Discussion
NPS, LKS, polyp, Rhinosinusitis, CRSwNP, malignancy, CRS, adult-onset asthma, diabetes
RECURRENCES, RECURRENCE, RHINOSINUSITIS, INFLAMMATION, DISEASE, INVERTED PAPILLOMA, DIABETES
CRS is associated with adult-onset asthma, significant morbidity, decreased health-related quality of life (HRQoL) (Several high-quality studies on preoperative topical steroids for CRSwNP show that they are safe and efficient, independent of the steroid and dosage used (Systemic steroid administration is widely used due to the reduction in inflammation, polyp size and the improvement in olfaction. Previous randomized controlled trials (In 2019, Shen et al. included patients (n=82) with topical steroid spray (mometasone furoate 100 µg) who were randomized postoperatively between an oral prednisolone course (15 mg twice a day for 2 weeks) and a placebo. At 1, 3 and 6 months, there was no difference in the SNOT-22 score. Concerning the LKS there was a trend towards lower scores at 6 months (p=0.05) in the prednisolone group. For a subgroup with high eosinophils there were significantly lower scores in the prednisolone group at 3 months and a trend at 6 months. However, these results were not corrected for multiple hypotheses testing. Dautremont et al, 2014 included n=36 postoperative patients after FESS. They combined budenoside irrigations (1 mg in 240 ml of saline) and a spacer (soaked with 2 ml of triamcinolone 40 mg/ml) with a randomization to prednisolone 30 mg (daily for 7 days) and a placebo. After their follow-up at 1 week, 3 weeks and 2 months, there were no significant differences in mean LKS or in the SNOT-22 scores.Arancibia et al (In the recent randomized controlled trial of n=72 patients by Chang et al, 2021 (The results of all previous trials are in accordance with our data. However, the longest follow-up was 6 months. As a consequence, we included patients in our study who had 1) a short-term follow-up up to 9 month and 2) a long-time follow-up of up to 24 months. Interestingly, our data showed a strong and significant effect of surgery. There was a significant change after surgery in the following outcome measures: NPS, the LKS, sinonasal symptoms, SNQoL, GQoL, and smell scores. For the biomarkers, there were also significant changes after surgery. All outcome measures improved after surgery, and levels remained relatively stable up to the end of the follow-up period of 2 years. This improvement is interesting considering that even the topical steroid was discontinued after 3 months. However, this study´s purpose is not to discuss the value of postoperative topical steroid sprays or nasal rinses, although selected data of short-term randomized controlled trials may point towards the fact that its value is decreasing and differences to placebo groups tend to be subtle (The physiological actions of prednisolone are well understood. Prednisolone binds to cytosolic receptors forming steroid-receptor complexes, which are activated and translocated into the nucleus. In the nucleus, the complex activates specific nuclear receptors, resulting in an altered gene expression and inhibition of proinflammatory cytokine production (This was the first RCT to analyze recurrence rates over a time period of 2 years. Due to the anti-inflammatory effects of prednisolone and their effect on the coagulation and fibrinolysis pathway (Depending on the condition, the intake of systemic prednisolone has been shown to improve patients´ QoL (Regarding the outcome of the 16-item smell identification test, previous RCTs showed that preoperative oral steroids, topical steroids, as well the combination of the two, lead to an improvement in subjective and objective olfactory outcomes in CRSwNP patients (Several mucus protein biomarkers were selected and analyzed over time. Selection was based on previous studies of our group and evaluation in the literature. PAPP-A, CST1/2 and Periostin were included as they were able to monitor disease severity over time in previous studies and predict early CRSwNP recurrences (Limitations of the study include the strong additional effect of surgery. This may always be the case for the study design of postoperative additional steroids; however, slight postoperative differences may be masked by the effect of surgery. Additionally, the power analysis was as usual made for the primary outcome measure only. The high number of study variables and the associated need for multiple corrections may have prevented the study to detect differences in our study cohort. Therefore, it is possible that the study is still underpowered and that a larger sample size would unmask differences between the steroid and the placebo group. However, mostly effect sizes were small or moderate which means that even a (slightly) larger sample size would not have been detected any differences. To answer this question, future multi-centered studies with a larger sample size are necessary.Furthermore, we have to look critically at the dropout rate. Only 80/106 patients finished the medication regime and were included into our intention-to-treat analysis. Whereas for some patients of both groups, the dropout was not associated with the disease (e.g. diagnosis of malignancy, diagnosis of inverted papilloma, diabetes) other patients dropped out because of long travel to hospital site or did not show up anymore for no reason. They also did not answer the phone calls or letters. This holds the potential bias that the remaining study group consists of a more uncontrolled group than the dropout group. Although Finally, it is important to mention that in our study only patients without previous surgery were selected in order keep the cohort as homogeneous as possible. Consequently, results may only be applied to CRSwNP patients with primary FESS and not for recurrent surgeries.For the postoperative setting, the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 (