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

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

EAACI Molecular Allergology User's Guide 2.0.

Since the discovery of immunoglobulin E (IgE) as a mediator of allergic diseases in 1967, our knowledge about the immunological mechanisms of IgE-mediated allergies has remarkably increased. In addition to understanding the immune response and clinical symptoms, allergy diagnosis and management depend strongly on the precise identification of the elicitors of the IgE-mediated allergic reaction. In the past four decades, innovations in bioscience and technology have facilitated the identification and production of well-defined, highly pure molecules for component-resolved diagnosis (CRD), allowing a personalized diagnosis and management of the allergic disease for individual patients. The first edition of the "EAACI Molecular Allergology User's Guide" (MAUG) in 2016 rapidly became a key reference for clinicians, scientists, and interested readers with a background in allergology, immunology, biology, and medicine. Nevertheless, the field of molecular allergology is moving fast, and after 6 years, a new EAACI Taskforce was established to provide an updated document. The Molecular Allergology User's Guide 2.0 summarizes state-of-the-art information on allergen molecules, their clinical relevance, and their application in diagnostic algorithms for clinical practice. It is designed for both, clinicians and scientists, guiding health care professionals through the overwhelming list of different allergen molecules available for testing. Further, it provides diagnostic algorithms on the clinical relevance of allergenic molecules and gives an overview of their biology, the basic mechanisms of test formats, and the application of tests to measure allergen exposure.

Effectiveness and safety of dupilumab in patients with chronic rhinosinusitis with nasal polyps and associated comorbidities: a multicentric prospective study in real life.

BACKGROUND: Biologics are currently one of the main treatment options for a number of diseases. The IgG4 monoclonal antibody dupilumab targets the Interleukin-4 receptor alpha chain, thus preventing the biological effects of the cytokines IL-4 and IL-13, that are essential for the Th2 response. Several controlled trials showed that dupilumab is effective and safe in patients with atopic dermatitis (AD), severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), thus resulting in approval by regulatory agencies. Aim of the study was to evaluate the efficacy and safety of dupilumab in adult patients with CRSwNP stratified by common overlapping comorbid conditions. METHODS: We performed a multicenter, observational, prospective study enrolling adult patients with severe CRSwNP who had started dupilumab treatment in the context of standard care from January 2021 to October 2021. Data were collected from twentynine Italian secondary care centers for allergy and clinical immunology, all of which were part of the Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC). A number of efficacy parameters were used. Patient data were compared using the Wilcoxon test for paired data. All statistical analyses were performed with SPSS version 20 (IBM, Armonk, NY, USA). RESULTS: In total, 82 patients with nasal polyposis were identified. A significant improvement was detected for all the applied efficacy parameters, i.e. 22-item Sino-Nasal Outcome Test (SNOT-22) and bilateral endoscopic nasal polyp score (NPS) scores for CRSwNP, Rhinitis Control Scoring System (RCSS) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores for allergic perennial rhinitis, Forced Expiratory Volume in the 1st second (FEV1) and Asthma Quality of Life Questionnaire (AQLQ) scores for asthma, Eczema Area and Severity Index (EASI) and Dermatology Life Quality Index (DLQI) scores for AD. A non-significant improvement was also obtained in the Urticaria Activity Score over 7 days (UAS7) for chronic spontaneous urticaria. Treatment with dupilumab was well tolerated. CONCLUSIONS: These data suggest that dupilumab treatment in patients suffering from CRSwNP and associated comorbidities may be suitable. Such outcome, although confirmation by trials is warranted, suggests the possibility to treat different disorders with a single therapy, with favorable effects especially under the cost-effectiveness aspect.

Peanut allergy in Italy: A unique Italian perspective.

Background: Peanut allergy has not been well characterized in Italy. Objective: Our aim was to better define the clinical features of peanut allergy in Italy and to detect the peanut proteins involved in allergic reactions. Methods: A total of 22 centers participated in a prospective survey of peanut allergy over a 6-month period. Clinical histories were confirmed by in vivo and/or in vitro diagnostic means in all cases. Potential risk factors for peanut allergy occurrence were considered. Levels of IgE to Arachis hypogea (Ara h) 1, 2, 3, 6, 8, and 9 and profilin were measured. Results: A total of 395 patients (aged 2-80 years) were enrolled. Of the participants, 35% reported local reactions, 38.2% reported systemic reactions, and 26.6% experienced anaphylaxis. The sensitization profile was dominated by Ara h 9 (77% of patients were sensitized to it), whereas 35% were sensitized to pathogenesis-related protein 10 (PR-10) and 26% were sensitized to seed storage proteins (SSPs). Sensitization to 2S albumins (Ara h 2 and Ara h 6) or lipid transfer protein (LTP) was associated with the occurrence of more severe symptoms, whereas profilin and PR-10 sensitization were associated with milder symptoms. Cosensitization to profilin reduced the risk of severe reactions in both Ara h 2- and LTP-sensitized patients. SSP sensitization prevailed in younger patients whereas LTP prevailed in older patients (P < .01). SSP sensitization occurred mainly in northern Italy, whereas LTP sensitization prevailed in Italy's center and south. Atopic dermatitis, frequency of peanut ingestion, peanut consumption by other family members, or use of peanut butter did not seem to be risk factors for peanut allergy onset. Conclusions: In Italy, peanut allergy is rare and dominated by LTP in the country's center and south and by SSP in the north. These 2 sensitizations seem mutually exclusive. The picture differs from that in Anglo-Saxon countries.

Systemic allergic reactions induced by labile plant-food allergens: Seeking potential cofactors. A multicenter study.

BACKGROUND: Heat-and-pepsin-sensitive plant food allergens (PR-10 and profilin) sometimes cause systemic reaction. OBJECTIVE: To detect the risk factors for systemic reactions induced by labile food allergens. METHODS: A retrospective multicenter study was performed on patients with a documented history of systemic allergic reaction to labile plant food allergens and on age-matched controls with a history of oral allergy syndrome (OAS) induced by the same foods. Offending foods, their amount, and state (solid or liquid), and potential cofactors (nonsteroidal anti-inflammatory drugs, protonic pump inhibitors, exercise, alcohol, and fasting) were considered. RESULTS: We studied 89 patients and 81 controls. Sensitization to PR-10 or profilin, IgE to Bet v 1 and/or Bet v 2, and foods causing OAS were similar in the two groups. Twenty patients experienced >1 systemic allergic reaction. Tree nuts, Rosaceae, Apiaceae, and soymilk were the main offending foods. Seventeen (19%) patients were taking a PPI when the systemic reaction occurred (vs 5% in controls; P < .025). The ingestion of the offending food in liquid form (soymilk) was frequent among patients (15%) but unusual among controls (2%; P < .025). Soy milk-induced systemic reactions were independent of PPI treatment. Fasting and excess of allergen, but not NSAID and exercise, were other relevant cofactors for systemic reactions. Systemic reactions occurred without any identifiable cofactor in 39 (44%) cases. CONCLUSION: PR-10- and profilin-induced systemic reactions are facilitated by PPI, ingestion of large amounts of unprocessed foods, and fasting. Soybean beverages represent a risk for PR-10 hypersensitive patients and should be avoided.

Alendronate soluble solution: a higher adherence rate in the treatment of osteoporosis.

INTRODUCTION: Since low adherence to a long-term therapy results in a poor clinical outcome and significantly increases healthcare costs, adherence to the treatment of chronic disorders is an issue of great interest. This is particularly true of the treatment of osteoporosis (OP). PURPOSE OF STUDY: Adherence to the osteoporosis therapy in patients treated with bisphosphonates in tablet form has been evaluated in comparison with the adherence of those taking alendronate in soluble solution. METHODS AND MATERIALS: Here we present a retrospective study of 245 patients treated with alendronate, risedronate and ibandronate tablets and a prospective study of 118 patients treated with soluble alendronate. In both studies, patients have been observed for a period of 12 months. RESULTS: The analysis of patients' persistence with the treatment plan, assessed at three, six and 12 months, revealed a significantly higher adherence (p < 0.005) in the cohort of patients treated with soluble alendronate (92.37% at 12 months) compared with those who followed the course of treatment with tablets (65.4 %, 12 months). CONCLUSIONS: The investigation showed higher adherence to the oral therapy with soluble alendronate, demonstrating that a formulation obtained by this method can contribute to a higher level of persistence with the treatment of a disease such as osteoporosis, which requires a long-term therapeutic plan.

[Chronic pain in the obese: a quali-quantitative observational study]. / Dolore cronico nell'obesità: studio osservazionale quali-quantitativo.

INTRODUCTION: Obesity (Ob) is one of the major issues for the public health care system with a constantly increasing prevalence. Chronic Pain (CP), on the other hand, is a pathological condition as severe and prevalent as the former. Ob and CP are not only pathological conditions, they also are important factors of risk for the onset of a number of morbid conditions. MATERIALS AND METHODS: In our study we have enrolled 182 patients with Ob, to whom we have asked to fill a brief questionnaire with the purpose of evaluating prevalence and characteristics of CP, therapeutic attitude and its results, as well as the knowledge of the Law n. 38 - 15/03/2010. RESULTS: From the analysis of gathered data, CP is present in the 39% of subjects with Ob (73.2% of females and 23.9% of males) and proportionally increases as BMI increases. The majority of patients (48%) shows pain at articular level, and a "pin" and a "gripping" pain are the two types of pain that are mostly described. Almost all the subjects enrolled (90%) suffer of a pain reported at a moderate to intense level. 15% circa of the patients do not take any therapy, while FANS have resulted to be the most used drugs among them (over 50% of the patients) and the 45% of the subjects have currently reported not to have a good control over the pain. The Law n. 38 has been reported unknown by the 8.2% of the investigated sample. CONCLUSIONS: The study has demonstrated a substantial association between the Ob and CP, particularly in the female gender, the clinical relevance of pain, its BMI-dependent tendency, the inadequacy of the therapy and the widespread lack of awareness and attention to the themes and issues of pain.

[Chronic pain in the diabetic patient: a quali-quantitative observational study]. / Dolore e diabete mellito: studio osservazionale quali-quantitativo.

AIM: The purpose of this study is to evaluate the prevalence and characteristics of pain in subjects affected by Diabetes Mellitus (DM), to assess approach and therapeutically valid outcomes as well as the knowledge of the Law n. 38/15/03/2010 of the Italian Government ("Dispositions to guarantee the access to the Palliative Cares and Pain Therapy"). MATERIALS AND METHODS: We have enrolled 462 patients affected by DM [242 (52.4%) males, 209 (42.5%) females; while in 11 (5.1%) cases the gender has not been specified], with characteristics as follows: 62 patients (13.4%) affected by T1DM (37 males and 25 females) e 400 patients (86.6%) affected by T2DM (224 males e 176 females). The average age was of 65.2 years old (range 20-91). All the patients have been presented with an original questionnaires based on 10 questions. RESULTS: 221 subjects (48%) have claimed to have experienced pain; 60% within the females, 38% within the males (p<0.001). 31% of these are to be included among the patients with T1DM, 50.5% among those with T2DM (p<0.01). The presence of chronic pain has been acknowledged by 162 subjects (35%). As per chronic pain, this has been described as articular pain by 128 patients (80%), while 63 (38%) located the pain through the spine and 29 (18%) throughout the muscles. Chronic pain was described as moderate by 73 subjects (45%), intense by 59 (36%), feeble by 15 (9%), utterly intense by 5 (3%), moderate/intense by 1 (1%). The drugs for treating the chronic pain used by the patients have been enlisted as follows: FANS (41%), paracetamol (30%), glucocorticoids (3%), weak opioids (2%); 27% of subjects have received no therapy. As for the Law 38/2010, only 8% have said they have had news of it. CONCLUSIONS: The data gathered in this study have drawn attention on the fact that the presence of pain is higher in female gender, with a prevalence of 60% compared to the 38% of the male gender. It has been observed no relation with the age range, in particular no proportional increase level of pain has been observed, although the higher peak of prevalence has been experienced in the age range between 70-79, both for pain in general and for chronic pain. Speaking about efficacy of the treatment, almost 50% of the subjects have received no improvement from the therapy.