Steinbach Maya-Leonie C, Eska Jakob, Weitzel Julia, Görges Alexandra R, Tietze Julia K, Ballmann Manfred
Children's and Adolescent Clinic, Department of Pneumology and Allergology, University Medical Center Rostock, 18057 Rostock, Germany.
Clinic for Dermatology and Venereology, University Medical Center Rostock, 18057 Rostock, Germany.
Cancers (Basel). 2024 May 30;16(11):2088. doi: 10.3390/cancers16112088.
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. 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. 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 ( = 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 ( = 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 ( = 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 ( = 0.734). 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.
免疫检查点阻断（ICB）在恶性肿瘤治疗方面取得了突破，提高了各种肿瘤患者的总生存率。ICB也可能导致免疫相关不良事件，如肺炎或间质性肺病。肺清除指数（LCI）是一种多次呼吸洗脱技术，除了传统的肺量计外，还能提供有关肺部病理的信息。它测量肺通气不均匀程度，并能早期检测肺部损伤，尤其是外周气道的损伤。这项横断面研究比较了接受程序性细胞死亡1（PD-1）和细胞毒性T淋巴细胞相关蛋白4（CTLA-4）抗体单独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的肺功能。根据美国胸科学会和欧洲呼吸学会的标准，使用肺量计、LCI和一氧化碳弥散量（DLCO）测量来评估肺功能。61名筛查患者和38名筛查对照产生了19对成功纳入的配对。ICB治疗患者的LCI为8.41±1.15（平均值±标准差），与对照组的8.07±1.17相比高0.32，但差异不显著（P = 0.452）。在测试时，接受ICB治疗不足5个月的患者的LCI（7.98±0.77）显著低于接受ICB治疗超过5个月的患者（9.63±1.22）（P = 0.014）。肺量计分析显示，与对照组相比，ICB治疗患者在用力肺活量的25%至75%之间的用力呼气量（FEF25-75%）显著降低（P = 0.047）。ICB患者的DLCO（%预测值并根据血红蛋白进行调整）为94.4±19.7，对照组为93.4±21.7（P = 0.734）。与对照组相比，接受ICB治疗的患者肺功能略有受损。ICB治疗时间较长导致LCI恶化，这可能是亚临床炎症过程的一个迹象。LCI是可行的，并且可以很容易地纳入临床日常工作中，有助于早期检测肺部（自身）炎症。
