Asthma management, focused on the use of oral corticosteroids: the opinions of Italian asthmatic patients.

OBJECTIVE: Patients' perceptions of asthma symptoms, and attitudes regarding diagnosis and management, can affect their ability to reach good asthma control. The aim of the study was to explore patients' perceptions of asthma management, with focus on treatment with oral corticosteroids (OCS). METHODS: A DOXAPHARMA survey was conducted. A questionnaire with 46 multiple choice questions was completed by 50 patients with severe uncontrolled asthma, and 258 with mild-moderate controlled or partly controlled asthma. Participants were representative of Italian asthmatic patients-with medium age, long asthma duration, delayed diagnosis, poor asthma control, and frequent exacerbations. RESULTS: Many asthmatics reported inadequate pharmacologic treatment. The majority but not all patients regularly used ICS/LABA. Oral treatment was common, mainly with OCS, particularly in severe asthmatics. One-fourth of patients did not regularly use inhaled therapy, and adherence was poor, resulting in frequent OCS use to treat exacerbations, which were common in mild-moderate cases. Patients were fairly satisfied with asthma therapies, but many had concerns about long-term corticosteroid use. Patients complained about poor management of comorbidities associated with asthma and OCS use, but were generally satisfied with their patient/doctor relationships. Many patients failed to achieve optimal health-related quality of life (HRQoL), mainly those with severe asthma who used OCS treatment and emphasized how OCS therapy impacted QoL. CONCLUSIONS: The survey results confirmed many problems related to mild-moderate and severe asthma management in Italy and highlighted the overuse of OCS rather than more effective and safe treatments, which had strong negative effects on HRQoL.

Molecular Characterization of the Allergenic Arginine Kinase from the Edible Insect Hermetia illucens (Black Soldier Fly).

SCOPE: Arginine kinase (AK) is an important enzyme for energy metabolism of invertebrate cells by participating in the maintenance of constant levels of ATP. However, AK is also recognized as a major allergen in insects and crustaceans capable of cross-reactivity with sera of patients sensitized to orthologous proteins. In the perspective of introducing insects or their derivatives in the human diet in Western world, it is of primary importance to evaluate possible risks for allergic consumers. METHODS AND RESULTS: This work reports the identification and characterization of AK from Hermetia illucens commonly known as the black soldier fly, a promising insect for human consumption. To evaluate allergenicity of AK from H. illucens, putative linear and conformational epitopes are identified by bioinformatics analyses, and Dot-Blot assays are carried out by using sera of patients allergic to shrimp or mites to validate the cross-reactivity. Gastrointestinal digestion reduces significantly the linear epitopes resulting in lower allergenicity, while the secondary structure is altered at increasing temperatures supporting the possible loss or reduction of conformational epitopes. CONCLUSION: The results indicate that the possible allergenicity of AK should be taken in consideration when dealing with novel foods containing H. illucens or its derivatives.

The 1st EoETALY Consensus on the Diagnosis and Management of Eosinophilic Esophagitis-Current Treatment and Monitoring.

The present document constitutes Part 2 of the EoETALY Consensus Statements guideline on the diagnosis and management of eosinophilic esophagitis (EoE) developed by experts in the field of EoE across Italy (i.e., EoETALY Consensus Group). Part 1 was published as a different document, and included three chapters discussing 1) definition, epidemiology, and pathogenesis; 2) clinical presentation and natural history and 3) diagnosis of EoE. The present work provides guidelines on the management of EoE in two final chapters: 4) treatment and 5) monitoring and follow-up, and also includes considerations on knowledge gaps and a proposed research agenda for the coming years. The guideline was developed through a Delphi process, with grading of the strength and quality of the evidence of the recommendations performed according to accepted GRADE criteria.This document has received the endorsement of three Italian national societies including the Italian Society of Gastroenterology (SIGE), the Italian Society of Neurogastroenterology and Motility (SINGEM), and the Italian Society of Allergology, Asthma, and Clinical Immunology (SIAAIC). The guidelines also involved the contribution of members of ESEO Italia, the Italian Association of Families Against EoE.

The 1st EoETALY Consensus on the Diagnosis and Management of Eosinophilic Esophagitis - Definition, Clinical Presentation and Diagnosis.

Eosinophilic esophagitis (EoE) is a chronic type 2-mediated inflammatory disease of the esophagus that represents the most common eosinophilic gastrointestinal disease. Experts in the field of EoE across Italy (i.e., EoETALY Consensus Group) including gastroenterologists, endoscopists, allergologists/immunologists, and paediatricians conducted a Delphi process to develop updated consensus statements for the management of patients with EoE and update the previous position paper of the Italian Society of Gastroenterology (SIGE) in light of recent evidence. Grading of the strength and quality of the evidence of the recommendations was performed using accepted GRADE criteria. The guideline is divided in two documents: Part 1 includes three chapters, namely 1) definition, epidemiology, and pathogenesis; 2) clinical presentation and natural history, and 3) diagnosis, while Part 2 includes two chapters: 4) treatment and 5) monitoring and follow-up. This document has received the endorsement of three Italian national societies including the SIGE, the Italian Society of Neurogastroenterology and Motility (SINGEM), and the Italian Society of Allergology, Asthma, and Clinical Immunology (SIAAIC). With regards to patients' involvement, these guidelines involved the contribution of members of ESEO Italia, the Italian Association of Families Against EoE.

The New Therapeutic Frontiers in the Treatment of Eosinophilic Esophagitis: Biological Drugs.

Eosinophilic esophagitis (EoE) is a multifaceted disease characterized by a wide heterogeneity of clinical manifestations, endoscopic and histopathologic patterns, and responsiveness to therapy. From the perspective of an effective approach to the patient, the different inflammatory mechanisms involved in the pathogenesis of EoE and biologics, in particular monoclonal antibodies (mAbs), targeting these pathways are needed. Currently, the most relevant is dupilumab, which interferes with both interleukin (IL)-4 and IL-13 pathways by binding IL-4 receptor α, and is the only mAb approved by the European Medicine Agency and US Food and Drug Administration for the treatment of EoE. Other mAbs investigated include mepolizumab, reslizumab, and benralizumab (interfering with IL-5 axis), cendakimab and dectrekumab (anti-IL-13s), tezepelumab (anti-TSLP), lirentelimab (anti-SIGLEG-8), and many others. Despite the undeniable economic impact of biologic therapies, in the near future, there will be room for further reflection about the opportunity to prescribe biologic agents, not only as a last-line therapy in selected cases such as patients with comorbidities involving common pathways. Although recent findings are very encouraging, the road to permanent success in the treatment of EoE is still long, and further studies are needed to determine the long-term effects of mAbs and to discover new potential targets.

Factors and co-factors influencing clinical manifestations in nsLTPs allergy: between the good and the bad.

Non-specific lipid transfer proteins (nsLTPs) are a family of plant pan-allergens that represent the primary cause of food allergies in the Mediterranean area, characterized by a wide range of clinical manifestations, ranging from the total absence of symptoms up to anaphylaxis. This wide variety of symptoms is related to the intrinsic capacity of nsLTPs to cause an allergic reaction in a specific subject, but also to the presence of co-factors exacerbating (i.e., exercise, NSAIDs, PPIs, alcohol, cannabis, prolonged fasting, menstruation, acute infections, sleep deprivation, chronic urticaria) or protecting from (i.e., co-sensitization to PR10, profilin or polcalcin) severe reactions. In this picture, recognizing some nsLTPs-related peculiarities (i.e., route, type and number of sensitizations, concentration of the allergen, cross-reactions) and eventual co-factors may help the allergist to define the risk profile of the single patient, in order to promote the appropriate management of the allergy from dietary advices up to the prescription of life-saving epinephrine autoinjector.

Causes of Non-Adherence to Allergen-Specific Immunotherapy: A Foundation towards a Patient-Personalized Approach.

BACKGROUND: Allergen-specific immunotherapy (AIT) is the only disease-modifying therapy for allergic conditions, resulting in a long-lasting tolerance beyond the duration of the treatment. Due to the strong relationship between the effectiveness, its optimal duration (at least three years) and the observation of the correct administration protocol, appropriate adherence to the plan of treatment represents a critical factor for the therapeutical success of AIT. METHODS: Analysis of studies about the rate of adherence in subcutaneous and sublingual immunotherapy, which are the main routes of administration of AIT. RESULTS: There are different causes leading to a premature interruption of the therapy or to it being incorrectly carried out; the most reported include erroneous expectations of the effectiveness and the adverse effects, economic issues, inconvenience and unrelated clinical conditions. CONCLUSIONS: An attentive analysis of the main causes of dropouts may be useful to improve the management of these patients and to develop new strategies for a personalized approach. These strategies should be dynamic, involving attentive communication between the physician and the patient about all the possible criticalities, especially in the initial phase of the therapy, and facilitating, as much as possible, access to healthcare providers over the course of the maintenance phase, including by exploiting technological tools.

Safety and adverse reactions in subcutaneous allergen immunotherapy: a review.

BACKGROUND: Allergen immunotherapy (AIT) is the only treatment which acts on the causes of allergic diseases by modifying their natural history. In the eighties subcutaneous immunotherapy (SCIT) with high biological power allergen extracts caused a number of severe systemic reactions and also fatalities in the UK and the US, resulting in its limitation and in the introduction of other routes of administration. A decisive advance for SCIT safety was understanding that the major cause of mortality was injecting the allergen extract to patients with uncontrolled asthma at the time of injection. AREAS COVERED: This awareness resulted in a significant decrease in fatalities, but not in their abolition. In 2019, an increase in SCIT-related mortality was observed, suggesting to continue the research for still unidentified factors favoring severe reactions, such as the administration of a wrong extract or of allergen doses higher than listed, unintentional intravenous administration, and missed dose reduction after protracted interruption. Moreover, in the context of the improving of the safety, the role played in tolerance-promoting by adjuvants such as CpG oligodeoxynucleotides has to be taken into account, as well as the potential preventive effect performed by the monoclonal anti-IgE antibody omalizumab against the exacerbation of severe reactions during SCIT. CONCLUSION: The safety of SCIT is good, but the research to improve it further must continue. In particular, the pathophysiological mechanisms related to AIT for inhalants and for Hymenoptera venom should be studied, based on the evident diversity demonstrated by the complete absence of fatal reactions to Hymenoptera venom immunotherapy from its introduction in comparison with the history of serious and fatal offenses examined in this review.

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.

Maximizing rehabilitation outcomes in geriatric hip fracture patients: the impact of surgical variables.

BACKGROUND AND AIM: Hip fracture is a major traumatic event with high mortality and disability rate. Its management in the acute setting and in the rehabilitation process is highly debated. This study evaluates the possible determinants of hip fracture rehabilitation outcome, among which surgical intervention type, weight-bearing status and hospitalization length Methods: The data of 738 hip fracture patients, who completed rehabilitation process in our centre, were collected and patients' functional abilities at the time of admission and discharge were analysed. RESULTS: It has been observed that functional recovery depends on several factors: the type of surgery, the post-operative course and related complications, the hospitalisation time, the surgeon's techniques and expertise and the Orthopaedics centre where the operation is performed. CONCLUSIONS: In conclusion, data integration in perspective of an individualised rehabilitation program appears crucial for the functional recovery of the hip fracture patient.

Intranasal corticosteroid and antihistamine combinations in the treatment of allergic rhinitis: the role of the novel formulation olopatadine/mometasone furoate.

INTRODUCTION: Allergic rhinitis (AR) is a common disease with an important impact on the quality of life and very high management costs. In many patients, the poor control of rhinitis symptoms often requires the use of different drugs, and polytherapy tends to reduce therapeutic adherence. According to the latest version of ARIA guidelines, the currently recommended drugs for the treatment of moderate-to-severe AR are second-generation antihistamines, intranasal corticosteroids, and their combination, even in a single nasal spray device. A single medication with a rapid onset of action, acting on breakthrough symptoms too, would be advantageous, also in terms of patient compliance. AREAS COVERED: GSP301 (olopatadine 600 µg - mometasone furoate 25 µg) is a novel intranasal formulation, combining the second-generation antihistamine olopatadine hydrochloride with mometasone furoate. Here, we review the evidence for GSP301, especially concerning the efficacy and safety profile of this intranasal combination in the treatment of AR. EXPERT OPINION: The evidence provided in the current review clearly supports the use of GSP301 as a novel intranasal corticosteroid/antihistamine combination with a well-documented efficacy and safety profile in terms of rapid symptom relief and good tolerability.

Skin reaction to COVID-19 vaccine: A report of 4 cases.

Since the beginning of the covid-vaccine campaign, a lot of local and systemic dermatologic reactions happening after the administration of Coronavirus disease 2019 (COVID-19) vaccines have been described, even if their exact biological mechanism is still debated. In this paper we report 4 cases of cutaneous manifestations arose within ten days after the first dose of messenger RNA (mRNA)-based COVID-19 vaccination: one case of giant urticaria, one case of head and neck redness and two cases of Erythema Multiforme (EM). In our experience these reactions were mild, transient and all of them resolved, not recurring after the second dose, so these manifestations shouldn't be considered as an absolute contraindication to the second dose of vaccine, that to date is fundamental.

Challenges in pulmonary rehabilitation: COVID-19 and beyond.

Pulmonary rehabilitation is a comprehensive multidisciplinary intervention requiring a team involving an expert chest physician, an exercise training specialist, a nutritional expert, a psychologist, a social worker, and an occupational therapist, who together aim at improving respiratory functional capacity in patients with chronic obstructive pulmonary disease (COPD). We aimed at evaluating the effectiveness of pulmonary rehabilitation in a large number of trials, systematic reviews, and meta­analyses in pre-COVID-19 conditions, and the impact of pulmonary rehabilitation during the COVID­19 pandemic was estimated based on results of abundant available studies. As many as 34 studies were selected to assess the global results of pulmonary rehabilitation in COPD patients before the pandemic, and 40 studies were selected from the literature concerning pulmonary rehabilitation during the COVID­19 pandemic.A large number of systematic reviews and meta­analyses reported on the efficacy of rehabilitation in COPD patients, based on the improvement in inspiratory muscle strength, exercise capacity, dyspnea, and quality of life. The response to rehabilitation in patients with COVID­19 is also satisfactory. The effectiveness of pulmonary rehabilitation in COPD patients shows an evolving need for health care professionals to design an individually tailored pulmonary rehabilitation program for patients with COVID-19 to alleviate the chronic symptoms and reduce complications.

Lipid transfer protein syndrome: How to save a life through careful education.

Introduction: Lipid transfer proteins (nsLTPs) are ubiquitous allergens. Patients affected by nsLTP syndrome experience symptoms to various plant-derived foods, ranging from local manifestations to anaphylaxis, the critical treatment of which is represented by self-administration of adrenaline. The principle aim of this study is to assess how dietary recommendations influence the occurrence of new and severe cases and if poly-sensitization to different nsLTPs may play a role. We also investigated about the appropriate use of adrenaline auto-injector during the episodes of anaphylaxis. Moreover, we examinated how other features (ie, co-sensitization to profilin and PR-10 and the presence of risk co-factors) affect these events. Materials and methods: We evaluated 78 patients allergic to nsLTPs, investigating adherence to diet and ability to use the adrenaline auto-injector. Number of sensitization to nsLTPs, co-sensitization to other panallergens, and presence of risk factors for new reactions were also assessed. Diagnosis was based on clinical history and positivity to in vivo and in vitro tests. During the follow-up, compliance, diet modifications, and new reactions were noted, and re-training for the use of epinephrine auto-injector was performed. At the last visit we evaluated the patients' ability to use the self-injector. Results: The whole of fruits belonging to the Rosaceae family emerged as the most frequent culprit foods (28%), followed by walnut (17%), peanut (17%), and hazelnut (10%). At the baseline visit 23% of the patients described the presence of a risk factor during the allergic reaction (mainly nonsteroidal anti-inflammatory drugs [NSAIDs] and exercise). Forty-five percent of the patients reported anaphylactic reactions; no association between the type of food and the severity of the reactions was found. The presence of sensitization to 4 or more nsLTPs was associated to more severe reactions (p < .05; OR 1.67). During the follow-up 38% of the patients experienced at least 1 new allergic reaction: in 79% of them the culprit food was previously tolerated, and in 69% the reaction was an anaphylaxis. Only 47% of the patients showed a proper use of adrenaline auto-injector during the final evaluation, but a significant correlation between periodic education and reduction of the probability of mistakes in the use was reported (p < .05; OR 0.34). Furthermore, an association between co-sensitization to PR-10 (in particular Bet v1) and profilin and less severe symptoms was found, but without a significant odds ratio. Conclusion: A careful education aimed to the prevention of new reactions, through dietary restrictions and avoidance of risk co-factors, and to the management of anaphylaxis, through the training for the correct use of adrenaline auto-injector, should be a routine practice in nsLTP syndrome.

Airborne anaphylaxis: highlighting an invisible enemy.

PURPOSE OF REVIEW: Airborne anaphylaxis is a rare disorder defined by the occurrence of anaphylactic reactions to inhaled allergens, which may arise not only in occupational exposure but also in common settings. Foods are the most common cause of airborne anaphylaxis, even organic mixtures scents. The other important cause is represented by drugs, while in the wide range of other causes, there are often reports on unique cases. This review aims to make an overview about the potential causes of airborne anaphylaxis, by analysing what is described in literature on this topic. RECENT FINDINGS: Concerning epidemiology, no data on specific prevalence of airborne allergy in adults are available. To date, only one study evaluated the specific prevalence of airborne allergy with anaphylaxis to foods in children, resulting in 5.9% of reactions due to exposure to aerosolized foods, compared with 78% of reactions caused by food ingestion. In addition to anaphylaxis, airborne-related reactions may also present with symptoms such as rhino-conjunctivitis, wheezing, dyspnoea and asthma. SUMMARY: A detailed anamnesis facilitates a correct diagnosis, which allows appropriate therapeutic and preventive interventions, but, similarly to rare diseases in general, only specialized doctors are able to implement it. The assumption of the approach used in emergency medicine for other causes of anaphylaxis, that is referring the patient at discharge to an allergist who will teach the basic notions to recognize symptoms and access the appropriate therapy, would allow the patient to avoid situations of serious danger.

Current treatment strategies for seasonal allergic rhinitis: where are we heading?

INTRODUCTION: Allergic rhinitis (AR) is very commonly caused by pollens. The symptoms of AR consist of sneezing, nasal congestion, rhinorrhea, nasal itching and airflow obstruction. The diagnosis has long been based on clinical history, skin prick tests and in vitro measurement of specific IgE, but the innovative approach of precision medicine has made diagnostic tools of much greater accuracy available. AREAS COVERED: This review covers the advances in the treatment of seasonal AR concerning the drugs to be used according to the grade of disease and the characteristics of the patients, and the role of allergen immunotherapy (AIT), which is the only treatment capable of acting, in addition to the symptoms, on the cause of AR and therefore to modify its natural history. EXPERT OPINION: Drug treatment of AR include a large number of agents, the choice of which depends on the severity of the disease. AIT has high evidence of efficacy demonstrated by meta-analyses, and further improvement is currently apparent, as for diagnosis, applying the means of precision medicine. However, when AIT is performed in current practice, without the strict rules of controlled trials, long-term low adherence is a major problem to be solved.

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.

Thoracic Ultrasound Strain Elastosonography as a Noninvasive Biomarker of Chronic Obstructive Pulmonary Disease-Associated Lung Injury: A Feasibility Study.

BACKGROUND: Transthoracic strain elastosonography (TSE) is being increasingly studied for estimating lung-pleura interface stiffness in pulmonary fibrosis. To date, no data exist on its application in chronic obstructive pulmonary disease (COPD). OBJECTIVES: The aim of this article was to describe the TSE pattern in patients with COPD and healthy subjects, either smokers or nonsmokers, and evaluate the feasibility of this technique for early detection of COPD in smokers. METHODS: Nineteen patients with COPD, twenty-one healthy smokers, and twenty healthy nonsmokers underwent spirometry and TSE. Elastosonography was performed by one ultrasound-certified operator on 12 different scans for each participant, on right and left sides, anteriorly and posteriorly, on upper and lower lobes. For each scan, lung-pleura interface stiffness index (SI) was calculated, and the average SI on all 12 scans (SI-12) and on posterior basal scans (SI-PB) was calculated and used for comparisons among groups of participants and correlations with spirometric parameters. RESULTS: Patients with lung injury (i.e., with COPD or healthy smokers) exhibited significantly increased lung-pleura interface stiffness on TSE, measured by SI-12 and SI-PB, than healthy nonsmokers (p < 0.05). Unlike SI-12, SI-PB was able to discriminate between subjects with lung injury and healthy nonsmokers on receiver operating characteristics analysis (area under the curve 0.846, 95% confidence interval 0.730-0.926, p < 0.001) and correlated with forced expiratory volume in the first second (r = -0.31, p = 0.018). CONCLUSION: The measurement of lung-pleura interface stiffness by TSE in posterior basal scans was able to discriminate patients with lung injury from healthy nonsmokers. The role of TSE for detecting early lung damage in COPD should be further investigated.