International Journal of COPD (Aug 2019)

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

  • Suzuki Y,
  • Inui N,
  • Karayama M,
  • Imokawa S,
  • Yamada T,
  • Yokomura K,
  • Asada K,
  • Kusagaya H,
  • Kaida Y,
  • Matsuda H,
  • Koshimizu N,
  • Toyoshima M,
  • Masuda M,
  • Hayakawa H,
  • Hozumi H,
  • Furuhashi K,
  • Enomoto N,
  • Fujisawa T,
  • Nakamura Y,
  • Suda T

Journal volume & issue
Vol. Volume 14
pp. 1867 – 1877

Abstract

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Yuzo Suzuki,1 Naoki Inui,1 Masato Karayama,1 Shiro Imokawa,2 Takashi Yamada,3 Koushi Yokomura,4 Kazuhiro Asada,5 Hideki Kusagaya,6 Yusuke Kaida,7 Hiroyuki Matsuda,8 Naoki Koshimizu,9 Mikio Toyoshima,10 Masafumi Masuda,11 Hiroshi Hayakawa,12 Hironao Hozumi,1 Kazuki Furuhashi,1 Noriyuki Enomoto,1 Tomoyuki Fujisawa,1 Yutaro Nakamura,1 Takafumi Suda11Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan; 2Department of Respiratory Medicine, Iwata City Hospital, Iwata, Japan; 3Department of Respiratory Medicine, Shizuoka City Shizuoka Hospital, Shizuoka, Japan; 4Department of Respiratory Medicine, Seirei-Mikatahara Hospital, Hamamatsu, Japan; 5Department of Respiratory Medicine, Shizuoka General Hospital, Shizuoka, Japan; 6Department of Respiratory Medicine, Shizuoka Saiseikai Hospital, Shizuoka, Japan; 7Department of Respiratory Medicine, JA Shizuoka Kohseiren Enshu Hospital, Hamamatsu, Japan; 8Department of Respiratory Medicine, Shizuoka Red Cross Hospital, Shizuoka, Japan; 9Department of Respiratory Medicine, Fujieda City Hospital, Fujieda, Japan; 10Department of Respiratory Medicine, Hamamatsu Rosai Hospital, Hamamatsu, Japan; 11Department of Respiratory Medicine, Shizuoka City Shimizu Hospital, Shizuoka, Japan; 12Department of Respiratory Medicine, Tenryu Hospital, National Hospital Organization, Hamamatsu, JapanCorrespondence: Yuzo SuzukiSecond Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama Higashi-ku, Hamamatsu, Shizuoka 431-3192, JapanTel +81 53 435 2263Fax +81 53 435 2354Email [email protected]: 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

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