Discovery and development of INNA-051, a TLR2/6 agonist for the prevention of complications resulting from viral respiratory infections.

Viral respiratory infection is associated with significant morbidity and mortality. The diversity of viruses implicated, coupled with their propensity for mutation, ignited an interest in host-directed antiviral therapies effective across a wide range of viral variants. Toll-like receptors (TLRs) are potential targets for the development of broad-spectrum antivirals given their central role in host immune defenses.

Evaluation of intranasal TLR2/6 agonist INNA-051: safety, tolerability and proof of pharmacology.

Background: Local priming of the innate immune system with a Toll-like receptor (TLR)2/6 agonist may reduce morbidity and mortality associated with viral respiratory tract infections, particularly for the elderly and those with chronic diseases. The objectives of the present study were to understand the potential of prophylactic treatment with a TLR2/6 agonist as an enhancer of innate immunity pathways leading to accelerated respiratory virus clearance from the upper airways.

Methods: Two randomised, double-blind, placebo-controlled clinical trials were conducted in healthy adult participants.

The COPD Foundation on Its Twentieth Anniversary.

This article does not contain an abstract.

Five-Year Outcomes among U.S. Bronchiectasis and NTM Research Registry Patients.

Nontuberculous mycobacteria (NTM) are prevalent among patients with bronchiectasis. However, the long-term natural history of patients with NTM and bronchiectasis is not well described. To assess the impact of NTM on 5-year clinical outcomes and mortality in patients with bronchiectasis.

Accelerated elastin degradation by age-disease interaction: a common feature in age-related diseases.

Aging is a major driving force for many diseases but the relationship between chronological age, the aging process and age-related diseases is not fully understood. Fragmentation and loss of ultra-long-lived elastin are key features in aging and several age-related diseases leading to increased mortality. By comparing the relationship between age and elastin turnover with healthy volunteers, we show that accelerated elastin turnover by age-disease interaction is a common feature of age-related diseases.

Circulating testosterone levels and health outcomes in chronic obstructive pulmonary disease: results from ECLIPSE and ERICA.

Unlabelled: The relationship of circulating testosterone levels with health outcomes in people with chronic obstructive pulmonary disease (COPD) is unknown.

Aim: To determine whether serum testosterone levels predict hospitalised acute exacerbations of COPD (H-AECOPD), cardiovascular disease outcome, and mortality in people with COPD.

Methods: Separate analyses were carried out on two observational, multicentre COPD cohorts, Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) and Evaluation of the Role of Inflammation in Chronic Airways Disease (ERICA), both of which had serum testosterone measured using a validated liquid chromatography assay at the same laboratory.

An Update on Outcomes for COPD Pharmacological Trials: A COPD Investigators Report - Reassessment of the 2008 American Thoracic Society/European Respiratory Society Statement on Outcomes for COPD Pharmacological Trials.

In 2008, a dedicated American Thoracic Society/European Respiratory Society task force published a paper on the possible use and limitations of clinical outcomes and biomarkers to evaluate the impact of pharmacological therapy in patients with chronic obstructive pulmonary disease. Since then, our scientific understanding of chronic obstructive pulmonary disease has increased considerably; there has been a progressive shift from a one-size-fits-all diagnostic and therapeutic approach to a personalized approach; and many new treatments currently in development will require new endpoints to evaluate their efficacy adequately. The emergence of several new relevant outcome measures motivated the authors to review advances in the field and highlight the need to update the content of the original report.

Airway dysbiosis accelerates lung function decline in chronic obstructive pulmonary disease.

Progressive lung function decline is a hallmark of chronic obstructive pulmonary disease (COPD). Airway dysbiosis occurs in COPD, but whether it contributes to disease progression remains unknown. Here, we show, through a longitudinal analysis of two cohorts involving four UK centers, that baseline airway dysbiosis in COPD patients, characterized by the enrichment of opportunistic pathogenic taxa, associates with a rapid forced expiratory volume in 1 s (FEV) decline over 2 years.

The COPD Foundation's COPD360Net Initiative Approach to Patient-Centric Drug Development: A Case Study in Using Patient Surveys to Inform New Treatments for Viral Respiratory Infections.

Patient-centric drug development is crucial to creating treatments that address unmet patient needs but is often ignored. The COPD Foundation's COPD360Net includes a multistakeholder approach for operationalizing patient-centric development of treatments where patients, caregivers, scientists, and clinicians review opportunities based on scientific merit, potential to address an unmet need, and feasibility of adoption. COPD360Net deploys large-scale online community surveys to review profiles of potential therapies based on those criteria.

A Telemedicine Approach for Monitoring COPD: A Prospective Feasibility and Acceptability Cohort Study.

Background: Telemedicine may help the detection of symptom worsening in patients with chronic obstructive pulmonary disease (COPD), potentially resulting in improved outcomes. This study aimed to determine the feasibility and acceptability of telemedicine among patients with COPD and physicians and facility staff in Japan.

Methods: This was a 52-week multicenter, prospective, single-arm, feasibility and acceptability cohort study of Japanese patients ≥40 years of age with COPD or asthma-COPD overlap.

A genome-wide association study of bronchodilator response in participants of European and African ancestry from six independent cohorts.

Introduction: Bronchodilator response (BDR) is a measurement of acute bronchodilation in response to short-acting β2-agonists, with a heritability between 10 and 40%. Identifying genetic variants associated with BDR may lead to a better understanding of its complex pathophysiology.

Methods: We performed a genome-wide association study (GWAS) of BDR in six adult cohorts with participants of European ancestry (EA) and African ancestry (AA) including community cohorts and cohorts ascertained on the basis of obstructive pulmonary disease.

Ambient Air Pollution and Dysanapsis: Associations with Lung Function and Chronic Obstructive Pulmonary Disease in the Canadian Cohort Obstructive Lung Disease Study.

Outdoor air pollution is a potential risk factor for lower lung function and chronic obstructive pulmonary disease (COPD). Little is known about how airway abnormalities and lung growth might modify this relationship. To evaluate the associations of ambient air pollution exposure with lung function and COPD and examine possible interactions with dysanapsis.

Exhaled volatile organic compounds and lung microbiome in COPD: a pilot randomised controlled trial.

Background: Breath analysis is a burgeoning field, with interest in volatile organic compounds (VOCs) as a noninvasive diagnostic tool or an outcome measure, but no randomised controlled trials (RCTs) have yet evaluated this technology in a clinical trial longitudinally. In a pilot RCT, our exploratory objectives were feasibility of measuring VOCs multiple techniques, assessing relationships between VOCs and colonisation and whether CXCR2 antagonism with danirixin altered lung microbiome composition in individuals with COPD.

Method: 43 participants had VOCs and sputum biomarkers evaluated.

Prevalence and Characteristics of Individuals with Preserved Ratio Impaired Spirometry (PRISm) and/or Impaired Lung Function in Japan: The OCEAN Study.

Purpose: Many individuals with obstructive airway disease (OAD), including chronic obstructive pulmonary disease (COPD) and asthma, remain undiagnosed, despite the potential for reducing disease burden through early detection and treatment. OCEAN aimed to determine the prevalence of, and characteristics associated with, impaired lung function in a Japanese population, with the goal of improving strategies for early OAD detection.

Methods: OCEAN was an observational, cross-sectional study in sequentially recruited Japanese individuals ≥40 years of age undergoing routine health examinations.

Investigation of the Clinical, Radiological and Biological Factors Associated with Disease Progression, Phenotypes and Endotypes of COPD in China (COMPASS): study design, protocol and rationale.

COPD is heterogeneous, and its presentation varies between countries. The major COPD cohort studies have only been performed in Western populations; the disease is not well characterised in other regions. The COMPASS (Investigation of the Clinical, Radiological and Biological Factors, Humanistic and Healthcare Utilisation Burden Associated with Disease Progression, Phenotypes and Endotypes of COPD in China; NCT04853225) is a prospective, 2.

Utility of Self-Administered Questionnaires for Identifying Individuals at Risk of COPD in Japan: The OCEAN (Okinawa COPD casE finding AssessmeNt) Study.

Purpose: A considerable proportion of patients with chronic obstructive pulmonary disease (COPD) remain undiagnosed and untreated even though they may have a burden of respiratory symptoms that impact quality of life. The OCEAN study assessed the ability of screening questionnaires to identify individuals with, or at risk of, COPD by comparing questionnaire outcomes with spirometric measures of lung function.

Methods: This observational study included participants ≥40 years of age presenting for their annual health examination at a single medical center in Okinawa, Japan.

InforMing the PAthway of COPD Treatment (IMPACT) trial: fibrinogen levels predict risk of moderate or severe exacerbations.

Background: Fibrinogen is the first qualified prognostic/predictive biomarker for exacerbations in patients with chronic obstructive pulmonary disease (COPD). The IMPACT trial investigated fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus FF/VI and UMEC/VI in patients with symptomatic COPD at risk of exacerbations. This analysis used IMPACT trial data to examine the relationship between fibrinogen levels and exacerbation outcomes in patients with COPD.

Validation of the Summit Lab Score in Predicting Exacerbations of Chronic Obstructive Pulmonary Disease Among Individuals with High Arterial Stiffness.

Introduction: The presence of cardiovascular (CV) risk factors and CV disease in patients with chronic obstructive pulmonary disease (COPD) leads to worse outcomes. A number of tools are currently available to stratify the risk of adverse outcomes in these patients with COPD. This post hoc analysis evaluated the Summit Lab Score for validation as a predictor of the first episode of moderate-to-severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and other outcomes, in patients with COPD and high arterial pulse wave velocity (aPWV).

Inflammatory Endotype-associated Airway Microbiome in Chronic Obstructive Pulmonary Disease Clinical Stability and Exacerbations: A Multicohort Longitudinal Analysis.

Understanding the role of the airway microbiome in chronic obstructive pulmonary disease (COPD) inflammatory endotypes may help to develop microbiome-based diagnostic and therapeutic approaches. To understand the association of the airway microbiome with neutrophilic and eosinophilic COPD at stability and during exacerbations. An integrative analysis was performed on 1,706 sputum samples collected longitudinally from 510 patients with COPD recruited at four UK sites of the BEAT-COPD (Biomarkers to Target Antibiotic and Systemic COPD), COPDMAP (Chronic Obstructive Pulmonary Disease Medical Research Council/Association of the British Pharmaceutical Industry), and AERIS (Acute Exacerbation and Respiratory Infections in COPD) cohorts.

Markers of disease activity in COPD: an 8-year mortality study in the ECLIPSE cohort.

Rationale: There are no validated measures of disease activity in COPD. Since "active" disease is expected to have worse outcomes ( mortality), we explored potential markers of disease activity in patients enrolled in the ECLIPSE cohort in relation to 8-year all-cause mortality.

Methods: We investigated 1) how changes in relevant clinical variables over time (1 or 3 years) relate to 8-year mortality; 2) whether these variables inter-relate; and 3) if any clinical, imaging and/or biological marker measured cross-sectionally at baseline relates to any activity component.

CXCL-8-dependent and -independent neutrophil activation in COPD: experiences from a pilot study of the CXCR2 antagonist danirixin.

https://bit.ly/32SeisO.

Bacteria and sputum inflammatory cell counts; a COPD cohort analysis.

Background: There is evidence that bacterial colonisation in chronic obstructive pulmonary disease (COPD) is associated with increased neutrophilic airway inflammation. This study tested the hypothesis that different bacterial phyla and species cause different inflammatory profiles in COPD patients.

Methods: Sputum was analysed by quantitative polymerase chain reaction (qPCR) to quantify bacterial load and 16S rRNA gene sequencing to identify taxonomic composition.