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Characterization of Codeine Treatment Responders Among Patients with Refractory or Unexplained Chronic Cough: A Prospective Real-World Cohort Study

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Abstract

Purpose

Codeine is a narcotic antitussive often considered for managing patients with refractory or unexplained chronic cough. This study aimed to evaluate the proportion and characteristics of patients who responded to codeine treatment in real-world practice.

Methods

Data from the Korean Chronic Cough Registry, a multicenter prospective cohort study, were analyzed. Physicians assessed the response to codeine based on the timing and degree of improvement after treatment initiation. Follow-up assessments included the Leicester Cough Questionnaire and cough severity visual analog scale at six months. In a subset of subjects, objective cough frequency was evaluated following the initiation of codeine treatment.

Results

Of 305 patients, 124 (40.7%) responded to treatments based on anatomic diagnostic protocols, while 181 (59.3%) remained unexplained or refractory to etiological treatments. Fifty-one subjects (16.7%) were classified as codeine treatment responders (those showing a rapid and clear response), 57 (18.7%) as partial responders, and 62 (20.3%) as non-responders. Codeine responders showed rapid improvement in objective cough frequency and severity scores within a week of the treatment. At 6 months, responders showed significantly improved scores in cough scores, compared to non-responders. Several baseline parameters were associated with a more favorable treatment response, including older age, non-productive cough, and the absence of heartburn.

Conclusions

Approximately 60% of chronic cough patients in specialist clinics may require antitussive drugs. While codeine benefits some, only a limited proportion (about 20%) of patients may experience rapid and significant improvement. This underscores the urgent need for new antitussive drugs to address these unmet clinical needs.

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Data Availability

No datasets were generated or analysed during the current study.

Abbreviations

RUCC:

Refractory or unexplained chronic cough

LCQ:

Leicester Cough Questionnaire

VAS:

Visual analog scale

CHQ:

Cough Hypersensitivity Questionnaire

PROs:

Patient-reported outcomes

GERD:

Gastroesophageal reflux disease

UACS:

Upper airway cough syndrome

FeNO:

Fractional exhaled nitric oxide

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Acknowledgements

The members contributing to the study include (in alphabetical order): Jin An, Kyung Hee University, Seoul, Korea; Surinder S. Birring, King’s College London, London, UK; Yoon-Seok Chang, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea; Sang-Heon Cho, Seoul National University Hospital, Seoul, Korea; Kian Fan Chung, Imperial College London, London, UK; Eun-Jung Jo, School of Medicine, Pusan National University, Busan, Korea; Noeul Kang, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; Sung-Yoon Kang, Gachon University Gil Medical Center, Incheon, Korea; Byung-Keun Kim, Korea University College of Medicine, Seoul, Korea; Mi-Yeong Kim, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea; Min-Hye Kim, College of Medicine, Ewha Womans University, Seoul, Korea; Sae-Hoon Kim, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea; Sang-Heon Kim, Hanyang University College of Medicine, Seoul, Korea; Sang-Hoon Kim, Eulji University College of Medicine, Seoul, Korea; Young-Chan Kim, Seoul National University Hospital, Seoul, Korea; Hyouk-Soo Kwon, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; Byung-Jae Lee, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; Ji-Ho Lee, Yonsei University Wonju College of Medicine, Wonju, Korea; Ji-Hyang Lee, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; Hwa Young Lee, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea; Seung-Eun Lee, Pusan National University Yangsan Hospital, Yangsan, Korea; Ji-Yong Moon, Hanyang University College of Medicine, Seoul, Korea; Ji-Yoon Oh, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; Han-Ki Park, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea; So-Young Park, Chung-Ang University College of Medicine, Seoul, Korea; Ji-Su Shim, College of Medicine, Ewha Womans University, Seoul, Korea; Woo-Jung Song, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; Ha-Kyeong Won, Veterans Health Service Medical Center, Seoul, Korea; Youngsang Yoo, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea.

Funding

The study was supported in part by a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme Corp.. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme Corp.

Author information

Authors and Affiliations

  1. Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Korea

    Ji-Yoon Oh, Ji-Hyang Lee & Woo-Jung Song

  2. Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea

    Sung-Yoon Kang

  3. Division of Allergy, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

    Noeul Kang & Byung-Jae Lee

  4. Department of Internal Medicine, Veterans Health Service Medical Center, Seoul, Korea

    Ha-Kyeong Won

  5. Department of Internal Medicine, School of Medicine, Pusan National University, Busan, Korea

    Eun-Jung Jo

  6. Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea

    Seung-Eun Lee

  7. Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea

    Ji-Su Shim & Min-Hye Kim

  8. Division of Allergy and Clinical Immunology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea

    Young-Chan Kim & Sang-Heon Cho

  9. Department of Allergy and Clinical Immunology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea

    Youngsang Yoo

  10. Department of Pulmonary, Allergy and Critical Care Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul, Korea

    Jin An

  11. Division of Allergy, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

    Hwa Young Lee

  12. Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea

    So-Young Park

  13. Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea

    Mi-Yeong Kim

  14. Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea

    Ji-Ho Lee

  15. Division of Pulmonology, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea

    Byung-Keun Kim

  16. Department of Allergy and Clinical Immunology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu, Korea

    Han-Ki Park

  17. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea

    Sae-Hoon Kim & Yoon-Seok Chang

  18. Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea

    Sang-Heon Kim

  19. Department of Internal Medicine, Eulji University College of Medicine, Seoul, Korea

    Sang-Hoon Kim

  20. National Heart and Lung Institute, Imperial College London, London, UK

    Kian Fan Chung

  21. Royal Brompton and Harefield Hospitals, London, UK

    Kian Fan Chung

Authors
  1. Ji-Yoon Oh
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  2. Sung-Yoon Kang
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  11. Jin An
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  14. Mi-Yeong Kim
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  15. Ji-Ho Lee
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  16. Byung-Keun Kim
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  18. Min-Hye Kim
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Consortia

The Korean Chronic Cough Registry Study Group

  • Jin An
  • , Surinder S. Birring
  • , Yoon-Seok Chang
  • , Sang-Heon Cho
  • , Kian Fan Chung
  • , Eun-Jung Jo
  • , Noeul Kang
  • , Sung-Yoon Kang
  • , Byung-Keun Kim
  • , Mi-Yeong Kim
  • , Min-Hye Kim
  • , Sae-Hoon Kim
  • , Sang-Heon Kim
  • , Sang-Hoon Kim
  • , Young-Chan Kim
  • , Hyouk-Soo Kwon
  • , Byung-Jae Lee
  • , Ji-Ho Lee
  • , Ji-Hyang Lee
  • , Hwa Young Lee
  • , Seung-Eun Lee
  • , Ji-Yong Moon
  • , Ji-Yoon Oh
  • , Han-Ki Park
  • , So-Young Park
  • , Ji-Su Shim
  • , Woo-Jung Song
  • , Ha-Kyeong Won
  •  & Youngsang Yoo

Contributions

Each of the authors confirms that this manuscript has not been previously published and is not currently under consideration by any other journal. Additionally, all authors have approved the contents of this paper and have agreed to the journal submission policies. WJS contributed to the design of the study. JYO and WJS performed the main analysis and wrote the original draft. SYK, NK, HKW, EJJ, SEL, JHL, JSS, YCK, YSY, JA, HYL, SYP, MYK, JHL and MHK assisted in the analysis and interpretation of the data. BKK, HKP, SHK, SHK, YSC, SHK, BJL, KFC, and SHC collected the data. All authors reviewed the manuscript.

Corresponding author

Correspondence to Woo-Jung Song.

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Conflict of interest

WJS declares grants from Merck Sharp & Dohme Corp. and AstraZeneca, consulting fees from Merck, AstraZeneca, Shionogi, Bellus, and GSK, and lecture fees from Merck, AstraZeneca, GSK, Sanofi, and Novartis. Other authors declare that they have no competing interests.

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Collaborators of the of the Korean Chronic Cough Registry Study Group are listed in Acknowledgment Section.

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Oh, JY., Kang, SY., Kang, N. et al. Characterization of Codeine Treatment Responders Among Patients with Refractory or Unexplained Chronic Cough: A Prospective Real-World Cohort Study. Lung 202, 97–106 (2024). https://doi.org/10.1007/s00408-024-00674-6

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