Original Article
Adjunctive Traditional Chinese Medicine Therapy for Patients with Chronic
Rhinosinusitis: A Population-based Study
Authors
Hung-Rong Yen, MD, PhD 1,2,4,5, Mao-Feng Sun, MD, PhD 2,4,5, Cheng-Li Lin, MSc 3,
Fung-Chang Sung, PhD, MPH 6, Chen-Chi Wang, MD 7,8, Kai-Li Liang, MD 7,8,9
Affiliations
1
Research Center for Traditional Chinese Medicine, Department of Medical Research,
2
Department of Chinese Medicine, 3 Health Data Management Office, China Medical
University Hospital, Taichung, Taiwan; 4 Chinese Medicine & Acupuncture Research
Center, 5 School of Chinese Medicine, 6 Graduate Institute of Clinical Medical Science,
China Medical University, Taichung, Taiwan;
7
Department of Otolaryngology,
Taichung Veterans General Hospital, Taichung, Taiwan;
8
Department of Medicine,
National Yang-Ming Medical University, Taipei, Taiwan;
Chung Shan Medical University, Taichung, Taiwan
Running title: Chinese medicine for chronic rhinosinusitis
Address for correspondence: Kai-Li Liang, M.D.
9
School of Medicine,
Department of Otolaryngology, Taichung Veterans General Hospital,
1650, Sect. 4, Taiwan Boulevard, Taichung 40705, Taiwan.
Tel: +886-4-23592525 ext. 5405
Fax: +886-4-23596868
E-mail: kelly1107@vghtc.gov.tw; kellyliang1107@gmail.com
ABSTRACT
Background Chronic rhinosinusitis (CRS) is a chronic illness with a high prevalence
worldwide. The purpose of this study was to investigate the characteristics of
adjunctive traditional Chinese medicine (TCM) use in patients with CRS.
Methods Data were retrieved from a dataset made available by the Taiwan National
Health Insurance Research Database containing the medical records of 1,000,000
randomly sampled beneficiaries insured in the year 2000. Patients newly diagnosed
with CRS in the year 2000 were enrolled, and their medical records during the period
2000-2011 were collected and analyzed.
Results A total of 14,806 CRS subjects were enrolled in this study: 10,512 were
non-TCM users and 4.294 were TCM users. TCM group had a significantly higher
proportion of females, were younger, and a greater proportion lived in urban areas
compared with the non-TCM group (all p < 0.0001). Ninety-seven percent of the
TCM users received herbal remedies. The most common Chinese herbal formula used
was Xin-Yi-Qing-Fei-Tang and the most commonly used single herb was Baizhi. The
hazard ratio for endoscopic sinus surgery (ESS) was 0.17 for TCM users (95% CI
=0.15 - 0.20) compared with non-TCM users after adjusting for age, sex, urbanization,
and co-morbidities.
Conclusions Our investigation found that 29% of CRS patients used TCM in addition
to Western medical treatment. A lower proportion of patients in the TCM group
underwent ESS compared with that in the non-TCM group. These findings may be of
value in further studies evaluating the efficacy and safety of TCM use in CRS
patients.
INTRODUCTION
Chronic rhinosinusitis (CRS) is a chronic illness with a prevalence of 10.9% in
Europe and 13-17% in the United States,
1, 2
which places a tremendous burden on the
patients and healthcare system.3 It is estimated that rhinosinusitis contributed to the
majority of 257,000 sinus surgeries in 2006 and an average loss of 5.67 workdays per
year (similar to that of acute asthma) in the United States.4, 5 Furthermore, it is often
related to allergies and should be taken into account by healthcare providers treating
allergic diseases due to its significant impact on lower airway diseases such as
bronchiectasis and asthma.6, 7
Although a number of international studies on CRS have been conducted such as
the GA²LEN study in Europe
Survey in the United States,
1
8
and the National Health and Nutrition Examination
large-scale surveys on the use of complementary and
alternative medicine (CAM) to treat CRS are lacking. CAM has grown in popularity
in many countries. It is believed that use of CAM is particularly prevalent among
patients
with
allergic
disorders
or
rhinosinusitis
particularly.9,10
Previous
questionnaire surveys and telephone interviews revealed that 65% of Scottish patients
in a rhinology clinic,11 42% of Californian adults with asthma or rhinosinusitis,12
15.6% of Canadian patients with CRS,13 and 21% of Israeli patients with CRS14 have
used CAM as a treatment modality.
Our previous study, which employed a questionnaire-based survey to evaluate
CRS
patients
in
a
medical
center,
found
that
34.4%
patients
with
rhinitis/rhinosinusitis had used Traditional Chinese Medicine (TCM). 15 TCM is an
important part of CAM as defined by the National Center for Complementary and
Alternative Medicine (NCCAM, U.S.A.), and has been a mainstay of treatment
modalities for many conditions and diseases in Asian countries for several
millennia.16 We have previously established TCM use in adults and children in
Taiwan based on nationwide population-based epidemiological data.17,
18
We also
explored the characteristics of TCM usage in patients with allergic disorders such as
asthma
19
and atopic dermatitis
20
in a large-scale study. However, the existing
knowledge of TCM use among patients with CRS is limited and thus comprehensive
studies to investigate the issue are necessary. While current conventional medications
and endoscopic sinus surgery (ESS) can alleviate most symptoms of CRS, 2, 21 there
are 10 -20% of CRS cases are recalcitrant to current treatment.22
In an effort to fill in gaps in our knowledge and to extend our understanding of
the
effect
of
TCM
in
the
treatment
of
CRS,
we
investigated
the
pharmaco-epidemiological data of adjunctive TCM use in patients with CRS and
determined whether this adjunction of TCM could minimize the need for surgery by
analyzing a cohort of one million national health beneficiaries randomly sampled
from the National Health Insurance Research Database (NHIRD) in Taiwan. This data
set is a nationwide population-based claims database with long-term follow-up. The
representative data from this claims database were also generalizable to the
population as a whole, and thus the potential for sampling bias was reduced to a
minimum.
MATERIALS AND METHODS
Data source
In this study, a dataset obtained from the National Health Insurance Research
Database (NHIRD) in Taiwan was analyzed. Taiwan launched the National Health
Insurance Program in March 1995. Western medical treatment as well as TCM
therapies have been available on Taiwan's NHI system since 1996.18 Approximately
23 million enrollees, comprising 99.89% of the total Taiwan’s population, were
covered by the program at the end of 2010.23 The NHIRD is a repository of health
insurance registration files and original claims data of all beneficiaries in the NHI
program, and anonymized datasets are made available for scientific research. In this
study, we investigated TCM use in patients with CRS in Taiwan using data from a
cohort of 1,000,000 persons enrolled in 2000 who were randomly sampled from the
NHIRD (Longitudinal Health Insurance Database 2000; LHID 2000). This study was
approved by the Institutional Review Board of China Medical University and Hospital
(CMU-REC-101-012). The data files were de-identified and further scrambled before
being released to researchers in accordance with privacy protocols. Thus, it was not
possible to query the data to identify individuals at any level using this database.
Study Subjects
The medical records and reimbursement claims of the sampled enrollees were
collected from January 2000 to December 2011. The data collection flowchart is
shown in Figure 1. The International Classification of Diseases, 9th Revision, Clinical
Modification (ICD-9-CM) and Procedure Coding System (ICD-9-PCS) were used to
establish patients’ diagnoses and treatment. We identified CRS cases (ICD-9-CM code:
473) from LHID 2000 who were newly diagnosed in the year 2000 and these patients
served as the study cohort. Patients who had been diagnosed as CRS before 2000, had
incomplete medical information, or were under 20 years old were excluded. All
enrolled cases were required to have been diagnosed with CRS by a Western medicine
doctors in the first instance, followed by outpatient visits to either Western medicine
or TCM doctors for CRS treatment at least twice. Four allergic diseases, common
co-morbidities of CRS (allergic rhinitis ICD-9: 477; asthma ICD-9: 493; atopic
dermatitis ICD-9: 691; urticaria (ICD-9: 708), were also identified in the study cohort.
The demographic information and claims data of the study cohort were collected
and analyzed. Those patients receiving TCM consultation, acupuncture, or herbal
treatment for CRS were considered to be TCM users. Otherwise, they were identified
as non-TCM users. Residence areas of the study cohort were divided into 4 levels of
urbanization which were defined by various criteria, including population density
(people/km2), the population ratio of different educational level, ratio of elderly
people, ratio of people of agriculture workers, and the number of physicians per
100,000 people.24 Level 1 had the highest degree of urbanization and level 4 had the
lowest. Urbanization levels 1 and 2 were defined as urban areas, while levels 3 and 4
were classified as rural areas.
Statistical Analysis
SAS software version 9.1 (SAS Institute, Inc., Cary, NC, USA) was used for
statistical analyses. The independent t-test was utilized to examine differences in age
between two groups. The Chi-square test was used to test for differences in sex,
urbanization status, and comorbidities between TCM and non-TCM users. A Cox’s
Proportional Hazards regression model was used to estimate the hazard ratio (HR) of
subsequent ESS between TCM users and non-TCM users, after adjustment for age,
sex, urbanization, and co-morbidities. A two-sided p of < 0.05 was considered
statistically significant.
RESULTS
Characteristics of study subjects
A total of 14,806 subjects who were newly diagnosed with CRS in the year 2000 were
included in the analysis (Table 1). Among them, 10,512 did not use TCM for
treatment of CRS in the follow-up period, and 4,294 had used adjunctive TCM
treatment for their CRS. TCM users were more likely to be female, younger, and
resident in an urban area (all p < 0.0001). The prevalence of allergic co-morbidities
was high in the study cohort. There were significantly more allergic rhinitis patients in
the TCM group and more asthmatic patients in the non-TCM group (both p < 0.0001).
Traditional Chinese Medicine prescription patterns for CRS
Most of the TCM users received herbal treatment, whereas only a few of them
underwent acupuncture. About 39% of the TCM users visited an outpatient
department more than 3 times (Table 2). The herbal prescription patterns are listed in
Table
3.
The
most
commonly prescribed
Chinese
herbal
formula
was
“Xin-Yi-Qing-Fei-Tang” (Magnolia Flower and Gypsum Combination), followed by
“Xiao-Qing-Long-Tang” (Minor Blue-green Dragon Decoction), “Xin-Yi-San”
(Magnolia Flower Powder), “Cang-Er-San” (Xanthium Powder) and “Ge-Gen-Tang”
(Pueraria Combination). The frequently used single herbs prescribed for CRS were
Baizhi (Radix Angelicae Dahuricae), Yuxingcao (Herba Houttuyniae), Jiegeng (Radix
Platycodi), Cangerzi (Fructus Xanthii), and Huangqin (Radix Scutellariae).
Hazard ratio of subsequent endoscopic sinus surgery (ESS)
Among the 10,512 non-TCM users, 2,226 underwent ESS during the study period.
However, only 176 TCM users underwent ESS for CRS treatment. A Cox’s regression
model was used to analyze the risk factors for ESS. The hazard ratio for ESS was 0.17
for TCM users (95% CI =0.15 - 0.20) compared with the non-TCM users after
adjusting for age, sex, urbanization, and co-morbidities (Table 4).
DISCUSSION
In this study, we analyzed a randomly sampled cohort of 1,000,000 persons
enrolled in the National Health Insurance program in Taiwan and investigated the
prevalence, demographic data, comorbidity of allergic disorders, prescription patterns,
and subsequent ESS among TCM and non-TCM users with CRS. The high prevalence
of CAM use in patients with CRS that was found in previous studies was determined
by questionnaires and interviews.9, 11-14 Previously, the GA(2)LEN study revealed a
strong association of CRS, asthma and allergic rhinitis.7,
8, 25
Ours and other’s
previous nationwide population-based studies have also characterized TCM use in
patients with allergic disorders such as asthma19 and allergic rhinitis.26 Herein, we
extended the current knowledge to examine TCM use among patients with CRS. We
identified that Xin-Yi-Qing-Fei-Tang (Magnolia Flower and Gypsum Combination)
and Baizhi (Radix Angelicae Dahuricae) were the most commonly used TCM herbal
formula and single herb, respectively. Those patients conjunctively used TCM had a
decreased need for subsequent ESS. This investigation is the first comprehensive
analysis of TCM use in patients with CRS.
Clinical diagnosis of CRS includes the presence of more than two of the
following symptoms: nasal blockage/obstruction/congestion, nasal discharge, facial
pain/pressure or reduction/loss of smell, plus either endoscopic signs or CT changes.2
Our investigation analyzed patients who were diagnosed with CRS by a Western
medicine doctor and who visited an outpatient clinic for follow-up (more than three
visits in total) in order to minimize selection bias and to ensure that similar disease
entities existed in TCM and non-TCM users. In the nationwide population-based
study cohort, nearly one-third of the patients had used TCM in conjunction with
Western medicine for their CRS. This is in line with the prevalence rates reported in
previous studies of CAM use among rhinosinusitis patients (range from 15.6% to
65%).11-14
In addition, we found that TCM users were significantly more likely to be female,
younger, and to have better access to medical resources (i.e., resident in an urban
area). Several studies have reported that females are more likely to use CAM.27, 28
This is also in accordance with a previous general population study indicating that
female gender, high socioeconomic status, and higher education levels were
associated with greater prevalence of TCM use.29
Although TCM
has
been
used
for
millennia in
the treatment
of
otorhinolaryngological conditions, 30 few randomized controlled studies on the use of
TCM herbs in rhinology have been published. Our recent randomized-controlled
study demonstrated that Chinese herbal remedies (Tsang-Erh-San and Yuxingcao)
had an efficacy similar to that of macrolides in the treatment of CRS without nasal
polyps.31 However, selection of an optimal herbal formula and single herb for a
clinical investigation is difficult due to the individualized nature of TCM treatment. In
this study, we further comprehensively analyzed the most commonly prescribed TCM
formulas and single herbs to establish a consensus of effective remedies for CRS. In
the literature, the benefits of TCM herbal formulae have been demonstrated in a
number of in vivo and animal experiments, as follows: “Xiao-Qing-Long-Tang” can
inhibit Th2 cytokines production and suppress histamine signaling, therefore reducing
allergic inflammation;32 “Ge-Gen-Tang” and “Long-Dan-Xie-Gan-Tang” have
anti-viral activities;33, 34 “Bu-Zhong-Yi-Qi-Tang” can reduce IgE production and has
an anti-allergic effect.35 Individual herbs including Cangerzi (Fructus Xanthii) and
Xinyi (Flos Magnoliae) have anti-allergic and anti-oxidative effects;36,
37
Baizhi
(Radix Angelicae Dahuricae) exhibits anti-microbial and cyclooxygenase-2
inhibition.38, 39 We found that 5 out of the top 10 TCM formulae for CRS were also
the most common TCM prescription for allergic rhinitis in Taiwan.26 The high
prevalence of comorbid allergic rhinitis in TCM users in the study cohort could
explain
at
least
in
part
this
commonality.
Surprisingly,
although
Xin-Yi-Qing-Fei-Tang has been frequently used for allergic rhinitis 26 and CRS in our
study, no high-quality randomized clinical trial has been conducted to date.
Multiple etiologies have been associated with the development of CRS,
including impaired mucociliary function, allergy, anatomic abnormalities, infection,
and environmental pollutants. The aforementioned factors contribute to chronic
inflammation in the nose and paranasal sinuses.2 The therapeutic effects of
acupuncture for CRS possibly result from reduced mucosal congestion and improved
mucociliary function.40 A randomized, double-blinded study with a small number of
patients demonstrated that acupuncture reduced nasal obstruction and improved the
results of rhinomanometry.41 A previous study conducted in California found that
acupuncture appeared to show good efficacy in the treatment of patients with chronic
sinus and nasal symptoms.42 Two studies compared the quality of life of CRS patients
who received acupuncture, sham acupuncture, or conventional medical treatment
(saline irrigation, antibiotics, oral steroids, and nasal decongestants) and both
demonstrated that there were no significant differences among the 3 groups.43, 44 The
limited effect of acupuncture in the present study may reflect the very small
percentage of patients who received acupuncture treatment and thus further
investigations are warranted.
ESS is the current standard surgical management for adult rhinosinusitis that
failed to respond to more conservative medical treatment.21 In this study, a
significantly lower proportion of patients who received adjunctive TCM treatment
underwent ESS compared to those patients who received Western medicine alone.
Although possible confounding factors (age, sex, urbanization and allergic
co-morbidities) were adjusted, we understand the disease severity at baseline could
not be evaluated in the NHIRD. However, patients who received combined treatment
might be reasonably postulated to have had a lower rate of medical treatment failure.
Our previous questionnaire-based survey revealed that rhinitis patients with worse
disease-specific quality of life had higher utilization of combined TCM treatment.15
An earlier questionnaire-based survey in 2002 conducted in Taiwan also indicated
that patients with self-reported poor health status tended to be more likely to visit a
TCM clinic.45 A nationwide study conducted in the U.S. revealed that most of the
study subjects used alternative therapies in conjunction with conventional medicine;
only a few of them relied primarily on alternative therapies. The use of alternative
therapies was not a result of dissatisfaction with conventional medicine; rather, the
CAM treatments were more congruent with their values and beliefs with respect to
health.
46
The better satisfaction in patients receiving combined Western and
alternative therapies may tend to make them more likely to decline further surgical
management.
It is important to note that difficult-to-treat rhinosinusitis does exist
and CRS is usually associated with allergic disorders.7, 25, 47, 48 As a recent pilot study
demonstrated, an integrated approach using Western and Eastern medicine may
improve the symptoms and quality of life of patients with recalcitrant CRS.49 Given
that adjunctive TCM treatment appears to have the potential to reduce the risk of
refractory CRS, further validation by high-quality clinical trials are warranted.
There were several potential limitations in our study. First, although the database
provides complete claims data of the enrolled subjects, factors such as disease
severity and smoking habit were not provided in the database. However, all patients
were diagnosed by Western medical doctors and visited the outpatient department for
follow-up at least three times, which minimized the bias in diagnosis. Second, the
allocation of TCM or non-TCM use was also based on the patients’ own request and
preferences. As shown in our previous survey and in other studies, adjunctive TCM
users might have worse disease severity or health status.15,
45
Studies have also
suggested patients with allergies are motivated to use CAM as a result of
dissatisfaction with conventional medication.10 Although our study suggested that
adjunctive TCM use could reduce the risk of subsequent ESS, further randomized
controlled clinical trials are necessary to confirm this finding.
CONCLUSION
Our investigation found that 29% of CRS patients used TCM in conjunction with
Western medicine. Xin-Yi-Qing-Fei-Tang and Baizhi (Radix Angelicae Dahuricae)
were the most commonly used TCM formula and single herb, respectively, for CRS.
Adjunctive TCM use might reduce the need for ESS. These data suggest that
adjunctive TCM treatment may provide an alternative choice of therapy to improve
CRS symptoms. Further investigations to evaluate the efficacy and safety of
adjunctive TCM treatment are warranted.
Abbreviations
CAM: complementary and alternative medicine; CRS: chronic rhinosinusitis; FESS:
functional endoscopic sinus surgery; NHIRD: National Health Insurance Research
Database TCM: Traditional Chinese Medicine; ICD-9-CM: the International
Classification of Diseases, 9th Revision, Clinical Modification; ICD-9-PCS: the
International Classification of Diseases, 9th Revision, Procedure Coding System.
Acknowledgments
This study was supported by China Medical University under the Aim for Top
University Plan of Taiwan’s Ministry of Education. This study was also supported in
part by Taiwan Ministry of Health and Welfare Clinical Trial and the Research Center
of Excellence (MOHW103-TDU-B-212-113002). Yen H-R. is supported by a
physician scientist grant (DMR-103-123) from China Medical University Hospital
and a career-developing grant (NHRI-EX101-10124SC, NHRI-EX102-10124SC and
NHRI-EX103-10124SC) from the National Health Research Institutes, Taiwan. This
study was based in part on data from the National Health Insurance Research
Database provided by the National Health Insurance Administration, Ministry of
Health and Welfare and managed by the National Health Research Institutes. The
interpretation and conclusions contained herein do not necessarily represent those of
the National Health Insurance Administration, Ministry of Health and Welfare or the
National Health Research Institutes.
Authors’ Contributions
HRY and KLL conceptualized the study. CLL and FCS performed the statistical
analysis. HRY and KLL drafted the manuscript and finalized the manuscript. HRY
and MFS contributed to the interpretation of TCM data. CCW and KLL interpreted
the data of Western medicine and surgical procedures. All of the authors read and
approved the final manuscript.
Conflicts of interest
The authors declare that they have no conflicts of interest.
REFERENCES
1.
Adams PF, Heyman KM, Vickerie JL. Summary health statistics for the U.S.
population: National Health Interview Survey, 2008. Vital Health Stat 10 2009:1-104.
2.
Fokkens WJ, Lund VJ, Mullol J, et al. European Position Paper on Rhinosinusitis
and Nasal Polyps 2012. Rhinol Suppl 2012:3 p preceding table of contents, 1-298.
3.
Sahlstrand-Johnson P, Ohlsson B, Von Buchwald C, et al. A multi-centre study
on quality of life and absenteeism in patients with CRS referred for endoscopic
surgery. Rhinology 2011;49:420-428.
4.
Bhattacharyya N. Contemporary assessment of the disease burden of sinusitis.
Am J Rhinol Allergy 2009;23:392-395.
5.
Bhattacharyya N. Ambulatory sinus and nasal surgery in the United States:
demographics and perioperative outcomes. Laryngoscope 2010;120:635-638.
6.
Guilemany JM, Angrill J, Alobid I, et al. United airways: the impact of chronic
rhinosinusitis and nasal polyps in bronchiectasic patient's quality of life. Allergy
2009;64:1524-1529.
7.
Jarvis D, Newson R, Lotvall J, et al. Asthma in adults and its association with
chronic rhinosinusitis: the GA2LEN survey in Europe. Allergy 2012;67:91-98.
8.
Hastan D, Fokkens WJ, Bachert C, et al. Chronic rhinosinusitis in Europe--an
underestimated disease. A GA(2)LEN study. Allergy 2011;66:1216-1223.
9.
Sibbritt D, Adams J, Lui CW, et al. Health services use among young Australian
women with allergies, hayfever and sinusitis: a longitudinal analysis. Complement
Ther Med 2012;20:135-142.
10. Li XM. Complementary and alternative medicine in pediatric allergic disorders.
Curr Opin Allergy Clin Immunol 2009;9:161-167.
11. Newton JR, Santangeli L, Shakeel M, et al. Use of complementary and
alternative medicine by patients attending a rhinology outpatient clinic. Am J Rhinol
Allergy 2009;23:59-63.
12. Blanc PD, Trupin L, Earnest G, et al. Alternative therapies among adults with a
reported diagnosis of asthma or rhinosinusitis : data from a population-based survey.
Chest 2001;120:1461-1467.
13. Rotenberg BW, Bertens KA. Use of complementary and alternative medical
therapies for chronic rhinosinusitis: a canadian perspective. J Otolaryngol Head Neck
Surg 2010;39:586-593.
14. Yakirevitch A, Bedrin L, Migirov L, et al. Use of alternative medicine in Israeli
chronic rhinosinusitis patients. J Otolaryngol Head Neck Surg 2009;38:517-520.
15. Koo M, Liang KL, Tsao H, et al. Factors Associated with the Use of Different
Treatment Modalities among Patients with Upper Airway Diseases in Taiwan: A
Cross-Sectional Survey Study. J Allergy (Cairo) 2013;2013:720879.
16. Park HL, Lee HS, Shin BC, et al. Traditional medicine in china, Korea, and
Japan: a brief introduction and comparison. Evid Based Complement Alternat Med
2012;2012:429103.
17. Huang TP, Liu PH, Lien AS, et al. A nationwide population-based study of
traditional Chinese medicine usage in children in Taiwan. Complement Ther Med
2014;22:500-510.
18. Yen HR, Huang TP, Sun MF. Chinese medicine usage in Taiwan: a nationwide
population-based study. RCHM Journal 2013;10:21-27.
19. Huang TP, Liu PH, Lien AS, et al. Characteristics of traditional Chinese
medicine use in children with asthma: a nationwide population-based study. Allergy
2013;68:1610-1613.
20. Lin JF, Liu PH, Huang TP, et al. Characteristics and prescription patterns of
traditional Chinese medicine in atopic dermatitis patients: ten-year experiences at a
medical center in Taiwan. Complement Ther Med 2014;22:141-147.
21. Khalil HS, Nunez DA. Functional endoscopic sinus surgery for chronic
rhinosinusitis. Cochrane Database Syst Rev 2006:CD004458.
22. Woodbury K, Ferguson BJ. Recalcitrant chronic rhinosinusitis: investigation and
management. Curr Opin Otolaryngol Head Neck Surg 2011;19:1-5.
23. Insurance BoNH. The National Health Insurance Annual Statistical Report, 2010.
Bureau of National Health Insurance, Taipei, Taiwan;2010.
24. Liu CY, Hung YT, Chuang YL, et al. Incorporating development stratification of
Taiwan townships into sampling design of large scale health interview survey (in
Chinese). J Health Manag 2006;4:1-22.
25. Hellings PW, Fokkens WJ, Akdis C, et al. Uncontrolled allergic rhinitis and
chronic rhinosinusitis: where do we stand today? Allergy 2013;68:1-7.
26. Kung YY, Chen YC, Hwang SJ, et al. The prescriptions frequencies and patterns
of
Chinese
herbal
medicine
for
allergic
rhinitis
in
Taiwan.
Allergy
2006;61:1316-1318.
27. Wolsko PM, Eisenberg DM, Davis RB, et al. Insurance coverage, medical
conditions, and visits to alternative medicine providers: results of a national survey.
Arch Intern Med 2002;162:281-287.
28. Neiberg RH, Aickin M, Grzywacz JG, et al. Occurrence and co-occurrence of
types of complementary and alternative medicine use by age, gender, ethnicity, and
education among adults in the United States: the 2002 National Health Interview
Survey (NHIS). J Altern Complement Med 2011;17:363-370.
29. Shih CC, Liao CC, Su YC, et al. Gender differences in traditional Chinese
medicine use among adults in Taiwan. PLoS One 2012;7:e32540.
30. Yap L, Pothula VB, Warner J, et al. The root and development of
otorhinolaryngology in traditional Chinese medicine. Eur Arch Otorhinolaryngol
2009;266:1353-1359.
31. Jiang RS, Wu SH, Tsai CC, et al. Efficacy of Chinese herbal medicine compared
with a macrolide in the treatment of chronic rhinosinusitis without nasal polyps. Am J
Rhinol Allergy 2012;26:293-297.
32. Kao ST, Lin CS, Hsieh CC, et al. Effects of xiao-qing-long-tang (XQLT) on
bronchoconstriction and airway eosinophil infiltration in ovalbumin-sensitized guinea
pigs: in vivo and in vitro studies. Allergy 2001;56:1164-1171.
33. Wu MS, Yen HR, Chang CW, et al. Mechanism of action of the suppression of
influenza
virus
replication
by
Ko-Ken
Tang
through
inhibition
of
the
phosphatidylinositol 3-kinase/Akt signaling pathway and viral RNP nuclear export. J
Ethnopharmacol 2011;134:614-623.
34. Cheng HY, Huang HH, Yang CM, et al. The in vitro anti-herpes simplex virus
type-1 and type-2 activity of Long Dan Xie Gan Tan, a prescription of traditional
Chinese medicine. Chemotherapy 2008;54:77-83.
35. Ishimitsu R, Nishimura H, Kawauchi H, et al. Dichotomous effect of a
traditional Japanese medicine, bu-zhong-yi-qi-tang on allergic asthma in mice. Int
Immunopharmacol 2001;1:857-865.
36. Huang MH, Wang BS, Chiu CS, et al. Antioxidant, antinociceptive, and
anti-inflammatory activities of Xanthii Fructus extract. J Ethnopharmacol
2011;135:545-552.
37. Shen Y, Pang EC, Xue CC, et al. Inhibitions of mast cell-derived histamine
release by different Flos Magnoliae species in rat peritoneal mast cells. Phytomedicine
2008;15:808-814.
38. Lin CH, Chang CW, Wang CC, et al. Byakangelicol, isolated from Angelica
dahurica, inhibits both the activity and induction of cyclooxygenase-2 in human
pulmonary epithelial cells. J Pharm Pharmacol 2002;54:1271-1278.
39. Lechner D, Stavri M, Oluwatuyi M, et al. The anti-staphylococcal activity of
Angelica dahurica (Bai Zhi). Phytochemistry 2004;65:331-335.
40. Taw MB, Nguyen CT, Wang MB. Complementary and integrative treatments:
rhinosinusitis. Otolaryngol Clin North Am 2013;46:345-366.
41. Sertel S, Bergmann Z, Ratzlaff K, et al. Acupuncture for nasal congestion: a
prospective, randomized, double-blind, placebo-controlled clinical pilot study. Am J
Rhinol Allergy 2009;23:e23-28.
42. Pletcher SD, Goldberg AN, Lee J, et al. Use of acupuncture in the treatment of
sinus and nasal symptoms: results of a practitioner survey. Am J Rhinol
2006;20:235-237.
43. Stavem K, Rossberg E, Larsson PG. Health-related quality of life in a trial of
acupuncture, sham acupuncture and conventional treatment for chronic sinusitis. BMC
Res Notes 2008;1:37.
44. Rossberg E, Larsson PG, Birkeflet O, et al. Comparison of traditional Chinese
acupuncture, minimal acupuncture at non-acupoints and conventional treatment for
chronic sinusitis. Complement Ther Med 2005;13:4-10.
45. Shih CC, Lin JG, Liao CC, et al. The utilization of traditional Chinese medicine
and associated factors in Taiwan in 2002. Chin Med J (Engl) 2009;122:1544-1548.
46. Astin JA. Why patients use alternative medicine: results of a national study.
JAMA 1998;279:1548-1553.
47. Bachert C, Van Bruaene N, Toskala E, et al. Important research questions in
allergy and related diseases: 3-chronic rhinosinusitis and nasal polyposis - a GALEN
study. Allergy 2009;64:520-533.
48. Ek A, Middelveld RJ, Bertilsson H, et al. Chronic rhinosinusitis in asthma is a
negative predictor of quality of life: results from the Swedish GA(2)LEN survey.
Allergy 2013;68:1314-1321.
49. Suh JD, Wu AW, Taw MB, et al. Treatment of recalcitrant chronic rhinosinusitis
with integrative East-West medicine: a pilot study. Arch Otolaryngol Head Neck Surg
2012;138:294-300.
Figure legend
Figure 1. Flow recruitment chart of subjects from the one million random samples
obtained from the National Health Insurance Research Database (NHIRD) in Taiwan.
LHID 2000 = Longitudinal Health Insurance Database 2000