Chronic Rhinosinusitis (CRS) is a group of chronic inflammatory diseases that frequently occur in the nasal cavity and sinus mucosa.1 As one of the most common conditions in otorhinolaryngology, CRS is characterized by multiple occurrences and recurrence. In addition, the morbidity of CRS is rising year by year, and about 8% of incidence of CRS has been reported in China.2,3 Difficult-to-Treat Rhinosinusitis (DTRS) is a subtype of CRS. As described by the European Position Paper on Rhinosinusitis and Nasal Polyps 2012, DTRS can be diagnosed if a CRS patient's symptoms are not still controlled after surgery, 1-year of nasal glucocorticoid treatment and 2 courses of systemic glucocorticoid or antibiotic treatment.4 Despite treatment by drugs and surgery, DTRS patients are still affected by clinical symptoms such as purulent nasal discharge, nasal obstruction, olfactory dysfunction or facial pain that occur repeatedly, seriously affecting their physical and mental health and quality of life. Moreover, long-term treatment also brings a huge financial burden to patients.5 Therefore, there is an urgent need to find a more efficient and feasible treatment for improving the outcomes of DTRS patients.

Endoscopic Posterior Nasal Nerve (PNN) resection, a highly selective vidian neurectomy, can inhibit secretion-promoting movement and suppress neurogenic inflammation induced by parasympathetic and sensory nerves. In recent years, endoscopic PNN has been commonly used to reduce the sensitivity of nasal mucosa in patients with allergic rhinitis and improve their clinical symptoms.6,7 Endoscopic surgery has the advantages of providing a clear field of view and easy removal of lesions and has been highly accepted by most patients and their families in clinical practice.8 However, the efficacy of surgical treatment is expected to be reserved for cases where anatomical/functional causes are identified that can be addressed by it, but in no way will it interrupt the course of the disease or its propensity to develop comorbidities. Drug treatment can relieve tissue edema and inflammation in patients, reduce the difficulty of endoscopic surgery, depress the recurrence of postoperative symptoms, and provide great help to control the patient's condition.9,10 It is reported that surgery combined with drugs can more effectively improve clinical treatment outcomes.11

The important pathological basis of DTRS is mainly inflammation, as increased levels of pro-inflammatory factors accelerate the progression of the disease and further aggravate the damage to the normal tissues of the nasal mucosa. Hence, anti-inflammatory therapy could be the key treatment direction of DTRS.10,11 In addition, nasal glucocorticoids can effectively alleviate and inhibit inflammatory response and reduce postoperative adverse reactions, thereby improving clinical efficacy. Nevertheless, the curative effect of glucocorticoids may be affected if they cannot completely reach and cover the surgical wound due to improper use by postoperative patients.12 Budesonide suspension, a respiratory tract nebulized inhaled steroid hormone, belongs to strong anti-inflammatory and anti-allergic drugs. Generally, budesonide suspension can inhibit the activation of various inflammatory cells in the nasal cavity, alleviate the inflammation damage of lesion sites and promote the absorption of mucosal edema, thereby accelerating the recovery of nasal function and relieving the symptoms such as nasal congestion and purulent nasal discharge.13 Currently, there are few studies on the comprehensive efficacy of PNN resection combined with budesonide suspension in treating DTRS. Therefore, a retrospective analysis was performed to explore the clinical effect of PNN resection combined with budesonide suspension on DTRS patients in this study.

DTRS is a medical condition characterized by nasal inflammation, presenting with primary symptoms such as nasal congestion, thick or purulent secretions, and headaches. If left untreated, DTRS can potentially impact patients' nerves and visual function, leading to adverse effects, including decreased eyesight. Additionally, it can lead to intracranial infections, manifesting as symptoms such as headaches, fever, and vomiting, thereby significantly compromising patients' overall health and disrupting their daily lives.17 At present, one of the primary treatment modalities for DTRS is nasal endoscopy surgery, which offers a clear view of anatomical structures and lesions, which increases the chance for improved therapeutic outcomes.18 However, it is essential to acknowledge that nasal endoscopy surgery may also inadvertently trigger an increase in the production of inflammatory mediators due to its invasive nature.19 Consequently, the supplementation of drug therapy alongside surgical intervention becomes imperative to enhance clinical efficacy. To date, limited research has explored the impact of budesonide suspension on DTRS. Therefore, in this research work, we compared the clinical efficacy of budesonide suspension in combination with surgical treatment versus surgical treatment alone.

This present study revealed no significant differences in SNOT-22 or Lund-Kennedy scores between the two groups before treatment initiation. However, following treatment, both groups exhibited a notable decrease in their respective scores, with the group receiving budesonide suspension in conjunction with PNN resection demonstrating superior efficacy compared to those receiving surgical treatment alone. Thus, the combination of budesonide suspension and surgical intervention led to a greater enhancement in patients' postoperative quality of life compared to surgical treatment alone. Additionally, the incidence of adverse reactions, including nasal adhesions, epistaxis, sinus orifice obstruction and lacrimal duct injuries, was lower in the study group compared to the control group. Furthermore, the study group displayed a significantly lower overall rate of adverse reactions. These findings underscore the enhanced efficacy of budesonide suspension when combined with surgical treatment for DTRS. Although the precise pathogenesis of DTRS remains incompletely understood, several contributing factors, including environmental, genetic, anatomical, and immune abnormalities, have been consistently identified as influencing factors. Inflammation has been confirmed as a key inducing factor in this condition.20 Presently, the significant role of eosinophilic infiltration in the pathogenesis of DTRS has been established.21 Specifically, local activation and degranulation of eosinophils lead to local epithelial damage, the production of inflammatory mediators, nasal mucosal edema, and the exacerbation of rhinosinusitis symptoms.21 As a chronic ailment, DTRS necessitates timely symptomatic treatment for the relief and suppression of patient symptoms. PNN resection has been substantiated as an effective treatment approach for DTRS. Thus, PNN resection can ameliorate clinical symptoms by removing a substantial portion of parasympathetic nerve fibers within the nasal cavity. This reduction in glandular secretion, inhibition of hemangiectasis, and decrease in inflammatory factor levels have been reported as key mechanisms through which PNN resection improves the condition.6 Notably, after PNN resection, a significant reduction in eosinophil counts within the nasal mucosa of patients with allergic rhinitis has been observed, accompanied by a marked decrease in inflammation occurrence.22

In addition to surgical interventions, patients with DTRS can be treated with anti-inflammatory drugs. Currently, glucocorticoids represent the primary pharmacological approach for managing DTRS. They can effectively temper the inflammatory response, reduce the release of inflammatory mediators, and facilitate the synthesis of anti-inflammatory factors through multiple mechanisms, primarily due to DTRS's increased sensitivity to glucocorticoid therapy.23 Additionally, glucocorticoids possess anti-biofilm properties and can facilitate the targeted delivery of medications to the afflicted mucosa within the nasal cavity or sinuses, thereby alleviating adverse reactions. An important aspect of treatment for DTRS involves the correct application of nasal glucocorticoids. It is essential to ensure that patients are well-informed and capable of properly applying these medications. Many patients struggle with the correct application of nasal glucocorticoids, leading to suboptimal drug delivery, unsatisfactory treatment outcomes, and delayed disease management.24 Budesonide suspension, categorized as a nebulized glucocorticoid, offers anti-inflammatory attributes and can effectively inhibit the activation of macrophages, eosinophils, and neutrophils. Notably, transnasal nebulization inhalation administration enables direct drug action on the local nasal and sinus mucosa, facilitating comprehensive drug absorption within the mucosal tissues, which amplifies the pharmacological efficacy of drugs, significantly ameliorating symptoms in individuals with sinusitis.25 Budesonide transnasal nebulization therapy effectively addresses the challenge of inadequate hormone delivery within the nasal cavity. Topical therapy, utilizing high-volume corticosteroid irrigation, is a viable option for DTRS patients, substantially enhancing SNOT-22 and Lund-Kennedy scores.26 High-volume irrigation has the advantage of precise drug distribution to the paranasal sinuses. Taken together, the methods have their own advantages and considerations. The choice between a nasal spray and nebulization often depends on the specific circumstances, including the patient's condition, the specific drug being administered, and the desired effects. Therefore, a robust patient-doctor dialogue is imperative to educate patients on the correct technique for nasal spray application. This interaction not only enhances treatment efficacy but also empowers patients to be active participants in their healthcare.

In our study, we observed that budesonide transnasal nebulization, as a form of glucocorticoid administration, offers a viable alternative, especially for patients who find it challenging to use nasal sprays correctly. The transnasal nebulization therapy provided direct and thorough drug contact with the lesions. Furthermore, nebulization facilitates aerosol penetration through the sinus orifices and sinus cavities. Due to the particulate nature of small aerosols, budesonide achieves localized deposition more readily, aided by air compression pumps, thus elevating drug concentrations and prolonging therapeutic effectiveness. Moreover, nebulization therapy garners higher patient acceptance due to its simplicity and minimal wound irritation. Thus, our combination of PNN resection with hormone transnasal nebulization significantly enhanced the SNOT-22 and Lund-Kennedy scores among DTRS patients compared to PNN resection alone, resulting in decreased adverse reactions and a more robust improvement in patients' physical and mental well-being.

However, it should also be noted that in the management of DTRS, it is important to conduct a comprehensive re-evaluation of the underlying diagnosis and to thoroughly assess any associated comorbidities before advancing to more complex treatments, including surgical interventions, especially via a multidisciplinary approach. Such a holistic approach would ensure that the treatment plan is tailored to the individual patient's needs, addressing not only the symptoms but also the root causes and related health issues, thereby contrasting with a solely surgical approach, which may not address the underlying pathology effectively. Implementing a comprehensive evaluation process can lead to more targeted and effective management of DTRS, potentially reducing the need for more invasive procedures and the risk of recurrences. In addition, it should also be noted that although combination treatment can improve clinical outcomes, this might also lead to increased risks of treatment-related complications, adverse events and financial constraints to the patients and their relatives. As a retrospective analysis, certain limitations, such as the small sample size, were inherent to this study. To further validate the findings of this investigation, future research could consider conducting large-scale, multi-center, prospective studies.

In conclusion, the combination of PNN resection and hormone transnasal nebulization treatment demonstrates favorable efficacy in addressing DTRS. This therapeutic approach effectively alleviates the symptoms experienced by DTRS patients, reduces the occurrence of adverse reactions, and enhances the overall quality of life for these individuals. Hence, the adoption of PNN resection in conjunction with hormone transnasal nebulization warrants consideration and promotion within clinical practice.

Xin-ke Wang conceived the study. Qi-ling Zheng extracted all dada. Jia-ning Sun wrote the paper. Xin-ke Wang, Qi-ling Zheng and Jia-ning Sun undertook the statistical analyses. All authors read and approved the final manuscript.

This work was supported by Yuyao Science and Technology Bureau Project (nº 2021YPT06).

The datasets used in this article are available from corresponding author on reasonable request.

All patients in this study signed informed consent. Besides, this study was approved by the ethics committee of Yuyao People's Hospital of Zhejiang Province (2023-03-007).

The authors declare no conflicts of interest.