Skip to main content
Top
Published in: Lung 2/2024

27-02-2024 | Codeine | COUGH

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

Authors: Ji-Yoon Oh, Sung-Yoon Kang, Noeul Kang, Ha-Kyeong Won, Eun-Jung Jo, Seung-Eun Lee, Ji-Hyang Lee, Ji-Su Shim, Young-Chan Kim, Youngsang Yoo, Jin An, Hwa Young Lee, So-Young Park, Mi-Yeong Kim, Ji-Ho Lee, Byung-Keun Kim, Han-Ki Park, Min-Hye Kim, Sae-Hoon Kim, Sang-Heon Kim, Yoon-Seok Chang, Sang-Hoon Kim, Byung-Jae Lee, Kian Fan Chung, Sang-Heon Cho, Woo-Jung Song, The Korean Chronic Cough Registry Study Group

Published in: Lung | Issue 2/2024

Login to get access

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.
Literature
1.
go back to reference Eddy NB, Friebel H, Hahn KJ, Halbach H (1968) Codeine and its alternates for pain and cough relief. I. Codeine, exclusive of its antitussive action. Bull World Health Organ 38(5):673–741PubMedPubMedCentral Eddy NB, Friebel H, Hahn KJ, Halbach H (1968) Codeine and its alternates for pain and cough relief. I. Codeine, exclusive of its antitussive action. Bull World Health Organ 38(5):673–741PubMedPubMedCentral
2.
go back to reference Song WJ, Yu CJ, Kang SH (2022) Cough characteristics and healthcare journeys of chronic cough patients in community-based populations in South Korea and Taiwan. Lung 200(6):725–736CrossRefPubMedPubMedCentral Song WJ, Yu CJ, Kang SH (2022) Cough characteristics and healthcare journeys of chronic cough patients in community-based populations in South Korea and Taiwan. Lung 200(6):725–736CrossRefPubMedPubMedCentral
3.
go back to reference Zeiger RS, Schatz M, Butler RK, Weaver JP, Bali V, Chen W (2020) Burden of specialist-diagnosed chronic cough in adults. J Allergy Clin Immunol Pract 8(5):1645–1657CrossRefPubMed Zeiger RS, Schatz M, Butler RK, Weaver JP, Bali V, Chen W (2020) Burden of specialist-diagnosed chronic cough in adults. J Allergy Clin Immunol Pract 8(5):1645–1657CrossRefPubMed
4.
go back to reference Jo EJ, Lee JH, Won HK et al (2023) Baseline cohort profile of the Korean chronic cough registry: a multicenter, prospective observational study. Lung 201(5):477–188CrossRefPubMed Jo EJ, Lee JH, Won HK et al (2023) Baseline cohort profile of the Korean chronic cough registry: a multicenter, prospective observational study. Lung 201(5):477–188CrossRefPubMed
5.
go back to reference Oh JY, Kang YR, An J et al (2023) Codeine prescription pattern and treatment responses in patients with chronic cough: a routinely collected institutional database analysis. J Thorac Dis 15(4):2344–2354CrossRefPubMedPubMedCentral Oh JY, Kang YR, An J et al (2023) Codeine prescription pattern and treatment responses in patients with chronic cough: a routinely collected institutional database analysis. J Thorac Dis 15(4):2344–2354CrossRefPubMedPubMedCentral
6.
go back to reference Aylward M, Maddock J, Davies DE, Protheroe DA, Leideman T (1984) Dextromethorphan and codeine: comparison of plasma kinetics and antitussive effects. Eur J Respir Dis 65(4):283–291PubMed Aylward M, Maddock J, Davies DE, Protheroe DA, Leideman T (1984) Dextromethorphan and codeine: comparison of plasma kinetics and antitussive effects. Eur J Respir Dis 65(4):283–291PubMed
7.
go back to reference Sevelius H, Colmore JP (1966) Objective assessment of antitussive agents in patients with chronic cough. J New Drugs 6(4):216–223CrossRefPubMed Sevelius H, Colmore JP (1966) Objective assessment of antitussive agents in patients with chronic cough. J New Drugs 6(4):216–223CrossRefPubMed
8.
go back to reference Sevelius H, McCoy JF, Colmore JP (1971) Dose response to codeine in patients with chronic cough. Clin Pharmacol Ther 12(3):449–455CrossRefPubMed Sevelius H, McCoy JF, Colmore JP (1971) Dose response to codeine in patients with chronic cough. Clin Pharmacol Ther 12(3):449–455CrossRefPubMed
9.
go back to reference Lee SP, Lee SM, Lee BJ, Kang SY (2022) Effectiveness and safety of codeine and levodropropizine in patients with chronic cough. J Korean Med Sci 37(36):e275CrossRefPubMedPubMedCentral Lee SP, Lee SM, Lee BJ, Kang SY (2022) Effectiveness and safety of codeine and levodropropizine in patients with chronic cough. J Korean Med Sci 37(36):e275CrossRefPubMedPubMedCentral
10.
go back to reference Smith J, Owen E, Earis J, Woodcock A (2006) Effect of codeine on objective measurement of cough in chronic obstructive pulmonary disease. J Allergy Clin Immunol 117(4):831–835CrossRefPubMed Smith J, Owen E, Earis J, Woodcock A (2006) Effect of codeine on objective measurement of cough in chronic obstructive pulmonary disease. J Allergy Clin Immunol 117(4):831–835CrossRefPubMed
11.
go back to reference Morice AH, Menon MS, Mulrennan SA, Everett CF, Wright C, Jackson J, Thompson R (2007) Opiate therapy in chronic cough. Am J Respir Crit Care Med 175(4):312–315CrossRefPubMed Morice AH, Menon MS, Mulrennan SA, Everett CF, Wright C, Jackson J, Thompson R (2007) Opiate therapy in chronic cough. Am J Respir Crit Care Med 175(4):312–315CrossRefPubMed
13.
go back to reference Crews KR, Gaedigk A, Dunnenberger HM et al (2014) Clinical pharmacogenetics implementation consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin Pharmacol Ther 95(4):376–382CrossRefPubMedPubMedCentral Crews KR, Gaedigk A, Dunnenberger HM et al (2014) Clinical pharmacogenetics implementation consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin Pharmacol Ther 95(4):376–382CrossRefPubMedPubMedCentral
14.
go back to reference Song DJ, Song WJ, Kwon JW et al (2018) KAAACI evidence-based clinical practice guidelines for chronic cough in adults and children in Korea. Allergy Asthma Immunol Res 10(6):591–613CrossRefPubMedPubMedCentral Song DJ, Song WJ, Kwon JW et al (2018) KAAACI evidence-based clinical practice guidelines for chronic cough in adults and children in Korea. Allergy Asthma Immunol Res 10(6):591–613CrossRefPubMedPubMedCentral
15.
go back to reference Song WJ, Chung KF (2020) Pharmacotherapeutic options for chronic refractory cough. Expert Opin Pharmacother 21(11):1345–1358CrossRefPubMed Song WJ, Chung KF (2020) Pharmacotherapeutic options for chronic refractory cough. Expert Opin Pharmacother 21(11):1345–1358CrossRefPubMed
16.
go back to reference Al-Sheklly B, Mitchell J, Issa B, Badri H, Satia I, Collier T, Sen S, Ford JW, Corfield D, Smith J (2017) Randomised control trial quantifying the efficacy of low dose morphine in a responder group of patients with refractory chronic cough. In: British Thoracic Society Winter Meeting. BMJ Publishing Group Ltd. Al-Sheklly B, Mitchell J, Issa B, Badri H, Satia I, Collier T, Sen S, Ford JW, Corfield D, Smith J (2017) Randomised control trial quantifying the efficacy of low dose morphine in a responder group of patients with refractory chronic cough. In: British Thoracic Society Winter Meeting. BMJ Publishing Group Ltd.
17.
go back to reference Irwin RS, French CL, Chang AB, Altman KW, Adams TM, Azoulay E, Barker AF, Birring SS, Blackhall F, Bolser DC (2018) Classification of cough as a symptom in adults and management algorithms: CHEST guideline and expert panel report. Chest 153(1):196–209CrossRefPubMed Irwin RS, French CL, Chang AB, Altman KW, Adams TM, Azoulay E, Barker AF, Birring SS, Blackhall F, Bolser DC (2018) Classification of cough as a symptom in adults and management algorithms: CHEST guideline and expert panel report. Chest 153(1):196–209CrossRefPubMed
18.
go back to reference Morice AH, Millqvist E, Bieksiene K et al (2020) ERS guidelines on the diagnosis and treatment of chronic cough in adults and children. Eur Respir J 55(1):1901136CrossRefPubMed Morice AH, Millqvist E, Bieksiene K et al (2020) ERS guidelines on the diagnosis and treatment of chronic cough in adults and children. Eur Respir J 55(1):1901136CrossRefPubMed
19.
go back to reference Kwon JW, Moon JY, Kim SH et al (2015) Reliability and validity of a korean version of the leicester cough questionnaire. Allergy Asthma Immunol Res 7(3):230–233CrossRefPubMed Kwon JW, Moon JY, Kim SH et al (2015) Reliability and validity of a korean version of the leicester cough questionnaire. Allergy Asthma Immunol Res 7(3):230–233CrossRefPubMed
20.
go back to reference Won HK, Kang SY, Kang Y et al (2019) Cough-related laryngeal sensations and triggers in adults with chronic cough: symptom profile and impact. Allergy Asthma Immunol Res 11(5):622–631CrossRefPubMedPubMedCentral Won HK, Kang SY, Kang Y et al (2019) Cough-related laryngeal sensations and triggers in adults with chronic cough: symptom profile and impact. Allergy Asthma Immunol Res 11(5):622–631CrossRefPubMedPubMedCentral
21.
go back to reference Rhatigan K, Hirons B, Kesavan H, Turner RD, Ebelthite C, Hull JH, Jolley CJ, Birring SS, Cho PSP (2023) Patient global impression of severity scale in chronic cough: validation and formulation of symptom severity categories. J Allergy Clin Immunol Pract 11(12):3706–3712CrossRefPubMed Rhatigan K, Hirons B, Kesavan H, Turner RD, Ebelthite C, Hull JH, Jolley CJ, Birring SS, Cho PSP (2023) Patient global impression of severity scale in chronic cough: validation and formulation of symptom severity categories. J Allergy Clin Immunol Pract 11(12):3706–3712CrossRefPubMed
22.
go back to reference Lee SE, Rudd M, Kim TH, Oh JY, Lee JH, Jover L, Small PM, Chung KF, Song WJ (2023) Feasibility and utility of a smartphone application-based longitudinal cough monitoring in chronic cough patients in a real-world setting. Lung 201(6):555–564CrossRefPubMed Lee SE, Rudd M, Kim TH, Oh JY, Lee JH, Jover L, Small PM, Chung KF, Song WJ (2023) Feasibility and utility of a smartphone application-based longitudinal cough monitoring in chronic cough patients in a real-world setting. Lung 201(6):555–564CrossRefPubMed
23.
go back to reference Morice AH, Jakes AD, Faruqi S et al (2014) A worldwide survey of chronic cough: a manifestation of enhanced somatosensory response. Eur Respir J 44(5):1149–1155CrossRefPubMed Morice AH, Jakes AD, Faruqi S et al (2014) A worldwide survey of chronic cough: a manifestation of enhanced somatosensory response. Eur Respir J 44(5):1149–1155CrossRefPubMed
24.
go back to reference Song WJ, Dupont L, Birring SS et al (2023) Consensus goals and standards for specialist cough clinics: the NEUROCOUGH international Delphi study. ERJ Open Res 9(6):00618–02023CrossRefPubMedPubMedCentral Song WJ, Dupont L, Birring SS et al (2023) Consensus goals and standards for specialist cough clinics: the NEUROCOUGH international Delphi study. ERJ Open Res 9(6):00618–02023CrossRefPubMedPubMedCentral
25.
go back to reference Lee Y, Lee JH, Park SY, Lee JH, Kim JH, Kim HJ, Kim SH, Chung KF, Song WJ (2023) Roles of real-world evidence in severe asthma treatment: challenges and opportunities. ERJ Open Res 9(2):00248–02022CrossRefPubMedPubMedCentral Lee Y, Lee JH, Park SY, Lee JH, Kim JH, Kim HJ, Kim SH, Chung KF, Song WJ (2023) Roles of real-world evidence in severe asthma treatment: challenges and opportunities. ERJ Open Res 9(2):00248–02022CrossRefPubMedPubMedCentral
26.
go back to reference Eccles R (2020) The powerful placebo effect in cough: relevance to treatment and clinical trials. Lung 198(1):13–21CrossRefPubMed Eccles R (2020) The powerful placebo effect in cough: relevance to treatment and clinical trials. Lung 198(1):13–21CrossRefPubMed
Metadata
Title
Characterization of Codeine Treatment Responders Among Patients with Refractory or Unexplained Chronic Cough: A Prospective Real-World Cohort Study
Authors
Ji-Yoon Oh
Sung-Yoon Kang
Noeul Kang
Ha-Kyeong Won
Eun-Jung Jo
Seung-Eun Lee
Ji-Hyang Lee
Ji-Su Shim
Young-Chan Kim
Youngsang Yoo
Jin An
Hwa Young Lee
So-Young Park
Mi-Yeong Kim
Ji-Ho Lee
Byung-Keun Kim
Han-Ki Park
Min-Hye Kim
Sae-Hoon Kim
Sang-Heon Kim
Yoon-Seok Chang
Sang-Hoon Kim
Byung-Jae Lee
Kian Fan Chung
Sang-Heon Cho
Woo-Jung Song
The Korean Chronic Cough Registry Study Group
Publication date
27-02-2024
Publisher
Springer US
Published in
Lung / Issue 2/2024
Print ISSN: 0341-2040
Electronic ISSN: 1432-1750
DOI
https://doi.org/10.1007/s00408-024-00674-6

Other articles of this Issue 2/2024

Lung 2/2024 Go to the issue

REVIEW: EXTRACORPOREAL LIFE SUPPORT (ECLS) IN ACUTE SEVERE ASTHMA

Outcomes of Extracorporeal Life Support (ECLS) in Acute Severe Asthma: A Narrative Review

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine