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Background/aims: Chronic obstructive pulmonary disease (COPD) management guidelines have increasingly emphasised the importance of exacerbation prevention, and the role of blood eosinophil count (BEC) as a biomarker for inhaled corticosteroids (ICS) response. This study aimed to describe the distribution and stability of BEC and understand real-world treatment patterns among COPD patients in South Korea., Methods: This was a retrospective database analysis using data obtained from the KOrea COPD Subgroup Study (KOCOSS) registry between January 2012 and August 2018. KOCOSS is an ongoing, longitudinal, prospective, multi-centre, non-interventional study investigating early COPD amongst South Korean patients. BEC stability was assessed by calculating the intra-class correlation (ICC) coefficient. "Exacerbators" were patients who had a record of ≥ 1 exacerbation in the 12 months prior to the visit., Results: The study included 2,661 patients with a mean age of 68.6 years. Most patients were male (92.0%). Mean BEC was significantly higher in exacerbators compared to non-exacerbators. Patients with ≥ 2 exacerbations at baseline had a less stable BEC over time (ICC = 0.44) compared to non-exacerbators (ICC = 0.57). Patients with BEC ≥ 300 cells/μL at baseline predominantly received triple therapy (43.8%)., Conclusion: This study may further develop current understanding on BEC profiles amongst COPD patients in South Korea. BEC measurements are stable and reproducible among COPD patients, which supports its use as a potential biomarker.

Background: Asthma is associated with accelerated rate of FEV1 decline. Objective: To determine predictive factors associated with accelerated FEV1 decline in adult asthma and evaluate sputum cytokines as potential biomarkers for airflow decline. Methods: We recruited 125 asthmatics evaluated at the asthma clinic of Liège and reevaluated them at least 5 years later. Clinical, functional and inflammatory characteristics were compared between patients with accelerated decline (FEV1 decline > 0.85% pred.y−1) and others. Predictive factors were highlighted with linear regression analysis. Sputum EGF, VEGF, FGF, IL5, IL8, TGF-β, and IgE levels were measured in 58 of these patients at both visits by Human XL cytokine Luminex Performance assay and Elisa. Results: Post-BD FEV1 decline was 0.06 ± 2.44% pred.y−1 in the overall population. Median (IQR) time between visits was 66 (62 – 86) months. The multivariable analysis showed that an increase in blood eosinophils over time (Δ BEC) (Reg. Coef. (95%CI): 0.002 (0.001 to 0.004), p = 0.005)) and onset of asthma (0.04 (0.003 to 0.07), p = 0.036) were independently associated with FEV1 decline. IL8 levels measured at baseline were higher (499 (408—603) pg/ml, p = 0.0040) in patients with accelerated decline compared to others (143 (88—308) pg/ml). Conclusion: In this study, we have confirmed that an increase in blood eosinophil counts over a follow-up of at least 5 years and later onset of asthma are associated with accelerated annual FEV1 decline. Moreover, high sputum IL8 levels could be a risk factor for accelerated decline in asthma patients. [ABSTRACT FROM AUTHOR]

Objective: This study assessed the prevalence of eosinophilic chronic obstructive pulmonary disease (COPD) among a selected Saudi population and examined its correlation with baseline characteristics, clinical outcomes, exacerbation risk, and current management. Materials and Methods: This retrospective single-center study was conducted over a 2-year period. The patients were divided into two groups based on the blood eosinophil count at the time of diagnosis: eosinophilic COPD (≥300 cells/μl) and non-eosinophilic COPD (<300 cells/μl) groups. Results: Overall, 156 patients were included, of which 76 (48.7%) and 80 (51.3%) patients belonged to the eosinophilic and non-eosinophilic COPD groups, respectively. There were no significant differences between both groups regarding age, gender, smoking status, coexisting morbidities, FEV1, FEV1/FVC, and COPD severity (for all, P >0.05). Besides, there were no significant differences between both groups regarding the frequency and numbers of exacerbations, emergency room visits, in-patient hospitalizations, and intensive care unit admissions (for all, P >0.05). Among patients with eosinophilic COPD, 64 patients (84.2%) were correctly receiving the triple therapy of long-acting β2 agonists + long-acting muscarinic antagonist + inhaled corticosteroids, whereas 4 patients (5.26%) were incorrectly receiving the dual therapy of long-acting β2 agonists + inhaled corticosteroids. Univariate regression analyses revealed that heart failure, GOLD 3 severity, use of triple therapy, and use of non-invasive ventilation were significantly correlated with a higher risk of COPD exacerbation. Conversely, higher FEV1 was significantly correlated with lower risk of COPD exacerbation. The eosinophilic COPD phenotype was not found to be a significant independent variable of COPD exacerbation. Conclusion: This study found that among Saudi patients with COPD, there was no clinically important relationship between baseline blood eosinophil count and the rate of exacerbation. [ABSTRACT FROM AUTHOR]

Background: REMIT is the first real-world study of mepolizumab effectiveness in patients with severe asthma (SA) in Taiwan. Objectives: The primary objective evaluated changes in clinically significant exacerbations (CSEs; defined as use of oral corticosteroids (OCS) or emergency department (ED) visits and/or hospitalizations) in the 12 months pre- and post-mepolizumab treatment. Secondary objectives assessed changes in the number of CSEs requiring ED visits/hospitalizations and daily maintenance OCS (mOCS) dosage 12 months pre- and post-mepolizumab treatment. Three- and four-component clinical remissions were analyzed based on OCS-free, exacerbation-free, and asthma control (± stability in lung function). Design: REMIT was a retrospective, observational, self-controlled study analyzing patients in Taiwan with SA who were newly prescribed subcutaneous mepolizumab 100 mg Q4W. Methods: Data were extracted from records of 15 medical centers in Taiwan for patients indexed between November 1, 2018 and October 31, 2020. Results: A total of 170 patients were included: mean age at index date, 58.7 years; 53.5% female; 100% Chinese; 7.1% with chronic rhinosinusitis with nasal polyps, 1.8% with eosinophilic granulomatosis with polyangiitis, 1.2% with hypereosinophilic syndrome; and 55.7% with blood eosinophil count >300/µL. Pre-treatment, 71.2% had ⩾2 exacerbations, and 28.7% were on mOCS; 75.3% had no prior biologic treatment, and 24.7% had switched from other biologics. Most patients (80.0%) completed ⩾10 mepolizumab doses. Following the first mepolizumab administration (index date), CSEs reduced by 46.0% (rate ratio (RR): 0.545, 95% confidence interval (CI): 0.418–0.710; p < 0.0001) in the 12 months post-index. Exacerbations requiring ED visits/hospitalization reduced by 46.9% (RR: 0.531, 95% CI: 0.349–0.808; p = 0.0031). Median mOCS dose reduced by 100% by end of study and 81.8% of patients discontinued mOCS post-treatment. After 1 year of mepolizumab treatment, 28% and 23% patients achieved three- and four-component clinical remission, respectively. Conclusion: Mepolizumab use in a patient population in Taiwan with SA significantly reduced CSEs and mOCS use in routine clinical practice. Plain language summary: Mepolizumab for the treatment of severe asthma in Taiwan Why was the study done? • Patients with severe asthma can experience flare-ups, when symptoms become worse than usual and may require extra treatment • Severe asthma is often treated with corticosteroids, which are oral medications (not inhalers) that can reduce asthma flare-ups, but with side effects that can impact patients' quality of life • Mepolizumab is a promising treatment for severe asthma. Clinical trials have shown that mepolizumab reduces flare-ups and corticosteroid use in patients with severe asthma, reducing corticosteroid side effects • We wanted to know how well mepolizumab controls severe asthma in Chinese patients in clinical practice What did we do? • We looked at data from 170 patients with severe asthma in Taiwan who were given mepolizumab for the first time, with injections once every 4 weeks • We compared the number of flare-ups 1 year before treatment with mepolizumab to the number of flare-ups after 1 year of mepolizumab • After 1 year of mepolizumab, we looked at: ○ Changes in flare-ups by measuring corticosteroid use and number of emergency department visits/hospitalizations ○ Whether patients reached high level disease control (known as remission), which is when a patient does not need corticosteroids, does not experience flare-ups, has no severe asthma symptoms, and/or has no changes in lung function What did we find? • We found that, after taking mepolizumab: ○ The average number of flare-ups in patients was almost halved ○ The number of flare-ups needing emergency department visits/hospitalizations was reduced by nearly half ○ All patients stopped taking their regular daily corticosteroids. More than three quarters of patients stopped using any corticosteroids ○ 28% of patients met 3 of the remission criteria, 23% met all 4 criteria What do the findings mean? • In Chinese patients with severe asthma, mepolizumab is effective at reducing flare-ups and corticosteroid use, helping patients achieve remission [ABSTRACT FROM AUTHOR]

Exacerbations of Chronic Obstructive Pulmonary Disease (COPD) have a substantial effect on overall disease management, health system costs, and patient outcomes. However, exacerbations are often underdiagnosed or recognized with great delay due to several factors such as patients' inability to differentiate between acute episodes and symptom fluctuations, delays in seeking medical assistance, and disparities in dyspnea perception. Self-management intervention plans, telehealth and smartphone-based programs provide educational material, counseling, virtual hospitals and telerehabilitation, and help COPD patients to identify exacerbations early. Moreover, biomarkers such as blood eosinophil count, fibrinogen, CRP, Serum amyloid A(SAA),together with imaging parameters such as the pulmonary artery-to-aorta diameter ratio, have emerged as potential predictors of exacerbations, yet their clinical utility is limited by variability and lack of specificity. In this review, we provide information regarding the importance of the early identification of exacerbation events in COPD patients and the available methods which can be used for this purpose. [ABSTRACT FROM AUTHOR]

Purpose: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease with varied clinical features and treatment effects. This study aimed to investigate the additive effect of blood and tissue eosinophilia on patients with CRSwNP. Methods: Based on the blood eosinophil (Beos) count and tissue eosinophil (Teos) count, we divided 144 CRSwNP patients into four groups, analysed their clinical features and histopathologic changes, and investigated their postoperative control. Results: Patients in the Beos+Teos+ (blood eosinophil count > 0.3 × 109/L, tissue eosinophil count > 10/HPF) group had a higher incidence of allergic rhinitis (AR) and asthma. Lund‐Mackay (LM) scores, hyposmia visual analogue scale (VAS) scores and Global Osteitis Scoring Scale (GOSS) scores were higher in the Beos+Teos+ group than those in the other groups. Tissue remodelling, such as connective tissue oedema and basement membrane thickening was more severe in the Beos+Teos+ group compared with other groups. There were more uncontrolled patients after surgery in Beos+Teos+, Beos+Teos− (blood eosinophil count > 0.3 × 109/L, tissue eosinophil count ≤ 10/HPF)and Beos−Teos+ (blood eosinophil count ≤ 0.3 × 109/L, tissue eosinophil count > 10/HPF)groups compared with the Beos−Teos− group. Conclusions: Eosinophilic inflammation both in blood and tissue was accompanied by more severe clinical features and tissue remodelling. Eosinophilia in blood or tissue indicated poorer disease control after surgery. [ABSTRACT FROM AUTHOR]

Introduction: Patients with uncontrolled, moderate-to-severe asthma have a higher risk for exacerbations, negatively impacting lung function and quality of life. Dupilumab, a fully human monoclonal antibody, blocks interleukins 4 and 13, key and central drivers of type 2 inflammation. Dupilumab has been effective in the treatment of certain types of moderate-to-severe asthma across several clinical trials. We describe the characteristics of patients enrolled in RAPID, a global prospective registry, who initiated dupilumab (primary indication: asthma) in a real-world clinical setting. Methods: A total of 205 patients (aged ≥ 12 years) were enrolled between March 2020 and October 2021 and are included in this analysis. Data are shown as mean (SD) unless stated otherwise. Results: Patients were aged 50.1 (17.4) years and were mostly female (65.4%) and white (74.1%). At enrollment, 24.4% reported being current/former smokers and 86.8% had moderate-to-severe asthma (Global Initiative for Asthma steps 3–5). A mean (SD) of 4.4 (6.4) severe asthma exacerbations were reported in the year before enrolling in the registry in 78 of 152 patients with available data. Patients had reduced lung function [pre-bronchodilator forced expiratory volume in 1 s (FEV1): 2.3 (1.1) L; pre-bronchodilator percent predicted FEV1: 70.3 (20.3) %] and poor asthma control [6-item Asthma Control Questionnaire: 2.4 (1.2); Asthma Quality of Life Questionnaire: 4.1 (1.3)]. The median (Q1–Q3) blood eosinophil count was 305 (200–695) cells/µL and the mean (SD) fractional exhaled nitric oxide levels were 42 (35) ppb (range: 4–186 ppb). Conclusion: Our findings suggest that most patients who enrolled in RAPID and initiated dupilumab in real-world clinical settings had a high disease burden, despite receiving current standard-of-care treatment at enrollment. Plain Language Summary: Severe asthma can be difficult to control with currently available medicines. Asthma attacks, also called asthma flare-ups or exacerbations, are episodes where symptoms such as coughing, wheezing, shortness of breath, or chest tightness can suddenly occur or worsen, severely affecting quality of life. Dupilumab is a prescription medication used, along with other medicines, to treat asthma. In clinical trials, dupilumab worked well in patients with moderate-to-severe asthma, reducing the number of asthma attacks and improving lung function, characterized by easier breathing. To determine how well dupilumab works outside of a clinical trial setting, we look at studies set in the real world (observational studies). The RAPID registry is an observational study in which adolescents and adults starting dupilumab treatment for asthma are monitored by their doctor. Here, we report information on the first 205 patients who enrolled in the RAPID study between March 2020 and October 2021. At the beginning of the study, doctors diagnosed most patients (87%) with moderate-to-severe asthma. More than half of the patients had at least one severe asthma attack in the previous year but many had more than one (average: 4.4 attacks). Overall, patients had poor lung function, asthma control, and quality of life. Many patients also showed increased levels of markers for type 2 inflammation, an immune response activating cells such as eosinophils, mast cells, and T-cells. Overall, most patients with asthma who started dupilumab in a real-world clinical setting had a high disease burden, despite receiving standard-of-care treatment at the time of enrollment. [ABSTRACT FROM AUTHOR]

Purpose: Mepolizumab was recently approved for treating Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) unresponsive to standard treatment or recurring after endoscopic sinus surgery (ESS). To date, few studies have assessed Mepolizumab's efficacy in severe type-2 CRSwNP. Our study aimed to analyze sinonasal outcomes in type-2 CRSwNP patients treated with 100 mg Mepolizumab administered subcutaneously every four weeks. Methods: We conducted a retrospective study of patients with severe, recalcitrant CRSwNP treated with Mepolizumab. Demographic and clinical characteristics were collected, including age, sex, and comorbidities such as asthma, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NERD), and allergic rhinitis (AR), as well as the number of previous ESS procedures and the interval since the last one. Patients were evaluated at baseline and after one year for blood eosinophil count, nasal polyp score (NPS), modified Lund-Kennedy score (mLKS), olfactory function (using a VAS scale and a 16-item Sniffin' identification test), SNOT-22, and sinus opacification on CT scans. The need for rescue ESS or systemic corticosteroids (SCS), response to treatment, and side effects were also recorded. Results: Data from 27 patients were collected. After one year, all scores showed significant improvement. NERD was the only factor associated with a less favorable improvement in olfactory function. There were no side effects reported, although 2 patients discontinued Mepolizumab as they were considered "non-responders." Conclusions: Mepolizumab is safe and effective in reducing the clinical, endoscopic, and radiological burden of disease, as well as in decreasing the need for salvage ESS or systemic steroids. [ABSTRACT FROM AUTHOR]

Rationale: Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of cardiovascular and cardiopulmonary events. In the phase III, 52-week ETHOS trial (NCT02465567), triple therapy with budesonide/glycopyrrolate/formoterol fumarate (BGF) reduced rates of moderate/severe exacerbations and all-cause mortality compared with dual therapy with glycopyrrolate/formoterol fumarate (GFF) or budesonide/formoterol fumarate (BFF). However, the effect of BGF on cardiovascular events versus GFF remains unevaluated. Furthermore, the effect of BGF on time to first severe exacerbation has not been reported. Objectives: To assess the effects of BGF 320/18/9.6 μg (BGF 320) and other inhaled corticosteroid–containing arms on cardiovascular and severe cardiopulmonary endpoints versus GFF in patients with COPD from the ETHOS trial. Methods: Patients with moderate to very severe COPD and a history of exacerbations were randomized to twice-daily BGF 320, BGF 160/18/9.6 μg, BFF 320/9.6 μg, or GFF 18/9.6 μg (GFF). Time to first severe COPD exacerbation was a prespecified endpoint; post hoc cardiovascular and severe cardiopulmonary endpoints included time to first major adverse cardiac event, time to first cardiovascular adverse event (AE) of special interest, time to first cardiac AE, and time to the composite endpoint of first severe cardiopulmonary event. Measurements and Main Results: BGF 320 reduced the rate of first occurrence (hazard ratio [95% confidence interval]) of cardiovascular and severe cardiopulmonary events versus GFF, including for time to first cardiovascular adverse event of special interest (0.63 [0.48, 0.82]), cardiac AE (0.60 [0.48, 0.76]), and severe cardiopulmonary event (0.80 [0.67, 0.95]). Conclusions: BGF had a benefit on cardiovascular endpoints and severe cardiopulmonary events versus GFF in patients with moderate to very severe COPD. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to compare the clinical characteristics and treatment outcomes of allergic patients (AP) and non-allergic patients (NAP) with severe eosinophilic asthma (SEA) treated with anti-IL5/IL5R biologic agents (mepolizumab, benralizumab, or reslizumab) over one year. Sub-analyses assessed treatment response variations between AP and NAP based on the biological used and compared outcomes among AP with and without fungal allergy. Methods: Observational retrospective analysis. Clinical characteristics, laboratory findings, pulmonary function tests, Asthma Control Test (ACT) scores, oral corticosteroid (OCS) usage, and exacerbation frequency were assessed at the initiation of biological treatment and after one year. Results: Sixty-five patients with SEA were included, 41 AP and 24 NAP. 55.4% were treated with mepolizumab, 33.8% with benralizumab, and 10.8% with reslizumab. Before anti-IL5/5R treatment, AP had worse baseline outcomes but there were no differences in pulmonary function. Mean annual exacerbation rate and percentage of patients requiring OCS and dose of prednisone were higher in AP than NAP. AP had significantly higher total IgE values. After one year of treatment, more AP discontinued OCS than NAP (p = 0.025). Both experienced a significant reduction in exacerbation frequency (p = 0.001) and improved respiratory function. 70.7% of AP and 60% of NAP improved ACT ≥3 points. There was no significant difference between AP and NAP using mepolizumab (p = 0.145) or benralizumab (p = 0.174) in reducing OCS. Conclusions: Anti-IL5/IL5R reduced the need for OCS and improved asthma control, regardless of allergic status. Fungal allergy led to lower ACT scores and higher exacerbations than other allergens; both groups improved with anti-IL5/ILR. [ABSTRACT FROM AUTHOR]

Background: The mechanism linking BMI and asthma remains unclear. Method: Mendelian Randomization (MR) analysis was conducted using summary-level GWAS data from the FinnGen Biobank and the Open GWAS project. The analysis considering potential variables as mediators, including blood cell counts, blood pressure, and blood biomarkers. Three commonly used MR methods—the inverse-variance-weighted (IVW) method, weighted median (WM) method, and MR-Egger method—were employed to infer causal links. A two-step approach was used in mediation analysis to evaluate the causal links among BMI, candidate mediators, and asthma. Result: Elevated BMI demonstrated a substantial correlation with increased asthma risk. Thirteen biomarkers mediated the relationship between BMI and asthma, mainly including leukocyte count (5.070%), apolipoprotein A levels (7.395%), cystatin C levels (5.345%), urate levels (9.057%), diastolic blood pressure (7.365%), and albumin levels (10.888%). These factors collectively explained over 50% of the increased asthma risk associated with BMI elevation. Additionally, eosinophil count and C-reactive protein were also identified as important mediators using the WM method. Conclusion: This study highlights the complex relationship between obesity, blood biomarkers, and asthma risk. Additional studies are required to validate these results and investigate causal relationships in various populations. [ABSTRACT FROM AUTHOR]

Objective: To explore the clinical significance of induced sputum in asthma through a retrospective analysis of induced sputum in patients with asthma. Data sources: The data and references cited in this article were obtained from PubMed, Sci-Hub, and Web of Science. Study selection: Observational studies with reliable data were selected. Conclusions: The cytological count, -omics, and pathogen detection of induced sputum are helpful for the clinical diagnosis of asthma and in guiding medication choices. [ABSTRACT FROM AUTHOR]

Biological sex is closely associated with the properties and extent of the immune response, with males and females showing different susceptibilities to diseases and variations in immunity. Androgens, predominantly in males, generally suppress immune responses, while estrogens, more abundant in females, tend to enhance immunity. It is also established that sex hormones at least partially explain sex biases in different diseases, particularly autoimmune diseases in females. These differences are influenced by hormonal, genetic, and environmental factors, and vary throughout life stages. The advent of gender-affirming hormone therapy offers a novel opportunity to study the immunological effects of sex hormones. Despite the limited studies on this topic, available research has revealed that testosterone therapy in transgender men may suppress certain immune functions, such as type I interferon responses, while increasing inflammation markers like TNF-α. Transgender women on estrogen therapy also experience alterations in coagulation-related and inflammatory characteristics. Furthermore, other possible alterations in immune regulation can be inferred from the assessment of inflammatory and autoimmune markers in transgender individuals receiving hormone therapy. Understanding the complex interactions between sex hormones and the immune system, particularly through the unique perspective offered by gender-affirming hormone therapies, may facilitate the development of targeted therapies for infections and autoimmune diseases while also improving healthcare outcomes for transgender individuals. Here we review immune dynamics throughout life in both sexes and provide a summary of novel findings drawn from studies exploring gender-affirming hormone therapy. [ABSTRACT FROM AUTHOR]

Introduction: Immune-related adverse events (irAEs) induced by immune checkpoint inhibitors are difficult to predict and can lead to severe events. Although it is important to develop strategies for the early detection of severe irAEs, there is a lack of evidence on irAEs associated with ipilimumab plus nivolumab therapy for metastatic renal cell carcinoma (RCC). Therefore, this study aimed to investigate the association between eosinophil and severe irAEs in patients receiving ipilimumab plus nivolumab therapy for RCC. Methods: In this retrospective study, 161 patients receiving ipilimumab plus nivolumab therapy for RCC were divided into three groups based on whether they experienced

Background: Uncontrolled severe eosinophilic chronic rhinosinusitis (eCRS) is associated with elevated levels of Th2 cells and raised immunoglobulin concentrations in nasal polyp tissue. eCRS is characterized by high eosinophilic infiltration and type 2 inflammation. Gαi1/3 proteins participate in allergic inflammation by regulating immune cells. Whether Gαi1/3 proteins have a role in the development of eCRS remains unknown. Objectives: To investigate the association between Gαi1/3 expression levels and CRS and the underlying mechanisms Methods: Western blotting and immunohistology were used to detect Gαi1/3 expression. Correlations between Gαi1/3 and immune cells and clinical parameters were analyzed. Signaling pathway activation in IL-5-induced Gαi1/3-knockout or knockdown mouse embryonic fibroblasts (MEFs) and eosinophils (EoL-1 cells) was detected by western blotting. EdU/DAPI was used to evaluate the proliferation of EoL-1 cells. A CRS model was established using Gαi1/3-knockout mice, and histological analysis and inflammatory cytokine measurements were performed. Results: Compared with the non-eCRS subset, the eCRS subset showed significantly increased Gαi1/3 expression levels. High nasal tissue Gαi1/3 levels were linked to high tissue eosinophil infiltration, and high disease severity and allergic conditions in CRS patients. Gαi1/3 were required for IL-5-induced Akt-mTOR and Erk activation in MEFs. In EoL-1 cells, Gαi1/3 was associated with IL-5-activated IL-5Rα, promoting IL-5Rα endocytosis and transducing downstream signaling. IL-5-induced EoL-1 cell proliferation and degranulation were suppressed after Gαi1/3 silencing. In a CRS murine model, immune cell infiltration and type 2 inflammation were largely impaired in Gαi1/3-double-knockout mice. Conclusion: Increased Gαi1/3 expression levels in nasal tissue are linked to eosinophil infiltration and increased disease severity in CRS patients. Gαi1/3 contributes to eosinophil activation and participates in regulating allergic inflammation in CRS patients. [ABSTRACT FROM AUTHOR]

Background: Cough variant asthma (CVA) is a specific type of asthma characterized by chronic cough as the sole or predominant symptom. Accurate diagnosis is crucial for effective treatment, yet bronchial provocation test is not always feasible in clinical settings. To identify independent predictors of CVA diagnosis, we developed a nomogram for predicting CVA. Univariate and multivariate logistic regression analyses were employed to construct the model, and the accuracy and consistency of the prediction model were subsequently validated. Methods: We conducted a retrospective review of clinical data from 241 outpatients with chronic cough (≥ 8 weeks) who underwent bronchial provocation test at our hospital between January 2018 and December 2021. Patients were categorized into CVA group and Non-CVA group based on diagnostic criteria. Univariate analysis (chi-square and t-tests) was performed, followed by multivariate logistic regression to identify independent predictors. A nomogram was constructed using these predictors and validated using Bootstrap resampling (B = 200) to calculate the C-index. Additionally, receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were employed to assess the model's accuracy. Results: Of the 241 outpatients, 156 (64.7%) were diagnosed with CVA. Multivariate analysis identified several independent predictors of CVA, including cough triggered by cold air (OR = 12.493, P = 0.019), exposure to pungent odors (OR = 3.969, P = 0.002), cough phasing (OR = 4.515, P < 0.001), history of allergic rhinitis (OR = 3.231, P = 0.018), and the percentage of the predicted value of maximum mid-expiratory flow (MMEF%pred) (OR = 0.981, P = 0.039) were independent predictors of CVA. The nomogram demonstrated good discrimination (AUC = 0.829) and calibration, with a sensitivity of 75.3% and specificity of 77.6% at the optimal cutoff. The C-index was 0.920, indicating excellent model performance. Conclusions: We successfully developed and validated a user-friendly nomogram that accurately predicted CVA diagnosis based on clinical characteristics and pulmonary function test. This nomogram model could assist clinicians in diagnosing CVA, especially in patients without bronchial provocation test or with contraindications to bronchial provocation test. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) exacerbations are major contributors to morbidity and mortality, highlighting the need to better understand their molecular mechanisms to improve prevention, diagnosis, and treatment. This study investigated differential gene expression profiles and key biological processes in COPD exacerbations categorized based on sputum microbiome profiling. An observational study was performed on a cohort of 16 COPD patients, who provided blood and sputum samples during exacerbations, along with five stable-state samples as controls. Exacerbations were classified using 16S rRNA sequencing to analyze the sputum microbiota and multiplex PCR to detect respiratory viruses. Blood transcriptomic profiling was conducted using Oxford Nanopore technology, followed by differential gene expression and pathway enrichment analyses. A total of 768 regulated genes were identified across the exacerbation groups, with 35 shared genes associated with neutrophil activation. Bacterial exacerbations activated pathways related to phagocytosis and toll-like receptor signaling, while viral exacerbations were linked to pro-inflammatory responses and mitochondrial damage. Exacerbations of unknown origin showed activation of pathways involved in protozoan defense and neutrophilic asthma. Biomarkers such as IFITM3 and ISG15 for bacterial exacerbations, DEFA3 for viral, and CD47 for unknown-origin exacerbations were identified. These findings highlight distinct transcriptomic profiles and biological pathways in COPD exacerbations, emphasizing the central role of neutrophil-driven inflammation and identifying potential biomarkers for improved differential diagnosis and personalized management. [ABSTRACT FROM AUTHOR]

In prednisone-dependent severe asthma, uncontrolled sputum eosinophilia is associated with increased numbers of group 2 innate lymphoid cells (ILC2s). These cells represent a relatively steroid-insensitive source of interleukin-5 (IL-5) and IL-13 and are considered critical drivers of asthma pathology. The abundance of ILC subgroups in severe asthma with neutrophilic or mixed granulocytic (both eosinophilic and neutrophilic) airway inflammation, prone to recurrent infective exacerbations, remains unclear. Here, we found by flow cytometry that sputum ILC3s are increased in severe asthma with intense airway neutrophilia, whereas equivalently raised sputum ILC2s and ILC3s were found in severe asthma with mixed granulocytic inflammation. Unbiased clustering analyses identified an "intermediate-ILC2" population displaying markers of both ILC2s (prostaglandin D2 receptor 2; CRTH2, IL-5, and IL-13) and ILC3s (c-kit and IL-17A) that were most abundant in severe asthma with mixed granulocytic airway inflammation. Intermediate ILC2s correlated with airway neutrophilia and were associated with increased amounts of IL-1β and IL-18 in sputum supernatants. Coculture of sort-purified canonical ILC2s with IL-1β and IL-18 in vitro up-regulated c-kit and IL-17A as well as gene expression profiles related to both type 2 and type 17 inflammatory pathways. Together, we have identified an intermediate-ILC2 phenotype in the airways of individuals with severe mixed granulocytic asthma, representing a candidate therapeutic target for controlling neutrophilic airway inflammation. Editor's summary: Although individuals with mild asthma generally respond well to standard-of-care treatment, severe asthma often cannot be controlled with the same therapies. This is, in part, because the drivers of the different subtypes of severe asthma are not clearly defined. Here, Ju et al. aimed to understand drivers of disease by phenotyping sputum samples from patients with severe asthma with eosinophilic, neutrophilic, or mixed granulocytic (both eosinophilic and neutrophilic) inflammation. Patients with eosinophilic inflammation had group 2 innate lymphoid cells (ILC2s) in their sputum that secreted IL-5 and IL-13; in contrast, individuals with mix granulocytic inflammation harbored a population of ILC2s that also expressed markers of group 3 innate lymphoid cells (ILC3s). These "intermediate ILC2s" secreted IL-17, expressed c-kit, and were associated with neutrophil abundance in the airway, a feature often associated with severe asthma. These data suggest that this intermediate population of ILC2s may contribute to poor treatment responses and that targeting this population may improve responses to existing therapies. —Courtney Malo [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is among the most relevant comorbidity associated with lung cancer. The advent of innovative triple treatment approaches for COPD has significantly improved patients' quality of life and outcomes. Few data are available regarding the impact of triple inhaler therapy on patients featuring COPD and lung cancer. Methods: We retrospectively evaluated the impact of triple inhale bronchodilators in a cohort of 56 patients with treated COPD who underwent lung surgery for primary cancer. Results: Triple bronchodilation can help to relieve the symptoms of the disease and improve lung function, allowing people with lung cancer to reduce the risk of serious exacerbations and improve their quality of life. Conclusions: Within the limits of the study, it should be underlined that bronchodilators can effectively affect the outcome and performance status after thoracic surgery. [ABSTRACT FROM AUTHOR]

Background/Objectives: Benralizumab is an anti-IL-5 receptor alpha monoclonal antibody that induces the near-complete depletion of eosinophils. This study aimed to evaluate the long-term safety and effectiveness of benralizumab in patients with severe eosinophilic asthma (SEA) over an extended 48-month follow-up period, offering one of the longest real-world perspectives available. Methods: This was a single-arm, retrospective, observational, multicenter study involving 123 SEA patients treated with benralizumab at a dosage of 30 mg every 4 weeks for the first 3 doses and then every 8 weeks. The safety endpoints focused on the frequency and nature of adverse events and the likelihood that they were induced by benralizumab. The efficacy endpoints focused on lung function, asthma exacerbations and control, and oral corticosteroid use. Results: Benralizumab, consistent with its mechanism of action, led to the rapid and nearly complete depletion of eosinophils. In total, 26 adverse events (21.1%) were observed, with 1.6% related to the treatment and 0.8% categorized as serious (vagal hypotension). Bronchitis was the most common unrelated adverse event (15.4%), occurring between months 36 and 38. Importantly, benralizumab effectiveness and safety were maintained consistently across the 48-month duration, resulting in significant improvements in lung function and reductions in oral corticosteroid use and exacerbation frequency. Conclusions: Benralizumab demonstrated a favorable safety profile, comparable to previously published studies, with perdurable effectiveness in controlling SEA and reducing oral corticosteroid use. Finally, this study provides evidence that near-complete eosinophil depletion does not increase long-term safety risks and supports benralizumab as a reliable treatment option for SEA patients. [ABSTRACT FROM AUTHOR]

COPD is one of the leading causes of death worldwide, so it represents a significant public health challenge. Over the years, new effective therapies have been proposed. However, the burden of COPD is still conditioned by frequent acute events defined as exacerbations (exacerbation of COPD-ECOPD), which have a significant impact not only on the patient's quality of life but also on the progression of the disease, morbidity, and mortality. Related to the severity of the condition, ECOPD may require hospital admission and often repeatedly more admissions (readmission). The phenomenon of readmissions is a significant problem, contributing substantially to the utilisation of healthcare resources and the economic burden of COPD. Related contributing factors are still poorly understood, and managing the patients readmitted to the hospital with ECOPD may be challenging. Hospital readmissions should be optimally managed, including supporting and preventive strategies. Although early readmissions (30 days from discharge) are a marker of the quality of the patient's care, we need to consider COPD patients globally. It is not sufficient to address just the acute events, so multidimensional management is necessary, able to follow the patient over time to identify, by a personalised approach, the correct treatment during and post hospitalisation and intercept any factor affecting the natural history of the disease, comprising the risk of hospital readmissions. In the context of the literature concerning respiratory medicine, particularly COPD patients, our narrative review analyses recent evidence regarding the current management of COPD hospital readmissions, aiming to propose preventive strategies helpful in clinical practice. The proposed strategies can potentially improve clinical outcomes and reduce healthcare costs when effectively implemented in practice. [ABSTRACT FROM AUTHOR]

Background/Objectives: Hypercapnic respiratory failure (HRF) is a primary cause of admittance to the intensive care unit (ICU). This study aimed to investigate the factors that affect the length of hospital stay in HRF patients. Methods: This study was designed as a retrospective, cross-sectional analysis of patients who were admitted to the ICU because of HRF between 2022 and 2024. The demographic and clinical characteristics of the patients and laboratory results were recorded. The Charlson Comorbidity Index (CCI) was calculated. The relationship between these parameters and the length of hospital stay was assessed. Results: A total of 138 patients were included in the study. The average length of hospital stay was 11.45 days, and 37% of the patients were included in the long-term hospitalization group. The degree of hypercapnia was not associated with the length of hospital stay. It was determined that the patients' albumin levels and CCI were significant determinants of the length of hospital stay. The combined assessment of these two parameters was found to be superior compared to their separate evaluations. Conclusions: In our study, hypoalbuminemia and a higher CCI were identified as predictors of a prolonged ICU stay in HRF patients. Albumin levels of <3.25 g/dL and CCI scores of ≥5 were linked to longer stays, with this combined evaluation offering greater predictive value. These factors can guide patient management. [ABSTRACT FROM AUTHOR]

This study aims to develop a protocol for respiratory disease-associated biomarker discovery by combining urine proteome studies with urinary exosome components analysis (i.e., miRNAs). To achieve this, urine was DTT treated to decrease uromodulin, then concentrated and ultracentrifuged. Proteomic analyses of exosome-free urine were performed using LC-MS/MS. Simultaneously, miRNA expression from urine exosomes was measured using either RTqPCR (pre-amplification) or nCounter Nanostring (non-amplication) analyses. We detected 548 different proteins in exosome-free urine samples (N = 5) with high confidence (FDR < 1%), many of them being expressed in different non-renal tissues. Specifically, lung-related proteins were overrepresented (Fold enrichment = 1.31; FDR = 0.0335) compared to whole human proteome, and 10–15% were already described as protein biomarkers for several pulmonary diseases. Urine proteins identified belong to several functional categories important in respiratory pathology. We could confirm the expression of miRNAs previously connected to respiratory diseases (i.e., miR-16-5p, miR-21-5p, miR-146a-5p, and miR-215-5p) in urine exosomes by RTqPCR. Finally, we detected 333 miRNAs using Nanostring, 15 of them up-regulated in T2high asthma (N = 4) compared to T2low asthma (N = 4) and healthy subjects (N = 4). Therefore, this protocol combining the urinary proteome (exosome free) with the study of urinary exosome components (i.e., miRNAs) holds great potential for molecular biomarker discovery of non-renal and particularly respiratory pathologies. [ABSTRACT FROM AUTHOR]