PMID- 37538538
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230805
IS  - 2589-5370 (Electronic)
IS  - 2589-5370 (Linking)
VI  - 62
DP  - 2023 Aug
TI  - Efficacy and safety of pharmacotherapy for refractory or unexplained chronic 
      cough: a systematic review and network meta-analysis.
PG  - 102100
LID - 10.1016/j.eclinm.2023.102100 [doi]
LID - 102100
AB  - BACKGROUND: Refractory chronic cough (RCC) has a significant impact on patient's 
      health-related quality of life and represents a challenge in clinical management. 
      However, the optimal treatment for RCC remains controversial. This study aimed to 
      investigate and compare the efficacy and safety of the current pharmacological 
      therapeutic options for RCC. METHODS: A systematic review was performed by 
      searching PubMed, Web of Science, Embase, and Ovid databases from January 1, 2008 
      to March 1, 2023. All randomised control trials (RCTs) reporting outcomes of 
      efficacy or/and safety were included in the Bayesian network meta-analysis. Here, 
      we compared the effects on Leicester Cough Questionnaire (LCQ), Visual Analogue 
      Scale (VAS), and objective cough frequency of patients with RCC. Besides, we also 
      compared the incidence of adverse events (AEs) for analysis of safety. PROSPERO 
      registration: CRD42022345940. FINDINGS: 19 eligible RCTs included 3326 patients 
      and 7 medication categories: P2X3 antagonist, GABA modulator, Transient Receptor 
      Potential (TRP) modulator, NK-1 agonist, opioid analgesic, macrolide, and sodium 
      cromoglicate. Compared with placebo, mean difference (MD) of LCQ and 24 h cough 
      frequency for P2X3 antagonist relief were 1.637 (95% CI: 0.887-2.387) and -11.042 
      (P = 0.035). Compared with placebo, effect sizes (MD for LCQ and cough severity 
      VAS) for GABA modulator were 1.347 (P = 0.003) and -7.843 (P = 0.003). In the 
      network meta-analysis, gefapixant is the most effective treatment for patients 
      with RCC (The Surface Under the Cumulative Ranking Curves (SUCRA) is 0.711 in 
      LCQ, 0.983 in 24 h cough frequency, and 0.786 in cough severity VAS). Lesogaberan 
      had better efficacy than placebo (SUCRA: 0.632 vs. 0.472) in 24 h cough 
      frequency. Eliapixant and lesogaberan had better efficacy than placebo in cough 
      severity VAS. However, TRP modulator had worse efficacy than placebo. In the 
      meta-analysis of AEs, the present study found P2X3 antagonist had a significant 
      correlation to AEs (RR: 1.129, 95% CI: 1.012-1.259), especially taste-related AEs 
      (RR: 6.216, P < 0.05). INTERPRETATION: In this network meta-analysis, P2X3 
      antagonist showing advantages in terms of efficacy is currently the most 
      promising medication for treatment of RCC. GABA modulator also showed potential 
      efficacy for RCC but with AEs of the central system. Nevertheless, the role of 
      TRP modulator needed to be revisited. Further research is needed to determine the 
      potential beneficiary population for optimizing the pharmacological management of 
      chronic cough. FUNDING: National Natural Science Foundation of China (81870079), 
      Guangdong Science and Technology Project (2021A050520012), Incubation Program of 
      National Science Foundation for Distinguished Young Scholars (GMU2020-207).
CI  - (c) 2023 The Author(s).
FAU - Zheng, Ziwen
AU  - Zheng Z
AD  - Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory 
      Disease, National Clinical Research Centre for Respiratory Disease, National 
      Centre for Respiratory Medicine, Guangzhou, Guangdong, China.
AD  - Clinical Medical College, Guangzhou Medical University, Guangzhou, Guangdong, 
      China.
AD  - Department of Allergy and Clinical Immunology, The First Affiliated Hospital of 
      Guangzhou Medical University, Guangzhou, Guangdong, China.
FAU - Huang, Junfeng
AU  - Huang J
AD  - Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory 
      Disease, National Clinical Research Centre for Respiratory Disease, National 
      Centre for Respiratory Medicine, Guangzhou, Guangdong, China.
AD  - Department of Allergy and Clinical Immunology, The First Affiliated Hospital of 
      Guangzhou Medical University, Guangzhou, Guangdong, China.
FAU - Xiang, Ziyuan
AU  - Xiang Z
AD  - Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory 
      Disease, National Clinical Research Centre for Respiratory Disease, National 
      Centre for Respiratory Medicine, Guangzhou, Guangdong, China.
AD  - Department of Allergy and Clinical Immunology, The First Affiliated Hospital of 
      Guangzhou Medical University, Guangzhou, Guangdong, China.
FAU - Wu, Tong
AU  - Wu T
AD  - Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory 
      Disease, National Clinical Research Centre for Respiratory Disease, National 
      Centre for Respiratory Medicine, Guangzhou, Guangdong, China.
AD  - Clinical Medical College, Guangzhou Medical University, Guangzhou, Guangdong, 
      China.
AD  - Department of Allergy and Clinical Immunology, The First Affiliated Hospital of 
      Guangzhou Medical University, Guangzhou, Guangdong, China.
FAU - Lan, Xiaoqing
AU  - Lan X
AD  - Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory 
      Disease, National Clinical Research Centre for Respiratory Disease, National 
      Centre for Respiratory Medicine, Guangzhou, Guangdong, China.
AD  - Clinical Medical College, Guangzhou Medical University, Guangzhou, Guangdong, 
      China.
AD  - Department of Allergy and Clinical Immunology, The First Affiliated Hospital of 
      Guangzhou Medical University, Guangzhou, Guangdong, China.
FAU - Xie, Shuojia
AU  - Xie S
AD  - Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory 
      Disease, National Clinical Research Centre for Respiratory Disease, National 
      Centre for Respiratory Medicine, Guangzhou, Guangdong, China.
AD  - Clinical Medical College, Guangzhou Medical University, Guangzhou, Guangdong, 
      China.
AD  - Department of Allergy and Clinical Immunology, The First Affiliated Hospital of 
      Guangzhou Medical University, Guangzhou, Guangdong, China.
FAU - Lin, Zikai
AU  - Lin Z
AD  - Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory 
      Disease, National Clinical Research Centre for Respiratory Disease, National 
      Centre for Respiratory Medicine, Guangzhou, Guangdong, China.
AD  - Clinical Medical College, Guangzhou Medical University, Guangzhou, Guangdong, 
      China.
AD  - Department of Allergy and Clinical Immunology, The First Affiliated Hospital of 
      Guangzhou Medical University, Guangzhou, Guangdong, China.
FAU - Tang, Kailun
AU  - Tang K
AD  - Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory 
      Disease, National Clinical Research Centre for Respiratory Disease, National 
      Centre for Respiratory Medicine, Guangzhou, Guangdong, China.
AD  - Clinical Medical College of Henan University, Zhengzhou, Henan, China.
AD  - Department of Allergy and Clinical Immunology, The First Affiliated Hospital of 
      Guangzhou Medical University, Guangzhou, Guangdong, China.
FAU - Morice, Alyn
AU  - Morice A
AD  - Centre for Clinical Sciences, Hull York Medical School, University of Hull, Hull, 
      UK.
FAU - Li, Shiyue
AU  - Li S
AD  - Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory 
      Disease, National Clinical Research Centre for Respiratory Disease, National 
      Centre for Respiratory Medicine, Guangzhou, Guangdong, China.
AD  - Department of Allergy and Clinical Immunology, The First Affiliated Hospital of 
      Guangzhou Medical University, Guangzhou, Guangdong, China.
FAU - Song, Woo-Jung
AU  - Song WJ
AD  - Department of Allergy and Clinical Immunology, Asan Medical Centre, University of 
      Ulsan College of Medicine, Seoul, South Korea.
FAU - Chen, Ruchong
AU  - Chen R
AD  - Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory 
      Disease, National Clinical Research Centre for Respiratory Disease, National 
      Centre for Respiratory Medicine, Guangzhou, Guangdong, China.
AD  - Department of Allergy and Clinical Immunology, The First Affiliated Hospital of 
      Guangzhou Medical University, Guangzhou, Guangdong, China.
LA  - eng
PT  - Journal Article
DEP - 20230720
PL  - England
TA  - EClinicalMedicine
JT  - EClinicalMedicine
JID - 101733727
PMC - PMC10393600
OTO - NOTNLM
OT  - Efficacy
OT  - Network meta-analysis
OT  - Pharmacotherapy
OT  - Refractory chronic cough
COIS- All authors declare that they have no conflict of interest.
EDAT- 2023/08/04 06:42
MHDA- 2023/08/04 06:43
PMCR- 2023/07/20
CRDT- 2023/08/04 04:03
PHST- 2023/04/15 00:00 [received]
PHST- 2023/06/24 00:00 [revised]
PHST- 2023/06/28 00:00 [accepted]
PHST- 2023/08/04 06:43 [medline]
PHST- 2023/08/04 06:42 [pubmed]
PHST- 2023/08/04 04:03 [entrez]
PHST- 2023/07/20 00:00 [pmc-release]
AID - S2589-5370(23)00277-8 [pii]
AID - 102100 [pii]
AID - 10.1016/j.eclinm.2023.102100 [doi]
PST - epublish
SO  - EClinicalMedicine. 2023 Jul 20;62:102100. doi: 10.1016/j.eclinm.2023.102100. 
      eCollection 2023 Aug.