Christos Kyriakopoulos

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treated AECOPD, alongside a fall in the blood eosinophil count, so that the type-2 label assigned on admission is no longer valid for most patients 48 h later.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.

Chronic obstructive pulmonary disease (COPD) is a major contributor to global respiratory morbidity and exhibits substantial sex- and gender-related differences in incidence, phenotype, pathophysiology, and outcomes across the life course. Historically regarded as a predominantly male disease due to higher smoking rates, COPD is now increasingly recognized among women, reflecting changing exposure patterns and enhanced diagnostic attention. Moreover, evidence indicates that women may be more biologically susceptible to the harmful effects of tobacco smoke and often develop COPD at younger ages. Clinical manifestations also differ, with women more frequently reporting dyspnea, anxiety, and depression, whereas men may exhibit more cough and sputum production. Imaging studies suggest that airway-predominant disease is more common in women, while men are more likely to demonstrate emphysema-predominant patterns. Furthermore, women face an increased risk of exacerbation, yet they are more likely to experience underdiagnosis or misdiagnosis. Treatment responses and comorbidity patterns also show sex- and gender-related variations. Despite these differences, most clinical guidelines and therapeutic strategies do not differentiate by sex and gender, highlighting a gap in personalized COPD management. Overall, growing evidence underscores the importance of incorporating sex and gender as biological and sociocultural variables in COPD research, diagnosis, and treatment. Recognizing sex/gender-specific risk profiles, symptom patterns, and disease phenotypes may improve early detection and enable more targeted, effective interventions. This narrative synthesis, derived from a meticulous search in PubMed and the critical selection of 74 articles from the 448 identified originally, integrates evidence from guideline statements, registry studies, mechanistic and preclinical research, imaging and physiology investigations, systematic reviews, and randomized controlled trials that report sex- and gender-disaggregated data.

Background: Multiple biologics targeting type 2 inflammation have been evaluated for the treatment of severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) separately. Objective: To evaluate the efficacy and safety of biologics in patients with comorbid asthma and CRSwNP. Methods: A systematic review of randomised controlled trials (RCTs) from Medline, Embase, Web of Science and Scopus (up to 31 October 2025) was conducted. Random-effects meta-analysis assessed efficacy and safety outcomes. Results: 16 studies involving 3598 patients were included in the meta-analysis. Overall, biologics reduced asthma exacerbations by 73% (rate ratio 0.27, 95% CI 0.21–0.34), increased forced expiratory volume in 1 s by 0.21 L (95% CI 0.11–0.30), improved asthma control questionnaire score by −0.70 points (95% CI −0.83–−0.56) and asthma quality of life questionnaire score by 0.71 points (95% CI 0.49–0.93). Regarding sino-nasal outcomes, the sino-nasal outcome test 22 (SNOT-22) score was reduced by 15.15 points (95% CI −19.64–−10.66), the nasal polyp score by 1.39 points (95% CI −1.88–−0.89), the Lund–Mackay computed tomography score by 6.64 points (95% CI −8.88–−4.40) and the nasal congestion/obstruction score by 0.84 points (95% CI −1.13–−0.54). Heterogeneity across biologic classes varied by outcome, ranging from low to substantial. Overall, biologics exhibited a favourable safety profile. Conclusions: Biologics significantly reduced asthma exacerbations, improved lung function, asthma control and quality of life, and alleviated sino-nasal outcomes in patients with comorbid asthma and CRSwNP, with an acceptable safety profile.

TB-IRIS is a rare complication of antitubercular therapy, particularly in immunocompetent patients. Timely recognition and initiation of corticosteroid therapy are crucial for effective management. https://bit.ly/4qH4RXB

Introduction: The efficacy of the fixed extrafine combination of beclomethasone/formoterol/glycopyrronium (BDP/FF/G 87/5/9 μg) has been evaluated in randomized controlled trials of patients with chronic obstructive pulmonary disease (COPD). However, only few data exist on its effectiveness on small airways dysfunction (SAD). Methods: The MASCOT (MAnaging Small airways dysfunction in COPD patients in real life on the fixed Triple combination of BDP/FF/G 87/5/9 μg pMDI) prospective observational study evaluated the effectiveness of this combination on SAD in a period of 4 weeks, after direct switch from long-acting β₂-agonists (LABA) and long-acting muscarinic antagonists (LAMA) in COPD patients with SAD (forced expiratory flow at 25– 75% of the vital capacity, FEF25-75% < 60% predicted). The primary endpoint was improvement in R5-19 in oscillometry; secondary endpoints included other oscillometry parameters, lung function and health status (COPD assessment test-CAT, Saint-George’s Respiratory Questionnaire-SGRQ). Results: Between May 2022 and July 2023 we recruited 93 COPD patients (mean age 68.5 years, 82% men) with forced expiratory volume in 1 second (FEV₁, mean ± SD) 1.53 ± 0.47L (53.4 ± 14.5% predicted) and small airways dysfunction (FEF25-75% predicted 27.7 ± 15.4%). We observed statistically significant improvement in R5-19 between baseline (V1) and follow-up (V2) visits [median (IQR) V2 0.70 (0.41– 1.10) vs V1 0.90 (0.60– 1.83); mean change (95% CI) − 0.49, − 0.66 to − 0.33 cmH₂O/L/sec, p < 0.0001). There were improvements in multiple parameters, including FEF25-75% (3.43, 1.20% to 5.66%, p = 0.0005), FEV₁ (0.142, 0.078 to 0.205 L, p < 0.0001) and RV/TLC (− 6.09, − 9.61% to − 2,56% predicted, p < 0.0001), as well as improvement in CAT score − 4.09 (− 5.09 to − 3.08) και SGRQ total score (− 8.75, − 11.58 to − 5.93 points, p < 0.0001). Conclusion: Extrafine triple therapy improved SAD and spirometric parameters, leading to improvement in health status at 4 weeks. These results need to be confirmed in longer studies.

Interstitial lung abnormalities (ILAs) are incidental radiologic abnormalities on chest computed tomography (CT) examination performed on people in whom interstitial lung disease (ILD) is not suspected. Despite the fact that most of these individuals are asymptomatic, ILAs are not synonymous with subclinical ILD, as a subset of them have symptoms and lung function impairment. On the other hand, not all ILAs progress to clinically significant ILD. Specific imaging features and patterns have been proven more likely to progress, while some individuals may comprise a higher risk group for progression. Numerous studies have demonstrated that ILAs are not only associated with an increased risk of progression toward pulmonary fibrosis and fibrosis-related mortality but are also linked to a greater incidence of lung cancer and a higher rate of all-cause mortality. Considering that the systematic evaluation of large cohorts has shown a prevalence of ILAs up to 7% and that the natural history of ILAs is unclear, successful screening and appropriate monitoring of ILAs is of particular significance for earlier diagnosis, risk factor modification, and treatment. The present review aims to summarize the current knowledge on ILAs and highlight the need to define those at greatest risk of progression to ILD and worse clinical outcomes.

Background/Objectives: Small airway disease/dysfunction (SAD) is crucial in obstructive airway diseases but is less investigated in interstitial lung disease (ILD). There are only a few physiological studies investigating SAD in the context of pulmonary fibrosis. Oscillometry is a simple technique that assesses SAD with minimal patient effort. In this study, we investigated the role of oscillometry in patients with mild pulmonary fibrosis without evident obstructive disorder, focusing on small airways. Methods: Oscillometry and pulmonary function test (PFT) data of consecutive patients newly diagnosed with pulmonary fibrosis of unknown etiology in a university hospital ILD clinic were collected and analyzed. Results: Data from 34 patients with mild pulmonary fibrosis were collected in 6 months. Disease severity, as evaluated by FVC, presented strong correlations with the oscillometry parameters: resistance (R5: r = −0.588, p < 0.001), reactance (X5: r = 0.671, p < 0.001), resonant frequency (Fres: r = −0.562, p = 0.001), and the area of reactance (AX: r = −0.515, p = 0.002). The oscillometry parameter R5-19-expressing was abnormal in 27% of patients, correlated with FEF25-75% (r = −0.370, p = 0.021) and was a predictor of a FEF25-75% < 60% pred. with AUC 0.738 (95%Cl 0.519–0.956). R5-19 correlated with FVC (r = −0.481, p = 0.004) and was the only SAD parameter that correlated with the composite physiologic index (CPI, r = 0.338, p = 0.04), while FEF 25-75% and RV/TLC% did not. Conclusions: Oscillometry is an easy to perform technique that may reveal early mechanical alterations caused by pulmonary fibrosis. Peripheral resistance, as expressed by R5-19, which identifies small airway dysfunction as a marker of peripheral lung pathology, may be complementary to pulmonary function testing and may also have prognostic implications for ILD patients.

Background: Three biologics targeting interleukin 5 (anti-IL-5) or its receptor-α (anti-IL-5Rα) are approved for patients with severe asthma.Methods: We systematically searched the literature published in Medline and Embase up to 1 May 2023 to identify observational studies and nonrandomised trials that assess the response to anti-IL-5/5Rα in real-life patients with severe eosinophilic asthma. We also performed random-effects meta-analyses.Results: We identified 6401 studies, of which 92 with 9546 patients were analysed. Biologics use was associated with a 62% reduction in severe exacerbations (risk ratio 0.38, 95% CI 0.29–0.50) and a 54% reduction in hospitalisations (risk ratio 0.46, 95% CI 0.35–0.61) at 12 months of treatment, compared to pre-treatment. Biologics improved asthma control (decrease in asthma control questionnaire score by 1.11 points (95% CI −1.29–−0.94) and increase in asthma control test score by 6.41 points (95% CI 5.66–7.16)) and increased the asthma quality of life questionnaire score by 1.08 points (95% CI 0.88–1.28) and forced expiratory volume in 1 s by 0.21 L (95% CI 0.15–0.27) at 12 months. There was a significant reduction in oral corticosteroids use of 51% (risk ratio 0.49, 95% CI 0.42–0.56), with a mean dose reduction of 6.01 mg·day⁻¹(95% CI −7.55–−4.48) at 12 months of treatment. Similar findings were observed at 3–4, 6 and 24 months. A biomarker-related response to treatment was also noted.Conclusions: This comprehensive meta-analysis summarises the significant clinical response to anti-IL-5/5Rα biologics in real-life studies, providing important insights for their use in clinical practice.

Background/Objectives: Obesity and overweight have become increasingly prevalent in different populations of people with type 1 diabetes (PwT1D). This study aimed to assess the effect of body weight on glycaemic indices in PwT1D. Methods: Adult PwT1D using continuous glucose monitoring (CGM) and followed up at a regional academic diabetes centre were included. Body weight, body mass index (BMI), waist circumference, glycated haemoglobin (HbA1c), and standard CGM glycaemic indices were recorded. Glycaemic indices were compared according to BMI, and correlation and linear regression analysis were performed to estimate the association between measures of adiposity and glycaemic indices. Results: A total of 73 PwT1D were included (48% normal weight, 33% overweight, and 19% obese). HbA1c was 7.2% (5.6–10), glucose management indicator (GMI) 6.9% (5.7–8.9), coefficient of variation (CV) for glucose 39.5% ± 6.4, mean glucose 148 (101–235) mg/dL, TIR (time in range, glucose 70–180 mg/dL) 66% (25–94), TBR₇₀ (time below range, 54–69 mg/dL) 4% (0–16), TBR₅₄ (250 mg/dL) 6% (0–40). Glycaemic indices and achievement (%) of optimal glycaemic targets were similar between normal weight, overweight, and obese patients. BMI was associated negatively with GMI, mean glucose, TAR₁₈₀, and TAR₂₅₀ and positively with TIR; waist circumference was negatively associated with TAR₂₅₀. Conclusions: CGM-derived glycaemic indices were similar in overweight/obese and normal weight PwT1D. Body weight and BMI were positively associated with better glycaemic control. PwT1D should receive appropriate ongoing support to achieve optimal glycaemic targets whilst maintaining a healthy body weight.

Background: Six biologic agents are now approved for patients with severe asthma. This meta-analysis aimed to assess the efficacy and safety of licensed biologic agents in patients with severe asthma, including the recently approved tezepelumab.Methods: We searched MEDLINE, Embase and CENTRAL to identify randomised controlled trials involving licensed biologics until 31 January 2023. We used random-effects meta-analysis models for efficacy, including subgroup analyses by individual agents and markers of T2-high inflammation (blood eosinophils and fractional exhaled nitric oxide), and assessed safety.Results: 48 studies with 16 350 patients were included in the meta-analysis. Biologics were associated with a 44% reduction in the annualised rate of asthma exacerbations (rate ratio 0.56, 95% CI 0.51–0.62) and 60% reduction of hospitalisations (rate ratio 0.40, 95% CI 0.27–0.60), a mean increase in the forced expiratory volume in 1 s of 0.11 L (95% CI 0.09–0.14), a reduction in asthma control questionnaire by 0.34 points (95% CI −0.46–−0.23) and an increase in asthma quality of life questionnaire by 0.38 points (95% CI 0.26–0.49). There was heterogeneity between different classes of biologics in certain outcomes, with overall greater efficacy in patients with T2 inflammation. Overall, biologics exhibited a favourable safety profile.Conclusions: This comprehensive meta-analysis demonstrated that licensed asthma biologics reduce exacerbations and hospitalisations, improve lung function, asthma control and quality of life, and limit the use of systemic corticosteroids, with a favourable safety profile. These effects are more prominent in patients with evidence of T2 inflammation.