Emerging Therapeutics in COPD: Mapping Innovation to Treatable Traits.

Chronic Obstructive Pulmonary Disease (COPD) is a complex, heterogeneous condition characterized by diverse clinical phenotypes and underlying pathobiological mechanisms. Traditional "one-size-fits-all" management strategies have limited effectiveness in addressing this heterogeneity. The Treatable Traits (TTs) approach represents a precision medicine paradigm that targets specific, identifiable, and modifiable traits in individual patients, regardless of diagnostic labels.

Comorbidities as treatable traits of chronic airway diseases.

Chronic airway diseases, including asthma, chronic obstructive pulmonary disease, and bronchiectasis, are increasingly recognized as heterogeneous conditions influenced not only by airway pathology but also by a wide range of extrapulmonary and behavioral comorbidities. The treatable traits (TT) model, as it has emerged in recent medical literature, offers a precision medicine framework that redefines comorbidities as clinically relevant, identifiable, and modifiable traits. This paradigm shifts the focus from conventional disease labels to a multidimensional approach that considers the individual's unique constellation of pulmonary, extrapulmonary, and psychosocial features.

Comparing major COPD triple therapy trials using a structured multi-criteria decision analysis: A deep dive into patient populations and outcomes.

Background: Triple inhaled therapy (ICS/LABA/LAMA) is widely recommended for managing COPD in patients with persistent symptoms or frequent exacerbations. However, variability in trial designs, populations, and pharmacologic formulations complicates direct comparison between regimens.

Objective: To evaluate the comparative performance of three triple therapies, FF/VI/UMEC, BUD/FOR/GLY, and BDP/FOR/GLY, using a multidimensional comparative decision analysis (MCDA) across key clinical domains.

Validation of "Clinical Red Flags" for RA-ILD in an Italian cohort.

Introduction: Rheumatoid arthritis (RA) is a systemic inflammatory disease, characterized by articular and extra-articular manifestations, including Interstitial Lung Disease (ILD). An early diagnosis of ILD can be essential in improving disease outcome. A clinical practice checklist has previously been proposed, highlighting red flags in signs and symptoms suggestive of RA-ILD.

Ensifentrine Plus a Long-Acting Muscarinic Antagonist in COPD: A Trifunctional Dual Bronchodilation Perspective.

Chronic obstructive pulmonary disease (COPD) management has evolved with the emergence of advanced pharmacological strategies, notably dual bronchodilation and bifunctional agents. Among these innovations, the selective inhaled phosphodiesterase (PDE)3/4 inhibitor ensifentrine represents a novel therapeutic class that combines bronchodilatory and anti-inflammatory properties within a single molecular entity. Dual bronchodilation, traditionally achieved through the combination of long-acting muscarinic antagonists (LAMAs) and long-acting β-agonists, has demonstrated superior efficacy compared with monotherapies, including enhanced pulmonary function, reduced symptom burden, and decreased exacerbation frequency.

A disproportionality analysis of diabetes mellitus in patients treated with biologics for asthma and related conditions using FAERS data.

Background: Biologics for asthma and related conditions target distinct immunologic pathways but may have differential effects on glucose metabolism. Emerging real-world evidence suggests a need to evaluate potential associations with diabetes mellitus (DM) and related metabolic adverse events (AEs).

Objective: To assess the disproportionality of DM and other metabolic AEs associated with six biologics approved for asthma and related conditions using data from the FDA Adverse Event Reporting System (FAERS).

Triple extrafine fixed-dose combination in asthma: from randomized controlled trials to real-world evidence.

Introduction: Small airway dysfunction affects 50-90% of asthmatic patients, leading to airway remodeling, worsening symptoms, and quality of life. Targeting small airway dysfunction with inhaled extrafine formulations, with a mass median aerodynamic diameter < 2 µm, is crucial. Triple extrafine fixed-dose combination with inhaled corticosteroids (ICS), long-acting β-agonists (LABA), and long-acting muscarinic antagonists (LAMA) been approved for uncontrolled asthma, supported by TRIMARAN and TRIGGER randomized controlled trials (RCT).

Biologics for severe asthma: deciphering what is best for the patient.

Introduction: Choosing the right biologic for the right patient is challenging. It requires evaluating patient characteristics and disease manifestations, understanding the scientific evidence supporting each biologic's efficacy and safety, and using a shared decision-making strategy with the patient.

Areas Covered: Based on a comprehensive review of the literature, in this narrative review we explore the latest approaches on the optimal selection of biologics in severe asthma.

Lung involvement in psoriatic arthritis patients: cross-sectional study on prevalence, clinical characteristics, and risk factors of a neglected comorbidity.

Objectives: We aimed to assess lung involvement in patients with psoriatic arthritis (PsA), hypothesising that lung diseases (LDs) represent a distinct comorbidity of PsA and that the association between these two conditions is not merely coincidental.

Methods: Cross-sectional study of 322 patients with a diagnosis of PsA from three Italian centres. Each patient underwent a chest high-resolution CT prior to the start of a biological DMARDs.

Real-World Effectiveness of Triple Extrafine Fixed-Dose Combination with Beclomethasone/Formoterol/Glycopyrronium on Symptoms and Lung Function in COPD: A Systematic Review and Meta-Analysis.

Introduction: Chronic obstructive pulmonary disease (COPD) is a significant global health issue characterized by persistent airflow limitation and inflammation. Triple fixed-dose combinations (FDCs) of inhaled corticosteroids (ICS), long-acting β2-agonists (LABA), and long-acting muscarinic antagonists (LAMA) show promise by potentially enhancing bronchodilation and anti-inflammatory effects. Although randomized controlled trials (RCTs) provide efficacy data, they may not fully represent real-world clinical practice, highlighting the value of real-world evidence (RWE).

The interplay between asthma and type 2 diabetes mellitus: mutual interactions and therapeutic implications.

Introduction: Asthma and type 2 diabetes mellitus (T2DM) are chronic diseases with a significant global health burden. Recent studies have highlighted the complex relationship between these two diseases, particularly regarding their pharmacological management.

Areas Covered: This review discusses the mechanisms linking asthma and T2DM and the interactions between asthma and T2DM therapies, highlighting the potential clinical implications.

Characterisation of the novel quinoline RCD405: Relaxant effects on cholinergic and histaminergic tone in human bronchi and small airways.

Background And Purpose: Increased contractility of human airway smooth muscle (hASM) is a hallmark of asthma and chronic obstructive pulmonary disease (COPD). Developing new classes of bronchodilators has proved to be challenging because of efficacy and safety concerns. Quinolines hold potential therapeutic applications for the treatment of respiratory disorders.

Skin prick test wheal size: a potential predictor of respiratory allergies?

Dear Editor, The skin prick test is the most commonly used method for diagnosing IgE-mediated sensitizations in conditions like bronchial asthma, allergic rhinitis, and food allergies...

Novel drug discovery strategies for chronic obstructive pulmonary disease: the latest developments.

Introduction: The journey from initial drug discovery to approval for respiratory diseases typically spans approximately 10.4 years and cost over $2.8 billion.

PI3K Inhibitors as Potential Therapeutic Agents for the Treatment of COPD with Associated Atherosclerosis.

Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) share a complex and multifactorial relationship characterized by overlapping risk factors, systemic inflammation, and intertwined pathophysiological mechanisms, with atherosclerosis emerging as a central inflammatory process connecting COPD and CVD, driven by systemic inflammation, oxidative stress, and endothelial dysfunction. While systemic inflammation is recognized as a critical link between these conditions, the precise pathways through which inflammation arises remain under investigation. There is therefore a need for therapeutic strategies to mitigate cardiovascular risks in patients with COPD.

Durability of benralizumab effectiveness in severe eosinophilic asthma patients with and without chronic rhinosinusitis with nasal polyps: a analysis from the ANANKE study.

Introduction: Severe eosinophilic asthma (SEA) often co-occurs with chronic rhinosinusitis with nasal polyps (CRSwNP), worsening asthma symptoms. Earlier studies have shown that benralizumab improves asthma outcomes with greater efficacy if patients present CRSwNP.

Methods: This analysis of the ANANKE study (NCT04272463) reports data on the long-term effectiveness of benralizumab between SEA patients with and without CRSwNP ( = 86 and  = 75, respectively) treated for up to 96 weeks.

Impact of Airway-Occluding Mucus Plugs on Mortality in Patients with COPD According to Disease Severity: A Subset Analysis of Data From COPDGene.

Background: Chronic mucus hypersecretion (CMH) in chronic obstructive pulmonary disease (COPD) is associated with severe outcomes, but its impact on mortality across COPD stages is not well understood. This study evaluated the risk of mortality according to mucus plugs and COPD severity.

Methods: A subset analysis was performed using secondary unadjusted data from published figures of a study on the COPDGene cohort.

An update on long-acting muscarinic agents for asthma therapy.

Introduction: The manifestations of asthma are influenced by the dysfunction of the autonomic nervous system, which results in elevated vagal tone within the airways. Acetylcholine (ACh) plays a pivotal role in the pathophysiology of asthma through its interaction with muscarinic acetylcholine receptors (mAChRs). Consequently, using mAChR antagonists to counteract the actions of ACh is scientifically sound.

Alteration of telomere length and mtDNA copy number in interstitial lung disease associated with rheumatoid arthritis.

Interstitial lung disease (ILD) is a common extra-articular manifestation of rheumatoid arthritis (RA). The inflammatory response in lung disease is characterized by severe oxidative stress, which enhances cellular senescence. Telomeric shortening and mitochondria dysregulation represent two hallmarks of cellular senescence.

Inhaled corticosteroids in chronic obstructive pulmonary disease: a systematic review and meta-analysis on mortality protection - making a long story short.

Introduction: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide, primarily due to persistent airflow limitation from tobacco and biomass smoke exposure. While inhaled corticosteroids (ICS) combined with long-acting bronchodilators, namely long-acting β-adrenoreceptor agonists (LABA) and long-acting muscarinic antagonists (LAMA), are recommended for symptom control and exacerbation reduction, their effect on mortality remains uncertain. Recent randomized controlled trials (RCTs) suggest potential mortality benefits with triple ICS/LABA/LAMA therapy, though findings are not definitive.

Genetic diversity of the immunoglobulin heavy chain locus in cohorts of patients affected with SARS-CoV-2.

Background: The Immunoglobulin Heavy Chain (IGH) genomic region is responsible for the production of circulating antibodies and warrants careful investigation for its association with COVID-19 characteristics. Multiple allelic variants within and across different IGH gene segments form a limited set of haplotypes. Previous studies have shown associations between some of these haplotypes and clinical outcomes of COVID-19.

Efficacy and safety of long-acting muscarinic antagonists in COPD: A meta-analysis and meta-regression with a focus on aging.

The increasing global elderly population, projected to reach 20 % of individuals aged 65 and over by 2030, faces significant pulmonary challenges, including chronic obstructive pulmonary disease (COPD). Aging is associated with a natural decline in lung function and structural changes that exacerbate respiratory issues. COPD, characterized by chronic respiratory symptoms and airflow obstruction, presents a unique challenge in older patients due to the accelerated decline in lung function.

Systematic Review and Meta-Analysis of the Application of T-PEP in the Therapeutic Management of COPD Patients.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide, characterized by chronic mucus hypersecretion (CMH) that exacerbates airway obstruction and accelerates disease progression. Effective airway clearance techniques are essential to improve respiratory function and reduce exacerbations. Temporary Positive Expiratory Pressure (T-PEP) is a novel airway clearance device that has shown promise in managing COPD.

Challenges in treating patients with comorbid asthma and bronchiectasis.

The management of patients with overlapping asthma and bronchiectasis requires a tailored approach, starting with a comprehensive assessment of the patient's clinical profile, including the severity of asthma and the extent of bronchiectasis. Inhaled corticosteroids (ICS) are often recommended, but their use should be carefully monitored because of the risk of increased infection. If asthma is well controlled and bronchiectasis remains stable, a gradual reduction in the dose of ICS may be considered.