The New Paradigm: The Role of Proteins and Triggers in the Evolution of Allergic Asthma.

Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. Rises in the epithelial barrier permeability of airways alter tissue homeostasis and allow the penetration of allergens and other external agents. Different factors contribute to barrier impairment, such as eosinophilic infiltration and allergen protease action-eosinophilic cationic proteins' effects and allergens' proteolytic activity both contribute significantly to epithelial damage. In the airways, allergen proteases degrade the epithelial junctional proteins, allowing allergen penetration and its uptake by dendritic cells. This increase in allergen-immune system interaction induces the release of alarmins and the activation of type 2 inflammatory pathways, causing or worsening the main symptoms at the skin, bowel, and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic protease-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance, and progression. Moreover, we will explore potential clinical and radiological biomarkers of airway remodeling in allergic asthma patients.

Unlocking the Long-Term Effectiveness of Benralizumab in Severe Eosinophilic Asthma: A Three-Year Real-Life Study.

Background: Benralizumab has been shown to restore good control of severe eosinophilic asthma (SEA). Robust data on benralizumab effectiveness over periods longer than 2 years are scarce. Methods: This retrospective multicentric study was conducted on 108 Italian SEA patients treated with benralizumab for up to 36 months. Partial and complete clinical remission (CR) were assessed. Data were analyzed with descriptive statistics or using linear, logistic, and negative binomial mixed-effect regression models. Results: At 36 months, benralizumab reduced the exacerbation rate by 89% and increased the forced expiratory volume in 1 second (FEV1) (+440 mL at 36 months, p < 0.0001). Benralizumab improved asthma control as well as sinonasal symptoms in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). Up to 93.33% of patients either reduced or discontinued OCS; benralizumab also decreased ICS use and other asthma medications. Overall, 84.31% of patients achieved partial or complete CR. Conclusions: Benralizumab improved asthma and sinonasal outcomes up to 36 months. These findings support the potential of benralizumab to induce CR, emphasizing its role as a disease-modifying anti-asthmatic drug for the management of SEA. Further research is warranted to expand these findings by minimizing data loss and assessing benralizumab's long-term safety.

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.

Multidisciplinary Decision-Making-ITAlian Consensus After Two Years of Real Practice on the Management of Severe Uncontrolled CRSwNP by Biologics (ITACA Study).

PURPOSE OF REVIEW: We aimed to reach an Italian multidisciplinary consensus on some crucial aspects of treatment decision making in CRSwNP, following 2 years of clinical experience in order to support specialists in the management of CRSwNP in clinical practice. We addressed issues relating to therapeutic decision-making and shared criteria for the treatment choice, as well as appropriate timing and criteria for evaluating treatment response, and highlighted the need for repeated multidisciplinary assessments. RECENT FINDINGS: A national survey has been conducted recently to understand how rhinology practice has changed in Italy with the advent of biologics and how this affects patients with uncontrolled, severe CRSwNP. Despite the many published consensus documents, practical recommendations, and protocols on the use of biologics in CRSwNP, heterogenous behaviors in practice are still observed mainly conditioned by the novelty of the topic. The consensus procedure followed a modified Delphi approach. The scientific board included 18 otorhinolaryngologists and 8 allergists, who selected the 4 main topics to be addressed and developed overall 20 statements. Consensus on these statements was sought by a larger group of 48 additional experts, through two rounds of voting, the first web-based, the second in presence with discussion and possible refinement of the statements. The statements reaching an average score ≥ 7 at the second voting round were approved. Five statements were proposed for each of the following topics: baseline evaluation of patients eligible for biologic therapy; choice between different therapeutic options; assessment of the response to biologic treatment; multidisciplinary management. At the first voting round, 19 out of the 20 statements reached a mean score ≥ 7. Following the discussion and a few consequent amendments, at the second round of voting all the 20 statements were approved.

The last step to achieve barrier damage control.

Heterogeneity characterises inflammatory diseases and different phenotypes and endotypes have been identified. Both innate and adaptive immunity contribute to the immunopathological mechanism of these diseases and barrier damage plays a prominent role triggering type 2 inflammation through the alarmins system, such as anti-Thymic Stromal Lymphopoietin (TSLP). Treatment with anti-TSLP monoclonal antibodies showed efficacy in severe asthma and clinical trials for other eosinophilic diseases are ongoing. The aim of this perspective review is to analyse current advances and future applications of TSLP inhibition to control barrier damage.

Long-Term Efficacy of Mepolizumab at 3 Years in Patients with Severe Asthma: Comparison with Clinical Trials and Super Responders.

The efficacy mepolizumab in severe asthmatic patients is proven in the literature. Primarily to study the effect of mepolizumab on exacerbations, steroid dependence, and the continuation of efficacy in the long term. Secondarily to evaluate the effect of the drug on nasal polyps. Analyzing data from SANI (Severe Asthma Network Italy) clinics, we observed severe asthmatic patients treated with mepolizumab 100 mg/4 weeks, for a period of 3 years. 157 patients were observed. Exacerbations were reduced from the first year (-84.6%) and progressively to 90 and 95% in the second and third ones. Steroid-dependent patients decreased from 54% to 21% and subsequently to 11% in the second year and 6% in the third year. Patients with concomitant nasal polyps, assessed by SNOT-22, showed a 49% reduction in value from baseline to the third year. The study demonstrated the long-term efficacy of mepolizumab in a real-life setting.

Eosinophil Cationic Protein Variation in Patients with Asthma and CRSwNP Treated with Dupilumab.

BACKGROUND: Asthma is a clinical syndrome characterized by recurrent episodes of airway obstruction, bronchial hyperresponsiveness and airway inflammation. Most patients with asthma present a "type 2" (TH2) inflammation. ILC2 and TH2 cells release cytokines IL4, IL-13 and IL-5. CRSwNP is a condition characterized by hyposmia or anosmia, nasal congestion, nasal discharge, and face pain or pressure that last for at least 12 weeks in a row without relief. Both asthma and CRSwNP are often characterized by a type 2 inflammation endotype and are often present in the same patient. Dupilumab is a fully human monoclonal antibody targeting the interleukin-4 receptor α (IL-4Rα) subunit, blocking IL4/IL-4Rα binding and IL13. It has been labelled for the treatment of moderate to severe asthma in patients from the age of 12 years with an eosinophilic phenotype, and it has demonstrated efficacy and acceptable safety. Our study aims to investigate the effects of dupilumab on type 2 inflammatory biomarkers, such as eosinophils and eosinophil cationic protein (ECP). ECP is an eosinophil-derived substance contained in granules that are released during inflammation and causes various biological effects, including tissue damage in asthmatic airways. METHODS: ECP, Eosinophil counts (EOS), and total immunoglobulin E (IgE) levels were longitudinally measured using immunoassays in the serum of 21 patients affected by CRSwNP, of which 17 had asthma as a comorbidity, receiving 300 mg dupilumab every two weeks. RESULTS: The EOS and ECP, after a first phase of significant increase due to the intrinsic characteristic of the block of IL-4 and IL-13, returned to the baseline 10 months after the initial administration of dupilumab. Fractional exhaled nitric oxide (FeNO) and serum total IgE decreased significantly after 9 months. Asthma Control Test (ACT) scores improved after dupilumab treatment. FEV1% and FEV1 absolute registered a significant improvement at 10 months. CONCLUSIONS: Patients who received 300 milligrams of dupilumab every two weeks first experienced a temporary increase in eosinophils (EOS) and eosinophil cationic protein (ECP), then exhibited a gradual decline in these variables with a subsequent return to the initial baseline levels. When compared to the baseline, we observed that the levels of IgE and FeNO decreased over time, while there was an increase in both FEV1 and FEV1%.

Severe Asthma Network Italy Definition of Clinical Remission in Severe Asthma: A Delphi Consensus.

Severe asthma affects about 10% of the population with asthma and is characterized by low lung function and a high count of blood leukocytes, mainly eosinophils. Various definitions are used in clinical practice and in the literature to identify asthma remission: clinical remission, inflammatory remission, and complete remission. This work highlights a consensus for asthma remission using a Delphi method. In the context of the Severe Asthma Network Italy, which accounts for 57 severe asthma centers and more than 2,200 patients, a board of six experts drafted a list of candidate statements in a questionnaire, which has been revised to minimize redundancies and ensure clear and consistent wording for the first round (R1) of the analysis. Thirty-two statements were included in the R1 questionnaire and then submitted to a panel of 80 experts, which used a 5-point Likert scale to measure agreement regarding each statement. Then, an interim analysis of R1 data was performed, and items were discussed and considered to produce a consistent questionnaire for round 2 (R2) of the analysis. Then, the board set the R2 questionnaire, which included only important topics. Panelists were asked to vote on the statements in the R2 questionnaire afterward. During R2, the criteria of complete clinical remission (the absence of the need for oral corticosteroids, symptoms, exacerbations or attacks, and pulmonary function stability) and those of partial clinical remission (the absence of the need for oral corticosteroids, and two of three criteria: the absence of symptoms, exacerbations or attacks, and pulmonary stability) were confirmed. This Severe Asthma Network Italy Delphi analysis defined a valuable and independent tool that is easy to use, to test the efficacy of different treatments in patients with severe asthma enrolled into the SANI registry.

Effects of house dust mite subcutaneous immunotherapy in real-life. Immunological and clinical biomarkers and economic impact analysis.

Background: Etiology of allergic rhinitis and asthma is frequently associated with house dust mite sensitization and allergen immunotherapy (AIT) represents the only disease modifying treatment. In a real world setting, clinicians would benefit from biomarkers to monitor or predict response to AIT. Methods: Twenty-four consecutive house dust mite (HDM) mono-sensitized rhinitic patients, treated with subcutaneous immunotherapy (SCIT) as per clinical practice, were enrolled. Multiple in vitro biomarkers such as basophil activation (BAT), IL-10 levels, and molecular allergen-specific IgE were performed during HDM SCIT, to monitor the effects of AIT and then correlated to in vivo scores (VAS, CMSS, RQLQ). Nasal cytology was performed at baseline and after 6 and 12 months of treatment. Finally, the economic impact of SCIT in this cohort of patients was evaluated. Results: Clinical biomarkers confirmed to be useful to monitor AIT efficacy. As for laboratory biomarkers, BAT showed a reduction trend, particularly for D2C1, suggesting that this is a useful parameter in monitoring patients. IL-10 levels tend to remain stable or slightly decrease during treatment. The economic analysis confirmed the favorable impact of immunotherapy. Conclusions: In this cohort of patients, SCIT confirmed its effectiveness in reducing symptoms and drug utilization. Clinical scores confirmed to be valid in monitoring patients and their response. BAT demonstrated to be useful in monitoring more than predicting response. Further studies are needed to better explore the usefulness of these biomarkers in AIT.

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.

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.

Evaluation and Updated Classification of Acute Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): NSAID-Exacerbated or -Induced Food Allergy.

BACKGROUND: There are hypersensitivity reactions (HRs) to foods in which nonsteroidal anti-inflammatory drugs (NSAIDs) act as aggravating factors (NSAID-exacerbated food allergy [NEFA]) or cofactors (NSAID-induced food allergy [NIFA]), often misdiagnosed as HRs to NSAIDs. Urticarial/angioedematous and/or anaphylactic reactions to two or more chemically unrelated NSAIDs do not meet current classification criteria. However, they may be considered part of a cross-reactive type of acute HR, which is NSAID-induced urticaria/angioedema with or without respiratory or systemic symptoms of anaphylaxis. OBJECTIVE: To evaluate patients reporting acute HRs to NSAIDs and classify them according to updated criteria. METHODS: We prospectively studied 414 patients with suspected HRs to NSAIDs. For all whom met these criteria, NEFA/NIFA was diagnosed: (1) mild reactions to (NEFA) or tolerance of (NIFA) the suspected foods without taking NSAIDs; (2) cutaneous and/or anaphylactic reactions to the combination foods plus NSAIDs; (3) positive allergy tests to the suspected foods; and (4) negative drug challenges (DCs) with the NSAIDs involved. RESULTS: A total of 252 patients were given the diagnosis of NSAID hypersensitivity (60.9%), 108 of whom had NSAID-induced urticaria/angioedema with or without respiratory or systemic symptoms of anaphylaxis. We excluded NSAID hypersensitivity in 162 patients (39.1%) who tolerated DCs with the suspected NSAIDs, nine of whom received a diagnosis of NEFA, and 66 of NIFA. Pru p 3 was implicated in 67 of those 75 patients who received a diagnosis of NEFA or NIFA. CONCLUSIONS: NEFA and NIFA account for about 18% of patients reporting HRs to NSAIDs, in which Pru p 3 is the main responsible food allergen. Therefore, patients with cutaneous and/or anaphylactic reactions to NSAIDs should be carefully questioned about all foods ingested within 4 hours before or after NSAID exposure, and targeted food allergy tests should be considered in the diagnostic workup of these patients. If testing is positive, DCs with the suspected NSAIDs should also be considered.

High Level of Blood Eosinophils and Localization of Bronchiectasis in Patients with Severe Asthma: A Pilot Study.

Background. Severe asthma and bronchiectasis are heterogeneous diseases that frequently coexist. The location of bronchiectasis is generally determined by specific underlying pathophysiological mechanisms. The aim of this study was to determine whether in a population suffering from both severe asthma and bronchiectasis there was a correlation between eosinophilic inflammation and localization of bronchiectasis. Methods. We enrolled 41 patients with coexisting bronchiectasis from eight different severe asthma center outpatient clinics and collected the following data: baseline characteristics, Asthma Control Test, Asthma Control Questionnaire, IgE level, blood count, high-resolution computed tomography and bronchiectasis-related parameters, skin prick test, FeNO50 and flow-volume spirometry. The study was retrospectively registered. Results. The presence of eosinophils > 1000 cells/µL was related to distribution of lower pulmonary bronchiectasis (9.1% upper lobes vs. 53.3% lower lobes, p = 0.014). Indeed, the presence of eosinophilic counts > 1000 increased the probability of lower localization of bronchiectasis compared to upper lobes (ODD 0.088 (0.010−0.772), p = 0.028). Conclusions. An increase in blood eosinophils > 1000 cells/µL seems to be associated with lower preferential localization of bronchiectasis with sparing of the upper lung lobes. This could represent a new potential radiological phenotype that could have a dedicated therapeutic strategy in the future.

Different aspects of severe asthma in real life: Role of Staphylococcus aureus enterotoxins and correlation to comorbidities and disease severity.

BACKGROUND: Asthma, with several phenotypes and endotypes, is considered particularly suited for precision medicine. The identification of different non-invasive biomarkers may facilitate diagnosis and treatment. Recently, Staphylococcus aureus and its enterotoxins (SE) have been found to have a role in inducing persistent type 2 airway inflammation in severe asthma, but also in such comorbidities as chronic rhinosinusitis with nasal polyposis (CRSwNP). METHODS: The aim of this retrospective study was to evaluate the prevalence of SE-IgE sensitization in a multicentric Italian cohort of severe asthmatic patients and correlate it with demographic and clinical characteristics. RESULTS: A total of 249 patients were included in the analysis, out of which 25.3% were staphylococcal enterotoxin B (SEB)-IgE positive. We found a meaningful association between SEB-IgE and female gender, a positive association was also measured between CRS and CRSwNP. No significant association was found between SEB-IgE sensitization and atopy, the occurrence of exacerbations and corticosteroid dosages. In the SEB-IgE-positive patient, blood eosinophil count does not appear to be correlated with the severity of the disease. Patients with SEB-IgE sensitization are, on average, younger and with an earlier disease onset, thus confirming the possibility to consider SEB-IgE sensitization as an independent risk factor for developing asthma. CONCLUSIONS: Our data confirm that the search for SE in the initial screening phase of these patients is helpful to better phenotype them, may predict the evolution of comorbidities and lead to a targeted therapeutic choice; in this point of view this represents a goal of precision medicine.

The Role of Gut Microbiota and Leaky Gut in the Pathogenesis of Food Allergy.

Food allergy (FA) is a growing public health concern, with an increasing prevalence in Western countries. Increasing evidence suggests that the balance of human gut microbiota and the integrity of our intestinal barrier may play roles in the development of FA. Environmental factors, including industrialization and consumption of highly processed food, can contribute to altering the gut microbiota and the intestinal barrier, increasing the susceptibility to allergic sensitization. Compositional and functional alterations to the gut microbiome have also been associated with FA. In addition, increased permeability of the gut barrier allows the translocation of allergenic molecules, triggering Th2 immune responses. Preclinical and clinical studies have highlighted the potential of probiotics, prebiotics, and postbiotics in the prevention and treatment of FA through enhancing gut barrier function and promoting the restoration of healthy gut microbiota. Finally, fecal microbiota transplantation (FMT) is now being explored as a promising therapeutic strategy to prevent FA in both experimental and clinical studies. In this review article, we aim to explore the complex interplay between intestinal permeability and gut microbiota in the development of FA, as well as depict potential therapeutic strategies.

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.

The Combined Use of Chronological and Morphological Criteria in the Evaluation of Immediate Penicillin Reactions: Evidence From a Large Study.

BACKGROUND: Immediate hypersensitivity reactions to penicillins are often labeled on the basis of a similar set of symptoms, but a key feature of these reactions that can be reproduced in diagnostic testing may be the timing of a reaction in relation to the dose administration. OBJECTIVE: To determine whether the timing of a reaction in response to the last dose of a penicillin would predict the results of diagnostic testing. METHODS: We evaluated 1074 patients by performing skin tests, serum specific IgE assays (ImmunoCAP), and challenges. Patients who were evaluated by us more than 6 months after their reactions and found negative were reevaluated within 2 to 4 weeks. RESULTS: Patients who had reacted within 1 hour after the first dose, within 1 hour after subsequent doses, more than 1 hour to within 6 hours after the first dose, or more than 1 hour to within 6 hours after subsequent doses were classified as group A (758 individuals), B (92), C (67), or D (157), respectively. Penicillin hypersensitivity was diagnosed in 707 patients (65.8%) by skin tests (407 patients, 57.6%), ImmunoCAP (47, 6.6%), both tests (232, 32.8%), or challenges (21, 3%). A conversion to allergy-test positivity occurred in 7 of 10 patients with anaphylactic reactions and in 1 of 28 patients with other reactions who were reevaluated after negative challenges. The rate of penicillin-allergic patients in groups A, B, C, and D was 85%, 35.9%, 35.8%, and 3.8%, respectively. Only 1 of 107 patients reporting cutaneous reactions lasting more than 1 day had positive results to allergy tests. CONCLUSIONS: IgE-mediated hypersensitivity can be diagnosed by skin tests in about 70% of subjects who react within 1 hour (eg, patients from groups A and B). This hypersensitivity can be lost over time, as demonstrated by the negativization of allergy tests in follow-up studies. In subjects with anaphylactic reactions, however, it is advisable to not consider this phenomenon definitive. In fact, a conversion to allergy test positivity can be observed in up to 20% of such subjects retested after negative challenges.

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.

Nasal Cytology: A Easy Diagnostic Tool in Precision Medicine for Inflammation in Epithelial Barrier Damage in the Nose. A Perspective Mini Review.

Nasal cytology is a diagnostic tool that can be used in precision rhinology medicine. Particularly in non-allergic rhinitis and chronic rhinosinusitis forms it can be useful to evaluate biomarkers of both surgical or biological therapy and especially in the follow-up it must be used to predict the prognostic index of recurrence of nasal polyposis. All inflammatory cytokines are also linked to the presence of cells such as eosinophils and mastcells and nasal cytology is a non-invasive and repeatable method to assess the situation in real life.