Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Department of Respiratory Medicine, Iwata City Hospital, Iwata, Japan.
Int J Chron Obstruct Pulmon Dis. 2019 Aug 21;14:1867-1877. doi: 10.2147/COPD.S214610. eCollection 2019.
Nivolumab, a programmed death 1 (PD-1) immune checkpoint inhibitor, has been shown to improve survival in non-small cell lung cancer (NSCLC). The possible involvement of PD-1 axis in the pathogenesis of inflammatory lung disease, such as chronic obstructive pulmonary disease (COPD) has also been reported. However, effects of PD-1 blockade on the respiratory system remain unknown.
This prospective study aimed to investigate whether inhibition of the PD-1 axis altered lung inflammation and pulmonary function in NSCLC patients with and without COPD.
This was a prospective multi-center study. Measurements of fractioned exhaled nitric oxide (FeNO) and pulmonary function were performed before and after 4 cycles of nivolumab therapy.
A total of 137 patients with NSCLC were initially enrolled, and subsequently 95 patients (41 COPD and 54 non-COPD) receiving 4 cycles of nivolumab administration were included. After anti-PD-1 therapy, FeNO levels were significantly elevated together with increase in peripheral eosinophils. Interestingly, significant FeNO elevation was only found in COPD patients without increased peripheral eosinophils, but this was not the case in non-COPD patients. Additionally, COPD patients exhibited significant increases in FVC and FEV but no changes in dyspnea scales, and acute exacerbation did not occur during the therapy.
Our observations suggest that anti-PD-1 therapy changed FeNO levels and pulmonary function in NSCLC patients. This therapy does not worsen COPD in terms of symptoms, pulmonary function, or acute exacerbation.
程序性死亡受体 1（PD-1）免疫检查点抑制剂纳武利尤单抗已被证明可改善非小细胞肺癌（NSCLC）患者的生存率。PD-1 轴在炎症性肺疾病（如慢性阻塞性肺疾病[COPD]）的发病机制中的可能作用也有报道。然而，PD-1 阻断对呼吸系统的影响尚不清楚。
本前瞻性研究旨在探讨 PD-1 轴抑制是否改变了合并或不合并 COPD 的 NSCLC 患者的肺部炎症和肺功能。
这是一项前瞻性多中心研究。在接受 4 个周期纳武利尤单抗治疗前后，分别进行了呼出气一氧化氮分数（FeNO）和肺功能的测量。
共纳入 137 例 NSCLC 患者，随后纳入了 95 例（41 例 COPD 和 54 例非 COPD）接受 4 个周期纳武利尤单抗治疗的患者。抗 PD-1 治疗后，FeNO 水平显著升高，外周嗜酸性粒细胞也随之增加。有趣的是，仅在 COPD 患者中观察到 FeNO 显著升高，而外周嗜酸性粒细胞没有增加，但在非 COPD 患者中则没有这种情况。此外，COPD 患者的 FVC 和 FEV 显著增加，但呼吸困难评分无变化，且治疗过程中无急性加重。
我们的观察结果表明，抗 PD-1 治疗改变了 NSCLC 患者的 FeNO 水平和肺功能。在症状、肺功能或急性加重方面，该治疗并未加重 COPD。
