Effect of PD-1 inhibitor on exhaled nitric oxide and pulmonary function in non-small cell lung cancer patients with and without COPD

Abstract

Background

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.

Objectives

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.

Method

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.

Results

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 FEV₁ but no changes in dyspnea scales, and acute exacerbation did not occur during the therapy.

Conclusion

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.

Keywords:

• immune checkpoint inhibitor
• programmed death 1, PD-1
• non-small cell lung cancer, NSCLC
• chronic obstructive pulmonary disease, COPD

Acknowledgments

We thank Editage for editing a draft of this manuscript. This work was supported by a grant-in-aid for scientific research (16K19448 to YS) from the Japan Society for the Promotion of Science.

Trial Registration

The study is registered in the University Hospital Medical Information Network in Japan.

Disclosure

The authors report no conflicts of interest in this work.