Association of Sinonasal Symptoms and Disease With Immune Checkpoint Inhibitor Therapy

IF 1.6 4区医学 Q2 OTORHINOLARYNGOLOGY

Laryngoscope Investigative Otolaryngology Pub Date : 2025-05-14 DOI:10.1002/lio2.70148

Jaynelle Gao, Ryan S. Chung, Jason Chwa, Kevin Hur

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Abstract

Background

Immune checkpoint inhibitors (ICIs) are widely used for cancer therapy and are associated with immune-related adverse events (irAEs) in various organ systems. However, data on sinonasal irAEs remain limited. This study investigates the association between ICI therapy and sinonasal conditions, including chronic rhinosinusitis (CRS) and nasal polyps, using a national health database.

Methods

This retrospective cohort study utilized the TriNetX US Network to analyze adults diagnosed with malignant neoplasms for which ICIs are an accepted treatment option. Patients treated with FDA-approved ICIs (pembrolizumab, nivolumab, cemiplimab, atezolizumab, durvalumab, avelumab, or ipilimumab) were compared to those not receiving ICIs. Exclusion criteria included sinonasal neoplasms and prior sinus surgery. Propensity score matching on age, race, sex, and asthma diagnosis was performed. Outcomes included first-time diagnoses of CRS, nasal polyps, and cardinal symptoms of CRS. Subgroup analyses by ICI mechanism of action and a post hoc analysis of all-cause mortality were conducted.

Results

ICI therapy was associated with a decreased likelihood of CRS diagnosis (OR 0.90, 95% CI 0.85–0.96), nasal polyp diagnosis (OR 0.65, 95% CI 0.51–0.83), and facial pain (OR 0.74, 95% CI 0.56–0.99). Conversely, patients receiving ICIs had an increased likelihood of anosmia/parosmia or parageusia (OR 1.86, 95% CI 1.68–2.07), and rhinorrhea (OR 1.16, 95% CI 1.10–1.22). Subgroup analyses supported these findings across different ICI categories. Risk of mortality was higher among ICI-treated patients (HR 4.09, 95% CI 4.02–4.16).

Conclusion

This is the first propensity-matched study to evaluate the relationship between ICI therapy and sinonasal conditions, revealing a decreased risk of CRS and nasal polyps in patients undergoing ICI therapy. Future studies are needed to explore the clinical significance and mechanism of ICI-related sinonasal symptoms.

Level of Evidence

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鼻症状和疾病与免疫检查点抑制剂治疗的关系

免疫检查点抑制剂（ICIs）广泛用于癌症治疗，并与多种器官系统的免疫相关不良事件（irAEs）相关。然而，关于鼻腔辐射的数据仍然有限。本研究利用国家卫生数据库调查了ICI治疗与鼻窦疾病（包括慢性鼻窦炎（CRS）和鼻息肉）之间的关系。方法：本回顾性队列研究利用TriNetX美国网络分析诊断为恶性肿瘤的成人，其中ICIs是一种可接受的治疗选择。接受fda批准的ICIs（派姆单抗、纳武单抗、塞米单抗、阿特唑单抗、杜伐单抗、阿维单抗或伊匹单抗）治疗的患者与未接受ICIs治疗的患者进行比较。排除标准包括鼻窦肿瘤和既往鼻窦手术。对年龄、种族、性别和哮喘诊断进行倾向评分匹配。结果包括首次诊断的CRS、鼻息肉和CRS的主要症状。通过ICI作用机制进行亚组分析，并对全因死亡率进行事后分析。结果ICI治疗与CRS诊断（OR 0.90, 95% CI 0.85-0.96）、鼻息肉诊断（OR 0.65, 95% CI 0.51-0.83）和面部疼痛（OR 0.74, 95% CI 0.56-0.99）的可能性降低相关。相反，接受ICIs的患者出现嗅觉缺失/嗅觉缺失或肺吸虫的可能性增加（or 1.86, 95% CI 1.68-2.07），鼻漏的可能性增加（or 1.16, 95% CI 1.10-1.22）。亚组分析支持不同ICI类别的这些发现。CI治疗的患者死亡风险较高（HR 4.09, 95% CI 4.02-4.16）。结论：这是第一个评估ICI治疗与鼻窦疾病之间关系的倾向匹配研究，揭示了接受ICI治疗的患者发生CRS和鼻息肉的风险降低。ci相关鼻窦症状的临床意义及发病机制有待进一步研究。证据水平

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