Position-Directed Budesonide Nasal Drops for CRS-associated Olfactory Dysfunction

Chronic rhinosinusitis (CRS)-related olfactory dysfunction may result from both obstruction of the olfactory cleft and persistent local inflammation. Conventional intranasal corticosteroid sprays may have limited and variable drug deposition in the olfactory cleft. This randomized controlled trial is designed to evaluate whether targeted delivery of budesonide nasal drops using the Wu's position (Wu's 45° Head-Hanging Reclination Position) provides greater olfactory improvement than conventional budesonide nasal spray in patients with eosinophilic/type 2 CRS-related olfactory dysfunction.

A total of 78 adults aged 18-65 years will be randomized 1:1 to receive either budesonide nasal drops administered in the Wu's position or conventional budesonide nasal spray for 12 weeks. Participants in the nasal-drop group will receive budesonide suspension, 20 drops per nostril twice daily, and will maintain the Wu's position for approximately 5 minutes after administration. Participants in the control group will receive conventional budesonide nasal spray, 2 actuations per nostril once daily in the upright sitting position.

Olfactory function will be assessed using Sniffin' Sticks, including odor threshold, discrimination, identification, and the composite TDI score. The primary outcome is the proportion of participants achieving a clinically meaningful TDI improvement of ≥5.5 points at Week 12. Additional assessments will include the Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS), Olfactory-Visual Analogue Scale (VAS), the Sino-Nasal Outcome Test 22 (SNOT-22), Nasal Obstruction Symptom Evaluation (NOSE), and 4-item Concise Aging adults Smell Test (4-CAST). Sinus CT will be used to evaluate olfactory cleft structural abnormalities, while computational fluid dynamics (CFD) analysis will characterize olfactory cleft airflow.

At Week 12, olfactory recovery will also be classified as fully reversible, partially reversible, or non-responsive/irreversible according to the magnitude and completeness of TDI improvement. Baseline olfactory cleft CT findings, CFD-derived airflow parameters, peripheral blood eosinophil count, nasal polyp status, olfactory severity, and other clinical assessment scores will be explored as potential predictors of treatment response.

Inclusion criteria

• Men and women aged 18-65 years old.
• Diagnosis of CRS according to the EPOS 2020, with olfactory dysfunction lasting ≥ 12 weeks.
• Evidence of eosinophilic/type 2 inflammatory CRS, defined by at least one of the following: JESREC score ≥11, peripheral blood eosinophils ≥5%, absolute blood eosinophil count ≥ 0.25 × 10⁹/L.
• Confirmation of OD via Sniffin' Sticks test: TDI score <30.75 (hyposmia: 16 < TDI < 30.75; anosmia: TDI ≤ 16).
• Sinus CT scan confirming olfactory cleft abnormalities (e.g., mucosal thickening, polypoid changes, obstruction).
• Willingness to participate in this study and sign the informed consent form (ICF).

Exclusion criteria

• Patients who have used systemic corticosteroids within the past 4 weeks or who have used intranasal corticosteroids within the past 2 weeks, or biologic therapy targeting type 2 inflammation within 6 months before enrolment.
• Patients with severe deviation of the nasal septum, nasal tumors, acute upper respiratory tract infection or uncontrolled allergic rhinitis.
• Patients with severe cardiovascular diseases, liver or kidney dysfunction, uncontrolled diabetes, or immune system disorders or other systemic disease that may interfere with study participation or safety.
• Patients with current pregnancy or plan to become pregnant during the study period.
• Patients with known hypersensitivity or contraindication to budesonide or any study medication component.
• Patients who are unable to complete the study or are unable to comply with the requirements of the study (including inability to tolerate olfactory function testing and treatment, memory or behavioral abnormalities, depression, smoking, heavy alcohol use or prior non-compliance, specifically early withdrawal from a study).