Clinical Outcomes Research Office, Department of Otolaryngology-Head & Neck Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri.
Medical College of Georgia, Augusta University, Augusta.
JAMA Otolaryngol Head Neck Surg. 2022 Sep 1;148(9):830-837. doi: 10.1001/jamaoto.2022.1573.
Recent studies suggest that theophylline added to saline nasal irrigation (SNI) can be an effective treatment for postviral olfactory dysfunction (OD), a growing public health concern during the COVID-19 pandemic.
To evaluate the efficacy and safety of theophylline added to SNI compared with placebo for COVID-19-related OD.
DESIGN, SETTING, AND PARTICIPANTS: This triple-blinded, placebo-controlled, phase 2 randomized clinical trial was conducted virtually between March 15 and August 31, 2021. Adults residing in Missouri or Illinois were recruited during this time period if they had OD persisting for 3 to 12 months following suspected COVID-19 infection. Data analysis was conducted from October to December 2021.
Saline sinus rinse kits and bottles of identical-appearing capsules with either 400 mg of theophylline (treatment) or 500 mg of lactose powder (control) were mailed to consenting study participants. Participants were instructed to dissolve the capsule contents into the saline rinse and use the solution to irrigate their nasal cavities in the morning and at night for 6 weeks.
The primary outcome was the difference in the rate of responders between the treatment and the control arms, defined as a response of at least slightly better improvement in the Clinical Global Impression-Improvement scale posttreatment. Secondary outcome measures included changes in the University of Pennsylvania Smell Identification Test (UPSIT), the Questionnaire for Olfactory Disorders, the 36-Item Short Form Health Survey on general health, and COVID-19-related questions.
A total of 51 participants were enrolled in the study; the mean (SD) age was 46.0 (13.1) years, and 36 (71%) participants were women. Participants were randomized to SNI with theophylline (n = 26) or to SNI with placebo (n = 25). Forty-five participants completed the study. At the end of treatment, 13 (59%) participants in the theophylline arm reported at least slight improvement in the Clinical Global Impression-Improvement scale (responders) compared with 10 (43%) in the placebo arm (absolute difference, 15.6%; 95% CI, -13.2% to 44.5%). The median difference for the UPSIT change between baseline and 6 weeks was 3.0 (95% CI, -1.0 to 7.0) for participants in the theophylline arm and 0.0 (95% CI, -2.0 to 6.0) for participants in the placebo arm. Mixed-model analysis revealed that the change in UPSIT scores through study assessments was not statistically significantly different between the 2 study arms. Eleven (50%) participants in the theophylline arm and 6 (26%) in the placebo arm had a change of 4 or more points in UPSIT scores from baseline to 6 weeks. The difference in the rate of responders as measured by the UPSIT was 24% (95% CI, -4% to 52%) in favor of theophylline.
This randomized clinical trial suggests that the clinical benefit of theophylline nasal irrigations on olfaction in participants with COVID-19-related OD is inconclusive, though suggested by subjective assessments. Larger studies are warranted to investigate the efficacy of this treatment more fully.
ClinicalTrials.gov Identifier: NCT04789499.
最近的研究表明，在生理盐水鼻腔冲洗（SNI）中加入茶碱可能是治疗病毒性嗅觉功能障碍（OD）的有效方法，这是 COVID-19 大流行期间日益受到关注的公共卫生问题。
评估与安慰剂相比，在 COVID-19 相关 OD 中加入 SNI 的茶碱的疗效和安全性。
设计、设置和参与者：这是一项在 2021 年 3 月 15 日至 8 月 31 日期间在线进行的、三盲、安慰剂对照、2 期随机临床试验。在此期间，如果成年人在疑似 COVID-19 感染后持续出现 3 至 12 个月的 OD，则居住在密苏里州或伊利诺伊州的成年人可以参与这项研究。数据分析于 2021 年 10 月至 12 月进行。
盐水鼻窦冲洗套件和装有 400 毫克茶碱（治疗）或 500 毫克乳糖粉（对照）的胶囊被邮寄给同意参与研究的参与者。参与者被指示将胶囊内容物溶解在盐水中，然后在早上和晚上用溶液冲洗鼻腔，持续 6 周。
主要结果是治疗组和对照组之间的应答率差异，定义为治疗后临床总体印象改善量表（Clinical Global Impression-Improvement scale）的至少略有改善。次要结果包括宾夕法尼亚嗅觉识别测试（University of Pennsylvania Smell Identification Test，UPSIT）、嗅觉障碍问卷（Questionnaire for Olfactory Disorders）、36 项简短健康调查（36-Item Short Form Health Survey）的一般健康状况以及与 COVID-19 相关的问题的变化。
共有 51 名参与者参与了这项研究；平均（SD）年龄为 46.0（13.1）岁，36 名（71%）参与者为女性。参与者被随机分配到 SNI 加茶碱（n = 26）或 SNI 加安慰剂（n = 25）组。共有 45 名参与者完成了研究。治疗结束时，13 名（59%）茶碱组参与者报告至少略有改善，而安慰剂组为 10 名（43%）（绝对差异，15.6%；95%CI，-13.2%至 44.5%）。参与者在基线和 6 周时 UPSIT 变化的中位数差异为 3.0（95%CI，-1.0 至 7.0），茶碱组为 0.0（95%CI，-2.0 至 6.0），安慰剂组为 0.0（95%CI，-2.0 至 6.0）。混合模型分析显示，通过研究评估 UPSIT 评分的变化在 2 个研究组之间没有统计学意义上的显著差异。茶碱组 11 名（50%）参与者和安慰剂组 6 名（26%）参与者 UPSIT 评分从基线到 6 周有 4 分或更多的变化。UPSIT 测量的应答率差异为 24%（95%CI，-4%至 52%），有利于茶碱。
这项随机临床试验表明，COVID-19 相关 OD 患者中，SNI 中加入茶碱对嗅觉的临床益处尚无定论，但主观评估提示可能有一定疗效。需要进行更大规模的研究来更全面地调查这种治疗方法的疗效。
ClinicalTrials.gov 标识符：NCT04789499。
