Background:Immune checkpoint blockade (ICB) has presented a breakthrough in the treatment of malignant tumors and increased the overall survival of patients with various tumor entities. ICB may also cause immune-related adverse events, such as pneumonitis or interstitial lung disease. The lung clearance index (LCI) is a multiple-breath washout technique offering information on lung pathology in addition to conventional spirometry. It measures the degree of pulmonary ventilation inhomogeneity and allows early detection of pulmonary damage, especially that to peripheral airways.Methods:This cross-sectional study compared the lung function of patients with melanoma or metastatic cutaneous squamous cell carcinoma who received programmed cell death 1 (PD-1) and cytotoxic T-Lymphocyte-associated Protein 4 (CTLA-4) antibodies, alone or in combination, to age- and sex-matched controls. Lung function was assessed using spirometry, according to American Thoracic Society and European Respiratory Society standards, the LCI, and a diffusion capacity of carbon monoxide (DLCO) measurement.Results:Sixty-one screened patients and thirty-eight screened controls led to nineteen successfully included pairs. The LCI in the ICB-treated patients was 8.41 ± 1.15 (mean ± SD), which was 0.32 higher compared to 8.07 ± 1.17 in the control group, but the difference was not significant (p= 0.452). The patients receiving their ICB therapy for under five months showed a significantly lower LCI (7.98 ± 0.77) compared to the ICB patients undergoing therapy for over five months (9.63 ± 1.22) at the point of testing (p= 0.014). Spirometric analysis revealed that the forced expiratory volume between 25 and 75% of the forced vital capacity (FEF25–75%) in the ICB-treated patients was significantly reduced (p= 0.047) compared to the control group. DLCO (%predicted and adjusted for hemoglobin) was 94.4 ± 19.7 in the ICB patients and 93.4 ± 21.7 in the control group (p= 0.734).Conclusions:The patients undergoing ICB therapy showed slightly impaired lung function compared to the controls. Longer periods of ICB treatment led to deterioration of the LCI, which may be a sign of a subclinical inflammatory process. The LCI is feasible and may be easily integrated into the clinical daily routine and could contribute to early detection of pulmonary (auto-)inflammation.
背景：免疫检查点阻断（ICB）在恶性肿瘤治疗中取得了突破性进展，提高了多种肿瘤患者的总体生存率。然而，ICB也可能引发免疫相关不良事件，如肺炎或间质性肺病。肺清除指数（LCI）是一种多呼吸冲洗技术，能够在常规肺活量测定之外提供肺部病理信息。该技术通过测量肺通气不均质程度，有助于早期发现肺部损伤，特别是外周气道损伤。 方法：本横断面研究比较了接受程序性细胞死亡蛋白1（PD-1）和细胞毒性T淋巴细胞相关蛋白4（CTLA-4）抗体单药或联合治疗的黑色素瘤或转移性皮肤鳞状细胞癌患者，与年龄和性别匹配的对照组人群的肺功能。根据美国胸科学会和欧洲呼吸学会标准，采用肺活量测定法、LCI及一氧化碳弥散量（DLCO）测量进行肺功能评估。 结果：经筛选的61例患者和38例对照者最终形成19对成功配对数据。ICB治疗组患者的LCI为8.41±1.15（均值±标准差），较对照组的8.07±1.17高出0.32，但差异无统计学意义（p=0.452）。治疗时间不足5个月的ICB患者LCI（7.98±0.77）显著低于治疗时间超过5个月的患者（9.63±1.22）（p=0.014）。肺活量分析显示，ICB治疗组患者25%-75%用力肺活量对应的用力呼气流量（FEF25-75%）较对照组显著降低（p=0.047）。经血红蛋白校正的DLCO（占预计值百分比）在ICB组为94.4±19.7，对照组为93.4±21.7（p=0.734）。 结论：与对照组相比，接受ICB治疗的患者肺功能呈现轻度受损。较长的ICB治疗时间会导致LCI恶化，这可能是亚临床炎症过程的征兆。LCI检测具有临床可行性，易于整合到日常诊疗流程中，可能有助于早期发现肺部（自身）炎症反应。
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