Efficacy of Chinese herbal medicine in treatment of allergic rhinitis in children: a meta-analysis of 19 randomized controlled trials

Abstract

This study aimed to systematically evaluate the effect of Chinese herbal medicine (CHM) for treating allergic rhinitis in children. We reviewed relevant studies retrieved from the following databases: MEDLINE (PubMed), Embase, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, the Cqvip Database, and the Wanfang Database. The analysis was conducted by Cochrane software Revman 5.3. Nineteen randomized, controlled trials were included. Meta-analysis showed that CHM had advantages in the efficacy rate (odds ratio [OR] 3.32; 95% confidence interval [CI], 2.32–4.76), recurrence rate (OR 0.30; 95% CI, 0.18–0.49), scores of symptoms, such as sneezing (mean difference [MD] −1.24; 95% CI, −2.33 to −0.14), running nose (MD −1.32; 95% CI, −2.58 to −0.05), and nasal congestion (MD −0.70; 95% CI, −1.05 to −0.36), but not nasal itching (MD −1.37; 95% CI, −3.96 to 1.22), compared with controls. CHM could also effectively decrease immunoglobulin E levels (MD −46.01, 95% CI, −57.53 to −34.48). The current evidence suggests that CHM is more effective in treating allergic rhinitis in children compared with controls. CHM may also decrease the recurrence and level of immunoglobulin E, and improve symptoms such as sneezing, running nose, and nasal congestion, compared with controls.

Keywords

Allergic rhinitis children Chinese herbal medicine randomized controlled trial meta-analysis immunoglobulin E

Introduction

Allergic rhinitis (AR), which is characterized by symptoms of sneezing, rhinorrhea, nasal congestion, and nasal itching, is a type of disease of the upper respiratory tract. Studies have shown that the prevalence of AR symptoms varies from 1.5% to 24.5%.¹ In China, the mean prevalence of childhood AR ranges from 3.9% to 16.8%.² A higher prevalence of AR exists as a single entity in boys than in girls during childhood.^3,4 Most patients complain of symptoms of AR before 20 years old, with 40% being symptomatic before 6 years old.⁵ Evidence has shown an association between AR and asthma in children.^6,7 Although AR is not a life-threatening disease, AR imposes a heavy financial burden on patients and society because of treatment and social costs.^8,9 Furthermore, AR can have a substantial negative effect on concentration and even academic performance in children.^10–12

Effective treatment is helpful in preventing children with rhinoconjunctivitis from asthma onset later in life.^13,14 Treatment for AR includes effective symptomatic control, allergen avoidance, standardized immunotherapy, and health education of patients.^15–18 Although medications can be effective at controlling the symptoms of nasal allergies, they are associated with adverse effects, such as local epistaxis, nasal dryness, irritation from intranasal medications, and drowsiness from antihistamines.^19,20 However, growth may be hindered by use of corticosteroids.²¹ AR is a manifestation of a single inflammatory process.²² Immunoglobulin E (IgE) as identified by Immunological methods is considered as a diagnostic marker and therapeutic target on AR.^23–25

There is a high prevalence of Chinese traditional medicine (TCM) use in the pediatric population in China. In Taiwan, parents of children with AR tend to ask for TCM treatment and Chinese herbal medicine (CHM) as the most common therapeutic approach.^26,27 Studies have shown that CHM is effective in adults.^28–30 Some clinical trials on AR in children treated with CHM have been reported.^31–49 However, to the best of our knowledge, there have been no meta-analyses for evaluating the efficacy of CHM. Therefore, this systematic review aimed to collect evidence to evaluate the effect of CHM treatment of AR in children.

Methods

Database and search strategies

The literature search was conducted by two authors (Zhipan Zheng and Zhenshuang Sun) independently. Any disagreement on the relevance of inclusion was resolved by discussion until a general consensus was reached. This study did not require ethical approval because it contained data from previously published studies.

The preliminary electronic databases that we searched were MEDLINE (PubMed), Embase, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure (CNKI), the Cqvip Database (VIP), and the Wanfang Database up to December 2017. Key words or free-text terms that we used were as follows: “allergic rhinitis”, “children”, “pediatrics”, “randomized, clinical trials”, “traditional Chinese medicine”, and “Chinese herbal medicine”.

Inclusion criteria

A study was eligible for inclusion if it met the following criteria: (1) a randomized, controlled trial (RCT) was designed by the study; (2) patients were diagnosed with AR as defined by the Chinese Medical Association or other well-recognized AR diagnostic criteria were included, were of either sex, and their age not older than 18 years; and (3) patients in the treatment group were treated with CHM. All RCTs were selected with no restrictions on language, population characteristics, blinding, and publication type.

Exclusion criteria

Studies were excluded if they met any one of the following criteria: (1) duplicated publications; (2) reviews, meeting abstracts, case reports, and comments; (3) patients whose age was older than 18 years; and (4) patients in the CHM group were treated with acupuncture, external application, or massage.

Outcomes

The outcome measures were as follows: (1) total effective rate (clinical cure rate + showing effectiveness rate); (2) recurrence rate; (3) scores of the symptoms, including sneezing, running nose, nasal congestion, and nasal itching; (4) IgE levels; and (5) adverse reactions.

According to the Guiding Principle of Clinical Research on New Drugs of TCM, the clinical efficacy of TCM was classified as a clinical cure, showing an effect, and no effect. A clinical cure was defined as disappearance of symptoms and signs, and no abnormal condition as checked by rhinoscopy. An effect was defined as relief of symptoms and signs, with turbinate swelling as checked by rhinoscopy. No effect was defined as no relief of symptoms and signs. Symptoms and signs included sneezing, running nose, nasal congestion, and nasal itching. Rhinoscopy was used to detect nasal mucosa with a pale color, hyperemia, turbinate swelling, and catarrh.

Study selection and data extraction

Two reviewers independently examined abstracts in the search results to identify potential relevance, and then screened full texts for final identification. The following information was extracted: authors, date of publication, sample size, sex and age of the participants, details of the interventions, outcomes measures, and adverse reactions. All included articles were judged by a third reviewer.

Quality assessment

The methodological quality of the trials was evaluated by two coauthors independently. The Jadad score criteria were used⁵⁰. The following three domains were assessed: method of randomization, blinding, dropouts, and withdrawals. Two points were allocated if the method of randomization was described in the study and it was appropriately conducted. One point was allocated if the method of randomization was not appropriate. Two points were allocated if the method of blinding was double-blind and the blinding method was described. One point was allocated if the method of blinding was not appropriate. One point was allocated if the study stated withdrawal or dropout. Otherwise, 0 points were allocated if the study did not describe withdrawal and dropout. Three points or more than 3 points were considered to indicate a high-quality study. The maximum number of points was 5. Fewer than 3 points was considered to indicate a low-quality study.

Data analysis

Data were analyzed by using Review Manager 5.3 software (The Nordic Cochrane Centre, Copenhagen, Denmark). Heterogeneity between similar studies was evaluated by the chi-square test and I² statistic. If I² was ≤50%, then the possibility of heterogeneity between the studies was low, and a fixed-effects model was used. If I² was >50%, there was heterogeneity between the studies, and a random-effects model was used. Enumeration data are expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Measurement data are expressed as the mean difference (MD) with the 95% CI. Statistical significant difference was set as P < 0.05. Publication bias was examined using a funnel plot by using Review Manager 5.3 software.

Description of included studies

An initial search identified 1149 potentially relevant citations, including 351 studies from CNKI, 372 from the Wanfang Database, 373 from VIP, 27 from PubMed, 19 from Embase, and 7 from Cochrane Central Register of Controlled Trials. A total of 555 duplicated articles were excluded using EndNote X7 software (Clarivate Analytics, Boston, MA, USA). After reading the titles and abstracts, 594 articles regarding animal experiments, experience reports, and other treatments and trials carried out on adults were eliminated. Two reviewers then carefully read the full text of the remaining 40 articles; 21 studies that did not meet all of the inclusion criteria were excluded. Therefore, 19 eligible trials were chosen for the meta-analysis.^31–49 A total of 1623 participants, of which there were 832 patients in the CHM group and 791 patients in control group, were involved (Figure 1).

Figure 1.

Flowchart of the study selection process

Methodological quality of included RCTs

Baseline information, such as interventions and outcome measurement, for the treatment and control groups is shown in Table 1. On the basis of the inclusion criteria, 19 relevant citations were included in this study. However, only six studies used the stochastic indicator method. The rest of the studies applied a randomized method, but none of them had a specific description. None of the studies had a precalculated sample size or used a double-blind method (Table 2).

Table 1.

Characteristics of the eligible studies

Study	Treatment intervention	n (M/F), age (mean ± SD and range, years)	Control intervention	n (M/F), age (mean ± SD and range, years)	Course (days)	Outcome measure
Luo et al., 2017³²	Suhuang Zhike capsules	30, NA	Loratadine tablets	30, NA	14	Efficacy, scores of the symptoms, adverse reaction
Hong et al., 2017³³	Decoction of CHM	60 (32/28),5.17 ± 2.50 (2–11)	Loratadine tablets	60 (29/31), 5.28 ± 2.64 (2–12)	28	Efficacy
Zhao et al., 2016³⁴	Decoction of CHM	50, NA (3–12)	Montelukast sodium chewable tablets	50, NA (3–12)	28	Efficacy
Wang et al., 2016³⁵	Decoction of CHM	47 (25/22), 5.28 ± 1.46 (2–13)	Loratadine syrup	47 (26/21), 5.34 ± 1.29 (2–12)	56	Efficacy, recurrence rate
Liang, 2016³⁶	Bimin San	32 (28/4), 9.2 ± 1.0 (5–14)	Cetirizine dihydrochloride tablets	28 (21/7), 8.8 ± 1.2 (6–13)	56	Efficacy, adverse reaction
Hu et al., 2016³⁷	Wenfei Zhiliu Dan	66 (35/31), 6.21 ± 1.44 (2–14)	Inhalebudesonideaerosol, Dermatophagoides farinae drops	66 (32/34), 6.67 ± 1.26 (3–13)	42	Efficacy, recurrence rate, adverse reaction
Liu, 2014³⁸	Decoction of CHM	55 (31/24), 5.17 ± 2.50 (2–11)	Loratadine syrup	55 (34/21), 5.28 ± 2.64 (2–12)	28	Efficacy, scores of the symptoms,
Yu, 2015³⁹	Decoction of CHM	48 (28/20), 6.58 ± 1.34 (4–13)	Budesonide aerosol, loratadine tablets	48 (30/18), 6.87 ± 1.35 (3–14)	56	Efficacy, recurrence rate
Zhou, 2014⁴⁰	Decoction of CHM	60 (35/25), NA (2–15)	Biyuang Tongqiao granules	60 (31/29), NA (3–14)	14	Efficacy
Zhang, 2014⁴¹	Decoction of CHM	40 (23/17), NA (5–14)	Prednisone acetate tablets, ketotifen fumarate tablets, ephedrine hydrochloride andnitrofurazone nasal drops	40 (24/16), NA (6–13)	14	Efficacy
Guo et al., 2014⁴²	Decoction of CHM	28 (15/13), NA (3.5–14)	Loratadine tablets	28 (14/14), NA (3.5–14)	14	Efficacy, recurrence rate
Chen, 2014⁴³	Decoction of CHM	30 (16/14), 6.60 ± 2.12	Loratadine tablets	30 (17/13), 7.20 ± 1.29	28	Efficacy
Wang, 2013⁴⁴	Decoction of CHM	50 (22/28), NA (4–14)	Loratadine tablets	50 (24/26), NA (4–12)	14	Efficacy, Scores of the symptoms
Luo, 2013⁴⁵	Decoction of CHM	70 (42/28), NA (2–11)	Loratadine tablets	70 (41/29), NA (2–11)	21	Efficacy, adverse reaction
Wang, 2012⁴⁶	Decoction of CHM	40 (23/17), NA (5–14)	Terfenadine tablets, prednisone acetate tablets, ephedrine hydrochloride nasal drops	20 (12/8), NA (6–14)	14	Efficacy
Yang, 2010⁴⁷	Yupingfeng granules	25 (14/11), NA (3–14)	Loratadine tablets	21 (12/9), NA (3–14)	56	Efficacy, recurrence rate
Chen, 2010⁴⁸	Decoction of CHM	35 (20/15), 4.86 ± 0.43 (1.5–10)	Loratadine tablets	35 (21/14), 4.76 ± 0.42 (1.8–11)	28	Efficacy
Yuan et al., 2009⁴⁹	Bimin oral liquid	30 (16/14), 10.0 ± 3.5 (6–17)	Loratadine tablets	30 (17/13), 11.0 ± 2.9 (5–16)	20	Efficacy, IgE
Zhao et al., 2006⁵⁰	Decoction of CHM	36 (19/16), NA (4–14)	Biyankang capsules	23 (13/10), NA (4.5–13)	10	Efficacy, IgE

M: Male; F: female; CHM: Chinese herbal medicine; NA: not available; IgE: immunoglobulin E

Table 2.

Methodological quality of included randomized, controlled trials

Study	Randomized method	Blinding	Dropouts or withdrawals	Jadad score
Luo et al., 2017³²	Claimed	Unclear	No	1
Hong et al., 2017³³	Stochastic indicator method	Unclear	No	2
Zhao et al., 2016³⁴	Claimed	Unclear	No	1
Wang et al., 2016³⁵	Stochastic indicator method	Unclear	No	2
Liang, 2016³⁶	Claimed	Unclear	No	1
Hu et al., 2016³⁷	Stochastic indicator method	Unclear	No	2
Liu, 2014³⁸	Stochastic indicator method	Unclear	No	2
Yu, 2015³⁹	Claimed	Unclear	No	1
Zhou, 2014⁴⁰	Claimed	Unclear	No	1
Zhang, 2014⁴¹	Claimed	Unclear	No	1
Guo et al., 2014⁴²	Claimed	Unclear	No	1
Chen, 2014⁴³	Stochastic indicator method	Unclear	No	2
Wang, 2013⁴⁴	Claimed	Unclear	No	1
Luo, 2013⁴⁵	Claimed	Unclear	No	1
Wang, 2012⁴⁶	Stochastic indicator method	Unclear	No	2
Yang, 2010⁴⁷	Claimed	Unclear	No	1
Chen, 2010⁴⁸	Claimed	Unclear	No	1
Yuan et al., 2009⁴⁹	Claimed	Unclear	No	1
Zhao et al., 2006⁵⁰	Claimed	Unclear	No	1

Meta-analysis of curing AR in children

Efficacy rate

As is shown in Figure 2, 11 studies mentioned the efficacy rate difference between CHM and loratadine.^{31,32,34,37,41–44,46–48} A total of 956 patients were included (480 patients in the CHM group, 476 patients in the control group). The fixed-effects model was applied for statistical analysis because the 11 studies did not show heterogeneity (chi-square = 4.53, P = 0.92, I² = 0%). Our analysis suggested that CHM could effectively improve the efficacy rate compared with loratadine (OR 3.32; 95% CI, 2.32–4.76; P < 0. 001) (Figure 2).

Figure 2.

Efficacy rate using CHM versus loratadine. CHM: Chinese herbal medicine

Scores of symptoms

Among all 19 studies, 2 of them selected scores of the symptoms as one of their outcome measures.^31,37 A total of 170 patients were included (85 patients in the CHM group, 85 patients in the control group). For the symptom of sneezing, there was statistical heterogeneity between these two clinical trials after testing for heterogeneity (chi-square = 24.78, P < 0.001, I² = 96%). Therefore, the random-effects model was used, and it showed a significant difference between the CHM and control groups (MD −1.24; 95% CI, −2.33 to −0.14; P = 0.03) (Figure 3a). For the symptom of a running nose, there was statistical heterogeneity between these two clinical trials after testing for heterogeneity (chi-square = 22.61, P < 0.001, I² = 96%). Therefore, the random-effects model was used, and it showed a significant difference between the CHM and control groups (MD −1.32; 95% CI, −2.58 to −0.05; P = 0.04) (Figure 3b). For the symptom of nasal congestion, there was statistical heterogeneity between these two clinical trials after testing for heterogeneity (chi-square = 4.97, P = 0.03, I² = 80%). Therefore, the random-effects model was used, and it showed a significant difference between the CHM and control groups (MD −0.70; 95% CI, −1.05 to −0.36; P < 0.001) (Figure 3c). For the symptom of nasal itching, there was statistical heterogeneity between these two clinical trials after testing for heterogeneity (chi-square = 29.44, P < 0.001, I² = 97%). Therefore, the random-effects model was used, but it showed no significant difference between the CHM and control groups (MD−1.37; 95% CI, −3.96 to 1.22, P = 0.30) (Figure 3d).

Figure 3.

Scores of the symptoms using CHM versus controls. (a) Sneezing. (b) Running nose. (c) Nasal congestion. (d) Nasal itching. CHM: Chinese herbal medicine

Recurrence rate

As shown in Figure 2, five studies described the difference in recurrence rate between CHM and loratadine.^{34,36,38,41,46} A total of 405 patients were included (205 patients in the CHM group, 200 patients in the control group). The fixed-effects model was applied for statistical analysis because the five studies did not show heterogeneity (chi-square = 1.95, P = 0.74, I² = 0%). The analysis showed that CHM could effectively improve the efficacy rate compared with controls (OR 0.30; 95% CI, 0.18 to 0.49; P < 0.001) (Figure 4).

Figure 4.

Recurrence rate using CHM versus controls. CHM: Chinese herbal medicine

IgE

Among the 19 studies, two of them selected IgE as one of their outcome measures.^33,48 A total of 118 patients were included (65 patients in the CHM group, 53 patients in the control group). The fixed-effects model was applied for statistical analysis because the two studies did not show heterogeneity (chi-square = 1.02, P = 0.31, I² = 2%). The analysis showed that CHM could effectively decrease IgE levels compared with the control group (MD −46.01; 95% CI, −57.53 to −34.48; P < 0.001) (Figure 5).

Figure 5.

IgE levels using CHM versus controls. CHM: Chinese herbal medicine

Publication bias

An “inverted funnel” pattern analysis was used to confirm publication bias. The asymmetrical figure indicated potential publication bias that might affect the results (Figure 6).

Figure 6.

Funnel plot. Annotations: comparison = CHM group versus the control group; outcome = effective rate. CHM: Chinese herbal medicine

Adverse reactions

Four patients experienced skin rash in the CHM group who were treated with Wenfei Zhiliu Dan,³⁶ and no other adverse reactions were reported. Adverse reactions in the control group included drowsiness, nosebleed, fever, thirst, skin rash, and fatigue. However, calculating the incidence of adverse reactions was difficult because of insufficient adverse events reported.

Discussion

In this study, we systematically evaluated and analyzed previous literature on RCTs regarding the efficacy of CHM in clinical treatment of AR in children. We found that CHM could effectively improve the efficacy rate compared with loratadine. CHM may have advantages in terms of the recurrence rate and the scores of symptoms, such as sneezing, running nose, and nasal congestion, but not nasal itching. CHM may also reduce IgE levels compared with controls.

According to the TCM theory, the nose is the orifice of the lung. The pathogeny of AR as “Feng Xie” leads to obstruction of lung-qi, which triggers symptoms, including sneezing, running nose, nasal congestion, and nasal itching. Therefore, therapeutic methods are focused on dispelling the Feng Xie and relaxing the depressed lung-qi. This type of theory is the foundation for CHM formula on AR. The mechanism of CHM on AR may include controlling the balance of T helper 1/T helper 2, suppressing eosinophilic activity, reducing IgE levels, regulating allergenic cell degranulation, and antihistamines.^51–55

There are some limitations concerning this study. First, the RCTs that were included in this study were limited and the sample sizes were small. Therefore, ruling out the influence of contingency factors is difficult. Second, the overall methodological quality of the included RCTs was not high. Although all of 19 studies stated that they used the random method, only 6 of them elaborated on the details of the stochastic method.^{32,34,36,37,42,45} No studies claimed a double-blind method. There was no withdrawal or dropout described. In fact, there was a high possibility of selection bias and measurement bias. Third, publication bias cannot be fully excluded without sufficient studies. In this review, an inverted funnel plot (Figure 6) showed that the publication bias might have affected the results. Some results of our study showed high heterogeneity (Figure 3). There was a high possibility of measurement bias. Finally, the intervention duration in the included articles ranged from 10 to 56 days. However, unfortunately, there is no relevant standard for the time of intervention.

Therefore, ensuring that the trials were properly conducted is difficult. Consequently, we are unable to make confirmative conclusions. High-quality, large-sample, RCTs still need to be performed in the future.

Footnotes

Declaration of conflicting interest

The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

References

Ait-Khaled

Pearce

Anderson

et al.

Global map of the prevalence of symptoms of rhinoconjunctivitis in children: The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three.

Allergy 2009; 64: 123–148.

Zhang

Prevalence of allergic rhinitis in China.

Allergy Asthma Immunol Res 2014; 6: 105–113.

Kurukulaaratchy

Karmaus

Arshad

SH.

Sex and atopy influences on the natural history of rhinitis.

Curr Opin Allergy Clin Immunol 2012; 12: 7–12.

Pinart

Keller

Reich

et al.

Sex-related allergic rhinitis prevalence switch from childhood to adulthood: a systematic review and meta-analysis.

Int Arch Allergy Immunol 2017; 172: 224–235.

Skoner

DP.

Allergic rhinitis: definition, epidemiology, pathophysiology, detection, and diagnosis.

J Allergy Clin Immunol 2001; 108: S2–S8.

Morais-Almeida

Gaspar

Pires

et al.

Risk factors for asthma symptoms at school age: an 8-year prospective study.

Allergy Asthma Proc 2007; 28: 183–189.

Leynaert

Neukirch

Demoly

et al.

Epidemiologic evidence for asthma and rhinitis comorbidity.

J Allergy Clin Immunol 2000; 106(5 Suppl): S201–S205.

Canonica

Bousquet

Mullol

et al.

A survey of the burden of allergic rhinitis in Europe.

Allergy 2007; 62 Suppl 85: 17–25.

Meltzer

Blaiss

Derebery

et al.

Burden of allergic rhinitis: results from the Pediatric Allergies in America survey.

J Allergy Clin Immunol 2009; 124: S43–S70.

10.

Walker

Khan-Wasti

Fletcher

et al.

Seasonal allergic rhinitis is associated with a detrimental effect on examination performance in United Kingdom teenagers: case- control study.

J Allergy Clin Immunol 2007; 120: 381–387.

11.

Simons

FE.

Learning impairment and allergic rhinitis.

Allergy Asthma Proc 1996; 17: 185–189.

12.

Ibero

Justicia

Alvaro

et al.

Diagnosis and treatment of allergic rhinitis in children: results of the PETRA study.

Allergol Immunopathol (Madr) 2012; 40: 138–143.

13.

Novembre

Galli

Landi

et al.

Coseasonal sublingual immunotherapy reduces the development of asthma in children with allergic rhinoconjunctivitis.

J Allergy Clin Immunol 2004; 114: 851–857.

14.

Inal

Altintas

Yilmaz

et al.

Prevention of new sensitizations by specific immunotherapy in children with rhinitis and/or asthma monosensitized to house dust mite.

J Investig Allergol Clin Immunol 2007; 17: 85–91.

15.

Bousquet

Khaltaev

Cruz

et al.

Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen).

Allergy 2008; 63 Suppl 86: 8–160.

16.

Bernstein

Schwartz

Bernstein

JA.

Allergic rhinitis: mechanisms and treatment. Immunol Allergy Clin North Am 2016; 36: 261–278.

17.

Bousquet

Van Cauwenberge

Bachert

et al.

Requirements for medications commonly used in the treatment of allergic rhinitis. European Academy of Allergy and Clinical Immunology (EAACI), Allergic Rhinitis and its Impact on Asthma (ARIA). Allergy 2003; 58: 192–197.

18.

Nurmatov

van Schayck

Hurwitz

et al.

House dust mite avoidance measures for perennial allergic rhinitis: an updated Cochrane systematic review.

Allergy 2012; 67: 158–165.

19.

Trangsrud

Whitaker

Small

RE.

Intranasal corticosteroids for allergic rhinitis. Pharmacotherapy 2002; 22: 1458–1467.

20.

Scadding

GK.

Intranasal steroid sprays in the treatment of rhinitis is one better than another?

J Laryngol Otol 2004; 118: 395–396; author reply 396.

21.

Skoner

Rachelefsky

Meltzer

et al.

Detection of growth suppression in children during treatment with intranasal beclomethasone dipropionate.

Pediatrics 2000; 105: E23.

22.

Brozek

Bousquet

Baena-Cagnani

et al.

Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision.

J Allergy Clin Immunol 2010; 126: 466–476.

23.

Ciprandi

Marseglia

Castagnoli

et al.

From IgE to clinical trials of allergic rhinitis.

Expert Rev Clin Immunol 2015; 11: 1321–1333.

24.

Chervinsky

Casale

Townley

et al.

Omalizumab, an anti-IgE antibody, in the treatment of adults and adolescents with perennial allergic rhinitis.

Ann Allergy Asthma Immunol 2003; 91: 160–167.

25.

Licari

Castagnoli

Panfili

et al.

An update on anti-IgE therapy in pediatric respiratory diseases.

Curr Respir Med Rev 2017; 13: 22–29.

26.

Huang

Liu

Lien

et al.

A nationwide population-based study of traditional Chinese medicine usage in children in Taiwan.

Complement Ther Med 2014; 22: 500–510.

27.

Kung

Chen

Hwang

et al.

The prescriptions frequencies and patterns of Chinese herbal medicine for allergic rhinitis in Taiwan.

Allergy 2006; 61: 1316–1318.

28.

Xue

Thien

Zhang

et al.

Treatment for seasonal allergic rhinitis by Chinese herbal medicine: a randomized placebo controlled trial. Altern Ther Health Med 2003; 9: 80–87.

29.

Zhang

Lan

Zhang

et al.

Chinese herbal medicine to treat allergic rhinitis: evidence from a meta-analysis.

Allergy Asthma Immunol Res 2018; 10: 34–42.

30.

Wang

Tang

Qian

et al.

Meta-analysis of clinical trials on traditional Chinese herbal medicine for treatment of persistent allergic rhinitis.

Allergy 2012; 67: 583–592.

31.

Luo

Zhang

Suhuang Zhike Capsule in the treatment of paediatric allergic rhinitis for 30 cases. Chinese Medicine Modern Distance Education of China 2017; 15: 94–95.

32.

Hong

Tong

Huang

WX.

Effect of Tongqiao decoction in treating allergic rhinitis in children. Zhejiang J Tradit Chin Med 2017; 52: 810.

33.

Zhao

and

Zheng

Clinical observation of Yangyin Yiqi decoction in the treatment of allergic rhinitis in children. Practical Clinical Journal of Integrated Traditional Chinese and Western Medicine 2016; 16: 16–18.

34.

Wang

XJ.

Clinical effect analysis of Xiaoqinglong decoction in treating allergic rhinitis in children. Health Care Today 2016; 1: 164–64.

35.

Liang

GQ.

The clinical observation of biminsan on 60 pediatric allergic rhinitis. Journal of Chinese Ophthalmology and Otorhinolaryngology 2016; 6: 143–144.

36.

Clinical observation of Wenfei Zhiliu Pill combined with Shenling Baizhu San in treatment of allergic rhinitis in children. Journal of Nw Cinese Mdicine 2016; 48: 137–139.

37.

Liu

A clinical observation on Guizhi decoction for allergic rhinitis in children. Henan Tradit Chin Med 2014; 34: 1885–1886.

38.

Treatment of allergic rhinitis in children by TCM. Medical Information 2015; 28: 39–39.

39.

Zhou

Shao

Lian

JL.

Curative effect analysis of 60 cases of pediatric allergic rhinitis treated with Shufengtongqiao decoction. J Pedia Tradit Chin Med 2014; 10: 48–50.

40.

Zhang

Effect of Buzhong Yiqi decoction combined with Yuping Feng San in treatment of allergic rhinitis in children. Medicine & People 2014; 27: 122.

41.

Guo

Cheng

WL.

Clinical observation of Biminyan decoction in treating allergic rhinitis in children. The Journal of Medical Theory and Practice 2014; 27: 3165–65, 66.

42.

Chen

QQ.

Treatment of pediatric allergic rhinitis by Xiaoqinglong decoction: a clinical study. Medical Information 2014; 2014: 55–55, 56.

43.

Wang

XL.

The clinical effect of Yupingfeng San combined with Guomin decoction on 50 allergic rhinitis in children. Journal of New Chinese Medicine 2013; 45: 80–81.

44.

Luo

GW.

Clinical research of Qingre Tongqiao San in treating allergic rhinitis in children. J Emerg Tradit Chin Med 2013; 22: 2095–2096.

45.

Wang

JC.

Treatment of allergic rhinitis in children by Wumei Cangerzi San: a clinical observation. Traditional Chinese Medicinal Research 2012; 25: 21–23.

46.

Yang

Clinical observation of Yupingfeng Granule in treating allergic rhinitis in children. J Pediatrics of TCM 2010; 6: 23–25.

47.

Chen

WY.

35 cases of pediatric allergic rhinitis of pulmonosplenic asthenia type treated by Gu Biao Jian Pi decoction. China Journal of Chinese Medicine 2010; 25: 316–317.

48.

Yuan

Han

Zhu

et al.

Clinical observation of Bimin mixture in the treatment of allergic rhinitis in children. Chinese Journal of Information on TCM 2009; 16: 74–75.

49.

Zhao

Gao

GQ.

Clinical research of Erma decoction in treating allergic rhinitis in children. Shandong Journal of Traditional Chinese Medicine 2006; 25: 166–167.

50.

Jadad

Moore

Carroll

et al.

Assessing the quality of reports of randomized clinical trials: is blinding necessary?

Control Clin Trials 1996; 17: 1–12.

51.

Yan

Jin

et al.

The possible mechanism of inhibitory effect of xanthium strumarium on mast cells activated by compound 48/80. Progress of Anatomical Sciences 2010; 16: 164–66 + 70.

52.

Wen

Zhou

et al.

Effect of Bimin tablet on nasal mucosa' histamine from the model of guinea pig allergic rhinitis. Hunan Guiding Journal of TCMP 2002; 8: 500–502.

53.

Wang

SP.

Effect of Mahuang Fuzi Xixin decoction on T lymphocyte subsets in allergic rhinitis. Liaoning Journal of Traditional Chinese Medicine 2002; 29: 562–563.

54.

Pei

Shu

HJ.

Clinical observation of Yupingfeng granule in treating allergic rhinitis. Chin J Otorhinolaryngol Integ Med 2003; 11: 241.

55.

Huang

Liu

et al.

Clinical and experimental research of Xiao Chaihu decoction in treating allergic rhinitis. Chin J Otorhinolaryngol Integ Med 1996; 4: 76–78.