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.

Efficacy without resolution: A critical appraisal of mepolizumab in eosinophilic COPD.

Mepolizumab reduces exacerbations in eosinophilic COPD but shows limited effects on symptoms, lung function, or quality of life. The MATINEE trial supports a precision medicine approach targeting high blood eosinophil counts. However, IL-5 blockade alone may be insufficient due to complex, overlapping inflammatory pathways and persistent lung-resident eosinophils.

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.

A precision medicine approach to the myelodysplastic syndrome with isolated deletion 5q 50 years after its discovery.

In 1974, Vanden Berghe et al described a distinct hematologic disorder associated with acquired, interstitial deletion of part of the long arm of chromosome 5. This condition is now classified as myelodysplastic syndrome (MDS) with isolated deletion 5q, or MDS-del(5q). The common deletion region 5q32-5q33 contains several genes and microRNAs whose expression levels are reduced in hematopoietic cells, consistent with the loss of one allele.

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.

Targeting neutrophilic inflammation in obstructive airway disease - A narrative review of brensocatib therapy.

Brensocatib is an oral inhibitor of dipeptidyl peptidase 1, an enzyme that activates neutrophil serine proteases. Its potential to reduce neutrophil-driven inflammation has generated interest across a range of chronic inflammatory and respiratory conditions, particularly non-cystic fibrosis (CF) bronchiectasis. As the body of evidence supporting brensocatib continues to expand, there is a clear need for a comprehensive, rigorous, and practical narrative review to consolidate current knowledge and highlight gaps for future research.

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).

Multimodal and Data-Driven Assessment of Myeloid Neoplasms Refines Classification across Disease States.

Unlabelled: The World Health Organization fifth edition and International Consensus Classification for myeloid neoplasms both incorporate empirical numerical thresholds to morphologic and molecular features defining certain disease entities. However, the clinical implications of these thresholds remain unclear. We analyzed a large cohort (N = 6,976) of patients with myeloid neoplasms to evaluate the impact of proposed yet different numerical thresholds for variant allele frequency of genetic mutations or hematologic parameters set forth by the World Health Organization fifth edition and International Consensus Classification for classification of SF3B1-mutated myelodysplastic neoplasms, NPM1-mutated acute myeloid leukemia (AML), and oligomonocytic chronic myelomonocytic leukemia.

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.

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.

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.

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.

The ongoing challenge of prevention of pertussis in infants: what's new in 2024?

Introduction: Pertussis, a respiratory disease caused primarily by , is undergoing a resurgence despite decades of high rates of vaccination. The prevention of pertussis in infants presents several challenges, including the waning immunity of the acellular pertussis (aP) vaccine, the limited protection afforded to newborns before they complete the vaccine series, and the existence of gaps in maternal vaccination. Furthermore, the unwillingness or refusal of a considerable number of individuals, including some healthcare workers, to receive vaccinations represents another significant challenge.

Mucolytic Therapy in COPD: Patient Usage and Preferences in Real-World Italian Settings.

Introduction: The Italian COPD Patient Association (Associazione Pazienti BPCO) conducted an online survey among its 2814 members with COPD to investigate the reasons for the widespread use of mucolytic therapies by patients, often including self-prescription using over the counter (OTC) alternatives.

Methods: After consulting with several respiratory specialists, the Association's steering committee developed a list of nine questions with possible answers that was posted on the website of the Association. The survey was open to all members of the Association, with responses to be e-mailed to the Association.

Clinical-genomic profiling of MDS to inform allo-HCT: recommendations from an international panel on behalf of the EBMT.

For patients with myelodysplastic neoplasm/syndrome (MDS), allogeneic hematopoietic cell transplantation (allo-HCT) represents the only potentially curative treatment, capable of eradicating disease-related mutant hematopoietic cells and establishing normal donor hematopoiesis. Biologic-assignment clinical trials have indicated that in eligible patients, allo-HCT is associated with superior clinical outcomes compared with nontransplant therapy. However, this therapeutic option is only available to a subset of patients, and the outcome is influenced by multiple factors inherent to the patient, the MDS subtype, and the allo-HCT procedure itself.

In vitro studies of human erythropoiesis using a 3D silk-based bone marrow model that generates erythroblastic islands.

The pursuit of ex vivo erythrocyte generation has led to the development of various culture systems that simulate the bone marrow microenvironment. However, these models often fail to fully replicate the hematopoietic niche's complex dynamics. In our research, we use a comprehensive strategy that emphasizes physiological red blood cell (RBC) differentiation using a minimal cytokine regimen.

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.

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.

How I manage patients with unexplained cytopenia.

The term "unexplained cytopenia" is used to describe a condition characterized by peripheral blood cytopenia that cannot be attributed to identifiable causes using conventional tests or to any concomitant diseases. Unexplained cytopenia requires clinical attention and further investigation to identify individuals at risk of developing a hematologic neoplasm. The available evidence suggests that somatic mutation analysis may effectively complement the diagnostic workup and clinical management of unexplained cytopenia.

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.