European Respiratory Journal

BackgroundPulmonary fibrosis (PF) is an incurable fibrotic lung disease with limited treatment options and a high mortality. Evidence is growing that short telomeres cause both heritable and idiopathic pulmonary fibrosis (IPF). Based on survival data, we hypothesised that sex hormones are protective against premature telomere attrition and could influence PF disease onset and/or progression. MethodsAssociations between IPF, sex hormone concentrations and measured leukocyte telomere length (LTL)...

IntroductionHypersensitivity pneumonitis (HP), a common interstitial lung disease (ILD), comprises two distinct but related forms, acute and fibrotic (fHP). HP is classically described as a disease triggered by antigen exposure. However, a wide range of triggers are described and in [~]50% of cases no cause is identified, rendering observational studies challenging. The British Pigeon Fanciers Genetics of ILD (BPF-GILD) study aims to address this by studying a population with a clear history of ...

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with limited treatment options. LTI-03 promotes alveolar epithelial cell survival and reduces profibrotic protein expression in experimental models of IPF. In this Phase 1b, placebo-controlled, dose-escalation study, 24 participants with IPF were randomized 3:1 into 2 sequential dose cohorts to LTI-03 (5 or 10 mg/day) or placebo for 14 days (ClinicalTrials.gov: NCT05954988). The primary endpoint was the incidence of treatme...

BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease trajectory. The aim of this study was to assess the potential of neutrophil-to-lymphocyte ratio (NLR) to predict outcomes for people with IPF. MethodWe adopted a two-stage discovery and validation design using patients from the UCL partners (UCLp) cohort. For the discovery analysis, we included 71 patients from UCLH. In the validation analysis, we included 928 people with IPF, using real-life ...

Sarcoidosis is often complicated by the development of pulmonary hypertension (PH). Sotatercept, a ligand trap for selected transforming growth factor {beta} superfamily members, is a novel, highly effective therapy approved for the treatment of pulmonary arterial hypertension. We conducted a retrospective study of patients with biopsy-proven sarcoidosis who received sotatercept for the treatment of sarcoidosis-associated pulmonary hypertension (PH) to assess the effect of sotatercept on lung fu...

BackgroundInterstitial lung disease (ILD) affects >40% of patients with systemic sclerosis (SSc/scleroderma) and is the leading cause of disease-related mortality. Although therapies may slow progression, outcomes remain poor, partly because ILD is often detected after irreversible lung injury has occurred. Although chest computed tomography (CT) is a sensitive tool for ILD detection and is recommended at SSc diagnosis, it is oftentimes not performed and even less often performed serially. We so...

RationaleRacial and ethnic differences in presentation and outcomes have been reported in systemic sclerosis (SSc) and SSc-interstitial lung disease (ILD). However, diverse cohorts and additional modeling can improve understanding of risk features and outcomes, which is important for reducing associated disparities. Objective(s)To determine if there are racial/ethnic differences associated with SSc-ILD risk and age; time intervals between SSc and ILD, and with emergency department (ED) visit or...

BackgroundIdiopathic pulmonary fibrosis (IPF) is a disease with very poor prognosis and no curative therapies. The G protein-coupled, calcium/cation-sensing receptor (CaSR) is activated by environmental pollutants and by arginine-derived polyamines, which are thought to play a role in IPF. Whether the CaSR is involved in the pathogenesis of pulmonary fibrosis is unknown. ObjectiveTo investigate the CaSR as a novel drug target for the treatment of pulmonary fibrosis (PF). Methods and resultsCaS...

BackgroundBone morphogenetic protein-7 (BMP-7) antagonises transforming growth factor-{beta} (TGF-{beta}). This study investigated the ability of a prodrug BMP-7, designed as micelle nanoparticles for nasal inhalation, to ameliorate pulmonary fibrosis in a bleomycin (BLM)-induced murine model. Materials and MethodsFluorescently labelled BMP-7 was delivered to murine lungs via nasal inhalation. Thirty-eight C57BL/6J mice were divided into three groups: control, BLM and BLM with prodrug BMP-7. We...

BackgroundPrimary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by deficient mucociliary clearance and development of chronic lung disease. Pulmonary exacerbations (PEx) in chronic lung diseases increase morbidity and lung function decline, but their frequency in PCD has been understudied. We aimed to prospectively determine the annual frequency of PEx in PCD and identify related risk factors. MethodsIn a multicentre, observational study conducted in 11 centres from seven co...

BackgroundNintedanib and pirfenidone are antifibrotic agents approved for the treatment of idiopathic pulmonary fibrosis (IPF) and progressive fibrosing interstitial lung diseases. Despite their clinical significance, national trends in Medicare Part D spending and utilization for these therapies remain insufficiently characterized. ObjectiveTo evaluate national trends in Medicare Part D spending, claims, and cost-per-claim for nintedanib and pirfenidone from 2019 to 2023. MethodsMedicare Part...

RationaleIn contrast to visual assessments, quantitative CT using multiple instance learning (MIL)-usual interstitial pneumonia (UIP) classifier and data-driven textural analysis (DTA) provides objective and reproducible measurements of disease pattern and extent, respectively. However, the understanding of their individual or combined relationships with outcomes in hypersensitivity pneumonitis (HP) remains limited. ObjectivesTo determine whether visual CT patterns of HP or UIP, a MIL-UIP class...

ObjectiveMyositis-associated interstitial lung disease (myositis-ILD) consists of two predominant radiologic patterns of lung injury--nonspecific interstitial pneumonia (NSIP) and organizing pneumonia (OP)--that oftentimes coexist. However, it remains unclear whether either is associated with clinical outcomes. We aimed to assess the therapeutic response in patients with NSIP-compared to those with OP-predominant myositis-ILD. MethodsThis retrospective, single-center cohort study recruited part...

Rationale: Up to 30% of COVID-19 patients experience persistent sequelae, including dyspnea, restrictive physiology, and early radiographic signs of pulmonary fibrosis (PF). The mechanisms that provoke post-COVID progressive PF are poorly understood, and biomarkers to identify at-risk patients are urgently needed. Methods: We evaluated a cohort of 14 symptomatic COVID survivors with impaired respiratory function and imaging worrisome for developing PF, including bilateral reticulation, traction ...

RationaleWhile many studies have examined gene expression in lung tissue, the gene regulatory processes underlying emphysema are still not well understood. Finding efficient non-imaging screening methods and disease-modifying therapies has been challenging, but knowledge of the transcriptomic features of emphysema may help in this effort. ObjectivesOur goals were to identify emphysema-associated biological pathways through transcriptomic analysis of bulk lung tissue, to determine the lung cell ...

IntroductionCoronavirus disease 2019 (COVID-19) is a respiratory infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This virus uses the angiotensin converting enzyme II (ACE-2) as the cellular entry receptor to infect the lower respiratory tract. Because individuals with chronic obstructive pulmonary disease (COPD) are at increased risk of severe COVID-19, we determined whether ACE-2 expression in the lower airways was related to COPD and cigarette smoking. Me...

ObjectiveCirculating fibrocytes are elevated in idiopathic pulmonary fibrosis, but the relationship between fibrocyte level with lung function decline and outcomes is lacking replication in prospective clinical study. We aim to validate the utility of circulating fibrocyte levels as a prognostic biomarker in idiopathic pulmonary fibrosis. MethodsWe tested associations between circulating fibrocyte levels, mortality, disease progression and longitudinal lung function in a well-defined prospectiv...

BackgroundWhile low body mass index (BMI) is associated with emphysema and obesity is associated with airway disease in chronic obstructive pulmonary disease (COPD), the underlying mechanisms are unclear. MethodsWe aggregated genetic variants from population-based genome-wide association studies to generate a polygenic score of BMI (PGSBMI). We calculated this score for participants from COPD-enriched and community-based cohorts and examined associations with automated quantification and visual...

RationaleChronic obstructive pulmonary disease (COPD) is characterized by pathologic changes in the airways, lung parenchyma, and persistent inflammation, but the links between lung structural changes and patterns of systemic inflammation have not been fully described. ObjectivesTo identify novel relationships between lung structural changes measured by chest computed tomography (CT) and systemic inflammation measured by blood RNA sequencing. MethodsCT scan images and blood RNA-seq gene expres...

BackgroundDiversity in response to exposition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is common and may be related to the innate immune response. The mucin MUC5B is an important component of the innate immune response and expression levels are associated with the MUC5B promoter polymorphism, rs35705950. The high expressing T-allele of rs35705950 is an accepted risk allele for a non-infectious aging lung disease called idiopathic pulmonary fibrosis (IPF). However, given th...