Sustained remission induced by 2 years of treatment with benralizumab in patients with severe eosinophilic asthma and nasal polyposis.

BACKGROUND AND OBJECTIVE: Several randomized controlled trials (RCTs) have shown that benralizumab is characterized by a good profile of efficacy and safety, thereby being potentially able to elicit clinical remission on-treatment of severe eosinophilic asthma (SEA). The main goal of this multicentre observational study was to verify the effectiveness of benralizumab in inducing a sustained remission on-treatment of SEA in patients with or without comorbid chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Throughout 2 years of treatment with benralizumab, a four-component evaluation of sustained remission of SEA was performed, including the assessment of SEA exacerbations, use of oral corticosteroids (OCSs), symptom control and lung function. RESULTS: The present study recruited 164 patients suffering from SEA. After 24 months of add-on biological therapy with benralizumab, 69 (42.1%) achieved the important target of sustained remission on-treatment (exacerbation rate = 0, OCS dose = 0, pre-bronchodilator FEV1 ≥80% pred., ACT score ≥ 20). During the same period, a persistent improvement of CRSwNP (SNOT-22 < 30, NP recurrence = 0) was observed in 33 (40.2%) out of 82 subjects with concomitant NP. The latter comorbidity and post-bronchodilator reversibility of airflow limitation were two independent predictors of sustained remission on-treatment (OR = 2.32, p < 0.05 and OR = 5.59, p < 0.01, respectively). CONCLUSION: Taken together, the results of this real-life clinical investigation indicate that benralizumab can induce a sustained remission on-treatment of SEA, especially in those patients with comorbid CRSwNP and reversible airflow limitation.

Diagnostic delay in bronchiectasis: an Italian perspective.

It takes ∼3.5 years to reach a diagnosis of bronchiectasis from onset of symptoms: the long patient's journey in Italy https://bit.ly/46XMWAz.

Real-world characteristics of "super-responders" to mepolizumab and benralizumab in severe eosinophilic asthma and eosinophilic granulomatosis with polyangiitis.

Background: The current definition of severe eosinophilic asthma (SEA) super-responders to biologic treatment does not include patients with other eosinophil-based comorbidities. Although eosinophilic granulomatosis with polyangiitis (EGPA) is frequently associated with SEA, we lack data on a possible super-response to biologic treatments in patients suffering from these two diseases. We aim to assess super-responder features in real-life patients with SEA and EGPA treated with mepolizumab and benralizumab. Methods: We enrolled 39 patients with SEA and EGPA eligible for treatment with mepolizumab or benralizumab. Super-responder assessment was performed considering oral corticosteroid (OCS) cessation, lack of exacerbations, forced expiratory volume in 1 s and Asthma Control Test (ACT) improvement. Results: Super-responders showed worse clinical baseline characteristics than non-super-responder patients, with a greater improvement in severe asthma exacerbations, OCS dose reduction and ACT score increase. Definition of super-responders was consistent only considering a 12-month course of monoclonal antibody, lacking sensitivity in earlier evaluations. Conclusion: Mepolizumab and benralizumab are safe and effective in patients with EGPA and SEA, since a consistent proportion of patients show a super-response after 12 months of treatment. Further studies will address specific criteria for super-responder assessment in these patients.

Personalized Medicine in Asthma: Current Approach and Future Perspectives.

Asthma is one of the most common chronic respiratory diseases, affecting over 300 million people worldwide [...].

Effectiveness and safety of anti-IL-5/Rα biologics in eosinophilic granulomatosis with polyangiitis: a two-year multicenter observational study.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare vasculitis characterized by asthma, systemic manifestations, and blood and tissue eosinophilia. Objective: To assess the effectiveness and safety of mepolizumab (anti-IL-5) and benralizumab (anti-IL-5Rα) in EGPA for 24 months. Methods: We conducted a multicenter observational study, including patients with EGPA treated with anti-IL-5/Rα biologics in 9 Italian specialized facilities. Systemic disease activity, remission and relapse rate were evaluated from 3 to 24 months after treatment initiation. Respiratory outcomes, hematological parameters, corticosteroid (OCS) and immunosuppressants consumption were also assessed. Results: 49 patients with relapsing-refractory EGPA were included [26 (53.1%) benralizumab 30mg, 20 (40.8%) mepolizumab 100mg, 3 (6.1%) mepolizumab 300mg]. Overall, 38.8% and 57.1% achieved remission after 12 and 24 months, respectively (69.2% benralizumab and 43.5% mepolizumab). Lower OCS intake and higher blood eosinophil count at baseline were associated with remission at 24 months. Both biologics exerted beneficial effects on severe asthma outcomes. Indeed, 61.2% (61.5% benralizumab and 60.8% mepolizumab) remained exacerbation-free during treatment. Lung function parameters showed improvements in the overall cohort (all p<0.05), but began to decline from month 12, especially with mepolizumab. Marked reduction in blood eosinophils was registered with mepolizumab (p<0.0001), while benralizumab depleted both eosinophils (p<0.0001) and basophils (p<0.0001). In general, 69.6% (76% benralizumab and 61.9% mepolizumab) of OCS-dependent patients lowered their daily dose by 75%, while 28.3% discontinued these drugs. Immunosuppressants were suspended in 88.2% of cases. Adverse events were reported in 8.2% of patients. Conclusions: These real-world data suggest that anti-IL-5/Rα biologics are effective and safe in the long-term as add-on treatments for patients with EGPA.

Switching Biological Therapies in Severe Asthma.

Currently, three classes of monoclonal antibodies targeting type 2 inflammation pathways are available in Italy for the treatment of severe asthma: anti-IgE (Omalizumab), anti-IL-5/anti-IL-5Rα (Mepolizumab and Benralizumab), and anti-IL-4Rα (Dupilumab). Numerous randomized controlled trials (RCTs) and real-life studies have been conducted to define their efficacy and identify baseline patients' characteristics potentially predictive of favorable outcomes. Switching to another monoclonal antibody is recommended in case of a lack of benefits. The aim of this work is to review the current knowledge on the impact of switching biological therapies in severe asthma as well as on predictors of treatment response or failure. Almost all of the information about switching from a previous monoclonal antibody to another comes from a real-life setting. In the available studies, the most frequent initial biologic was Omalizumab and patients who were switched because of suboptimal control with a previous biologic therapy were more likely to have a higher baseline blood eosinophil count and exacerbation rate despite OCS dependence. The choice of the most suitable treatment may be guided by the patient's clinical history, biomarkers of endotype (mainly blood eosinophils and FeNO), and comorbidities (especially nasal polyposis). Due to overlapping eligibility, larger investigations characterizing the clinical profile of patients benefiting from switching to different monoclonal antibodies are needed.

Benralizumab Effectiveness in Severe Eosinophilic Asthma with Co-Presence of Bronchiectasis: A Real-World Multicentre Observational Study.

Introduction: The co-presence of bronchiectasis (BE) in severe eosinophilic asthma (SEA) is common. Data about the effectiveness of benralizumab in patients with SEA and BE (SEA + BE) are lacking. Aim: The aim of this study was to evaluate the effectiveness of benralizumab and remission rates in patients with SEA compared to SEA + BE, also according to BE severity. Methods: We conducted a multicentre observational study, including patients with SEA who underwent chest high-resolution computed tomography at baseline. The Bronchiectasis Severity Index (BSI) was used to assess BE severity. Clinical and functional characteristics were collected at baseline and after 6 and 12 months of treatment. Results: We included 74 patients with SEA treated with benralizumab, of which 35 (47.2%) showed the co-presence of bronchiectasis (SEA + BE) with a median BSI of 9 (7-11). Overall, benralizumab significantly improved the annual exacerbation rate (p < 0.0001), oral corticosteroids (OCS) consumption (p < 0.0001) and lung function (p < 0.01). After 12 months, significant differences were found between SEA and SEA + BE cohorts in the number of exacerbation-free patients [64.1% vs. 20%, OR 0.14 (95% CI 0.05-0.40), p < 0.0001], the proportion of OCS withdrawal [-92.6% vs. -48.6, p = 0.0003], and the daily dose of OCS [-5 mg (0 to -12.5) vs. -12.5 mg (-7.5 to -20), p = 0.0112]. Remission (zero exacerbations + zero OCS) was achieved more frequently in the SEA cohort [66.7% vs. 14.3%, OR 0.08 (95% CI 0.03-0.27), p < 0.0001]. Changes in FEV1% and FEF25-75% were inversely correlated with BSI (r = -0.36, p = 0.0448 and r = -0.41, p = 0.0191, respectively). Conclusions: These data suggest that benralizumab exerts beneficial effects in SEA with or without BE, although the former achieved less OCS sparing and fewer respiratory-function improvements.

Real-life effects of dupilumab in patients with severe type 2 asthma, according to atopic trait and presence of chronic rhinosinusitis with nasal polyps.

Background: The efficacy of dupilumab as biological treatment of severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) depends on its ability to inhibit the pathophysiologic mechanisms involved in type 2 inflammation. Objective: To assess in a large sample of subjects with severe asthma, the therapeutic impact of dupilumab in real-life, with regard to positive or negative skin prick test (SPT) and CRSwNP presence or absence. Methods: Clinical, functional, and laboratory parameters were measured at baseline and 24 weeks after the first dupilumab administration. Moreover, a comparative evaluation was carried out in relation to the presence or absence of SPT positivity and CRSwNP. Results: Among the 127 recruited patients with severe asthma, 90 had positive SPT, while 78 reported CRSwNP. Compared with the 6 months preceding the first dupilumab injection, asthma exacerbations decreased from 4.0 (2.0-5.0) to 0.0 (0.0-0.0) (p < 0.0001), as well as the daily prednisone intake fell from 12.50 mg (0.00-25.00) to 0.00 mg (0.00-0.00) (p < 0.0001). In the same period, asthma control test (ACT) score increased from 14 (10-18) to 22 (20-24) (p < 0.0001), and sino-nasal outcome test (SNOT-22) score dropped from 55.84 ± 20.32 to 19.76 ± 12.76 (p < 0.0001). Moreover, we observed relevant increases in forced expiratory volume in one second (FEV1) from the baseline value of 2.13 L (1.62-2.81) to 2.39 L (1.89-3.06) (p < 0.0001). Fractional exhaled nitric oxide (FeNO) values decreased from 27.0 ppb (18.0-37.5) to 13.0 ppb (5.0-20.0) (p < 0.0001). These improvements were quite similar in subgroups of patients characterized by SPT negativity or positivity, and CRSwNP absence or presence. No statistically significant correlations were detected between serum IgE levels, baseline blood eosinophils or FeNO levels and dupilumab-induced changes, with the exception of FEV1 increase, which was shown to be positively correlated with FeNO values (r = 0.3147; p < 0.01). Conclusion: Our results consolidate the strategic position of dupilumab in its role as an excellent therapeutic option currently available within the context of modern biological treatments of severe asthma and CRSwNP, frequently driven by type 2 airway inflammation.

High-flow nasal oxygen versus conventional oxygen therapy in patients with COVID-19 pneumonia and mild hypoxaemia: a randomised controlled trial.

RATIONALE: In patients with COVID-19 pneumonia and mild hypoxaemia, the clinical benefit of high-flow nasal oxygen (HFNO) remains unclear. We aimed to examine whether HFNO compared with conventional oxygen therapy (COT) could prevent escalation of respiratory support in this patient population. METHODS: In this multicentre, randomised, parallel-group, open-label trial, patients with COVID-19 pneumonia and peripheral oxygen saturation (SpO2) ≤92% who required oxygen therapy were randomised to HFNO or COT. The primary outcome was the rate of escalation of respiratory support (ie, continuous positive airway pressure, non-invasive ventilation or invasive mechanical ventilation) within 28 days. Among secondary outcomes, clinical recovery was defined as the improvement in oxygenation (SpO2 ≥96% with fractional inspired oxygen (FiO2) ≤30% or partial pressure of arterial carbon dioxide/FiO2 ratio >300 mm Hg). RESULTS: Among 364 randomised patients, 55 (30.3%) of 181 patients assigned to HFNO and 70 (38.6%) of 181 patients assigned to COT underwent escalation of respiratory support, with no significant difference between groups (absolute risk difference -8.2% (95% CI -18% to +1.4%); RR 0.79 (95% CI 0.59 to 1.05); p=0.09). There was no significant difference in clinical recovery (69.1% vs 60.8%; absolute risk difference 8.2% (95% CI -1.5% to +18.0%), RR 1.14 (95% CI 0.98 to 1.32)), intensive care unit admission (7.7% vs 11.0%, absolute risk difference -3.3% (95% CI -9.3% to +2.6%)), and in hospital length of stay (11 (IQR 8-17) vs 11 (IQR 7-20) days, absolute risk difference -1.0% (95% CI -3.1% to +1.1%)). CONCLUSIONS: Among patients with COVID-19 pneumonia and mild hypoxaemia, the use of HFNO did not significantly reduce the likelihood of escalation of respiratory support. TRIAL REGISTRATION NUMBER: NCT04655638.

Female Sex Affects Respiratory Function and Exercise Ability in Patients Recovered from COVID-19 Pneumonia.

Background: Coronavirus-19 Disease (COVID-19) may cause persistent symptoms and functional respiratory impairment, known as long COVID. Determinants of long COVID are unclear. Although males experience more severe acute illness, the impact of sex on the occurrence of long-term sequelae is unknown. The aim of this study was to establish whether sex affects pulmonary function, exercise capacity, and clinical outcomes in patients recovered from COVID-19 pneumonia. Materials and Methods: We performed a retrospective analysis on patients evaluated in our "Post-COVID Clinic" after a median follow-up of 128 days from the acute disease. Tests performed included standard spirometry, diffusion capacity of the lung for carbon monoxide (DLCO), and 6-minute walk test (6-MWT). Results: A total of 157 patients (mean age 59.9 ± 12, 91 males) recovered from mild to severe pneumonia, without previous respiratory disease, were included. No differences in demographic data and in the severity of the acute illness were observed between the two study groups, males and females. Abnormal alveolar diffusion was more common and severe among females (DLCO <80% in 31% of males vs. 53% of females, p < 0.01; DLCO <70%, in 20% of males vs. 40% of females, p < 0.01). Severe reduction in 6-MWT was observed in 20% of males versus 46% of females (p < 0.01). Multiple logistic regression showed that female sex was an independent predictor of abnormal DLCO and 6-MWT. The prevalence of symptoms and radiological abnormalities was similar in the two groups. Conclusions: These data show that at 4 months follow-up women recovered from COVID-19 pneumonia are more likely to exhibit a reduced alveolar diffusion capacity and exercise tolerance than men, although a similar severity of the acute disease.

Long-Term Domiciliary High-Flow Nasal Therapy in Patients with Bronchiectasis: A Preliminary Retrospective Observational Case-Control Study.

High-flow nasal therapy (HFNT) provides several pathophysiological benefits in chronic respiratory disorders. We aimed to evaluate the effectiveness of long-term HFNT in patients with bronchiectasis (BE). METHODS: This is a retrospective bicentric case-control study of outpatients with BE on optimized medical treatment with a severe exacerbation requiring hospitalization in the previous year. Patients on long-term home HFNT (cases) and patients on optimized medical treatment alone (controls) were matched by age, sex, bronchiectasis severity index, and exacerbations in the previous year. Data on BE exacerbations, hospitalizations/year, mucus features, respiratory symptoms, and pulmonary function were collected. The primary outcome was the change from baseline in the exacerbation rates at 12 months between groups. RESULTS: 20 patients in the HFNT group and 20 controls were included. A significant reduction in exacerbations [-1.9 (-2.8 to -0.9), p = 0.0005] and hospitalizations [-0.7 (-1.1 to -0.3), p = 0.0006] was found in the HFNT group vs controls. A slight improvement in pulmonary function [FEV1% +6,1% (+1% to +11.3%) (p = 0.0219), FVC% +4.6% (+0.8% to +8.3%) (p = 0.0188) and FEF25-75% +13.4 (+11 to +15.9) (p = 0.0189) was also found in the HFNT group compared to controls. CONCLUSIONS: In this preliminary study, long-term domiciliary HFNT improved the clinical course of patients with BE.

Acute and long-term management of severe bronchiectasis with high flow nasal therapy: A case report.

Bronchiectasis (BE) is a long-term, chronic lung condition featured by widened and scarred airways. These can alter the physiological mucociliary clearance, making it difficult to clear mucus and microorganisms, leading to frequent exacerbations. High flow nasal therapy (HFNT) is a noninvasive respiratory support that delivers heated and humidified gas eventually enriched with oxygen, through a nasal cannula.  Humidification is crucial for adequate airways mucociliary clearance, improving ciliary function and consequently reducing airways inflammation and recurrent infections. HFNT has been mostly used in patients with acute hypoxemic respiratory failure and in selected patients with chronic respiratory failure due to COPD. Still, evidence about its use in acute and long-term home setting in patients with clinically relevant BE are lacking. We report a case of severe widespread BE, already on top medical therapy and pulmonary rehabilitation, still suffering from difficult mucus expectoration and recurrent exacerbations, who has been additionally treated with HFNT, both in hospital and domiciliary, reporting significant improvements on relevant clinical and patient-centered outcomes. Thus, HFNT may confer additional benefits as an add-on treatment of patients with severe BE and respiratory failure.

Sleep quality and mental health during the COVID-19 pandemic in patients with severe obstructive sleep apnea.

BACKGROUND: The first wave of the COVID-19 pandemic has produced remarkable effects on the sleep quality and mental status of the general population and more dramatic effects on patients with chronic illness. Patients with obstructive sleep apnea (OSA), already suffering from disordered sleep, might be more susceptible to the effect of the pandemic on their sleep quality and mental health. We therefore performed a case-control study to compare sleep quality, depression and anxiety symptoms reported by patients with severe OSA and age-matched healthy subjects during the first wave of the COVID-19. In June-July 2020 we enrolled a total of 222 patients with severe OSA, all treated with continuous positive airway pressure, and 164 healthy controls. Self-reported sleep quality was assessed using the Pittsburg Sleep Quality Index (PSQI). Symptoms of depression were assessed using the Patient Health Questionnaire module 9 (PHQ-9), while the specific "Coronavirus Anxiety Scale" (CAS) evaluated the level of anxiety. RESULTS: Patients with OSA (61% males, 65 ± 9.6 years old, BMI 30.5 ± 3.6) and healthy controls had similar characteristics except for BMI slightly lower in controls. The perceived quality of sleep, referred to the pre-pandemic period, was significantly worse in patients with OSA than in controls. During the pandemic the rate of reported sleep disturbance increased from 54 to 66% in patients with OSA and from 29 to 40% in controls. A high percentage of patients and controls reported symptoms of depression (61% OSA and 65% controls), whereas lower levels of anxiety, similar in the two groups, were observed. In patients with OSA the PSQI score significantly positively correlated with the PHQ-9 score (r2 = 0.81) and the CAS score (r2 = 0.65). CONCLUSION: The rate of reported sleep disturbance in patients with OSA during the first wave of the COVID-19 pandemic is one of the highest evidenced in literature so far. As for the general population, in these patients there is a strict link between the perceived sleep quality and the psychological distress caused by the pandemic. A further deterioration of sleep quality is a fearsome event in the life of these patients who face life-long sleep problems.

Impact of asthma on bronchiectasis severity and risk of exacerbations.

OBJECTIVE: Asthma is a frequent comorbidity of bronchiectasis, with possible implications for exacerbation and severity. We investigated the clinical impact of asthma on bronchiectasis in terms of disease severity and exacerbation risk. METHODS: We collected demographic, clinical, and functional characteristics of patients with a confirmed diagnosis of bronchiectasis. All patients were investigated for concomitant diagnosis of asthma. The Bhalla score was used to assess radiological severity of bronchiectasis, and the Bronchiectasis Severity Index (BSI) was used to assess the clinical severity. Blood and sputum samples were collected to assess blood cell count, erythrocyte sedimentation rate, c-reactive protein, immunological status (IgA, IgE, IgM, IgG, and IgG subclasses), and microbiological analysis. RESULTS: A total of 106 patients were enrolled in the study; 30.2% had concomitant asthma and were characterized by higher frequency of bronchiectasis exacerbation, despite higher Bhalla score and lower BSI compared to patients without asthma. Pseudomonas aeruginosa was more frequently isolated from the sputum of bronchiectasis patients without asthma. Total serum IgG, IgG1, and IgG3 were lower in patients with asthma. Blood eosinophils and exhaled nitric oxide were higher in patients with associated asthma. The presence of asthma and presence of Pseudomonas in sputum were the only significant determinants of frequent exacerbations in a binary logistic regression analysis. CONCLUSION: The coexistence of asthma and bronchiectasis is associated with an independent increase in the risk of bronchiectasis exacerbation despite lower radiological and clinical severity indexes. Asthmatic airway inflammation could promote an enhanced "Cole's Cycle" that is responsible for a higher frequency of exacerbations.

Effectiveness of benralizumab in severe eosinophilic asthma: Distinct sub-phenotypes of response identified by cluster analysis.

BACKGROUND: Benralizumab is effective in severe eosinophilic asthma (SEA), but suboptimal responses are observed in some patients. Although several factors have been associated with benralizumab response, no cluster analysis has yet been undertaken to identify different responsiveness sub-phenotypes. OBJECTIVE: To identify SEA sub-phenotypes with differential responsiveness to benralizumab. METHODS: One hundred and five patients diagnosed with SEA who had completed 6 months of benralizumab treatment were included in a hierarchical cluster analysis based on a set of clinical variables that can be easily collected in routine practice (age, age at disease onset, disease length, allergen sensitization status, blood eosinophil count, IgE levels, FEV1 % predicted, nasal polyposis, bronchiectasis). RESULTS: Four clusters were identified: Clusters 2 and 3 included patients with high levels of both IgE and eosinophils (type-2 biomarkers high), whereas Clusters 1 and 4 included patients with only one type-2 biomarker at a high level: IgE in Cluster 1 and eosinophils in Cluster 4. Clusters 2 and 3 (both type-2 biomarkers high) showed the highest response rate to benralizumab in terms of elimination of exacerbations (79% and 80% respectively) compared to Clusters 1 and 4 (52% and 60% respectively). When super-response (the absence of exacerbation without oral corticosteroid use) was assessed, Cluster 2, including patients with more preserved lung function than the other clusters, but comparable exacerbation rate, oral corticosteroid use and symptom severity, was the most responsive cluster (87.5% of patients). CONCLUSIONS: Our cluster analysis identified benralizumab differential response sub-phenotypes in SEA, with the potential of improving disease treatment and precision management.

Tezepelumab for asthma.

The epithelium, once simply considered a protective barrier against harmful agents, has in recent times gained considerable relevance as an entity that can promote and regulate inflammatory processes through the production of cytokines, namely interleukin (IL)-25, IL-33 and thymic stromal lymphopoietin (TSLP), known as "alarmins". TSLP, in particular, has been extensively studied as a possible therapeutic target in patients with severe asthma because it is involved in the inflammatory processes of both type 2-high and type 2-low inflammation. In this regard, tezepelumab (AMG-157/MEDI-9929), a TSLP-targeted first-in-class fully human monoclonal antibody, has been shown in phase II and III studies to be effective and safe in treating patients with severe asthma, regardless of the underlying endotype or phenotype and irrespective of baseline biomarkers, such as blood eosinophil count and fraction of exhaled nitric oxide. Here, we provide a comprehensive review of TSLP function in airway inflammatory processes, the clinical development of tezepelumab for severe asthma as well as its possible future indications.

Type 2-High Severe Asthma with and without Bronchiectasis: A Prospective Observational Multicentre Study.

INTRODUCTION: Type 2-high severe asthma (T2-SA) is often associated with several comorbidities. To this extent, the coexistence of T2-SA and bronchiectasis (BE) is considered an emerging phenotype. METHODS: We performed a prospective observational multicentre study, including T2-SA patients. Chest HRCT confirmed the presence of BE. Data on exacerbations, pulmonary function, Asthma Control Test (ACT), chronic mucus hypersecretion (CMH), chronic rhinosinusitis (CRS), oral corticosteroid (OCS) dosage, eosinophils in peripheral blood and FeNO were recorded. The Bhalla score was used for radiological assessment of T2-SA+BE patients and the Bronchiectasis Severity Index (BSI) was calculated. RESULTS: A total of 113 patients (mean age 55 ± 11 years, 59.3% female) were enrolled. Co-presence of BE was confirmed in 50/113 (44.2%) patients who identified the T2-SA+BE group. CRS and CRSwNP were more prevalent in T2-SA+BE vs T2-SA [respectively, 42/50 (84%) vs 37/63 (58.7%), p = 0.004 and 27/50 (54%) vs 27/63 (42.9%), p = 0.0165]. Furthermore, T2-SA+BE patients reported more CMH compared to T2-SA [29/50 (58%) vs 15/63 (23.8%), p = 0.0004], were more frequently on chronic OCSs intake [28/50 (56%) vs 22/63 (34.9%), p = 0.0357] and experienced more exacerbations/year [10 (4-12) vs 6 (4-12), p = 0.0487]. In a multivariate logistic regression model, the presence of CRS, CMH and daily OCS intake were associated with BE presence with a 78% (95% CI: 69-88) accuracy. Median Bhalla score was 18.3 (16-20) (Mild radiological severity). Median BSI was 6 (4-8) and only 6/50 (12%) had a BSI score ≥9. Significant inverse linear relationship between BSI and ACT (r = -0.6095, p < 0.0001), FEV1% (r = -0.3297, p = 0.0353) and FEV1 mL (r = -0.4339, p = 0.0046) were found. CONCLUSION: Type 2 inflammation could have a causative role in BE development. Chest HRCT is mandatory when a diagnosis of T2-SA is made, especially in presence of CRS, CMH and chronic OCS intake. Early BE detection may be crucial to improve T2-SA patients' outcomes.

Switch from Omalizumab to Benralizumab in Allergic Patients with Severe Eosinophilic Asthma: A Real-Life Experience from Southern Italy.

BACKGROUND: The wide availability of monoclonal antibodies for the add-on therapy of severe asthma currently allows for the personalization of biologic treatment by selecting the most appropriate drug for each patient. However, subjects with overlapping allergic and eosinophilic phenotypes can be often eligible to more than one biologic, so that the first pharmacologic choice can be quite challenging for clinicians. Within such a context, the aim of our real-life investigation was to verify whether allergic patients with severe eosinophilic asthma, not adequately controlled by an initial biologic treatment with omalizumab, could experience better therapeutic results from a pharmacologic shift to benralizumab. PATIENTS AND METHODS: Twenty allergic patients with severe eosinophilic asthma, unsuccessfully treated with omalizumab and then switched to benralizumab, were assessed for at least 1 year in order to detect eventual changes in disease exacerbations, symptom control, oral corticosteroid intake, lung function, and blood eosinophils. RESULTS: In comparison to the previous omalizumab therapy, after 1 year of treatment with benralizumab our patients experienced significant improvements in asthma exacerbation rate (p < 0.01), rescue medication need (p < 0.001), asthma control test (ACT) score (p < 0.05), forced expiratory volume in the first second (FEV1) (p < 0.05), and blood eosinophil count (p < 0.0001). Furthermore, with respect to the end of omalizumab treatment, the score of sino-nasal outcome test-22 (SNOT-22) significantly decreased after therapy with benralizumab (p < 0.05). CONCLUSION: The results of this real-life study suggest that the pharmacologic shift from omalizumab to benralizumab can be a valuable therapeutic approach for allergic patients with severe eosinophilic asthma, not adequately controlled by anti-IgE treatment.

Benralizumab Effectiveness in Severe Eosinophilic Asthma with and without Chronic Rhinosinusitis with Nasal Polyps: A Real-World Multicenter Study.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) affects around 60% of patients with severe eosinophilic asthma (SEA). Benralizumab was recently approved for SEA add-on treatment. OBJECTIVE: To assess the real-world effectiveness of benralizumab in SEA with or without CRSwNP. METHODS: We conducted a multicenter observational study, including patients with SEA treated with benralizumab for 24 weeks in 12 Italian specialized facilities. Asthma exacerbations, Asthma Control Test (ACT), lung function, oral corticosteroid (OCS) dosage, and eosinophil and basophil count in peripheral blood were recorded at baseline and after 4, 12, and 24 weeks. The 22-item Sino-Nasal Outcome Test (SNOT-22) and Lund-Mackay scores were assessed at baseline and after 24 weeks in SEA+CRSwNP. RESULTS: A total of 137 patients with late-onset SEA were included; 57.7% (79 of 137) showed the copresence of CRSwNP. Overall, severe asthma exacerbations decreased from 4 (3-6) to 0 (0-2) (P < .0001) after 24 weeks of treatment, and significant improvements were observed as early as 4 weeks in ACT score, OCS dosage, forced expiratory volume in the 1st second (FEV1)%, FEV1 (L), forced vital capacity (FVC)%, FEV1/FVC% (P < .0001), and forced expiratory flow between 25% and 75% of FVC (FEF25-75)% (P = .0022). Eosinophils and basophils in peripheral blood were rapidly depleted. In patients with SEA+CRSwNP, SNOT-22 decreased from 46 (39.5-64.5) to 32 (19-46) (P < .0001). Furthermore, in comparison with SEA, they showed enhanced responses with regard to ACT minimal clinically important difference (P = .0387), FEV1% (P = .017), FEV1 (L) (P = .02), and FEF25-75% (P = .0362). CONCLUSIONS: These real-world data suggest that benralizumab can represent a valid add-on therapeutic option for patients with SEA, especially with comorbid CRSwNP.

Mepolizumab effectiveness in patients with severe eosinophilic asthma and co-presence of bronchiectasis: A real-world retrospective pilot study.

BACKGROUND: The association of bronchiectasis (BE) in patients with severe eosinophilic asthma (SEA) is quite frequent. Mepolizumab is a well-recognized treatment for SEA; we aim to evaluate its effectiveness in SEA patients with and without BE in real-life. METHODS: We performed a single-center retrospective pilot study, including patients with SEA treated with mepolizumab for one year. Asthma control test (ACT), lung function, annual exacerbations rate, oral corticosteroid dosage, FeNO, chronic mucous secretions, blood and sputum eosinophils were recorded at baseline and after 6 and 12 months. RESULTS: we included 32 patients (mean age: 52.3 ± 10, 59% female). 50% showed co-presence of bronchiectasis, (SEA + BE). Significant improvements were found in ACT [(13.8 ± 4.6 to 20.7 ± 4.1, p = 0.0009) and (13 ± 4.8 to 20.7 ± 4.6, p = 0.0003)], annual exacerbations rate [from 7 (4-12) to 0 (0.00-0.75) and from 8 (4-12) to 0 (0-1), p < 0.0001], and blood eosinophils count [748 cells/µL (400-1250) vs. 84 cells/µL (52.5-100), and from 691 cells/µL (405-798) vs. 60 cells/µL (41-105), p < 0.0001] in SEA and SEA + BE group respectively, already after 6 months of treatment. A reduction in daily oral corticosteroids intake at 12 months was shown [from 15 mg (0-25) to 0 mg (0-0), p = 0.003 and from 8.8 mg (0-25) to 0 mg (0-0) (p = 0.01)] in both SEA and SEA + BE, respectively. Similar results were found, comparing SEA + BE patients based on the severity of bronchiectasis. CONCLUSIONS: Mepolizumab effectively improves asthma symptoms control, reducing annual exacerbations and corticosteroid intake in all patients with SEA, even in the subgroup with coexisting bronchiectasis, independently of their severity.