Early clinical improvement of anosmia and sinus nitric oxide in chronic rhinosinusitis with nasal polyps subjects treated with dupilumab

Background/Objective: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have a high morbidity of anosmia, yet there are few noninvasive biomarkers to measure treatment response. Nitric oxide (NO) is found in the paranasal sinuses at 100 times higher levels than in the lungs and is vital for antimicrobial and/or mucociliary activities and vasodilatory properties. Dupilumab has been shown to improve anosmia in 2 weeks as measured by the University of Pennsylvania Smell Identification Test (UPSIT), 22-item Sinonasal Outcome Test (SNOT-22), and Loss of Smell (LoS) scoring. We examined the use of NO in various collection methods to monitor anosmia improvement with dupilumab treatment. Methods: Adults with CRSwNP confirmed by computer tomography or endoscopy consented to receive dupilumab 300 mg every two weeks for 16 weeks. Subjects with polyposis despite treatment with steroids and/or a history of sinus surgery were recruited. Measurements of sinus NO (sNO) from the nostril while humming, nasal NO (nNO) while breath-holding, and fractional exhaled nitric oxide (FeNO) while exhaling were collected at baseline and at 1, 2, 4, 8, 12, 16 weeks. Olfactory impairment was measured by using the UPSIT, SNOT-22, and LoS scoring at every visit. Results: Sixteen adults, with a mean (range) age of 43 years (25‐53 years) were predominantly women (12/16). Baseline mean (range) sNO values of 434 ppb (203‐665 ppb) significantly increased at 2 weeks to a mean (range) of 1150 ppb (684‐1616 ppb) (p < 0.05). Significant improvements in the UPSIT, SNOT-22, and LoS scores were found at 2 weeks; a weak correlation of the sNO level with the UPSIT and SNOT-22 scores was noted. No significant changes in the FeNO or nNO values were found. Significant improvement was found specifically with anosmia by the end of 2 weeks. Conclusion: Our small pilot study revealed increased sNO levels in the sinuses as early as 2 weeks after the initial dupilumab administration. Thus, in patients with CRSwNP without asthma, the sNO value has the potential to be used as a noninvasive, objective biomarker for early treatment improvement in anosmia.