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THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINEVolume 16, Number 7, 2010, pp. 787–793ª Mary Ann Liebert, Inc.
DOI: 10.1089/acm.2009.0311 A Comparison of the Effect of Honey, Dextromethorphan, and Sleep Quality in Children and Their Parents Mahmood Noori Shadkam, MD,1 Hassan Mozaffari-Khosravi, PhD,2 and Mohammad Reza Mozayan, MSc3 Objectives: Coughing is a prevalent symptom of upper respiratory infections (URIs) that cause disturbance inthe sleep of children and their parents. There is as yet no reliable treatment to control URIs and their relatedcough; however, drugs such as dextromethorphan (DM) and diphenhydramine (DPH) are now mainly used inthe world. The aim of this study is to compare the effect of honey, DM, and DPH on the nightly cough and sleepquality of children and their parents.
Design: This was a clinical trial study in which 139 children aged 24–60 months suffering from coughing due toURIs were selected and assigned randomly to 4 groups. The first group received honey (HG), the second oneDM (DMG), the third DPH (DPHG), but the fourth group or control group (CG) was assigned to a supportivetreatment.
Outcome measures: After approximately a 24-hour intervention, the 4 groups were reexamined and their coughfrequency, cough severity, and sleep quality in children and their parents were recorded by using the ques-tionnaire with Likert-type questions.
Results: The mean of cough frequency score HG is 4.09 Æ 0.72 and 1.93 Æ 0.65 before and after the intervention,respectively, while these figures for the CG are 4.11 Æ 0.78 and 3.11 Æ 0.57, respectively. After the intervention,the difference of the mean score of the variables in all groups became statistically significant. The mean score ofall variables in HG has stood significantly higher than those in other groups. There is also a significant rela-tionship between the DMG and CG groups, even though there is no statistically difference between DMG andDPHG groups.
Conclusions: The result of the study demonstrated that receiving a 2.5-mL dose of honey before sleep has a morealleviating effect on URIs-induced cough compared with DM and DPH doses.
form of cough. Most of the symptoms emerge during the first3 days but are fortunately relieved in a week; the cough, Upper respiratory tract infections (URIs) are the however, may remain for a longer time.3 Coughing, espe- prevalent diseases among children, sending many of cially during the night, can cause trouble and disturbance for these patients to physicians every year.1,2 Each year, children the children’s and parents’ sleep.4 Each year, billions of are usually affected 6–8 times by the disease; however, its dollars are spent to control and cure cough while the cough prevalence among adults is 2–3 times.2 Normally, viruses, and in less than 10% of the cases, bacteria, are the producers There is as yet no appropriate and acceptable treatment of these infections.1 The URIs are usually ameliorated for URIs and the resultant cough. The antitussive drug that is spontaneously. Even though they are not associated with frequently utilized for children is dextromethorphan (DM); disability and mortality, they can cause morbidity and however, this drug has not yet been confirmed by the Pe- medical costs. The typical signs and symptoms of the disease diatrics Academy of America.6,7 Diphenhydramine (DPH) is are the following: rhinorrhea, sneeze, malaise, a slight fever, also another drug that is used in relation to coughs, but its and cough.2 These, in around 50% of people, are in the form relieving effect is controversial.1 In the present study, the of dry and sore throat, while in 40% others they appear in the effect of both DM and DPH has been compared with honey Departments of Pediatrics,1 Nutrition,2 and English Language,3 Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
especially in a larger population, whereas in Paul’s study4 antihistamine, DPH, or DM 4 hours before sleep or had consumed cytochrome P450 inhibitors simultaneously (i.e., In traditional medicine, honey is used to treat the signs serotonin-reabsorption selective inhibitors) were also ex- and symptoms of URIs, especially coughing.4,8,9 Honey has cluded from the study. Parents were also excluded if they also been used to repair sores and injuries in children.4,10–13 were using a drug and herbal that had an effect on sleeping, Also, the World Health Organization recently recommended honey for controlling cough and other URI symptoms.14Compared with the drugs, honey is less expensive, more available, and especially safer to be used for children. The A standard researcher-made questionnaire previously relieving effect of honey has been known to be from its an- designed for the purpose and formerly used in other studies tioxidant and cytokine-releasing features, thus justifying its was filled in by asking questions of the children’s mothers.4,8 antimicrobial effect.15–19 Regardless of these, honey is also The questionnaire in the first part included demographic considered a food substance consisting of various nutrients, variables such as age and gender. In the second part (i.e., the energy, and different phytochemicals, which have both cur- main part), it included four key questions related to cough, severity of cough, sleep quality of the child as well as those of In view of the prevalent problems of coughing due to parent, respectively (Fig. 1). The answers to the questions URIs in children and the fact that a reliable treatment for this were categorized on the basis of a Likert-type scale graded has not yet been found, the aim of this study was to compare from 0 ( ¼ not at all) to 6 ( ¼ extremely). The questionnaire the effects of DM, DPH, and honey on the nightly cough and was completed by each mother in the presence of a pedia- sleep quality of children and their parents.
trician before and after a 1-night intervention. (Note that inIran, children are referred to physicians mostly through their mothers; mothers also take care of children at home.) Any ambiguous question for the mother, if any, was answered bya pediatrician. Thus, after a physician visited the patient, the This is a clinical trial study that began in December 2008 questionnaire was completed and on the following day each and ended in May 2009. The subjects were 160 children aged mother and child revisited the doctor and the relevant 24–60 months suffering from URI-induced cough. On the questionnaire was completed once more but after the inter- basis of the previous studies (i.e., power ¼ 80% and a ¼ 0.05), a total of 140 children were randomly assigned to 4 groups(35 in each group). To be on the safe side (i.e., if a subject would not come back or would not perform the medicalorders appropriately), 5 others were added to each group, Using Table of Random Numbers, the subjects were thus totaling 160 children (40 in each group) who partici- placed in 1 of the 4 groups. The first group (HG) received pated in the study. All or some of these children were suf- 2.5 mL of natural honey from Kafi-Abad (a village in Yazd) fering from symptoms such as rhinorrhea, sneeze, sore before sleep. The second (DMG) and third (DPHG) groups throat, and stuffed nose. Their coughing had lasted 5 days.
received 2.5 mL of DM syrup (7.5 mg, Pour-Sina drug Those with the diseases such as asthma, pneumonia, laryn- gotracheobronchitis, sinusitis, allergic rhinitis, chronic lung 1228051241), and 2.5 mL of DPH syrup (6.25 mg, Ramoo- disease, congenital heart disease, malignancy, and diabetes Farmon drug manufacturing company, Registered No.
were not included in the study. Those who had consumed 1228056772), respectively, before sleep. The honey and other 1) How frequent was your child’s cough last night? 2) How much did last night’s cough affect your child’s ability to sleep? 3) How much did last night’s cough affect your ability to sleep? 4) How severe was your child’s cough last night? Survey questions about nightly cough and sleep difficulty. Adapted with permission from the study by Paul et al.,4 Arch Pediatr Adolesc Med 2007;16(12):1140–1146. ª2007 American Medical Association. All rights reserved.
Table 1. Mean and Frequency of Variables of the 4 Groups at the Beginning of the Study dw2.
HG, honey group; DMG, dextromethorphan group; DPHG, diphenhydramine group; CG, control group.
drugs are usually used at room temperature of about 22– was used to compare the frequency distribution between 268C. The fourth group (CG), however, was given only groups. The p-values were considered significant at p < 0.05.
supportive treatment recommended for other groups as well.
The supportive treatments included saline nose drops, water vapor, cleaning a blocked nose, and using acetaminophen if A consent form was obtained from each child’s mother.
fever existed. All mothers were offered the same standard on They could quit the study freely whenever they liked. The the disease and how to use liquids, nose drops, and hu- Research Ethics Committee of the Shahid Sadoughi Uni- midifier by a pediatrician. All 4 groups were examined the versity of Medical Sciences approved the relevant research following day and the same questionnaire was completed for them once more. The subjects who for any reason had con-sumed an inappropriate dose of the drugs were excludedfrom the survey.
Of 160 participants, 21 were excluded from the study for not visiting the physician as scheduled or inappropri- Data were analyzed by SPSS software version 11 (SPSS ately using the drugs (7, 4, 6, and 4 patients from HG, Inc., Chicago, IL). For comparing the average mean of each DMG, DPHG, and CG groups, respectively), so 139 pa- of the quantifiable variables for pre- and postintervention, a tients’ data were finally analyzed. In general, the aver- paired t-test was used; one-way analysis of variance and age mean age of the children was 37.75 Æ 11.12 months. Of multiple comparison tests were used for comparing the av- the patients, 71 (51.1%) were girls and 68 (48.9%) were erage mean of quantifiable variables between groups; w2 test Table 2. Mean of Variables of the Four Groups Before and After the Study aPaired t-test.
HG, honey group; DMG, dextromethorphan group; DPHG, diphenhydramine group; CG, control group.
Table 3. Mean of Variables of the 4 Groups at the End of the Study aOne-way analysis of variance.
HG, honey group; DMG, dextromethorphan group; DPHG, diphenhydramine group; CG, control group.
The mean and frequency of variables of the 4 groups at the the groups, the multiple comparison test was used, the result beginning of the study are shown in Table 1. As is indicated, of which is summarized in Table 4. According to the results, none of the variables were statistically significant between the mean score of all variables in the HG has stood signifi- cantly higher than those in other groups. On the other hand, In Table 2 the mean scores of cough frequency, cough there is also a significant relationship between DMG and CG severity, and sleep quality in children and their parents in all group even though there is no statistically significant dif- groups have been compared and as demonstrated the dif- ference between the DMG and DPHG groups.
ference in each group before and after the intervention isstatistically significant. This difference is not, however, the same in all groups. As an example, the mean of cough fre-quency for HG is 4.09 Æ 0.76 and 1.93 Æ 0.65 before and after The results of this study demonstrated that honey com- the intervention, respectively, while these figures for the CG pared with other groups had a significantly more effective are 4.19 Æ 0.78 and 3.11 Æ 0.57, respectively.
curing impact on cough frequency, cough severity, and sleep A comparison of the average mean score of the dependent quality of children and their parents. DM and DPH had also a variables in all groups after the intervention is also shown in relieving effect on the factors mentioned compared with CG.
Tables 3 and 4. As is evident from Table 3, after approxi- However, no difference was found between the two groups mately a 24-hour intervention the difference of the mean statistically. Also, in a study by Paul et al., it was demon- score of the variables in all groups has become statistically strated that honey could have a curing effect on cough and different. However, in order to check the difference among sleep pattern of children and their parents; however, the study Table 4. Multiple Comparisons Between Groups at the End of the Study aPost hoc multiple comparisons.
HG, honey group; DMG, dextromethorphan group; DPHG, diphenhydramine group; CG, control group.
found that DM compared with the no-treatment group did not study by Yoder et al., it was indicated that somnolence can have a better effect on URI-induced cough.4 In another study be taken as one of the complications of DPH.20 No compli- carried out by Yoder et al. on 37 children aged 6–18 years old, cation was found for the DM group in our study.
no significant relationship was found for the relieving effect of A limitation of this study has been its intervention period.
DM and DPH and placebo on the cough produced by URI- As was explained, each patient received just one dose of induced cough.20 Also, the results of the study by Bjorns- honey or drugs, and it is clear that if the intervention period dotlir et al. indicated that DM and DPH would have no had been longer (i.e., each patient had used more than one relieving effect on the nightly symptoms of URI.21 dose of drugs), the results would be more reliable and of Our study confirmed the results of the previous studies more value. On the other hand, there would be more op- regarding the curing effect of honey on children’s nightly portunity for the demonstration of complications, if any.
cough induced by URIs. This study, however, indicated that Therefore, for further studies this limitation has to be taken DM and DPH also have a relieving effect on this cough but into consideration. The fact that this study was not blinded compared with honey, their effect is less, which is statisti- can be regarded as another limitation for this study, thus Several studies have also reported the antimicrobial and In conclusion, the finding of the study suggests that re- antioxidant effect of honey.15,17,22,23 It has been suggested ceiving a 2.5-mL dose of honey before sleep has a more re- that these effects can lead to healing of wound, thus justi- lieving effect on the nightly cough of children and others fying our results. Honey possesses various phenolic com- compared with DM or DPH. Thus, in these conditions it is pounds as well, which are related to its antioxidant feature.17, 18,24 Eccles has recently demonstrated some usefuleffects of honey.25 He has suggested that the sweet sub- stances of honey normally reflexively secrete saliva, which We would like to thank all those who have assisted in the might cause secretion of mucus in the airways. The secretion fulfillment of this study, including mothers and their chil- of mucus can have a relieving effect on the larynx and dren for their participation in the survey as well as the pharynx, thus alleviating cough, especially the dry cough.
Deputy for Health Services in Shahid Sadoughi University of He also adds that consuming sweet substances causes the production of internal opioids as well. The interaction effectbetween the sensory fibers responding to opioids and gus- tatory sensory fibers may help in producing the antitussiveeffect of the sweet substances associated with a central ner- The authors declare that they have no conflicts of interest.
This study was fully funded by the Department of Research DM is currently used to treat coughs in the United Administration, Shahid Sadoughi University of Medical States.5–7,26–29 Although in a cohort study it was found that this is well tolerated, over-the counter studies reveal that Dr. Mahmood Noori Shadkam is a scientific member of this drug can produce side-effects such as dystonia,30 ana- the Pediatric Department at SSUMS that participated in case phylaxis,31 mastocytosis,32 dependence,33,34 psychosis,35 selection and supervising the study. Dr. Hassan Mozaffari- mania,36,37 hallucination,38 ataxia,39,40 somnolence,40 insulin- Khosravi is a Senior Lecturer in the Human Nutrition De- dependent diabetes,41 peripheral neuropathy,42 cerebral de- partment at SSUMS and facilitated with the designing, data generation,19 megaloblastic anemia, and death43 if used at a analysis, and writing the manuscript. Mohammad Reza high dose. There are reports that DPH is increasingly mis- Mozayan facilitated with writing the manuscript. All of au- used by adults.44,45 DPH, as the first-generation antihista- thors are employed by SSUMS and all critically reviewed the mine, also has its own side-effects. This type of antihistamine manuscript and approved the final version submitted for has been known to cause somnolence but occasionally it may also create restlessness, nervousness, and sleeplessness.46,47Standard doses of DPH have some relation with acute dys- tonia48 and impaired driving ability.49,50 Long-term use andhigh dose of this drug can cause habit formation,51,52 psy- 1. Fahey T, Stocks N, Thomas T. Systematic review of the chosis,53–55 cardiac dysrhythmia and long QT,53,56–59 rhab- treatment of upper respiratory tract infection. Arch Dis domyolysis,60,61 epilepsy,53,56 and death.62,63 In this study, 2 children, who had been affected by otitis 2. Ronald BT, Gregory FH. The common cold. In: Robert MK, Richard EB, Hall BJ, Bonita FS, eds. Nelson Text Book of media on their following visit, were then treated by antibi- Pediatrics. Philadelphia: Saunders Elsevier, 2007:1747–1749.
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