Sustained Effectiveness of Benralizumab in Naïve and Biologics-Experienced Severe Eosinophilic Asthma Patients: Results from the ANANKE Study.

Purpose: Severe eosinophilic asthma (SEA) patients often present overlapping inflammatory features rendering them eligible for multiple biologic therapies; switching biologic treatment is a strategy adopted to optimize asthma control when patients show partial or no response to previous biologics. Patients and Methods: ANANKE is a retrospective, multicenter Italian study (NCT04272463). Here, we outline the characteristics and long-term clinical outcomes in naïve-to-biologics and biologics-experienced patients treated with benralizumab for up to 96 weeks. Bio-experienced patients were split into omalizumab and mepolizumab subsets according to the type of biologic previously used. Results: A total of 124 (76.5%) naïve and 38 (23.5%) bio-experienced patients were evaluated at index date; 13 patients (34.2%) switched from mepolizumab, 21 patients (55.3%) switched from omalizumab, and four patients (10.5%) received both biologics. The mepolizumab subset was characterized by the longest SEA duration (median of 4.6 years), the highest prevalence of chronic rhinosinusitis with nasal polyposis (CRSwNP) (76.5%), and the greatest oral corticosteroid (OCS) daily dosage (median of 25 mg prednisone equivalent). The omalizumab group showed the highest severe annual exacerbation rate (AER) (1.70). At 96 weeks, treatment with benralizumab reduced any and severe AER by more than 87% and 94%, respectively, across all groups. Lung function was overall preserved, with major improvements observed in the mepolizumab group, which also revealed a 100% drop of the median OCS dose. Asthma Control Test (ACT) score improved in the naïve group while its increment was more variable in bio-experienced patients; among these, a marked difference was noticed between omalizumab and mepolizumab subsets (median ACT score of 23.5 and 18, respectively). Conclusion: Benralizumab promotes durable and profound clinical benefits in naïve and bio-experienced groups, indicating that a nearly complete depletion of eosinophils is highly beneficial in the control of SEA, independently of previous biologic use.

TRITRIAL: The Impact of Fixed Triple Therapy with Beclometasone/Formoterol/Glycopyrronium on Health Status and Adherence in Chronic Obstructive Pulmonary Disease in an Italian Context of Real Life.

Purpose: The TRITRIAL study assessed the effects of beclometasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G) fixed combination in patients with chronic obstructive pulmonary disease (COPD) in a real-world setting, focusing on patient's experience and perspective through the use of patients reported outcomes. Patients and Methods: TRITRIAL was a multicenter, prospective, observational study conducted on patients with moderate-severe COPD treated with BDP/FF/G fixed therapy for 12 months. The main objective was to evaluate the impact of BDP/FF/G on health status through the COPD Assessment Test (CAT) score. Additional assessments included adherence and satisfaction, measured by the TAI-10/12 questionnaire and a specifically designed eight-item questionnaire, quality of life through the EQ-5D-5L test, sleep quality through the COPD and Asthma Sleep Impact Scale (CASIS), as well as safety and disease-related outcomes. Results: Data from 655 patients were analyzed in the study. The mean total CAT score significantly improved (from 22.8 at baseline to 18.1 at 6 months and 16.5 at 12 months; p < 0.0001), as well as all the eight CAT sub-items, which decreased on average by 0.5-0.9 points during the study. Adherence and usability of the inhaler also improved during the study, with a decrease in poor compliance (from 30.1% to 18.3%) and an increase in good compliance (from 51.8% to 58.3%) according to the TAI score. Patients also benefited from significantly improved quality of life (EQ Index from 0.70 to 0.80; EQ-5D VAS score from 55.1 to 63.1) and sleep quality (CASIS score from 41.1 to 31.8). Finally, patients reported a significant reduction in exacerbation during the study. Conclusion: TRITRIAL showed that the BDP/FF/G fixed combination is effective and safe in patients with moderate-severe COPD and poorly controlled disease, improving patients' HRQoL, sleep quality, adherence and inhaler usability and reducing COPD symptoms and the risk of exacerbation in a real-life setting.

Impact of biologics on lung hyperinflation in patients with severe asthma.

BACKGROUND: In asthma, inflammation affects both the proximal and distal airways and can cause significant hyperinflation, which is thought to be a major cause of dyspnea. METHODS: This is a retrospective observational study evaluating the effect of three months of treatment with different biologic drugs (benralizumab, dupilumab and omalizumab) on pulmonary hyperinflation in a cohort of patients with severe asthma already receiving regular triple inhaled therapy. Changes in RV, RV/TLC ratio, FRC and FRC/TLC ratio were the primary efficacy measures. Secondary outcomes included FEV1, FVC, FEV1/FVC ratio, IC, IC/TLC ratio, asthma control test, the percentage of eosinophils in the blood and fractional FENO. RESULTS: Benralizumab led to significant changes (p < 0.001) in RV, RV/TLC, FRC, and FRC/TLC. Dupilumab demonstrated a notable reduction in RV (p = 0.017) and RV/TLC (p = 0.002), but the decreases in FRC and FRC/TLC were merely numerical and not as pronounced as those induced by benralizumab. Omalizumab's positive impact on RV (p = 0.057) and RV/TLC (p = 0.085), as well as FRC (p = 0.202) and FRC/TLC (p = 0.096), was also predominantly numerical, with a tendency towards efficacy, albeit excluding the effect on FRC. Treatment with biologics resulted in improvements in all other lung function parameters assessed and a decrease in FENO levels. CONCLUSION: This study, although limited by small sample size, lack of a placebo control, and unbalanced group sizes, suggests that biological agents are effective in reducing lung hyperinflation even after a relatively short treatment.

Features of severe asthma response to anti-IL5/IL5r therapies: identikit of clinical remission.

Introduction: Clinical remission (CliR) achievement has been recognized as a new potential outcome in severe asthma. Nevertheless, we still lack a detailed profile of what features could better identify patients undergoing clinical remission. In this study, we aim to address this issue, tracing a possible identikit of patients fulfilling remission criteria. Methods: We enrolled 266 patients with severe eosinophilic asthma (SEA) treated with a 12-month course of anti-IL5/IL5 receptor (IL5r) monoclonal antibodies. Patients with no exacerbation, OCS withdrawal, ACT ≥ 20 and FEV1 ≥ 80% after 1 year of biologic treatment were classified as in clinical remission. Results: 30.5% of the enrolled patients achieved remission after biologic administration. CliR group showed a lower number of baseline asthma exacerbations and better lung function parameters, with a trend for higher ACT scores and a less frequent history of a positive skin prick test. CliR achievement was unlikely in presence of a higher BMI, a positive skin prick test, an increased number of asthma exacerbations before biologic treatment, anti-muscarinic administration, and a previous diagnosis of EGPA, bronchiectasis or osteoporosis. In contrast, a better lung function, an increased blood eosinophilic count, the presence of chronic rhinosinusitis with nasal polyps and a more frequent use of reliever therapy predicts remission development. Changes in exacerbations number, OCS use, ACT scores and FEV1% between remittent and non-remittent patients arise at specific follow up timepoints and are positively associated with CliR achievement. Discussion: anti-IL5/IL5r biologics can induce CliR in a proportion of patients with SEA. Patients achieving remission demonstrate specific clinical, functional and inflammatory features, as well as a specific moment of improvement in all the CliR items.

Patient and physician perspectives on biological treatment in severe asthma: a Severe Asthma Network Italy survey.

Patients with severe asthma perceive beneficial effects of biologics and good self-reported adherence to treatment, even when self-administered at home https://bit.ly/48vP70w.

Pollen respiratory allergy: Is it really seasonal?

Allergic rhinitis (AR) is a highly prevalent respiratory condition that carries a heavy burden and can have a significant impact on patient quality of life. AR is caused by seasonal or perennial exposure to outdoor pollens and molds as well as indoor allergic triggers. In this review article, we discuss the factors associated with the development of AR throughout the year and the fact that patients with AR need continuous treatment rather than seasonal treatment. Conventionally, AR has been mainly categorized into seasonal AR and perennial AR, but these classes do not seem to be well-adapted. Climate changes, temperature changes, and high carbon dioxide (CO2) concentration affect the growth of plants and increase the length of pollen seasons and pollen allergenicity. Air pollution aggravates allergic sensitization symptoms in AR sensitized individuals. Due to increased air pollution and indefinite pollen seasons AR symptoms are present throughout the year. Patients with AR often need continuous treatment, which should be considered while making the strategy for treating allergic rhinitis sufferers. Management of AR involves avoiding the allergen, medications for symptomatic relief, anti-inflammatory therapies, and allergy immunotherapy. Although the first-generation H1-antihistamines reduce AR symptoms, they cause sedation and impair cognitive functions; thus, second-generation antihistamines (ie, levocetirizine, loratadine, bilastine, fexofenadine) are preferred. The efficacy and safety of fexofenadine for the treatment of seasonal allergic rhinitis (SAR) symptoms have been demonstrated by numerous clinical studies, irrespective of the season and underlying allergen. In this review, we discuss the allergic rhinitis classification, the role of climate change, air pollution, and factors contributing to year-round symptoms in patients with AR and the need for continuous pharmacological treatment for management.

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.

Long-term effectiveness of benralizumab in severe eosinophilic asthma patients treated for 96-weeks: data from the ANANKE study.

BACKGROUND: The efficacy of benralizumab has been broadly demonstrated in severe eosinophilic asthma (SEA), but only few real-life studies evaluated its long-term effects. Here we present novel data from the ANANKE study in which a large cohort of SEA patients was treated for up to 96 weeks. METHODS: ANANKE (NCT04272463) is an observational retrospective Italian study investigating the key characteristics of SEA patients (collected during the 12 months prior to benralizumab initiation) and the clinical outcomes during benralizumab treatment (annual exacerbation rate [AER], lung function, asthma control, OCS use, healthcare resource utilization). A post hoc analysis was also conducted in groups of patients based on history of previous biologic therapy (bio-experienced versus naïve patients). Analyses were descriptive only. RESULTS: Before benralizumab initiation, evaluable SEA patients (N = 162, 61.1% females, mean age 56.0 ± 12.7) showed a median blood eosinophil count (BEC) of 600 cells/mm3 (IQR: 430-890). Patients experienced frequent exacerbations (annualized exacerbation rate [AER]: 4.10, severe AER: 0.98), with impaired lung function and poor asthma control (median ACT score: 14) despite 25.3% reported oral corticosteroid (OCS) use. Nasal polyposis was present in 53.1% patients; 47.5% patients were atopic. After 96 weeks since the start of benralizumab, nearly 90% patients were still on treatment; benralizumab dramatically decreased exacerbations (AER: - 94.9%; severe AER: - 96.9%), improved respiratory parameters (median increase in pre-bronchodilator forced expiratory volume [pre-BD FEV1]: + 400 mL) and asthma control (median ACT score: 23) while eliminating OCS in 60% patients. Importantly, benralizumab effects were either maintained or progressively improved over time, accompanied by a nearly complete depletion of BEC. Benralizumab reduced AER both in naïve (any AER: - 95.9%; severe AER: - 97.5%) and bio-experienced patients (any AER: - 92.4%; severe AER: - 94.0%). CONCLUSIONS: Profound and sustained improvements in all asthma outcomes were observed with benralizumab. The correct identification of patients' eosinophilic-driven asthma phenotype was essential to ensure the achievement of such remarkable results. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04272463.

Genetic heritage of the Baphuthi highlights an over-ethnicized notion of "Bushman" in the Maloti-Drakensberg, southern Africa.

Using contemporary people as proxies for ancient communities is a contentious but necessary practice in anthropology. In southern Africa, the distinction between the Cape KhoeSan and eastern KhoeSan remains unclear, as ethnicity labels have been changed through time and most communities were decimated if not extirpated. The eastern KhoeSan may have had genetic distinctions from neighboring communities who speak Bantu languages and KhoeSan further away; alternatively, the identity may not have been tied to any notion of biology, instead denoting communities with a nomadic "lifeway" distinct from African agro-pastoralism. The Baphuthi of the 1800s in the Maloti-Drakensberg, southern Africa had a substantial KhoeSan constituency and a lifeway of nomadism, cattle raiding, and horticulture. Baphuthi heritage could provide insights into the history of the eastern KhoeSan. We examine genetic affinities of 23 Baphuthi to discern whether the narrative of KhoeSan descent reflects distinct genetic ancestry. Genome-wide SNP data (Illumina GSA) were merged with 52 global populations, for 160,000 SNPs. Genetic analyses show no support for a unique eastern KhoeSan ancestry distinct from other KhoeSan or southern Bantu speakers. The Baphuthi have strong affinities with early-arriving southern Bantu-speaking (Nguni) communities, as the later-arriving non-Nguni show strong evidence of recent African admixture possibly related to late-Iron Age migrations. The references to communities as "San" and "Bushman" in historic literature has often been misconstrued as notions of ethnic/biological distinctions. The terms may have reflected ambiguous references to non-sedentary polities instead, as seems to be the case for the eastern "Bushman" heritage of the Baphuthi.

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.

Climate change, air pollution, pollen allergy and extreme atmospheric events.

PURPOSE OF REVIEW: Respiratory allergy correlates strictly with air pollution and climate change. Due to climate change, the atmospheric content of trigger factors such as pollens and moulds increase and induce rhinitis and asthma in sensitized patients with IgE-mediated allergic reactions.Pollen allergy is frequently used to evaluate the relationship between air pollution and allergic respiratory diseases. Pollen allergens trigger the release of immunomodulatory and pro-inflammatory mediators and accelerate the onset of sensitization to respiratory allergens in predisposed children and adults. Lightning storms during pollen seasons can exacerbate respiratory allergy and asthma not only in adults but also in children with pollinosis. In this study, we have focalized the trigger (chemical and biologic) factors of outdoor air pollution. RECENT FINDINGS: Environmental pollution and climate change have harmful effects on human health, particularly on respiratory system, with frequent impact on social systems.Climate change is characterized by physic meteorological events inducing increase of production and emission of anthropogenic carbon dioxide (CO 2 ) into the atmosphere. Allergenic plants produce more pollen as a response to high atmospheric levels of CO 2 . Climate change also affects extreme atmospheric events such as heat waves, droughts, thunderstorms, floods, cyclones and hurricanes. These climate events, in particular thunderstorms during pollen seasons, can increase the intensity of asthma attacks in pollinosis patients. SUMMARY: Climate change has important effects on the start and pathogenetic aspects of hypersensitivity of pollen allergy. Climate change causes an increase in the production of pollen and a change in the aspects increasing their allergenic properties. Through the effects of climate change, plant growth can be altered so that the new pollen produced are modified affecting more the human health. The need for public education and adoption of governmental measures to prevent environmental pollution and climate change are urgent. Efforts to reduce greenhouse gases, chemical and biologic contributors to air pollution are of critical importance. Extreme weather phenomena such as thunderstorms can trigger exacerbations of asthma attacks and need to be prevented with a correct information and therapy.

The Comorbid Patient in the Spotlight: Efficacy of Benralizumab on Chronic Rhinosinusitis with Nasal Polyp Outcomes in Presence of Severe Asthma.

PURPOSE OF REVIEW: The present review aims to systematically assess published data to elucidate benralizumab efficacy on nasal outcomes in comorbid patients. RECENT FINDINGS: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease of the nasal cavity often associated with severe asthma (SA), contributing to a global disease burden in asthmatics. The two pathologies share common underlying mechanisms (e.g., type-2 inflammation), which sustain symptoms and poor comorbid patient quality of life. Therefore, it is of primary importance to identify the correct therapeutic option in order to achieve the optimal management of patients affected by both pathologies. Benralizumab is a humanized monoclonal antibody directed at the α subunit of the interleukin-5 receptor (IL-5Rα) approved for the treatment of severe eosinophilic asthma. Increasing body of literature provides data on its efficacy also on CRSwNP in the comorbid SA patient. Based on the data described in this review, when benralizumab is administered to comorbid patients, it does not only control severe asthma but also improves CRSwNP clinical outcomes, although we need further studies to add stronger evidence and to improve the correct pheno-endotyping of the comorbid patient.

Severe Asthma Remissions Induced by Biologics Targeting IL5/IL5r: Results from a Multicenter Real-Life Study.

Add-on biological therapy has proven to be effective in many patients with severe eosinophilic asthma. In this observational multicenter retrospective study, we report the results obtained with mepolizumab and benralizumab in severe asthmatics treated for 12 months in a real-life setting. In these patients, peripheral eosinophil levels, pulmonary function trends, exacerbation rates, systemic corticosteroid use, and symptom control were evaluated during the observation period, to understand which patients met all the criteria in order to be considered in disease remission. The percentage of remittent patients was 30.12% in the mepolizumab-treated subgroup, while in the benralizumab-treated subgroup, patients in complete disease remission were 40%, after 12 months. The results of this study confirm the efficacy of anti-IL-5 biologic drugs in the treatment of severe eosinophilic asthma in a real-life setting.

Effectiveness of Benralizumab in OCS-Dependent Severe Asthma: The Impact of 2 Years of Therapy in a Real-Life Setting.

Patients with severe OCS-dependent asthma can be considered a subgroup of asthma patients with severe disease and great risk of complications, related to chronic OCS use. The introduction of biological drugs has represented a turning point in the therapeutic strategy for severe asthma, offering a valid alternative to OCS. Benralizumab, like other anti-IL-5 agents, has been shown to reduce exacerbations and OCS intake/dosage and improve symptom control and lung function. While these findings have also been confirmed in real-life studies, data on long-term efficacy are still limited. METHODS: In this retrospective study, we evaluated the effects of 2 years of treatment with benralizumab on 44 patients with OCS-dependent severe asthma by analyzing clinical, biological and functional data. RESULTS: After 2 years of benralizumab, 59.4% discontinued OCS and patients who continued to use OCS had their mean dose reduced by approximately 85% from baseline. Meanwhile, 85% of patients had their asthma well-controlled (ACT score > 20) and had no exacerbations, and 41.6% had normal lung function. CONCLUSIONS: Our findings support the long-term effectiveness of benralizumab in severe OCS-dependent asthma in a real-life setting, suggesting potential reductive effects on costs and complications such as adverse pharmacological events.

Clinical Features and Efficacy of Benralizumab in Patients with Blood Eosinophil Count Between 300 and 450 Cells/mm3: A Post Hoc Analysis from the ANANKE Study.

Purpose: Benralizumab effectively reduces severe eosinophilic asthma (SEA) exacerbations in patients with a wide range of baseline blood eosinophil count (BEC). Patients included in real-world studies are often characterized by high mean/median BEC, while patients with BEC close to 300 cells/mm3 are poorly represented. This post hoc analysis from the Italian study ANANKE aims to define the clinical features and corroborate the efficacy of benralizumab in real world in the BEC 300-450 cells/mm3 subset of patients. Patients and Methods: Post hoc analysis of the Italian, multicenter, observational, retrospective real-life study ANANKE (NCT04272463). Baseline clinical and laboratory characteristics were collected in the 12 months prior to benralizumab treatment and presented for a BEC 300-450 cells/mm3 subgroup of patients. Change over time of BEC, annualized exacerbation rate (AER), asthma control (ACT), lung function and oral corticosteroid (OCS) use at 16, 24 and 48 weeks after benralizumab introduction were collected. Results: A total of 164 patients were analyzed, 34 of whom with a BEC of 300-450 cells/mm3. This subgroup was more likely to be female (64.7%), with lower rates of severe exacerbations at baseline when compared to the total population (0.69 vs 1.01). After 48 weeks of benralizumab treatment, the BEC 300-450 subset showed similar reductions in AER (-94.8% vs -92.2%) and OCS use (median dose reduction of 100% in both groups), as well as improvement in ACT score (median scores 22.5 vs 22) and lung function (pre-BD FEV1: +200 mL vs +300 mL) when compared to the total population. No discontinuations for safety reasons were registered. Conclusion: At baseline, apart from lower severe exacerbation rate, the BEC 300-450 cells/mm3 subset of patients is comparable to the total population prescribed with benralizumab. In this real-life study, benralizumab is as effective in BEC 300-450 patients as in the total population.

Switching from one biologic to benralizumab in patients with severe eosinophilic asthma: An ANANKE study post hoc analysis.

Background: Severe asthma is a heterogeneous inflammatory disease driven by eosinophilic inflammation in the majority of cases. Despite biologic therapy patients may still be sub-optimally controlled, and the choice of the best biologic is a matter of debate. Indeed, switching between biologics is common, but no official guidelines are available and real-world data are limited. Materials and methods: In this post hoc analysis of the Italian, multi-center, observational, retrospective study, ANANKE. Patients with severe eosinophilic asthma treated with benralizumab were divided in two groups based on history of previous biologic therapy (biologic-experienced [suboptimal response] vs naïve). Baseline clinical and laboratory characteristics were collected in the 12 months prior to benralizumab treatment. Change over time in blood eosinophils, annualized exacerbation rate (AER), asthma control (ACT), lung function and oral corticosteroid (OCS) use following benralizumab initiation were collected in the two groups. Results: A total of 147 biologic-naïve and 58 biologic-experienced (34 omalizumab, 19 mepolizumab, and 5 omalizumab-mepolizumab) patients were enrolled. Biologic-experienced patients were more likely to be atopic and have a higher AER despite more frequent OCS use. Similar reductions in AER (>90% in both groups), OCS use (≥49% reduction in dosage and ≥41% able to eliminate OCS), ACT improvement (≥7 points gained in 48 weeks) and lung function (≥300 mL of FEV1 improvement in 48 weeks) were observed after benralizumab introduction within the two groups. There were no registered discontinuations of benralizumab for safety reasons. Conclusion: In this post hoc analysis, patients who were switched to benralizumab because of suboptimal control with a previous biologic therapy were more likely to be atopic and more often treated with omalizumab. Benralizumab is effective in both naïve patients and those previously treated with a biologic.

A machine learning approach to characterize patients with asthma exacerbation attending an acute care setting.

BACKGROUND: One of the main problems in poorly controlled asthma is the access to the Emergency Department (ED). Using a machine learning (ML) approach, the aim of our study was to identify the main predictors of severe asthma exacerbations requiring hospital admission. METHODS: Consecutive patients with asthma exacerbation were screened for inclusion within 48 hours of ED discharge. A k-means clustering algorithm was implemented to evaluate a potential distinction of different phenotypes. K-Nearest Neighbor (KNN) as instance-based algorithm and Random Forest (RF) as tree-based algorithm were implemented in order to classify patients, based on the presence of at least one additional access to the ED in the previous 12 months. RESULTS: To train our model, we included 260 patients (31.5% males, mean age 47.6 years). Unsupervised ML identified two groups, based on eosinophil count. A total of 86 patients with eosinophiles ≥370 cells/µL were significantly older, had a longer disease duration, more restrictions to daily activities, and lower rate of treatment compared to 174 patients with eosinophiles <370 cells/µL. In addition, they reported lower values of predicted FEV1 (64.8±12.3% vs. 83.9±17.3%) and FEV1/FVC (71.3±9.3 vs. 78.5±6.8), with a higher amount of exacerbations/year. In supervised ML, KNN achieved the best performance in identifying frequent exacerbators (AUROC: 96.7%), confirming the importance of spirometry parameters and eosinophil count, along with the number of prior exacerbations and other clinical and demographic variables. CONCLUSIONS: This study confirms the key prognostic value of eosinophiles in asthma, suggesting the usefulness of ML in defining biological pathways that can help plan personalized pharmacological and rehabilitation strategies.

Management of Patients with Severe Asthma and Chronic Rhinosinusitis with Nasal Polyps: A Multidisciplinary Shared Approach.

Chronic rhinosinusitis (CRS) is one of the most frequent comorbidities associated with asthma and it contributes to an amplified global disease burden in asthmatics. CRS prevalence is much higher in asthmatic patients compared to the general population and it is more frequently related to severe asthma, especially in presence of nasal polyps (chronic rhinosinusitis with nasal polyps, CRSwNP). Moreover, asthma exacerbation has a higher occurrence in CRSwNP. From a pathologic point of view, CRS and asthma share similar and connected mechanisms (e.g., type-2 inflammation). A multidisciplinary approach represents a crucial aspect for the optimal management of patients with concomitant asthma and CRSwNP and improvement of patient quality of life. An Italian panel of clinicians with different clinical expertise (pulmonologists, ear, nose and throat specialists, immunologists and allergy physicians) identified three different profiles of patients with coexisting asthma and nasal symptoms and discussed the specific tracks to guide a comprehensive approach to their diagnostic and therapeutic management. Currently available biological agents for the treatment of severe asthma act either on eosinophil-centered signaling network or type-2 inflammation, resulting to be effective also in CRSwNP and representing a valid option for patients with concomitant conditions.

Benralizumab in Patients With Severe Eosinophilic Asthma With and Without Chronic Rhinosinusitis With Nasal Polyps: An ANANKE Study post-hoc Analysis.

Background: Severe eosinophilic asthma (SEA) in the presence of chronic rhinosinusitis with nasal polyps (CRSwNP) indicates the presence of a more extensive eosinophilic inflammation. Post-hoc analyses from a pivotal clinical trial have demonstrated the enhanced efficacy of benralizumab on asthma outcomes in patients with CRSwNP as a comorbidity. Methods: This is a post-hoc analysis from the Italian multi-center observational retrospective ANANKE study. Patients were divided into two groups based on self-reported CRSwNP. Baseline clinical and laboratory features in the 12 months prior to benralizumab prescription were collected. Data of change over time of blood eosinophils, annualized exacerbations rates (AER), asthma control, lung function, oral corticosteroids (OCS) use, and benralizumab discontinuation were collected during the observation period. Results: At baseline, the 110 patients with CRSwNP were less frequently female (50.9% vs 74.2%) and obese (9.1% vs. 22.6%) with higher eosinophils (605 vs. 500 cells/mm3) and OCS use when compared to patients without CRSwNP. Similar reductions of AER were seen (-95.8% vs. -91.5% for any exacerbation and -99.1% vs. -92.2% for severe exacerbations in patients with and without CRSwNP, respectively). During benralizumab treatment, comorbid SEA+CRSwNP was associated with a lower risk of any exacerbation (p = 0.0017) and severe exacerbations (p = 0.025). After a mean ± SD exposure of 10.3 ± 5.0 months, half of the SEA+CRSwNP patients eliminated OCS use. No discontinuation for safety reasons was recorded. Conclusions: This study helped to confirm the baseline clinical features that distinguish patients with and without CRSwNP being prescribed benralizumab. Numerically enhanced OCS reduction and lower exacerbation risk were observed in patients with SEA and comorbid CRSwNP treated with benralizumab.