The Prevalence of Immediate Hypersensitivity Reactions to the BNT162b2 mRNA Vaccine against SARS-CoV-2: Data from the Vaccination Campaign in a Large Academic Hospital.

The anti-SARS-CoV-2 vaccination has probably been the most effective tool for preventing the infection and negative outcomes of the COVID-19 disease, and therefore for interrupting the pandemic state. The first licensed SARS-CoV-2 vaccine was BNT162b2, an mRNA vaccine that has been widely used since the earliest stages of the global vaccination campaign. Since the beginning of the vaccination campaign, some cases of suspected allergic reactions to BNT162b2 have been described. Epidemiological data, however, have provided reassuring results of an extremely low prevalence of these hypersensitivity reactions to anti-SARS-CoV-2 vaccines. In this article, we describe the results of a survey carried out through the use of a questionnaire, administered to all the health personnel of our university hospital after the first two doses of the BNT162b2 vaccine, which investigated the development of adverse reactions after a vaccination. We analyzed the responses of 3112 subjects subjected to the first dose of the vaccine; among these, 1.8% developed symptoms compatible with allergic reactions and 0.9% with clinical manifestations of possible anaphylaxis. Only 10.3% of the subjects who had allergic reactions after the first injection experienced similar reactions after the second dose and none of them experienced anaphylaxis. In conclusion, the anti-SARS-CoV-2 vaccination is rarely associated with severe allergic reactions and the second dose of vaccine is safe for this group of patients.

Polyethylene Glycol and Polysorbate 80 Skin Tests in the Context of an Allergic Risk Assessment for Hypersensitivity Reactions to Anti-SARS-CoV-2 mRNA Vaccines.

Concern has arisen about hypersensitivity reactions in patients with allergic reactions to drugs containing polyethylene glycol (PEG) or polysorbate 80 (PS80), excipients of currently available anti-SARS-CoV-2 mRNA vaccines. However, the actual utility of PEG and PS80 skin allergy testing is currently still debated. We retrospectively analyzed all cases of patients on whom we performed allergometric skin tests for PEG and PS80 in the context of a pre-vaccination screening (for patients with multiple hypersensitivity reactions to drugs for which these excipients were among the suspected agents) or following suspected hypersensitivity reactions to anti-SARS-CoV-2 vaccines. A total of 134 tests were performed for PEG and PS80, eight of which produced uninterpretable results (due to dermographism or non-specific reactions). Of the remaining 126 cases (85 pre-vaccinal and 41 post-vaccine reactions), 16 (12.7%) were positive for PEG and/or PS80. Stratifying by clinical indication, there were no statistically significant differences in the proportion of positive tests between patients evaluated in the context of the pre-vaccination screening and those evaluated after a vaccine reaction (10.6% vs. 17.1%, respectively, p = 0.306). Allergometric skin tests for PEG and PS80 in our case series resulted positive in an unexpectedly high proportion of patients, suggesting that testing for allergy to these two excipients should not be ignored in case of reasonable clinical suspicion.

Oral Corticosteroid Abuse and Self-Prescription in Italy: A Perspective from Community Pharmacists and Sales Reports before and during the COVID-19 Era.

(1) Background: Corticosteroids are commonly used for a variety of conditions, but their use might come with significant side effects. Self-medication practices increased during the COVID-19 pandemic, potentially favoring corticosteroid misuse. Studies on this topic are lacking, thus we aim to characterize the misuse of corticosteroids in Italy through pharmacists' perspectives and sales reports. (2) Methods: We sent to territorial pharmacists a survey that aimed to investigate corticosteroid misuse before and during the pandemic. In parallel, sales reports of the major oral corticosteroids were obtained from IQVIA. (3) Results: We found that 34.8% of clients demanded systemic corticosteroids without a valid prescription, with a rise to 43.9% during the pandemic (p < 0.001). Adults and patients suffering from upper airway diseases or obstructive airway diseases most frequently asked for corticosteroids without an appropriate prescription. The greatest increase after the beginning of the pandemic was seen for lung diseases. Although sales of the major oral corticosteroids decreased during the pandemic, sales of those used for COVID-19 increased. (4) Conclusions: Self-medication with corticosteroids is common and might lead to avoidable toxicities. This tendency increased during the pandemic probably because of incorrect beliefs about the inappropriate use of corticosteroids for treating COVID-19 itself. The development of shared strategies between doctors and pharmacists is essential in defining protocols guiding appropriate patient referral in order to minimize corticosteroid misuse.

Desensitization Protocols for Anti-SARS-CoV-2 Vaccines in Patients with High Risk of Allergic Reactions.

Vaccines for SAR-CoV-2 are the most effective preventive treatment able to reduce the risk of contracting the infection and experiencing worse outcomes whenever the infection is contracted. Despite their rarity, hypersensitivity reactions to the anti-SARS-CoV-2 vaccine have been described and could become the reason not to complete the vaccination. Desensitization protocols for other vaccines have been described and validated, while the use of this approach for anti-SARS-CoV-2 vaccines is still anecdotal. We herein describe our experience with 30 patients with previous allergic reactions to anti-SARS-CoV-2 vaccines or to any of their excipients, proving that they are effective and safe; only two patients experienced hypersensitivity reaction symptoms during the desensitization procedure. Moreover, in this article, we propose desensitization protocols for the most common anti-SARS-CoV-2 vaccines.

Cross-Cultural Validation of the Short Version of the Questionnaire of Olfactory Disorders-Negative Statements into Italian: Towards Personalized Patient Care.

Given the high burden of olfactory dysfunction worldwide, recently increased due to the COVID-19 pandemic, it is mandatory to adopt a specific questionnaire to assess the impact of olfactory impairment on quality of life, to be used in clinical practice. The aim of this study is to adapt and validate the short version of the Questionnaire of Olfactory Disorders-Negative Statements (svQOD-NS) for Italian. In the pilot phase, the Italian version of the questionnaire (ITA-svQOD-NS) was produced following recommended guidelines. It was then given to 50 healthy subjects and 50 patients (affected by either nasal polyposis or septal deviation), and results were compared to those of other widely used questionnaires. Test-retest reliability was assessed on a sample of 25 patients. All 50 patients repeated the questionnaires at one and nine months after surgery. The internal consistency of ITA-svQOD-NS measured with Cronbach α was excellent (α = 0.92). The intraclass correlation coefficient for test-retest reliability was also optimal (0.93; 95%CI: 0.90-0.96). Concurrent validity tested with the Pearson coefficient was significant with all other tests administered; also, concerning responsiveness, statistically significant differences were obtained between pre- and post-operative conditions. ITA-svQOD-NS showed high internal consistency, test-retest reliability, and significant correlation with all most-used clinical questionnaires; thus, it can be efficiently applied to assess olfaction-related QoL in the Italian population.

A Renewed Charter: Key Principles to Improve Patient Care in Severe Asthma.

Asthma is a heterogenous respiratory disease, usually associated with chronic airway inflammation and hyper-responsiveness, which affects an estimated 339 million people worldwide. Severe asthma affects approximately 5-10% of patients with asthma, approximately 17-34 million people globally, more than half of whom have uncontrolled disease. Severe asthma carries a substantial burden of disease, including unpredictable symptoms and potentially life-threatening flare-ups. Furthermore, severe asthma has a substantial burden on health care systems and economies worldwide. In 2018, a group of experts from the clinical community, patient support groups, and professional organisations joined together to develop the Severe Asthma Patient Charter, which set out six principles to define what patients should expect for the management of their severe asthma and what should constitute a basic standard of care. Since the publication of that original Charter in 2018, several important changes have occurred, including an improved understanding of asthma and effective asthma management; several new therapies have become available; and finally, the COVID-19 pandemic has placed a spotlight on respiratory conditions, the workforces that treat them, and the fundamental importance of health care system resilience. With those developments in mind, we, representatives of the academic, clinical, and patient advocacy group communities, have updated the Charter to Improve Patient Care in Severe Asthma with a focus on six principles: (1) I deserve a timely, comprehensive assessment of my asthma and its severity; (2) I deserve a timely, straightforward referral to an appropriate specialist for my asthma when it is not well controlled; (3) I deserve to understand what makes my asthma worse; (4) I deserve access to treatment and care that reduces the impact of asthma on my daily life; (5) I deserve not to be reliant on systemic corticosteroids; (6) I deserve to be involved in decisions about my treatment and care.

REALITI-A Study: Real-World Oral Corticosteroid-Sparing Effect of Mepolizumab in Severe Asthma.

BACKGROUND: Patients with severe asthma may require maintenance oral corticosteroids (mOCS) for disease control as well as systemic corticosteroid (SCS) bursts for clinically significant exacerbations. However, mOCS and SCS use are associated with adverse effects, which increases patient disease burden. OBJECTIVE: To assess the real-world corticosteroid-sparing effect of mepolizumab in patients with severe asthma. METHODS: REALITI-A was a 24-month international, prospective, observational cohort study involving 84 centers across Europe, Canada, and the United States, with a 1-year pre-post mepolizumab treatment preplanned interim analysis. A total of 822 adults with a clinical diagnosis of asthma and a physician decision to initiate mepolizumab treatment (100 mg subcutaneously) were included. End points included daily mOCS dose at baseline (penultimate 28 days of pretreatment) and 1 year after treatment; percent reduction from baseline in mOCS dose; patients discontinuing mOCS 1 year after treatment; and the rate of clinically significant exacerbations (those requiring OCS for 3 days or more [or parenteral administration], emergency room visit, and/or hospital admission) before and after treatment. RESULTS: A total of 319 patients received mOCS at baseline (median [interquartile range]: 10.0 [5.0-15.0] mg/d). At 1 year after treatment, median mOCS dose was reduced by 75% (2.5 [0.0-5.0] mg/d); 64% of patients had a reduction in mOCS dose of 50% or greater compared with baseline and 43% discontinued mOCS. Clinically significant exacerbations decreased between pretreatment and posttreatment (rate ratio [95% confidence interval] 0.29 [0.26-0.32]; P < .001). CONCLUSION: This 1-year analysis demonstrates that real-world mepolizumab treatment is clinically effective in patients with severe asthma, providing disease control while reducing the need for mOCS and SCS bursts.

Impact of COVID-19 in allergen immunotherapy: An Italian survey.

Allergen immunotherapy (AIT) is a common treatment for patients with allergic asthma and allergic rhinoconjunctivitis. There is evidence that the COVID-19 pandemic could have altered the administration of AIT in patients in some countries, as the pandemic caused major limitations to healthcare access and delivery. The objective of this study was to evaluate the impact of the disruption imposed by the pandemic on the perceptions and administration of AIT therapies in Italy. An online survey was carried out among Italian allergists between 22 February 2021 and 12 April 2021. The results show that Italian physicians (N=66) did not consider that the COVID-19 pandemic presented an added risk to patients with allergic asthma or rhinitis receiving AIT. Although most treatments continued, there were reduced rates of AIT therapy initiations and sublingual AIT was favored over subcutaneous AIT.

Patient's Adherence and Compliance and Quality of Life During/After VIT.

Adherence and compliance, respectively considered as a more positive, proactive behavior, resulting in a patient's lifestyle change to follow a daily regimen, and, as a more enforced response to an external command, are a critical aspect of any medical therapy, since it is estimated that less than half of the patients who are prescribed a therapy perform it, respecting the doses and duration. As far as aeroallergen immunotherapy is concerned, current data show that adherence is respected in about 50% of subcutaneous immunotherapy and in percentages even lower than 20% in sublingual immunotherapy treatments. This review analyzes the adherence to venom immunotherapy (VIT), in which, given its purpose of preventing potentially fatal anaphylactic reactions to insect stings, this aspect plays a critical role. In fact, protection from stings already takes place when the maintenance dose is reached, but VIT interruption before the recommended duration of 5 years exposes patients to new sting reactions. The data on adherence to VIT are far less abundant than that for aeroallergen immunotherapy. One of the first studies reported poor adherence in Austria, but the model used, consisting in the estimate of the percentage of patients with systemic reactions who accepted or rejected VIT, does not meet the criteria that define adherence to treatment. As for appropriate adherence studies, rates higher than 70% were reported in the United States and European countries. Studies from Italy found that good adherence were observed also in patients receiving, after 4 years of VIT, 3 months extended maintenance dose, as well as in patients treated during the COVID-19 pandemic, <10% of whom stopped VIT. Instead, only 35% of the patients treated for allergy to imported fire ant remained adherent after 1 year of treatment. However, also concerning honeybees and vespids, although adherence is satisfactory, it is possible to further improve it by increasing information and support for patients. Health-related quality of life (HRQL) is an efficient measure to estimate the effectiveness and safety of medical treatment. Tools designed to make patients aware of its improvement through VIT and, in particular, of the complete prevention of the risk of fatal reactions have an important role in reinforcing adherence. However, aspects not yet evaluated, such as the possible relationship between the efficacy of VIT and HRQL or its particular features in patients with mastocytosis, deserve specific studies.

The Present and Future of Allergen Immunotherapy in Personalized Medicine.

Allergic diseases are particularly suitable for personalized medicine, because they meet the needs for therapeutic success, which include a known molecular mechanism of the disease, a diagnostic tool for that disease and a treatment that blocks this mechanism. A range of tools is available for personalized allergy diagnosis, including molecular diagnostics, treatable traits and omics (i.e., proteomics, epigenomics, metabolomics, transcriptomics and breathomics), to predict patient response to therapies, detect biomarkers and mediators and assess disease control status. Such tools enhance allergen immunotherapy. Higher diagnostic accuracy results in a significant increase (based on a greater performance achieved with personalized treatment) in efficacy, further increasing the known and unique characteristics of a treatment designed to work on allergy causes.

WAO-ARIA consensus on chronic cough - Part III: Management strategies in primary and cough-specialty care. Updates in COVID-19.

Background: Chronic cough management necessitates a clear integrated care pathway approach. Primary care physicians initially encounter the majority of chronic cough patients, yet their role in proper management can prove challenging due to limited access to advanced diagnostic testing. A multidisciplinary approach involving otolaryngologists and chest physicians, allergists, and gastroenterologists, among others, is central to the optimal diagnosis and treatment of conditions which underly or worsen cough. These include infectious and inflammatory, upper and lower airway pathologies, or gastro-esophageal reflux. Despite the wide armamentarium of ancillary testing conducted in cough multidisciplinary care, such management can improve cough but seldom resolves it completely. This can be due partly to the limited data on the role of tests (eg, spirometry, exhaled nitric oxide), as well as classical pharmacotherapy conducted in multidisciplinary specialties for chronic cough. Other important factors include presence of multiple concomitant cough trigger mechanisms and the central neuronal complexity of chronic cough. Subsequent management conducted by cough specialists aims at control of cough refractory to prior interventions and includes cough-specific behavioral counseling and pharmacotherapy with neuromodulators, among others. Preliminary data on the role of neuromodulators in a proof-of-concept manner are encouraging but lack strong evidence on efficacy and safety. Objectives: The World Allergy Organization (WAO)/Allergic Rhinitis and its Impact on Asthma (ARIA) Joint Committee on Chronic Cough reviewed the recent literature on management of chronic cough in primary, multidisciplinary, and cough-specialty care. Knowledge gaps in diagnostic testing, classical and neuromodulator pharmacotherapy, in addition to behavioral therapy of chronic cough were also analyzed. Outcomes: This third part of the WAO/ARIA consensus on chronic cough suggests a management algorithm of chronic cough in an integrated care pathway approach. Insights into the inherent limitations of multidisciplinary cough diagnostic testing, efficacy and safety of currently available antitussive pharmacotherapy, or the recently recognized behavioral therapy, can significantly improve the standards of care in patients with chronic cough.

The effect of the COVID-19 pandemic on severe asthma care in Europe: will care change for good?

Background: The coronavirus disease 2019 (COVID-19) pandemic has put pressure on healthcare services, forcing the reorganisation of traditional care pathways. We investigated how physicians taking care of severe asthma patients in Europe reorganised care, and how these changes affected patient satisfaction, asthma control and future care. Methods: In this European-wide cross-sectional study, patient surveys were sent to patients with a physician-diagnosis of severe asthma, and physician surveys to severe asthma specialists between November 2020 and May 2021. Results: 1101 patients and 268 physicians from 16 European countries contributed to the study. Common physician-reported changes in severe asthma care included use of video/phone consultations (46%), reduced availability of physicians (43%) and change to home-administered biologics (38%). Change to phone/video consultations was reported in 45% of patients, of whom 79% were satisfied or very satisfied with this change. Of 709 patients on biologics, 24% experienced changes in biologic care, of whom 92% were changed to home-administered biologics and of these 62% were satisfied or very satisfied with this change. Only 2% reported worsening asthma symptoms associated with changes in biologic care. Many physicians expect continued implementation of video/phone consultations (41%) and home administration of biologics (52%). Conclusions: Change to video/phone consultations and home administration of biologics was common in severe asthma care during the COVID-19 pandemic and was associated with high satisfaction levels in most but not all cases. Many physicians expect these changes to continue in future severe asthma care, though satisfaction levels may change after the pandemic.

New Onset of Eosinophilic Granulomatosis with Polyangiitis Following mRNA-Based COVID-19 Vaccine.

Anti-SARS-CoV-2 vaccines are safe and effective, also in individuals with allergic and immune-mediated diseases (IMDs). There are reports suggesting that vaccines may be able to trigger de-novo or exacerbate pre-existing IMDs in predisposed individuals. Eosinophilic granulomatosis with polyangiitis (EGPA) is a small-vessel vasculitis characterized by asthma, eosinophilia, and eosinophil-rich granulomatous inflammation in various tissues. We describe the case of a 63-year-old man who experienced cardiac, pulmonary, and neurological involvement one day after the administration of the booster dose of anti-SARS-CoV-2 vaccine (mRNA-1273). A diagnosis of EGPA was made and the patient was treated with high-dose steroids and cyclophosphamide, with a good clinical response. Interestingly, our patient had experienced a significant worsening of his pre-existing asthma six months earlier, just after the first two vaccine shots with the ChAdOx1 anti-SARS-CoV-2 vaccine. It is impossible to know whether our patient would have had developed EGPA following natural SARS-CoV-2 infection or at some point in his life regardless of infectious stimuli. Nevertheless, our report may suggest that caution should be paid during the administration of additional vaccine doses in individuals who experienced an increase in IMD severity that persisted over time following previous vaccine shots.

WAO-ARIA consensus on chronic cough - Part II: Phenotypes and mechanisms of abnormal cough presentation - Updates in COVID-19.

BACKGROUND: Chronic cough can be triggered by respiratory and non-respiratory tract illnesses originating mainly from the upper and lower airways, and the GI tract (ie, reflux). Recent findings suggest it can also be a prominent feature in obstructive sleep apnea (OSA), laryngeal hyperresponsiveness, and COVID-19. The classification of chronic cough is constantly updated but lacks clear definition. Epidemiological data on the prevalence of chronic cough are informative but highly variable. The underlying mechanism of chronic cough is a neurogenic inflammation of the cough reflex which becomes hypersensitive, thus the term hypersensitive cough reflex (HCR). A current challenge is to decipher how various infectious and inflammatory airway diseases and esophageal reflux, among others, modulate HCR. OBJECTIVES: The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on classification, epidemiology, presenting features, and mechanistic pathways of chronic cough in airway- and reflux-related cough phenotypes, OSA, and COVID-19. The interplay of cough reflex sensitivity with other pathogenic mechanisms inherent to airway and reflux-related inflammatory conditions was also analyzed. OUTCOMES: Currently, it is difficult to clearly ascertain true prevalence rates in epidemiological studies of chronic cough phenotypes. This is likely due to lack of standardized objective measures needed for cough classification and frequent coexistence of multi-organ cough origins. Notwithstanding, we emphasize the important role of HCR as a mechanistic trigger in airway- and reflux-related cough phenotypes. Other concomitant mechanisms can also modulate HCR, including type2/Th1/Th2 inflammation, presence or absence of deep inspiration-bronchoprotective reflex (lower airways), tissue remodeling, and likely cough plasticity, among others.

What we know and still ignore on COVID-19 immune pathogenesis and a proposal based on the experience of allergic disorders.

The coronavirus disease 2019 (COVID-19) pandemic started in March 2020 and caused over 5 million confirmed deaths worldwide as far August 2021. We have been recently overwhelmed by a wide literature on how the immune system recognizes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and contributes to COVID-19 pathogenesis. Although originally considered a respiratory viral disease, COVID-19 is now recognized as a far more complex, multi-organ-, immuno-mediated-, and mostly heterogeneous disorder. Though efficient innate and adaptive immunity may control infection, when the patient fails to mount an adequate immune response at the start, or in advanced disease, a high innate-induced inflammation can lead to different clinical outcomes through heterogeneous compensatory mechanisms. The variability of viral load and persistence, the genetic alterations of virus-driven receptors/signaling pathways and the plasticity of innate and adaptive responses may all account for the extreme heterogeneity of pathogenesis and clinical patterns. As recently applied to some inflammatory disorders as asthma, rhinosinusitis with polyposis, and atopic dermatitis, herein we suggest defining different endo-types and the related phenotypes along COVID-19. Patients should be stratified for evolving symptoms and tightly monitored for surrogate biomarkers of innate and adaptive immunity. This would allow to preventively identify each endo-type (and its related phenotype) and to treat patients precisely with agents targeting pathogenic mechanisms.

Real-life survey on severe asthma patients during COVID-19 lockdown in Italy.

Introduction: The SARS-CoV-2 pandemic has deeply revolutionized our lives and consequently the management of patients, specifically ones with severe asthma.Objective: A survey was conducted to evaluate the effects on adherence, exacerbations and quality of life in patients with severe asthma during the COVID-19 pandemic period.Methods: 100 severe asthma patients, who accepted to participate to the survey, were asked to respond to different questionnaires in order to assess asthma symptoms (Asthma Control Test - ACT, and Asthma Control Quality - ACQ) and rino-sinusal ones (Sino-nasal outcome test - SNOT-22).Results: 31 out of 100 patients reported worsening of respiratory symptoms requiring a step-up in therapy dosage or frequency during the observational period; however, exacerbation rate was very low. Only 17 (17%) of the 100 participants experienced a severe asthma exacerbation. Moreover, there was no confirmed diagnosis of COVID-19 in this population.Conclusion: Patients with severe asthma did not show higher rates of exacerbations during the pandemic outbreak as well as no increased risk of contracting COVID-19 infection or developing the disease. Self-administration of biological drugs could be useful to maintain high rates of adherence to therapy, and, at the same time, to decrease the risk of exacerbations or Intensive Care Unit (ICU) room access.

Successful SARS-CoV-2 vaccine allergy risk-management: The experience of a large Italian University Hospital.

BACKGROUND: Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines have been approved recently, and public concern regarding the risk of anaphylactic reactions arose after a few cases during the first days of mass vaccination. Polyethylene glycol (PEG) has been suggested as the most probable culprit agent for allergic reactions. OBJECTIVE: We describe the allergy work-up protocol implemented for the vaccination campaign in our Center, aiming to allow the greatest number of people to be vaccinated safely. METHODS: The protocol included the self-report of a history of suspected drug or vaccine allergies, and subsequent teleconsultation and allergometric tests for PEG and Polysorbate 80 (PS80). A desensitizing protocol of vaccine administration was applied to patients sensitized only to PS80, and to those with a suspect allergic reaction after the first vaccine dose. RESULTS: 10.2% (414 out of 4042) of the entire vaccine population have been screened: only one patient resulted allergic to PEG and therefore excluded from the vaccination. Another patient was sensitized to PS80 only and safely vaccinated applying the desensitizing protocol. Seven subjects without a previous history of allergic disease experienced suspect hypersensitivity reactions to the first administered dose: one of them resulted allergic to PEG and was excluded from the second dose, while the others safely completed the vaccination with the desensitizing protocol. CONCLUSION: A careful allergological risk-assessment protocol significantly reduces the number of patients who would have avoided SARS-CoV-2 vaccination for their allergies and to effectively identify and manage those rare patients with sensitization to PEGs and/or PS80.