Basophil Membrane Expression of Epithelial Cytokine Receptors in Patients with Severe Asthma.

BACKGROUND: Severe asthma is a heterogeneous disease, which is characterized by airway damage and remodeling. All triggers of asthma, such as allergens, bacteria, viruses, and pollutants, interact with the airway epithelial cells, which drive the airway inflammatory response through the release of cytokines, particularly IL-25, IL-33, and thymic stromal lymphopoietin (TSLP). OBJECTIVES AND METHODS: To investigate whether the expression of the IL-25, IL-33, and TSLP receptors on the basophil membrane are associated with asthma severity. Twenty-six patients with asthma (11 severe and 15 moderate/mild) and 10 healthy subjects (controls) were enrolled in the study. The results of the basophil activation test and flow cytometry analysis were assessed to investigate basophil membrane expression of IL-25, TSLP, and IL-33 receptors before and after IgE stimulation. RESULTS: IL-25 and IL-33 receptor expression on the basophil membrane at baseline were significantly higher in patients with severe asthma than in those with mild/moderate asthma or healthy subjects, independent of atopy, eosinophilia, asthma control, and exacerbation frequency. Following IgE stimulation, a significantly higher increase in the IL-25 and IL-33 receptors was observed in mild/moderate versus severe asthma. CONCLUSIONS: The high expression of the IL-25 and IL-33 receptors on the basophil membrane of patients with severe asthma indicates an overstimulation of basophils by these cytokines in severe asthma. This finding can possibly be used as a biomarker of asthma severity.

Anxiety and Depression Effects During Drug Provocation Test.

BACKGROUND: Drug provocation test (DPT) represents the gold standard for the diagnosis of drug allergy. A DPT can be performed in a single-blind placebo-controlled manner. In anxiety and depressive disorders, patients need to be evaluated to understand the nature of placebo reactions. OBJECTIVE: The aim of this study was to evaluate the psychological profile of patients with reactions to placebo during a DPT. METHODS: We consecutively enrolled patients with suspected drug allergy undergoing a DPT preceded by the administration of the placebo. All patients underwent the Hospital Anxiety and Depression Scale (HADS), a questionnaire aimed to identify anxiety and depression, before the challenge test. RESULTS: A total of 196 patients were enrolled into this study: 8 (4%) patients resulted positive to the DPT, 60 (30.6%) demonstrated anxiety or depression based on the HADS, and 54 had at least 1 placebo reaction during drug provocation. There were statically significant correlations between the positivity of the HADS and the finding of a placebo reaction (Fisher's exact test: P < .001), and between the latter and a history of severe reactions to drug (Fisher's exact test: P < .001). CONCLUSIONS: There is a significant and strong correlation between the loss of psychic equilibrium and the development of a placebo reaction during a DPT. We suggest the use the HADS or other validated questionnaire in clinical practice before a DPT to evaluate the possible psychiatric components.

Regulation of B-cell-activating factor expression on the basophil membrane of allergic patients.

BACKGROUND: To investigate the modulation of B-cell-activating factor (BAFF) expression on the basophil membrane of allergic patients. BAFF is an important regulator of B-cell activation, proliferation and immunoglobulin production, which may play a role in respiratory allergic diseases in promoting the production of IgE by B cells. METHODS: Peripheral blood samples of 10 patients with allergic rhinitis, 3 with severe asthma and fungal sensitization (SAFS), 3 with allergic bronchopulmonary aspergillosis (ABPA) and 11 healthy controls were assessed regarding BAFF (CD257) expression using the basophil activation test before and after stimulation with IgE and allergens, as well IgE-independent stimuli, like fMLP, lipotheichoic acid from Staphylococcus aureus (LTA-SA) and lipopolysaccharide (LPS). RESULTS: BAFF membrane expression did not change after IgE and allergen stimulation both in patients and controls, while it was upregulated by Aspergillus stimulation, both in sensitized patients and controls. In both patients and controls, BAFF expression was significantly upregulated following LTA-SA and ß-1,3-glucan exposure (toll-like receptor-2 ligands), but not following LPS stimulation. CONCLUSIONS: Basophils from allergic and healthy subjects constitutively express membrane BAFF, which is not upregulated by IgE or specific allergens but by TLR-2 ligands (LTA-SA and ß-1,3-glucan). Aspergillus fumigatus stimulation was able to upregulate BAFF expression on the basophils of sensitized asthmatic patients, but not via IgE-dependent mechanisms, since results did not differ between the patient and control groups. These findings suggest that basophils may contribute to the polyclonal production of IgE commonly observed in patients with SAFS and ABPA.

Acute urticaria presenting in the emergency room of a general hospital.

BACKGROUND: Acute urticaria is a common disorder that often prompts patients to seek treatment in the emergency room (ER). There are few data on acute urticaria presenting in ER. OBJECTIVES: This study aimed to provide demographic and clinical data of patients presenting with acute urticaria at an ER of an Italian general hospital covering an area of about 90,000 inhabitants. The predictive factors of the length of stay in the ER had also been investigated. METHODS: The database of ER patients was searched for urticaria by ICD-9 code and by keywords in the diagnosis description. All the medical records of the identified patients were reviewed and the length of stay in ER was noted. RESULTS: A total of 459 patients were admitted to ER with acute urticaria in a 1-year period corresponding to 1.01% of total ER visits and to 1.2 admission per day. Angioedema was present in 139 cases (30.3%), fever in 55 (12%). Twenty-nine patients fulfilled the criteria of anaphylaxis. Triggers could be identified in 193 cases (42%): drugs in 20.7%, insects bites (10.2%), foods (7.4%) and contact urticaria in 3.7%. Anaphylaxis (p<0.001), food (p<0.05) and drugs (p<0.05) as triggers were significant and independent predictive factors of the length of stay in ER. CONCLUSIONS: Patients with acute urticaria are frequently referred to the emergency room, but only in a few cases urticaria is associated with severe allergic manifestations. Drug and food hypersensitivity, together with anaphylaxis, are the best predictors of the length of stay in ER.

Incidence of food anaphylaxis in Piemonte region (Italy): data from registry of Center for Severe Allergic Reactions.

There are wide differences in estimated incidence and prevalence of anaphylaxis because of the absence, until recently, of a universal consensus on the definition of anaphylaxis and the different source of collected data. We aimed to estimate the incidence of food anaphylaxis based on the database of Piemonte Region (Italy) Reference Center for Severe Allergic Reactions. All cases of severe food allergic reactions reported in 2010 were studied. Clinical data associated to the reports were evaluated according to National Institute of Allergy and Infectious Disease and Food Allergy and Anaphylaxis Network diagnostic criteria of anaphylaxis. 75 % of the 778 cases were classified as food anaphylaxis (incidence of 13/100,000 person-years, ranging from 9.9 in adults to 29/100,000 person-years in children). Nuts were the most frequent foods causing anaphylaxis. Milk and eggs were responsible for anaphylaxis more often in children, while peach, vegetables and crustaceans were in adults. Cardiovascular symptoms were more frequent in adults. Gastrointestinal involvement was more frequent in children. A high prevalence of respiratory allergic comorbidities was observed. Food is an important cause of anaphylaxis, particularly in subjects with respiratory allergic comorbidities. Children and adults differ in triggers and clinical presentation of anaphylaxis.

Itraconazole as 'bridge therapy' to anti-IgE in a patient with severe asthma with fungal sensitisation.

Sensitisation to fungi has been reported to play an important role in a particular phenotype of severe asthma, the so-called severe asthma with fungal sensitisation, characterised by high levels of total IgE, which may be an obstacle to anti-IgE therapy. We describe here the case of a polysensitised woman with refractory asthma, sensitised to Aspergillus fumigatus with high total IgE values (1793 kUA/l), but without the diagnostic criteria for allergic bronchopulmonary aspergillosis. Additional therapy with itraconazole leads to the decrease of total IgE to the limits recommended for proper omalizumab dosing (30-1500 kUA/l). Itraconazole, used as bridge therapy, provided us the opportunity to start anti-IgE treatment in a patient with high levels of total IgE, beyond the upper limits recommended for proper prescription of omalizumab.