Association of Ambroxol Hydrochloride and Clenbuterol Hydrochloride Oral Solution with Respiratory Symptom Improvement and Safety in Chinese Children with Pneumonia: A Real-World Propensity Score–Matched Study

Ying Liang,1,* Yesheng Ling,1,* Bing Hu,2 Yingxue Zou,3 Enmei Liu,4 Jinhai Ma,5 Changshan Liu,6 Quan Lu,7 Xiaoyan Dong,7 Huifen Zi,8 Chuangli Hao,9 Rongjun Lin,10 Xiangrong Zheng,11 Bingfei Li,12 Lingping Zhu,1 Mei Fang,13 Weimin Tian,14 Zhiqiang Zhuo,15 Deyu Zhao,16 Zhimin Chen,17 Yuejie Zheng,18 Jingyang Zheng,19 Yong Yin,20 Qiuyu Tang,21 Liqun Wu,22 Li Gu,23 Jinzhun Wu,24 Liyi He,25 Tao Ai,26 Ning Wang,27 Minjun Zhang,28 Hailin Zhang,29 Hanmin Liu,30 Youxiang Zhang,31 Jianguo Hong,32 Zhiying Han,33 Yunbo Mo,34 Hongmei Qiao,35 Zhiliang Tian,36 Lixia Li,1 Pingping Zhang11Department of Pediatrics, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China; 2Department of Pediatrics, Yichun People’s Hospital, Yichun, 336000, People’s Republic of China; 3Department of Pulmonology, Tianjin Children’s Hospital (Tianjin University Children’s Hospital), Tianjin, 300074, People’s Republic of China; 4Department of Respiratory Medicine, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China; 5Department of Pediatrics, General Hospital of Ningxia Medical University, Yinchuan, 750004, People’s Republic of China; 6Department of Pediatrics, The Second Hospital of Tianjin Medical University, Tianjin, 300211, People’s Republic of China; 7Department of Pulmonology, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, People’s Republic of China; 8Department of Pediatrics, Baotou Central Hospital, Baotou, 014040, People’s Republic of China; 9Department of Respiratory Medicine, Children’s Hospital of Soochow University, Suzhou, 215003, People’s Republic of China; 10Department of Pediatrics, The Affiliated Hospital of Qingdao University, Qingdao, 266100, People’s Republic of China; 11Department of Pediatrics, Xiangya Hospital Central South University, Changsha, 410008, People’s Republic of China; 12Department of Pediatrics, Ganzhou Women and Children’s Health Care Hospital, Ganzhou, 341000, People’s Republic of China; 13Department of Pediatrics, Xiamen Medical College Affiliated Haicang Hospital, Xiamen, 361026, People’s Republic of China; 14Department of Pediatrics, Shanghai Public Health Clinical Center, Shanghai, 201500, People’s Republic of China; 15Department of Infectious Diseases, Xiamen Hospital (Xiamen Children’s Hospital), Children’s Hospital of Fudan University, Xiamen, 361006, People’s Republic of China; 16Department of Respiratory Medicine, Children’s Hospital of Nanjing Medical University, Nanjing, 210008, People’s Republic of China; 17Department of Pulmonology, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, People’s Republic of China; 18Department of Respiratory Disease, Shenzhen Children’s Hospital, Shenzhen, 518038, People’s Republic of China; 19Department of Respiratory Disease, Quanzhou Municipal Children’s Hospital, Quanzhou, 362000, People’s Republic of China; 20Department of Respiratory Disease, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, People’s Republic of China; 21Department of Respiratory, Fujian Branch of Shanghai Children’s Medical Center, Fujian Children’s Hospital, Fuzhou, 350014, People’s Republic of China; 22Department of Pediatrics, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, People’s Republic of China; 23Department of Pediatrics, Shanghai Tenth People’s Hospital, Shanghai, 200072, People’s Republic of China; 24Department of Pediatrics, Women and Chilren’s Hospital, School of Medicine, Xiamen University, Xiamen, 361003, People’s Republic of China; 25Department of Pediatrics, The First People’s Hospital of Foshan, Foshan, 528000, People’s Republic of China; 26Department of Pediatric Respiratory Medicine, Chengdu Women and Children’s Central Hospital, Chengdu, 610073, People’s Republic of China; 27Respiratory Asthma Center, Xi’an Children’s Hospital, Xi’an, 710003, People’s Republic of China; 28Department of Pediatrics, Fujian Maternity and Child Health Hospital, Fuzhou, 350001, People’s Republic of China; 29Department of Pediatric Respiratory Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China; 30Department of Pediatric Pulmonology and Immunology, West China Second University Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 31Department of Pediatrics, Guangzhou First People’s Hospital, Guangzhou, 510180, People’s Republic of China; 32Department of Pediatrics, Shanghai General Hospital, Shanghai, 200080, People’s Republic of China; 33Department of Respiratory Medicine, Shanxi Children’s Hospital, Taiyuan, 030001, People’s Republic of China; 34Department of Children’s Respiratory, Chongqing University Three Gorges Hospital, Chongqing, 404000, People’s Republic of China; 35Department of Pediatric Respiratory, The First Hospital of Jilin University, Changchun, 130021, People’s Republic of China; 36Department of Pediatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Pingping Zhang, Department of Pediatrics, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou, 510630, People’s Republic of China, Email [email protected] Lixia Li, Department of Pediatrics, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou, 510630, People’s Republic of China, Email [email protected]: To evaluate the association of ambroxol hydrochloride and clenbuterol hydrochloride oral solution (AHCHOS) with respiratory symptom improvement and safety in Chinese children with pneumonia using real-world data.Methods: A propensity score-matched (PSM) cohort study was conducted. Children patients (≤ 14 years) with a diagnosis of pneumonia between May, 2018 and July, 2019 were considered as the study population. The main outcome of interest was the overall rate of improvement of respiratory symptoms in treatment groups with or without AHCHOS at day 7 using respiratory symptom scores (QS) and Visual Analog Scale (VAS) score of severity of respiratory signs. Secondary end points include medication adherence assessment and safety assessment.Results: A total of 3103 children with a diagnosis of pneumonia were included. After propensity score matching, a sample of 1428 patients was analyzed. AHCHOS use was associated with greater improvement in cough score (p=0.01) and day 7 clinical sign improvement rate (p=0.03) compared with no AHCHOS use. Exploratory subgroup analyses suggested larger differences in children aged 3– 6 years and in selected severity strata. Medication adherence assessmentdid not differ significantly between groups at days 4, 7, 14, and 28. Adverse events were similar between groups.Conclusion: In this real-world propensity score-matched analysis, AHCHOS use was associated with improved respiratory symptom outcomes in children with pneumonia and appeared to have an acceptable safety profile. These findings should be interpreted as observational and hypothesis-generating.Trial Registration Number: The study was registered at Chinese Clinical Trial Registry (https://www.chictr.org.cn/, ChiCTR1800015818).Keywords: ambroxol hydrochloride and clenbuterol hydrochloride, childhood pneumonia, respiratory symptom scores, safety assessment, real-world