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Very rapid improvement of extended nitric oxide parameters, associated with clinical and functional betterment, in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) treated with Dupilumab

Paoletti G1,2, Casini M1,2, Malvezzi L1, Pirola F1,2, Russo E1,2, Nappi E1,2, Quintina Muci G1,2, Montagna C1,2, Messina MR1,2, Ferri S1, Racca F1, Lamacchia D1, Cataldo G1, Puggioni F1, De Virgilio A1,2, Ferreli F1,2, Mercante G1,2, Spriano G1,2, Canonica GW1,2, Heffler E1,2

1IRCCS Humanitas Research Hospital -, via Manzoni 56, 20089 Rozzano, Milan, Italy
2Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy

J Investig Allergol Clin Immunol 2023; Vol. 33(6)
doi: 10.18176/jiaci.0851

Background: Dupilumab, an anti-IL-4 receptor alpha monoclonal antibody, has been recently approved for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate to severe asthma, demonstrating a rapid onset of clinical effects. CRSwNP is characterized by an extended type-2 inflammatory involvement that can be assessed by extended nitric oxide analysis.
Objective: In this study we investigated whether Dupilumab is associated with a rapid improvement in extended nitric oxide parameters, lung function and clinical outcomes in patients with CRSwNP.
Methods: Consecutive patients with CRSwNP and indication to be treated with Dupilumab were evaluated for extended nitric oxide analysis (exhaled, FENO; bronchial, JawNO and alveolar, CalvNO components; nasal, nNO) and lung function 15 and 30 days after treatment initiation, and for clinical outcomes (nasal polyps score, NPS; quality of life questionnaires; visual analogue scales, VAS, for main symptoms, asthma control test, ACT) after 30 days of treatment initiation.
Results: 33 patients were enrolled. All extended nitric oxide and lung function parameters significantly improved after 15 days of treatment remaining stable at 30 days. NPS, VAS for main CRSwNP symptoms, quality of life questionnaires and ACT significantly improved after 30 days of treatment initiation.
Conclusions: Dupilumab is associated with very rapid improvement in type 2 inflammation in all airway districts and this is associated with improved lung function and clinical parameters in patients with CRSwNP.

Key words: Chronic rhinosinusitis, Nasal Polyps, Asthma, Dupilumab, Biologics, Nitric oxide, Breath analysis, Lung function