Mild/Moderate Asthma Network in Italy (MANI): a long-term observational study.

OBJECTIVE: 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. METHODS: 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). RESULTS AND CONCLUSION: 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. ABBREVIATIONS: MANI:Mild/Moderate Asthma Network of ItalySANI:Severe Asthma Network ItalyGINA:Global Initiative for AsthmaSABA:short acting ß2-agonistsICS:inhaled corticosteroidsCRF:Case Report Form.

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.

Risk of anaphylaxis in patients with large local reactions to hymenoptera stings: a retrospective and prospective study.

BACKGROUND: In the few studies available, the risk of developing systemic reactions (SR) to hymenoptera stings in patients with previous large local reactions (LLRs) to stings ranges from 0 to 7 %. We evaluated both retrospectively and prospectively the risk of SRs in patients with LLRs to stings. METHODS: An overall number of 477 patients, 396 with an SR as the first manifestation of allergy and 81 with a history of only LLRs after hymenoptera stings, were included in the study. All patients had clinical history and allergy testing (skin tests and/or specific IgE) indicative of allergy to venom of only one kind of Hymenoptera. Of the 81 patient with LLRs, 53 were followed-up for 3 years by annual control visits, while the 396 patients with SR were evaluated retrospectively. RESULTS: Among the 396 patients with an SR, only 17 (4.2 %) had had a previous LLR as debut of allergy, after an history of normal local reactions to Hymenoptera stings. All the 81 patients with a history of only LLRs had previously had at least two LLRs, with an overall number of 238 stings and no SR. Among the 53 patients who were prospectively evaluated we found that 31 of them (58.3 %) were restung by the same type of insect, with an overall number of 59 stings, presenting only LLRs and no SR. CONCLUSIONS: Our findings confirm that patients with repeated LLRs to stings had no risk of SR, while a single LLR does not exclude such risk. This has to be considered in the management of patients with LLRs.

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.

Oral CorticoSteroid sparing with biologics in severe asthma: A remark of the Severe Asthma Network in Italy (SANI).

According to the data derived from several national and international registries, including SANI (Severe Asthma Network Italy), and considering the strong impact that frequent or regular use of oral corticosteroid has on quality of life (QoL) of severe asthmatics, as well as on the costs for managing corticosteroid-related diseases, oral corticosteroid sparing up to withdrawal should be considered a primary outcome in the management of severe asthma. New biologics have clearly demonstrated that this effect is possible, with concomitant reduction in the rate of exacerbations and in symptom control. Then, there is no reason for using so frequently oral corticosteroid before having explored all alternatives currently available for a large part of severe asthmatics.

Role of nitric oxide in the impairment of circular muscle contractility of distended, uninflamed mid-colon in TNBS-induced acute distal colitis in rats.

AIM: To evaluate the role of nitric oxide (NO) in the motor disorders of the dilated uninflamed mid-colon (DUMC) from trinitrobenzene sulfonic acid (TNBS)-induced acute distal colitis in rats. METHODS: Colitis was induced in male Sprague-Dawley rats by a single intracolonic administration of TNBS. Control rats received an enema of 0.9% saline. The rats were killed 48 h after TNBS or saline administration. Macroscopic and histologic lesions of the colon were evaluated. Myeloperoxidase (MPO) and nitric oxide synthase (NOS) activity were measured on the colonic tissue. In TNBS rats, we evaluated spontaneous and evoked contractile activity in circular muscle strips derived from DUMC in comparison to the same colonic segment of control rats, both in the presence and in the absence of a non-selective NOS isoforms inhibitor N-nitro-L-arginine (L-NNA). Pharmacological characterization of electric field stimulation (EFS)-evoked contractile responses was also performed. RESULTS: In TNBS rats, the distal colon showed severe histological lesions and a high MPO activity, while the DUMC exhibited normal histology and MPO activity. Constitutive NOS activity was similar in TNBS and control rats, whereas inducible NOS activity was significantly increased only in the injured distal colon of TNBS rats. Isometrically recorded mechanical activity of circular muscle strips from DUMC of TNBS rats showed a marked reduction of the force and frequency of spontaneous contractions compared to controls, as well as of the contractile responses to a contracting stimulus. In the presence of L-NNA, the contractile activity and responses displayed a significantly greater enhancement compared to controls. The pharmacological characterization of EFS contractile responses showed that a cooperative-like interaction between cholinergic muscarinic and tachykinergic neurokinin 1 and 2 receptors mediated transmission in DUMC of TNBS rats vs a simple additive interaction in controls. CONCLUSION: The results of this study show that, during TNBS-induced acute distal colitis, circular muscle intrinsic contractile mechanisms and possible enteric neural excitatory activity are inhibited in the distended uninflamed mid-colon. Suppression of NO synthesis markedly improves spontaneous and evokes muscle contractions, in spite of any evident change in local NO activity.

Chloramine-induced anaphylaxis while showering: a case report.

INTRODUCTION: Sodium-N-chlorine-p-toluene sulfonamide, commonly known as chloramine-T, is a derivative of chlorine which is widely used as a disinfectant. For many years, chloramine-T has been described as a cause of immediate-type hypersensitivity, especially with regard to asthma and rhinitis, and as a cause of occupational dermatoses in cleaning personnel in hospitals, although no anaphylactic reaction has yet been reported. Hence, to the best of our knowledge we present the first case of anaphylaxis to chloramine-T with evidence of specific immunoglobulin E antibodies. CASE PRESENTATION: We describe the case of a 25-year-old Caucasian woman who was in good health and with a negative history for atopy, including no respiratory symptoms of rhinitis or asthma, and with no professional exposure to chloramine-T. She, while showering, applied a chloramine-T solution to a skin area with folliculitis on her leg, and within a few minutes developed generalized urticaria and angioedema, followed by vomiting and collapse with loss of consciousness. A skin prick test with a chloramine-T solution at 10mg/mL concentration was positive, and specific immunoglobulin E to chloramine-T was quantified at a value of 2.9 optical density as measured by the enzyme allergosorbent test technique. CONCLUSION: The strict cause-effect relationship and the results of the skin test and the in vitro test make certain the causative role of chloramine-T in this case of anaphylaxis. This suggests that chloramine-T, based on its wide use as a disinfectant, should be considered a possible cause in anaphylaxis of unknown origin.