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.

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).

Post-COVID-19 exaggerated exertional tachycardia: Relationship with pulmonary and cardiac sequelae.

Background: Long-COVID patients frequently complain of an Exaggerated Exertional Tachycardia (EET) and may represent a specific phenotype of post-COVID tachycardia syndrome. So far, no studies have investigated the factors contributing to EET.

Objectives: To determine the predictor factors of EET, seventy-nine Long-COVID-19 patients underwent comprehensive cardiologic and respiratory evaluations at follow-up visit after a median of 23 weeks from the acute phase of the disease.

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.

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.

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.

Breathing pattern and ventilatory response to exercise in patients with Chronic Obstructive Pulmonary Disease.

Background: Patients with Chronic Obstructive Pulmonary Disease (COPD) show ventilatory limitation to exercise due to dynamic hyperinflation (DH). Breathing pattern can be expressed by T/T (inspiratory time/total time) and V/T (tidal volume/inspiratory time). Both parameters significantly increase during exertional hyperpnea in healthy subjects, but they have never been studied in COPD.

Animal models of chronic obstructive pulmonary disease and their role in drug discovery and development: a critical review.

Introduction: The use of laboratory animals is essential to understand the mechanisms underlying COPD and to discover and evaluate new drugs. However, the complex changes associated with the disease in humans are difficult to fully replicate in animal models.

Areas Covered: This review examines the most recent literature on animal models of COPD and their implications for drug discovery and development.

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.

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.

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.

Clinical efficacy of inhaled corticosteroids in equine asthma: A meta-analysis and number needed to treat.

Equine asthma, a prevalent chronic inflammatory condition affecting the equine population, significantly compromises the performance and quality of life in affected horses. Inhaled corticosteroids (ICS) are often the first-line pharmacological intervention due to their potent anti-inflammatory properties. This meta-analysis investigates the clinical efficacy of ICS in treating equine asthma, emphasizing the number needed to treat (NNT) and the likelihood of achieving a clinical response.

The need for inhaled phosphodiesterase inhibitors in chronic obstructive pulmonary disease.

Introduction: The therapeutic implications of phosphodiesterase (PDE) inhibitors have attracted interest because PDEs are regarded as an intracellular target to be exploited for therapeutic advancements in the treatment of COPD. At present, the only approved approach for the treatment of COPD with PDE inhibitors is the use of an oral PDE4 inhibitor. However, this treatment is not widely employed, primarily due to the narrow therapeutic index associated with oral PDE4 inhibitors, which significantly limits the tolerable dose.

Emerging Anti-Inflammatory COPD Treatments: Potential Cardiovascular Impacts.

Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory condition often complicated by cardiovascular disease (CVD) due to shared inflammatory pathways. This review explores the cardiovascular impacts of emerging anti-inflammatory therapies in COPD. Phosphodiesterase (PDE) inhibitors may offer anti-inflammatory effects with improved lung function but pose potential risks for arrhythmias when PDE3 is inhibited although PDE4 inhibitors reduce cardiovascular events by improving endothelial function and reducing thrombosis.

Impact of N-Acetylcysteine on Mucus Hypersecretion in the Airways: A Systematic Review.

Mucus clearance is crucial for airway protection, and its dysfunction leads to chronic obstructive pulmonary disease (COPD) characterized by mucus hypersecretion (MHS) and impaired clearance. MUC5AC and MUC5B mucin proteins are key components of airway mucus, with MUC5AC being particularly responsive to environmental stimuli, making it a potential COPD biomarker. N-acetylcysteine (NAC) is a mucolytic agent with known effects on mucus viscosity and clearance, but its precise mechanisms in COPD remain unclear.

β-Blockers and Asthma: Surprising findings from the FAERS database.

Introduction: β-Blockers are essential for cardiovascular disease management but can induce respiratory issues, particularly with non-selective β-blockers. Their safety in asthmatic patients is debated.

Objective: This study investigates the link between different classes of β-blockers and the risk of asthma and asthma-like adverse events (AEs) using data from the Food and Drug Administration's Adverse Event Reporting System (FAERS).

Real-World Efficacy of Biological Therapies in Severe Asthma: A Focus on Small Airways.

: Severe asthma is a challenging condition that often resists traditional treatments and requires high-dose inhaled corticosteroids and other controllers to manage uncontrolled symptoms. Recent advances include the use of biologic agents targeting specific inflammation pathways, which have improved symptom control and quality of life, although their effects on small airways remain less understood. : This prospective observational study, conducted at Tor Vergata University Hospital in Rome from July 2021 to March 2024, aims to evaluate the efficacy of treatments in patients with uncontrolled severe asthma.