Chinese Medicinal Herbs for Childhood Pneumonia: A Systematic Review of Effectiveness and Safety

Abstract

Objective. To assess the efficacy and safety of Chinese medicinal herbs for Childhood Pneumonia. Methods. We included randomized controlled trials (RCTs). The searched electronic databases included PubMed, the Cochrane Central Register of Controlled Trials, EMBASE, CBM, CNKI, and VIP. All studies included were assessed for quality and risk bias. Review Manager 5.1.6 software was used for data analyses, and the GRADEprofiler software was applied to classify the systematic review results. Results. Fourteen studies were identified . Chinese herbs may increase total effective rate (risk ratio (RR) 1.18; 95% confidence interval (CI), 1.11–1.26) and improve cough (total mean difference (MD), 2.18; 95% CI, 2.66)–1.71)), fever (total MD, 1.85; 95% CI, 2.29)–1.40)), rales (total MD, 1.53; 95% CI, 1.84)–1.23)), and chest films (total MD, 3.10; 95% CI, 4.11)–2.08)) in Childhood Pneumonia. Chinese herbs may shorten the length of hospital stay (total MD, 3.00; 95% CI, (−3.52)–2.48)), but no significant difference for adverse effects (RR, 0.39; 95% CI, 0.09–1.72) was identified. Conclusion. Chinese herbs may increase total effective rate and improve symptoms and signs. However, large, properly randomized, placebo-controlled, double-blind studies are required.

1. Introduction

Childhood Pneumonia is an acute virus, bacterial, or fungal respiratory infection that affects the lungs [1]. The symptoms and signs of Childhood Pneumonia include cough, fever, rapid or difficult breathing, loss of appetite, and lower chest wall indrawing [2]. Auscultation reveals rales. However, severe Childhood Pneumonia is defined as cough or difficult breathing combined with lower chest wall indrawing [3]. Childhood Pneumonia has been identified as a mixed viral-bacterial infection in 23%–33% of cases [4]. Respiratory syncytial virus is the most common viral cause of children pneumonia, and Streptococcus pneumoniae is the most common cause of bacterial pneumonia in children [5]. Each year, pneumonia kills an estimated 1.4 million children <5 years of age, accounting for 18% of all deaths worldwide [6]. Pneumonia is the most common reason for hospitalization in children <2 years of age [7]. The cost of antibiotic treatment for all children with pneumonia in 42 of the poorest countries is estimated to be about US $600 million per year. The estimated incidence rates are 0.29 and 0.05 episodes per child-year in low-income and high-income countries, respectively. Approximately 156 million new episodes occur each year, the majority in India (43 million), China (21 million), Pakistan (10 million), Bangladesh, Indonesia, and Nigeria (6 million each) [8].

Administering appropriate antibiotics at the early stage of pneumonia improves outcomes, particularly when the causative agent is bacterial [9]. However, antibiotic treatment of pneumonia in children remains mostly empirical because determining the etiologic pathogen is difficult in this age group [10]. According to the results of a questionnaire, the following agents have been used against Childhood Pneumonia: ampicillin, ampicillin/sulbactam, second/third generation cephalosporins, azithromycin, vancomycin, clindamycin, and linezolid. In subsequent analyses, we categorized ampicillin, ampicillin/sulbactam, and cephalosporins as beta-lactam antibiotics and vancomycin, clindamycin, and linezolid as antimethicillin-resistant Staphylococcus aureus antibiotics. Respondents were asked to select the duration of antibiotic therapy they would recommend for uncomplicated and parapneumonic empyema cases using the following categories: 3–5 days, 6-7 days, 8–10 days, 11–14 days, 15–21 days, and >21 days [11]. Empirical antibiotic administration is relied upon in most instances to meet the public health goal of reducing child mortality due to pneumonia. This is necessary in view of the inability of most commonly available laboratory tests to identify causative pathogens. Empirical antibiotic administration is the main treatment for Childhood Pneumonia. Multiple antibiotics are prescribed for treating pneumonia, so it is important to know which work best for pneumonia in children [12].

Traditional Chinese Medicine (TCM) follows a particular theoretical and methodological approach to estimate the cause of a disease, leading to diagnosis and treatment [13]. Pneumonia is equivalent to the TCM cough category. Ma Xing Shi Gan Tang, San Ao Tang, Zhi Sou San, and other self-developed TCM prescriptions are Chinese medicinal formulas that have been used to treat Childhood Pneumonia for many years. In recent years, preparations of Chinese herbal medicines, such as Tanreqing injection, Chuanhuning injection, and Reduning injection have been used to treat Childhood Pneumonia in China. Chinese herbal medicine formulas function to clear heat, resolve phlegm, ventilate the lungs, dissipate phlegm, relieve cough, and reduce sputum. The function of Chinese herbal medicine preparations is to clear heat and remove toxicity. A study showed that the pharmacological action of Ma Xing Shi Gan Tang includes antiasthmatic, antitussive, and antiviral effects as well as bacteriostatic and immunoregulatory functions [14].

Although these formulae and other Chinese herbal medicine preparations have been used widely to treat Childhood Pneumonia in China, their effects and safety have not been reviewed systematically.

2. Methods

2.1. Criteria for Considering Studies for this Paper

2.1.1. Types of Studies

Only randomized controlled trials (RCTs) were included.

2.1.2. Types of Participants

Studies that enrolled patients with pneumonia in children who had cough, fever >37.5°C, raised respiratory rate, lower chest wall indrawing, rales, and changes on chest films were included. Patients with Childhood Pneumonia of either gender, any ethnic group, and ages of 1 month to 18 years were included. Studies were excluded if they included children suffering from other debilitating diseases.

2.1.3. Types of Interventions

There were Chinese medicinal herbs versus other drugs, formulas, and placebo alone; Chinese medicinal herbs plus basic therapy versus basic therapy. Antibiotics were one of the main basic therapies for Childhood Pneumonia. Prohibited or suspended Chinese herbal preparations were excluded.

2.1.4. Types of Outcome Measures

Primary outcomes included mortality and total effective rate (e.g., ratio of signs and symptoms improvement or recovery); secondary outcomes included time to clinical recovery (e.g., cough, fever, rales, and chest films), relapse rate, length of hospital stay, and adverse effects (e.g., nausea, diarrhea, vomiting, and gastrointestinal bleeding). TCM outcomes such as tongue coat, pulse condition, and economic index were included.

2.2. Search Methods for Identification Studies

We searched for all relevant studies in the following electronic databases: PubMed (1966–July 2012), the Cochrane Central Register of Controlled Trials, EMBASE (1980–July 2012), the Chinese Biomedicine Database (CBM) (1976–July 2012), Chinese National Knowledge Internet (CNKI) (1979–July 2012), and Chinese Biomedical Journals (VIP) (1989–July 2012). All studies included were analyzed according to Cochrane Handbook criteria. The following search terms were used: (Chinese herbs OR Chinese traditional herbs OR Chinese medicinal herbs OR traditional Chinese herbs OR Chinese herbal medicines) AND (child pneumonia OR children pneumonia OR Childhood Pneumonia OR Pediatric Pneumonia OR Infantile Pneumonia). We conducted a manual search for the Journal of Guangzhou University of Traditional Chinese Medicine. We attempted to contact original authors to obtain the protocol for the studies.

2.3. Data Collection and Analysis

2.3.1. Study Selection

Two review authors independently browsed the titles and abstracts of all articles identified by the literature search. The same review authors independently estimated whether the trials met the inclusion criteria. Disagreements were resolved by discussion or consultation with a third author. We assessed abstracts from the initial search independently to identify studies that met the inclusion criteria. We telephone-interviewed authors of Chinese language articles and emailed the original authors of English articles to identify the randomization procedure and other methodological questions to ensure that the included studies were RCTs. If the required information was not available or if the required information did not meet the inclusion criteria, the article was excluded.

2.3.2. Data Extraction and Management

We extracted data including methodological details and data from publications using a data extraction form. We extracted data on study characteristics, including methods, participants, interventions, and outcomes. There were no disagreements among the authors.

We extracted the formulation contents of the included studies, and the names of the herbs are provided in three languages (e.g., Chinese, Latin, and English) in Table 1.

2.3.3. Assessment of Risk of Bias in Included Studies

The following items were independently assessed by our authors using the risk of bias assessment tool. (1) Was there adequate sequence generation (selection bias)? (2) Was allocation adequately concealed (selection bias)? (3) Was knowledge of the allocated interventions adequately prevented during the study (e.g., participants and personnel, outcome assessors) (detection bias)? (4) Were incomplete outcome data adequately addressed (attrition bias)? (5) Are reports of the study free of suggesting selective outcome reporting (reporting bias)? (6) Was the study apparently free of other problems that could put it at risk for bias?

2.3.4. Measures of Treatment Effect

Data analyses were performed using the Cochrane Collaboration’s RevMan software, version 5.1.6. Results are expressed as risk ratios (RR) and 95% confidence intervals (CIs) for dichotomous outcomes (e.g., mortality, effective rate, adverse effects, and relapse rate) and as mean differences (MD) with 95% CIs for continuous outcomes (such as time to clinical recovery and length of hospital stay).

2.3.5. Assessment of Heterogeneity

Heterogeneity was analyzed using the chi-square test on degrees of freedom, and an alpha of 0.05 was used for statistical significance with the test. values of 25, 50, and 75% corresponded to low, medium, and high levels of heterogeneity, respectively.

2.3.6. Data Synthesis

We used fixed-effects and random-effects models for the pooled data analysis. We performed a pooled analysis for the 14 studies.

2.3.7. Subgroup Analyses

Subgroup analyses were performed according to formula type and Chinese medicinal herb preparation type, using the same comparators (e.g., same types of antibiotics).

2.3.8. Sensitivity Analyses

Sensitivity analyses were conducted by excluding low-quality studies (based on descriptions of randomization, allocation concealment, blinded assessment of outcomes, and description/analyses of withdrawals and dropouts) and a comparison of the merger analysis results for the fixed- and random-effects models.

3. Results

3.1. Search Results

An initial search identified 2,502 potentially relevant articles. Of these, 15 were in the English database. A total of 891 articles were initially included after duplicate publications were removed and any obviously irrelevant were excluded; 800 articles were later excluded, because they did not meet the inclusion criteria. Of the 91 potentially eligible reports, 77 were excluded for further assessment because telephone interviews with the original authors revealed that they were not RCTs. Therefore, 14 studies (1,824 participants) were included in this paper. All 14 studies were published in Chinese (Figure 1).

Figure 1 

Summary of the search results in a flow diagram.

3.2. Included Studies

3.2.1. Participants

The ratio of male to female participants in the 14 studies was 879/615 [15–21, 23–28]. One study [22] did not report the number of males and females. In total, 1,824 children were included in the 14 studies, and all were from China [15–28]. The ages of the patients were 1 month–15 years. The average size of the trials was 130 participants (range 60–200 participants).

3.2.2. Inclusion Criteria

The diagnostic criteria for childhood pneumonia in all studies included fever >37.5°C, chest recession, increased respiratory rate, cough, rales, or difficulty breathing combined with fast breathing and a change on chest films.

3.2.3. Intervention

Chinese medicinal herbs interventions were given as oral decoctions or intravenous infusions. The longest therapy duration was 3 weeks, and the shortest was 5 days. Follow-up duration was not mentioned by any of the authors. All 14 studies compared Chinese medicinal herbs plus basic therapy versus basic therapies.

3.2.4. Outcomes

All 14 studies [15–28] reported the total effective rate; seven studies [15, 17, 18, 21, 23, 25, 28] reported clinical recovery of cough, fever, rales, and chest films; four [16, 22, 24, 26] reported clinical recovery of cough, fever, and rales; one [27] reported clinical recovery of fever; three [15, 21, 22] reported adverse effects (e.g., nausea, vomiting, diarrhea, and gastrointestinal bleeding); and one [28] reported the length of hospital stay. The description of studies is detailed in the characteristics of included studies in Table 2.

3.3. Risk of Bias in Included Studies

The methodological quality of each study’s randomization sequence, allocation concealment, blinding, incomplete outcome data, selective outcome reporting, and potential threats are summarized in Figures 2 and 3.

Figure 2 

Methodological quality. Judgments about each item are presented as percentages across all included studies.

Figure 3 

Methodological quality summary.

3.3.1. Randomization and Allocation Concealment

Ten studies [15–20, 23, 25–27] reported using a random-number table, and four [21, 22, 24, 28] reported using a computer-generated random-number table. None of the trials used allocation concealment. Therefore, all studies had a high risk of selection bias.

3.3.2. Blinding

Ten studies [15–17, 20–24, 26, 27] used single blinding (outcome assessment was blinded). We interviewed the original authors by telephone to determine blinding because the blinding methods were not described. Thus, these studies had a low risk of performance bias and low detection bias. The other studies [18, 19, 25, 28] did not use blinding methods and had a high risk of performance bias or a strong detection bias.

3.3.3. Flow of Participants and Intention-to-Treat

None of the studies reported withdrawal, dropout, and/or loss during followup. The method of handling missing data regarding intention-to-treat or per-protocol analysis was not addressed.

3.3.4. Selective Reporting (Reporting Bias)

No detailed evidence of selective reporting was found in any of the 14 studies [15–28]. However, we believed there is a high risk of selective reporting bias because we were unable to compare the protocol with published studies.

3.3.5. Other Potential Sources of Bias

None of the 14 studies [15–28] did not describe patient compliance. The appropriateness of the statistical analyses used was assessed, and the methods of all studies were considered appropriate. Although we conducted comprehensive searches and tried to avoid bias, we could not exclude potential publication bias because all 14 studies were published in China.

4. Effects of Interventions

All studies compared Chinese medicinal herbs plus basic therapy to basic therapy alone. The Chinese medicinal herb treatments included the modified Ma Xing Shi Gan Tang formula, the San Ao Tang formula, the Zhi Sou San formula, a self-developed TCM prescription, Tanreqing injection, Reduning injection, and Chuanhuning injection. Antibiotics were one of main basic therapies for Childhood Pneumonia.

4.1. Total Effective Rate

A significant increase in total effective rate was observed with Chinese medicinal herbs plus basic therapy versus basic therapy (Figure 4, analysis 1.1; RR, 1.18; 95% CI, 1.11–1.26).

Figure 4 

Comparison. Chinese medicinal herbs plus basic therapy versus basic therapy: outcome 1 total effective rate.

Subgroup five studies [15–19] compared the modified Ma Xing Shi Gan Tang formula plus azithromycin versus azithromycin and showed a significant increase in total effective rate (Figure 4; analysis 1.1.1 of analysis 1.1; RR, 1.18; 95% CI, 1.09–1.27).

Subgroup one study [20] compared the modified Ma Xing Shi Gan Tang formula plus ceftazidime versus ceftazidime and showed no difference in total effective rate (Figure 4; analysis 1.1.2 of analysis 1.1; RR, 1.11; 95% CI, 0.98–1.27).

Subgroup one study [21] compared the San Ao Tang formula plus azithromycin versus azithromycin and showed no difference in total effective rate (Figure 4; analysis 1.1.3 of analysis 1.1; RR, 0.99; 95% CI, 0.91–1.08).

Subgroup one study [22] compared the modified Zhi Sou San formula plus erythrocin versus erythrocin and showed a significant increase in total effective rate (Figure 4; analysis 1.1.4 of analysis 1.1; RR, 1.41; 95% CI, 1.24–1.61).

Subgroup one study [23] compared a self-developed TCM prescription plus erythrocin versus erythrocin and showed no difference in total effective rate (Figure 4; analysis 1.1.5 of analysis 1.1; RR, 1.13; 95% CI, 0.91–1.39).

Subgroup one study [24] compared Tanreqing injection plus antibiotics versus antibiotics and showed a significant difference in total effective rate (Figure 4; analysis 1.1.6 of analysis 1.1; RR, 1.28; 95% CI, 1.10–1.50).

Subgroup three studies [25–27] compared Reduning injection plus azithromycin versus azithromycin and showed a significant difference in total effective rate (Figure 4; analysis 1.1.7 of analysis 1.1; RR, 1.23; 95% CI, 1.04–1.46).

Subgroup one study [28] compared Chuanhuning injection plus piperacillin versus piperacillin and showed a significant difference in total effective rate (Figure 4; analysis 1.1.8 of analysis 1.1; RR, 1.14; 95% CI, 1.05–1.24).

4.2. Adverse Effects

Three studies [15, 21, 22] compared Chinese medicinal herbs plus basic therapy versus basic therapy and showed no difference in adverse effects (Figure 5; analysis 1.2; RR, 0.39; 95% Cl, 0.09–1.72).

Figure 5 

Comparison. Chinese medicinal herbs plus basic therapy versus basic therapy: outcome 2 adverse effects.

Subgroup one study [15] compared the modified Ma Xing Shi Gan Tang formula plus azithromycin versus azithromycin and showed no difference in adverse effects (Figure 5; analysis 1.2.1 of analysis 1.2; RR, 1.00; 95% CI, 0.34–2.90).

Subgroup one study [21] compared the San Ao Tang formula plus azithromycin versus azithromycin and showed no difference in adverse effects (Figure 5; analysis 1.2.2 of analysis 1.2; RR, 0.60; 95% CI, 0.15–2.41).

Subgroup one study [22] compared the modified Zhi Sou San formula plus erythrocin versus erythrocin and showed a significant decrease in adverse effects (Figure 5; analysis 1.2.3 of analysis 1.2; RR, 0.13; 95% CI, 0.07–0.23).

4.3. Time (Day) to Clinical Recovery Including Cough, Fever, Rales, and Chest Films

Studies investigating Chinese medicinal herbs plus basic therapy versus basic therapy showed a significant difference in cough (Figure 6; analysis 1.3; total MD, −2.18; 95% Cl, (−2.66)–(−1.71)), fever (Figure 7; analysis 1.4; total MD, −1.85; 95% Cl, (−2.29)–(−1.40)), rales (Figure 8; analysis 1.5; total MD, −1.53; 95% Cl, (−1.84)–(−1.23)), and chest films (Figure 9; analysis 1.6; total MD, −3.10; 95% Cl, (−4.11)–(−2.08)).

Figure 6 

Comparison. Chinese Medicinal herbs plus basic therapy versus basic therapy: outcome 3 cough.

Figure 7 

Comparison. Chinese medicinal herbs plus basic therapy versus basic therapy: outcome 4 fever.

Figure 8 

Comparison. Chinese medicinal herbs plus basic therapy versus basic therapy: outcome 5 rales.

Figure 9 

Comparison. Chinese medicinal herbs plus basic therapy versus basic therapy: outcome 6 chest films.

Subgroup two studies [16, 18] compared the modified Ma Xing Shi Gan Tang formula plus azithromycin versus azithromycin and showed a significant difference for cough (Figure 6; analysis 1.3.1 of analysis 1.3; MD, −2.55; 95% Cl, (−3.47)–(−1.63)), fever (Figure 7; analysis 1.4.1 of analysis 1.4; MD, −1.62; 95% Cl, (−2.49)–(−0.75)), and rales (Figure 8; analysis 1.5.1 of analysis 1.5; MD, −1.42; 95% Cl, (−2.40)–(−0.43)). Subgroup one study [18] compared the modified Ma Xing Shi Gan Tang formula plus azithromycin versus azithromycin and showed a significant difference on chest films (Figure 9; analysis 1.6.1 of analysis 1.6; MD, −1.77; 95% Cl, (−2.62)–(−0.92)).

Subgroup one study [21] compared the San Ao Tang formula plus azithromycin versus azithromycin and showed a significant difference in cough (Figure 6; analysis 1.3.2 of analysis 1.3; MD, −2.10; 95% Cl, (−2.94)–(−1.26)), fever (Figure 7; analysis 1.4.2 of analysis 1.4; MD, −2.50; 95% Cl, (−3.28)–(−1.72)), rales (Figure 8; analysis 1.5.2 of analysis 1.5; MD, −0.80; 95% Cl, (−1.42)–(−0.18)), and chest films (Figure 9; analysis 1.6.2 of analysis 1.6; MD, −5.00; 95% Cl, (−7.08)–(−2.92)).

Subgroup one study [22] compared the modified Zhi Sou San formula plus erythrocin versus erythrocin and showed a significant difference in cough (Figure 6; analysis 1.3.3 of analysis 1.3; MD, −1.70; 95% CI, (−2.03)–(−1.37)), fever (Figure 7 analysis 1.4.3 of analysis 1.4; MD, −2.36; 95% Cl, (−2.55)–(−2.17)), and rales (Figure 8 analysis 1.5.3 of analysis 1.5; MD, −2.02; 95% Cl, (−2.36)–(−1.68)).

Subgroup one study [23] compared a self-developed TCM prescription plus erythrocin versus erythrocin and showed a significant difference in cough (Figure 6 analysis 1.3.4 of analysis 1.3; MD, 3.20; 95% CI, (−5.07)–(−1.33)), rales (Figure 8 analysis 1.5.4 of analysis 1.5; MD, −2.11; 95% Cl, (−3.73)–(−0.49)), and chest films (Figure 9 analysis 1.6.3 of analysis 1.6; MD, −3.06; 95% Cl, (−4.53)–(−1.59)), but no difference in fever (Figure 7 analysis 1.4.4 of analysis 1.4; MD, −1.07; 95% Cl, −2.57–0.43).

Subgroup one study [24] compared Tanreqing injection plus antibiotics versus antibiotics and showed a significant difference in cough (Figure 6 analysis 1.3.5 of analysis 1.3; MD, −1.20; 95% CI, (−1.37)–(−1.03)), fever (Figure 7 analysis 1.4.5 of analysis 1.4; MD, −1.20; 95% Cl, (−1.69)–(−0.71)), and rales (Figure 8 analysis 1.5.5 of analysis 1.5; MD, −1.44; 95% Cl, (−1.56)–(−1.32)).

Subgroup two studies [25, 26] compared Reduning injection plus azithromycin versus azithromycin and showed a significant difference in cough (Figure 6 analysis 1.3.6 of analysis 1.3; MD, −2.48; 95% CI, (−3.22)–(−1.75)) and rales (Figure 8 analysis 1.5.6 of analysis 1.5; MD, −2.00; 95% CI, (−2.94)–(−1.05)). Subgroup three studies [25–27] compared Reduning injection plus azithromycin versus azithromycin and showed a significant difference in fever (Figure 7 analysis 1.4.6 of analysis 1.4; MD, −1.96; 95% CI, (−3.37)–(−0.55)). Subgroup one study [25] compared Reduning injection plus azithromycin versus azithromycin and showed a significant difference on chest films (Figure 9 analysis 1.6.4 of analysis 1.6; MD, −2.90; 95% CI, (−5.26)–(−0.54)).

Subgroup one study [28] compared Chuanhuning injection plus piperacillin versus piperacillin and showed a significant difference in cough (Figure 6 analysis 1.3.7 of analysis 1.3; MD, −2.47; 95% CI, (−2.89)–(−2.05)), fever (Figure 7 analysis 1.4.7 of analysis 1.4; MD, −1.48; 95% CI, (−1.90)–(−1.06)), rales (Figure 8 analysis 1.5.7 of analysis 1.5; MD, −1.70; 95% CI, (−2.18)–(−1.22)), and chest films (Figure 9 analysis 1.6.5 of analysis 1.6; MD, −3.48; 95% CI, (−3.94)–(−3.02)).

4.4. Length of Hospital Stay

One study [28] compared Chuanhuning injection plus piperacillin versus piperacillin and showed a significant difference in length of hospital stay (Figure 10 analysis 1.7; total MD, −3.00; 95% CI, (−3.52)–(−2.48)).

Figure 10 

Comparison. Chinese medicinal herbs plus basic therapy versus basic therapy: outcome 7 length of hospital stay.

4.5. Other Outcomes

Mortality, relapse rate, TCM outcomes (e.g., tongue coat and pulse condition), and economic index were not reported in any of the 14 studies.

5. GRADE Quality of Evidence

The “GRADEprofiler” of the Cochrane Collaboration Network was used to classify the systematic review results. The quality of evidence was low to very low (Table 3).

6. Discussion

Based on the 14 [15–28] RCTs conducted in China, Chinese medicinal herbs increased total effective rates (e.g., ratio of signs and symptoms improvement or recovery) and improved clinical symptoms and signs (e.g., cough, fever, rales, and chest films). However, the evidence that Chinese medicinal herbs decreased adverse effects, mortality, or improved TCM outcomes (e.g., tongue coat and pulse condition) was insufficient. The quality of the evidence was weak due to selective bias, measurement bias, selective reporting bias, and imprecision. Therefore, evidence from the included studies was not enough to make any recommendations.

First, randomization was mentioned in all 14 studies. However, one study [25] described the randomization method in detail, whereas 13 did not [15–24, 26–28]. We interviewed the authors by telephone and determined that a random number table or a computer-generated random-number table was used to generate the allocation sequence. Second, none of the studies mentioned a blinding method, but we interviewed the authors by telephone and found that 10 studies [15–17, 20–24, 26, 27] used single blinding (i.e., the outcome assessment was blinded), and four [18, 19, 25, 28] did not. The lack of blinding participants, health-care providers, and assessors can introduce performance and detection bias. Third, none of the studies addressed the incomplete outcome data, such as missing data due to attrition or exclusion. The inadequate handling of missing data can compromise statistical analyses. Fourth, the majority of experimental Chinese herbal medicine interventions were prepared by the investigators without detailed information describing their underlying rationale for the formulation, dosage, or the manufacturing process, and the quality control processes for their tested interventions are unknown. Thus, independent validation of these findings is necessary.

This paper has several methodological limitations. First, although all data were collected from reports or from direct contact with the authors, many items on the “risk of bias” assessment tool could only be classified as “unclear.” Second, different Chinese herbal medicine interventions were grouped together for analysis in some cases. The results might have been compromised by the heterogeneity within each Chinese herbal medicine intervention and the study design. Third, the concept of TCM syndrome was not considered when analyzing the data, as all studies only considered Childhood Pneumonia, not TCM symptoms. Therefore, the actual therapeutic effect might not have been fully captured.

Based on these reasons, the TCM RCTs should be conducted in accordance with the Consolidated Standards of Reporting Trials for Traditional Chinese Medicine [29] detailed report.

7. Conclusions

Chinese herbal medicines may increase total effective rates, improve clinical symptoms and signs, and shorten the length of hospital stay for children with pneumonia. In a word, Chinese herbal medicines are effective for Childhood Pneumonia. However, there is insufficient evidence to confirm whether Chinese herbal medicines decrease adverse effects, mortality, and TCM outcomes (such as tongue coat and pulse condition). All results were supported by poor methodological quality studies. Thus, larger, multicenter, high methodological quality studies of Chinese herbal medicines for Childhood Pneumonia are needed. These studies should include patients with Childhood Pneumonia and interventions with Chinese herbal medicines. More data, particularly concerning adverse events, are necessary. Meanwhile, future studies should determine the most appropriate drug and dosage for Childhood Pneumonia. So, further trials would help to clarify the validity of the findings of this paper and could determine more clearly the role of Chinese herbal medicines in Childhood Pneumonia in comparison with other therapies. Consequently, the purpose is to guide our application in clinical.

Conflict of Interests

The authors declare no conflict of interests.

Acknowledgments

The authors thank the Department of Nephrology Laboratory, Guangdong Province Hospital of Chinese Medicine. The authors thank the Department of Nephropathy Medicine, Guangdong Province Hospital Of Chinese Medicine. The project was support by the Scientific Research Project of Public Welfare Industry, State Administration of Traditional Chinese Medicine of China (no. 200707004).

References

1. A. L. Cohen, T. B. Hyde, J. Verani et al., “Integrating pneumonia prevention and treatment interventions with immunization services in resource-poor countries,” Bulletin of the World Health Organization, vol. 90, pp. 289–294, 2012. View at: Google Scholar
2. J. Anthony, G. Scott, C. Wonodi, J. C. Moisi et al., “The definition of pneumonia, the assessment of severity, and clinical standardization in the pneumonia etiology research for child health study,” Clinical Infectious Diseases, vol. 54, no. S2, pp. S109–S116, 2012. View at: Google Scholar
3. M. Mathisen, T. A. Strand, B. N. Sharma et al., “RNA viruses in community-acquired childhood pneumonia in semi-urban Nepal; a cross-sectional study,” BMC Medicine, vol. 7, article no. 35, 2009. View at: Publisher Site | Google Scholar
4. I. C. Michelow, K. Olsen, J. Lozano et al., “Epidemiology and clinical characteristics of community-acquired pneumonia in hospitalized children,” Pediatrics, vol. 113, no. 4 I, pp. 701–707.e7, 2004. View at: Publisher Site | Google Scholar
5. S. Tafuri, D. Martinelli, A. Grimaldi et al., “23-valent pneumococcal vaccine failure in a patient who developed pneumonia: a case report,” The New Microbiologica, vol. 34, pp. 417–420, 2011. View at: Google Scholar
6. United Nations Children's Fund, Pneumonia: the Forgotten Killer of Children, United Nations Children's Fund, New York, NY, USA, 2006.
7. G. M. Zhao, S. Black, H. Shinefield, and J. Eskola, “Rates of hospitalization and mortality for pneumonia and respiratory illness in China,” in Proceedings of the 5th International Symposium on Pneumococci and Pneumococcal Diseases, 2006, PO2.08. View at: Google Scholar
8. I. Rudan, C. Boschi-Pinto, Z. Biloglav, K. Mulholland, and H. Campbell, “Epidemiology and etiology of childhood pneumonia,” Bulletin of the World Health Organization, vol. 86, no. 5, pp. 408–416, 2008. View at: Publisher Site | Google Scholar
9. The WHO Young Infant Study Group, “Bacterial etiology of serious infections in young infants in developing countries: results of multicentre study,” Pediatric Infectious Diseases Journal, vol. 18, pp. 17–22, 1999. View at: Google Scholar
10. M. Korppi, O. Kiekara, T. Heiskanen-Kosma, and S. Soimakallio, “Comparison of radiological findings and microbial aetiology of childhood pneumonia,” Acta Paediatrica, International Journal of Paediatrics, vol. 82, no. 4, pp. 360–363, 1993. View at: Google Scholar
11. A. L. Hersh, D. J. Shapiro, J. G. Newland, P. M. Polgreen, S. E. Beekmann, and S. S. Shah, “Variability in pediatric infectious disease consultants' recommendations for management of community-acquired pneumonia,” PLoS ONE, vol. 6, no. 5, Article ID e20325, pp. 1–6, 2011. View at: Publisher Site | Google Scholar
12. S. K. Kabra, R. Lodha, and R. M. Pandey, “Antibiotics for community acquired pneumonia in children,” Cochrane Database of Systematic Reviews. In press. View at: Publisher Site | Google Scholar
13. T. Wu, J. Zhang, Y. Qiu, L. Xie, and G. J. Liu, “Chinese medicinal herbs for the common cold,” Cochrane Database of Systematic Reviews, no. 1, Article ID CD004782, 2007. View at: Publisher Site | Google Scholar
14. X. Li, Y. P. Zhang, and J. B. Lou, “Ma Xing Shi Gan Tang to treat respiratory disease research progress,” Journal of Guiyang College of Traditional Chinese Medicine, vol. 32, no. 5, pp. 66–68, 2010. View at: Google Scholar
15. H. M. Wang, J. L. Ge, and D. Mo, “Azithromycin combined with traditional Chinese Ma Xing Shi Gan Tang for children pneumonia and mycoplasma in 106 cases,” Medical Journal of Chinese People's Health, vol. 21, no. 19, pp. 2387–2389, 2009. View at: Google Scholar
16. X. C. Zhao and W. Y. Ji, “Maxing Shigan decoction combined with azithromycin for children pneumonia clinical observation,” Chinese Journal of Drug Abuse Prevention and Treatment, vol. 15, no. 6, pp. 358–360, 2009. View at: Google Scholar
17. X. H. Guo, “Integration of traditional Chinese and Western medicine for Children Pneumonia on 86 cases,” Fujian Medical Journal, vol. 21, no. 2, article 90, 1999. View at: Google Scholar
18. Y. M. Zhang, “San Ao Tang auxiliary treatment for children mycoplasma pneumonia infection observation of curative effect,” Chinese Traditional and Herbal Drugs, vol. 43, no. 2, pp. 341–342, 2012. View at: Google Scholar
19. D. J. He, “Combination of traditional Chinese and Western medicine for Childhood pneumonia in observation of clinical effect,” Journal China Health Monthly, vol. 30, no. 7, pp. 10–11, 2011. View at: Google Scholar
20. G. P. He, H. X. Lei, and H. H. Du, “Combination of traditional Chinese and Western medicine for 40 cases of pneumonia cough,” Journal of Shaanxi College of Traditional Chinese Medicine, vol. 34, no. 6, pp. 36–37, 2011. View at: Google Scholar
21. Y. M. Zhang, “San Ao Tang auxiliary treatment for children mycoplasma pneumonia infection observation of curative effect,” Chinese Traditional and Herbal Drugs, vol. 43, no. 2, pp. 341–342, 2012. View at: Google Scholar
22. S. Y. Wang, W. D. Pang, Q. Y. Chu et al., “Modified Zhi Sou San combined with erythromycin in treatment of Mycoplasma pneumonia curative effect analysis,” Modern Journal of Integrated Traditional Chinese and Western Medicine, vol. 18, no. 23, pp. 2797–2798, 2009. View at: Google Scholar
23. S. Q. Lv, D. Xie, S. F. Xia et al., “Combination of traditional Chinese and Western medicine for childhood mycoplasma pneumonia clinical practice,” Chinese Journal of Maternal and Child Health Care, vol. 24, no. 22, pp. 3093–3094, 2009. View at: Google Scholar
24. Z. Lei, “Combination of traditional Chinese and Western medicine for 80 cases childhood pneumonia clinical observation,” Journal of Traditional Chinese Medicine Information, vol. 2, no. 1, article 91, 2010. View at: Google Scholar
25. Y. F. Shi, “Combination of traditional Chinese and Western medicine for childhood mycoplasma pneumonia in 40 cases,” Chinese Pediatrics of Integrated Traditional and Western Medicine, vol. 1, no. 4, pp. 364–365, 2009. View at: Google Scholar
26. W. Q. Pan, “Combined medication for community acquired pneumonia in children 70 cases,” Chinese Medicine Modern Distance Education of China, vol. 9, no. 20, pp. 56–57, 2011. View at: Google Scholar
27. X. Z. Duan and X. C. Feng, “Reduning Injection for childhood Mycoplasma pneumoniae on clinical study,” Journal of Changchun University of Traditional Chinese Medicine, vol. 27, no. 2, pp. 171–172, 2011. View at: Google Scholar
28. H. Wei and S. K. Feng, “Observation on effect of Chuanhuning Injection for childhood pneumonia,” Journal of Youjiang Medical College for Nationalities, vol. 25, no. 4, article 516, 2003. View at: Google Scholar
29. T. X. Wu, H. C. Shang, and Z. X. Bian, “Randomized controlled pragmatic trial: concept, design, practice,” Chinese Journal of Evidence-Based Medicine, vol. 9, no. 12, pp. 1277–1280, 2009. View at: Google Scholar

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Copyright © 2013 Qianchun Yang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.