Chronic rhinosinusitis with nasal polyposis and biological agents: the ARIA-ITALY Survey.

Summary: Background. Chronic rhinosinusitis (CRS) is an inflammatory disease that affects the nasal mucosa and the paranasal sinuses. CRS can be associated by nasal polyposis (CRSwNP phenotype) in up to 30% of patients and it is frequently associated with bronchial asthma. CRSwNP shows predominantly an underlying activation of type 2 inflammatory pathways with the involvement of eosinophils, IgE, interleukin (IL)-4, IL-5 and IL-13. Biological drugs that target these inflammatory cytokines are currently a therapeutic option recognized by guidelines for the treatment of uncontrolled form of the disease. Methods. As part of the activity of the "ARIA-Italy" working group, a panel of 255 Italian Ear, Nose and Throat (ENT) specialists, pneumologists and immuno-allergologists actively participated in this national survey and answered a series of questions geared toward understanding the main criteria for patient characterization and therapeutic decision, highlighting multidisciplinarity, and the implementation of the management of CRSwNP patients, as a part of the precision medicine concept and the appropriate use of the biologicals. Results. Two hundred and fifty-five experts and specialists participated in the survey. Conclusions. The results of this survey obtained from an extensive number of active specialists throughout Italy allow some important concluding remarks to be drawn. The main points of agreement were that multidisciplinary care teams provide many benefits but that, once the team is established, meetings and communication between members must be coordinated. Finally, the dissemination of national disease registries and the continuous updating of guidelines and position papers related to CRSwNP and comorbidities should be encouraged.

Severe asthma management in the era of biologics: insights of the Italian Registry on Severe Asthma (IRSA).

Summary: Background. The Italian Registry on Severe Asthma (IRSA) is the most recent and largestregistry in Italy. Objective. To improve the knowledge on the clinical and biological features of severe asthma (SA), and to monitor its treatments. Methods. To analyze clinical,functional, inflammatory, and treatment characteristics of severe asthmatics from the IRSA registry. Results. 851 subjects were enrolled. 31.8% and 64.5% of patients were submitted to oral corticosteroids (OCS), and monoclonal antibodies (MABs), respectively. At least tw ocomorbidities affected 77.4% patients. Asthma was uncontrolled in 62.2% patients. Uncontrolled patients had a higher frequency of exacerbations, and hospitalization, showing a highere osinophilic phenotype, a greater use of OCS, and being treated with MAB less frequently. However, uncontrolled patients treated with MAB had a lower use of OCS and a lower rateof hospitalization. Comparing SA patients with atopy and without atopy, the latter showeda greater use of OCS, and more frequent nasal polyposis and osteoporosis. Among SA patients with atopy treated with MAB, 36% were on a treatment targeting the IL-5 pathway. Conclusions and clinical relevance. This study shows the features of the greatest Italian registryof SA patients, revealing at the time of enrollment a poor disease control, and the use of OCSand MABs in about one third and two thirds of patients, respectively. SA is a complex diseasethat requires a more precise phenotyping and a greater disease control.

Nerve ablation after bronchial thermoplasty and sustained improvement in severe asthma.

BACKGROUND: Bronchial thermoplasty (BT) is a non-pharmacological intervention for severe asthma whose mechanism of action is not completely explained by a reduction of airway smooth muscle (ASM). In this study we analyzed the effect of BT on nerve fibers and inflammatory components in the bronchial mucosa at 1 year. METHODS: Endobronchial biopsies were obtained from 12 subjects (mean age 47 ± 11.3 years, 50% male) with severe asthma. Biopsies were performed at baseline (T0) and after 1 (T1), 2 (T2) and 12 (T12) months post-BT, and studied with immunocytochemistry and microscopy methods. Clinical data including Asthma Quality of Life Questionnaire (AQLQ) and Asthma Control Questionnaire (ACQ) scores, exacerbations, hospitalizations, oral corticosteroids use were also collected at the same time points. RESULTS: A statistically significant reduction at T1, T2 and T12 of nerve fibers was observed in the submucosa and in ASM compared to T0. Among inflammatory cells, only CD68 showed significant changes at all time points. Improvement of all clinical outcomes was documented and persisted at the end of follow up. CONCLUSIONS: A reduction of nerve fibers in epithelium and in ASM occurs earlier and persists at one year after BT. We propose that nerve ablation may contribute to mediate the beneficial effects of BT in severe asthma. TRIAL REGISTRATION: Registered on April 2, 2013 at ClinicalTrials.gov Identifier: NCT01839591 .

Training and practice in bronchoscopy a national survey in Italy.

BACKGROUND AND AIM: Bronchoscopy is performed in a variety of different settings in Italy. The surveys conducted so far have highlighted the heterogeneity of the procedures and the frequent inability to adhere to the guidelines. The aim of this survey was to analyse procedures, training, and opinions of Italian respiratory physicians performing interventional bronchology in the clinical practice. METHODS: The study was conducted retrospectively on 300 pulmonologists. From January to June 2008, these were invited to participate in an email survey to be sent out monthly to each participant for four consecutive months. RESULTS: Two hundred and one respiratory physicians took part in the study, most of whom (83.5%) work in either Pulmonology or Interventional Pulmonology Units. The year before the survey, 21.2% of the participants had performed fewer than 100 examinations, 42.3% 100 to 300, and 36.6% more than 300 bronchoscopies; 53.9% were familiar with the international guidelines on the topic. Among the responders, 34.1% had received less than 6 months training, 55.3% considered further training in rigid bronchoscopy, laser procedures and thoracoscopy, invaluable for their professional activity. Adequate training for transbronchial needle aspirates, was reported by 49.6% of respondents. CONCLUSIONS: Our data show that interventional bronchoscopy procedures are regularly performed according to current recommendations by over half of the Italian Pulmonologists participating in our survey. The need for more comprehensive basic education and training was put forward by the majority of physicians.

Sarcoidosis and multiple sclerosis: systemic toxicity associated with the use of interferon-beta therapy.

Sarcoidosis is a multi-systemic inflammatory disease of unknown origin characterized by the presence of noncaseating epitheloid cell granulomas in multiple organs. Diagnosis is made on the basis of a compatible clinical-radiological scenario and the histological demonstration of the typical granulomas in the affected tissues. Interferons are immuno-modulators that have been used in a wide range of diseases, including hepatitis C virus infection, multiple sclerosis, and multiple myeloma and other types of tumours, including leukemia, lymphomas, Kaposi's sarcoma, and melanoma. Interferon-alpha-induced sarcoidosis has been reported repeatedly and there are two reports in the literature of cases of pulmonary sarcoidosis treated with interferon-1b therapy: one for advanced renal cell carcinoma and the other for multiple myeloma. A 35-year-old man on chronic immune-modulant Interferon-1b-based therapy for multiple sclerosis presented to the Neurology Unit with mild dyspnoea, dry cough, and transient pain to right upper abdomen. Lungs, spleen, liver, and almost all lymphnode stations of abdomen and mediastinum were clearly involved on ultrasound examination, chest X-ray, and computed tomography. A transbronchial biopsy showed non-caseating granuloma on histopathologic evaluation of the lungs. To the best of our knowledge, this is the first report of a chronic multisystemic sarcoidosis that was associated with interferon-beta treatment.

Omalizumab: when the non-responder is a late-responder.

UNLABELLED: Omalizumab is an anti-IgE monoclonal antibody available since 2006 for the treatment of GINA step 4 asthma. We studied a 41-year old male who has been suffering from severe steroid-resistant asthma with severe co-morbidity and treated with Omalizumab. He was found to be non-responder to the treatment until the 48th week, starting from which we began to see a distinct improvement in the symptoms and all the correlated parameters, in addition to remission of the co-existent allergy to milk. CONCLUSIONS: we wish to point out the late response to Omalizumab, which occurred way beyond the times envisaged in literature. It seems possible that some patients are late responders to the drug.