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Morphine for dyspnoea in chronic obstructive pulmonary disease: a before–after efficacy study
  1. Yoshinobu Matsuda1,
  2. Tatsuya Morita2,
  3. Hirotaka Matsumoto3,
  4. Keita Hosoi4,
  5. Kayo Kusama5,
  6. Yasuo Kohashi6,
  7. Hiroshi Morishita7,
  8. Sawako Kaku8,
  9. Keisuke Ariyoshi9,
  10. Shunsuke Oyamada10,
  11. Yoshikazu Inoue11,
  12. Satoru Iwase12,
  13. Takuhiro Yamaguchi13 and
  14. Mitsunori Nishikawa14
  1. 1Department of Psychosomatic Internal Medicine, Kinki Chuo Chest Medical Center, Sakai, Japan
  2. 2Department of Palliative and Supportive Care, Seirei Mikatahara General Hospital, Hamamatsu City, Shizuoka, Japan
  3. 3Department of Respiratory Medicine, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan
  4. 4Department of Respiratory Medicine, Itami City Hospital, Itami, Japan
  5. 5Department of Respiratory Medicine, Sakai City Medical Center, Sakai, Japan
  6. 6Department of Respiratory Medicine, HARUHI Respiratory Medical Hospital, Kiyosu, Japan
  7. 7Department of Respiratory Medicine, Osaka Habikino Medical Center, Habikino, Japan
  8. 8Palliative and Supportive Care Division, Seirei Mikatahara General Hospital, Hamamatsu, Amagasaki, Japan
  9. 9Department of Data Management, JORTC Data Center, Tokyo, Japan
  10. 10Department of Biostatistics, JORTC Data Center, Tokyo, Japan
  11. 11Clinical Research Center National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai, Japan
  12. 12Department of Palliative Medicine, Saitama Medical University, Moroyama, Japan
  13. 13Division of Biostatistics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
  14. 14Department of Palliative Care, National Center for Geriatrics and Gerontology, Obu, Japan
  1. Correspondence to Dr Yoshinobu Matsuda, Department of Psychosomatic Internal Medicine, Kinki Chuo Chest Medical Center, Sakai, Japan; matsuda.yoshinobu.tx{at}


Objectives Dyspnoea in patients with chronic obstructive pulmonary disease (COPD) is frequent and often persists despite conventional treatment. This study aimed to evaluate the efficacy and safety of oral morphine for dyspnoea in Japanese COPD patients.

Methods We conducted a multi-institutional, prospective, before–after study of morphine in COPD patients with dyspnoea at rest in seven hospitals. Patients received 12 mg of oral morphine per day (or 8 mg per day if low body weight or renal impairment). Primary outcome was change in the numerical rating scale (NRS) of current dyspnoea in the evening from Day 0 to Day 2. Secondary outcomes included changes in dyspnoea intensity in the evening from Day 0 to Day 1, dyspnoea intensity between the morning from Day 0 to Day 1 and Day 2, vital signs, nausea, somnolence, anorexia and other adverse events (AEs).

Results A total of 35 patients were enrolled in this study between October 2014 and January 2018. One patient did not receive study treatment. Data from 34 patients was analysed. The NRS of dyspnoea intensity in the evening significantly decreased from 3.9 on Day 0 (95% CI: 3.1 to 4.8) to 2.4 on Day 2 (95% CI: 1.7 to 3.1; p=0.0002). Secondary outcomes significantly improved in a similar manner. There were no apparent changes in the mean scores of the opioid-related AEs and vital signs. One patient experienced grade 3 lung infection not associated with morphine. Other AEs were mild.

Conclusion Oral morphine is effective in alleviating dyspnoea in Japanese COPD patients.

Trial registration

UMIN000015288 (

  • dyspnoea
  • morphine
  • clinical trials and COPD

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  • Contributors YM, TM, KA, YI, SI, TY and MN conceptualized, planned and constructed the study. YM, HM, KH, KK, YK, HM, SK and KA contributed to data collection. SO and TY led on analysis. All authors were involved in data interpretation. YM and TM drafted the manuscript. All authors edited the manuscript and approved the final version.

  • Funding The study was supported by the Research Funding for Longevity Sciences from National Center for Geriatrics & Gerontology grant (25-9, 28-12).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Our protocol was reviewed and approved by the JORTC Protocol Review Committee and the Institutional Review Boards at each study site.

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • Data availability statement No data are available.

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