鼻塞及羟甲唑啉与皮质类固醇治疗：一项随机临床试验

文献信息

中文摘要

重要性： 长期使用羟甲唑啉（一种高效的鼻减充血剂）与反跳性鼻塞相关，但既往文献显示鼻内类固醇可能预防快速耐受和反跳，从而可能使慢性鼻塞患者能够长期联合使用羟甲唑啉/鼻内类固醇。
目的： 确定长期联合羟甲唑啉/布地奈德鼻喷雾剂能否缓解慢性鼻炎相关的鼻塞，而不引起药物性鼻炎的症状或组织病理学证据。
设计、场所和参与者： 本研究为单中心、双盲、随机临床试验，于2024年10月至2025年7月在圣路易斯华盛顿大学/巴恩斯犹太医院开展。关键入选标准包括患有慢性鼻塞、既往局部类固醇治疗失败且无慢性鼻窦炎的成人。
干预： 参与者使用提供的鼻喷雾剂，每日两次，含羟甲唑啉/布地奈德或单用布地奈德，进行4周积极治疗，随后3周逐渐减量期。10名参与者接受了治疗前和治疗后下鼻甲活检，用于组织病理学变化分析。
主要结局和指标： 主要结局指标是应答者比例，定义为治疗4周后临床总体印象-改善量表上至少中度改善。反跳性鼻塞或减量困难的指标通过临床总体印象-严重度量表评分变化评估。
结果： 在筛查的87人中，61名参与者签署知情同意书，60名参与者被随机分组并完成基线评估。在随机分组参与者中，31名接受羟甲唑啉/布地奈德喷雾剂（入组时平均[SD]年龄46.0[18.7]岁；18名[58.1%]女性；13名[41.9%]男性），29名单用布地奈德（平均[SD]年龄51.2[17.1]岁；17名[58.6%]女性；12名[41.4%]男性）。羟甲唑啉/布地奈德组有24/29（83%）为治疗应答者，而单用布地奈德组为10/28（36%），差异为47个百分点（95% CI，25-70个百分点）。羟甲唑啉组无参与者在积极治疗期间出现提示反跳性鼻塞的鼻塞加重。所有参与者均顺利停用羟甲唑啉。
结论和意义： 在这项随机临床试验中，羟甲唑啉组应答者比例大幅且具有临床意义的更高，研究期间无药物性鼻炎体征或症状。所有参与者均成功停用羟甲唑啉。对于局部类固醇治疗失败的慢性鼻塞患者，可考虑联合羟甲唑啉/布地奈德的长期治疗，但不能排除更长期使用导致反跳性鼻塞的风险。
试验注册： ClinicalTrials.gov标识符：NCT06830109。

英文摘要

IMPORTANCE: Prolonged use of oxymetazoline, a highly effective nasal decongestant, is associated with rebound obstruction, but previous literature has shown potential for intranasal steroids to prevent tachyphylaxis and rebound, thereby potentially allowing for long-term combined oxymetazoline/intranasal steroid use in patients with chronic nasal obstruction.
OBJECTIVE: To determine whether long-term combined oxymetazoline/budesonide nasal spray could alleviate the nasal obstruction associated with chronic rhinitis without inducing symptoms or histopathologic evidence of rhinitis medicamentosa.
DESIGN, SETTING, AND PARTICIPANTS: This study was a single-center, double-blind, randomized clinical trial conducted at Washington University in St Louis/Barnes Jewish Hospital from October 2024 to July 2025. Key selection criteria included adults with chronic nasal obstruction, prior failure of topical steroids, and no chronic sinusitis.
INTERVENTION: Participants used a provided nasal spray twice daily containing either oxymetazoline/budesonide or budesonide alone for 4 weeks of active treatment followed by a 3-week wean period. Ten participants underwent pretreatment and posttreatment inferior turbinate biopsies for histopathological analysis of change.
MAIN OUTCOMES AND MEASURES: The primary outcome measure is the rate of responders, defined as at least moderate improvement on the Clinical Global Impressions-Improvement scale, assessed after 4 weeks of treatment. Measures of rebound obstruction or difficulty weaning were assessed by score changes on the Clinical Global Impression-Severity scale.
RESULTS: From 87 individuals screened, 61 participants signed informed consent, and 60 participants were randomized and completed baseline assessments. Of the randomized participants, 31 participants received oxymetazoline/budesonide spray (mean [SD] age at enrollment, 46.0 [18.7] years; 18 [58.1%] female; 13 [41.9%] male), and 29 participants received budesonide alone (mean [SD] age, 51.2 [17.1] years; 17 [58.6%] female; 12 [41.4%] male). There were 24 of 29 (83%) responders to treatment in the oxymetazoline/budesonide arm, compared with 10 of 28 (36%) in the budesonide-only arm, a difference of 47 percentage points (95% CI, 25-70 percentage points). None of the participants in the oxymetazoline arm developed worsening obstruction concerning for rebound obstruction during active treatment. All successfully weaned off oxymetazoline without issue.
CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, there was a large and clinically meaningful greater proportion of responders in the oxymetazoline arm, without signs or symptoms of rhinitis medicamentosa during the study. All participants successfully weaned off oxymetazoline. For patients with chronic nasal obstruction failing topical steroids, chronic therapy with combination oxymetazoline/budesonide may be considered, though risks of rebound congestion with longer-term use cannot be excluded.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06830109.