## 4 Discussion
A previous review looking at studies evaluating olfactory outcomes following oral ASA desensitisation demonstrated improvements in patient-reported and objective assessments of olfactory function [22; 23; 31]. Interestingly, in one of these, [PERSON] et al. [32] compared individuals who were on long-term oral ASA therapy and those who discontinued therapy for a variety of reasons and observed statistically significant improvement in the PROMs while on ASA with a subsequent worsening of symptoms after discontinuation. Although we previously demonstrated improved olfaction in patients on long-term nasal ATAD, as measured by a 6-item identification test (Nez du Vin) [14], in this study there was no statistically significant difference in the patients' reported olfaction (both at the sVAS and the SNOT-22 item \"decreased sense of smell/taste\") between those on intranasal LAS or not. This could be because subjective olfaction measures are less sensitive than objective ones [33]. In this regard, it is interesting to mention that [PERSON] et al. [34] observed that healthy subjects are usually unable to accurately self-report their sense of smell but the accuracy of this self-assessment improves after undergoing olfactory testing, forcing them to pay conscious attention to their sense of smell. Despite several studies showing an improvement of HRQoL in N-ERD patients whilst on ATAD, aspirin desensitisation remains an underutilized treatment modality as confirmed by our study of allergists and fellows conducted in the United States in 2016 [35]. More recently, biologics have set their scene on the treatment of severe CRSwNP and, although not specific for N-ERD, they have been shown to be very effective in CRSwNP in N-ERD patients [36; 37]. In this regard, duplimumab, an anti-interleukin-4 and -13, has gained increased popularity since its approval as a treatment for severe or refractory CRSwNP in 2019 and several studies have demonstrated effective reduction in both objective and subjective measurements [38; 39; 40]. So far, duplumab is the only biologic showing a difference between aspirin-tolerant and aspirin-intolerant CRSwNP patients with N-ERD patients reporting significantly greater improvement in nasal congestion and SNOT-22 scores after treatment [41]. In a previous study, [PERSON] and colleagues [42] reported a higher improvement in the total SNOT-22 score when using duplimumab if compared to our study (mean change of \(-34.4\) and \(-34.5\) at month 1 and 3, respectively; all \(p<0.0001\)). Additionally, differently from our results, an improvement in all five SNOT-22 domains at 6 months has also been demonstrated in patients on duplumab, with the most marked improvements observed for nasal, sleep, and function domains [26]. However, no direct trials with ATAD and biologic therapy in N-ERD patients exist, which makes it difficult to choose the best alternative to use when maximal medical and surgical treatments have failed. Only recently, [PERSON] and colleagues [43] conducted an observational real-life study including 59 N-ERD patients receiving ATAD or biologics (either omalizumab or mepolizumab) and found no significant difference in the SNOT-22 scores between patients who received ATAD only and/or biologics although SNOT-22 scores were lower in those who received mepolizumab. Biologics have also been demonstrated to significantly improve olfactory function in several studies [38; 44; 45]. Moreover, [PERSON] and colleagues [46] did not show any differences for partial or total improvement in sense of smell when comparing N-ERD (35.7%) and non-N-ERD patients (37%) in patients undergoing long-term treatment with omalizumab, mepolizumab, reslizumab, or benzlizumab. However, there remains a need for further studies to demonstrate the effectiveness of biologics more clearly against ATAD for the decision of which biologics are beneficial in patients with both eosinophil and atopy.