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Comparison of Zataria multiflora Extract Syrup and Diphenhydramine in the Treatment of Common Cold-Induced Cough in Children: A Double-Blind, Randomized, Clinical Trial

AUTHORS

Firozeh Hosseini 1 , Hossein Mahjoub 2 , Ali Amanati 3 , Mohammad Mehdi Fazlian 4 , Iraj Sedighi 1 , *

1 Department of Pediatrics, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, IR Iran

2 Department of Statistics, Faculty of Health, Hamadan University of Medical Sciences, Hamadan, IR Iran

3 Professor Alborzi Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran

4 Department of Emergency, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, IR Iran

How to Cite: Hosseini F, Mahjoub H, Amanati A, Fazlian M M, Sedighi I. Comparison of Zataria multiflora Extract Syrup and Diphenhydramine in the Treatment of Common Cold-Induced Cough in Children: A Double-Blind, Randomized, Clinical Trial, Arch Pediatr Infect Dis. 2016 ; 4(3):e35495. doi: 10.5812/pedinfect.35495.

ARTICLE INFORMATION

Archives of Pediatric Infectious Diseases: 4 (3); e35495
Published Online: May 30, 2016
Article Type: Research Article
Received: December 13, 2015
Revised: February 26, 2016
Accepted: April 17, 2016
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Abstract

Background: Management of cold-associated cough is a challenging aspect of supportive care for the common cold for pediatricians and parents worldwide. Herbal compounds have traditionally been used for the treatment of cold-related cough. Among these compounds, Zataria multiflora (ZM) has been found to be effective for cough relief.

Objectives: The aim of this study is to compare a thyme mixture with diphenhydramine in the treatment of cold-related cough in a double-blind, randomized, clinical trial.

Patients and Methods: A total of 52 pediatric patients (2 - 12 years old) with common colds were included in the study. The patients were randomly divided into two treatment groups: one group received diphenhydramine compound and the other received ZM syrup, each for five days. The severity of cold-related symptoms and the efficacy of each drug were determined seven days later by asking the parents to complete a prepared questionnaire. sedation, sleepiness, a four-point scale of cough status, and a two-point scale of consumption convenience were also evaluated in these questionnaires.

Results: Our results showed that sedation and sleepiness occurred in 30.8% and 19.2% of the patients in the diphenhydramine and ZM groups, respectively (P = 0.54). Also, 65.4% and 84.6% of the patients in the diphenhydramine and ZM groups, respectively, reported convenient usage (P = 0.10). The patients who received ZM syrup had significantly better outcomes (P = 0.036).

Conclusions: Herbal compounds, such as ZM mixtures, are acceptably efficacious in cough relief with fewer adverse effects than chemical compounds in the treatment of cold-related cough, especially in infants and younger children.

Keywords

Common Cold Zataria Multiflora Cough Children

Copyright © 2016, Pediartric Infections Research Center. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

1. Background

The cold is one of the most common reasons for pediatric visits to clinics, and it is estimated that each child suffers from an average of 6 - 8 colds per year. Cough is one of the most frequent complications of a cold, especially in children (1). Herbal compounds and other non-chemical agents are frequently used for symptom relief as an alternative option for patients with a poor response to conventional drugs (2). In the United States, there is a public trend toward the use of these agents for cough or cold (3). These products are currently used to an extent that causes concern about adverse effects and interactions with other agents (4, 5). Many homemade indigenous herb preparations for colds have been weakly evaluated. Previous studies showed inconclusive results for the efficacy of cough medicines in the treatment of cold-related cough in adults and children, and it seems that high-quality research is still needed to provide evidence-based recommendations for herbal agents (6-8). There have been only four clinical trials that compared cough medicines with placebo in children (9-12).

Among both over-the-counter (OTC) and homemade preparations, thyme has been shown to be effective in the treatment of cold-related cough. The most common variety is Thymus vulgaris, which is indigenous in many countries in Europe. T. vulgaris is not native to Iran, but is presently cultivated in several parts of this country (especially in the outskirts of the Zagros Mountains in western Iran), and it is widely refined as a tea, spice, and herbal medicine (13, 14). Zataria multiflora (ZM; Shirazi thyme) is a thyme-like flowering plant of the Lamiaceae family, and is native to Iran (15). ZM is chemically similar to T. vulgaris, and its leaf is listed in the Herbal Pharmacopoeia (15). Many studies have demonstrated the antibacterial and anti-inflammatory effects of ZM extract (16-19). Although there are inconclusive results about ZM products used for the relief of gastrointestinal syndromes, few studies have been carried out on the antitussive effects of this indigenous plant (20, 21).

2. Objectives

We conducted the present study to compare a ZM mixture with diphenhydramine in the treatment of cold-related cough in children, using a double-blind, randomized, placebo-controlled clinical trial.

3. Patients and Methods

A total of 52 children aged 2 - 12 years with common colds, who were referred to the outpatient pediatric clinics of Hamadan University of Medical Sciences, Hamadan, Iran, were enrolled. We included children with typical signs and symptoms of common cold, after ruling out any similar conditions, such as acute sinusitis or other respiratory tract infections. Additional exclusion criteria included a previous history of antibiotic treatment, chronic concomitant disorders (e.g., asthma), and other coexisting conditions that interfered with our patients’ cough self-evaluation (e.g., mental retardation) or with evaluation by their parents (e.g., failure of close observation).

The patients were randomly allocated to one of two treatments groups. One group (n = 26) was given diphenhydramine compound (1.25 mg/kg three times a day) and the other group (n = 26) was given ZM syrup (2 mg/kg three times a day), each prescribed for five consecutive days. The ZM extract was provided by Tolid-Darou, Tehran, Iran. Each child received the drug in an unlabeled bottle. The bottles were pre-numbered in consecutive order according to the patient’s time of enrollment. The patients were blinded to the drugs until the end of the study. All clinical evaluations were performed by a single pediatrician who was blinded to the contents of the drugs used.

The parents were asked to complete a questionnaire seven days later about the severity of their child’s cold-related symptoms and the efficacy of each drug. These questionnaires also contained parameters such as the induction of sedation and sleepiness (mild to severe), a five-point scale of cough status (completely improved, moderately improved, somewhat improved, not improved, and worsened), and a two-point scale of consumption convenience (good or bad). Demographic data was also obtained.

This study was approved by the ethics committee of Hamadan University of Medical Sciences and Health Services, and informed consent was obtained from all parents.

Statistical analyses were performed on all collected data using SPSS version 13 (SPSS, Chicago, IL, USA). The chi-square test, the Mann-Whitney U test, and student’s t-test were used for non-parametric and parametric variables, respectively. P values of 0.05 or lower were considered statistically significant.

4. Results

A total of 52 patients (22 females, 30 males) were randomized, and half received the trial medication. The patients had an average age of 52.55 ± 28.55 months, and there was no difference between the genders (P = 0.70). The parents’ education levels did not differ statistically significantly between the two groups (P > 0.05). The patients’ weights were 16.78 ± 5.6 kg, with no significant difference between the two groups (P = 0.77).

Our results showed that sedation and sleepiness occurred in 30.8% and 19.2% of the patients in the diphenhydramine and ZM groups, respectively (P = 0.54). Meanwhile, 65.4% and 84.6% of the patients in the diphenhydramine and ZM groups, respectively, reported convenient usage (P = 0.10). In comparison to the diphenhydramine group, cough status statistically significantly improved (P = 0.036) in the ZM group (Table 1).

Table 1. Cough Status in the Diphenhydramine and ZM Groupsa
GroupCough Status
WorsenedNot ImprovedSomewhat ImprovedModerately ImprovedCompletely Improved
Diphen hydramine6 (23.1)6 (23.1)4 (15.4)7 (26.9)3 (11.5)
Zataria multiflora04 (15.4)5 (19.2)7 (26.9)10 (38.5)

aP Value = 0.036.

5. Discussion

Our data confirmed that the clinical efficacy of Zataria multiflora (Shirazi thyme) extract syrup was statistically significant and clinically relevant in decreasing the severity of cold-related cough in children. Herbal compounds with antitussive properties are widely used for the treatment of cold-related symptoms (8, 22). There are considerable differences between countries with regard to the availability and recommended use of traditional and complementary medicine (T&CM), which continues to be a challenging issue in other aspects, such as safety, effectiveness, and quality (8, 23). However, there is an increasing trend toward the use of T&CM in developed countries (24, 25). Despite the worldwide popularity of T&CM, there is little evidence to support its use based on satisfactory clinical trials that evaluate safety and efficacy (8, 26). As previously noted, there have been only a few studies on the use of non-chemical agents in children (4, 8, 27).

The immunopharmacological potential of T. vulgaris has been established by various in vitro and in vivo models (28). Meanwhile, in a clinical evaluation, Buechi et al. concluded that thyme herbs are useful for reducing cough in the symptom-score system, with acceptable tolerability for the treatment of common cold, bronchitis, and other respiratory tract diseases (29). In contrast, the results of a study by Taylor did not support the use of certain herbs (such as Echinacea purpurea) for the treatment of URI symptoms in children (30).

The most recent Cochrane review re-emphasized previous conclusions (22, 31) that there is a “lack of good evidence for or against the effectiveness of over the counter (OTC) medications in acute cough” (8). Some authors explicitly recommend against the use of these medications (7).

To the best of our knowledge, there have been few studies on the usefulness of thyme extract for upper respiratory tract infections. The present study is the first double-blind, randomized, clinical trial of the antitussive effects of Zataria multiflora in children (32, 33).

Our study found no side effects from ZM in the treatment of cough in the interventional group, and the parents were satisfied with using ZM for their children.

5.1. Conclusion

The results of this prospective randomized clinical trial confirmed the efficacy and safety of ZM in the treatment of cough caused by the common cold.

Acknowledgements

Footnotes

References

  • 1.

    Miller EK, Williams JV. The common cold, in Nelson text book of pediatrics. 2016;

  • 2.

    Ghazi-Moghadam K, Inancli HM, Bazazy N, Plinkert PK, Efferth T, Sertel S. Phytomedicine in otorhinolaryngology and pulmonology: clinical trials with herbal remedies. Pharmaceuticals (Basel). 2012; 5(8) : 853 -74 [DOI][PubMed]

  • 3.

    Kogan MD, Pappas G, Yu SM, Kotelchuck M. Over-the-counter medication use among US preschool-age children. JAMA. 1994; 272(13) : 1025 -30 [PubMed]

  • 4.

    Du Y, Wolf IK, Zhuang W, Bodemann S, Knoss W, Knopf H. Use of herbal medicinal products among children and adolescents in Germany. BMC Complement Altern Med. 2014; 14 : 218 [DOI][PubMed]

  • 5.

    Kaufman DW, Kelly JP, Rosenberg L, Anderson TE, Mitchell AA. Recent patterns of medication use in the ambulatory adult population of the United States: the Slone survey. JAMA. 2002; 287(3) : 337 -44 [PubMed]

  • 6.

    Eccles R. The powerful placebo in cough studies? Pulm Pharmacol Ther. 2002; 15(3) : 303 -8 [DOI][PubMed]

  • 7.

    Schroeder K, Fahey T. Systematic review of randomised controlled trials of over the counter cough medicines for acute cough in adults. BMJ. 2002; 324(7333) : 329 -31 [PubMed]

  • 8.

    Smith SM, Schroeder K, Fahey T. Over-the-counter (OTC) medications for acute cough in children and adults in community settings. Cochrane Database Syst Rev. 2014; 11[DOI][PubMed]

  • 9.

    Taylor JA, Novack AH, Almquist JR, Rogers JE. Efficacy of cough suppressants in children. J Pediatr. 1993; 122(5 Pt 1) : 799 -802 [PubMed]

  • 10.

    Korppi M, Laurikainen K, Pietikainen M, Silvasti M. Antitussives in the treatment of acute transient cough in children. Acta Paediatr Scand. 1991; 80(10) : 969 -71 [PubMed]

  • 11.

    Bhattacharya M, Joshi N, Yadav S. To compare the effect of dextromethorphan, promethazine and placebo on nocturnal cough in children aged 1-12 y with upper respiratory infections: a randomized controlled trial. Indian J Pediatr. 2013; 80(11) : 891 -5 [DOI][PubMed]

  • 12.

    Paul IM, Yoder KE, Crowell KR, Shaffer ML, McMillan HS, Carlson LC, et al. Effect of dextromethorphan, diphenhydramine, and placebo on nocturnal cough and sleep quality for coughing children and their parents. Pediatrics. 2004; 114(1) -90 [PubMed]

  • 13.

    Javed H, Erum S, Tabassum S, Ameen F. An overview on medicinal importance of thymus vulgaris. J Asian Sci Res. 2013; 3(10) : 974

  • 14.

    Rustaiyan A, Masoudi S, Monfared A, Kamalinejad M, Lajevardi T, Sedaghat S, et al. Volatile constituents of three Thymus species grown wild in Iran. Planta Med. 2000; 66(2) : 197 -8 [DOI][PubMed]

  • 15.

    Sajed H, Sahebkar A, Iranshahi M. Zataria multiflora Boiss. (Shirazi thyme)--an ancient condiment with modern pharmaceutical uses. J Ethnopharmacol. 2013; 145(3) : 686 -98 [DOI][PubMed]

  • 16.

    Amirghofran Z, Ahmadi H, Karimi MH. Immunomodulatory activity of the water extract of Thymus vulgaris, Thymus daenensis, and Zataria multiflora on dendritic cells and T cells responses. J Immunoassay Immunochem. 2012; 33(4) : 388 -402 [DOI][PubMed]

  • 17.

    Eftekhar F, Zamani S, Yusefzadi M, Hadian J, Ebrahimi SN. Antibacterial activity of zataria multiflora boiss essential oil against extended spectrum β lactamase produced by urinary isolates of klebsiella pneumonia. Jundishapur J Microbiol. 2011; 4(5) : 43 -9

  • 18.

    Malekinejad H, Bazargani-Gilani B, Tukmechi A, Ebrahimi H. A cytotoxicity and comparative antibacterial study on the effect of Zataria multiflora Boiss, Trachyspermum copticum essential oils, and Enrofloxacin on Aeromonas hydrophila. Avicenna J Phytomed. 2012; 2(4) : 188 -95 [PubMed]

  • 19.

    Motevasel M, Okhovat MA, Zomorodian K, Farshad S. A study of the effect of zataria multiflora extract on methicillin resistant staphylococcus aureus. Jundishapur J Microbiol. 2013; 6(5)[DOI]

  • 20.

    Sodouri M, Masoudi Alavi N, Fathizadeh N, Taghizadeh M, Azarbad Z, Memarzadeh M. Effects of Zataria Multi-Flora, Shirazi thyme, on the Severity of Premenstrual Syndrome. Nurs Midwifery Stud. 2013; 2(4) : 57 -63 [PubMed]

  • 21.

    Vafaarani Z, Khosravi S, Hekmatpou D, Rafiei F. Effect of zataria multiflora (shirazi thyme) on gastrointestinal symptoms in intensive care units nurses. Complement Med J faculty of Nurs Mid. 2015; 5(1) : 1054 -64

  • 22.

    Smith SM, Schroeder K, Fahey T. Over-the-counter (OTC) medications for acute cough in children and adults in ambulatory settings. Cochrane Database Syst Rev. 2008; 1

  • 23.

    WHO traditional medicine strategy: 2014-2023. 2013;

  • 24.

    De Smet PA. Herbal remedies. N Engl J Med. 2002; 347(25) : 2046 -56 [DOI][PubMed]

  • 25.

    Zuzak TJ, Bonkova J, Careddu D, Garami M, Hadjipanayis A, Jazbec J, et al. Use of complementary and alternative medicine by children in Europe: published data and expert perspectives. Complement Ther Med. 2013; 21 Suppl 1 -47 [DOI][PubMed]

  • 26.

    Cravotto G, Boffa L, Genzini L, Garella D. Phytotherapeutics: an evaluation of the potential of 1000 plants. J Clin Pharm Ther. 2010; 35(1) : 11 -48 [DOI][PubMed]

  • 27.

    Menniti-Ippolito F, Forcella E, Bologna E, Gargiulo L, Traversa G, Raschetti R. Use of unconventional medicine in children in Italy. Eur J Pediatr. 2002; 161(12) : 690 [PubMed]

  • 28.

    Bodinet C, Lindequist U, Teuscher E, Freudenstein J. Effect of an orally applied herbal immunomodulator on cytokine induction and antibody response in normal and immunosuppressed mice. Phytomedicine. 2002; 9(7) : 606 -13 [DOI][PubMed]

  • 29.

    Buechi S, Vogelin R, von Eiff MM, Ramos M, Melzer J. Open trial to assess aspects of safety and efficacy of a combined herbal cough syrup with ivy and thyme. Forsch Komplementarmed Klass Naturheilkd. 2005; 12(6) : 328 -32 [DOI][PubMed]

  • 30.

    Taylor J, Evans C. Cough and cold medication use in young children: Pharmacist reaction to changes in Canada. J Am Pharm Assoc (2003). 2009; 49(6) : 783 -6 [DOI][PubMed]

  • 31.

    Smith SM, Schroeder K, Fahey T. Over-the-counter medications for acute cough in children and adults in ambulatory settings. Cochrane Database Syst Rev. 2008; (1)[DOI][PubMed]

  • 32.

    Kemmerich B. Evaluation of efficacy and tolerability of a fixed combination of dry extracts of thyme herb and primrose root in adults suffering from acute bronchitis with productive cough. A prospective, double-blind, placebo-controlled multicentre clinical trial. Arzneimittelforschung. 2007; 57(9) : 607 -15 [DOI][PubMed]

  • 33.

    Kemmerich B, Eberhardt R, Stammer H. Efficacy and tolerability of a fluid extract combination of thyme herb and ivy leaves and matched placebo in adults suffering from acute bronchitis with productive cough. A prospective, double-blind, placebo-controlled clinical trial. Arzneimittelforschung. 2006; 56(9) : 652 -60 [DOI][PubMed]

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