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The diagnosis of allergic reactions to penicillins (AR-PEN) is very complex as there is a loss of sensitization over time, which leads to negative skin tests (STs) and specific IgE in serum, and even to tolerance to the drug involved. However, STs may become positive after subsequent exposure to the culprit drug (resensitization), with the risk of inducing potentially severe reactions. The exact rate of resensitization to penicillins is unknown, ranging from 0% to 27.9% in published studies.To analyze the rate of resensitization in patients with suggestive AR-PEN by repeating STs (retest) after an initial evaluation (IE).Patients with suspected AR-PEN were prospectively evaluated between 2017 and 2020. They underwent STs, and a randomized group also underwent a drug provocation test (DPT) with the culprit. Only patients with negative STs and/or DPT were included. All included cases were retested by STs at 2-8 weeks.A total of 545 patients were included: 296 reporting immediate reactions (IRs) and 249 non-immediate reactions (NIRs). Eighty (14.7%) cases had positive results in retest (RT+): 63 (21.3%) IRs and 17 (6.8%) NIRs (p 0.0001). The rate of RT+ was higher in anaphylaxis compared with all other reactions (45.8% vs 9.1%, p 0.0001). The risk of RT+ was higher from the fifth week after IE (OR: 4.64, CI: 2.1-11.6; p 0.001) and increased with the patient's age (OR: 1.02; CI: 1.01-1.04; p = 0.009).Due to the high rate of resensitization, retest should be included in the diagnostic algorithm of IRs to penicillins after an initial negative study, especially in anaphylaxis, to avoid potentially severe reactions after subsequent prescriptions of these drugs.

Purpose of review Anaphylactic reactions reported after Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) RNA vaccines were expected to be more frequent in atopic subjects and attributed to its polyethylene glycol component. Recent findings Anaphylaxis to SARS-CoV2 RNA vaccines is no more frequent than in any vaccine and direct proofs for the role of its polyethylene glycol component are lacking. Summary Vaccines against coronavirus disease 2019 (COVID-19) are an essential global intervention to control the current pandemic situation. Anaphylactic reactions have rapidly been reported after SARS-CoV2 RNA vaccines. This risk is now measured at 2.5-11/1 000 000 in the context of vaccine safety surveillance programs and only one case was documented to be due to polyethylene glycol. Suggestions for its role are indirect. The COVID-19 vaccination is rolling out vastly and surveillance programs are key to monitor severe adverse reactions, such as anaphylaxis. Anaphylaxis due to vaccine is extremely rare and specific cases should receive individualized investigation and care, highlighting the key role of allergists in the vaccination programmes.

Background Data from phase 3 trials have demonstrated the efficacy and safety of benralizumab in patients with severe eosinophilic asthma (SEA). We conducted a real-world study examining the baseline characteristics of a large SEA population treated with benralizumab in clinical practice and assessed therapy effectiveness. Methods ANANKE is an Italian multi-center, retrospective cohort study including consecutive SEA patients who had started benralizumab therapy ≥ 3 months before enrolment (between December 2019 and July 2020), in a real-world setting. Data collection covered (1) key patient features at baseline, including blood eosinophil count (BEC), number and severity of exacerbations and oral corticosteroid (OCS) use; (2) clinical outcomes during benralizumab therapy. We also conducted two post-hoc analyses in patients grouped by body mass index and allergic status. Analyses were descriptive only. Results Of 218 patients with SEA enrolled in 21 Centers, 205 were evaluable (mean age, 55.8 ± 13.3 years, 61.5% females). At treatment start, the median BEC was 580 cells/mm3 (interquartile range [IQR]: 400–850); all patients were on high-dose inhaled controller therapy and 25.9% were on chronic OCS (median dose: 10 mg/die prednisone-equivalent [IQR: 5–25]); 92.9% experienced ≥ 1 exacerbation within the past 12 months (annualized exacerbation rate [AER] 4.03) and 40.3% reported ≥ 1 severe exacerbation (AER 1.10). During treatment (median duration: 9.8 months [IQR 6.1–13.9]; ≥ 12 months for 34.2% of patients), complete eosinophil depletion was observed; exacerbation-free patients increased to 81% and only 24.3% reported ≥ 1 severe event. AER decreased markedly to 0.27 for exacerbations of any severity (− 93.3%) and to 0.06 for severe exacerbations (− 94.5%). OCS therapy was interrupted in 43.2% of cases and the dose reduced by 56% (median: 4.4 mg/die prednisone-equivalent [IQR: 0.0–10.0]). Lung function and asthma control also improved. The effectiveness of benralizumab was independent of allergic status and body mass index. Conclusions We described the set of characteristics of a large cohort of patients with uncontrolled SEA receiving benralizumab in clinical practice, with a dramatic reduction in exacerbations and significant sparing of OCS. These findings support benralizumab as a key phenotype-specific therapeutic strategy that could help physicians in decision-making when prescribing biologics in patients with SEA. Trial registration ClinicalTrials.gov Identifier: NCT04272463

BACKGROUND: A higher risk for COVID-19 infection and severity for men compared to women has been described since the beginning of the pandemic. The role of androgens has been recently highlighted as they control two key steps of coronavirus infection mediated through the transmembrane protease serin 2 (TMPRRS2) and the angiotensin-converting enzyme 2 (ACE2) receptor in the lung tissue. Furthermore, a high incidence of androgenic alopecia among males with COVID-19 disease have been reported. OBJECTIVE: This study aims to evaluate the telogen effluvium (TE) prevalence and its relationship with clinical and immunologic parameters in a sample of patients consecutively evaluated after recovery from COVID-19 pneumonia in Northern Italy. METHODS: Overall 104 patients were recruited within three months from COVID-19 pneumonia recovery; 80 (77%) had been hospitalized in a Respiratory Intensive Care Unit and the remaining ones had been treated at home. The extent of TE was assessed with a visual analogic scale for thick bundle of hairs. Demographic and clinical data and systemic inflammation biomarkers were also evaluated. RESULTS: Thirty-two patients reported a history of TE and their mean TE-VAS score was 5.78 +/- 1.72 (range 3-9). Women had about a 5-fold higher risk (odds) of complaining of TE compared to males (OR = 4.69, 95%CI: 1.91, 11.49; p = .001), and the association became stronger when adjusted for COVID-19 severity (hospital admission vs home care: OR = 6.09, 95%CI: 2.34, 15.88; p < .001). Levels of C-reactive protein >1.90 mg/l (ORadj: 2.43, 95%CI 0.85, 7.05, p = 0.096) or IL 1 beta > 5 ng/l (ORadj 4.72, 95%CI: 1.31, 23.19, p = .03) were also significantly associated with TE. CONCLUSION: This exploratory study raises the hypothesis that hair shedding is more strictly related to the severity of COVID-19 disease and the underlying inflammation rather than to patients' hormonal status.

Introduction: Allergic rhinitis (AR) is a disease characterized by IgE-mediated hypersensitivity responses akin to allergic asthma. Although common in children and young adults, AR can be particularly vexing in the elderly: several studies have underlined its impact on the patient’s self-perceived health-related quality of life (HR-QoL). Available literature data on AR-affected elderly patients remain sparse and often focused on specific characteristics. mHealth solutions such as MASK-air® can be used in assessing salient clinical characteristics and unique shifts in self-perceived HR-QoL in old age people. With this pilot study, we aim to assess these variables in two cohorts of AR-affected elderly patients – one actively involved in the daily use of mHealth applications and the other having never used such a solution – by applying a widespread, validated, and standardized tool. Methods: AR-affected patients aged ≥65 years accessing the outpatient clinic of the Bari Geriatric Immuno-allergology Unit between March and July 2021 were enrolled and assigned to “mHealth” (MASK-air®) and “non-mHealth” cohorts accordingly. Each participant was given a 19-item questionnaire delivered via a custom software solution, with the EuroQoL EQ-5D-5L used to assess HR-QoL. Results: 93 patients (51 mHealth users, 43 non-mHealth users) were enrolled. AR was often either standalone or associated with asthma and conjunctivitis, and 57.4% of the participants reported a negative influence of AR on daily activities. Analysis of HR-QoL showed significantly worse scores in mobility and anxiety/depression dimensions for female patients regardless of app usage, while male non-mHealth users had worse self-care scores. Female mHealth users had worse scores for the self-care and activity dimensions, whereas female non-mHealth users showed worse scores on the pain scale. In general, mHealth users showed a greater degree of anxiety/depression when compared to non-mHealth users, relating to a greater awareness of their health status. Conclusion: The use of an mHealth solution, along with a concise, clinically-validated, comprehensive HR-QoL assessment toolset such as the EQ-5D, can prove beneficial in defining the unique characteristics of AR in the elderly. It can enable a detailed exploration of the impact on specific aspects of quality of life in old age. Raising patient awareness towards a health condition can improve compliance to treatment as well as follow-up. A lack of uniformity in approach, along with missing data pertaining to the general population are critical issues that require further studies. A more thorough diffusion of mHealth usage is also necessary among the geriatric population.

Conventional vaccines have been widely studied, along with their risk of causing allergic reactions. These generally consist of mild local reactions and only rarely severe anaphylaxis. Although all the current COVID-19 vaccines marketed in Europe have been shown to be safe overall in the general population, early post-marketing evidence has shown that mRNA-based vaccines using novel platforms (i.e., lipid nanoparticles) were associated with an increased risk of severe allergic reactions as compared to conventional vaccines. In this paper we performed an updated literature review on frequency, risk factors, and underlying mechanisms of COVID-19 vaccine-related allergies by searching MEDLINE and Google Scholar databases. We also conducted a qualitative search on VigiBase and EudraVigilance databases to identify reports of "Hypersensitivity" and "Anaphylactic reaction" potentially related to COVID-19 vaccines (Comirnaty, Spikevax, Vaxzevria and COVID-19 Janssen Vaccine), and in EudraVigilance to estimate the reporting rates of "Anaphylactic reaction" and "Anaphylactic shock" after COVID-19 vaccination in the European population. We also summarized the scientific societies' and regulatory agencies' recommendations for prevention and management of COVID-19 vaccine-related allergic reactions, especially in those with a history of allergy.

International audience; Background: Although rare, anaphylaxis during pregnancy implies a risk to both mothers and newborns.Objective: This systematic review is intended to identify key issues in the diagnosis and management of this condition to support prevention strategies and decrease the risk for death related to anaphylaxis during pregnancy.Methods: We searched MEDLINE, Cochrane, LILACS, SciELO, and Science Direct databases for manuscripts concerning the term "anaphylaxis during pregnancy," without language restrictions. We screened studies, extracted data, and assessed the risk for bias independently in duplicate.Results: We selected 12 articles. Frequency of anaphylaxis during maternity was estimated to be 1.5 to 3.8 per 100,000 pregnancies. Only one study provided anaphylaxis mortality data in pregnant women; the rate of anaphylaxis-related maternal mortality was estimated at 0.05/100,000 live births. No standard definition of anaphylaxis severity has been used. A total of 49% to 74% of anaphylaxis cases were described during caesarean section. Beta-lactam antibiotics (58%), latex (25%), and anesthetic agents (17%) were the main causes. In 17% of reports, causative agents were proven by allergy testing. Moreover, 72% of articles proposed the same management and treatment for a clinical episode of anaphylaxis during pregnancy as for nonpregnant patients, and the use of epinephrine in the patient's care during anaphylaxis in pregnancy.Conclusions: Few studies address anaphylaxis during pregnancy. Most have been produced by nonallergy specialists. Collaboration among different specialists involved in the care of pregnant women should be established to support preventive strategies and reduce avoidable deaths.

Background\ud \ud Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as “may contain traces of” is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin.\ud \ud \ud \ud Methods\ud \ud MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results.\ud \ud \ud \ud Results\ud \ud In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds.\ud \ud \ud \ud Conclusion\ud \ud Based on the literature studied for this review, it can be stated that cross-contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement “this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product” for a voluntary declaration on processed food packages. This level of avoidance of cross-contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However, it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged.

The prevalence of asthma in Italy is estimated to be around 4%; it affects approximately 2,000,000 citizens, and up to 80-90% of patients have mild-to-moderate asthma. Despite the clinical relevance of mild-to-moderate asthma, longitudinal observational data are very limited, including data on disease progression (worsening vs. improvement), the response to treatment, and prognosis. Studies are needed to develop long-term, observational, real-life research in large cohorts. The primary outcomes of this study will be based on prospective observation and the epidemiological evolution of mild and moderate asthma. Secondary outcomes will include patient-reported outcomes, treatments over time, disease-related functional and inflammatory patterns, and environmental and life-style influences.This study, called the Mild/Moderate Asthma Network of Italy (MANI), is a research initiative launched by the Italian Respiratory Society and the Italian Society of Allergology, Asthma and Clinical Immunology. MANI is a cluster-based, real world, cross-sectional, prospective, observational cohort study that includes 20,000 patients with mild-to-moderate asthma. (ClinicalTrials.gov Identifier: NCT04796844).Despite advances in asthma care, several research gaps remain to be addressed through clinical research. This study will add important new knowledge about long-term disease history, the transferability of clinical research results to daily practice, the efficacy of currently recommended strategies, and their impact on the burden and evolution of the disease.MANI:Mild/Moderate Asthma Network of ItalySANI:Severe Asthma Network ItalyGINA:Global Initiative for AsthmaSABA:short acting β2-agonistsICS:inhaled corticosteroidsCRF:Case Report Form.

Coronavirus SARS-CoV-2 has represented, and still represents, a real challenge from a clinical, diagnostic and therapeutic point of view. During acute infection, the increased levels of pro-inflammatory cytokines, which are involved in the pathology of disease and the development of SARS-CoV-2-induced acute respiratory disease syndrome, the life-threatening form of this infection, are correlated with patient survival and disease severity. IL-33, a key cytokine involved in both innate and adaptive immune responses in mucosal organs, can increase airway inflammation, mucus secretion and Th2 cytokine synthesis in the lungs, following respiratory infections. Similar to cases of exposure to known respiratory virus infections, exposure to SARS-CoV-2 induces the expression of IL-33, correlating with T-cell activation and lung disease severity. In this work, we analyse current evidence regarding the immunological role of IL-33 in patients affected by COVID-19, to evaluate not only the clinical impact correlated to its production but also to identify possible future immunological therapies that can block the most expressed inflammatory molecules, preventing worsening of the disease and saving patient lives.

Background: ANDHI was done to assess the efficacy of benralizumab, including onset of effect and impact on health-related quality of life (HRQOL), exacerbation rate, lung function, and nasal polyposis symptoms. Methods: This phase 3b, randomised, double-blind, parallel-group, placebo-controlled ANDHI study was completed in adults (aged 18–75 years) with severe eosinophilic asthma with at least 2 exacerbations in the previous year, despite high-dose inhaled corticosteroid plus additional controllers, screening blood eosinophil counts of at least 150 cells per μL, and an Asthma Control Questionnaire 6 (ACQ-6) score of 1·5 or more. Patients who met eligibility criteria were randomly assigned (2:1; stratified by previous exacerbation count [two, or three or more], maintenance oral corticosteroid use, and region), using an integrated web-based response system, to receive benralizumab at 30 mg every 8 weeks (first three doses given 4 weeks apart) or matched placebo for 24 weeks. Primary efficacy measure was annualised asthma exacerbation rate, with rate ratio (RR) calculated over the approximate 24-week follow-up. Secondary efficacy measures included change from baseline to end of treatment (week 24) in St George's Respiratory Questionnaire (SGRQ) total score (key secondary endpoint), FEV1, peak expiratory flow (PEF), ACQ-6, Predominant Symptom and Impairment Assessment (PSIA), Clinician Global Impression of Change (CGI-C), Patient Global Impression of Change (PGI-C), and Sino-Nasal Outcome Test-22 (SNOT-22). All efficacy analyses, except for SNOT-22, were summarised and analysed using the full analysis set on an intention-to-treat population (all randomly assigned patients receiving investigational product, regardless of protocol adherence or continued participation in the study). SNOT-22 was summarised for the subgroup of patients with physician-diagnosed nasal polyposis with informed consent. This study is registered with ClinicalTrials.gov, NCT03170271. Findings: Between July 7, 2017, and Sept 25, 2019, 656 patients received benralizumab (n=427) or placebo (n=229). Baseline characteristics were consistent with severe eosinophilic asthma. Benralizumab significantly reduced exacerbation risk by 49% compared with placebo (RR estimate 0·51, 95% CI 0·39–0·65; p5%) were nasopharyngitis (30 [7%]), headache (37 [9%]), sinusitis (28 [7%]), bronchitis (22 [5%]), and pyrexia (26 [6%]). Fewer serious adverse events were reported for benralizumab (23 [5%]) versus placebo (25 [11%]), and the only common serious adverse event (experienced by >1% of patients) was worsening of asthma, which was reported for nine (2%) patients in the benralizumab group and nine (4%) patients in the placebo group. Interpretation: Our results extend the efficacy profile of benralizumab for patients with severe eosinophilic asthma, showing early clinical benefits in patient-reported outcomes, HRQOL, lung function, and nasal polyposis symptoms. Funding: AstraZeneca.

Background Asthma control and monitoring still represents a challenge worldwide. Although the international guidelines suggest the interplay between secondary and primary care services as an effective strategy to control the disease, community pharmacies’ are seldom involved in asthma control assessment. The present cross-sectional study aimed at providing a picture of the relationship between asthma severity and control in community pharmacies within the health district of the city of Verona (Veneto Region, North-Eastern Italy). Methods A call for participation was launched through the Pharmacists’ Association of Verona. Patients referring to the participating pharmacies with an anti-asthmatic drug medical prescription and an asthma exemption code were asked to complete the Asthma Control Test (ACT) and a brief questionnaire collecting information on their age, sex, smoking status, aerobic physical exercise and usual asthma therapy, which also defined asthma severity. A multinomial logistic regression model was fitted to investigate the risk of uncontrolled as well as poorly controlled vs. controlled asthma (base). Results were expressed as relative risk ratios (RRR) with 95% confidence interval (95%CI). Results Fifty-seven community pharmacies accepted to participate and 584 asthmatic patients (54% females; mean-age: 51 ± 19 years) were consecutively recruited from 1st January to 30th June 2018 (6 months). Based upon ACT score 50.5% patients had a controlled asthma, 22.3% a poorly controlled and 27.2% uncontrolled. A variable proportion of patients with uncontrolled asthma were observed for every level of severity, although more frequently with mild persistent form of asthma. Most patients (92%) self-reported regular compliance with therapy. At multinomial regression analysis, patients under regular asthma treatment course (RRR = 0.33; 95%CI: 0.15; 0.77) were less likely to have an ACT Conclusions Overall, our findings highlighted an unsatisfactory asthma control in the general population, independently of the severity level of the disease. Community pharmacies could be a useful frontline interface between patients and the health care services, supporting an effective asthma management plan, from disease assessment and monitoring treatment compliance to referral of patients to specialist medical consultancies.

Pulmonary fibrosis (PF), a pathological outcome of chronic and acute interstitial lung diseases associated to compromised wound healing, is a key component of the “post-acute COVID-19 syndrome” that may severely complicate patients’ clinical course. Although inconclusive, available data suggest that more than a third of hospitalized COVID-19 patients develop lung fibrotic abnormalities after their discharge from hospital. The pathogenesis of PF in patients recovering from a severe acute case of COVID-19 is complex, and several hypotheses have been formulated to explain its development. An analysis of the data that is presently available suggests that biomarkers of susceptibility could help to identify subjects with increased probability of developing PF and may represent a means to personalize the management of COVID-19’s long-term effects. Our review highlights the importance of both patient-related and disease-related contributing risk factors for PF in COVID-19 survivors and makes it definitely clear the possible use of acute phase and follow-up biomarkers for identifying the patients at greatest risk of developing this disease.

We read with great interest the Brief Report "Use of Biologics to Treat Relapsing and/or Refractory Eosinophilic Granulomatosis with Polyangiitis: data from a European Collaborative Study" by Canzian et al, recently published in Arthritis & Rheumatology (1). It probably provides the largest real-life contribution on EGPA and biologic drugs. Despite the increasing evidence on the topic, including clinical trials and real life studies (2,3), identifying the most appropriate biologic treatment still represents a challenge.

This observational study aims to assess the outcome and safety of O2-therapy by high-flow nasal cannula (HFNC) in 28 consecutive patients with severe hypoxemic acute respiratory failure (hARF) consequent to SARS-CoV-2 infection, unresponsive to conventional O2-therapy. Nineteen patients had a positive response. Nine patients required escalation of treatment to non-invasive ventilation (five subsequently intubated). None of the staff had a positive swab testing during the study period and the following 14 days. Severity of hypoxemia and C reactive protein level were correlated with HFNC failure. These data suggest HFNC to be a safe treatment for less severe patients with SARS-CoV-2 hARF and efficacy will need to be assessed as part of a clinical trial.

By selectively targeting specific steps of the immune inflammation cascade, biologic drugs for severe asthma have substantially contributed to increase the standard of care, to reduce drug-related morbidity. and most importantly to ameliorate patients' quality of life. Upcoming molecules are going to provide a chance for severe phenotypes besides Th2 high through the interaction with epithelial and innate immunity. Some practical aspects including optimal treatment duration, the possibility of a dose treatment modulation, the place and relevance of ICS in best responders are still under debate. Long-term safety, especially when interacting with innate immunity needs to be further investigated.

Summary: Allergic rhinitis (AR) is a common disease affecting up to 40% of the general population worldwide. In the Coronavirus 2019 (COVID-19) pandemic era, many observational studies analysing the effect of asthma and chronic obstructive pulmonary disease on the risk of developing COVID-19 were conducted, while data on AR are limited.In this paper, we review the risk of developing SARS-Cov-2 infection carried by AR patients, the outcomes of those with COVID-19 disease, and the COVID-19 influence on the allergic and nasal symptoms and the psychological status of AR patients, in both adult and paediatric populations.AR patients seem to be protected from COVID 19 infection. Even if data about the influence of AR on the severity of COVID-19 disease are still not conclusive, it seems that being an AR patient does not increase the risk of poor COVID-19 prognoses. The clinical manifestation of AR can be distinguished by COVID-19 symptoms. Treating AR adequately is also strongly recommended, especially during pandemic.

Intimate behaviours may represent an unusual way of exposure to a culprit allergen, or the frame for sex-related allergies due to triggers typically linked to that situation. The present review aims at summarizing the state of the art about the topic, in order to spread the awareness and the basic know-how in the field of sexual-related allergies.Kiss-related IgE-mediated reactions are caused in sensitized partners mainly by the passive transport of allergenic molecules through saliva, skin or oral mucosa. It has also been recently suggested that kissing may act as an epicutaneous way for induction of allergic sensitization. Among food and drugs, not only but mostly, peanuts and beta-lactams, respectively, are the usual trigger. Although controversial, 1-hour wait before kissing and a proper mouth cleaning have been suggested as prevention strategies. Sexual intercourse related local or systemic symptoms can be caused by seminal plasma hypersensitivity, an IgE-mediated/type IV reaction due to prostate-specific antigen, which carries high homology to the canine prostatic kallikrein (Can f 5). Although applied to few patients, successful desensitization and immunotherapy protocols have been proposed.Intimate behaviours are possible modalities of contact with the allergen. The exact prevalence of such hypersensitivity reactions is not known, but for its implications on Quality of Life and reproductive wishes, the possible link between sex and allergy should become part of the personal culture of clinical allergists and every clinician, in order to extend and improve the diagnosis of unusual or unexplained conditions.

Introduction: Venom immunotherapy (VIT) is an effective treatment for Hymenoptera venom allergy. The occurrence of severe reactions (SRs) to VIT, although infrequent, hampers the achievement of tolerance to insect stings. Risk factors for such reactions include allergy to honeybee venom, concomitant mast cell disorders, and the build-up phase of VIT. A role for omalizumab has come forward in recent years. Areas covered: This article reviews the available literature on the efficacy of omalizumab in preventing SRs and allowing the attainment of VIT maintenance doses. Pre- and co-treatments with omalizumab were evaluated, with positive overall results. Adding omalizumab to VIT in patients with SRs generally results in tolerance to VIT, thus restoring its precious preventive value. Expert opinion: VIT is effective for patients with Hymenoptera venom allergy and is recommended to prevent further (possibly fatal) reactions to stings. Omalizumab has shown efficacy in protecting patients from VIT-related SRs, particularly in those at high risk of SRs because of mast cell disorders and/or honeybee venom allergy. Notwithstanding, the accepted dose and time course of omalizumab for achieving tolerability and ensuring safety during VIT are not yet defined. In the future, other biologicals may play a role in preventing SRs during VIT.

Aim: We assessed the safety of allergoid adjuvanted by monophosphoryl lipid A (uSCIT-MPL-4) in a real-life setting. Materials & methods: Patients treated with uSCIT-MPL-4 were followed-up for 1 year. Systemic reactions (SRs) were registered and the association with potential risk factors was evaluated. Results: 2929 patients were included. Grade 0, 1, 2, 3 and 4 SR reactions were observed respectively in 3.3, 1.5, 0.31, 0.07 and 0.07% of patients. A significant association was detected between Grade ≥1 SRs and: female gender, number of administrations, previous local reactions. Conclusion: uSCIT-MPL-4 is safe. Local reactions should be accurately assessed as they may represent a risk factor for Grade ≥1 SRs, together with gender and number of doses/year.

Background: Few studies have provided real-world evidence of mepolizumab efficacy and safety. We aimed to evaluate mepolizumab for severe eosinophilic asthma in daily clinical practice. Research design and methods: Patients included in the RINOVA (Interdisciplinary Network for the management of severe asthma in Veneto region, Italy) database were investigated. Blood eosinophil count, forced expiratory volume in 1 second, % of predicted (FEV1%), fractional exhaled nitric oxide (FeNO), asthma control test (ACT), oral steroid (OCS) intake, and exacerbation rate were evaluated during mepolizumab treatment. Results: 69 patients were enrolled (mean age: 55.1years; 60.9% females). A significant improvement was detected at one month with respect to blood eosinophils (median level at baseline: 710/μl; −620/μl, p

Background: There are few studies regarding severe chronic upper-airway disease (SCUAD) that represents an important socioeconomic problem for the treatment of rhinitis and associated comorbidities, particularly asthma. Objectives: The aim of our study is to evaluate the prevalence of this pathology in patients with allergic rhinitis (AR) in real life, to phenotype allergic patients with SCUAD, and to identify which factors are related to the severity of the disease. Methods: We studied 113 patients with uncontrolled AR despite optimal adherence to therapy according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in a multicenter Italian study, analyzing comorbidity, use of additional drugs, not scheduled visits, and the number of emergency room admissions. Results: Our data suggest that polysensitization is the only statistically significant factor correlating with SCUAD. Asthma does not seem to represent a correlating factor. An important finding is the poor use (20%) of allergy immunotherapy (AIT), although patients were suffering from AR and the ARIA guidelines recommend the use of AIT in moderate/severe AR. Conclusions: The SCUAD population seems not to have a specific phenotype; there is a greater presence of SCUAD in polysensibilized patients, perhaps a sign of greater inflammation.

A bulk of literature demonstrated that respiratory allergy, and especially asthma, is prevalent in males during childhood, while it becomes more frequent in females from adolescence, i.e., after menarche, to adulthood. The mechanisms underlying the difference between females and males are the effects on the immune response of female hormones and in particular the modulation of inflammatory response by estrogens, as well as the result of the activity of various cells, such as dendritic cells, innate lymphoid cells, Th1, Th2, T regulatory (Treg) and B regulatory (Bregs) cells, and a number of proteins and cytokines, which include interleukin (IL)-4, IL-5, IL-10, and IL-13. As far as sexual dimorphism is concerned, a gender difference in the expression profiles of histamine receptors and of mast cells was demonstrated in experimental studies. A critical phase of hormone production is the menstrual cycle, which often is associated with asthma deterioration, as assessed by worsening of clinical symptoms and increase of bronchial hyperresponsiveness. In asthmatic woman, there is a high risk to develop more severe asthma during menstruation. The higher prevalence of asthma in females is confirmed also in the post-menopause age, but the underlying mechanisms are not yet understood. In pregnancy, asthma may worsen but may also improve or remain unchanged, with no significant difference in frequency of these three outcomes. For allergic rhinitis, the available studies indicate, likewise asthma, a male predominance in prevalence in childhood that shifts to a female predominance in adolescence and adulthood, but further investigation is needed.

Severe asthma is a disease with a heavy socio-economic burden and a relevant impact on the life of patients. Mepolizumab (MEP) was recently introduced in practice. The previous data were favourable as efficacy and safety are concerned. Nowadays, we can report the clinical data after more than one year of use of MEP in the real-life setting.To evaluate the efficacy and safety of MEP in a real life framework, mainly concerning asthma exacerbations, steroid dependence, effects on respiratory function and adverse events.This retrospective analysis was performed on 138 patients, treated with MEP for at least 12 months, and referred to eleven severe asthma clinics in Italy. All patients met the criteria for severe uncontrolled asthma according to ATS/ERS guidelines and prescribing MEP conditions according to the Italian Drug Agency (AIFA).We could observe 138 patients (78 female, age 58 ± 10 years). The average age of onset of asthma was 34 ± 16 years. The blood eosinophil count decreased from 822 ± 491/μL at baseline to 117 ± 96/μL (p .0001) after 12 months of therapy. Exacerbations decreased from 3.8/year to 0.7/year (-81%; p .0001). Steroid-dependent patients before MEP (80%) with a daily dose of 10.1 ± 9.4 mg prednisone decrease at 28% after 12 months with a mean of 2.0 ± 4.2 mg/day (p .0001). The occurrence of adverse events was overall low.In this real-life setting, MEP confirmed its efficacy and safety profile, already shown in clinical trials. This was apparent concerning exacerbation rate, systemic steroids intake and safety.

There is controversy about the diagnostic criteria, prevalence, symptoms, and spirometry characteristics of asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO). Recent data indicate that the fixed method for diagnosing airway obstruction (AO) may overestimate ACO prevalence in the elderly, and a variable method may be more accurate. We aimed at estimating ACO prevalence in a general population sample and comparing patient and clinical features in subjects with ACO, COPD, and asthma.We analyzed data from a cross-sectional study estimating COPD prevalence in randomly selected adults aged 20-79 years in Verona, Italy, and estimated prevalence and analyzed characteristics of asthma, COPD, and ACO. ACO was defined as AO (Forced Expiratory Volume in one second-FEVOne thousand two hundred and thirty-six patients were included; 207 (16.7%) had asthma, COPD, or ACO (mean ages: 61.2, 59.7, and 57.2 years, respectively). The 3 groups had similar clinical and demographic variables; however, spirometry revealed differences between ACO and COPD patients, particularly post-bronchodilator FEVACO prevalence in Northern Italy was estimated at 2.1%, in the range of values reported by previous studies. Marked differences between ACO and COPD revealed by spirometry may have important clinical implications in terms of treatment for patients with ACO.

Background Asthma prevalence among COVID-19 patients seems to be surprisingly low. However the clinical profile of COVID-19 asthmatic patients and potential determinants of higher susceptibility/worse outcome have been scarcely investigated. We aimed to describe the prevalence and features of asthmatic patients hospitalized for COVID-19 and to explore the association between their clinical asthma profile and COVID-19 severity. Methods Medical records of patients admitted to COVID-Units of six Italian cities major hospitals were reviewed. Demographic and clinical data were analyzed and compared according to the COVID-19 outcome (death/need for ventilation vs discharge at home without requiring invasive procedures). Results Within the COVID-Units population (n = 2000) asthma prevalence was 2.1%. Among the asthmatics the mean age was 61.1 years and 60% were females. Around half of patients were atopic, blood eosinophilia was normal in most of patients. An asthma exacerbation in the 6 months before the Covid-Unit admittance was reported by 18% of patients. 24% suffered from GINA step 4–5 asthma, and 5% were under biologic treatment. 31% of patients were not on regular treatment and a negligible use of oral steroid was recorded. Within the worse outcome group, a prevalence of males was detected (64 vs 29%, p = 0.026); they suffered from more severe asthma (43 vs 14%, p = 0.040) and were more frequently current or former smokers (62 vs 25%, p = 0.038). Conclusions Our report, the first including a large COVID-19 hospitalized Italian population, confirms the low prevalence of asthma. On the other side patients with GINA 4/5 asthma, and those not adequately treated, should be considered at higher risk., Highlights • The prevalence of asthma in a large COVID-19 hospitalized Italian population was low (2.1%). • Male severe asthmatics had a worse COVID-19 outcome. • GINA 4/5 asthma patients, and those not adequately treated, should be considered at higher risk of worse COVID-19 outcome.

Severe asthma occurs in 5-10% of asthmatic patients, with nasal polyposis as one of the most frequent comorbidity. Benralizumab was recently marketed, thus we could analyse its effects in real-life in severe asthma, and compare the effects of the drug in patients with and without polyposis.Patients with severe asthma, receiving Benralizumab were enrolled in Italian asthma centres. The efficacy criteria for asthma (exacerbation rate, oral corticosteroid intake, hospitalizations, pulmonary function, exhaled nitric oxide) were evaluated at baseline and after 24 weeks of treatment. Patients were then sub-analysed according to the presence/absence of nasal polyposis.Fifty-nine patients with severe uncontrolled asthma (21 males, age range 32-78) and treated with benralizumab for at least 24 weeks has been evaluated, showing significant improvements in asthma-related outcomes, except for pulmonary function and exhaled nitric oxide. This included a reduction in the sino-nasal outcome-22 score versus baseline of 13.7 points (p = .0037) in the 34 patients with nasal polyposis. Anosmia disappeared in 31% patients (p = .0034). When comparing the groups with and without nasal polyposis, a similar reduction of exacerbations was seen, with a greater reduction of the steroid dependence in patients with polyposis (-72% vs -53%; p .0001), whereas lung function was significantly more improved (12% vs 34%, p = .0064) without polyposis patients.Benralizumab, after 6 months of treatment, confirmed its efficacy in severe asthma, and also in nasal polyposis, which is the most frequent comorbidity. The efficacy of Benralizumab in reducing steroid dependence was even higher in patients with polyposis.

Minimal clinically important difference (MCID) can be defined as the smallest change or difference in an outcome measure that is perceived as beneficial and would lead to a change in the patient's medical management.The aim of the current expert consensus report is to provide a “state-of-the-art” review of the currently available literature evidence about MCID for end-points to monitor asthma control, in order to facilitate optimal disease management and identify unmet needs in the field to guide future research.A series of MCID cut-offs are currently available in literature and validated among populations of asthmatic patients, with most of the evidence focusing on outcomes as patient reported outcomes, lung function and exercise tolerance. On the contrary, only scant and partial data are available for inflammatory biomarkers. These clearly represent the most interesting target for future development in diagnosis and clinical management of asthma, particularly in view of the several biologic drugs in the pipeline, for which regulatory agencies will soon require personalised proof of efficacy and treatment response predictors.

Mepolizumab (anti IL-5, monoclonal antibody) is commercially available in Italy since more than one year for the treatment of severe hypereosinophilic asthma. Its efficacy and safety were evaluated in several regulatory trials. The characteristics of this drug in real life began to be assessed only recently. We describe herein the drop-out rate observed with mepolizumab in real life, because this datum can indirectly reflect the safety and tolerability aspects. The demographic and clinical data of patients receiving mepolizumab for severe asthma were collected, and the number and reasons for discontinuation of the treatment were analyzed. The database involves 143 patients (67 male, age range 19-80 year) who received at least one dose of mepolizumab. The observed discontinuation rate was 6/143 (4.2%). Five out of 6 discontinuations were due to lack of response, and one was an adverse event (urticaria) probably related to the treatment. There was no clinical difference between the drop-out group and the patients still ongoing. As compared to the clinical trials published the discontinuation rate was lower in our population, especially for adverse events (7% vs 23.7%). Thus, the tolerability of mepolizumab, as derived from discontinuations, seems to be better in real-life than in clinical trials.

In the last decades, bronchial asthma has represented a main focus of both basic and pharmacological research. In fact, the knowledge about pathophysiological mechanisms and phenotypes as well as t...

Background Omalizumab therapy is effective and safe in patients with chronic spontaneous urticaria (CSU) resistant to nonsedating histamine 1 (H 1 ) antihistamines (nsAHs). Objective To evaluate the efficacy and safety of omalizumab in elderly (aged ≥65 years) patients with nonsedating H 1 -antihistamine–refractory CSU in a real-life setting. Methods Patients with nonsedating H 1 -antihistamine–refractory CSU (n = 322) treated with omalizumab administered every 4 weeks in doses of 300 mg for 24 weeks were divided into 2 groups according to age at omalizumab treatment onset: 15 to 64 years and 65 years or older. Treatment response was assessed using a 7-day urticaria activity score (UAS7). Adverse effects of omalizumab therapy were recorded. Results Among patients, 32 (9.9%) were 65 years or older. At baseline, CSU characteristics were generally similar among the groups, although the presence of angioedema was statistically significantly lower in patients younger than 65 years. Any differences in weekly itch severity score, hive score, and UAS7 between the 2 age groups were not significant at weeks 4, 12, and 24, with the exception of the hive score at 24 weeks and the UAS7 at week 24. No significant between-group differences were seen in the proportion of patients with a UAS7 of 6 or lower and with a UAS7 score of 0 at weeks 4, 12, 24, and 40. The proportion of patients with at least one adverse event reported as suspected to be caused by study drug was 10% in the younger group vs 6.3% in the older group ( P = .53). Conclusion Our study found that omalizumab is a well-tolerated and effective therapy for elderly patients with nonsedating H 1 -antihistamine–refractory CSU.

Background Severe Asthma Network in Italy (SANI) is a registry of patients recruited by accredited centers on severe asthma. Objective To analyze epidemiological, clinical, inflammatory, functional, and treatment characteristics of severe asthmatics from the SANI registry. Methods All consecutive patients with severe asthma were included into the registry, without exclusion criteria to have real-life data on demographics, asthma control, treatments (including biologics), inflammatory biomarkers, and comorbidities. Results A total of 437 patients (mean age: 54.1 years, 57.2% females, 70.7% atopics, 94.5% in Global Initiative for Asthma severity step V) were enrolled into the study. The mean annual exacerbation rate was 3.75. The mean blood eosinophil level was 536.7 cells/mcL, and the average serum total IgE was 470.3 kU/L. Approximately 64% of patients were on regular oral corticosteroid treatment, 57% with omalizumab and 11.2% with mepolizumab. Most common comorbidities were rhinitis, nasal polyposis, and bronchiectasis. Patients with nasal polyposis had higher age of disease onset, higher blood eosinophil count, and lower frequency of atopy and atopic eczema. Bronchiectasis was associated with more frequent severe exacerbations, higher blood eosinophils, and total IgE. Stratifying patients, those with late-onset asthma were less frequently atopic (with less frequent allergic rhinitis and food allergy), and more frequently with nasal polyposis and higher serum total IgE levels. Conclusions This study revealed a high frequency of relevant comorbidities and that a substantial proportion of patients have late-onset asthma; all these features define specific different disease phenotypes. Severe asthma complexity and comorbidities require multidisciplinary approaches, led by specifically trained pulmonologists and allergists.

There is a need for validated tools to assess health-related quality of life (HRQoL) in routine clinical practice.The aim of this study was to validate the Chronic Urticaria Patient Perspective (CUPP) for assessment of patients with chronic urticaria (CU) in clinical practice.A provisional CUPP was developed from candidate items identified by following an iterative process in a retrospective analysis of 249 Chronic Urticaria Quality of Life Questionnaire questionnaires. The psychometric properties of the CUPP were then tested on a sample of patients enrolled in 13 Italian centers.The study population in the validation phase comprised 152 patients. The 10-item version of the CUPP showed satisfactory internal consistency (Cronbach's alpha values of 0.76 at visit 1 and 0.90 at visit 2), good criteria, and discriminative and convergent validity. Reliability was assessed in 34 patients with no changes in health (Global Rating Scale = 0 at visit 2) and was satisfactory (CCC [concordance correlation coefficient] = 0.9). Changes in CUPP scores were significantly associated with changes in Urticaria Activity Score (UAS)-Hive count (r = 0.36, P .001), UAS-Itch severity (r = 0.48, P.001), and UAS-Total score (r = 0.342, P.001), all of which indicated good responsiveness. The minimal important difference was 1.5.CUPP is a simple 10-question tool with good psychometric properties that provides a valid, reliable, and standardized measurement of HRQoL in patients with CU.

Objectives: The real incidence of pneumomediastinum (PNM) in adult patients with severe acute asthma exacerbation continues to be unknown. The current study aims to investigate the occurrence of PN...

In recent years the relationship between bone, metabolism and many pathophysiologic mechanisms involving other organs and the immune system, was increasingly apparent. This observation concerns vitamin D, osteopontin and periostin (PO). PO is expressed in the periosteum of long bones but also in many other tissues and organs, including heart, kidney, skin and lungs, being enhanced by mechanical stress or injury. PO has a relevant physiological function in promoting injury repair in a large number of tissues. However, its overexpression was observed in different diseases characterized by inflammation, fibrosis and tumorigenesis. Here we review the current knowledge on the role of PO in physiologic and pathologic pathways of different diseases. A specific focus regards the correlation between the level of PO and lung diseases and the identification of PO also as an inflammatory key effector in asthma, strongly associated with airways eosinophilia. In fact PO seems to be a useful biomarker of "Th2-high" asthma compared to "Th2-low" asthma phenotype and a predictor of response to therapeutic agents. Currently, a growing number of studies suggests a possible role of PO as a new diagnostic marker and/or therapeutic target for different diseases and its usefulness in clinical practice should be supported and confirmed by further and larger studies.