Very Rapid Improvement in Extended Nitric Oxide Parameters Is Associated With Clinical and Functional Improvement in Patients With Chronic Rhinosinusitis With Nasal Polyps Treated With Dupilumab

Abstract

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.

Outcome measures for chronic rhinosinusitis with nasal polyps

“…FeNO in CRS so far has focused on predicting the presence of occult asthma (331)(332)(333) , as well as tracking improvement in asthma after treatment of CRS (334,335) . Nasal nitric oxide (nNO) has been described as a marker of and outcome measure for eosinophilic or type-2 CRS that can improve with treatment of CRS (335) but its measurement is confounded by physical obstruction of sinus ostia.…”

“…FeNO in CRS so far has focused on predicting the presence of occult asthma (331)(332)(333) , as well as tracking improvement in asthma after treatment of CRS (334,335) . Nasal nitric oxide (nNO) has been described as a marker of and outcome measure for eosinophilic or type-2 CRS that can improve with treatment of CRS (335) but its measurement is confounded by physical obstruction of sinus ostia. For example, despite the higher prevalence of type-2 inflammation, CRSwNP is associated with lower nNO levels compared to CRSsNP or control patients (336) and ESS can increase nasal FeNO due to enlarged sinus ostia, despite the lack of obvious mucosal inflammation (337,338) .…”

Airways Type-2 Related Disorders: Multiorgan, Systemic or Syndemic Disease?

“…Nevertheless, nNO normalization has been demonstrated after both medical and surgical opening of sinonasal ostia, thus providing evidence of its possible application as a marker of treatment response [104]. Moreover, Paoletti et al demonstrated the effectiveness of anti-IL-4 receptor alpha monoclonal antibody (dupilumab), proving a rapid improvement in nNO values and other markers of disease severity as early as 15 days after the initiation of treatment [105].…”

Oxidative Stress and Air Pollution: Its Impact on Chronic Respiratory Diseases

“…Additionally, dupilumab, an anti-IL-4 receptor alpha monoclonal antibody, has been used recently in the treatment of CRSwNP. Patients with CRSwNP treated with dupilumab were evaluated through extended nitric oxide analyses (exhaled, FENO; bronchial, JawNO; alveolar, CalvNO components; nasal, nNO) where the results showed that nitric oxide significantly improved after 15 days of treatment [21].…”