Characteristics of Traditional Chinese Medicine Use in Children with Asthma: A Nationwide Population-Based Study
Short Title: TCM use in pediatric asthma Authors:
Tzu-Ping Huang1,2*, Pi-Hua Liu3*, Angela Shin-Yu Lien4, Shu-Ling Yang1,2, Heng-Hong Chang1,2, Hung-Rong Yen1,2,5,6,7
* These authors contributed equally to this work. Affiliations:
1Department of Traditional Chinese Medicine, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital; 2Graduate Institute of Traditional Chinese Medicine, School of Traditional Chinese Medicine, 3Clinical Informatics and Medical Statistics Research Center, 4School of Nursing, College of Medicine, and 5Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan. 6Research Center for Traditional Chinese Medicine, Department of Traditional Chinese Medicine and Department of Medical Research, China Medical University Hospital, 7School of Traditional Chinese Medicine, China Medical University, Taichung 404, Taiwan.
Corresponding Author:
Hung-Rong Yen, M.D., Ph.D.
Department of Traditional Chinese Medicine, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital
123 Ding-hu Road, Kweishan, Taoyuan 333, Taiwan Office: +886-3-319-6200 ext 2611
Fax: +886-3-329-8995
E-mail: hungrongyen@gmail.com
ABSTRACT
Asthma is a chronic inflammatory airway disease accounting for severe morbidity and mortality in children. To determine the characteristics of Traditional Chinese Medicine (TCM) used to treat pediatric asthma, we conducted a nationwide population-based study by analyzing a cohort of one million randomly sampled patients from the beneficiaries of the National Health Insurance Program in Taiwan from 2002 to 2010. Children under 18 years of age with newly diagnosed asthma (ICD-9-CM code: 493, N=45,833) were enrolled and 57.95% (N=26,585) of them had used TCM. The number of TCM users was significantly more than non-TCM users in school-aged children. The most commonly prescribed TCM formula is Ding-chuan-tang, or Xing-ren (Semen Armeniacae Amarum) for the single herb. Our study is the first to reveal characteristics and prescription patterns of the use of TCM in children with asthma. Further research is needed to elucidate the efficacy and safety of these Chinese herbal products.
Keywords: Complementary and Alternative Medicine, Pediatric Asthma, Traditional Chinese Medicine.
Introduction
Asthma is one of the most common chronic diseases of childhood. Although there are some international studies on pediatric asthma such as the International Study of Asthma and Allergies in Childhood (ISAAC) , there is a lack of large-scale investigations on the use of Traditional Chinese Medicine (TCM) to treat asthma. Clinical studies on TCM formulas such as Mai-men-dong-tang, Ding-chuan-tang,and anti-asthma herbal medicine intervention (ASHMI) have demonstrated substantial evidences of efficacy and safety in patients with asthma . However, the variety of TCM formulas and herbs makes it difficult to choose a suitable candidate for laboratory or clinical investigations.
In Taiwan, the National Health Insurance (NHI) program covers nearly all of Taiwanese inhabitants since 1996. All claims data were collected in the National Health Insurance Research Database (NHIRD). TCM services including Chinese herbal products (CHPs), acupuncture and manipulative therapies provided by licensed TCM doctors in the outpatient setting are covered by the NHI . To characterize the characteristics of TCM use in children with asthma, we analyzed a randomly sampled cohort of one million beneficiaries from the NHIRD during 2002-2010.
Methods
This study used data from the NHIRD in Taiwan. At the end of 2010, approximately 99.89% of the total 23 million Taiwanese population were enrolled . In this study, a cohort of one million patients was assembled by a random sample of all beneficiaries of the NHI program. The sampled population was representative of all NHI beneficiaries.
31, 2010, there were 227,056 persons under the age of 18. Children without asthma (N =162,826) were excluded, limiting the subjects to asthmatic (ICD-9-CM code: 493) patients only. Children diagnosed with asthma before the end of 2001 (N =18,847) were also excluded to ensure that all subjects had been newly diagnosed after the year 2002. After these criteria were applied, 45,833 study subjects were included in the study cohort. Children with a record of at least one TCM outpatient clinical visit between 2002 and 2010 were defined as TCM users (N=26,558), while children with no recorded TCM outpatient visits during this period were defined as non-TCM users (N=19,275). The CHPs were further categorized according to their therapeutic actions and indications base on TCM theory .
Data analysis consisted of descriptive statistics, including the frequency of prescriptions for TCM users stratified by patients’ demographic characteristics and the most frequently prescribed herbal formulas and herbs for treating pediatric asthma. Primary indications were classified according to their ICD-9-CM codes. The data were analyzed using SAS software, version 9.2 (SAS Institute Inc., Cary, NC, U.S.A.).
Results
Among the 45,833 newly diagnosed asthmatic patients, 57.95% (N=26,585) had used TCM (Table 1). Demographic characteristics of these TCM users versus non-TCM users were listed in Table 1. For school-age children and adolescents, the number of TCM users was significantly more than non-TCM users (P<0.001). The data from 420,058 TCM visits in the TCM user group from 2002 to 2010 were used for further analysis. Approximately 65% of the TCM users had more than three visits during the study period. Local clinics provided the majority of TCM
services (90.14%). The most common modality of TCM treatment was CHPs (344,050 visits; 81.9%), while the remaining visits yielded treatments with acupuncture or manipulative therapies (76,008 visits; 18.09%). Diseases of the respiratory system were the most common indication for TCM use by TCM users (49.2%), followed by diseases diagnosed by symptoms/signs (23.33%) and gastrointestinal diseases (9.07%).
Details of the most commonly prescribed Chinese herbal formulas and single herbs for treating pediatric asthma are provided in Table 2. Among the most common herbal formulas are Ding-chuan-tang (26.93%) and Maxing-gan- shi-tang (13.87%), which are used to treat the Hot Syndrome. Xiao-qing-long-tang (24.92%) and Su-zi-jiang-qi-tang (7.76%) are used to treat the Cold Syndrome. Other formulas have different therapeutic actions and indications for comorbidities, tonification of Qi or releasing the exterior. Of the ten most common single herbs prescribed by TCM doctors, Xing-ren (Semen Armeniacae Amarum; 13.54%) was the most frequently prescribed, followed by Gan-cao (Glycyrrhizae Radix; 11.84%) and Bei-mu (Fritillariae Bulbus; 11.59%).
Discussion
Our study is the first to analyze comprehensive characteristics of TCM use and prescription patterns of CHPs for children with asthma by using a nationwide population-based database. In the study cohort, 57.95% of the patients suffering from asthma had received TCM treatment. Studies on CAM use in children have found that children preferred herbal remedies over acupuncture . Most of the pediatric TCM users in our study also chose to receive CHPs.
Ding-chuan-tang, the most commonly prescribed herbal formula for pediatric asthma, was used to treat the Hot Syndrome. Ding-chuan-tang can inhibit bronchoconstriction and the migration of eosinophils into the airway . It also can improve airway hyper-responsiveness and clinical symptoms in children aged 8-15 years with mild to moderate persistent asthma .The second (Xiao-qing-long-tang) and third (Ma-xing-gan-shi-tang) most commonly prescribed herbal formula for pediatric asthma have proven anti-inflammatory, anti-airway remodeling and immunoregulatory effects in animal models but not in well-designed clinical trials. It is interesting to determine whether these formulas can benefit all asthma patients or only one specific type of asthmatic patients because, in TCM, they are used to treat different types of asthma (the Cold Syndrome versus the Hot Syndrome, respectively.)
Xing-ren (Semen Armeniacae Amarum), the most commonly prescribed single herb in this study, has anti-asthmatic activity by reducing airway hyper-responsiveness and inhibiting the Th2 cells . Other frequently used single herbs have been reported to have anti-asthmatic activity . It is important to integrate the result of our nationwide claims database with those yielded from other pharmacological/chemical screening databases to select the potential herbs for the further investigations.
In conclusion, the use of TCM in children with asthma is popular in Taiwan. Our study provides a comprehensive list of CHPs to guide further high-quality studies in the determination of the safety and efficacy of TCM in children with asthma.
Abbreviations
TCM: Traditional Chinese Medicine; CHP: Chinese Herbal Products; NHI: National Health Insurance; NHIRD: National Health Insurance Research Database; ICD-9-CM: International Classification of Disease, 9th Revision, Clinical Modification
Acknowledgments
This study is based on a portion of data from the National Health Insurance Research Database provided by the Bureau of National Health Insurance, Department of Health, and managed by the National Health Research Institutes in Taiwan. The interpretation and conclusions contained herein do not represent those of the Bureau of National Health Insurance, the Department of Health, or National Health Research Institutes. This research was supported by a grant from the Chang Gung Medical Reach Project (CMRPG1B0051) to TPH. HRY is an investigator of the Chinese Herbal Medicine Research Team supported by a grant from the Healthy Aging Research Center, Chang Gung University (EMRPD1C0311).
Author’s Contributions
HRY, PHL and ASYL conceptualized the study. TPH and PHL performed the statistical analysis. TPH and HRY drafted the manuscript. PHLand HRY finalized the manuscript. SLY, HHC and HRY contributed to the interpretation of the TCM data. All of the authors read and approved the final manuscript.
Conflict of interest
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Table 1. Characteristics of TCM and non-TCM users in children with asthma Characteristics
2002-2010
TCM users Non-TCM users
N (%) N (%) No. of cases 26,558 (57.95) 19,275 (42.05) Gender Female 11,355 (42.76) 8,448 (43.83) Male 15,203 (57.24) 10,827 (56.17) Age, y *
Infant and Toddler, 0-2 4,904 (18.47) 5,978 (31.01)
Preschool, 3-5 10,405 (39.18) 7,897 (40.97)
School age, 6-12 8,923 (33.6) 4,236 (21.98)
Adolescence, 13-18 2,326 (8.76) 1,164 (6.04)
Comorbidity
Allergic rhinitis (AR) * 22,112 (83.26) 13,309 (69.05) Atopic dermatitis (AD) * 9,896 (37.26) 7,933 (41.16)
AR and AD * 8,676 (32.67) 5,979 (31.02)
Number of personal TCM outpatient visits
1-3 9,483 (35.73)
4-6 3,941 (14.84)
7-10 3,138 (11.82)
11-20 4,118 (15.52)
>20 5,864 (22.09)
Accreditation level of hospital
Hospitals 41,448 (9.86)
Local clinics 378,610 (90.14)
Frequency of TCM visits by major disease category
Diseases of respiratory system 206,657 (49.2)
Chronic sinusitis 3,584
Allergic rhinitis 65,909
Asthma 3,931
Symptoms, signs, and ill-defined
conditions 80,665 (19.2)
Diseases of digestive system 31,278 (7.45) *p value between TCM users and non-TCM users < 0.001
Table 2. Ten most common herbal formulas and single herbs prescribed by TCM doctors for the treatment of children with asthma from 2002 to 2010 in Taiwan.
TCM prescription English name or Latin pharmaceutical name Therapeutic actions and indications Frequency of prescription N (%) Average daily dosage (g) Average duration of prescription (day) Herbal formulas
Ding-chuan-tang Panting-Stabilizing Decoction The Hot Syndrome 1,048(26.93) 4.01 8.32 Xiao-qing-long-tang Minor Green-Blue Dragon Decoction The Cold Syndrome 970(24.92) 3.33 12.52 Ma-xing-gan-shi-tangEphedra, Apricot Kernel, Licorice, and
Gypsum Decoction
The Hot Syndrome 540(13.87) 3.33 8.34 Xin-yi-san Magnolia Flower Powder Comorbidities (AR) 453(11.64) 3.44 14.57 Xin-yi-qing-fei-tang Magnolia Flower Lung-Clearing Decoction Comorbidities (AR) 350 (8.99) 3.11 10.12 Su-zi-jiang-qi-tang Perilla Fruit Qi-Downbearing Decoction The Cold Syndrome 302 (7.76) 5 7.44 Cang-er-san Xanthium Powder Comorbidities (AR) 265 (6.81) 2.98 10.16 Xiang-sha-liu-jun-zi-tang Costusroot and Amomum Six Gentlemen Decoction Tonification of Qi 257 (6.60) 2.35 15.03 Yu-ping-feng-san Jade Wind-Barrier Powder Tonification of Qi 220 (5.65) 2.91 10.53 Ge-gen-tang Pueraria Decoction Releasing theExterior 191 (4.91) 3.32 16.33 Single Herbs
Xing-ren Semen Armeniacae
Amarum Panting-calming 527(13.54) 0.93 9.66
Gan-cao Glycyrrhiza uralensis Panting-calming 461(11.84) 0.69 8.26 Bei-mu Fritillariae Bulbus transformationPhlegm 451(11.59) 0.84 8.4 Yu-xing-cao Houttuynia cordata Anti-allergic effect 283 (7.27) 1.03 9.74 Jie-geng Platycodons Radix transformationPhlegm 263 (6.76) 0.77 8.21 Ting-li-zi SemenLepidii Semen
Desurainiae Panting-calming 252 (6.47) 0.78 8.03
Wu-mei Mume Fructus Anti-allergic effect 225 (5.78) 0.65 10.27 Hou-po Magnoliae Officinalis Cortex Panting-calming 219 (5.63) 0.9 11.58 Chan-tui Cicadae Periostracum Anti-allergic effect 219 (5.63) 0.81 10.05
