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Francesco Livrieri,1 Giulia Ghidoni,1 Roberto Piro,1 Francesco Menzella,1 Alberto Cavazza,2 Claudia Lazzaretti,3 Marco Massari,3 Gloria Montanari,1 Matteo Fontana,1 Nicola Cosimo Facciolongo1 1Department of Medical Specialties, Pneumology Unit, Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia- IRCCS, Reggio Emilia 42123, Italy; 2Pathology Unit, Azienda USL/IRCCS di Reggio Emilia, Reggio Emilia 42100, Italy; 3Infectious Diseases, Azienda Unità Sanitaria Locale, IRCCS di Reggio Emilia, Reggio Emilia, ItalyCorrespondence: Francesco LivrieriDepartment of Medical Specialties, Pneumology Unit, Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia- IRCCS, Reggio Emilia 42123, ItalyEmail francesco.livrieri@ausl.re.itAbstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing a massive outbreak throughout the world. In this period, diseases other than coronavirus disease (COVID-19) have not disappeared; however, it is hard for doctors to diagnose diseases that can mimic the clinical, radiological, and laboratory features of COVID-19, especially rare lung diseases such as acute eosinophilic pneumonia (AEP). We report the clinical case of a young patient who presented to the Emergency Department with respiratory failure and clinical symptoms, radiological aspects, and blood tests compatible with COVID-19; two swabs and a serology test for SARS-CoV-2 were performed, both resulted negative, but the respiratory failure worsened. Peripheral eosinophilia guided us to consider the possibility of a rare disease such as AEP, even if radiology findings were not pathognomonic. Therefore, we decided to perform a flexible bronchoscopy with bronchoalveolar lavage (BAL) at the lingula, which showed the presence of eosinophilia greater than 40%. As a consequence, we treated the patient with high-dose corticosteroids that completely resolved the respiratory symptoms. This case report highlights the difficulty of making alternative diagnoses during the COVID-19 pandemic, especially for rare lung diseases such as AEP, which may have initial characteristics similar to COVID-19.Keywords: COVID-19, acute eosinophilic pneumonia, bronchoalveolar lavage, ground glass opacities

Francesco Menzella,1 Gloria Montanari,1 Giulia Patricelli,2 Alberto Cavazza,3 Carla Galeone,1 Patrizia Ruggiero,1 Diego Bagnasco,4 Nicola Facciolongo11Department of Medical Specialties, Pneumology Unit, Azienda USL di Reggio Emilia, Arcispedale Santa Maria Nuova- IRCCS, Reggio Emilia, Italy; 2Pneumology Unit, A. Perrino Hospital, Brindisi, Italy; 3Department of Pathology, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy; 4Allergy & Respiratory Diseases, University of Genoa, Genoa, ItalyAbstract: The increasing knowledge on inflammatory pathways has driven the development of targeted biological therapies for severe refractory asthma. Among the recently developed biologics, the fully human monoclonal antibody dupilumab is an interesting therapeutic option, given its ability to inhibit the biological effects of both IL-4 and IL-13. We describe the case of a male, Caucasian, 56-year-old patient with allergic and eosinophilic severe asthma. Given the poor asthma control, he started treatment with add-on dupilumab, and after the tenth injection, he presented with a fever and bilateral pulmonary thickening. A significant increase in blood eosinophilia was also reported. The patient underwent a fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB/TBB). BAL revealed eosinophils alveolitis (60%) while TBB showed findings compatible with chronic eosinophilic pneumonia (CEP). After prolonged treatment with oral corticosteroids, the clinical picture improved with resolution of CEP. Since the beginning of dupilumab treatment, simultaneously to a great improvement in asthma control, the patient showed a progressive increase in blood eosinophils count and subsequent onset of clinical-radiological pattern suggestive of CEP. Based on published data, dupilumab may have induced an alteration of the complex immunological pathway of our patient. This pathway is affected by both allergic and eosinophilic asthmatic endotypes, and consequently, the concomitant action of allergenic stimuli and eosinophils may have caused the appearance of eosinophilic pneumonia. To our knowledge, this is the first reported case of CEP as a possible severe side effect of dupilumab administration.Keywords: monoclonal antibodies, dupilumab, severe asthma, eosinophilic pneumonia, eosinophils, fiberoptic bronchoscopy

Francesco Menzella, Mirco Lusuardi, Gloria Montanari, Carla Galeone, Nicola Facciolongo, Luigi ZucchiDepartment of Cardio-Thoracic-Vascular and Intensive Care Medicine, Pneumology Unit, IRCCS – Arcispedale Santa Maria Nuova, Reggio Emilia, ItalyAbstract: Asthma is a chronic inflammatory disorder of the airways with variable clinical severity from very mild and occasional symptoms to recurrent critical exacerbations, at risk of fatal or near-fatal outcome, in a small percentage of patients. Within the different inflammatory cascades involved in asthma, eosinophils play a central role in the pathogenesis and largely influence disease severity. Interleukin-5 (IL-5) is the main cytokine controlling eosinophil activity and proliferation at the site of inflammation. Mepolizumab was the first biological humanized anti-IL-5 monoclonal antibody tested in randomized clinical trials on eosinophilic asthma and other eosinophilic diseases. On the basis of several positive clinical efficacy data, it has recently been approved by the US Food and Drug Administration for the treatment of severe eosinophilic asthma. Unfortunately, high costs are at present a critical issue. Future studies will probably help in the correct selection of a potential “responder phenotype”, allowing the prescription of this promising therapy to appropriate patients and best define cost-effectiveness issues.Keywords: asthma, mepolizumab, phenotype, IL-5, effectiveness, biomarkers

With reference to a questionnaire aimed at assessing the performance of Italian nursing homes on the basis of the health conditions of their patients, we investigate two relevant issues: dimensionality of the latent structure and discriminating power of the items composing the questionnaire. The approach is based on a multidimensional item response theory model, which assumes a two-parameter logistic parameterization for the response probabilities. This model represents the health status of a patient by latent variables having a discrete distribution and, therefore, it may be seen as a constrained version of the latent class model. On the basis of the adopted model, we implement a hierarchical clustering algorithm aimed at assessing the actual number of dimensions measured by the questionnaire. These dimensions correspond to disjoint groups of items. Once the number of dimensions is selected, we also study the discriminating power of every item, so that it is possible to select the subset of these items which is able to provide an amount of information close to that of the full set. We illustrate the proposed approach on the basis of the data collected on 1,051 elderly people hosted in a sample of Italian nursing homes. (Contains 10 tables and 1 figure.)