Severe chronic rhinosinusitis treated with dupilumab, a real-life analysis of early effectiveness.

OBJECTIVE: The present study evaluated the safety and efficacy of dupilumab in severe uncontrolled type 2 chronic rhinosinusitis with nasal polyps (CRSwNP). PATIENTS AND METHODS: A retrospective analysis was conducted on a cohort of adult patients affected by severe CRSwNP treated with dupilumab. Maxillofacial computed tomography, evaluation of blood eosinophils and serum IgE levels, measurement of nasal polyp score (NPS), smell identification test (SSIT-16), sinonasal outcome test-22 (SNOT-22) and asthma control test (ACT) were performed. Follow-up was conducted at 2 weeks, and at 1, 3, and 6 months. Adverse events and the efficacy of treatment were monitored. RESULTS: 23 patients were enrolled. After 15 days, scores of the SNOT-22, NPS and SSIT-16 significantly improved. These outcomes were also maintained after 1, 3, and 6 months (p < 0.001). At this latter follow-up time, SNOT-22 showed a change of -33.10 (p < 0.001), NPS -3.36 (p < 0.001) and SSIT-16 +5.60 (p < 0.001). In all, 26.1% of patients experienced early minor complications. CONCLUSIONS: In the present study, dupilumab was effective in the treatment of severe uncontrolled CRSwNP, demonstrating a quick significant improvement in both questionnaires and endoscopic evaluation. Only minor complications were observed.

Role(s) of formyl-peptide receptors expressed in nasal epithelial cells.

Chronic rhinosinusitis is one of the most frequent chronic diseases in humans. Little is known about stimuli initiating tissue remodeling process that determines the morphological expression of the disease. N-formyl peptide receptors (FPRs) are innate immunity receptors important in tissue remodeling of gastric and intestinal epithelium. The expression and functions of FPRs in nasal epithelial cells were examined to evaluate whether they could be important in the remodeling of nasal mucosa. The aim of this study is to examine FPR expression in a nasal epithelial cell line (RPMI-2650) at mRNA and protein levels. To determine whether FPRs were functional, chemotaxis experiments were carried out. In addition the effects of FPRs agonists on the expression (PCR and ELISA) of VEGF-A and TGF-beta, two key mediators of tissue remodelling, were examined. Here we demonstrate that RPMI-2650 express FPR and FPRL2, but not FPRL1. fMLP, a bacterial product active on FPR, and uPAR(84-95), an inflammatory mediator agonist for FPRL2, stimulated migration of nasal epithelial cells. fMLP and uPAR(84-95) induce expression and secretion of VEGF-A and TGF-beta. Our results suggest a possible mechanisms initiating tissue remodeling observed during chronic rhinosinusitis. This study provides further evidence that FPRs play a more complex role in human pathophysiology than bacterial recognition.

One year follow-up of a HIV seropositive jail population.

A jail population has been followed for one year to study the risk of HIV-seroconversion. Our data show that life in jail is not necessarily a condition for HIV spread. In fact no variation of seropositivity distribution has been found.