Search Results (269)

Background/Objectives: Respiratory pathogens are frequently detected during asthma exacerbations in children. This study aimed to evaluate the distribution of respiratory pathogens, associated clinical features, and factors related to severe exacerbation in children hospitalized for asthma exacerbations during a two-year period. Methods: This retrospective observational study included children aged 1–18 years hospitalized for asthma exacerbation between April 2023 and April 2025. Demographic, clinical, laboratory, and pathogen data were retrospectively obtained from medical records and analyzed. Results: A total of 312 children were included; 135 patients (43.3%) were female, and the median age was 5.70 years (IQR, 3.42–8.79). A respiratory pathogen was detected in 235 patients (75.3%). Among patients with single infections (n = 203), rhinovirus (RV) was the most common pathogen (n = 130), followed by respiratory syncytial virus (RSV) (n = 18). Compared with RSV infection, RV infection was associated with higher frequencies of allergic rhinitis and aeroallergen sensitization, as well as higher neutrophil and eosinophil counts and higher total IgE levels. RV was detected throughout the year, peaking in autumn, whereas RSV occurred predominantly in winter. RSV infection was observed in younger children and was associated with more frequent severe exacerbations in unadjusted comparisons; however, only younger age and moderate-to-severe asthma remained independently associated with severe exacerbation in multivariable analysis. Conclusions: Respiratory pathogens were detected in most children hospitalized for asthma exacerbation, with RV being the predominant pathogen. Younger age and moderate-to-severe asthma were the main factors associated with severe exacerbation. Full article

The complement system is a key link between innate and adaptive immunity, contributing to pathogen elimination, immune regulation, and tissue homeostasis. Its activation is not only crucial in infections, such as COVID-19, but also plays a major role in the pathomechanism of several non-infectious respiratory diseases, such as asthma, COPD, sarcoidosis and lung cancer. Complement components can modulate the quality of the adaptive immune responses, including through the regulation of T2 immunity and eosinophilic inflammation, thereby linking natural defense to complex immune processes. In recent years, it has become increasingly clear that dysregulated complement activity contributes to inflammation, thrombosis and tissue damage in a wide range of respiratory diseases. The study of the various components of this cascade system may therefore be promising from both a diagnostic and therapeutic point of view. Some of its components may serve as biomarkers for distinguishing between different phenotypes of certain lung diseases, while their targeted inhibition or modulation may open the way towards new treatment options. A better understanding of the complement system’s integrative and regulatory role not only allows for a deeper insight into immunological interactions but may also bring us closer to phenotype-oriented, immunology-based pulmonology, which may have real clinical benefits in the future. Full article

Background/Objectives: Tezepelumab targets thymic stromal lymphopoietin and has broad efficacy in severe asthma, yet real-world evidence on patient-reported trigger burden remains limited. We assessed 12-month outcomes after tezepelumab, focusing on clinical remission, biomarkers, and trigger profiling as complementary dimensions of response. Methods: In this multicenter longitudinal real-world observational cohort based on routine clinical follow-up and Severe Asthma Network in Italy (SANI) registry data, 43 adults with severe asthma treated with tezepelumab at four Italian SANI reference centers were evaluated at baseline and, when available, after 1, 3, 6, and 12 months. Outcomes included exacerbations, lung function, type 2 biomarkers, the Asthma Control Test, SNOT-22, trigger categories, Asthma Trigger Inventory (ATI) scores, and SANI-defined clinical remission. Results: Among 22 patients with 12-month follow-up data, mean annualized exacerbations decreased from 4.30 ± 2.77 to 0.36 ± 0.49 (p < 0.001), and 14/22 (63.6%) were exacerbation-free. Asthma control improved, whereas FEV1 remained stable. FeNO and blood eosinophils decreased at selected time points. The number of reported trigger categories was lower at 6 months (p < 0.001), and physical exertion, smoke, irritants, and infection-related ATI domains improved longitudinally. Complete clinical remission was achieved in 5/22 patients (22.7%). Conclusions: Tezepelumab was associated with reduced exacerbations, improved asthma control, and lower patient-reported trigger burden. Structured trigger profiling may provide an exploratory patient-centered dimension for assessing treatment response in severe asthma. Full article

Background: The GALERNA study is a retrospective real-world observational study conducted across 21 hospitals in Spain, aiming to evaluate long-term clinical benefits and adherence to benralizumab in 255 adult patients with severe eosinophilic asthma (SEA) over a follow-up period of up to 144 weeks. Objectives: Primary objectives focused on assessing adherence to benralizumab, while secondary objectives included the description of severe asthma exacerbation rates, systemic corticosteroid (SCS) use, persistence to benralizumab, lung function, asthma control, and the proportion of patients achieving super-response or clinical remission. Data were collected at baseline (48 weeks prior to benralizumab initiation/index date), follow-up 1 (FUP1) (0–48 weeks), FUP2 (49–96 weeks), and FUP3 (97–144 weeks) after the index date. Results: At baseline, patients demonstrated a substantial disease burden characterised by impaired lung function, poorly controlled asthma, and frequent severe exacerbations. The results indicated high adherence rates to benralizumab, with 92.9% of patients receiving each of the prescribed doses of benralizumab at week 48 and 70.6% at week 144. Patients showed substantial and sustained clinical improvements, with a reduction in the proportion of individuals presenting at least one severe exacerbation from baseline to FUP3 and a 74% decrease in SCS use for the same period. Lung function also improved, with the proportion of patients achieving pre-bronchodilator FEV₁ ≥ 80% rising to 52% at 144 weeks. Furthermore, mean Asthma Control Test (ACT) scores increased to 20.5, with 68.5% of patients achieving well-controlled asthma (ACT ≥ 20). By the end of the study, 63.6% of patients achieved super-response and 39.1% showed clinical remission, with an overall benralizumab persistence of 79.8% during all follow-up periods. Conclusions: The GALERNA study provides compelling real-world evidence that benralizumab affords marked and sustained clinical benefits together with high long-term adherence in Spanish SEA patients, reinforcing its usefulness as a long-term therapeutic option in routine clinical practice. Full article

Background/Objectives: Airway inflammation and small airway dysfunction (SAD) are key features of asthma. Inflammation can be assessed by blood eosinophil count (Eos) and exhaled nitric oxide (NO) parameters, including fractional exhaled nitric oxide (FeNO), bronchial NO flux (J’awNO), and alveolar NO concentration (CANO), the latter reflecting distal airway inflammation. We aimed to evaluate the association between Eos and the degree of airway inflammation as specified by exhaled NO parameters and to assess the relationships between exhaled NO parameters and small airway dysfunction using spirometric and plethysmographic indices. Methods: We conducted an observational study of asthmatic outpatients who underwent spirometry, plethysmography, and exhaled NO measurements. Multivariable regression models were used to estimate associations between Eos and FeNO, J’awNO, CANO, and spirometric/plethysmographic indices, adjusting for age, sex, body mass index, and relevant covariates. Results: The analytic cohort included 121 patients (49 men; 72 women; median age 54.2 years). Small airway obstruction and a range of airway inflammation severity were observed. Mean (SD) or median [IQR] values, as appropriate, were: FEF₇₅ z-score −0.62 (0.96); FEF_25–75 z-score −1.27 (1.29); RV z-score 1.26 (0.94); RV/TLC z-score 1.60 (1.10); J’awNO 60.20 nL/min (102.80); FeNO 23.61 ppb (37.61); CANO 3.80 ppb (4.12); and Eos 260 cells/µL (430). Log-transformed Eos (log[Eos]) was associated with FeNO, J’awNO, and CANO (adjusted marginal slope [95% CI]: 12.11 [9.35–14.69], 33.56 [25.34–41.19], and 1.14 [0.84–1.43], respectively). Log(Eos) was also positively associated with RV and RV/TLC, but negatively associated with FEF_25–75, FEF₇₅, and FEV₁. Similarly, CANO was positively associated with RV and RV/TLC and inversely associated with FEF_25–75 and FEF₇₅. No significant associations were observed for FeNO or J’awNO. Conclusions: Blood eosinophils were independently associated with all exhaled NO parameters. The association between CANO and small airway ventilatory function indices supports a link between distal airway inflammation and SAD in asthma. Full article

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare and heterogeneous autoimmune disease involving multiple organs and systems, characterized by asthma, eosinophilia, and granulomatous or vasculitic involvement of several organs. Most of the initial symptoms include rhinitis, sinusitis, and asthma. The primary consultation departments are typically allergy, otolaryngology, and respiratory. EGPA lacks effective biomarkers for early diagnosis, and most patients have experienced serious multiple organ damage at the time of diagnosis, which makes it more difficult to treat. Therefore, as an allergist, improving the understanding of EGPA, especially the early identification of EGPA in the rhinitis, asthma, or sinusitis stage, will effectively shorten the overall course of EGPA and reduce the mortality and disability rates. Based on this, the author compiled a diagnosis and treatment pathway to outline the clinical manifestations; examination, diagnosis, and treatment pathways; differential diagnosis; disease management; and other aspects of EGPA in the allergic department, aiming to promote early detection, identification, and diagnosis by allergists. Full article

Background: Asthma is a heterogeneous chronic airway disease characterized by inflammation, airflow obstruction, hyperresponsiveness, and remodeling. Severe eosinophilic asthma is driven by eosinophilic inflammation, which contributes to tissue damage, recurrent exacerbations, and progressive impairment of airway structure and function. Eosinophils play a central role through the release of cytokines, cytotoxic granule proteins, and extracellular traps, and their persistence in the airways is sustained by type 2 inflammatory pathways, particularly interleukin-5-mediated signaling. A better understanding of eosinophil biology has promoted the development of targeted therapies, including anti-interleukin-5/interleukin-5 receptor agents and biologics that indirectly modulate eosinophilic inflammation, such as anti-interleukin-4 receptor alpha and anti-thymic stromal lymphopoietin antibodies. Aim: This narrative review summarizes the immunopathology of eosinophilic asthma and links eosinophil biology to current and emerging pharmacological strategies. We discuss biologics that directly target the IL-5/IL-5 receptor axis, as well as agents that indirectly modulate eosinophilic inflammation, including IL-4 receptor alpha and TSLP blockade. We also review the clinical positioning of available biologics, focusing on blood eosinophils, FeNO, exacerbation history, oral corticosteroid exposure, lung function, type 2 comorbidities, treatment response, remission and switching. Conclusions: Overall, eosinophilic inflammation remains a central therapeutic target and a key component of precision medicine in severe asthma, but biologic selection should be individualized and reassessed through multidomain clinical outcomes. Full article

Multiple interacting risk factors can influence the origin of asthma. Asthma is characterized by different clinical phenotypes, each of which includes different endotypes. There are four main clinical asthma phenotypes: (1) early-onset mild allergic asthma; (2) early-onset allergic moderate-to-severe remodeled asthma; (3) late-onset non-allergic eosinophilic asthma; and (4) late-onset non-eosinophilic non-allergic asthma. The main endotypes of asthma are T-helper (Th)-2 low and Th-2 high. The identification of asthma endotypes might help precision-based care move toward the personalized management of airway inflammation. In this scenario, it is important to know how the risk factors affect the pathophysiology of asthma. Accordingly, we focus our attention on the impact of obesity and air pollutants and how these risk factors together with epigenetic alterations influence the asthma phenotype/endotype and the pathogenesis of airway diseases. Our aim is to disseminate the progress of studies in this area by reporting recent observations on the topic. Finally, we believe that data/observations enclosed in this review suggest the need of further epidemiological studies to be useful to examine simultaneously the effect of more than one risk factor on clinical and biologic parameters of asthma. Full article

Interleukin-5 (IL-5) has long been positioned as a lineage-restricted cytokine primarily responsible for eosinophil differentiation and survival. However, emerging mechanistic and clinical evidence supports a broader conceptual shift: IL-5 should no longer be viewed solely as an eosinophil growth factor, but as a context-dependent regulator embedded within dynamic airway immune networks. Drawing on advances in eosinophil subset biology, receptor signaling, and tissue-level immune crosstalk, this review reframes IL-5 biology through the lens of systems-level inflammatory regulation across airway and systemic eosinophilic diseases. Recent data reveal functional heterogeneity between resident and inflammatory eosinophil subsets, challenging the assumption that blood eosinophilia uniformly reflects pathogenic activity. In parallel, functional IL-5 receptor expression has been identified on multiple structural and immune cell populations—including epithelial cells, mast cells, plasma cells, basophils, neutrophils, and fibroblasts—supporting a broader tissue-signaling paradigm. Experimental and translational studies further link IL-5 to epithelial integrity, airway remodeling, and mucus pathology, suggesting structural and network-level effects beyond simple eosinophil depletion. Comparative analyses across asthma, chronic rhinosinusitis with nasal polyps, and COPD demonstrate that eosinophilic inflammation is biologically heterogeneous and context-dependent. While IL-5-targeted therapies yield consistent benefit in severe asthma, therapeutic responses in other airway diseases appear to be shaped by local tissue architecture and mixed inflammatory programs. Together, these observations illustrate a paradigm shift from pathway-specific inhibition toward network-informed disease control and highlight key areas for future mechanistic investigation. Full article

Background: The study aims to analyze the safety and efficacy of Mepolizumab and Dupilumab in the treatment of patients affected by severe chronic rhinosinusitis not controlled with nasal polyposis (CRSwNP) from a tertiary care regional referral center, with the aim of improving the concept of personalized medicine. Methods: A retrospective study was conducted on 72 adult patients selected for biologic therapy according to EPOS/EUFOREA criteria. The patients received either Mepolizumab or Dupilumab. Primary endpoints were reduction in nasal polyp size, improvement in disease-specific quality of life (sinonasal outcome test-22, visual analog scale), olfactory recovery, and asthma control. Secondary outcomes were the assessment of adverse events. Results: Both monoclonal antibodies significantly improved nasal polyps score (NPS), sinonasal outcome test-22 (SNOT-22), and asthma control test (ACT) over time, with no statistically significant differences between Mepolizumab and Dupilumab. In contrast, blood eosinophil counts showed significant differences: Dupilumab was associated with a transient increase in eosinophil levels (absolute Δ = 660.08% Δ = 9%; p < 0.001), while Mepolizumab produced a marked reduction (absolute Δ = 192.52% Δ = 2%; p < 0.001). Both treatments were well tolerated, with only mild adverse events reported. Conclusions: Mepolizumab and Dupilumab are both effective and safe in improving sinonasal symptoms and quality of life in severe uncontrolled CRSwNP. While improvements in NPS, SNOT-22, and ACT scores were comparable, Mepolizumab achieved a significant reduction in eosinophil counts, whereas Dupilumab was associated with faster clinical improvement but a transient eosinophilia. These findings suggest that biologic choice may be guided by individual patient profiles and inflammatory patterns. Full article

Background/Objectives: Severe asthma in routine practice often involves long-standing disease, multimorbidity, and prior biologic failure—settings underrepresented in pivotal tezepelumab trials. This study evaluated 52-week real-world effectiveness and safety of tezepelumab in a highly comorbid, predominantly T2-high, biologic-experienced severe asthma cohort from the Canary Islands. Methods: TEZNERIFE is a multicenter, retrospective study including consecutive adolescents and adults with GINA Step 5 severe uncontrolled asthma treated with tezepelumab 210 mg every 4 weeks for 12 months. Clinical outcomes, lung function, type 2 biomarkers, upper airway symptoms, and Biologics Asthma Response Score (BARS) were assessed at baseline, 26 weeks, and 52 weeks. Results: Fifty-six patients (mean age 53.5 years, 71% female, mean asthma duration 30 years, 84% T2-high; 71% with ≥1 prior biologic) were analyzed. ACT improved from 11.5 ± 3.7 to 15.9 ± 4.7 at 26 weeks and 17.5 ± 4.7 at 52 weeks (both p < 0.0001), while annualized exacerbations declined from 2.79 ± 2.0 to 0.50 ± 0.72 and 0.51 ± 0.89 (both p < 0.0001). Maintenance oral corticosteroid dose fell from 10.2 ± 8.3 to 6.9 ± 2.4 mg/day at 52 weeks (p = 0.014). FEV1% predicted increased from 69.3 ± 19.2% to 75.3 ± 17.7% and 76.2 ± 20.6% (p = 0.004 and p = 0.001), and blood eosinophils decreased from 234 ± 231 to 146 ± 120 and 147 ± 110 cells/µL (p = 0.001 and p = 0.013). At one year, 18.9% and 67.9% were classified as good and intermediate responders by BARS; 13.2% were insufficient responders. Two patients discontinued due to non-serious adverse events, while no treatment-related serious events occurred. Conclusions: In this difficult-to-treat, multimorbid, biologic-experienced population, tezepelumab achieved sustained improvements in asthma control, exacerbations, lung function, eosinophilic inflammation, and corticosteroid exposure over 52 weeks, supporting upstream alarmin inhibition as a versatile strategy in complex severe asthma. Full article

Background/Objectives: Dupilumab is a fully human IgG4 monoclonal antibody targeting the interleukin-4 receptor α subunit, inhibiting interleukin-4 and interleukin-13 signalling, and suppressing type 2 inflammation. It is approved for several eosinophilic and type 2 inflammatory diseases, including chronic rhinosinusitis with nasal polyps, asthma, atopic dermatitis, eosinophilic oesophagitis, and, more recently, eosinophilic chronic obstructive pulmonary disease. Although generally well tolerated, dupilumab has been associated with peripheral eosinophilia and, rarely, eosinophil-mediated complications. This study aims to describe cases of eosinophilic granulomatosis with polyangiitis (EGPA) occurring after dupilumab initiation and to review available evidence on this association. Methods: We describe two cases of new-onset EGPA developing after the introduction of dupilumab therapy, analysing clinical features, laboratory findings, management, and outcomes. A narrative review of published case reports and literature addressing dupilumab-associated eosinophilia and EGPA was also performed. Results: Both patients developed EGPA after starting dupilumab, presenting with marked peripheral eosinophilia and systemic manifestations consistent with the disease. Clinical improvement was observed following dupilumab discontinuation and initiation of appropriate immunosuppressive treatment. The literature review identified a small number of similar reports describing EGPA onset or unmasking in temporal association with dupilumab, mainly in patients with underlying type 2 inflammatory disorders. Conclusions: While a causal relationship between dupilumab and EGPA remains unproven, these findings highlight the importance of clinical awareness. Dupilumab remains an effective therapy for severe type 2 inflammatory diseases; careful monitoring may allow early recognition and management of rare eosinophilic complications. Full article

Background: Severe asthma remains associated with substantial morbidity despite optimized inhaled therapy. Biologic agents targeting type 2 inflammation improve clinical outcomes; however, real-world evidence regarding the durability of these effects beyond the first treatment year remains limited. The present study extends the follow-up of a previously reported real-world cohort in which 12-month outcomes of biologic therapy were evaluated. Methods: We conducted a retrospective observational longitudinal study of adults with severe asthma treated with omalizumab, benralizumab, or dupilumab at a tertiary center in Târgu-Mureș, Romania, between 2020 and 2025, extending follow-up of a previously published real-world cohort. The same patient cohort was followed for an additional period, with longitudinal data collected up to 24 months after biologic therapy initiation. Clinical, functional, and biomarker outcomes were assessed at baseline, 12 months, and 24 months, including Asthma Control Test (ACT) score, forced expiratory volume in one second (FEV₁% predicted), annual exacerbation rate, blood eosinophil count, and fractional exhaled nitric oxide (FeNO). Remission was defined as clinical (ACT ≥ 20, no severe exacerbations, and no maintenance oral corticosteroids), biological (FeNO < 20 ppb and blood eosinophils < 150/µL), and complete (both clinical and biological). Longitudinal changes were analyzed using the Friedman test with post hoc Wilcoxon signed-rank tests. Results: Forty-eight patients were included at baseline, and 41 had available data at 24 months. ACT scores improved from 12 (IQR 11–14) at baseline to 23 (21–25) at 12 months and remained stable at 22 (20–25) at 24 months (p < 0.001). Predicted FEV₁% increased from 50 (39–59) to 78 (68–88) at 12 months and 79 (66–96) at 24 months (p < 0.001). Blood eosinophil counts were markedly suppressed, and FeNO levels continued to decrease over time. Exacerbations declined from 2 (2–3) per year at baseline to 0 and 0.5 (0–1) at 12 and 24 months, respectively (p < 0.001). At 24 months, clinical, biological, and complete remission were observed in 61.0%, 78.0%, and 41.5% of patients with available paired data, respectively. Conclusions: Biologic therapy was associated with sustained clinical and functional improvement over 24 months, accompanied by sustained improvement in type 2 airway inflammation and increasing proportions of patients meeting remission criteria in real-world practice. Full article

Eosinophils are multifunctional granulocytes with central roles in the pathobiology of chronic airway diseases. While systemic eosinophilia (>300 cells/μL) is a well-established biomarker to guide therapeutic decision-making, accumulating evidence indicates that eosinophils are not a uniform population but instead exhibit substantial phenotypic and functional heterogeneity across biological compartments, inflammatory states, and disease contexts. In this review, we synthesize the current understanding of eosinophil heterogeneity in airway diseases and critically evaluate the strengths and limitations of surface marker-based approaches, with emphasis on CD62L/L-selectin-defined subpopulations. Although CD62L-based stratification has provided valuable insight into eosinophil activation and tissue localization, its limited specificity, inconsistent clinical associations, and reliance on murine models restrict its utility as a framework for eosinophil subtyping in humans. We highlight how transcriptomic and proteomic profiling has transformed the field by revealing that peripheral blood eosinophils are largely quiescent, whereas disease-relevant functional specialization is predominantly acquired within inflamed tissues in response to cues from the local microenvironment. These molecular studies support a model in which eosinophil heterogeneity represents a continuum of activation rather than discrete, fixed subsets. A refined, integrative approach to understanding eosinophil heterogeneity is critical for improving patient stratification, predicting therapeutic responsiveness, and optimizing precision medicine strategies in chronic airway diseases. Full article

Background: Tezepelumab has demonstrated efficacy in severe uncontrolled asthma (SUA), although real-world evidence remains limited. Methods: We included patients with SUA who completed at least 6 months of treatment. Lung function, eosinophil counts, IgE, FeNO, comorbidities, and changes in asthma control were assessed using ACT, ACQ, the VAS, and quality of life (AQLQ), as well as severe exacerbations (hospital admissions and emergency visits), oral corticosteroid (OCS) courses, OCS withdrawal/dose reduction, and reductions in maintenance and reliever medication. Response was evaluated using the FEOS and EXACTO scales. Baseline (T0) and 6-month (T6) outcomes were compared in the overall cohort and according to T2-high (eosinophilic/allergic) vs. T2-low phenotype. Results: A total of 33 patients were analyzed (58 ± 12 years; 94% women), with a high burden of comorbidities (88%), mainly rhinosinusitis (79%), obesity (41%), and smoking (37%). Of these, 45.5% had received prior biologic therapy. All patients were on high-dose ICS + LABA, frequently with LAMA and other controllers; 30% were on maintenance OCS. In the previous year, 49% had been hospitalized, 97% had attended the emergency department, and 100% required OCS courses. After 10 ± 3 months, the overall group showed significant improvement in VAS, ACT, ACQ, and AQLQ (p < 0.001), with a reduction in eosinophils, but no significant change in FEV1%. Severe exacerbations, emergency visits, hospitalizations, and OCS courses decreased markedly (p < 0.001). Among 10 patients on maintenance OCS, OCS were discontinued in 7 and reduced in 3; maintenance/reliever medication was also reduced. The T2-high phenotype showed a higher likelihood of “complete response” (52% vs. 17% in non-T2), although “good response” predominated in non-T2; this difference was significant (p = 0.04). Conclusions: Tezepelumab improved asthma control and reduced healthcare utilization and corticosteroid use in both T2 and non-T2 patients, achieving clinical remission in 40%, with better outcomes in T2. Full article