Thompson, M., Vodicka, T. A., Blair, P. S., Buckley, D. I., Heneghan, … · 2017. 2. 15. · 10.1136/bmj.f7027 Link to publication record in Explore Bristol Research PDF-document

Thompson, M., Vodicka, T. A., Blair, P. S., Buckley, D. I., Heneghan, C.,Hay, A. D., & TARGET Programme Team (2013). Duration of symptoms ofrespiratory tract infections in children: systematic review. BMJ, 347, [f7027].DOI: 10.1136/bmj.f7027

Publisher's PDF, also known as Version of record

License (if available):CC BY-NC

Link to published version (if available):10.1136/bmj.f7027

Link to publication record in Explore Bristol ResearchPDF-document

This is the final published version of the article (version of record). It first appeared online via BMJ athttp://www.bmj.com/content/347/bmj.f7027. Please refer to any applicable terms of use of the publisher.

University of Bristol - Explore Bristol ResearchGeneral rights

This document is made available in accordance with publisher policies. Please cite only the publishedversion using the reference above. Full terms of use are available:http://www.bristol.ac.uk/pure/about/ebr-terms.html

brought to you by COREView metadata, citation and similar papers at core.ac.uk

provided by Explore Bristol Research

https://core.ac.uk/display/73981109?utm_source=pdf&utm_medium=banner&utm_campaign=pdf-decoration-v1

http://dx.doi.org/10.1136/bmj.f7027

http://research-information.bristol.ac.uk/en/publications/duration-of-symptoms-of-respiratory-tract-infections-in-children(d5f419ac-4eb4-4443-9689-291211c45349).html

http://research-information.bristol.ac.uk/en/publications/duration-of-symptoms-of-respiratory-tract-infections-in-children(d5f419ac-4eb4-4443-9689-291211c45349).html

Duration of symptoms of respiratory tract infectionsin children: systematic review

OPEN ACCESS

Matthew Thompson Helen D Cohen endowed professor of family medicine 1, Talley A Vodickaconsultant 2, Peter S Blair senior research fellow 3, David I Buckley assistant professor 2, CarlHeneghan professor 4, Alastair D Hay professor of primary care and NIHR research professor 5, onbehalf of the TARGET Programme Team

1Department of Family Medicine, Box 354696, University of Washington, Seattle, WA 98195-4696, USA; 2Department of Primary Care HealthSciences, University of Oxford, Oxford, UK; 3School of Social and Community Medicine, Level D, St Michael’s Hospital, University of Bristol, Bristol,UK; 4Departments of Family Medicine, Medical Informatics and Clinical Epidemiology, Public Health and Preventive Medicine, Oregon Health andScience University, Portland, OR, USA; 5Centre for Academic Primary Care, School of Social and Community Medicine, University of Bristol, Bristol,UK

AbstractObjective To determine the expected duration of symptoms of commonrespiratory tract infections in children in primary and emergency care.

Design Systematic review of existing literature to determine durationsof symptoms of earache, sore throat, cough (including acute cough,bronchiolitis, and croup), and common cold in children.

Data sources PubMed, DARE, and CINAHL (all to July 2012).

Eligibility criteria for selecting studies Randomised controlled trialsor observational studies of children with acute respiratory tract infectionsin primary care or emergency settings in high income countries whoreceived either a control treatment or a placebo or over-the-countertreatment. Study quality was assessed with the Cochrane risk of biasframework for randomised controlled trials, and the critical appraisalskills programme framework for observational studies.

Main outcome measures Individual study data and, when possible,pooled daily mean proportions and 95% confidence intervals for symptomduration. Symptom duration (in days) at which each symptom hadresolved in 50% and 90% of children.

Results Of 22 182 identified references, 23 trials and 25 observationalstudies met inclusion criteria. Study populations varied in age andduration of symptoms before study onset. In 90% of children, earachewas resolved by seven to eight days, sore throat between two and sevendays, croup by two days, bronchiolitis by 21 days, acute cough by 25days, common cold by 15 days, and non-specific respiratory tractinfections symptoms by 16 days.

Conclusions The durations of earache and common colds areconsiderably longer than current guidance given to parents in the UnitedKingdom and the United States; for other symptoms such as sore throat,acute cough, bronchiolitis, and croup the current guidance is consistentwith our findings. Updating current guidelines with new evidence willhelp support parents and clinicians in evidence based decision makingfor children with respiratory tract infections.

IntroductionRespiratory tract infections are particularly common in children;most are self limiting and the risk of complications is small.Recommended management therefore typically involves selfcare and treatment of symptoms. Nevertheless, such infectionsstill account for over a third of paediatric consultations toprimary care in the United Kingdom and the United States,1 2

and antibiotics are commonly prescribed in many countriesdespite limited evidence of effectiveness.One of the most common questions that parents ask whenconsulting healthcare services is “how long will my child’ssymptoms last?” Accurate information about the expected courseof respiratory tract infections in children is essential for bothclinicians and parents, as it sets expectations and lets them knowwhen the illness is deviating from the expected.3 4 This directlyinforms parents’ decisions to seek medical attention, whetherto re-consult, and when to use delayed prescriptions ofantibiotics, as well as clinicians’ decisions on when to prescribeantibiotics or consider other treatments.3 5-7

Correspondence to: M Thompson [email protected]

Extra material supplied by the author (see http://www.bmj.com/content/347/bmj.f7027?tab=related#webextra)

Appendix 1: Search strategiesAppendix 2: Characteristics of included studiesAppendix 3: Quality assessment

No commercial reuse: See rights and reprints http://www.bmj.com/permissions Subscribe: http://www.bmj.com/subscribe

BMJ 2013;347:f7027 doi: 10.1136/bmj.f7027 (Published 11 December 2013) Page 1 of 19

Research

RESEARCH

http://creativecommons.org/licenses/by-nc/3.0/

http://www.bmj.com/content/347/bmj.f7027?tab=related#webextra

http://www.bmj.com/permissions

http://www.bmj.com/subscribe

http://crossmark.crossref.org/dialog/?doi=10.1136/bmj.f7027&domain=pdf&date_stamp=2013-12-11

Commonly used estimates of the expected time course ofsymptoms of common respiratory tract infections are highlyvariable and not always evidence based. For example, the 2008National Institute for Health and Care Excellence guidelinesfor treatment of respiratory tract infections include estimates ofaverage duration of the illness (before and after seeing a doctor)of four days for acute otitis media, one week for acute sorethroat, one and a half weeks for the common cold, and threeweeks for acute cough or bronchitis.8 By contrast, informationfor patients from the US Centers for Disease Control andPrevention describe sore throat as lasting one to two weeks,common cold lasting up to two weeks, and cough durationranging from two to eight weeks.9 The durations quoted in thesesources reflect findings based on expert opinion or fromindividual studies rather than from data synthesis of multiplestudies and are not child specific. We therefore conducted asystematic review of the literature on symptom durations of themost common respiratory tract infections (earache, sore throat,cough, and common cold) in children presenting to primarycare.

MethodsSelectionStudies were eligible for inclusion if they recruited otherwisehealthy children (birth to 18 years) with acute respiratoryinfections presenting to primary care or emergency departmentsettings; were conducted in high income countries, as definedby the Organisation for Economic Co-operation andDevelopment10; provided data on time to resolution of symptomsor complete duration of symptoms; involved placebo or notreatment arms of controlled non-surgical treatment trials orprospective observational studies; and reported in English.Although respiratory tract infections can include a cluster ofvarious symptoms, certain symptoms (such as cough)predominate in clinical experience and in published trials,depending on a child’s illness, ability to describe his or hersymptoms, and/or parental recognition and interpretation ofsymptoms.11 Given this, we chose to not only include studiesof children presenting with clustered symptoms (such ascommon cold or undifferentiated respiratory tract infections)but also those of individual symptoms (such as sore throat). Weincluded studies of children presenting with primary complaintsof earache (acute otitis media), sore throat (or pharyngitis ortonsillitis), cough (or acute bronchitis, bronchiolitis, or croup),and common cold (or upper respiratory tract infection).We excluded studies of children with chronic, recurrent, orcomplicated infections; experimentally induced infection; ormedical conditions associated with a high risk of seriousinfections (such as cystic fibrosis, immunodeficiency). We alsoexcluded studies conducted in inpatient settings or in low ormiddle income countries as defined by the Organisation forEconomic Co-operation and Development, where the risk ofcomplications from infection might be higher. Studies thatreported data on both children and adults were included only ifdata were presented separately by age. We excluded trialscomparing two active treatments, those of prophylactic oradjuvant treatments, and retrospective studies; studies withfollow-up of 24 hours or less; and studies that presentedsymptom duration only before consultation, assessed onlyincidence or prevalence, or presented duration of symptoms bysymptom score or individual pathogen.

SearchWe identified relevant intervention trials and observationalstudies using two search strategies (appendix 1). Firstly, weconducted searches in PubMed, DARE, and CINAHL (alldatabases searched through July 2012) to identify randomisedcontrolled trials and systematic reviews of trials for each of thefour symptoms of respiratory tract infection (sore throat, cough,common cold, and earache). Search terms included clinicalsyndromes and symptoms, study design, and paediatricpopulation with both MeSH and free text terms. We also handsearched the Cochrane Acute Respiratory Infections and Ear,Nose and Throat Groups for systematic reviews of randomisedcontrolled trials. Secondly, we searched PubMed (1966-July2012) for observational studies of children with acute sore throat,cough, common cold, or earache using terms for clinicalsyndromes and symptoms, child, and limited by publicationtype (that is, excluding clinical trials and systematic reviews ofclinical trials). We reviewed reference lists of selected studiesidentified using both of these strategies and searched relatedcitations to identify additional references. One author (TAV)screened titles and abstracts using the inclusion and exclusioncriteria. Two authors (TAV and MT) reviewed the full text ofall potentially relevant studies to determine final inclusion.

Data extractionTwo authors (TAV andMT) independently extracted data usinga predetermined template. Authors were not blinded to anyaspect of the studies during extraction, and disagreements wereresolved by consensus (TAV, MT, and DIB/CH). We extracteddata on country and setting of study; population; length offollow-up; description of presenting symptom(s) and/ordiagnostic criteria; description of intervention and control;definition of usual care in placebo arms of trials; specifiedoutcome(s); outcome assessor (parent, child, clinician, orinvestigator); method of outcome assessment; and data onadverse events (complications, re-consultations, admission tohospital).The outcomes of interest were time to resolution of symptomsor duration of symptoms. These included time taken forprespecified proportions (such as 50%) of children’s symptomsto have resolved, the study population, proportion of childrenwith unresolved symptoms at follow-up, or mean or medianduration of symptoms. For studies of common cold orundefined/non-specific respiratory tract infections, we extracteddata on symptom duration for the cluster of symptomscomprising a cold as defined in each study (reported in appendix2). We extracted data from studies that reported proportions ofchildren with symptoms at time points, provided continuousdata from which proportions could be inferred, or presentedmean (and 95% confidence interval) durations of symptoms.When available we also extracted data on symptom durationbefore consultation. We extracted data only from thenon-intervention (that is, placebo) arms of included randomisedcontrolled trials. Data from line graphs were extracted withDigitizeIt software (DigitizeIt 2010, version 4.0.2, Carrascal).

Quality assessmentTwo authors (TAV and MT) independently assessed quality ofincluded studies using the Cochrane risk of bias framework forrandomised controlled trials12 and the critical appraisal skillsprogramme13 framework for observational studies.Disagreements were resolved by consensus (TAV, MT, andDIB/CH). Judgment regarding risk of bias (“high,” “low,” or“unclear risk of bias”) was made for each criterion.



RESEARCH



Data synthesisWe report data on duration of symptoms for each symptomcategory from each study.When possible (that is, at time pointsincluded in two or more studies) we calculated the pooled dailymean proportions and 95% confidence intervals for symptomduration and presented summary data visually. Given theheterogeneity in study populations and inconsistent methods ofassessment, we have also presented the individual study datain addition to pooled means to display the variation in symptomdurations. We identified the mean time point (as number ofwhole days) at which the symptom was resolved in 50% and in90% of children with that particular symptom. Though we hadplanned to carry out subgroup analyses based on age andsymptom duration before enrolment, we were unable to do sobecause of insufficient data.

ResultsThe search for randomised controlled trials identified 10 829papers; after review of titles and/or abstracts we excluded 10637 (fig 1⇓). Based on full text review of 192 papers, weexcluded a further 169 and included 23 trials in the analysis.The search for observational studies identified 11 353 papers;after review of titles and/or abstracts we excluded 11 226 (fig2⇓), and after review of the full text of 127 we excluded 102,leaving 25 observational studies in the analysis. We presentresults separately by type of symptom of respiratory tractinfection.

EaracheWe included data from seven trials with 958 children14-20 andthree observational studies with 451 children21-23 (tables 1⇓ and2⇓). Included trials and studies came from the UK,14 23 USA,16Netherlands,15 Sweden,19 Denmark,18 Finland,20 Canada,17Poland,22 and Israel21 (appendix 2).Earache was generally present less than four days before studyentry, and follow-up ranged from eight days to four months inrandomised controlled trials, and 21 days to a year inobservational studies. In most studies, parents assessed symptomduration14-17 19-23 using daily symptom diaries, telephoneinterviews, or in person questionnaires. Most studies had lowrisk of bias, though assessment of bias was difficult because ofunclear methods in two studies18 23 (appendix 3). Risk of biaswas highest in the study by Neumark and colleagues,19 whichused an open trial design with no blinding among parents orclinicians.Among the five studies that reported mean duration, symptomsof earache lasted from half a day to nine days14 15 19 21 22 (table1⇓). Based on the pooled results from 10 studies, 50% ofchildren’s symptoms had resolved at day three and 90% by daysseven to eight (fig 3⇓). Damoiseaux and colleagues15 andGreenberg and colleagues21 reported fever (as well as earache)lasting three days (median) and 2.9 days (mean, SD 2.6),respectively.

Sore throatWe included six trials on 241 children24-29 and one observationalstudy of 103 infants.22 Most trials took place in NorthAmerica,24 26 27 with the remainder from the UK,25 Italy,28 andthe Netherlands.29 The single observational study was conductedin Poland.22

Characteristics of patients varied across studies (appendix 2).Average duration of illness before entry into the study rangedfrom less than one to less than four days. Outcomes were

assessed by parents in all studies,22 24-29 clinicians in twostudies,26 28 and children in three studies,25 27 28 with length offollow-up ranging from two days to a week or, in two studies,22 27until symptoms resolved. Most studies had a low risk of bias,except one in which blinding of outcome assessors wasimpossible because of the mode of intervention delivery(intramuscular penicillin v oral placebo)26 (appendix 3).Measurement of outcomes varied considerably across studies,involving different methods, assessors, and lengths of follow-up.Outcomemeasurement was based on standardised scales in onlytwo studies24 27; the remainder22 25 29 used parental assessment(by questionnaire, symptom diary, or overall parentalassessment), or clinician assessment.28

Among the four studies that reported mean duration, symptomsof sore throat lasted from two days to 6.7 days22 24 27 29 (table3⇓). Though we could not pool data from the three studies thatreported the proportion of children with symptoms because ofinsufficient data at several time points, 33-37% of children stillhad sore throat symptoms at day three25 26 28 (fig 4⇓, table 3⇓).Based on visual inspection of the data, time to completeresolution did not seem to be related to group A β haemolyticstreptococcal infection or duration of symptoms beforeenrolment. The single study that reported on duration of feverreported that 17% of children had fever for less than a day, 11%had fever one to two days, 44% had fever for two to three days,and 28% had fever for more than three days.26

Cough (acute cough, bronchiolitis, and croup)We included six trials of acute cough,30 croup,31-33 orbronchiolitis,34 35 providing data on 700 children. Five trials tookplace in North America30-32 34 35 and one in Australia.33 Weincluded six observational studies of 1063 children withcough3 22 36 37 or bronchiolitis,38 39 from the UK,3 36 Poland,22Australia,37 USA,38 and Canada39 (appendix 2).Cough was present five to 14 days before study entry amongchildren with acute cough, four days among children withbronchiolitis, and one day among children with croup. In moststudies follow-up lasted two to three weeks or until symptomsresolved (range one to four weeks). Parents assessed outcomesin all trials and studies that used symptom scales orscores,30-32 34 39 symptom diaries,3 36-38 standardisedquestionnaire,22 or interview.39 Studies had either a low ormoderate risk of bias; those with moderate risk of bias generallylacked details of randomisation or sequence allocation30 33

(appendix 3).Among the five studies that reported mean duration of illness,the time to resolution of cough ranged from one to 25days3 22 30 36 37 (table 4⇓). Based on the pooled results from fivestudies that reported proportions of children with symptoms,cough had resolved in 50% of children at 10 days, and 90% by25 days (table 5⇓, fig 5⇓). Symptom duration was relativelyshorter in two studies,22 30 of which one30 was small (n=23) andenrolled children with symptoms lasting up to 14 days beforerecruitment, and the other22 recruited only infants.The mean duration of croup was two and three days in the twostudies that reported this information32 33 (table 4⇓), and, basedon the pooled data from two studies,31 32 symptoms of croupresolved in 50% of children at day one and 80% by two days(table 5, fig 6⇓).Finally, the mean time to resolution of cough for bronchiolitisranged from eight34 to 1538 days (table 4, fig 7⇓). Based onpooled data from four studies that reported proportions ofchildren with symptoms,34 35 38 39 50% of children improved byday 13 (table 5⇓). Though we were unable to determine the time



RESEARCH



for 90% to improve, based on the data presented in figure 7 thiswas estimated at 21 days.

Common cold; undefined or non-specificrespiratory tract infectionsWe included four trials involving 457 children40-43 and 15observational studies involving 4870 children.7 22 37 44-55 Includedtrials and studies were from the US,40 42 43 49 50-52 55 the UK,7 44 53

Finland,41 48 Canada,45 47 Poland,22 Australia,37 Denmark,54 andGermany46 (appendix 2).Follow-up ranged from two to 21 days in randomised controlledtrials; in observational studies, follow-up generally lasted twoto three weeks. The mean duration of symptoms before trialentry ranged from up to one day43 to 8.7 (SD 5.1) days.41Outcome assessment was performed by parents (using interviewsor symptom diaries) in three trials40 41 43 and by both parents andchildren (symptom diary) in one.42Overall, included studies hadlow to moderate risk of bias (appendix 3). Treatment andplacebo lozenges were dissimilar in appearance in onerandomised controlled trial, which raised the risk of bias frominadequate blinding.42 Several studies failed to reportrandomisation,40 cohort selection,49 52 or inclusion criteria.7 44 46

Among the four studies that reported mean duration, commoncold symptoms lasted from seven to 15 days22 42 46 51 (fig 8⇓,table 6⇓). Based on the pooled data from five studies,22 40 42 49 51

by day 10 about 50% of children had improved. We did nothave sufficient data to determine the time at which 90%improved, but based on visual inspection from figure 8 weestimated this as about 15 days. The largest study (n=1314)reported common cold symptoms lasting 1.8 weeks (SD 1.3)for children aged 7 or younger.46

Themean duration of non-specific respiratory symptoms rangedfrom four to 16 days7 43 45 47 48 50 53-55 (table 6⇓). Data on theproportion of children with symptoms was obtained from 11studies7 37 41 43-45 47 48 50 53 54 and was highly variable acrossindividual studies: 50% of children had improved by day sevento eight and 80% by day 14; we could not identify the time for90% resolution, although a projected estimate would be aroundday 16 (table 7⇓, fig 9⇓). The studies that reported symptomsat day 14, however, showed an extremely wide range in theproportion still symptomatic, from 6%44 to 60%.48 The shorterlength of symptom duration reported by both Butler andcolleagues44 and Jacobs and colleagues47 could be explained byslightly longer average duration of symptoms before study entry.Taylor and colleagues reported duration of fever of 0.64 meandays (SD 1.16).43

DiscussionOur review provides parents, clinicians, and policy makers withup-to-date evidence based estimates of the expected length ofsymptoms for children presenting with the most commonrespiratory tract infections in primary care and emergencydepartment settings in high income countries: earache, sorethroat, cough, and non-specific cold symptoms. These infectionswere selected because they are common and drive most primarycare consultations and antibiotic prescribing for children in highincome countries. We used data from systematic searches forboth randomised controlled trials (placebo arms) andobservational studies conducted in high income countries. Formany symptoms of respiratory tract infection the data werehighly heterogeneous in terms of age, definition of infection,outcome assessment, and duration of illness before study entry;however, our data provide the most robust estimates available.

For some symptoms of respiratory tract infections our estimatesof duration are much longer than those currently used (table8⇓). For example, for earache (otitis media) we found that 90%of children are better by seven to eight days, which isconsiderably longer than the average duration of four days citedby the UK National Institute for Health and Care Excellenceand two days cited by the US Centers for Disease Control andPrevention. In contrast, for some symptoms current estimatesseem to overestimate the expected duration.We found that acutecough symptoms are better in 50% of children by 10 days, incontrast with the longer average duration of 21 days cited byNational Institute for Health and Care Excellence. Finally, forother symptoms, the currently cited estimates of symptomduration match closely (or are slightly longer) with ourfinding—for example, for sore throat/tonsillitis we found that90% are better by two to seven days, whereas National Institutefor Health and Care Excellence and the Centers for DiseaseControl and Prevention cite average durations of seven daysand seven to 14 days, respectively. Similarly, the common coldseems to last from 10 (50% better) to 15 days (90% better),similar to advice from both National Institute for Health andCare Excellence (10-11 days) and the Centers for DiseaseControl and Prevention (<14 days).

Strengths and limitationsWe believe this is the first systematic review of the duration ofillness for common respiratory tract infections in children. Ourstrategy of including data from placebo arms of randomisedcontrolled trials and from observational studies not onlyincreases the available data but also provides more generalisablepopulations of children. This approach inevitably includedchildren whomight have been given over-the-counter treatmentsfor symptoms and, in a few cases, antibiotics. We consider thatit would be unrealistic to restrict our review to children withrespiratory tract infections whowere not given any symptomatictreatment.While symptomatic treatmentsmight reduce symptomseverity, however, they are unlikely to influence the overallduration of illness. It is possible that excluding studies ofexperimentally induced infection might have reduced eligiblestudies, though we do not consider that these types of usuallysingle pathogen infections reflect the reality of clinical practice,where patients typically present with clinical syndromes ratherthan pathogen specific infections. In synthesising our results,we opted to present the number of days when 50% and 90% ofchildren were reported to be asymptomatic. Although the datawere not available for all the respiratory tract infections, webelieve that this additional information avoids the ambiguity ofterms such as “average duration” for parents and clinicians. Ourestimates of duration also apply to children who are given(usually symptomatic) drugs rather than those given nothing atall, thereby providing more valuable information for how mostchildren are managed in the community. As many trials andstudies will have excluded children with severe symptoms, ourfindings might not be generalisable to such children or those inlow or middle income countries where risks of complicationsare higher. While we included data from both randomisedcontrolled trials and prospective observational studies, weexcluded retrospective studies, which could be subject to recallor recording bias.As with any systematic review, our findings and complexity ofsynthesis are limited by the number and quality of includedstudies and the data these provided. The included studies wereinevitably clinically heterogeneous in many aspects. Thedefinition of the respiratory tract infection syndromes differed(or were poorly defined) in some studies, which could affect



RESEARCH



less discrete conditions (such as the common cold) more thanothers (such as croup); though this is a problem with muchresearch in this area. Secondly, the duration of illness beforestudy entry varied and was not consistently recorded, whichprevented us from calculating what would have been potentiallymore useful for parents—namely, the duration of illness frominitial onset rather than presentation. However, this mirrors thesituation in primary care where patients present in exactly thisway. Thirdly, the lack of sufficient data on age in includedstudies meant that we were not able to conduct age specificanalyses. For some infections, however, the age ranges ofchildren in included studies were relatively narrow (such as forbronchiolitis and croup) as would be predicted clinically, sosubgroup analysis might not have contributed much to theirinterpretation. For other infections, such as sore throat or cough,the age ranges were much broader and subgroup analysis basedon age would have been useful clinically. Fourthly, the methodsused in individual studies to measure and report symptoms werehighly variable, and the absence of consistent (daily) reportingfor similar durations of follow-up for each respiratory tractinfection meant that we were not able to pool data for allinfections studied. When possible, we attempted to pool resultsby calculating mean proportions and 95% confidence intervals,but this does not take account of the lack of homogeneitybetween studies. We attempted to mitigate this by including theindividual study data in all our figures to give some idea of thevariability in symptom projection. Thus, pooled means need tobe interpreted cautiously.

Implications for clinicians, policy, andresearchOur review provides evidence that can be put to daily use byclinicians and parents caring for children with respiratory tractinfections, as well as informing health policy and evidence basedtreatment guidelines. We provide data as far as possible fornumber of days for 50% and 90% of children’s symptoms tohave improved; we anticipate that clinicians and parents couldinterpret these values into absolute terms as the “time for halfof children” to get better, and “time for 9 out of 10 children” toget better (table 8⇓). There are two key clinical decisions thesedata could inform. First is the parents’ decision to consultprimary care, with its attendant implications for appropriate useof healthcare resources. Here, the data could inform algorithmsused by healthcare providers (in writing, by telephone, or inperson) to give parents information about expected length oftime that symptoms might last, helping to reassure parents andtrigger consultations more appropriately when the illness seemsto deviate from course. Second is the clinician’s decision toprescribe antibiotics. Once again, these data could help reassureclinicians regarding the “normality” of some respiratorysymptoms lasting for longer than previously appreciated andnot necessarily requiring antimicrobial intervention.We found limited data for the duration of illness for severalrespiratory tract infections (such as croup), which suggests thatobservational studies would be helpful to increase certainty ofour estimates of duration of symptoms. What parents andclinicians still need are better ways of predicting which childrenwill have an adverse or prolonged illness and need additionaltreatment (such as antibiotics) or more intensive monitoring(such as repeated visits). Results of ongoing research effortssuch as the TARGET study (www.targetstudy.org.uk/) will helpto provide these prediction tools. Future research should alsofocus the evaluation of new and existing interventions inchildren with the most severe illness trajectories.

ConclusionsParents, clinicians, and policymakers should use these evidencebased estimates of symptom duration when making decisionregarding healthcare seeking and prescribing, and also whendeveloping clinical guidelines for respiratory tract infections inchildren. Widespread dissemination of these data will improveparental and clinician awareness of how long symptoms last inchildren with respiratory tract infections.

TARGET team: Alastair D Hay, Andrew Lovering, Brendan Delaney,Christie Cabral, Hannah Christensen, Hannah Thornton, Jenny Ingram,JeremyHorwood, John Leeming,Margaret Fletcher, Matthew Thompson,Niamh Redmond, Patricia J Lucas, Paul Little, Peter S Blair, PeterBrindle, Peter Muir, Sandra Hollinghurst, Sue Mulvenna, Talley AVodicka, and Tim Peters.c Crown Copyright 2013Contributors: MT and ADH were responsible for the concept of thisresearch study. MT, ADH, CH, DIB, and PSB were responsible for themethods used for the systematic review. MT, TAV, DIB, and CH wereresponsible for the searches and identification of included studies, forassessing quality, and extracting data from included studies. TAV, MT,and PSB were responsible for data analyses and presentation of results.All authors were involved in reviewing, commenting, and editing draftsof the manuscript and all approved of the final manuscript. MT isguarantor.Funding: This study was funded by the National Institute for HealthResearch (NIHR) under its programme grants for applied researchfunding scheme (RP-PG-0608-10018) and from a career developmentfellowship (for MT) supported by the National Institute for HealthResearch. The views expressed in this publication are those of theauthor(s) and not necessarily those of the NHS, the NIHR or theDepartment of Health. The funding agency had no involvement in thestudy design, data collection, analysis, writing of the manuscript, ordecision to submit it for publication.Competing interests: All authors have completed the ICMJE uniformdisclosure form at www.icmje.org/coi_disclosure.pdf and declare: nosupport from any organisation for the submitted work; no financialrelationships with any organisations that might have an interest in thesubmitted work in the previous three years; no other relationships oractivities that could appear to have influenced the submitted work.Ethical approval: Not required.Data sharing: No additional data available.Transparency: MT affirms that the manuscript is an honest, accurate,and transparent account of the study being reported; that no importantaspects of the study have been omitted; and that any discrepanciesfrom the study as planned (and, if relevant, registered) have beenexplained.

1 Hay AD, Heron J, Ness A; ALSPAC study team. The prevalence of symptoms andconsultations in pre-school children in the Avon Longitudinal Study of Parents and Children(ALSPAC): a prospective cohort study. Fam Pract 2005;22:367-74.

2 Fendrick A, Monto AS, Nightengale B, Sarnes M. The economic burden ofnon-influenza-related viral respiratory tract infection in the United States. Arch Intern Med2003;163:487-94.

3 Hay AD,Wilson A, Fahey T, Peters TJ. The duration of acute cough in pre-school childrenpresenting to primary care: a prospective cohort study. Fam Pract 2003;20:696-705.

4 Butler CC, Hood K, Kinnersley P, Robling M, Prout H, Houston H. Predicting the clinicalcourse of suspected acute viral upper respiratory tract infection in children. Fam Pract2005;22:92-5.

5 Butler CC, Rollnick S, Kinnersley P, Tapper-Jones L, Houston H. Communicating aboutexpected course and re-consultation for respiratory tract infections in children: anexploratory study. Br J Gen Pract 2004;54:536-8.

6 Rosenfeld RM, Singer M, Jones S. Systematic review of antimicrobial therapy in patientswith acute rhinosinusitis. Otolaryngol Head Neck Surg 2007;137:S32-45.

7 Mitra A, Hannay D, Kapur A, Baxter G. The natural history of acute upper respiratory tractinfections in children. Prim Health Care Res Dev 2011;12:329-34.

8 NICE Short Clinical Guidelines Technical Team. Respiratory tract infections—antibioticprescribing. Prescribing of antibiotics for self-limiting respiratory tract infections in adultsand children in primary care. National Institute for Health and Care Excellence, 2008.

9 Centers for Disease Control and Prevention (CDC). Get smart: respiratory illnesses. www.cdc.gov/getsmart/antibiotic-use/URI/index.html.



RESEARCH

http://www.targetstudy.org.uk/

http://www.icmje.org/coi_disclosure.pdf

http://www.cdc.gov/getsmart/antibiotic-use/URI/index.html

http://www.cdc.gov/getsmart/antibiotic-use/URI/index.html



What is already known on this topic

Respiratory tract infections in children are responsible for more primary care consultations that any other group of illnessesParents need to know how long symptoms will last to guide help seeking behaviour and use of antibioticsThe scientific basis for current estimates of duration of illness of common respiratory tract infections is not clear and differs betweeninternational bodies such as the UK National Institute for Health and Care Excellence and the US Centers for Disease Control andPrevention

What this study adds

This systematic review provides new evidence based estimates of the expected duration of the most common respiratory symptoms ofchildhood respiratory tract infections, including earache, sore throat, cough, and common coldThere are clinically important differences between the duration estimates we found and those previously published. In most (90%)children earache was resolved by seven to eight days, sore throat by two to seven days, croup by two days, bronchiolitis by 21 days,acute cough by 25 days, common cold by 15 days, and non-specific respiratory tract infections symptoms by 16 daysAccurate estimates of duration will help to direct more appropriate help seeking behaviours by parents and use of antibiotics. Resultswill help clinicians and parents distinguish normal from abnormal respiratory tract infections

10 World Bank. Country and lending groups: high-income OECD members. Annual Report,2011.

11 Laine MK, Tahtinen PA, Ruuskanen O, Huovinen P, Ruohola A. Symptoms orsymptom-based scores cannot predict acute otitis media at otitis-prone age. Pediatrics2010;125:e1154-61.

12 Higgins JPT, Green S, eds. Cochrane handbook for systematic reviews of interventions.Version 5.1.0. Cochrane Collaboration, 2011. www.cochrane-handbook.org.

13 Critical Appraisal Skills Programme (CASP). www.casp-uk.net/.14 Burke P, Bain J, Robinson D, Dunleavey J. Acute red ear in children: controlled trial of

non-antibiotic treatment in general practice. BMJ 1991;303:558-62.15 Damoiseaux RA, van Balen FA, Hoes AW, Verheij TJ, de Melker RA. Primary care based

randomised, double blind trial of amoxicillin versus placebo for acute otitis media in childrenaged under 2 years. BMJ 2000;320:350-4.

16 Hoberman A, Paradise JL, Rockette HE, Shaikh N,Wald ER, Kearney DH, et al. Treatmentof acute otitis media in children under 2 years of age. N Engl J Med 2011;364:105-15.

17 Le Saux N, Gaboury I, Baird M, Klassen TP, MacCormick J, Blanchard C, et al. Arandomized, double-blind, placebo-controlled noninferiority trial of amoxicillin for clinicallydiagnosed acute otitis media in children 6 months to 5 years of age. CMAJ2005;172:335-41.

18 Mygind N, Meistrup-Larsen KI, Thomsen J, Thomsen VF, Josefsson K, Sorensen H.Penicillin in acute otitis media: a double-blind placebo-controlled trial. Clin OtolaryngolAllied Sci 1981;6:5-13.

19 Neumark T, Molstad S, Rosen C, Persson LG, Torngren A, Brudin L, et al. Evaluation ofphenoxymethylpenicillin treatment of acute otitis media in children aged 2-16. Scand JPrim Health Care 2007;25:166-71.

20 Tahtinen PA, Laine MK, Huovinen P, Jalava J, Ruuskanen O, Ruohola A. Aplacebo-controlled trial of antimicrobial treatment for acute otitis media. N Engl J Med2011;364:116-26.

21 Greenberg D, Bilenko N, Liss Z, Shagan T, Zamir O, Dagan R. The burden of acute otitismedia on the patient and the family. Eur J Pediatr 2003;162:576-81.

22 Jedrychowski W, Galas A, Pac A, Flak E, Camman D, Rauh V, et al. Prenatal ambientair exposure to polycyclic aromatic hydrocarbons and the occurrence of respiratorysymptoms over the first year of life. Eur J Epidemiol 2005;20:775-82.

23 Smith L, Ewings P, Smith C, Thompson M, Harnden A, Mant D. Ear discharge in childrenpresenting with acute otitis media: observational study from UK general practice. Br JGen Pract 2010;60:101-5.

24 Bulloch B, Kabani A, Tenenbein M. Oral dexamethasone for the treatment of pain inchildren with acute pharyngitis: a randomized, double-blind, placebo-controlled trial. AnnEmerg Med 2003;41:601-8.

25 Chapple PA, Franklin LM, Paulett JD, Tuckman E, Woodall JT, Tomlinson AJ, et al.Treatment of acute sore throat in general practice; therapeutic trial, with observations onsymptoms and bacteriology. BMJ 1956;i:705-8.

26 Nelson JD. The effect of penicillin therapy on the symptoms and signs of streptococcalpharyngitis. Pediatr Infect Dis 1984;3:10-3.

27 Olympia RP, Khine H, Avner JR. Effectiveness of oral dexamethasone in the treatmentof moderate to severe pharyngitis in children. Arch Pediatr Adolesc Med 2005;159:278-82.

28 Ruperto N, Carozzino L, Jamone R, Freschi F, Picollo G, Zera M, et al. A randomized,double-blind, placebo-controlled trial of paracetamol and ketoprofren lysine salt for paincontrol in children with pharyngotonsillitis cared by family pediatricians. Ital J Pediatr2011;37:48.

29 Zwart S, Rovers MM, de Melker RA, Hoes AW. Penicillin for acute sore throat in children:randomised, double blind trial. BMJ 2003;327:1324.

30 Bernard DW, Goepp JG, Duggan AK, Serwint JR, Rowe PC. Is oral albuterol effective foracute cough in non-asthmatic children? Acta Paediatr 1999;88:465-7.

31 Bjornson CL, Klassen TP, Williamson J, Brant R, Mitton C, Plint A, et al. A randomizedtrial of a single dose of oral dexamethasone for mild croup. N Engl J Med2004;351:1306-13.

32 Cruz MN, Stewart G, Rosenberg N. Use of dexamethasone in the outpatient managementof acute laryngotracheitis. Pediatrics 1995;96:220-3.

33 Geelhoed GC, Turner J, Macdonald WB. Efficacy of a small single dose of oraldexamethasone for outpatient croup: a double blind placebo controlled clinical trial. BMJ1996;313:140-2.

34 Patel H, Gouin S, Platt RW. Randomized, double-blind, placebo-controlled trial of oralalbuterol in infants with mild-to-moderate acute viral bronchiolitis. J Pediatr2003;142:509-14.

35 Plint AC, Johnson DW, Patel H, Wiebe N, Correll R, Brant R, et al. Epinephrine anddexamethasone in children with bronchiolitis. N Engl J Med 2009;360:2079-89.

36 Hay AD, Gorst C, Montgomery A, Peters TJ, Fahey T. Validation of a clinical rule to predictcomplications of acute cough in preschool children: a prospective study in primary care.Br J Gen Pract 2007;57:530-7.

37 Kusel MM, de Klerk N, Holt PG, Landau LI, Sly PD. Occurrence and management ofacute respiratory illnesses in early childhood. J Paediatr Child Health 2007;43:139-46.

38 Petruzella FD, Gorelick MH. Duration of illness in infants with bronchiolitis evaluated inthe emergency department. Pediatrics 2010;126:285-90.

39 Plint AC, Johnson DW, Wiebe N, Bulloch B, Pusic M, Joubert G, et al. Practice variationamong pediatric emergency departments in the treatment of bronchiolitis. Acad EmergMed 2004;11:353-60.

40 Hutton N, Wilson MH, Mellits ED, Baumgardner R, Wissow LS, Bonuccelli C, et al.Effectiveness of an antihistamine-decongestant combination for young children with thecommon cold: a randomized, controlled clinical trial. J Pediatr 1991;118:125-30.

41 Kristo A, Uhari M, Luotonen J, Ilkko E, Koivunen P, Alho OP. Cefuroxime axetil versusplacebo for children with acute respiratory infection and imaging evidence of sinusitis: arandomized, controlled trial. Acta Paediatr 2005;94:1208-13.

42 Macknin ML, Piedmonte M, Calendine C, Janosky J, Wald E. Zinc gluconate lozengesfor treating the common cold in children: a randomized controlled trial. JAMA1998;279:1962-7.

43 Taylor JA, Weber W, Standish L, Quinn H, Goesling J, McGann M, et al. Efficacy andsafety of echinacea in treating upper respiratory tract infections in children: a randomizedcontrolled trial. JAMA 2003;290:2824-30.

44 Butler CC, Kinnersley P, Hood K, Robling M, Prout H, Rollnick S, et al. Clinical course ofacute infection of the upper respiratory tract in children: cohort study. BMJ2003;327:1088-9.

45 Carabin H, Gyorkos TW, Soto JC, Joseph L, Collet JP. Comparison between two commonmethods for reporting cold and diarrhoea symptoms of children in daycare centre research.Child Care Health Dev 2000;26:471-85.

46 Gruber C, Keil T, Kulig M, Roll S, Wahn U, Wahn V. History of respiratory infections inthe first 12 yr among children from a birth cohort. Pediatr Allergy Immunol 2008;19:505-12.

47 Jacobs B, Young NL, Dick PT, Ipp MM, Dutkowski R, Davies HD, et al. Canadian AcuteRespiratory Illness and Flu Scale (CARIFS): development of a valid measure for childhoodrespiratory infections. J Clin Epidemiol 2000;53:793-9.

48 Kristo A, Uhari M, Kontiokari T, Glumoff V, Kaijalainen T, Leinonen M, et al. Nasal middlemeatal specimen bacteriology as a predictor of the course of acute respiratory infectionin children. Pediatr Infect Dis J 2006;25:108-12.

49 Pappas DE, Hendley JO, Hayden FG, Winther B. Symptom profile of common colds inschool-aged children. Pediatr Infect Dis J 2008;27:8-11.

50 Samet JM, Cushing AH, Lambert WE, Hunt WC, McLaren LC, Young SA, et al.Comparability of parent reports of respiratory illnesses with clinical diagnoses in infants.Am Rev Respir Dis 1993;148:441-6.

51 Steinweg KK. Natural history and prognostic significance of purulent rhinitis. J Fam Pract1983;17:61-4.

52 Taylor JA, Weber WJ, Martin ET, McCarty RL, Englund JA. Development of a symptomscore for clinical studies to identify children with a documented viral upper respiratorytract infection. Pediatr Res 2010;68:252-7.

53 Turner Cobb JM, Steptoe A. Psychosocial influences on upper respiratory infectiousillness in children. J Psychosom Res 1998;45:319-30.

54 Von Linstow ML, Holst KK, Larsen K, Koch A, Andersen PK, Hogh B. Acute respiratorysymptoms and general illness during the first year of life: a population-based birth cohortstudy. Pediatr Pulmonol 2008;43:584-93.

55 Wald ER, Guerra N, Byers C. Upper respiratory tract infections in young children: durationof and frequency of complications. Pediatrics 1991;87:129-33.

Accepted: 08 November 2013

Cite this as: BMJ 2013;347:f7027This is an Open Access article distributed in accordance with the Creative CommonsAttribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute,remix, adapt, build upon this work non-commercially, and license their derivative workson different terms, provided the original work is properly cited and the use isnon-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/.



RESEARCH

http://www.cochrane-handbook.org

http://www.casp-uk.net/

http://creativecommons.org/licenses/by-nc/3.0/



Tables

Table 1| Duration of earache in children in seven randomised controlled trials and three observation studies

Proportion of children with symptomsremaining at follow-up:

Mean (SD)time to

Mean (SD)symptom

Concurrenttreatment

Mean or rangeageFollow-up

No insampleStudy

durationbefore study

entry

symptomresolution(days) 8 days6 days3 days

Randomised controlled trials

13%18%46%3.3430.1 hoursAB (14%); S3-10 years3 months113Burke, 1991*

—72% (89/123)—9 (medianduration of painand crying)

54% hadsymptoms

lasting >3 days

S13.3 months6 weeks105Damoiseaux,2000

47%52%70%—<2 daysS6-23 months21 days139Hoberman,2011†

——78%(193/246)

—<4 daysS2.87 years4 months246Le Saux, 2005‡

——38%—≤24 hoursS4.1 years3 months77Mygind, 1981

17%25%56%0.5 (0-5)§<4 daysS5.9 years3 months87Neumark, 2007

04%45%—NRS16 months8 days158Tahtinen, 2011

Observational studies

———6.5 (5.2)NRAB (% NR); S14.8 (SD 8.3)months

21 days150Greenberg, 2003

———8.6<48 hoursNR<1 yearUntil symptomresolution

45Jedrychowski,2005

34% (13/38) withear discharge;20% (44/218)with no eardischarge

———NRAB: 92% (eardischarge),44% (no eardischarge)

Median 3 (IQR1-5) years

3 months256Smith, 2010

AB=antibiotics; NR=not reported; S=symptomatic treatment; IQR=interquartile range.*Outcome presented is proportion of children with “whose initial episode had persisted up to or beyond that time.”14

†Outcome presented corresponds to the second recording of AOM-SOS of 0 or 1.‡Outcome presented is proportion of children with ear pain.



RESEARCH



Table 2| Proportion of children with earache on days one to eight in seven randomised controlled trials and three observation studies

Proportion of children (numbers) with symptoms remaining at follow-up

Study Day 8Day 7Day 6Day 5Day 4Day 3Day 2Day 1


13 (15/118)13 (15/118)18 (21/118)23 (27/118)31 (37/118)46 (54/118)67 (79/118)67 (79/118)Burke, 1991*

————72 (89/123)———Damoiseaux, 2000

—47 (69/147)52 (76/147)55 (81/147)64 (94/147)70 (103/147)86 (126/147)100 (147/147)Hoberman, 2011†

—————22 (53/246)33 (83/250)42 (106/254)Le Saux, 2005‡

—————38——Mygind, 1981

—17 (15/87)25 (22/87)30 (26/87)44 (38/87)56 (49/87)75 (65/87)95 (83/87)Neumark, 2007

0 (0/0)4 (6/160)4 (6/160)17 (27/160)25 (40/160)45 (72/160)63 (101/160)100 (160/160)Tahtinen, 2011


—34 (13/38)§; 20 (44/218)¶——————Smith, 2010

*Outcome presented is proportion of children with “whose initial episode had persisted up to or beyond that time.”14

†Outcome presented corresponds to second recording of AOM-SOS of 0 or 1.‡Outcome presented is proportion of children with ear pain.§Children with ear discharge.¶Children without ear discharge.



RESEARCH



Table 3| Duration of sore throat in children in six randomised controlled trials and one observation study

Proportion of children with sore throatremaining at follow-upTime to symptom

resolution

Symptomduration beforestudy entry

ConcurrenttreatmentAge (years)

Follow-up(days)*

No insampleStudy ≥Day 3Day 2Day 1


———48 hours (95% CI38.0 to 58.0)

<48 hoursS10.1 (3)†251Bulloch, 2003

33% (57/174)———<48 hoursS2-9357Chapple, 1956

—35% (6/17)53% (9/17)—24 hours(median)

N5-11317Nelson, 1984

———70.8 (49.6)† hours‡NRS11.3Untilresolution

25Olympia, 2005

37% (12/32)———<1 weekNR8.1 (1.7)†432Ruperto, 2011

———3.5 days (95% CI2.9 to 4.1)§; 4.7

days (84 to 141.6)‡

3.8 days (mean)S10.1 (3.9)†756Zwart, 2003

Observational study

———6.7 days<48 hours¶NR0-1Untilresolution

103Jedrychowski,2005

NR=not reported; S=symptomatic.*Follow-up for outcome of symptom duration.†Mean (SD)‡Children without group A streptococcal infection or other culture.§Children with group A streptococcal infection.¶To be counted as episode, child must show symptoms for at least one day.



RESEARCH



Table 4| Duration of cough in children in six randomised controlled trials and six observational studies

Proportion of children with cough remainingat follow-upTime to

symptomresolution

Symptomduration

before studyentry

ConcurrenttreatmentAgeFollow-up

No insampleStudy Weeks 2-4Day 10Day 6Day 3

Acute cough

Randomised controlled trials:

—13%18%58%—1-14 daysAB (38%); S1-10 years7 days23Bernard, 1999

Observational studies:

10% (day25)

50%75%93%—Median 5 (IQR3-14) days

AB (18%); SMedian 21 (IQR8.6-35) months

Until symptomresolution

228Hay, 2003

25%50% (day9)

75%——Median 7 daysAB (24%); SMedian 24 (IQR12-37) months


154Hay, 2007

————Cough: mean 7.3days; barkingcough: 5.7 days

<48 hoursNR<1 yearUntil symptomresolution


6% (2-4weeks)

22% (1-2weeks)

52% (4-7days)

83%—NRAB (23%); S<5 yearsUntil symptomresolution

198Kusel, 2007*

Croup


———22%—Mean 0.8 (SD2.4) days

AB (%NR); SMean 35 (SD 23)months

21 days348Bjornson,2004†

———58%Median 3 daysMean 1.04 (SD1.0) days

SMean 21 (SD 8)months

7-10 days19Cruz, 1995

————Mean 2 (SD 1.6)days

21 (54) hoursNRMean 45 (SD 26)months

7-10 days48Geelhoed,1996

Bronchiolitis


—37%73%96%Median 8.4 (3.7)days; 8.0 days(95% CI 7 to 9)

Median 4 (IQR3-7) days

NRMean 5.1 (SD2.6) months

2 weeks or untilsymptomresolution

61Patel, 2003

————Median 13.3days (IQR8.2-19.5)

Median (IQR) 4(2-6) days

NRMedian 5 (IQR3-7) months

22 days201Plint, 2009


25% (day20)

77%97%100%Median 15 (IQR11-20)

NRNRMedian 4 (IQR3-7) months

4 weeks or untilsymptomresolution

95Petruzella,2010

————Median 12 (IQR8-20)

Median 4 daysSMedian 5 (IQR2-8) months

2-3 weeks163Plint, 2004

IQR=interquartile range; NR=not reported; S=symptomatic.*Outcome is duration of proportion of episodes with cough.†Outcome is proportion of children with Telephone Outpatient Score of zero.



RESEARCH



Table 5| Proportion of children with cough on days 1-7, 10, 15, and 25 in six randomised controlled trials and six observational studies

Proportion of children with cough remaining at follow-up

Study Day 25Day 15Day 10Day 7Day 6Day 5Day 4Day 3Day 2Day 1

Acute cough


———13% (4/29)18% (5/29)27% (8/29)34% (10/29)58% (17/29)83% (24/29)100% (29/29)Bernard, 1999


10% (22/228)25% (57/228)50%(114/228)

67% (153/228)75%(171/228)

80%(182/228)

85%(194/228)

93%(212/228)

96%(218/228)

98%(223/228)

Hay, 2003

—25% (41/164)50%(82/164)(day 9)

——75%(123/164)

————Hay, 2007

6% (12/198)(2-4 weeks)

22% (44/198)(1-2 weeks)

—52% (103/198)(4-7 days)

———83%(164/198) (1-3

days)

——Kusel, 2007*

Croup


———————22% (79/361)47%(170/361)

70%(253/361)

Bjornson,2004†

—————————58% (11/19)Cruz, 1995

Bronchiolitis


—25% (16/65)37% (24/65)70% (46/65)73% (47/65)86% (56/65)91% (61/65)96% (62/65)100%(65/65)

100% (65/65)Patel, 2003

25% (at 19.5days)

50% (at 13.3days)

—75% (at 8.2days)

——————Plint 2010


25% (28/112)50% (56/112)77%(86/112)

95% (106/112)97%(109/112)

100%(112/112)

100%(112/112)

100%(112/112)

100%(112/112)

100%(112/112)

Petruzella,2010

25% (at 20days)

50% (at 12days)

—75% (at 8days)

——————Plint, 2004

IQR=interquartile range; NR=not reported; S=symptomatic.*Outcome is duration of proportion of episodes of cough.†Outcome is proportion of children with Telephone Outpatient Score of zero.



RESEARCH



Table 6| Duration of common cold and non-specific respiratory illness in children in randomised controlled trials and observational studies(studies by Grüber, Taylor, and Wald studies not included in line graphs because outcome reported as a range, not mean)


Mean (SD) time tosymptom resolution

Mean(SD)

ConcurrenttreatmentAgeFollow-upSampleStudy

symptomdurationbeforestudyentry Week 2Day 10Day 6Day 3

Common cold


———29% (7/24)*—NRS†Mean 25 (SD15.7) months

48 hours24*Hutton, 1991

30† ——43%(13/30)†

17%39%80%98%Median 9.0 days (95%CI 8 to 9)

NRNRMedian 13 (IQR6-16) years


122Macknin, 1998


————1.8 (1.3) weeksNRNR0-7 yearsUntil symptomresolution

1314Grüber,2007‡ 1.5 (1.6) to 1.8 (2.4)

weeksInfants

2.1 (3.2) weeks3 years

1.3 (1.4) weeks7 years

————7.6 days< 48 hoursNR<1 yearUntil symptomresolution


—74%90%100—NRSNR10 days81Pappas,2008§

————Clear rhinorrhoea: 13.5(3.5) days

NRNR25 monthsUntil symptomresolution

40Steinweg,1983

Purulent rhinorrhoea:14.8 (4.2) days

Respiratory tract infection


43%(16/37)

————8.7 (5.1)days

NRMean 6.9 (SD2.0) years

2 weeks37Kristo, 2005

————Median 9 days (95% CI8 to 10)

≤24 hoursAB (7.3%)Mean 5.4 (SD)2.5 years

Until symptomresolution (≤21

days)

244Taylor, 2003


6%(10/169)

9%(15/171)

32%(57/179)

71%(131/184)

—3.3 (2.18)days

Intranasalsodium

cromoglicateor saline(100%)

Mean 5.1 (SD3.4) years

2 weeks169Butler,2002/03

—50%——10.22 days (95% CI9.14 to 11.29);

median 7.86 days

NRNRMean 24.55 (SD6.12) months

10 days333Carabin, 2000

5%10%50%75%Median 4.5 days<72 hoursAB (24%)Median 3.2years

2 weeks206Jacobs, 2000

60%81%98%100Middle meatalpathogen: present: 16.7

(7.0) days;

4 daysAB (6%); SMedian 9.8(IQR 6-13)years

3 weeks38Kristo, 2006

43%67%90%100Middle meatal pathogenabsent: 13.1 (6.0) days

42

23% (1-2wks)

—59% (4-7days)

91% (1-3days)

—NRAB (21%); S<5 yearsUntil symptomresolution

236Kusel, 2007¶

25%50%75%—Median 7 days (IQR5-11)

NRNRMean 8 yearsUntil symptomresolution (≤21

days)

223Mitra, 2011

——50%—Median 6 days≥ 2 daysNRInfant30 days1209Samet, 1993



RESEARCH



Table 6 (continued)


Mean (SD) time tosymptom resolution

Mean(SD)

symptomdurationbeforestudyentry

ConcurrenttreatmentAgeFollow-upSampleStudy Week 2Day 10Day 6Day 3

——48.3%Sneezing:66.1%

—NRNRMean 6 (SD2.7) years

4 days148Taylor,2010**

——50.9%Runny nose:41%

——39%Cough:37.7%

——44.1%Nasalcongestion:

59%

———8.28 (4) days≥ 24 hoursNRMean 9.31 (SD2.4) years

15 weeks116Turner Cobb,1998

————Median 4.7 days; (IQR2-6) days

NRAB (38%); S<1 yearUntil symptomresolution

217von Linstow,2008

————HC: 7.33 (5.54) days;GC: 8.32 (6.19) days;DC: 8.87 (6.72) days

≥ 24 hoursNR<1 yearUntil symptomresolution

244Wald, 1991

HC: 6.63 (5.13) days;GC: 7.98 (6.67) days;DC: 7.29 (6.54) days

1-2 years

HC: 6.79 (4.96) days;GC: 7.20 (5.84) days;DC: 7.82 (6.40) days

2-3 years

AB=antibiotics, HC=home care; GC=group care; DC=day care; NR=not reported; S=symptomatic.*Placebo.†No treatment.‡Outcomes are means (standard deviation).§Outcome is “proportion of children reporting any symptom by day of illness in 81 common colds.”¶Outcome is duration of proportion of episodes.**Outcomes are for children with viral RTI.



RESEARCH



Table 7| Proportion of children with common cold and non-specific respiratory illness on days 1-14

Proportion of children with symptoms remaining at follow-up:

Study 1413121110987654321

Common cold


————————————71%(17/24)*;57%

(17/30)†

—Hutton,1991

17%(21/124)

23%(29/124)

25%(31/124)

28%(34/124)

39%(48/124)

51%(63/124)

60%(74/124)

68%(84/124)

80%(99/124)

88%(109/124)

98%(122/124)

98%(122/124)

100%(124/124)

100%(124/124)

Macknin,1998


————74%(60/81)

80%(64/81)

82%(66/81)

88%(71/81)

90%(73/81)

97%(79/81)

97%(79/81)

100%(81/81)

100%(81/81)

100%(81/81)

Pappas,2008‡

Respiratory tract infection


43%(16/37)

—————————————Kristo,2005


6% (10/169)

6%(10/169)

7%(12/169)

8%(14/169)

9%(15/171)

11%(19/175)

16%(28/175)

26%(49/189)

32%(57/179)

39%(71/181)

56%(101/181)

71%(131/184)

91%(171/188)

96%(185/193)

Butler,2002/03

——————50%(167/333)

———————Carabin,2000

5%(11/220)

———10%(22/220)

——25%(55/220)

—50%(110/220)

—75%(165/220)

——Jacobs,2000

Kristo, 2006:

60%(23/38)

63%(24/38)

69%(26/38)

79%(30/38)

81%(31/38)

90%(34/38)

95%(36/38)

97%(37/38)

98%(37/38)

100%(38/38)

100%(38/38)

100%(38/38)

100%(38/38)

100%(38/38)

Middlemeatalpathogen

43%(18/42)

52%(22/42)

61%(25/42)

63%(26/42)

67%(28/42)

79%(33/42)

81%(34/42)

86%(36/42)

90%(38/42)

99%(41/42)

100%(42/42)

100%(42/42)

100%(42/42)

100%(42/42)

Nomiddlemeatalpathogen

23%(1-2wks)

(46/198)

——————59% (4-7days)

(117/198)

———91% (1-3days)

(180/198)

——Kusel,2007§

———25%(143/570)

———50%(285/570)

—75%(428/570)

————Mitra, 2011

————————50%(658/1315)

—————Samet,1993

————25%(65/261)

50%(131/261)

75%(196/261)

———————Taylor,2003

Taylor, 2010:

——————————48.3%(72/150)

——: 66.1%(99/150)

Sneezing

——————————50.9%(76/150)

41%(62/150)

47.5%(71/150)

: 38.7%(58/150)

Runnynose

——————————39%(59/150)

37.7%(57/150)

41%(62/150)

30.7%(46/150)

Cough:

——————————44.1%(66/150)

59%(89/150)

——Nasalcongestion

*Placebo.†No treatment‡Outcome presented is “proportion of children reporting any symptom by day of illness in 81 common colds.”§Outcome presented is duration of proportion of episodes.



RESEARCH



Table 8| Duration of common respiratory tract infections in children in current systematic review compared with current advice from UKNational Institute for Health and Care Excellence (NICE) and the US Centers for Disease Control and Prevention (CDC)

Average illness duration(days)Time (days, unless otherwise stated) for symptoms to

resolve

CDCNICE8In 90% of childrenIn 50% of children

——2*1Croup

2-3†47-83Earache/otitis media

7-14§72-7‡—Sore throat/tonsillitis

——16¶7Non-specific respiratory tractinfection

14††10-1115**10Common cold

10-14‡‡212510Acute cough

——21§§13Bronchiolitis

*No of days to 80% resolution.†Data from www.cdc.gov/getsmart/campaign-materials/info-sheets/child-otitismedia.pdf‡Data not sufficient to calculate pooled proportions or time to 50% or 90% resolution; figures shown are ranges from included studies for days to complete resolution.§Data from www.cdc.gov/getsmart/antibiotic-use/URI/sore-throat.html¶Data from pooled proportions did not extend beyond time to 80% resolution (14 days), data presented is estimate for time to 90% resolution from fig 9.**Data from pooled proportions did not extend beyond time to 60% resolution (10 days), figure shown is estimate for time to 90% resolution from fig 8.††Data from www.cdc.gov/getsmart/campaign-materials/info-sheets/child-rhin-vs-sinus.pdf‡‡Data from www.cdc.gov/getsmart/campaign-materials/info-sheets/child-cough-illness.pdf§§No of days estimated from fig 7. Time to 60% resolution was 16 days.



RESEARCH

http://www.cdc.gov/getsmart/campaign-materials/info-sheets/child-otitismedia.pdf

http://www.cdc.gov/getsmart/antibiotic-use/URI/sore-throat.html

http://www.cdc.gov/getsmart/campaign-materials/info-sheets/child-rhin-vs-sinus.pdf

http://www.cdc.gov/getsmart/campaign-materials/info-sheets/child-cough-illness.pdf



Figures

Fig 1 Flow of included randomised controlled trials of respiratory tract infections in children



RESEARCH



Fig 2 Flow of included observational studies of respiratory tract infections in children

Fig 3 Proportion of children with symptoms of earache. Symptom duration before study onset was less than four days infive studies (Burke,14Damoiseaux,15 Le Saux,17Neumark,19 Jedrychowski22) and was not reported in three studies (Tahtinen,20Greenberg,21 Smith23)



RESEARCH



Fig 4 Proportion of children with symptoms of sore throat. Symptom duration before study onset ranged between 24 hours(median) (Nelson26) to less than one week (Ruperto28) and was not reported in one study (Olympia27). *Children with groupA streptococcal infection; †children without group A streptococcal infection or other culture. (Pooling not possible becauseof lack of data)

Fig 5 Proportion of children with symptoms of cough. Symptom duration before study onset ranged between <48 hours(Jedrychowski22) to <14 days (Bernard30) and was not reported in one study (Kusel37)

Fig 6 Proportion of children with symptoms of croup. Mean symptom duration before study onset was reported as 0.8 (2.4)days (Bjornson31), 1.04 (1) days (Cruz32), and 21 (54) hours (Geelhoed33)



RESEARCH



Fig 7 Proportion of children with symptoms of bronchiolitis. Symptom duration before study was median four days in threestudies (Patel,34 Plint 2009,35 Plint 200439) and not reported in one study (Petruzella38)

Fig 8 Proportion of children with symptoms of common cold. Symptom duration before study onset was not reported in fivestudies (Hutton, Macknin, Gruber, Pappas, Steinweg), Jedrychowski et al reported duration <48 hours.22 *Placebo arm;†no treatment arm; ‡children with clear rhinorrhoea; §children with purulent rhinorrhoea

Fig 9 Proportion of children with non-specific respiratory symptoms. Symptom duration before study onset ranged between≤24 hours (Taylor 200343) to 8.7 (5.1) mean days (Kristo41) and was not reported in five studies (Carabin,45 Kusel,37 Mitra,7Taylor 2010,52 Von Linstow54). *Middle meatal pathogen present; †middle meatal pathogen absent



RESEARCH



Documents

Thompson, M., Vodicka, T. A., Blair, P. S., Buckley, D. I., Heneghan, … · 2017. 2. 15. · 10.1136/bmj.f7027 Link to publication record in Explore Bristol Research PDF-document