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蜂蜜治疗小儿急性咳嗽

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Referencias

Ahmadi 2013 {published data only}

Ahmadi M, Moosavi SM, Zakeri S. Comparison of the effect of honey and diphenhydramine on cough alleviation in 2‐5 year‐old children with viral upper respiratory tract infection. Journal of Gorgan University of Medical Science 2013;15(2):8‐13. CENTRAL

Cohen 2012 {published data only}

Cohen HE, Rozen J, Kristal H, Laks Y, Berkovitch M, Uziel Y, et al. Effect of honey on nocturnal cough and sleep quality: a double‐blind, randomised, placebo‐controlled study. Pediatrics 2012;130(3):465‐71. [DOI: 10.1542/peds.2011‐3075]CENTRAL

Paul 2007 {published and unpublished data}

Paul IM, Beiler J, McMonagle A, Shaffer ML, Duda L, Berlin CM. Effect of honey, dextromethorphan, and no treatment on nocturnal cough and sleep quality for coughing children and their parents. Archives of Pediatrics and Adolescent Medicine 2007;161(12):1140‐6. CENTRAL

Peixoto 2016 {published data only}

Peixoto DM, Rizzo JA, Schor D, Silva AR, Cavalcanti de Oliveira D, Solé D, et al. Use of honey associated with Ananas comosus (Bromelin) in the treatment of acute irritative cough [Uso do mel de abelha associado ao Ananas comosus (Bromelin) no tratamentoda tosse irritativa aguda]. Revista Paulista de Pediatria 2016;34(4):412‐7. CENTRAL

Shadkam 2010 {published data only}

Shadkam MN, Mozaffari‐Khosravi H, Mozayan MR. A comparison of the effect of honey, dextromethorphan, and diphenhydramine on nightly cough and sleep quality in children and their parents. Journal of Alternative and Complementary Medicine (New York, NY) 2010;16(7):787‐93. [DOI: 10.1089/acm.2009.0311]CENTRAL

Waris 2014 {published data only}

Waris A, Macharia WM, Njeru EK, Essajee F. Randomised double blind study to compare effectiveness of honey, salbutamol and placebo in treatment of cough in children with common cold. East African Medical Journal 2014;91(2):50‐6. CENTRAL

Ahmed 2013a {published data only}

Ahmed N, Sutcliffe A, Tipper C. Feasibility study: honey for treatment of cough in children. Pediatric Reports 2013;5(e8):31‐4. [DOI: 10.4081/pr.2013.e8]CENTRAL

Ayazi 2017 {published data only}

Ayazi P, Mahyar A, Yousef‐Zanjani M, Allami A, Esmailzadehha N, Beyhaghi T. Comparison of the effect of two kinds of Iranian honey and diphenhydramine on nocturnal cough and the sleep quality in coughing children and their parents. PLoS ONE 2017;12(1):e0170277. [DOI: 10.1371/journal.pone.0170277]CENTRAL

Baker 2016 {published data only}

Baker SJ. Honey for acute cough in children. Paediatrics and Child Health 2016;21(4):199‐200. CENTRAL

Cohen 2017 {published data only}

Cohen HA, Hoshen M, Gur S, Bahir A, Laks Y, Blau H. Efficacy and tolerability of a polysaccharide‐resin‐honey based cough syrup as compared to carbocysteine syrup for children with colds: a randomized, single‐blinded, multicenter study. World Journal of Pediatrics 2017;13(1):27‐33. [DOI: 10.1007/s12519‐016‐0048‐4]CENTRAL

Gilbert 2008 {published data only}

Gilbert G. Single dose of honey effective for cough in kids. Journal of the National Medical Association 2008;100(4):459. CENTRAL

Miceli Sopo 2014 {published data only}

Miceli Sopo S, Greco M, Monaco S, Varrasi G, Di Lorenzo G, Simeone G, Milk Honey Study Group. Effect of multiple honey doses on non‐specific acute cough in children. An open randomised study and literature review. Allergologia et Immunopathologia 2014;43(5):449‐55. CENTRAL

Warren 2007 {published data only}

Warren MD, Pont SJ, Barkin SL, Callahan ST, Caples TL, Carroll KN, et al. The effect of honey on nocturnal cough and sleep quality for children and their parents. Archives of Pediatrics and Adolescent Medicine 2007;161(12):1149‐53. CENTRAL

IRCT2014090819037N1 {published data only}

IRCT2014090819037N1. Comparison of the effect of two kinds of Iranian honey and diphenhydramine on nocturnal cough and sleep quality in coughing children and their parents. apps.who.int/trialsearch/Trial2.aspx?TrialID=IRCT2014090819037N1 (first received 23 September 2013). CENTRAL

NCT03218696 {unpublished data only}

NCT03218696. Comparison of a protective cough syrup against placebo on night cough in children 1‐5 years coughing since 1‐2 days due to common cold. clinicaltrials.gov/ct2/show/NCT03218696 (first received 14 July 2017). CENTRAL

UMIN000020651 {unpublished data only}

UMIN000020651. Effectiveness of honey and expectorant for nocturnal cough in children with acute upper respiratory infection: a prospective interventional study. rctportal.niph.go.jp/en/detail?trial_id=UMIN000020651 (first received 25 January 2016). CENTRAL

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Ahmed M, Djebli N, Aissat S, Khiati B, Meslem A, Bacha S. In vitro activity of natural honey alone and in combination with curcuma starch against Rhodotorula mucilaginosa in correlation with bioactive compounds and diastase activity. Asian Pacific Journal of Tropical Biomedicine 2013;3(10):816‐21.

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Characteristics of studies

Characteristics of included studies [ordered by study ID]

Ahmadi 2013

Methods

Study design: RCT

Study duration: 2010 to November 2012

Participants

  • Setting: a paediatric outpatient clinic, Shariatee Hospital, Bandar Abbas

  • Country: Iran

  • Health status: viral upper respiratory tract infection with complaints of sneezing, blocked nose, sore throat, cough, mild headache

  • Number: treatment (63); control (63)

  • Age (mean ± SD)

    • treatment: 45.21 ± 11.39 months

    • control: 43.98 ± 11.95 months

  • Sex (M/F): 60/66

    • treatment (M/F): 27/36

    • control (M/F): 33/30

Exclusion criteria

Onset of otitis or sinusitis symptoms; onset of symptoms of lower respiratory tract involvement; adding a bacterial infection (purulent nasal discharge, high fever, difficulty breathing, periorbital oedema, facial pain); not using recommended treatments; adding other drugs to recommended treatment; conflicting reports of the carers of the participants

Interventions

Treatment group

  • Intervention: honey (Mahram)

  • Dose, duration, frequency, administration: honey was placed in glasses similar to those belonging to diphenhydramine and with a similar concentration, mixed with distilled lukewarm water, administered 3 times a day, with last dose given an hour before sleeping.

Control group

  • Intervention: 5 mg/kg diphenhydramine syrup

  • Dose, duration, frequency, administration: 5 mg/kg body weight, 3 times a day, with last dose given an hour before sleeping

Honey was given in the same volume, frequency, and duration of use as diphenhydramine.

Outcomes

  • Severity of cough

  • Frequency of cough

Notes

  • Funding source: unknown

  • Contact with study authors for additional information: we contacted authors for additional information but received no response.

  • A volunteer translated the study from Farsi to English.

  • A 7‐point Likert‐like scale was used for cough assessment.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Not described but likely done. Randomisation was done by the hospital pharmacist who was not involved in the study.

Allocation concealment (selection bias)

Low risk

Not described but probably done. Quote: "The classification of patients was done by the hospital pharmacist"

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Honey was placed in glasses similar to those belonging to diphenhydramine and with a similar concentration, mixed with distilled lukewarm water. The honey and diphenhydramine mixtures were prepared by the pharmacist, who was not part of the study. The paediatricians and parents were unaware of the nature of the treatment each child received.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: "the treating doctor and the mother were unaware of the nature of the medication (honey or diphenhydramine)"; "In order to prevent the confounding factor of mother’s anxiety or her personal situation, her reports were only accepted if they were corroborated by the reports of a third person close to the child"

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All children randomised to treatment arms completed the 2‐day study.

Selective reporting (reporting bias)

Low risk

Both outcomes listed in the methods section were reported.

Other bias

Unclear risk

Results were presented as the proportion of children with reduced symptom cough instead of the actual mean symptom scores. Furthermore, the scale used for measurement was not clear (a 7‐point Likert‐like scale was used for cough assessment). The protocol was registered retrospectively after completion of the study.

Cohen 2012

Methods

Study design: RCT

Study duration: January 2009 to December 2009

Participants

  • Setting: 6 paediatric community clinics

  • Country: Israel

  • Health status: children with upper respiratory infection who "were ill with a mean ± SD of 2.8 ± 2.0 days before enrolment". Upper respiratory infection was "defined by the presence of cough and rhinorrhea of #7 days’ duration".

  • Number (total = 300):

    • treatment 1, eucalyptus honey (N = 75)

    • treatment 2, citrus honey (N = 75)

    • treatment 3, Labiatae honey (N = 75)

    • control, placebo (N = 75)

  • Age: median age of children who completed the study was 29 months (range 12 to 71 months).

    • treatment:

      • eucalyptus honey: mean 27.5 months ± 13.9

      • citrus honey: mean age 29 months ± 13.5

      • Labiatae honey: mean age 30 months ± 16.6

    • control: mean age 29 months ± 14.9

  • Sex: unclear

Exclusion criteria

Quote: "children were excluded if they had signs or symptoms of asthma, pneumonia, laryngotracheobronchitis, sinusitis, and/or allergic rhinitis. Children were also excluded if they had used any cough or cold medication or honey on the night before entering the study"

Interventions

Treatment group

  • Intervention: eucalyptus honey, citrus honey, or Labiatae honey (3 intervention arms)

  • Dose, duration, frequency, administration: single 10 g dose administered 30 minutes before bedtime

Control group

  • Intervention: silan (date) extract (similar structure, colour, and taste to honey)

  • Dose, duration, frequency, administration: single 10 g dose administered 30 minutes before bedtime

Outcomes

  • Cough frequency

  • Cough severity

  • Bothersome nature of cough

  • Child and parent sleep quality

  • The combined score of these 4 measures

Notes

  • Funding source: quote: "Supported in part by a research grant from Israel Ambulatory Paediatric Association, Maternal Infant Nutrition Research Institute and the Honey Board of Israel"

  • Contact with study authors for additional information: we contacted the authors to confirm the proportion of boys to girls of the 300 children randomised. Authors did not respond to our query.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation was in blocks of 4.

Allocation concealment (selection bias)

Low risk

The envelopes containing the codes for the study preparations were stored at the office of the Ministry of Agriculture, Extension service, Beekeeping Department and were not opened until after the statistical analysis was completed.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

The 3 honeys and the placebo were prepared by someone not involved in the study; interventions were packed in small plastic containers marked A, B, C, and D and distributed to the paediatric community clinics. Silan date extract was used as a placebo because its structure, brown colour, and taste are similar to that of honey. The parents, physicians, and investigators did not know the content of the preparation that was dispensed.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

The parents, physicians, and investigators did not know the content of the preparation that was dispensed. Interventions were packed in small plastic containers marked A, B, C, and D and distributed to the paediatric community clinics. Silan date extract was used as a placebo because its structure, brown colour, and taste are similar to that of honey.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

14 (19%), 13 (18%), 2 (3%), and 4 (5%) children were lost to follow‐up in the eucalyptus honey, citrus honey, Labiatae honey, and placebo groups, respectively. The authors stated that the reasons for loss to follow‐up were unknown. However, attrition was significantly high in the eucalyptus honey and citrus honey groups. It is unclear if the reasons for attrition in the treatment groups were related to the study or not and if the reasons were similar.

Selective reporting (reporting bias)

Low risk

All outcomes listed in the protocol were reported.

Other bias

Low risk

Not detected

Paul 2007

Methods

RCT

Participants

  • Setting: a single outpatient general paediatric practice

  • Country: USA

  • Health status: "The URIs were characterized by the presence of rhinorrhea and cough for 7 or fewer days’ duration. Other symptoms may have included but were not limited to congestion, fever, sore throat, myalgias, and headache" (p. 1141)

  • Number (total = 108):

    • honey (N = 35)

    • control:

      • dextromethorphan (N = 34)

      • no treatment (N = 39)

  • Age: 2 to 18 years; median age of the 105 children completing the study was 5.22 years (range 2.22 to 16.92 years)

    • treatment (median ± interquartile range, years): honey = 5.43 ± 3.81

    • control (median ± interquartile range, years):

      • dextromethorphan = 4.42 ± 3.83

      • no treatment = 5.22 ± 4.33

  • Sex: unclear

Exclusion criteria

Quote: "patients were excluded if they had signs or symptoms of a more treatable disease (e.g., asthma, pneumonia, laryngotracheobronchitis, sinusitis, allergic rhinitis). They were also ineligible when they had a history of reactive airways disease, asthma, or chronic lung disease or were using a drug known to inhibit the metabolism of dextromethorphan, such as selective serotonin reuptake inhibitors. Subjects were also excluded if on the prior evening they had taken a medication that included an antihistamine or dextromethorphan hydrobromide within 6 hours of bedtime or dextromethorphan polistirex within 12 hours of bedtime on the evening prior to or on the day of enrolment" (p. 1141)

Interventions

Treatment group

  • Intervention: buckwheat honey

  • Dose, duration, frequency, administration: "For the honey group, the volume of honey dispensed was equivalent to the age‐driven volume dispensed for DM [dextromethorphan]"

Control group

  • Intervention: "artificially honey‐flavoured DM [dextromethorphan], (17 mg/5 mL prepared using DM hydrobromide powder [100% pure United States Pharmacopeia grade], artificial honey flavoring, coloring, stevia liquid extract, methocel, and simple syrup [Professional Compounding Centers of America, Houston, Texas])", no treatment = empty syringe

  • Dose, duration, frequency, administration: "dosage for DM [dextromethorphan] approximated typical OTC label recommendations, with children aged 2 to 5 years receiving 8.5 mg/dose (1/2 teaspoon), children aged 6 to 11 years receiving 17 mg/dose (1 teaspoon), and children aged 12 to 18 years receiving 34 mg/dose (2 teaspoons). Of note, these concentrations slightly exceed typical OTC products, which contain 15 mg/5 mL, and were the result of the compounding process but may be more likely to achieve a beneficial effect based on our previous analyses"

Parents were instructed that their child’s treatment could be given with a non‐caffeinated beverage and should be administered within 30 minutes of the child going to sleep. Intervention and control were in a 10‐millilitre opaque syringe and kept in brown paper bags.

Outcomes

  • Cough frequency

  • Cough severity

  • Bothersome nature of cough

  • Cough impact on sleep quality for child and parent

  • The combined score of these 4 measures

Notes

  • Funding source: "this study was supported by an unrestricted research grant from the National Honey Board, an industry‐funded agency of the USA Department of Agriculture"

  • Contact with study authors for additional information: we contacted the lead author for additional information on the proportion of boys to girls of the 108 children randomised and other missing data. Authors responded that they could not provide the information because they no longer have the data.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Not described but probably done. Quote: "The randomisation sequence was constructed by a statistician not affiliated with the study and was then used by the study coordinators to assign treatment group"

Allocation concealment (selection bias)

Low risk

Not described but probably done. Treatment allocation was concealed in 10‐millilitre opaque syringe and kept in brown paper bags.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

The syringes used for all 3 treatment groups were opaque and placed in a brown paper bag to conceal the treatments from the investigators. The no‐treatment group was not blinded to their treatment, but the honey and dextromethorphan arms were blinded.

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Although all participants were given syringes in brown paper bags, the no‐treatment group had empty syringes, which could influence the assessment of the outcome.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

2 children from the no‐treatment group were lost to follow‐up; 1 was withdrawn from the dextromethorphan group because the participant did not take the treatment.

Selective reporting (reporting bias)

Low risk

All outcomes were adequately reported.

Other bias

Low risk

It is unclear whether any of the no‐treatment group revealed to any of the assessors during phone conversations that they were given no treatment. Children lost to follow‐up or withdrawn were not included in the final analysis.

Peixoto 2016

Methods

RCT

Participants

  • Setting: a paediatric service of Clinica Amaury Coutinho, linked to Recife City Hall

  • Country: Brazil

  • Health status: "irritative cough for at least 24 hours, which led to the need for medical consultation, participated in the study. Patients should have acute cough due to viral upper airway infection, thus considered due to the presence of mild fever or fever associated with hyaline or catarrhal rhinorrhea, lasting less than 72 hours, without clinical manifestations of associated bronchospasm"

  • Number (total = 60):

    • treatment: honey (N = 29)

    • control: bromelin (N = 31)

  • Age: age in years, mean (25 to 75 percentiles):

    • treatment: honey: mean 5.6 years (2.0 to 7.5 years)

    • control: bromelin: mean 5.3 years (3.0 to 7.5 years)

  • Sex of children who completed study (M/F):

    • treatment: honey (13/16)

    • control: bromelin (13/18)

Exclusion criteria

Children with history of obstructive pulmonary disease, cystic fibrosis, neuropathies, heart disease, diabetes, or identifiable primary or secondary immunodeficiencies

Interventions

Treatment group

  • Intervention: honey

  • Dose, duration, frequency, administration: children up to 20 kg received 5 mL; for those weighing > 20 kg, 1 mL was administered for every 5 kg additional weight.

Control group

  • Intervention: the combination of honey and Ananas comosus extract HBS19820501 (rich in bromelin) as syrup formulation

  • Dose, duration, frequency, administration: children up to 20 kg received 5 mL; for those weighing > 20 kg, 1 mL was administered for every 5 kg additional weight.

Quote: "the quality of the honey was certified in both groups and approved by the regulatory agencies and the National Health Surveillance Agency (Anvisa) for sale; the honey had been recently produced and underwent strict bacteriological control"

Outcomes

  • Cough frequency

  • Reduction in cough severity

Notes

  • Funding source: Hebron Indústrias Químicas

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation was carried out according to a table generated in Microsoft Excel.

Allocation concealment (selection bias)

Low risk

Not described but very likely. Treatments were labelled A and B. Quote: "Neither the investigator nor the patient, nor the family knew which product was used"; "The treatment groups were revealed only after the analysis of the study results"

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "neither the investigator nor the patient, nor the family knew which product was used. The treatment groups were revealed only after the analysis of the study results"

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: "neither the investigator nor the patient, nor the family knew which product was used. The treatment groups were revealed only after the analysis of the study results"

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All participants randomised were included in the final analysis.

Selective reporting (reporting bias)

Low risk

All outcomes listed in the study protocol and methods section were reported.

Other bias

Unclear risk

Used an unvalidated 5‐point cough scale that differed from the cough scale used by the other included studies

Shadkam 2010

Methods

RCT

Participants

  • Setting: 6 paediatric community clinics

  • Country: Iran

  • Health status: "2 to 5 years of age with URTIs, nocturnal symptoms and illness duration of 5 days. All or some of these children were suffering from symptoms such as rhinorrhoea, sneeze, sore throat, and stuffed nose. Their coughing had lasted 5 days"

  • Number (total = 160):

    • treatment: honey (N = 40)

    • control:

      • dextromethorphan (N = 40)

      • diphenhydramine (N = 40)

      • no treatment (N = 40)

  • Age (children who completed the study): 37.75 ± 11.12 months

    • treatment: honey: mean age 37 ± 11.4 months

    • control:

      • dextromethorphan: mean age 37 ± 11.1 months

      • diphenhydramine: mean age 38 ± 11.4 months

      • no treatment: mean age 37.8 ± 10.9 months

  • Sex: not reported

Exclusion criteria

"asthma, pneumonia, laryngotracheobronchitis, sinusitis, allergic rhinitis, chronic lung disease, congenital heart disease, malignancy, and diabetes were not included in the study. antihistamine, diphenhydramine, or dextromethorphan 4 hours before sleep or had consumed cytochrome P450 inhibitors simultaneously (i.e. serotonin‐reabsorption selective inhibitors) were also excluded from the study. Parents were also excluded if they were using a drug and herbal that had an effect on sleeping, such as sedatives"

Interventions

Treatment group

  • Intervention: a single dose of natural honey from Kafi‐Abad (a village in Yazd, Iran)

  • Dose, duration, frequency, administration: received 2.5 mL of natural honey before sleep

Control group

  • Intervention: dextromethorphan, diphenhydramine, or no treatment (received supportive treatment recommended for other groups as well)

  • Dose, duration, frequency, administration: the second (dextromethorphan) and third (diphenhydramine) groups received 2.5 mL of dextromethorphan syrup (7.5 mg, Pour‐Sina drug manufacturing company in Tehran, Registered No. 1228051241) and 2.5 mL of diphenhydramine syrup (6.25 mg, RamooFarmon drug manufacturing company, Registered No. 1228056772), respectively, before sleep.

  • All treatment arms were advised to take supportive treatment with saline nose drops, water vapour, cleaning of a blocked nose, and use of paracetamol for fever, if necessary. All mothers were offered the same standard on the disease and how to use liquids, nose drops, and humidifier by a paediatrician.

Outcomes

  • Cough frequency

  • Cough severity

  • Child sleep score

  • Parents' sleep quality

Notes

  • Funding source: Department of Research Administration, Shahid Sadoughi University of Medical Sciences (SSUMS) in Yazd, Iran

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation was by random numbers table.

Allocation concealment (selection bias)

Unclear risk

It was not clear whether treatment allocation was concealed.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Neither the investigators nor caregivers were blinded to treatments given, which could greatly influence the assessment of outcome.

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Neither the investigators nor caregivers were blinded to treatments given, which could greatly influence the assessment of outcome.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

7 participants from the honey group, 4 from the dextromethorphan group, 6 from the diphenhydramine group, and 4 from the no‐treatment group were either lost to follow‐up or withdrawn for violating the protocol. Attrition was high for the honey and diphenhydramine groups. Participants were excluded from analysis for not visiting the physician as scheduled or using the drugs inappropriately. The proportion of children who did not visit physician as scheduled or violated protocol per group was unclear.

Selective reporting (reporting bias)

Low risk

All outcomes listed in the protocol were reported.

Other bias

Unclear risk

Some of the questions put to mothers were answered by the paediatrician because the questions were ambiguous, which could also have influenced the assessment of outcomes. Since mothers were filling in the questionnaire in the presence of the physician, it is unclear if this could have influenced the assessment of outcomes (p. 788)

Waris 2014

Methods

RCT

Participants

  • Setting: the paediatric casualty of the Aga Khan University Hospital Nairobi. This is a national tertiary referral and teaching hospital serving the middle‐ and upper‐income society in Nairobi and its environment.

  • Country: Kenya

  • Health status: an uncomplicated acute upper respiratory infection (authors did not define acute upper respiratory infection)

  • Number (total = 145):

    • treatment: honey (N = 57)

    • control:

      • salbutamol (N = 43)

      • placebo (N = 45)

  • Age: 1 to 12 years

    • treatment: not clear

    • control: not clear

  • Sex of children who completed study (M/F):

    • honey (30/24)

    • control:

      • salbutamol (unclear)

      • placebo: (unclear)

Exclusion criteria

Prior use (48 hours) of any cough mixture, study agents, oral antihistamines, nasal decongestants, steroids, or antibiotics. Other exclusions were any past history of atopy, asthma, or any chronic lung disease as well as hospitalisation for lower respiratory tract infection in the past 6 months.

Interventions

Treatment group

  • Intervention: the darkest locally available honey was used.

  • Dose, duration, frequency, administration: 2.5 mL (age 1 to 2 years), 5 mL (age 2 to 6 years), 7.5 mL (age 6 to 12 years); all were administered 3 times daily for 5 days

Control group

  • Intervention:

    • salbutamol has 2 mg of active ingredient per 5 mL.

    • placebo was a brown‐coloured sugar and alcohol‐free syrup with an inert thickening agent whose ingredients included sodium citrate, citric acid monohydrate hypromellose, sodium benzoate, saccharin sodium, sodium chloride, caramel colour, and water.

  • Dose, duration, frequency, administration: 2.5 mL (age 1 to 2 years), 5 mL (age 2 to 6 years), 7.5 mL (age 6 to 12 years); all were administered 3 times daily for 5 days

Outcomes

  • Cough frequency

  • Cough severity

  • Bothersome cough

  • Cough effect on children's sleep

  • Cough effect on parents' sleep

  • Combined symptom score

Notes

  • Funding source: Universal Corporation Ltd prepared all study drugs at no cost.

  • Contact with study authors for additional information: we contacted the authors for additional information on cough scores and mean age of children randomised.

  • It is unclear if the salbutamol was oral or inhaled. It was most likely oral because parents were given all study drugs to administer to their children at home.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Dispensing study drugs was undertaken following a random order previously generated by a statistician not involved in care of study participants.

Allocation concealment (selection bias)

Low risk

Not described, but risk of bias unlikely. All 3 study drugs were prepared, bottled, packaged, and labelled as Study Drug A, B, and C by Universal Corporation Ltd, who also held the code until after statistical analysis was completed.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

All 3 study drugs were prepared, bottled, packaged, and labelled as Study Drug A, B, and C by Universal Corporation Ltd, who also held the code until after statistical analysis was completed.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

All 3 study drugs were prepared, bottled, packaged, and labelled as Study Drug A, B, and C by Universal Corporation Ltd, who also held the code until after statistical analysis was completed.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

13%, 7%, and 5% of children in the placebo, honey, and salbutamol groups, respectively, were lost to follow‐up or were in violation of study protocol. It is unclear if the reasons for not completing the study were the same across study groups. It is possible that more participants in the placebo group left because their condition worsened.

Selective reporting (reporting bias)

Low risk

Not detected

Other bias

Low risk

Unlikely

ITT: intention‐to‐treat; OTC: over‐the‐counter; RCT: randomised controlled trial; SD: standard deviation; URTI: upper respiratory tract infection

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Ahmed 2013a

Not an RCT; this was a feasibility study of honey for the treatment of cough in children

Ayazi 2017

Quasi‐RCT

Baker 2016

Not an RCT; commentary on a previous version of this review (Oduwole 2014a)

Cohen 2017

Wrong intervention: compared polysaccharide‐resin‐honey to carbocysteine syrup. The study examined honey‐based cough syrup (polysaccharide‐resin‐honey) versus a non‐honey‐based cough syrup (carbocysteine syrup). We would have included this study if the comparisons had been polysaccharide‐resin‐honey versus honey alone/polysaccharide‐resin alone or carbocysteine syrup + honey versus carbocysteine syrup alone.

Gilbert 2008

Not an RCT

Miceli Sopo 2014

Wrong intervention: compared honey and milk versus dextromethorphan and honey and milk versus levodropropizine

Warren 2007

Not an RCT

RCT: randomised controlled trial

Characteristics of studies awaiting assessment [ordered by year of study]

IRCT2014090819037N1

Methods

Randomised clinical trial

Participants

Children aged 2 to 12 years

Interventions

2 types of honey versus diphenhydramine

Outcomes

Cough frequency, bothersome nature of cough, and severity

Notes

Completed

Characteristics of ongoing studies [author‐defined order]

NCT03218696

Trial name or title

Comparison of a protective cough syrup against placebo on night cough in children 1 to 5 years coughing since 1 to 2 days due to common cold

Methods

Randomised controlled trial

Participants

Children aged 1 to 5 years (i.e. 1 day before the 6th birthday, males and females)

Inclusion criteria: cough attributed to infection of the upper respiratory tract present in the child for not more than 2 days

Interventions

Cough syrup containing specific plant extracts (Poliflav MA) and honey versus placebo

Outcomes

Primary

  • night cough frequency score reduction

Secondary

  • night cough bothersome score reduction

  • night cough intensity score reduction

  • reduction of influence of cough on child sleep score

  • reduction of influence of cough on combined night score

  • reduction of influence of cough on parent sleep score

(Time frame: First and only night of treatment)

Starting date

September 2017

Contact information

Prof Herman A Cohen

Email: [email protected]

Affiliation: Clalit Health Services

Notes

This study is not yet open for participant recruitment (November 2017).

UMIN000020651

Trial name or title

Effectiveness of honey and expectorant for nocturnal cough in children with acute upper respiratory infection: a prospective interventional study

Methods

Parallel randomised

Participants

Children aged 2 to 16 years

Inclusion criteria:

  • Patient diagnosed with acute upper respiratory infection with cough for 7 or fewer days duration

  • Nocturnal cough score 3 or more (using a 7‐point Likert scale)

Interventions

Honey (5 g for those age 2 to 5 years, 10 g for those aged 6 years and above) orally before bedtime for a week versus carbocysteine (30 mg/kg/day) and ambroxol (0.9 mg/kg/day) orally for a week

Outcomes

Primary outcome: change in frequency of nocturnal cough on the next day when honey or expectorant had been given prior to bedtime compared to that on the first day of presentation when no medication had been given

Secondary outcomes:

Change in severity of nocturnal cough, bothersome cough, appetite, and quality of sleep at night on the next day when honey or expectorant had been given prior to bedtime compared to that on the first day of presentation when no medication had been given.

Improvement of nocturnal cough 1 week after honey or expectorant had been given prior to bedtime compared to that on the first day of presentation when no medication had been given

Starting date

25 January 2016

Contact information

Name: Kazushi Agata; Shun Kishibe

Address: 1163 Tatemachi, Hachioji, Tokyo, Japan; 2‐8‐29 Musashidai, Fuchu‐shi, Tokyo, Japan

Email: [email protected]; [email protected]

Affiliation: Tokyo Medical University Hachioji Medical Center Pediatrics; Tokyo Metropolitan Children's Medical Center Pediatric Emergency Medicine

Notes

Data and analyses

Open in table viewer
Comparison 1. Pair‐wise comparison

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Honey versus dextromethorphan Show forest plot

2

Mean Difference (Random, 95% CI)

Subtotals only

Analysis 1.1

Comparison 1 Pair‐wise comparison, Outcome 1 Honey versus dextromethorphan.

Comparison 1 Pair‐wise comparison, Outcome 1 Honey versus dextromethorphan.

1.1 Frequency of cough (mean reduction in cough frequency)

2

149

Mean Difference (Random, 95% CI)

‐0.07 [‐1.07, 0.94]

1.2 Severity of cough (mean reduction in severity of cough)

2

149

Mean Difference (Random, 95% CI)

‐0.13 [‐1.25, 0.99]

1.3 Bothersome cough (mean reduction in bothersome cough)

1

69

Mean Difference (Random, 95% CI)

0.29 [‐0.56, 1.14]

1.4 Children's sleep (mean reduction in cough impact on sleep score)

2

149

Mean Difference (Random, 95% CI)

0.03 [‐1.12, 1.19]

1.5 Parents' sleep (mean reduction in cough impact on sleep score)

2

149

Mean Difference (Random, 95% CI)

‐0.16 [‐0.84, 0.53]

1.6 Combined cough score (reduction in combined cough score)

1

69

Mean Difference (Random, 95% CI)

2.32 [‐1.24, 5.88]

2 Honey versus diphenhydramine Show forest plot

1

Mean Difference (Random, 95% CI)

Subtotals only

Analysis 1.2

Comparison 1 Pair‐wise comparison, Outcome 2 Honey versus diphenhydramine.

Comparison 1 Pair‐wise comparison, Outcome 2 Honey versus diphenhydramine.

2.1 Frequency of cough (mean reduction in cough frequency)

1

80

Mean Difference (Random, 95% CI)

‐0.57 [‐0.90, ‐0.24]

2.2 Severity of cough (mean reduction in severity of cough)

1

80

Mean Difference (Random, 95% CI)

‐0.6 [‐0.94, ‐0.26]

2.3 Children's sleep (mean reduction in cough impact on sleep score)

1

80

Mean Difference (Random, 95% CI)

‐0.55 [‐0.87, ‐0.23]

2.4 Parents' sleep (mean reduction in cough impact on sleep score)

1

80

Mean Difference (Random, 95% CI)

‐0.48 [‐0.76, ‐0.20]

3 Honey versus no treatment Show forest plot

2

Mean Difference (Random, 95% CI)

Subtotals only

Analysis 1.3

Comparison 1 Pair‐wise comparison, Outcome 3 Honey versus no treatment.

Comparison 1 Pair‐wise comparison, Outcome 3 Honey versus no treatment.

3.1 Frequency of cough (mean reduction in frequency of cough)

2

154

Mean Difference (Random, 95% CI)

‐1.05 [‐1.48, ‐0.62]

3.2 Severity of cough (mean reduction in severity of cough)

2

154

Mean Difference (Random, 95% CI)

‐1.03 [‐1.59, ‐0.47]

3.3 Bothersome cough (mean reduction in bothersome cough)

1

74

Mean Difference (Random, 95% CI)

‐0.93 [‐1.98, 0.12]

3.4 Children's sleep (mean reduction in cough impact on sleep score)

2

154

Mean Difference (Random, 95% CI)

‐1.04 [‐1.57, ‐0.51]

3.5 Parents' sleep (mean reduction in cough impact on sleep score)

2

154

Mean Difference (Random, 95% CI)

‐0.88 [‐1.23, ‐0.52]

3.6 Combined reduction in symptoms score

1

74

Mean Difference (Random, 95% CI)

‐4.31 [‐6.77, ‐1.85]

4 Honey versus placebo (Day 1) Show forest plot

2

Mean Difference (Random, 95% CI)

Subtotals only

Analysis 1.4

Comparison 1 Pair‐wise comparison, Outcome 4 Honey versus placebo (Day 1).

Comparison 1 Pair‐wise comparison, Outcome 4 Honey versus placebo (Day 1).

4.1 Frequency of cough (mean reduction in frequency of cough)

2

402

Mean Difference (Random, 95% CI)

‐1.62 [‐3.02, ‐0.22]

4.2 Severity of cough (mean reduction in severity of cough)

2

402

Mean Difference (Random, 95% CI)

‐1.07 [‐2.43, 0.30]

4.3 Bothersome cough (mean reduction in bothersome cough)

2

402

Mean Difference (Random, 95% CI)

‐1.40 [‐2.82, 0.03]

4.4 Children's sleep (mean reduction in cough impact on sleep score)

2

402

Mean Difference (Random, 95% CI)

‐1.21 [‐2.61, 0.19]

4.5 Parents' sleep (mean reduction in cough impact on sleep score)

2

402

Mean Difference (Random, 95% CI)

‐1.29 [‐2.71, 0.13]

5 Honey versus placebo (Day 2) Show forest plot

1

Mean Difference (Random, 95% CI)

Subtotals only

Analysis 1.5

Comparison 1 Pair‐wise comparison, Outcome 5 Honey versus placebo (Day 2).

Comparison 1 Pair‐wise comparison, Outcome 5 Honey versus placebo (Day 2).

5.1 Frequency of cough (mean reduction in frequency of cough)

1

102

Mean Difference (Random, 95% CI)

‐0.71 [‐1.22, ‐0.20]

5.2 Severity of cough (mean reduction in severity of cough)

1

102

Mean Difference (Random, 95% CI)

‐0.63 [‐1.36, 0.10]

5.3 Bothersome cough (mean reduction in bothersome cough)

1

102

Mean Difference (Random, 95% CI)

‐1.11 [‐1.79, ‐0.43]

5.4 Children's sleep (mean reduction in cough impact on sleep score)

1

102

Mean Difference (Random, 95% CI)

‐0.69 [‐1.43, 0.05]

5.5 Parents' sleep (mean reduction in cough impact on sleep score)

1

102

Mean Difference (Random, 95% CI)

‐0.87 [‐1.59, ‐0.15]

6 Honey versus placebo (Day 3) Show forest plot

1

Mean Difference (Random, 95% CI)

Subtotals only

Analysis 1.6

Comparison 1 Pair‐wise comparison, Outcome 6 Honey versus placebo (Day 3).

Comparison 1 Pair‐wise comparison, Outcome 6 Honey versus placebo (Day 3).

6.1 Frequency of cough (mean reduction in frequency of cough)

1

102

Mean Difference (Random, 95% CI)

‐1.13 [‐1.71, ‐0.55]

6.2 Severity of cough (mean reduction in severity of cough)

1

102

Mean Difference (Random, 95% CI)

‐0.85 [‐1.41, ‐0.29]

6.3 Bothersome cough (mean reduction in bothersome cough)

1

102

Mean Difference (Random, 95% CI)

‐1.33 [‐1.87, ‐0.79]

6.4 Children's sleep (mean reduction in cough impact on sleep score)

1

102

Mean Difference (Random, 95% CI)

‐0.93 [‐1.42, ‐0.44]

6.5 Parents' sleep (mean reduction in cough impact on sleep score)

1

102

Mean Difference (Random, 95% CI)

‐0.88 [‐1.38, ‐0.38]

7 Honey versus placebo (Day 4) Show forest plot

1

Mean Difference (Random, 95% CI)

Subtotals only

Analysis 1.7

Comparison 1 Pair‐wise comparison, Outcome 7 Honey versus placebo (Day 4).

Comparison 1 Pair‐wise comparison, Outcome 7 Honey versus placebo (Day 4).

7.1 Frequency of cough (mean reduction in frequency of cough)

1

102

Mean Difference (Random, 95% CI)

‐1.16 [‐1.83, ‐0.49]

7.2 Severity of cough (mean reduction in severity of cough)

1

102

Mean Difference (Random, 95% CI)

‐0.88 [‐1.59, ‐0.17]

7.3 Bothersome cough (mean reduction in bothersome cough)

1

102

Mean Difference (Random, 95% CI)

‐0.90 [‐1.76, ‐0.04]

7.4 Children's sleep (mean reduction in cough impact on sleep score)

1

102

Mean Difference (Random, 95% CI)

‐0.7 [‐1.25, ‐0.15]

7.5 Parents' sleep (mean reduction in cough impact on sleep score)

1

102

Mean Difference (Random, 95% CI)

‐0.90 [‐1.51, ‐0.29]

8 Honey versus placebo (Day 5) Show forest plot

1

Mean Difference (Random, 95% CI)

Subtotals only

Analysis 1.8

Comparison 1 Pair‐wise comparison, Outcome 8 Honey versus placebo (Day 5).

Comparison 1 Pair‐wise comparison, Outcome 8 Honey versus placebo (Day 5).

8.1 Cough duration (mean number of days)

1

102

Mean Difference (Random, 95% CI)

‐0.72 [‐1.31, ‐0.13]

8.2 Frequency of cough (mean reduction in frequency of cough)

1

102

Mean Difference (Random, 95% CI)

‐0.48 [‐2.95, 1.99]

8.3 Severity of cough (mean reduction in severity of cough)

1

102

Mean Difference (Random, 95% CI)

‐0.43 [‐2.21, 1.35]

8.4 Bothersome cough (mean reduction in bothersome cough)

1

102

Mean Difference (Random, 95% CI)

‐0.51 [‐3.01, 1.99]

8.5 Children's sleep (mean reduction in cough impact on sleep score)

1

102

Mean Difference (Random, 95% CI)

‐0.55 [‐1.79, 0.69]

8.6 Parents' sleep (mean reduction in cough impact on sleep score)

1

102

Mean Difference (Random, 95% CI)

‐0.57 [‐1.59, 0.45]

9 Honey versus salbutamol (Day 1) Show forest plot

1

Mean Difference (Random, 95% CI)

Subtotals only

Analysis 1.9

Comparison 1 Pair‐wise comparison, Outcome 9 Honey versus salbutamol (Day 1).

Comparison 1 Pair‐wise comparison, Outcome 9 Honey versus salbutamol (Day 1).

9.1 Frequency of cough (mean reduction in frequency of cough)

1

100

Mean Difference (Random, 95% CI)

‐0.26 [‐3.14, 2.62]

9.2 Severity of cough (mean reduction in severity of cough)

1

100

Mean Difference (Random, 95% CI)

‐0.1 [‐0.39, 0.19]

9.3 Bothersome cough (mean reduction in bothersome cough)

1

100

Mean Difference (Random, 95% CI)

‐0.21 [‐0.90, 0.48]

9.4 Children's sleep (mean reduction in cough impact on sleep score)

1

100

Mean Difference (Random, 95% CI)

0.09 [‐0.05, 0.23]

9.5 Parents' sleep (mean reduction in cough impact on sleep score)

1

100

Mean Difference (Random, 95% CI)

0.05 [‐0.03, 0.13]

10 Honey versus salbutamol (Day 2) Show forest plot

1

Mean Difference (Random, 95% CI)

Subtotals only

Analysis 1.10

Comparison 1 Pair‐wise comparison, Outcome 10 Honey versus salbutamol (Day 2).

Comparison 1 Pair‐wise comparison, Outcome 10 Honey versus salbutamol (Day 2).

10.1 Frequency of cough (mean reduction in frequency of cough)

1

100

Mean Difference (Random, 95% CI)

‐0.67 [‐1.35, 0.01]

10.2 Severity of cough (mean reduction in severity of cough)

1

100

Mean Difference (Random, 95% CI)

‐0.42 [‐1.16, 0.32]

10.3 Bothersome cough (mean reduction in bothersome cough)

1

100

Mean Difference (Random, 95% CI)

‐0.27 [‐0.52, ‐0.02]

10.4 Children's sleep (mean reduction in cough impact on sleep score)

1

100

Mean Difference (Random, 95% CI)

0.17 [‐0.04, 0.38]

10.5 Parents' sleep (mean reduction in cough impact on sleep score)

1

100

Mean Difference (Random, 95% CI)

0.03 [‐0.00, 0.06]

11 Honey versus salbutamol (Day 3) Show forest plot

1

Mean Difference (Random, 95% CI)

Subtotals only

Analysis 1.11

Comparison 1 Pair‐wise comparison, Outcome 11 Honey versus salbutamol (Day 3).

Comparison 1 Pair‐wise comparison, Outcome 11 Honey versus salbutamol (Day 3).

11.1 Frequency of cough (mean reduction in frequency of cough)

1

100

Mean Difference (Random, 95% CI)

‐0.69 [‐1.13, ‐0.25]

11.2 Severity of cough (mean reduction in severity of cough)

1

100

Mean Difference (Random, 95% CI)

‐0.34 [‐0.64, ‐0.04]

11.3 Bothersome cough (mean reduction in bothersome cough)

1

100

Mean Difference (Random, 95% CI)

‐0.24 [‐0.38, ‐0.10]

11.4 Children's sleep (mean reduction in cough impact on sleep score)

1

100

Mean Difference (Random, 95% CI)

0.31 [0.13, 0.49]

11.5 Parents' sleep (mean reduction in cough impact on sleep score)

1

100

Mean Difference (Random, 95% CI)

0.21 [0.06, 0.36]

12 Honey versus salbutamol (Day 4) Show forest plot

1

Mean Difference (Random, 95% CI)

Subtotals only

Analysis 1.12

Comparison 1 Pair‐wise comparison, Outcome 12 Honey versus salbutamol (Day 4).

Comparison 1 Pair‐wise comparison, Outcome 12 Honey versus salbutamol (Day 4).

12.1 Frequency of cough (mean reduction in frequency of cough)

1

100

Mean Difference (Random, 95% CI)

‐0.61 [‐0.96, ‐0.26]

12.2 Severity of cough (mean reduction in severity of cough)

1

100

Mean Difference (Random, 95% CI)

‐0.43 [‐0.78, ‐0.08]

12.3 Bothersome cough (mean reduction in bothersome cough)

1

100

Mean Difference (Random, 95% CI)

‐0.3 [‐0.59, ‐0.01]

12.4 Children's sleep (mean reduction in cough impact on sleep score)

1

100

Mean Difference (Random, 95% CI)

0.22 [0.05, 0.39]

12.5 Parents' sleep (mean reduction in cough impact on sleep score)

1

100

Mean Difference (Random, 95% CI)

0.15 [0.04, 0.26]

13 Honey versus salbutamol (Day 5) Show forest plot

1

Mean Difference (Random, 95% CI)

Subtotals only

Analysis 1.13

Comparison 1 Pair‐wise comparison, Outcome 13 Honey versus salbutamol (Day 5).

Comparison 1 Pair‐wise comparison, Outcome 13 Honey versus salbutamol (Day 5).

13.1 Cough duration (mean number of days)

1

100

Mean Difference (Random, 95% CI)

‐0.54 [‐0.98, ‐0.10]

13.2 Frequency of cough (mean reduction in frequency of cough)

1

100

Mean Difference (Random, 95% CI)

‐0.54 [‐1.03, ‐0.05]

13.3 Severity of cough (mean reduction in severity of cough)

1

100

Mean Difference (Random, 95% CI)

‐0.41 [‐0.78, ‐0.04]

13.4 Bothersome cough (mean reduction in bothersome cough)

1

100

Mean Difference (Random, 95% CI)

‐0.27 [‐0.48, ‐0.06]

13.5 Children's sleep (mean reduction in cough impact on sleep score)

1

100

Mean Difference (Random, 95% CI)

0.15 [0.04, 0.26]

13.6 Parents' sleep (mean reduction in cough impact on sleep score)

1

100

Mean Difference (Random, 95% CI)

0.04 [0.01, 0.07]

Open in table viewer
Comparison 2. Pre‐ and postintervention comparison

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Cough frequency (mean reduction in frequency) Show forest plot

4

Mean Difference (Fixed, 95% CI)

Subtotals only

Analysis 2.1

Comparison 2 Pre‐ and postintervention comparison, Outcome 1 Cough frequency (mean reduction in frequency).

Comparison 2 Pre‐ and postintervention comparison, Outcome 1 Cough frequency (mean reduction in frequency).

1.1 Honey

4

357

Mean Difference (Fixed, 95% CI)

‐1.71 [‐2.28, ‐1.13]

1.2 Dextromethorphan

2

74

Mean Difference (Fixed, 95% CI)

‐1.54 [‐2.30, ‐0.78]

1.3 Diphenhydramine

1

40

Mean Difference (Fixed, 95% CI)

‐1.73 [‐2.72, ‐0.74]

1.4 Placebo

2

120

Mean Difference (Fixed, 95% CI)

‐0.99 [‐1.79, ‐0.18]

1.5 Salbutamol Day 1

1

43

Mean Difference (Fixed, 95% CI)

‐0.52 [‐6.28, 5.24]

1.6 No treatment

2

79

Mean Difference (Fixed, 95% CI)

‐0.98 [‐1.38, ‐0.59]

1.7 Buckwheat honey

1

35

Mean Difference (Fixed, 95% CI)

‐1.89 [‐2.96, ‐0.81]

1.8 Natural honey from Kafi‐Abad (Iran)

1

40

Mean Difference (Fixed, 95% CI)

‐2.16 [‐3.40, ‐0.92]

1.9 Eucalyptus honey

1

75

Mean Difference (Fixed, 95% CI)

‐1.77 [‐3.22, ‐0.32]

1.10 Labiatae honey

1

75

Mean Difference (Fixed, 95% CI)

‐1.82 [‐3.30, ‐0.34]

1.11 Citrus honey

1

75

Mean Difference (Fixed, 95% CI)

‐1.95 [‐3.55, ‐0.35]

1.12 Salbutamol Day 5

1

43

Mean Difference (Fixed, 95% CI)

‐2.19 [‐3.55, ‐0.83]

1.13 African honey Day 5

1

57

Mean Difference (Fixed, 95% CI)

‐2.65 [‐4.32, ‐0.98]

1.14 Placebo Day 5

1

45

Mean Difference (Fixed, 95% CI)

‐1.95 [‐4.42, 0.52]

2 Severity of cough (mean reduction in severity) Show forest plot

4

Mean Difference (Fixed, 95% CI)

Subtotals only

Analysis 2.2

Comparison 2 Pre‐ and postintervention comparison, Outcome 2 Severity of cough (mean reduction in severity).

Comparison 2 Pre‐ and postintervention comparison, Outcome 2 Severity of cough (mean reduction in severity).

2.1 Honey

4

357

Mean Difference (Fixed, 95% CI)

‐1.65 [‐2.39, ‐0.91]

2.2 Dextromethorphan

2

74

Mean Difference (Fixed, 95% CI)

‐1.52 [‐2.24, ‐0.80]

2.3 Diphenhydramine

1

40

Mean Difference (Fixed, 95% CI)

‐1.83 [‐2.88, ‐0.78]

2.4 Salbutamol Day 1

1

43

Mean Difference (Fixed, 95% CI)

‐0.74 [‐2.87, 1.39]

2.5 No treatment

2

79

Mean Difference (Fixed, 95% CI)

‐1.13 [‐1.54, ‐0.72]

2.6 Placebo

2

120

Mean Difference (Fixed, 95% CI)

‐0.80 [‐1.47, ‐0.13]

2.7 Buckwheat honey

1

35

Mean Difference (Fixed, 95% CI)

‐1.80 [‐2.88, ‐0.72]

2.8 Natural honey from Kafi‐Abad (Iran)

1

40

Mean Difference (Fixed, 95% CI)

‐2.33 [‐3.67, ‐0.99]

2.9 Eucalyptus honey

1

75

Mean Difference (Fixed, 95% CI)

‐1.78 [‐2.82, ‐0.74]

2.10 Labiatae honey

1

75

Mean Difference (Fixed, 95% CI)

‐1.94 [‐3.07, ‐0.81]

2.11 Citrus honey

1

75

Mean Difference (Fixed, 95% CI)

‐1.77 [‐2.74, ‐0.80]

2.12 Salbutamol Day 5

1

43

Mean Difference (Fixed, 95% CI)

‐2.08 [‐4.21, 0.05]

2.13 African honey Day 5

1

57

Mean Difference (Fixed, 95% CI)

‐2.62 [‐5.04, ‐0.20]

2.14 Placebo Day 5

1

45

Mean Difference (Fixed, 95% CI)

‐1.96 [‐3.74, ‐0.18]

3 Bothersome cough (mean reduction in bothersome cough) Show forest plot

3

Mean Difference (Fixed, 95% CI)

Subtotals only

Analysis 2.3

Comparison 2 Pre‐ and postintervention comparison, Outcome 3 Bothersome cough (mean reduction in bothersome cough).

Comparison 2 Pre‐ and postintervention comparison, Outcome 3 Bothersome cough (mean reduction in bothersome cough).

3.1 Honey

3

317

Mean Difference (Fixed, 95% CI)

‐2.22 [‐3.24, ‐1.21]

3.2 Dextromethorphan

1

34

Mean Difference (Fixed, 95% CI)

‐1.94 [‐3.05, ‐0.83]

3.3 Salbutamol Day 1

1

43

Mean Difference (Fixed, 95% CI)

‐1.0 [‐4.28, 2.28]

3.4 No treatment

1

39

Mean Difference (Fixed, 95% CI)

‐1.30 [‐2.07, ‐0.53]

3.5 Placebo

2

120

Mean Difference (Fixed, 95% CI)

‐1.08 [‐2.06, ‐0.10]

3.6 Buckwheat honey

1

35

Mean Difference (Fixed, 95% CI)

‐2.23 [‐3.50, ‐0.96]

3.7 Eucalyptus honey

1

75

Mean Difference (Fixed, 95% CI)

‐2.0 [‐3.82, ‐0.18]

3.8 Labiatae honey

1

75

Mean Difference (Fixed, 95% CI)

‐2.07 [‐4.03, ‐0.11]

3.9 Citrus honey

1

75

Mean Difference (Fixed, 95% CI)

‐2.16 [‐4.20, ‐0.12]

3.10 Salbutamol Day 5

1

43

Mean Difference (Fixed, 95% CI)

‐2.47 [‐4.73, ‐0.21]

3.11 African honey Day 5

1

57

Mean Difference (Fixed, 95% CI)

‐2.74 [‐5.27, ‐0.21]

3.12 Placebo Day 5

1

45

Mean Difference (Fixed, 95% CI)

‐1.85 [‐3.56, ‐0.14]

4 Children's sleep (mean reduction in cough impact on sleep score) Show forest plot

4

Mean Difference (Random, 95% CI)

Subtotals only

Analysis 2.4

Comparison 2 Pre‐ and postintervention comparison, Outcome 4 Children's sleep (mean reduction in cough impact on sleep score).

Comparison 2 Pre‐ and postintervention comparison, Outcome 4 Children's sleep (mean reduction in cough impact on sleep score).

4.1 Honey

4

357

Mean Difference (Random, 95% CI)

‐2.23 [‐2.87, ‐1.59]

4.2 Dextromethorphan

2

74

Mean Difference (Random, 95% CI)

‐1.75 [‐2.46, ‐1.04]

4.3 Diphenhydramine

1

40

Mean Difference (Random, 95% CI)

‐1.64 [‐2.58, ‐0.70]

4.4 No treatment

2

79

Mean Difference (Random, 95% CI)

‐1.28 [‐1.81, ‐0.76]

4.5 Placebo

2

120

Mean Difference (Random, 95% CI)

‐1.03 [‐2.05, 0.00]

4.6 Salbutamol Day 5

1

43

Mean Difference (Random, 95% CI)

‐2.47 [‐3.84, ‐1.10]

4.7 African honey Day 5

1

57

Mean Difference (Random, 95% CI)

‐2.32 [‐3.63, ‐1.01]

4.8 Placebo Day 5

1

45

Mean Difference (Random, 95% CI)

‐1.68 [‐2.63, ‐0.73]

5 Parents' sleep (mean reduction in cough impact on sleep score) Show forest plot

4

Mean Difference (Fixed, 95% CI)

Subtotals only

Analysis 2.5

Comparison 2 Pre‐ and postintervention comparison, Outcome 5 Parents' sleep (mean reduction in cough impact on sleep score).

Comparison 2 Pre‐ and postintervention comparison, Outcome 5 Parents' sleep (mean reduction in cough impact on sleep score).

5.1 Honey

4

357

Mean Difference (Fixed, 95% CI)

‐2.25 [‐2.89, ‐1.61]

5.2 Dextromethorphan

2

74

Mean Difference (Fixed, 95% CI)

‐1.97 [‐2.77, ‐1.17]

5.3 Diphenhydramine

1

40

Mean Difference (Fixed, 95% CI)

‐1.89 [‐2.97, ‐0.81]

5.4 No treatment

2

79

Mean Difference (Fixed, 95% CI)

‐1.46 [‐2.06, ‐0.87]

5.5 Placebo

2

120

Mean Difference (Fixed, 95% CI)

‐1.44 [‐2.28, ‐0.61]

5.6 Salbutamol Day 5

1

43

Mean Difference (Fixed, 95% CI)

‐2.33 [‐3.91, ‐0.75]

5.7 African honey Day 5

1

57

Mean Difference (Fixed, 95% CI)

‐2.29 [‐3.86, ‐0.72]

5.8 Placebo Day 5

1

45

Mean Difference (Fixed, 95% CI)

‐1.54 [‐2.60, ‐0.48]

6 Combined reduction in symptoms score Show forest plot

3

Mean Difference (Fixed, 95% CI)

Subtotals only

Analysis 2.6

Comparison 2 Pre‐ and postintervention comparison, Outcome 6 Combined reduction in symptoms score.

Comparison 2 Pre‐ and postintervention comparison, Outcome 6 Combined reduction in symptoms score.

6.1 Honey

3

317

Mean Difference (Fixed, 95% CI)

‐10.60 [‐14.43, ‐6.77]

6.2 Dextromethorphan

1

34

Mean Difference (Fixed, 95% CI)

‐8.39 [‐10.95, ‐5.84]

6.3 No treatment

1

39

Mean Difference (Fixed, 95% CI)

‐6.41 [‐8.82, ‐3.99]

6.4 Placebo

2

132

Mean Difference (Fixed, 95% CI)

‐7.11 [‐10.78, ‐3.44]

6.5 Honey Day 5

1

57

Mean Difference (Fixed, 95% CI)

‐12.68 [‐14.06, ‐11.30]

6.6 Placebo Day 5

1

45

Mean Difference (Fixed, 95% CI)

‐8.69 [‐14.17, ‐3.21]

6.7 Salbutamol Day 5

1

43

Mean Difference (Fixed, 95% CI)

‐11.37 [‐17.55, ‐5.19]

Open in table viewer
Comparison 3. Adverse events

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Honey versus dextromethorphan Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 3.1

Comparison 3 Adverse events, Outcome 1 Honey versus dextromethorphan.

Comparison 3 Adverse events, Outcome 1 Honey versus dextromethorphan.

1.1 Nervousness, insomnia, hyperactivity

2

149

Risk Ratio (M‐H, Fixed, 95% CI)

2.94 [0.74, 11.71]

1.2 Stomachache, nausea, and vomiting

1

69

Risk Ratio (M‐H, Fixed, 95% CI)

4.86 [0.24, 97.69]

1.3 Drowsiness

1

69

Risk Ratio (M‐H, Fixed, 95% CI)

2.92 [0.12, 69.20]

2 Honey versus diphenhydramine Show forest plot

1

80

Risk Ratio (M‐H, Fixed, 95% CI)

0.14 [0.01, 2.68]

Analysis 3.2

Comparison 3 Adverse events, Outcome 2 Honey versus diphenhydramine.

Comparison 3 Adverse events, Outcome 2 Honey versus diphenhydramine.

2.1 Somnolence

1

80

Risk Ratio (M‐H, Fixed, 95% CI)

0.14 [0.01, 2.68]

3 Honey versus placebo Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 3.3

Comparison 3 Adverse events, Outcome 3 Honey versus placebo.

Comparison 3 Adverse events, Outcome 3 Honey versus placebo.

3.1 Stomachache, nausea, and vomiting

2

402

Risk Ratio (M‐H, Fixed, 95% CI)

1.91 [1.12, 3.24]

3.2 Diarrhoea

1

102

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.33, 2.55]

3.3 Tachycardia

1

102

Risk Ratio (M‐H, Fixed, 95% CI)

1.58 [0.15, 16.86]

4 Honey versus salbutamol Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Analysis 3.4

Comparison 3 Adverse events, Outcome 4 Honey versus salbutamol.

Comparison 3 Adverse events, Outcome 4 Honey versus salbutamol.

4.1 Stomachache, nausea, and vomiting

1

100

Risk Ratio (M‐H, Random, 95% CI)

1.74 [1.04, 2.92]

4.2 Rash

1

100

Risk Ratio (M‐H, Random, 95% CI)

0.19 [0.02, 1.63]

4.3 Tachycardia

1

100

Risk Ratio (M‐H, Random, 95% CI)

1.51 [0.14, 16.10]

4.4 Diarrhoea

1

100

Risk Ratio (M‐H, Random, 95% CI)

0.59 [0.24, 1.45]

5 Honey versus no treatment Show forest plot

2

302

Odds Ratio (M‐H, Fixed, 95% CI)

6.99 [1.55, 31.58]

Analysis 3.5

Comparison 3 Adverse events, Outcome 5 Honey versus no treatment.

Comparison 3 Adverse events, Outcome 5 Honey versus no treatment.

5.1 Nervousness, insomnia, hyperactivity

2

154

Odds Ratio (M‐H, Fixed, 95% CI)

9.40 [1.16, 76.20]

5.2 Stomachache, nausea, and vomiting

1

74

Odds Ratio (M‐H, Fixed, 95% CI)

5.90 [0.27, 127.14]

5.3 Drowsiness

1

74

Odds Ratio (M‐H, Fixed, 95% CI)

3.43 [0.14, 87.09]

Study flow diagram (2018 update).
Figuras y tablas -
Figure 1

Study flow diagram (2018 update).

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figuras y tablas -
Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
Figuras y tablas -
Figure 3

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.

Comparison 1 Pair‐wise comparison, Outcome 1 Honey versus dextromethorphan.
Figuras y tablas -
Analysis 1.1

Comparison 1 Pair‐wise comparison, Outcome 1 Honey versus dextromethorphan.

Comparison 1 Pair‐wise comparison, Outcome 2 Honey versus diphenhydramine.
Figuras y tablas -
Analysis 1.2

Comparison 1 Pair‐wise comparison, Outcome 2 Honey versus diphenhydramine.

Comparison 1 Pair‐wise comparison, Outcome 3 Honey versus no treatment.
Figuras y tablas -
Analysis 1.3

Comparison 1 Pair‐wise comparison, Outcome 3 Honey versus no treatment.

Comparison 1 Pair‐wise comparison, Outcome 4 Honey versus placebo (Day 1).
Figuras y tablas -
Analysis 1.4

Comparison 1 Pair‐wise comparison, Outcome 4 Honey versus placebo (Day 1).

Comparison 1 Pair‐wise comparison, Outcome 5 Honey versus placebo (Day 2).
Figuras y tablas -
Analysis 1.5

Comparison 1 Pair‐wise comparison, Outcome 5 Honey versus placebo (Day 2).

Comparison 1 Pair‐wise comparison, Outcome 6 Honey versus placebo (Day 3).
Figuras y tablas -
Analysis 1.6

Comparison 1 Pair‐wise comparison, Outcome 6 Honey versus placebo (Day 3).

Comparison 1 Pair‐wise comparison, Outcome 7 Honey versus placebo (Day 4).
Figuras y tablas -
Analysis 1.7

Comparison 1 Pair‐wise comparison, Outcome 7 Honey versus placebo (Day 4).

Comparison 1 Pair‐wise comparison, Outcome 8 Honey versus placebo (Day 5).
Figuras y tablas -
Analysis 1.8

Comparison 1 Pair‐wise comparison, Outcome 8 Honey versus placebo (Day 5).

Comparison 1 Pair‐wise comparison, Outcome 9 Honey versus salbutamol (Day 1).
Figuras y tablas -
Analysis 1.9

Comparison 1 Pair‐wise comparison, Outcome 9 Honey versus salbutamol (Day 1).

Comparison 1 Pair‐wise comparison, Outcome 10 Honey versus salbutamol (Day 2).
Figuras y tablas -
Analysis 1.10

Comparison 1 Pair‐wise comparison, Outcome 10 Honey versus salbutamol (Day 2).

Comparison 1 Pair‐wise comparison, Outcome 11 Honey versus salbutamol (Day 3).
Figuras y tablas -
Analysis 1.11

Comparison 1 Pair‐wise comparison, Outcome 11 Honey versus salbutamol (Day 3).

Comparison 1 Pair‐wise comparison, Outcome 12 Honey versus salbutamol (Day 4).
Figuras y tablas -
Analysis 1.12

Comparison 1 Pair‐wise comparison, Outcome 12 Honey versus salbutamol (Day 4).

Comparison 1 Pair‐wise comparison, Outcome 13 Honey versus salbutamol (Day 5).
Figuras y tablas -
Analysis 1.13

Comparison 1 Pair‐wise comparison, Outcome 13 Honey versus salbutamol (Day 5).

Comparison 2 Pre‐ and postintervention comparison, Outcome 1 Cough frequency (mean reduction in frequency).
Figuras y tablas -
Analysis 2.1

Comparison 2 Pre‐ and postintervention comparison, Outcome 1 Cough frequency (mean reduction in frequency).

Comparison 2 Pre‐ and postintervention comparison, Outcome 2 Severity of cough (mean reduction in severity).
Figuras y tablas -
Analysis 2.2

Comparison 2 Pre‐ and postintervention comparison, Outcome 2 Severity of cough (mean reduction in severity).

Comparison 2 Pre‐ and postintervention comparison, Outcome 3 Bothersome cough (mean reduction in bothersome cough).
Figuras y tablas -
Analysis 2.3

Comparison 2 Pre‐ and postintervention comparison, Outcome 3 Bothersome cough (mean reduction in bothersome cough).

Comparison 2 Pre‐ and postintervention comparison, Outcome 4 Children's sleep (mean reduction in cough impact on sleep score).
Figuras y tablas -
Analysis 2.4

Comparison 2 Pre‐ and postintervention comparison, Outcome 4 Children's sleep (mean reduction in cough impact on sleep score).

Comparison 2 Pre‐ and postintervention comparison, Outcome 5 Parents' sleep (mean reduction in cough impact on sleep score).
Figuras y tablas -
Analysis 2.5

Comparison 2 Pre‐ and postintervention comparison, Outcome 5 Parents' sleep (mean reduction in cough impact on sleep score).

Comparison 2 Pre‐ and postintervention comparison, Outcome 6 Combined reduction in symptoms score.
Figuras y tablas -
Analysis 2.6

Comparison 2 Pre‐ and postintervention comparison, Outcome 6 Combined reduction in symptoms score.

Comparison 3 Adverse events, Outcome 1 Honey versus dextromethorphan.
Figuras y tablas -
Analysis 3.1

Comparison 3 Adverse events, Outcome 1 Honey versus dextromethorphan.

Comparison 3 Adverse events, Outcome 2 Honey versus diphenhydramine.
Figuras y tablas -
Analysis 3.2

Comparison 3 Adverse events, Outcome 2 Honey versus diphenhydramine.

Comparison 3 Adverse events, Outcome 3 Honey versus placebo.
Figuras y tablas -
Analysis 3.3

Comparison 3 Adverse events, Outcome 3 Honey versus placebo.

Comparison 3 Adverse events, Outcome 4 Honey versus salbutamol.
Figuras y tablas -
Analysis 3.4

Comparison 3 Adverse events, Outcome 4 Honey versus salbutamol.

Comparison 3 Adverse events, Outcome 5 Honey versus no treatment.
Figuras y tablas -
Analysis 3.5

Comparison 3 Adverse events, Outcome 5 Honey versus no treatment.

Summary of findings for the main comparison. Honey compared to dextromethorphan for acute cough in children

Honey compared to dextromethorphan for acute cough in children

Patient or population: acute cough in children
Setting: ambulatory
Intervention: honey
Comparison: dextromethorphan

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with dextromethorphan

Risk with honey

Duration of cough

Not assessed

Frequency of cough1

The mean frequency of cough (reduction in frequency of cough score) was ‐1.54.

MD 0.07 score lower
(1.07 lower to 0.94 higher)

149
(2 RCTs)

⊕⊕⊝⊝
LOW 2, 3

Follow‐up: mean 1 day

Severity of cough1

The mean severity of cough (reduction in severity of cough score) was ‐1.52.

MD 0.13 score lower
(1.25 lower to 0.99 higher)

149
(2 RCTs)

⊕⊕⊝⊝
LOW 2, 3

Follow‐up: mean 1 day

Bothersome cough1

The mean bothersome cough (reduction in bothersome nature of cough score) was ‐1.94.

MD 0.29 score higher
(0.56 lower to 1.14 higher)

69
(1 RCT)

⊕⊕⊕⊝
MODERATE 5

Follow‐up: mean 1 day

Cough impact on children's sleep1

The mean cough impact on children's sleep (cough impact on children' sleep score) was ‐1.75.

MD 0.03 score higher
(1.12 lower to 1.19 higher)

149
(2 RCTs)

⊕⊕⊝⊝
LOW 2, 3

Follow‐up: mean 6 days

Cough impact on parents' sleep1

The mean cough impact on parents' sleep (cough impact on parents' sleep score) was ‐1.97.

MD 0.16 score lower
(0.84 lower to 0.53 higher)

149
(2 RCTs)

⊕⊕⊝⊝
LOW 2, 3

Follow‐up: mean 1 day

Adverse events

Population

Nervousness, insomnia, hyperactivity

3 per 100

8 per 100

(2 to 32)

RR 2.94
(0.74 to 11.71)

149
(2 RCTs)

⊕⊕⊝⊝
LOW 4

Follow‐up: mean 1 day

Stomachache, nausea, and vomiting

1 per 100

7 per 100

(0 to 100)

RR 4.86
(0.24 to 97.69)

69
(1 RCT)

⊕⊕⊝⊝
LOW 5

Drowsiness

1 per 100

4 per 100
(0 to 100)

RR 2.92
(0.12 to 69.20)

69
(1 RCT)

⊕⊕⊝⊝
LOW 5

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

1Assessed on a 7‐point Likert scale from 0 to 6; lower score is better.
2Downgraded by one level because of study limitations: it was unclear if Shadkam 2010 concealed allocation; there was no blinding, which could increase the risk of bias in the study outcomes.
3Downgraded by one level for serious heterogeneity, which could be due to difference in dextromethorphan dose. In Paul 2007, 8.5 mg/2.5 mL dextromethorphan was given compared to 7.5 mg/2.5 mL given to children aged under 5 years by Shadkam 2010.
4Downgraded by two levels for risk of bias, inconsistency, and imprecision; the studies were underpowered to detect differences.
5Downgraded by two levels for very serious imprecision. Data were available from only Paul 2007, which had a small sample size.

Figuras y tablas -
Summary of findings for the main comparison. Honey compared to dextromethorphan for acute cough in children
Summary of findings 2. Honey compared to diphenhydramine for acute cough in children

Honey compared to diphenhydramine for acute cough in children

Patient or population: acute cough in children
Setting: ambulatory
Intervention: honey
Comparison: diphenhydramine

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with diphenhydramine

Risk with honey

Cough duration

Not assessed

Frequency of cough1

The mean frequency of cough (reduction in cough frequency score) was ‐1.73.

MD 0.57 lower
(0.9 lower to 0.24 lower)

80
(1 RCT)

⊕⊕⊝⊝
LOW 2, 3

Follow‐up: mean 1 day

Severity of cough1

The mean severity of cough (reduction in cough severity score) was ‐1.83.

MD 0.6 lower
(0.94 lower to 0.26 lower)

80
(1 RCT)

⊕⊕⊝⊝
LOW 2, 3

Follow‐up: mean 1 day

Cough impact on children's sleep1

The mean cough impact on children's sleep (cough impact on children' sleep score) was ‐1.64.

MD 0.55 score lower
(0.87 lower to 0.23 lower)

80
(1 RCT)

⊕⊕⊝⊝
LOW 2, 3

Follow‐up: mean 6 days

Cough impact on parents' sleep1

The mean cough impact on parents' sleep (cough impact on parents' sleep score) was ‐1.89.

MD 0.48 lower
(0.76 lower to 0.2 lower)

80
(1 RCT)

⊕⊕⊝⊝
LOW 2, 3

Follow‐up: mean 1 day

Adverse event: Somnolence

Population

1 per 100
(0 to 20)

RR 0.14
(0.01 to 2.68)

80
(1 RCT)

⊕⊕⊝⊝
LOW 2, 3

Follow‐up: mean 1 day

8 per 100

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

1Assessed on a 7‐point Likert scale from 0 to 6; lower score is better.
2Downgraded by one level because of study limitations: it was unclear if Shadkam 2010 concealed allocation; there was no blinding, which could increase the risk of bias in the study outcomes.
3Downgraded by one level for serious imprecision: data were from one small study (Shadkam 2010).

Figuras y tablas -
Summary of findings 2. Honey compared to diphenhydramine for acute cough in children
Summary of findings 3. Honey compared to no treatment for acute cough in children

Honey compared to no treatment for acute cough in children

Patient or population: acute cough in children
Setting: ambulatory
Intervention: honey
Comparison: 'no treatment'

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with no treatment

Risk with honey

Cough duration

Not assessed

Frequency of cough1

The mean frequency of cough (reduction in cough frequency score) was ‐0.98.

MD 1.05 lower
(1.48 lower to 0.62 lower)

154
(2 RCTs)

⊕⊕⊕⊝
MODERATE 2, 3

Follow‐up: mean 1 day

Severity of cough1

assessed with: 7‐point Likert scale
Scale from 0 to 6

The mean severity of cough (reduction in severity of cough score) was ‐1.13.

MD 1.03 score lower
(1.59 lower to 0.47 lower)

154
(2 RCTs)

⊕⊕⊕⊝
MODERATE 2, 3

Follow‐up: mean 1 day

Bothersome cough1
assessed with: 7‐point Likert scale
Scale from 0 to 6

The mean bothersome cough (reduction in bothersome nature of cough score) was ‐1.30.

MD 0.93 score lower
(1.98 lower to 0.12 higher)

74
(1 RCT)

⊕⊕⊝⊝
LOW 2, 4

Follow‐up: mean 1 day

Cough impact on children's sleep1
assessed with: 7‐point Likert scale
Scale from 0 to 6

The mean cough impact on children's sleep (cough impact on children' sleep score) was ‐1.28.

MD 1.04 score lower
(1.57 lower to 0.51 lower)

154
(2 RCTs)

⊕⊕⊕⊝
MODERATE 2, 3

Follow‐up: mean 6 days

Cough impact on parents' sleep1

assessed with: 7‐point Likert scale
Scale from 0 to 6

The mean cough impact on parents' sleep (cough impact on parents' sleep score) was ‐1.46.

MD 0.88 score lower
(1.23 lower to 0.52 lower)

154
(2 RCTs)

⊕⊕⊕⊝
MODERATE 2, 3

Follow‐up: mean 1 day

Adverse events

Population

Nervousness, insomnia, hyperactivity

1 per 100

6 per 100
(1 to 33)

RR 9.40 (1.16 to 76.20)

154
(2 RCTs)

⊕⊕⊝⊝
LOW 2, 4

Follow‐up: mean 1 day

Stomachache, nausea, and vomiting

1 per 100

7 per 100
(0 to 62)

RR 5.90 (0.27 to 127.14)

74
(1 RCT)

⊕⊕⊝⊝
LOW 2, 4

Drowsiness

1 per 100

4 per 100
(0 to 53)

RR 3.43 (0.14 to 87.09)

74
(1 RCT)

⊕⊕⊝⊝
LOW 2, 4

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

1Assessed on a 7‐point Likert scale from 0 to 6; lower score is better.
2Downgraded by one level for risk of bias. Participants in the no‐treatment arm were not blinded; knowledge of receiving no treatment may have influenced assessment of this subjective outcome (Paul 2007; Shadkam 2010).
3Downgraded by one level for imprecision and risk of bias.
4Downgraded by one level for serious imprecision: data from one small study (Paul 2007).

Figuras y tablas -
Summary of findings 3. Honey compared to no treatment for acute cough in children
Summary of findings 4. Honey compared to placebo for acute cough in children

Honey compared to placebo for acute cough in children

Patient or population: acute cough in children
Setting: ambulatory
Intervention: honey
Comparison: placebo

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with placebo

Risk with honey

Day 1

Frequency of cough1

The mean frequency of cough (reduction in cough frequency score) was ‐0.99.

MD 1.62 score lower
(3.02 lower to 0.22 lower)

402
(2 RCT)

⊕⊕⊕⊝
MODERATE 2

Follow‐up: mean 1 day

Severity of cough1

The mean severity of cough (reduction in severity of cough score) was ‐0.80.

MD 1.07 score lower
(2.43 lower to 0.3 higher)

402
(2 RCT)

⊕⊕⊕⊝
MODERATE 2

Bothersome cough (mean improvement score)1

The mean bothersome cough (reduction in bothersome nature of cough) was ‐1.08.

MD 1.4 score lower
(2.82 lower to 0.03 higher)

402
(2 RCTs)

⊕⊕⊕⊝
MODERATE 2

Cough impact on children's sleep1

The mean cough impact on children's sleep (cough impact on children' sleep score) was ‐1.03.

MD 1.21 score lower
(2.61 lower to 0.19 higher)

402
(2 RCTs)

⊕⊕⊕⊝
MODERATE 2

Follow‐up: mean 6 days

Cough impact on parents' sleep1

The mean cough impact on parents' sleep (cough impact on parents' sleep score) was ‐1.44.

MD 1.29 score lower
(2.71 lower to 0.13 higher)

402
(2 RCTs)

⊕⊕⊕⊝
MODERATE 2

Follow‐up: mean 1 day

Day 3

Frequency of cough1

The mean frequency of cough (reduction in frequency of cough score) was ‐0.9.

MD 1.13 score lower
(1.71 lower to 0.55 lower)

102
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Follow‐up: mean 6 days

Severity of cough1

The mean severity of cough (reduction in severity of cough score) was ‐1.08.

MD 0.85 score lower
(1.41 lower to 0.29 lower)

102
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Bothersome cough1

The mean bothersome cough (reduction in bothersome nature of cough score) was ‐0.99.

MD 1.33 score lower
(1.87 lower to 0.79 lower)

102
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Cough impact on children's sleep1

The mean cough impact on children's sleep (cough impact on children's sleep score) was ‐0.46.

MD 0.93 score lower
(1.42 lower to 0.44 lower)

102
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Cough impact on parents' sleep3

The mean cough impact on parents' sleep (cough impact on parents' sleep score) was ‐1.04.

MD 0.88 score lower
(1.38 lower to 0.38 lower)

102
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Day 5

Cough duration

The mean cough duration was 5.18 days.

MD 0.72 days lower
(1.31 lower to 0.13 lower)

102
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Follow‐up: mean 6 days; assessed with: 7‐point Likert scale
Scale from 0 to 6

Frequency of cough1

The mean frequency of cough (reduction in frequency of cough score) was ‐1.95.

MD 0.48 score lower
(2.95 lower to 1.99 higher)

102
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Severity of cough1

The mean severity of cough (reduction in severity of cough score) was ‐1.96.

MD 0.43 score lower
(2.21 lower to 1.35 higher)

102
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Bothersome cough1

The mean bothersome cough (reduction in bothersome nature of cough score) was ‐1.85.

MD 0.51 score lower
(3.01 lower to 1.99 higher)

102
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Cough impact on children's sleep1

The mean cough impact on children's sleep (cough impact on children' sleep score) was ‐1.68.

MD 0.55 score lower
(1.79 lower to 0.69 higher)

102
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Cough impact on parents' sleep

The mean cough impact on parents' sleep (cough impact on parents' sleep score) was ‐1.54.

MD 0.57 score lower
(1.59 lower to 0.45 higher)

102
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Adverse events

Population

Stomachache, nausea, and vomiting

11 per 100

21 per 100
(12 to 35)

RR 1.91
(1.12 to 3.24)

402
(2 RCTs)

⊕⊕⊕⊝
MODERATE2

Follow‐up: mean 6 days

Diarrhoea

13 per 100

12 per 100
(4 to 34)

RR 0.92
(0.33 to 2.55)

102
(1 RCT)

⊕⊕⊝⊝
LOW 3

Tachycardia

2 per 100

4 per 100
(0 to 37)

RR 1.58
(0.15 to 16.86)

102
(1 RCT)

⊕⊕⊝⊝
LOW 3

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

1Assessed on a 7‐point Likert scale from 0 to 6; lower score is better.
2Downgraded by one level for serious imprecision.
3Downgraded by two levels for very serious imprecision: Waris 2014 was insufficiently powered to detect differences.

Figuras y tablas -
Summary of findings 4. Honey compared to placebo for acute cough in children
Summary of findings 5. Honey compared to salbutamol for acute cough in children

Honey compared to salbutamol for acute cough in children

Patient or population: acute cough in children
Setting: ambulatory
Intervention: honey
Comparison: salbutamol

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with salbutamol

Risk with honey

Day 1

Frequency of cough (mean improvement score)1

The mean frequency of cough (reduction in frequency of cough score) was ‐0.52.

MD 0.26 lower
(3.14 lower to 2.62 higher)

100
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Follow‐up: mean 6 days

Severity of cough (mean improvement score)1

The mean severity of cough (reduction in severity of cough score) was ‐0.74.

MD 0.1 lower
(0.39 lower to 0.19 higher)

100
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Bothersome cough (mean improvement score)1

The mean bothersome cough (reduction in bothersome nature of cough score) was ‐1.00.

MD 0.21 lower
(0.9 lower to 0.48 higher)

100
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Cough impact on children's sleep1

The mean cough impact on children's sleep (cough impact on children' sleep score) was ‐1.24.

MD 0.09 higher
(0.05 lower to 0.23 higher)

100
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Cough impact on parents' sleep1

The mean cough impact on parents' sleep (cough impact on parents' sleep score) was ‐1.22.

MD 0.05 higher
(0.03 lower to 0.13 higher)

100
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Day 3

Frequency of cough1

The mean frequency of cough (reduction in frequency of cough score) was ‐1.34.

MD 0.69 lower
(1.13 lower to 0.25 lower)

100
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Follow‐up: mean 4 days

Severity of cough1

The mean severity of cough (reduction in severity of cough score) was ‐1.59.

MD 0.34 lower
(0.64 lower to 0.04 lower)

100
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Bothersome cough1

The mean bothersome cough (reduction in bothersome nature of cough score) was ‐2.08.

MD 0.24 lower
(0.38 lower to 0.1 lower)

100
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Cough impact on children's sleep1

The mean cough impact on children's sleep (cough impact on children' sleep score) was ‐2.25.

MD 0.31 higher
(0.13 higher to 0.49 higher)

100
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Follow‐up: mean 6 days

Cough impact on parents' sleep1

The mean cough impact on parents' sleep (cough impact on parents' sleep score) was ‐2.13.

MD 0.21 higher
(0.06 higher to 0.36 higher)

100
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Follow‐up: mean 4 days

Day 5

Cough duration
assessed (days)

The mean cough duration was 5 days.

MD 0.54 days lower
(0.98 lower to 0.1 lower)

100
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Follow‐up: mean 6 days

Frequency of cough (mean improvement score)1

The mean frequency of cough (reduction in frequency of cough score) was ‐2.19.

MD 0.54 lower
(1.03 lower to 0.05 lower)

100
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Severity of cough (mean improvement score)1

The mean severity of cough (reduction in severity of cough score) was ‐2.08.

MD 0.41 lower
(0.78 lower to 0.04 lower)

100
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Bothersome cough (mean improvement score)1

The mean bothersome cough (reduction in bothersome nature of cough score) was ‐2.47.

MD 0.27 lower
(0.48 lower to 0.06 lower)

100
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Cough impact on children's sleep1

The mean cough impact on children's sleep (cough impact on children's sleep score) was ‐2.47.

MD 0.15 higher
(0.04 higher to 0.26 higher)

100
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Cough impact on parents' sleep1

The mean cough impact on parents' sleep (cough impact on parents' sleep score) was ‐2.33.

MD 0.04 higher
(0.01 higher to 0.07 higher)

100
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Adverse events

Population

Stomachache, nausea, and vomiting

30 per 100

53 per 100
(31 to 88)

RR 1.74
(1.04 to 2.92)

100
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Follow‐up: mean 6 days

Rash

9 per 100

2 per 100
(0 to 15)

RR 0.19
(0.02 to 1.63)

100
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

Tachycardia

2 per 100

4 per 100
(0 to 39)

RR 1.51 (0.14 to 16.10)

100
(1 RCT)

⊕⊕⊝⊝
LOW 3

Diarrhoea

21 per 100

12 per 100
(5 to 30)

RR 0.59
(0.24 to 1.45)

100
(1 RCT)

⊕⊕⊕⊝
MODERATE 2

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

1Assessed on a 7‐point Likert scale from 0 to 6; lower score is better.
2Downgraded by one level for serious imprecision. Data were from one small study (Waris 2014).
3Downgraded by two levels for very serious imprecision. Data were from one small study (Waris 2014).

Figuras y tablas -
Summary of findings 5. Honey compared to salbutamol for acute cough in children
Table 1. Pre‐ and postintervention comparison of honey on cough frequency and severity expressed as medians

Study ID

Cough

Honey

(N = 29)

Bromelin
(pineapple extract) + honey

(N = 31)

P value

Certainty of the evidence

Peixoto 2016

Frequency of cough1

Before, median (P25 to P75)

After, median (P25 to P75)

Mean ± SD

3 (2 to 4)

1 (1 to 1)

1.76 ± 0.87

3 (2 to 3)

1 (1 to 1)

1.71 ± 0.78

0.832

0.943

⊕⊕⊕⊝
MODERATE 4

Severity of cough1

Mean ± SD

assessed with: unvalidated 5‐point cough scale from 0 to 4

‐0.86 ± 0.45

‐0.97 ± 0.62

0.322 0.223

⊕⊕⊕⊝
MODERATE 4

Honey

(N = 63)

Diphenhydramine

(N = 63)

Ahmadi 2013

Proportion of children with reduction in frequency and severity of daytime cough5

84.1%

(N = 53)

58.7% (N = 37)

"< 0.02"

⊕⊕⊕⊝
MODERATE 4

Proportion of children with reduction in frequency and severity of nighttime cough5

79.4%

(N = 50)

58.7% (N = 37)

"< 0.02"

⊕⊕⊕⊝
MODERATE 4

SD: standard deviation
P: percentile

1Assessed on an unvalidated 5‐point cough scale from 0 to 4; lower score is better.
2Student's t test.
3Chi².
4Downgraded by one level for risk of bias and imprecision.
5Assessed on a 7‐point Likert scale from 0 to 6; lower score is better.

Figuras y tablas -
Table 1. Pre‐ and postintervention comparison of honey on cough frequency and severity expressed as medians
Comparison 1. Pair‐wise comparison

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Honey versus dextromethorphan Show forest plot

2

Mean Difference (Random, 95% CI)

Subtotals only

1.1 Frequency of cough (mean reduction in cough frequency)

2

149

Mean Difference (Random, 95% CI)

‐0.07 [‐1.07, 0.94]

1.2 Severity of cough (mean reduction in severity of cough)

2

149

Mean Difference (Random, 95% CI)

‐0.13 [‐1.25, 0.99]

1.3 Bothersome cough (mean reduction in bothersome cough)

1

69

Mean Difference (Random, 95% CI)

0.29 [‐0.56, 1.14]

1.4 Children's sleep (mean reduction in cough impact on sleep score)

2

149

Mean Difference (Random, 95% CI)

0.03 [‐1.12, 1.19]

1.5 Parents' sleep (mean reduction in cough impact on sleep score)

2

149

Mean Difference (Random, 95% CI)

‐0.16 [‐0.84, 0.53]

1.6 Combined cough score (reduction in combined cough score)

1

69

Mean Difference (Random, 95% CI)

2.32 [‐1.24, 5.88]

2 Honey versus diphenhydramine Show forest plot

1

Mean Difference (Random, 95% CI)

Subtotals only

2.1 Frequency of cough (mean reduction in cough frequency)

1

80

Mean Difference (Random, 95% CI)

‐0.57 [‐0.90, ‐0.24]

2.2 Severity of cough (mean reduction in severity of cough)

1

80

Mean Difference (Random, 95% CI)

‐0.6 [‐0.94, ‐0.26]

2.3 Children's sleep (mean reduction in cough impact on sleep score)

1

80

Mean Difference (Random, 95% CI)

‐0.55 [‐0.87, ‐0.23]

2.4 Parents' sleep (mean reduction in cough impact on sleep score)

1

80

Mean Difference (Random, 95% CI)

‐0.48 [‐0.76, ‐0.20]

3 Honey versus no treatment Show forest plot

2

Mean Difference (Random, 95% CI)

Subtotals only

3.1 Frequency of cough (mean reduction in frequency of cough)

2

154

Mean Difference (Random, 95% CI)

‐1.05 [‐1.48, ‐0.62]

3.2 Severity of cough (mean reduction in severity of cough)

2

154

Mean Difference (Random, 95% CI)

‐1.03 [‐1.59, ‐0.47]

3.3 Bothersome cough (mean reduction in bothersome cough)

1

74

Mean Difference (Random, 95% CI)

‐0.93 [‐1.98, 0.12]

3.4 Children's sleep (mean reduction in cough impact on sleep score)

2

154

Mean Difference (Random, 95% CI)

‐1.04 [‐1.57, ‐0.51]

3.5 Parents' sleep (mean reduction in cough impact on sleep score)

2

154

Mean Difference (Random, 95% CI)

‐0.88 [‐1.23, ‐0.52]

3.6 Combined reduction in symptoms score

1

74

Mean Difference (Random, 95% CI)

‐4.31 [‐6.77, ‐1.85]

4 Honey versus placebo (Day 1) Show forest plot

2

Mean Difference (Random, 95% CI)

Subtotals only

4.1 Frequency of cough (mean reduction in frequency of cough)

2

402

Mean Difference (Random, 95% CI)

‐1.62 [‐3.02, ‐0.22]

4.2 Severity of cough (mean reduction in severity of cough)

2

402

Mean Difference (Random, 95% CI)

‐1.07 [‐2.43, 0.30]

4.3 Bothersome cough (mean reduction in bothersome cough)

2

402

Mean Difference (Random, 95% CI)

‐1.40 [‐2.82, 0.03]

4.4 Children's sleep (mean reduction in cough impact on sleep score)

2

402

Mean Difference (Random, 95% CI)

‐1.21 [‐2.61, 0.19]

4.5 Parents' sleep (mean reduction in cough impact on sleep score)

2

402

Mean Difference (Random, 95% CI)

‐1.29 [‐2.71, 0.13]

5 Honey versus placebo (Day 2) Show forest plot

1

Mean Difference (Random, 95% CI)

Subtotals only

5.1 Frequency of cough (mean reduction in frequency of cough)

1

102

Mean Difference (Random, 95% CI)

‐0.71 [‐1.22, ‐0.20]

5.2 Severity of cough (mean reduction in severity of cough)

1

102

Mean Difference (Random, 95% CI)

‐0.63 [‐1.36, 0.10]

5.3 Bothersome cough (mean reduction in bothersome cough)

1

102

Mean Difference (Random, 95% CI)

‐1.11 [‐1.79, ‐0.43]

5.4 Children's sleep (mean reduction in cough impact on sleep score)

1

102

Mean Difference (Random, 95% CI)

‐0.69 [‐1.43, 0.05]

5.5 Parents' sleep (mean reduction in cough impact on sleep score)

1

102

Mean Difference (Random, 95% CI)

‐0.87 [‐1.59, ‐0.15]

6 Honey versus placebo (Day 3) Show forest plot

1

Mean Difference (Random, 95% CI)

Subtotals only

6.1 Frequency of cough (mean reduction in frequency of cough)

1

102

Mean Difference (Random, 95% CI)

‐1.13 [‐1.71, ‐0.55]

6.2 Severity of cough (mean reduction in severity of cough)

1

102

Mean Difference (Random, 95% CI)

‐0.85 [‐1.41, ‐0.29]

6.3 Bothersome cough (mean reduction in bothersome cough)

1

102

Mean Difference (Random, 95% CI)

‐1.33 [‐1.87, ‐0.79]

6.4 Children's sleep (mean reduction in cough impact on sleep score)

1

102

Mean Difference (Random, 95% CI)

‐0.93 [‐1.42, ‐0.44]

6.5 Parents' sleep (mean reduction in cough impact on sleep score)

1

102

Mean Difference (Random, 95% CI)

‐0.88 [‐1.38, ‐0.38]

7 Honey versus placebo (Day 4) Show forest plot

1

Mean Difference (Random, 95% CI)

Subtotals only

7.1 Frequency of cough (mean reduction in frequency of cough)

1

102

Mean Difference (Random, 95% CI)

‐1.16 [‐1.83, ‐0.49]

7.2 Severity of cough (mean reduction in severity of cough)

1

102

Mean Difference (Random, 95% CI)

‐0.88 [‐1.59, ‐0.17]

7.3 Bothersome cough (mean reduction in bothersome cough)

1

102

Mean Difference (Random, 95% CI)

‐0.90 [‐1.76, ‐0.04]

7.4 Children's sleep (mean reduction in cough impact on sleep score)

1

102

Mean Difference (Random, 95% CI)

‐0.7 [‐1.25, ‐0.15]

7.5 Parents' sleep (mean reduction in cough impact on sleep score)

1

102

Mean Difference (Random, 95% CI)

‐0.90 [‐1.51, ‐0.29]

8 Honey versus placebo (Day 5) Show forest plot

1

Mean Difference (Random, 95% CI)

Subtotals only

8.1 Cough duration (mean number of days)

1

102

Mean Difference (Random, 95% CI)

‐0.72 [‐1.31, ‐0.13]

8.2 Frequency of cough (mean reduction in frequency of cough)

1

102

Mean Difference (Random, 95% CI)

‐0.48 [‐2.95, 1.99]

8.3 Severity of cough (mean reduction in severity of cough)

1

102

Mean Difference (Random, 95% CI)

‐0.43 [‐2.21, 1.35]

8.4 Bothersome cough (mean reduction in bothersome cough)

1

102

Mean Difference (Random, 95% CI)

‐0.51 [‐3.01, 1.99]

8.5 Children's sleep (mean reduction in cough impact on sleep score)

1

102

Mean Difference (Random, 95% CI)

‐0.55 [‐1.79, 0.69]

8.6 Parents' sleep (mean reduction in cough impact on sleep score)

1

102

Mean Difference (Random, 95% CI)

‐0.57 [‐1.59, 0.45]

9 Honey versus salbutamol (Day 1) Show forest plot

1

Mean Difference (Random, 95% CI)

Subtotals only

9.1 Frequency of cough (mean reduction in frequency of cough)

1

100

Mean Difference (Random, 95% CI)

‐0.26 [‐3.14, 2.62]

9.2 Severity of cough (mean reduction in severity of cough)

1

100

Mean Difference (Random, 95% CI)

‐0.1 [‐0.39, 0.19]

9.3 Bothersome cough (mean reduction in bothersome cough)

1

100

Mean Difference (Random, 95% CI)

‐0.21 [‐0.90, 0.48]

9.4 Children's sleep (mean reduction in cough impact on sleep score)

1

100

Mean Difference (Random, 95% CI)

0.09 [‐0.05, 0.23]

9.5 Parents' sleep (mean reduction in cough impact on sleep score)

1

100

Mean Difference (Random, 95% CI)

0.05 [‐0.03, 0.13]

10 Honey versus salbutamol (Day 2) Show forest plot

1

Mean Difference (Random, 95% CI)

Subtotals only

10.1 Frequency of cough (mean reduction in frequency of cough)

1

100

Mean Difference (Random, 95% CI)

‐0.67 [‐1.35, 0.01]

10.2 Severity of cough (mean reduction in severity of cough)

1

100

Mean Difference (Random, 95% CI)

‐0.42 [‐1.16, 0.32]

10.3 Bothersome cough (mean reduction in bothersome cough)

1

100

Mean Difference (Random, 95% CI)

‐0.27 [‐0.52, ‐0.02]

10.4 Children's sleep (mean reduction in cough impact on sleep score)

1

100

Mean Difference (Random, 95% CI)

0.17 [‐0.04, 0.38]

10.5 Parents' sleep (mean reduction in cough impact on sleep score)

1

100

Mean Difference (Random, 95% CI)

0.03 [‐0.00, 0.06]

11 Honey versus salbutamol (Day 3) Show forest plot

1

Mean Difference (Random, 95% CI)

Subtotals only

11.1 Frequency of cough (mean reduction in frequency of cough)

1

100

Mean Difference (Random, 95% CI)

‐0.69 [‐1.13, ‐0.25]

11.2 Severity of cough (mean reduction in severity of cough)

1

100

Mean Difference (Random, 95% CI)

‐0.34 [‐0.64, ‐0.04]

11.3 Bothersome cough (mean reduction in bothersome cough)

1

100

Mean Difference (Random, 95% CI)

‐0.24 [‐0.38, ‐0.10]

11.4 Children's sleep (mean reduction in cough impact on sleep score)

1

100

Mean Difference (Random, 95% CI)

0.31 [0.13, 0.49]

11.5 Parents' sleep (mean reduction in cough impact on sleep score)

1

100

Mean Difference (Random, 95% CI)

0.21 [0.06, 0.36]

12 Honey versus salbutamol (Day 4) Show forest plot

1

Mean Difference (Random, 95% CI)

Subtotals only

12.1 Frequency of cough (mean reduction in frequency of cough)

1

100

Mean Difference (Random, 95% CI)

‐0.61 [‐0.96, ‐0.26]

12.2 Severity of cough (mean reduction in severity of cough)

1

100

Mean Difference (Random, 95% CI)

‐0.43 [‐0.78, ‐0.08]

12.3 Bothersome cough (mean reduction in bothersome cough)

1

100

Mean Difference (Random, 95% CI)

‐0.3 [‐0.59, ‐0.01]

12.4 Children's sleep (mean reduction in cough impact on sleep score)

1

100

Mean Difference (Random, 95% CI)

0.22 [0.05, 0.39]

12.5 Parents' sleep (mean reduction in cough impact on sleep score)

1

100

Mean Difference (Random, 95% CI)

0.15 [0.04, 0.26]

13 Honey versus salbutamol (Day 5) Show forest plot

1

Mean Difference (Random, 95% CI)

Subtotals only

13.1 Cough duration (mean number of days)

1

100

Mean Difference (Random, 95% CI)

‐0.54 [‐0.98, ‐0.10]

13.2 Frequency of cough (mean reduction in frequency of cough)

1

100

Mean Difference (Random, 95% CI)

‐0.54 [‐1.03, ‐0.05]

13.3 Severity of cough (mean reduction in severity of cough)

1

100

Mean Difference (Random, 95% CI)

‐0.41 [‐0.78, ‐0.04]

13.4 Bothersome cough (mean reduction in bothersome cough)

1

100

Mean Difference (Random, 95% CI)

‐0.27 [‐0.48, ‐0.06]

13.5 Children's sleep (mean reduction in cough impact on sleep score)

1

100

Mean Difference (Random, 95% CI)

0.15 [0.04, 0.26]

13.6 Parents' sleep (mean reduction in cough impact on sleep score)

1

100

Mean Difference (Random, 95% CI)

0.04 [0.01, 0.07]

Figuras y tablas -
Comparison 1. Pair‐wise comparison
Comparison 2. Pre‐ and postintervention comparison

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Cough frequency (mean reduction in frequency) Show forest plot

4

Mean Difference (Fixed, 95% CI)

Subtotals only

1.1 Honey

4

357

Mean Difference (Fixed, 95% CI)

‐1.71 [‐2.28, ‐1.13]

1.2 Dextromethorphan

2

74

Mean Difference (Fixed, 95% CI)

‐1.54 [‐2.30, ‐0.78]

1.3 Diphenhydramine

1

40

Mean Difference (Fixed, 95% CI)

‐1.73 [‐2.72, ‐0.74]

1.4 Placebo

2

120

Mean Difference (Fixed, 95% CI)

‐0.99 [‐1.79, ‐0.18]

1.5 Salbutamol Day 1

1

43

Mean Difference (Fixed, 95% CI)

‐0.52 [‐6.28, 5.24]

1.6 No treatment

2

79

Mean Difference (Fixed, 95% CI)

‐0.98 [‐1.38, ‐0.59]

1.7 Buckwheat honey

1

35

Mean Difference (Fixed, 95% CI)

‐1.89 [‐2.96, ‐0.81]

1.8 Natural honey from Kafi‐Abad (Iran)

1

40

Mean Difference (Fixed, 95% CI)

‐2.16 [‐3.40, ‐0.92]

1.9 Eucalyptus honey

1

75

Mean Difference (Fixed, 95% CI)

‐1.77 [‐3.22, ‐0.32]

1.10 Labiatae honey

1

75

Mean Difference (Fixed, 95% CI)

‐1.82 [‐3.30, ‐0.34]

1.11 Citrus honey

1

75

Mean Difference (Fixed, 95% CI)

‐1.95 [‐3.55, ‐0.35]

1.12 Salbutamol Day 5

1

43

Mean Difference (Fixed, 95% CI)

‐2.19 [‐3.55, ‐0.83]

1.13 African honey Day 5

1

57

Mean Difference (Fixed, 95% CI)

‐2.65 [‐4.32, ‐0.98]

1.14 Placebo Day 5

1

45

Mean Difference (Fixed, 95% CI)

‐1.95 [‐4.42, 0.52]

2 Severity of cough (mean reduction in severity) Show forest plot

4

Mean Difference (Fixed, 95% CI)

Subtotals only

2.1 Honey

4

357

Mean Difference (Fixed, 95% CI)

‐1.65 [‐2.39, ‐0.91]

2.2 Dextromethorphan

2

74

Mean Difference (Fixed, 95% CI)

‐1.52 [‐2.24, ‐0.80]

2.3 Diphenhydramine

1

40

Mean Difference (Fixed, 95% CI)

‐1.83 [‐2.88, ‐0.78]

2.4 Salbutamol Day 1

1

43

Mean Difference (Fixed, 95% CI)

‐0.74 [‐2.87, 1.39]

2.5 No treatment

2

79

Mean Difference (Fixed, 95% CI)

‐1.13 [‐1.54, ‐0.72]

2.6 Placebo

2

120

Mean Difference (Fixed, 95% CI)

‐0.80 [‐1.47, ‐0.13]

2.7 Buckwheat honey

1

35

Mean Difference (Fixed, 95% CI)

‐1.80 [‐2.88, ‐0.72]

2.8 Natural honey from Kafi‐Abad (Iran)

1

40

Mean Difference (Fixed, 95% CI)

‐2.33 [‐3.67, ‐0.99]

2.9 Eucalyptus honey

1

75

Mean Difference (Fixed, 95% CI)

‐1.78 [‐2.82, ‐0.74]

2.10 Labiatae honey

1

75

Mean Difference (Fixed, 95% CI)

‐1.94 [‐3.07, ‐0.81]

2.11 Citrus honey

1

75

Mean Difference (Fixed, 95% CI)

‐1.77 [‐2.74, ‐0.80]

2.12 Salbutamol Day 5

1

43

Mean Difference (Fixed, 95% CI)

‐2.08 [‐4.21, 0.05]

2.13 African honey Day 5

1

57

Mean Difference (Fixed, 95% CI)

‐2.62 [‐5.04, ‐0.20]

2.14 Placebo Day 5

1

45

Mean Difference (Fixed, 95% CI)

‐1.96 [‐3.74, ‐0.18]

3 Bothersome cough (mean reduction in bothersome cough) Show forest plot

3

Mean Difference (Fixed, 95% CI)

Subtotals only

3.1 Honey

3

317

Mean Difference (Fixed, 95% CI)

‐2.22 [‐3.24, ‐1.21]

3.2 Dextromethorphan

1

34

Mean Difference (Fixed, 95% CI)

‐1.94 [‐3.05, ‐0.83]

3.3 Salbutamol Day 1

1

43

Mean Difference (Fixed, 95% CI)

‐1.0 [‐4.28, 2.28]

3.4 No treatment

1

39

Mean Difference (Fixed, 95% CI)

‐1.30 [‐2.07, ‐0.53]

3.5 Placebo

2

120

Mean Difference (Fixed, 95% CI)

‐1.08 [‐2.06, ‐0.10]

3.6 Buckwheat honey

1

35

Mean Difference (Fixed, 95% CI)

‐2.23 [‐3.50, ‐0.96]

3.7 Eucalyptus honey

1

75

Mean Difference (Fixed, 95% CI)

‐2.0 [‐3.82, ‐0.18]

3.8 Labiatae honey

1

75

Mean Difference (Fixed, 95% CI)

‐2.07 [‐4.03, ‐0.11]

3.9 Citrus honey

1

75

Mean Difference (Fixed, 95% CI)

‐2.16 [‐4.20, ‐0.12]

3.10 Salbutamol Day 5

1

43

Mean Difference (Fixed, 95% CI)

‐2.47 [‐4.73, ‐0.21]

3.11 African honey Day 5

1

57

Mean Difference (Fixed, 95% CI)

‐2.74 [‐5.27, ‐0.21]

3.12 Placebo Day 5

1

45

Mean Difference (Fixed, 95% CI)

‐1.85 [‐3.56, ‐0.14]

4 Children's sleep (mean reduction in cough impact on sleep score) Show forest plot

4

Mean Difference (Random, 95% CI)

Subtotals only

4.1 Honey

4

357

Mean Difference (Random, 95% CI)

‐2.23 [‐2.87, ‐1.59]

4.2 Dextromethorphan

2

74

Mean Difference (Random, 95% CI)

‐1.75 [‐2.46, ‐1.04]

4.3 Diphenhydramine

1

40

Mean Difference (Random, 95% CI)

‐1.64 [‐2.58, ‐0.70]

4.4 No treatment

2

79

Mean Difference (Random, 95% CI)

‐1.28 [‐1.81, ‐0.76]

4.5 Placebo

2

120

Mean Difference (Random, 95% CI)

‐1.03 [‐2.05, 0.00]

4.6 Salbutamol Day 5

1

43

Mean Difference (Random, 95% CI)

‐2.47 [‐3.84, ‐1.10]

4.7 African honey Day 5

1

57

Mean Difference (Random, 95% CI)

‐2.32 [‐3.63, ‐1.01]

4.8 Placebo Day 5

1

45

Mean Difference (Random, 95% CI)

‐1.68 [‐2.63, ‐0.73]

5 Parents' sleep (mean reduction in cough impact on sleep score) Show forest plot

4

Mean Difference (Fixed, 95% CI)

Subtotals only

5.1 Honey

4

357

Mean Difference (Fixed, 95% CI)

‐2.25 [‐2.89, ‐1.61]

5.2 Dextromethorphan

2

74

Mean Difference (Fixed, 95% CI)

‐1.97 [‐2.77, ‐1.17]

5.3 Diphenhydramine

1

40

Mean Difference (Fixed, 95% CI)

‐1.89 [‐2.97, ‐0.81]

5.4 No treatment

2

79

Mean Difference (Fixed, 95% CI)

‐1.46 [‐2.06, ‐0.87]

5.5 Placebo

2

120

Mean Difference (Fixed, 95% CI)

‐1.44 [‐2.28, ‐0.61]

5.6 Salbutamol Day 5

1

43

Mean Difference (Fixed, 95% CI)

‐2.33 [‐3.91, ‐0.75]

5.7 African honey Day 5

1

57

Mean Difference (Fixed, 95% CI)

‐2.29 [‐3.86, ‐0.72]

5.8 Placebo Day 5

1

45

Mean Difference (Fixed, 95% CI)

‐1.54 [‐2.60, ‐0.48]

6 Combined reduction in symptoms score Show forest plot

3

Mean Difference (Fixed, 95% CI)

Subtotals only

6.1 Honey

3

317

Mean Difference (Fixed, 95% CI)

‐10.60 [‐14.43, ‐6.77]

6.2 Dextromethorphan

1

34

Mean Difference (Fixed, 95% CI)

‐8.39 [‐10.95, ‐5.84]

6.3 No treatment

1

39

Mean Difference (Fixed, 95% CI)

‐6.41 [‐8.82, ‐3.99]

6.4 Placebo

2

132

Mean Difference (Fixed, 95% CI)

‐7.11 [‐10.78, ‐3.44]

6.5 Honey Day 5

1

57

Mean Difference (Fixed, 95% CI)

‐12.68 [‐14.06, ‐11.30]

6.6 Placebo Day 5

1

45

Mean Difference (Fixed, 95% CI)

‐8.69 [‐14.17, ‐3.21]

6.7 Salbutamol Day 5

1

43

Mean Difference (Fixed, 95% CI)

‐11.37 [‐17.55, ‐5.19]

Figuras y tablas -
Comparison 2. Pre‐ and postintervention comparison
Comparison 3. Adverse events

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Honey versus dextromethorphan Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 Nervousness, insomnia, hyperactivity

2

149

Risk Ratio (M‐H, Fixed, 95% CI)

2.94 [0.74, 11.71]

1.2 Stomachache, nausea, and vomiting

1

69

Risk Ratio (M‐H, Fixed, 95% CI)

4.86 [0.24, 97.69]

1.3 Drowsiness

1

69

Risk Ratio (M‐H, Fixed, 95% CI)

2.92 [0.12, 69.20]

2 Honey versus diphenhydramine Show forest plot

1

80

Risk Ratio (M‐H, Fixed, 95% CI)

0.14 [0.01, 2.68]

2.1 Somnolence

1

80

Risk Ratio (M‐H, Fixed, 95% CI)

0.14 [0.01, 2.68]

3 Honey versus placebo Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 Stomachache, nausea, and vomiting

2

402

Risk Ratio (M‐H, Fixed, 95% CI)

1.91 [1.12, 3.24]

3.2 Diarrhoea

1

102

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.33, 2.55]

3.3 Tachycardia

1

102

Risk Ratio (M‐H, Fixed, 95% CI)

1.58 [0.15, 16.86]

4 Honey versus salbutamol Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

4.1 Stomachache, nausea, and vomiting

1

100

Risk Ratio (M‐H, Random, 95% CI)

1.74 [1.04, 2.92]

4.2 Rash

1

100

Risk Ratio (M‐H, Random, 95% CI)

0.19 [0.02, 1.63]

4.3 Tachycardia

1

100

Risk Ratio (M‐H, Random, 95% CI)

1.51 [0.14, 16.10]

4.4 Diarrhoea

1

100

Risk Ratio (M‐H, Random, 95% CI)

0.59 [0.24, 1.45]

5 Honey versus no treatment Show forest plot

2

302

Odds Ratio (M‐H, Fixed, 95% CI)

6.99 [1.55, 31.58]

5.1 Nervousness, insomnia, hyperactivity

2

154

Odds Ratio (M‐H, Fixed, 95% CI)

9.40 [1.16, 76.20]

5.2 Stomachache, nausea, and vomiting

1

74

Odds Ratio (M‐H, Fixed, 95% CI)

5.90 [0.27, 127.14]

5.3 Drowsiness

1

74

Odds Ratio (M‐H, Fixed, 95% CI)

3.43 [0.14, 87.09]

Figuras y tablas -
Comparison 3. Adverse events