囊性纤维化中的嗅觉功能：结局指标、嗅觉障碍患病率及管理的影响——系统综述与Meta分析

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中文摘要

背景： 嗅觉障碍（OD）是囊性纤维化（CF）中日益被认识但研究不足的共病。其患病率、评估方法以及对CF导向治疗（包括高效调节剂治疗（HEMT））的反应仍未被完全阐明。
方法： 我们开展了一项符合PRISMA 2020的系统综述（PROSPERO：CRD420251060317），数据库检索从建库至2025年12月。若研究纳入确诊CF的参与者并报告明确的嗅觉结局，则符合纳入标准。两名评价者独立筛选标题和摘要；全文筛选和Joanna Briggs Institute批判性评价最初由一名评价者完成，并由第二名评价者对随机子集进行复核。叙述性综合是主要方法。预先指定了一项探索性随机效应患病率Meta分析。进行了敏感性分析以及按OD病例定义和评估方法进行的探索性Meta回归，并进行了成人/儿童亚组分析。
结果： 共纳入29篇出版物，代表21个独特研究人群，并识别出15种不同的评估工具。探索性Meta分析汇总的OD患病率（所有评估方法）为51.9%（95% CI：29.1-74.3%；PI 0.0%-100%；I2 = 98.2%）。在仅心理物理学方法的敏感性分析中，汇总患病率为58.6%（95% CI：41.6-74.6%；I2 = 92.0%），成人显著更高（p < 0.0001），为76.4%（95% CI：66.5-85.1%；n = 319），而儿童为27.3%（95% CI：9.8-48.7%；n = 118）。汇总的Sniffin' Sticks Test评分为26.5（95% CI：22.0-31.0；95% PI：17.7-35.4；n = 127），使该队列处于嗅觉减退范围。汇总的SNOT-22总评分为35.8（95% CI：27.6-44.1；95% PI：10.2-61.4），反映总体鼻窦鼻腔和健康相关生活质量负担显著。汇总的Lund-Mackay评分为13.5（95% CI：11.1-15.9），提示中度至重度影像学鼻窦鼻腔疾病负担。HEMT持续改善鼻窦鼻腔疾病的影像学标志物，但患者报告的健康相关生活质量改善不一，且在大多数研究中未达到统计学显著性。没有纳入研究显示HEMT后心理物理学嗅觉表现有统计学显著改善，并且在有报告的情况下未达到嗅觉最小临床重要差异。
结论： OD是CF的重要共病，估计影响总体51.9%的CF患者，成人高于儿童。汇总患病率因OD病例定义和评估方法而存在实质性差异。多维心理物理学测试应被视为参考性功能评估，并辅以嗅觉特异性患者报告结局指标。在现有研究中，HEMT似乎不能恢复心理物理学嗅觉功能，支持在调节剂时代继续进行客观嗅觉筛查。需要从儿童期开始的前瞻性纵向研究。

英文摘要

BACKGROUND: Olfactory dysfunction (OD) is an increasingly recognized but under-investigated comorbidity of cystic fibrosis (CF). Its prevalence, assessment methods, and response to CF-directed treatment, including highly effective modulator therapy (HEMT) remains incompletely characterized.
METHODS: We conducted a PRISMA 2020-compliant systematic review (PROSPERO: CRD420251060317) with a database search from inception to December 2025. Studies were eligible if they included participants with confirmed CF and reported an explicit olfactory outcome. Two reviewers independently screened titles and abstracts; full-text screening and Joanna Briggs Institute critical appraisal were initially completed by one reviewer, with a second-reviewer re-check of a random subset. Narrative synthesis was the primary method. An exploratory random-effects prevalence meta-analysis was pre-specified. Sensitivity analyses and exploratory meta-regression by OD case definition and assessment method, and adult/pediatric subgroup analysis were performed.
RESULTS: Twenty-nine publications representing 21 unique study populations were included, and 15 distinct assessment instruments were identified. Exploratory meta-analysis pooled OD prevalence (all assessment methods) was 51.9% (95% CI: 29.1-74.3%; PI 0.0%-100%; I2 = 98.2%). In the psychophysical-only sensitivity analysis, pooled prevalence was 58.6% (95% CI: 41.6-74.6%; I2 = 92.0%), with it being significantly higher (p < 0.0001) in adults 76.4% (95% CI: 66.5-85.1%; n = 319) than in children (27.3% (95% CI: 9.8-48.7% n = 118). The pooled Sniffin' Sticks Test score was 26.5 (95% CI: 22.0-31.0; 95% PI: 17.7-35.4; n = 127), placing the cohort within the hyposmic range. The pooled total SNOT-22 score was 35.8 (95% CI: 27.6-44.1; 95% PI: 10.2-61.4), reflecting substantial overall sinonasal and HRQoL burden. The pooled Lund-Mackay score was 13.5 (95% CI: 11.1-15.9), indicating moderate-to-severe radiological sinonasal disease burden. HEMT consistently improved radiological markers of sinonasal disease, but patient-reported HRQoL improvement was variable and did not reach statistical significance in most studies. No included study demonstrated a statistically significant improvement in psychophysical olfactory performance after HEMT, and olfactory minimum clinically important difference was not reached where reported.
CONCLUSIONS: OD is an important comorbidity of CF affecting an estimated 51.9% of people with CF overall, with higher rates in adults than children. Pooled prevalence varies materially by OD case definition and assessment method. Multidimensional psychophysical testing should be considered the reference functional assessment, complemented by olfaction-specific patient-reported outcome measures. HEMT does not appear to restore psychophysical olfactory function in the available studies, supporting continued objective olfactory screening in the modulator era. Prospective longitudinal studies commencing in childhood are needed.