Comment on “Effect of Budesonide Nasal Irrigation in Patients With Chronic Rhinosinusitis With Nasal Polyps Without Prior Sinus Surgery: A Randomized, Double‐Blind, Placebo‐Controlled Study”

1.

To the Editor:

We read with great interest the randomized controlled trial by Sant'Ana et al. examining budesonide nasal irrigation in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) without prior sinus surgery [1]. The study addresses an important clinical question, and the authors are to be commended for conducting what appears to be the first double‐blind, placebo‐controlled trial in this specific population. However, several methodological aspects warrant closer examination that may affect the interpretation of the findings.

First, I noted a substantial disparity in attrition rates between the two arms. While the budesonide group had a 100% completion rate, 9 out of 26 patients (34.6%) in the placebo group discontinued the intervention, primarily due to “no improvement.” The authors employed the Last Observation Carried Forward (LOCF) method for their intention‐to‐treat analysis. While LOCF is a common approach, it carries the inherent assumption that a patient's status remains stable after withdrawal. In cases where patients drop out specifically because the treatment is failing, LOCF may inadvertently carry forward a more favorable score from an earlier visit, potentially underestimating the true failure rate of the placebo. It would be enlightening to hear if the authors considered a “worst‐case” sensitivity analysis or multiple imputation to see if the magnitude of the 18.1‐point SNOT‐22 difference remained robust.

Furthermore, the clinical performance of the saline‐only control group was quite striking. These patients achieved a mean SNOT‐22 improvement of 15.1 points. Given that the established minimal clinically important difference (MCID) for this instrument is 14 points, the saline irrigation alone provided a clinically meaningful benefit. This reinforces the high therapeutic value of high‐volume saline irrigation itself in “surgically naive” anatomy. High‐volume saline irrigation itself has documented efficacy in CRSwNP, as shown in prior studies [2]. Rather than framing the conclusion as budesonide being effective for “symptom control,” the authors might consider emphasizing that budesonide irrigation offers additional benefit beyond saline irrigation alone. This distinction matters for clinical decision‐making and patient counseling.

While the study demonstrates significant improvements in subjective SNOT‐22 scores and objective Nasal Polyp Scores (NPS), the findings regarding olfactory function as measured by the CCCRC test warrant a more cautious interpretation. Despite a numerically greater mean improvement in the budesonide group (+0.58) compared to the placebo group (+0.34), the between‐group difference of 0.24 points failed to reach statistical significance (p = 0.63). Furthermore, although the manuscript highlights a higher proportion of patients reaching the MCID for olfaction in the budesonide arm (42.3% vs. 23.1%), the statistical non‐significance of this comparison (p = 0.139) suggests that these trends should be viewed as preliminary rather than definitive clinical evidence. These results likely underscore the unique anatomical challenges inherent in surgically naive patients; the presence of extensive polyps may physically obstruct the olfactory cleft, preventing high‐volume, low‐pressure irrigation from effectively reaching and treating the superior sinonasal mucosa. Consequently, while the intervention appears effective for general sinonasal symptom control, its impact on the core symptom of olfactory dysfunction remains unproven within this 4‐week framework.

The observed SNOT‐22 between‐group difference of 18.1 points carries a 95% confidence interval spanning 29.4 points (3.4 to 32.8), indicating considerable uncertainty around the effect estimate. Combined with the single‐center design and 4‐week follow‐up, the evidence strength may be more limited than the conclusions suggest. Larger, multi‐center trials with longer follow‐up—such as the Tait et al. study [3] involving 100 patients—would help confirm whether these promising findings translate into durable clinical benefits and meaningful reductions in surgical requirements.

These points are raised not to diminish the contribution of this meticulously conducted pilot study, but to refine the roadmap for future research. By demonstrating the short‐term efficacy of budesonide irrigation in surgically naive patients, the authors have identified an accessible and practical therapeutic alternative for those in urgent need of symptom control. We hold this work in high regard as an essential first step, and we look forward to seeing the field evolve through the continued exploration of the insights provided by this study.

Sincerely

Author Contributions

Zusheng Du: writing – original draft. Huikang Wang: writing – review and editing. Yu Zhang: conceptualization. Xicheng Song: conceptualization. All authors reviewed and approved the manuscript.

Funding

This research was supported by the National Natural Science Foundation of China (82271147, 82571287, 82271146).

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The authors have nothing to report.