## 4 Discussion
Nevertheless, up to 30% of patients may not respond to ATAD [12]. In a previous audit on intranasal LAS, our team found that 18.7% of patients reported no efficacy following intranasal ATAD at their 3-month follow-up. With this in mind, a common issue is to determine how long a patient should be trialled before considering him to be a non-respondor to ATAD. In this regard, a total score of 20 at the SNOT-22 has been defined to be the threshold to distinguish responders (SNOT-22 \(<\) 20) from non-responders (SNOT-22 \(\geq\) 20) [24]. Moreover, a recent study from [PERSON] et al. [25] found that the SNOT-22 score obtained at 6 months post-desensitisation had the greatest predictive value for long-term outcomes at 24 months post-desensitisation, with an OR of 16.5, proposing a 6-month time point of ATAD as a predictor for long-term success. In our practice, we tend to consider a patient a good responder to the treatment when their SNOT-22 score significantly improves from baseline (SNOT-22 before treatment). In this regard, the minimal clinically important difference (MCID) for the SNOT-22 total score has been reported to be 8.9 points and this is the minimal improvement in the SNOT-22 total score we usually seek for in order to consider a patient a responder to the treatment. In our population, 11.8% (4/34) were previously considered non-responders to intranasal ATAD (based on our medical records), although this percentage could have been higher considering that the remaining 9 patients never started intranasal LAS. Assessing domains and item scores of the SNOT-22 separately can provide clinicians with a better understanding of which individual aspect of CRSwNP has the greatest impact on patients' HRQoL and, thus, offer valuable information in view of personalised treatment decision making. In our study, the domain \"rhinologic symptoms\" remained the most affected domain across both groups of patients (on or off LAS) with the items \"nasal obstruction\", \"thick nasal discharge\", and \"post-nasal discharge\" reported to be the most important items from our N-ERD respondents. This corroborates previous results of a recent randomized double-blind placebo-controlled study which included patients with CRSwNP considered hard to treat, including patients with N-ERD [26]. Moreover, in our study patients on LAS had significantly lower scores in the rhinologic domain (\(p\) = 0.05) when compared to their counterparts not on nasal LAS, suggesting that LAS is effective in controlling nasal polyps and the local inflammatory burden, confirming results from our previous retrospective study [14]. We also observed significant improvements in the domains function (\(p\) = 0.02) and emotion (\(p\) = 0.01), which could simply reflect the indirect effect of improved sinonasal symptoms on other aspects of health. Loss of smell in N-ERD negatively impacts QoL and has been reported to be more severe as compared to patients with ASA-tolerant CRSwNP [27]. In our population, more than 80% of the patients reported having at least a moderate problem with their sense of smell at the SNOT-22 and almost 60% of the respondents confirmed this was one of the five most important items affecting their health. This suggests that, from a patient's perspective, OD remains an important marker of disease severity and, thus, a critical outcome measure of treatment efficacy. The cause of OD in N-ERD seems to be multifactorial. Contributingfactors include the high nasal polyp burden and swelling of the sinonasal mucosa in the olfactory area which could cause a physical obstruction preventing odorants from reaching the olfactory epithelium. In addition, the long-standing chronic inflammation within the olfactory epithelium may also be a causative mechanism for OD in these patients [28]. In fact, elevated nasal mucous levels of IL-2, IL-5, and IL-13 have been associated with altered olfaction suggesting a potential immunological cause for OD in these patients [29; 30].