF.

Ex vivo tissue perturbations coupled to single-cell RNA-seq reveal multilineage cell circuit dynamics in human lung fibrogenesis.

Pulmonary fibrosis develops as a consequence of failed regeneration after injury. Analyzing mechanisms of regeneration and fibrogenesis directly in human tissue has been hampered by the lack of organotypic models and analytical techniques. In this work, we coupled ex vivo cytokine and drug perturbations of human precision-cut lung slices (hPCLS) with single-cell RNA sequencing and induced a multilineage circuit of fibrogenic cell states in hPCLS.

Ultrasonographic Presentation and Anatomic Distribution of Lung Involvement in Patients with Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is a chronic auto-immune disease, typically affecting the joints, which can also present with lung involvement (pleuritis, interstitial lung disease, pulmonary nodules, etc.). Lung ultrasound (LUS) is an upcoming tool in the detection of these pulmonary manifestations.