Konstantinos Kostikas

Background: The behavior of fractional exhaled nitric oxide (FeNO) during treated COPD exacerbations and its agreement with blood eosinophil counts are poorly characterized. Objectives: To describe serial FeNO trajectories across hospitalized COPD exacerbations (AECOPDs), assess concordance between FeNO and blood eosinophils, and test whether these can predict length of stay (LOS). Methods: Prospective cohort of patients hospitalized for AECOPD. FeNO was measured on admission, on day 2 and at discharge; blood eosinophils and post-bronchodilator spirometry on admission and before discharge; and arterial blood gases on admission and on day 2. The admission measurements preceded the first dose of corticosteroid. All patients received guideline-directed treatment, including systemic corticosteroids. Results: Most patients were male (94.7%), with a mean age of 71.7 ± 8.3 years. FeNO fell from 16 (IQR 10–25) ppb on admission to 13.5 (7–20) ppb on day 2 and 9 (6–18) ppb at discharge (p < 0.001). Blood eosinophils fell from 60 (20–150) to 0 (0–40) cells/µL (p < 0.001), and FEV1 increased from 38% to 45% predicted (p < 0.001). Agreement between biomarkers on admission was poor (ρ = 0.21, p = 0.07; κ = 0.08, 95% CI −0.15 to +0.30), and 31 patients (40.8%) were classified differently by the two markers. Admission FeNO (ρ = 0.03, p = 0.79), ΔFeNO (ρ = −0.12, p = 0.31), and admission eosinophils (ρ = −0.08, p = 0.49) were not associated with LOS. Of the patients who were type-2-high on admission (FeNO ≥ 20 ppb), 57% had fallen below that threshold by day 2 and 62% by discharge (71% and 71%, respectively, at ≥25 ppb). Over the admission-to-discharge interval, the changes in the two markers were unrelated once each was adjusted for its own admission value (partial ρ = 0.05, p = 0.73), and there was no agreement on the direction of change (κ = 0.03). Conclusions: FeNO progressively declines during treated AECOPD, alongside a fall in the blood eosinophil count, so that the type-2 label assigned on admission is no longer valid for most patients 48 h later. FeNO and blood eosinophils identified largely non-overlapping patients, and no biomarker predicted length of stay.

Background: Dupilumab, mepolizumab, and benralizumab have each demonstrated efficacy in placebo-controlled trials for chronic obstructive pulmonary disease (COPD) with type 2 inflammation. However, no head-to-head trials or real-world comparative effectiveness studies have been reported. We aimed to compare the effectiveness of dupilumab, mepolizumab, and benralizumab in patients with COPD using propensity score-matched cohort analyses. Design: Retrospective cohort study using the TriNetX US Collaborative Network. Methods: Adults with COPD initiating dupilumab, mepolizumab, or benralizumab between 2022 and 2025 were identified. Biologic-naive new users were included in two pairwise comparisons: dupilumab versus mepolizumab and dupilumab versus benralizumab. Propensity score matching (1:1) balanced baseline characteristics. The primary outcome was COPD exacerbation; secondary outcomes included acute respiratory failure, pneumonia, and bronchitis over 365 days. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Results: Propensity score matching identified 3078 dupilumab–mepolizumab pairs and 2109 dupilumab–benralizumab pairs. Compared with mepolizumab, dupilumab was associated with a numerically lower risk of COPD exacerbation (HR, 0.76; 95% CI, 0.57– 1.01) and a significantly lower risk of bronchitis (HR, 0.69; 95% CI, 0.49– 0.98). No significant differences were observed between dupilumab and benralizumab for COPD exacerbation (HR, 0.98; 95% CI, 0.70– 1.40), acute respiratory failure, pneumonia, or bronchitis. Conclusion: In this large real-world cohort study, no statistically significant difference in COPD exacerbation risk was observed between dupilumab and mepolizumab or between dupilumab and benralizumab. However, blood eosinophil counts and baseline lung function measurements were not available in the dataset, so residual confounding cannot be excluded.

Purpose: Patient adherence and satisfaction are critical for effective asthma and chronic obstructive pulmonary disease (COPD) management, as adherence strongly influences symptoms and prognosis. Patient-reported outcomes, including treatment satisfaction and quality of life, provide valuable insights into the effectiveness of therapeutic interventions from the perspective of individual patients. This study evaluated patient satisfaction with the Elpenhaler device and its impact on quality of life in routine clinical practice. Patients and methods: Individual participant data were pooled from seven real-life studies of fixed-dose combinations delivered via the Elpenhaler device (asthma, budesonide/formoterol: BOREAS, SKIRON, COMPLETE, NOTOS; COPD, salmeterol/fluticasone: AEOLOS, AHEAD, RETRIEVE). Patient satisfaction was assessed with the Feeling of Satisfaction with Inhaler (FSI-10) questionnaire in the four studies in which it was administered, and quality of life in asthma with the mini Asthma Quality of Life Questionnaire (mAQLQ) at baseline, 3 and 6 months. The minimum clinically important difference (MCID) was defined as a change of at least 0.5 units in the mAQLQ total score. Results: In 4333 patients with evaluable FSI-10 score, overall satisfaction was high (mean total score 44.1, standard deviation 5.4), with 94.5% of patients expressing confidence in correct usage. Multivariable analysis showed that age ≥ 65 years, male sex and lower education level were independently associated with lower satisfaction, whereas never smoking predicted higher satisfaction. In 4212 patients with asthma, mAQLQ total score improved from 4.52 at baseline to 6.06 at 3 months and 6.27 at 6 months; the MCID was achieved by 83.4% and 87.8% of evaluable patients, respectively. Never smoking and lower education level predicted MCID achievement. Conclusion: Treatment delivered via the Elpenhaler is associated with high patient satisfaction and with significant and sustained improvements in quality of life, supporting its effectiveness in real-world respiratory care. The identification of factors associated with satisfaction and quality of life improvement may help in personalising treatment and optimising care.

Background: Chronic obstructive pulmonary disease (COPD) is frequently complicated by acute respiratory failure, pneumonia, exacerbations, and premature mortality, particularly in patients with comorbid type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) possess anti-inflammatory and metabolic properties that may confer protective effects against COPD-related respiratory complications, but comparative evidence remains limited. Methods: We conducted a retrospective cohort study using data from the TriNetX global federated health research network. Adults aged 40 years or older with both COPD and T2D who newly initiated GLP-1RAs, dipeptidyl peptidase-4 inhibitors (DPP-4is), sulfonylureas (SUs), or metformin between 1 January 2017 and 31 May 2025 were identified. An active-comparator, new-user design with 1:1 propensity score matching was applied. The primary outcome was incident acute respiratory failure. Secondary outcomes included all-cause mortality, all-cause hospitalization, acute exacerbation of COPD, and pneumonia, assessed over 1 year of follow-up. Results: After propensity score matching, GLP-1RA use was associated with significantly lower risk of acute respiratory failure compared with DPP-4is (HR, 0.77; 95% CI, 0.73–0.81), SUs (HR, 0.80; 95% CI, 0.76–0.84), and metformin (HR, 0.91; 95% CI, 0.85–0.98). GLP-1RA use was also consistently associated with reduced risks of all-cause mortality, all-cause hospitalization, acute exacerbation of COPD, and pneumonia across all three comparator groups. Subgroup analyses demonstrated consistent protective trends across sex, age, exacerbation history, and inhaled bronchodilator regimen. Conclusions: In patients with COPD and T2D, initiation of GLP-1RAs was associated with significantly lower risks of acute respiratory failure, pneumonia, acute exacerbation, hospitalization, and all-cause mortality compared with DPP-4is, SUs, and metformin. These findings suggest that GLP-1RA therapy may offer meaningful respiratory and survival benefits in this high-risk population.

Purpose: Time to biologic initiation for the treatment of severe asthma (SA) is affected by many factors, including ease of access to biologics, which is often subject to approval by regulatory authorities and reimbursement criteria by relevant agencies. We investigated the association between ease of biologic access (using the biologic accessibility score [BACS] as a proxy) and post-biologic asthma outcomes, including remission. Methods: This ecological study, using data from CHRONICLE (a US severe asthma registry), the International Severe Asthma Registry (ISAR), and the Optimum Patient Care Research Database (OPCRD), included patients with SA from 21 countries. Associations at the country level, between BACS, a composite score of prescription criteria for biologics in SA, and the proportion of patients with a favorable asthma outcome 1-year post-biologic in each setting (ie ISAR country or in the CHRONICLE or OPCRD datasets) were tested. Several definitions of favorable outcome were used, including proportion of patients who achieved clinical remission (defined using 2, 3 and 4 domains), experienced no exacerbations, had well- or partly controlled asthma, a percent predicted forced expiratory volume in 1 second (ppFEV₁) or percent predicted peak expiratory flow rate (ppPEFR) ≥ 80%, and no long-term oral corticosteroid (LTOCS) use. Results: A total of 9,183 patients were included. A higher BACS (as a proxy of easier access to biologics) was associated with a higher likelihood of achieving clinical remission (p≤ 0.001), no exacerbations (p< 0.001), well- or partly controlled asthma (p=0.047), a ppFEV₁ or ppPEFR ≥ 80% (p=0.004), and no need for LTOCS (p=0.045) 1 year post-biologic initiation. Conclusion: Easier access to biologics for patients with SA, a prerequisite for shorter time-to-initiation, was associated with a greater probability of achieving clinical remission and other favorable asthma outcomes. Initiating biologics earlier in the asthma disease course may help unlock greater therapeutic potential in SA. These findings warrant confirmation in additional studies to further establish the causal relationship between biologic accessibility, timing of initiation, and clinical outcomes in SA.

Background: COPD control evaluates changes in patients’ status based on clinical impact and stability. There are limited data on the effectiveness of dual bronchodilation on COPD control. Methods: REDACT was a multicenter, prospective, single-arm, longitudinal real-life observational study that evaluated COPD control in uncontrolled COPD patients after 12 weeks of treatment with aclidinium/formoterol (Duaklir Genuair^®). Eligible patients were previously receiving any inhaled medication except triple therapy (fixed or open combinations). The primary objective was to assess the proportion of patients who achieved COPD control after 12 weeks. Secondary aims included changes in COPD assessment test (CAT) and forced expiratory volume in 1 second (FEV₁). Results: A total of 1038 patients with uncontrolled COPD, mean age 68.9 years, 69.6% male, were recruited and 1014 (97.7%) completed follow-up. The proportion of patients who achieved COPD control at 12 weeks was 83.7% (95% CI 81.3 to 86.0%). Low baseline FEV₁ (% pred), history of moderate/severe exacerbation in the past year and history of cardiovascular disease were predictors of lack of control. Change from baseline in FEV₁ was 124.8 mL (95% CI 108.7 to 141.0 mL, p< 0.001) and in CAT score − 7.6 points (95% CI − 7.9 to 7.3 points, p< 0.001). Proportions of patients that achieved the minimally clinically important difference of +100 mL in FEV₁ and − 2 points in the CAT score were 50.4% and 90.5%, respectively. Conclusion: After 12 weeks of treatment with aclidinium/formoterol, a significant proportion of uncontrolled COPD patients achieved COPD control, with significant improvements in lung function and health status.

The management of chronic obstructive pulmonary disease (COPD) has changed significantly in this century, the most important element being the introduction of long-acting bronchodilators (LABD) as the basis of the treatment of patients with symptomatic disease. The benefits of dual bronchodilators versus mono-bronchodilators have been shown in randomized trials and in real-life observational studies and include, besides the expected improvement in lung function, improvement in symptoms, quality of life and exercise capacity, better exacerbation prevention and potential cardiovascular benefits in patients with hyperinflation, with an acceptable safety profile. Dual bronchodilators can be the first-line agents in all symptomatic patients, as well as in exacerbating patients (especially if they have lower blood eosinophils and their exacerbations were treated with antibiotics). The place for mono-LABD (mainly long-acting muscarinic antagonists [LAMA]) remains for the less symptomatic patients without severe hyperinflation. Modern COPD management incorporates the individualized approach of each COPD patient with the appropriate treatment.

IntroductionAsthma is a complex and heterogenous disease marked by chronic airway inflammation, and variable respiratory symptoms (1). Severe asthma, defined as asthma that remains difficult to man...

Background/Objectives: The coexistence of chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2D) poses significant clinical challenges due to overlapping mechanisms of systemic inflammation, oxidative stress, hypoxia, and metabolic dysregulation. Patients with both conditions face higher risks of exacerbations, prolonged hospitalizations, cardiovascular events, and reduced quality of life. This review aims to summarize current evidence on the pathophysiological interplay between COPD and T2D and to evaluate the impact of lifestyle and pharmacologic interventions. Methods: A narrative review of the literature was conducted to evaluate the pathophysiological links between COPD and T2D, assess the effects of pharmacologic and lifestyle interventions, and highlight key gaps and priorities for future research, with an emphasis on integrated, evidence-based management for this high-risk population. Results: Lifestyle interventions, including smoking cessation and structured physical activity, remain foundational to management. Emerging evidence indicates that antidiabetic therapies, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium–glucose cotransporter-2 inhibitors (SGLT-2is), may confer additional pulmonary, metabolic, and cardiovascular benefits. These agents modulate systemic inflammation, oxidative stress, endothelial function, and insulin sensitivity, potentially reducing COPD exacerbations, improving lung function, and enhancing survival. Safety concerns, including glucocorticoid-induced hyperglycaemia and hypoxia-related metabolic complications, underscore the need for careful monitoring and individualized therapy COPD patients. Conclusions: Optimal care requires a multidisciplinary, patient-centred approach integrating pulmonology, endocrinology, primary care, nutrition, and rehabilitation, alongside shared decision-making and patient education. Despite promising findings, critical knowledge gaps remain. Large, well-designed randomized controlled trials and standardized definitions are needed to guide personalized therapeutic strategies.