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Abstract
Objective Data on the aetiology of persistent cough at the transitional stage from subacute to chronic cough (>4 weeks duration) are scarce. We aimed to (1) identify the prevalence of chronic cough following acute respiratory illness (ARI) and (2) determine the diagnostic outcomes of children with chronic cough.
Design Prospective cohort study.
Setting A paediatric emergency department (ED) in Brisbane, Australia.
Patients Children aged <15 years presenting with an ARI with cough.
Interventions Children were followed weekly for 28 days;those with a persistent cough at day 28 were reviewed by a paediatric pulmonologist.
Main outcome measures Cough persistence at day 28 and pulmonologist diagnosis.
Results 2586 children were screened and 776 (30%) were ineligible; 839 children (median age=2.3 years, range=0.5 months to 14.7 years, 60% male) were enrolled over 2 years. Most children (n=627, 74.8%) had cough duration of <7 days at enrolment. At day 28, 171/839 (20.4%, 95% CI 17.7 to 23.1) children had persistent cough irrespective of cough duration at enrolment. The cough was wet in 59/171 (34.5%), dry in 45/171 (26.4%) and variable in 28/171 (16.1%). Of these 117 children , 117 (68.4%) were reviewed by a paediatric pulmonologist. A new and serious chronic lung disease was diagnosed in 36/117 (30.8%) children; 55/117 (47.0%) were diagnosed with protracted bacterial bronchitis.
Conclusions When chronic cough develops post-ARI, clinical review is warranted, particularly if parents report a history of prolonged or recurrent cough. Parents of children presenting acutely to ED with cough should be counselled about the development of chronic cough, as an underlying respiratory condition is not uncommon.
- chronic cough
- acute respiratory illness
- clinical outcomes
- children
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What is already known on this topic?
Cough is one of the most common reasons for medical encounters in children internationally.
Cough places a significant burden on families and the healthcare sector.
Chronic cough is a key symptom of underlying chronic lung disease.
What this study adds?
Persistent cough in children 4 weeks following the presentation to an emergency department with a respiratory illness with cough as a symptom is not uncommon.
Underlying respiratory pathology is not uncommon in these children.
Discharge planning should include counselling parents to return for appropriate physician review and consideration of underlying lung disease if their child continues to cough for 4 weeks.
Introduction
Cough in children is symptomatic of a broad range of respiratory illnesses (RI), ranging from mild and transient upper respiratory tract infections to serious chronic disease.1 Acute respiratory illness (ARI), a leading cause of cough in children, is one of the most common reasons for medical encounters both in Australia2 and internationally.3 4 Although acute cough typically resolves within 1–3 weeks following ARI 5 6 in some children, it may progress to chronic cough (CC) (>4 weeks duration).7 8 CC is often the sole presenting symptom of an underlying chronic RI,9 and in some conditions, if left untreated, it may result in irreversible lung damage and chronic lung disease.9 Furthermore, CC impairs quality of life (QoL) and stresses parents, both of which normalise when the cough resolves.10 11
Despite the importance of CC as an indicator of chronic lung disease in children, data on its prevalence following ARI are scarce. Current data suggest that approximately 10% of children will cough for 20–25 days following ARI;5 6 12 13 however, most data are from children <4 years attending primary care. Furthermore, there are no published data on the diagnostic outcomes of the children who continue to cough. These limitations restrict generalisability to older children and those attending tertiary care.
A lack of robust data for the outcomes of CC post-ARI in children limits the ability of clinicians to implement early preventative and management measures. Such data would assist in counselling parents and increase the likelihood of timely medical representation. On the basis of all published paediatric CC guidelines (except for the British guidelines),14 15 we defined CC as duration of cough >4 weeks. We, thus, aimed to (1) identify the prevalence of CC and (2) determine the diagnostic outcomes of children with CC at day 28 following ED presentation. Predictors of CC following ED presentation (including upper airway microbiota) have previously been described.16 17
Materials and methods
Setting
The Royal Children’s Hospital (RCH), Brisbane (now the Lady Cilento Children’s Hospital) is the only tertiary paediatric public hospital in the state of Queensland, Australia. At the time of the study, the RCH ED serviced an average of 29 000 children per year.
Study design
The study was a prospective cohort study of children aged <15 years attending the ED for an RI that included parent-reported cough as a symptom. The full study protocol has been published.18 Children were followed for 28 days to ascertain cough status following enrolment. Children with CC at day 28 were reviewed by a paediatric pulmonologist. The microbiological data collected during the study and their relationship to clinical outcomes have been previously published.16 17
Study subjects
Children were recruited by research nurses who obtained written consent. Nurse cover for this study approximated 60 hours/week; hence, not all children presenting to the ED were screened. Children were eligible for inclusion if (1) they were aged <15 years, (2) the parent/guardian reported cough as a symptom and (3) they were present in the ED between 06:00 and 21:00 hours from Monday to Saturday. Children were excluded if they (1) had a known diagnosis of chronic lung disease (excluding asthma) and/or immunosuppression, (2) had used immune-modulating drugs (other than oral or inhaled steroids) in the 30 days prior to presentation, (3) were interstate or overseas residents and/or (4) had insufficient knowledge of English to understand study requirements.
Data collection
At enrolment, a comprehensive questionnaire18 was completed using parental interview, consulting with the treating team and medical record review. Parents completed a cough diary (verbal category descriptive (VCD)19 score) for 28 days, supplemented by weekly contacts by study staff. Three contact attempts were made at each time point. Diary items included cough persistence and frequency, medication use and whether they sought further medical advice for the cough. A bilateral anterior nasal swab was collected and tested as previously reported.16 At day 28, if the child had not stopped coughing for a period of >3 consecutive days (criteria previously used to define clinical response in chronic cough studies20 21) during the follow-up period, he/she was reviewed by a paediatric pulmonologist within 2 weeks.
At review, a comprehensive assessment was completed in accordance with cough management guidelines.14 15 20 This included another bilateral nasal swab. Attribution of a final diagnosis had to be contemporaneously related to treatment and/or objective tests confirming the diagnosis. Additional tests (eg, chest CT scan and bronchoscopy) were undertaken as deemed necessary by the pulmonologist in accordance with guidelines.14 15 20 Children were offered two appointments with the pulmonologist as a part of the study protocol with further follow-up if deemed necessary by the pulmonologist.
Loss to follow-up (LTFU) during the 28-day period was defined as two consecutive weeks in which contact attempts were unsuccessful. If it was identified that the child had stopped coughing prior to LTFU, CC at day 28 was classified as ‘no’.
Analyses and sample size
Data were tabulated and expressed as proportions and/or means. When continuous data were not normally distributed, medians and interquartile ranges were calculated. The primary analysis was the proportion of children with CC at day 28(+3) post-ED. Univariate analyses were performed to evaluate the association between child characteristics at baseline and the persistence of cough at day 28; ORs and the corresponding 95% CIs were calculated. Given multivariable modelling was previously undertaken to determine predictors of persistent cough that included microbiological data,17modelling was not undertaken in this analysis and corrections for multiple comparisons were not performed. On the basis of preliminary data, we predicted a prevalence of chronic cough of 20% per year. To detect this prevalence (α=0.05% and 90% power), an annual minimum of 246 children enrolled and with complete data at day 28 were required.
Results
Between December 2011 and August 2014 (142 weeks), 2586 children were screened and 876 were enrolled (figure 1). The numbers of children not screened were not collected. The median age was 2.3 years (range 0.5 months to 14.7 years) and 60% were male. Reasons for non-enrolment included ineligibility (n=776, 30%), refusal (n=653, 25.3%) and other reasons (n=281, 10.9%) (eg, inability to approach in ED given clinical priorities). Children were less likely to be enrolled if they were of a less urgent triage category (p=0.001) or presented during spring (p<0.001).
Screening, enrolment and follow-up of children aged <15 years presenting with cough as a symptom to a tertiary paediatric emergency department. *Other reasons: child too unwell to approach or given other clinical priorities or rapid assessment and discharge. LTFU, lost to follow-up.
Thirty-seven (4.2%) children were subsequently excluded from this analysis (34 were second enrolments and three were protocol violations) leaving 839 children for analysis. Overall attrition by day 28 was 33.5% (n=281/839); 255 children were LTFU and 43 parents withdrew consent at various time points. However, it was known that the cough had stopped prior to withdrawal in 124 (44.1%) of these children and they were classified as ‘negative’ for CC at day 28. Predictors of LTFU have been previously reported17 and included having a household income of <AUD$26 000 (adjusted OR (aOR) 3.53 95% CI 1.37 to 9.10), being enrolled in autumn (aOR 1.77, 95% CI 1.06 to 2.96) or spring (aOR 2.70, 95% CI 1.46 to 4.99), and having a cough duration of 14–21 days at the time of enrolment (aOR 2.84, 95% CI 1.33 to 6.07).
At the time of enrolment, 627 (74.8%) children had a cough duration of <7 days and 529 (63%) had sought prior healthcare for the illness. Sixty-three children (7.5%) had being coughing for ≥28 days and 50 (79%) of these children had sought healthcare prior to ED presentation for their cough. Of these 50 children, 28 (44%) had a chest X-ray performed in ED. Two hundred and forty-five of the 839 children (29.2%) had received oral or inhaled steroids in the 7 days prior to presentation.
Cough persistence post-ED (by duration at the time of presentation) is presented in table 1. Cough persistence at days 7, 14, 21 and 28 was 64.7% (95% CI 61.5 to 67.9), 39.0% (95% CI 35.7 to 42.3), 25.9% (95% CI 22.9 to 28.8) and 20.3% (95% CI 17.7 to 23.1), respectively (table 1). Sixty-four percent (n=110) of children with CC post-ED had acute cough of <7 days duration at the time of presentation. Forty-one percent of those with cough duration at the time of presentation ≥28 days (26/63) were still coughing 4 weeks later. This includes six children treated with antibiotics post-ED.
C ough persistence, in days, in children following presentation to ED with cough as symptom, by duration of cough at the time of presentation
Of those with CC at day 28 (n=171), 59 (34.5%) had wet cough, 45 (26.4%) had dry cough, 28 (16.1%) reported variable cough and cough type was unknown in 23% (n=39) (data not completed on diary cards or was unknown/not sure at weekly contact). The baseline characteristics of children, at the time of presentation by cough status at day 28 are presented in the online supplementary tables 1-3.
Supplementary file 1
Paediatric pulmonologist diagnoses* 4–6 weeks after ED presentation, by number of days cough was present on enrolment (n=117 children with >28 days cough, post-ED presentation for illness with cough as a symptom)
Diagnostic outcomes of children with chronic cough
One hundred and seventeen (68.4%) of the 171 children with CC at day 28 were clinically reviewed. Reviews were not undertaken on the remainder as parents either declined as the cough had resolved by the time the appointment was due (n=13) or they were LTFU (n=23) or other reasons (n=18, eg, moved from study area, diary card returned too late to meet study criteria, parent did not want to attend for other reasons). Two of the children not clinically reviewed were PCR positive for pertussis in nasal swabs collected at baseline and one was positive for Mycoplasma pneumoniae.
Of the 117 children, 84 (71.8%) had a specific respiratory disorder and the remaining had diagnoses of non-specific cough, postviral cough or recurrent upper respiratory tract infection. Importantly, a new chronic underlying lung disease (diagnosis of asthma by reversibility on spiromtery and/or response to medications, aspiration by videofluroscopic swallow study showing laryngeal penetration,22 bronchiectasis by chest CT, obstructive sleep apnoea by sleep polysomnography, tracheo-broncho-malacia by flexible bronchoscopy) was found in 36 children (table 2). The proportion of those found with a chronic lung disease was similar in the group with <7 days of cough to that with >28 days at the point of ED presentation (table 2). Given the difference in the definition of CC between the British and rest of the world guidelines, we presented diagnoses by the duration of cough at ED presentation in table 2.
Overall, protracted bacterial bronchitis (PBB, diagnosed using our clinical criteria23) was the most common diagnosis made at pulmonologist review (n=55/117, 47.0%) and 37/117 (31.6%) children had more than one diagnosis. Only one child reviewed was diagnosed with pertussis (confirmed PCR-positive on nasal swab at enrolment and at the time of specialist review) and none were positive for M. pneumoniae. Recurrent upper respiratory infections were diagnosed in 14/117 (12.0%) children, pneumonia in four and aspiration disorders in four (three were previously undiagnosed). Forty of the 117 children (34.2%) had one or more chronic RI: asthma (17/117, 14.5%, 9 of which were new diagnoses), tracheobronchomalacia (13/117, 11.1%, 12 of which were new diagnoses), obstructive sleep apnoea (4/117, 3.4%), aspiration disorder (4/117, 3.4%) and bronchiectasis (4/117, 3.4%).
Discussion
This is the first study to systematically evaluate the development of CC and its outcomes in children who were presented to an ED for illnesses with cough as a symptom. Twenty percent of children had parent-reported CC 28 days following ED presentation and, of these, one-third reported wet cough, a key symptom of persistent lower airway bacterial infection when chronic cough is present.9 Notably, of the 117 children with CC who were reviewed by a pulmonologist, a third were identified to have a previously undiagnosed underlying chronic respiratory illness (asthma, aspiration, bronchiectasis, obstructive sleep apnoea or tracheobronchomalacia) and 47% had PBB.
In our cohort, the prevalence of CC at day 28 is higher than that reported elsewhere (approximately 10%).5 6 12 24 This potentially reflects the different setting in which our study was conducted (in ED vs primary care), particularly given that 63% of parents reported they had consulted other healthcare providers for their child’s cough prior to ED presentation. Acuity, parental concern and distress over their child’s cough and the severity and stage of the child’s illness are likely to have influenced the decision to present to an ED, the decision to enrol in the study and to complete the full period of follow-up. Indeed, we11 25 and others26 have shown that although the presence of cough is minimised by healthcare professionals, it is distressing to parents.
Data on the aetiology of CC, particularly at the time of transition from subacute cough to chronic cough, are scarce despite being commonly attributed to postinfectious cough.27 None of the prior studies that reported cough duration post-ARI evaluated the outcomes of children who had CC. In one of the better cohort studies involving 169 861person-weeks of data, Leder et al 28 found that while the number of children still coughing post-ARI reduced from the peak of 3–4 to 20 days, there was another peak at the 3-week to 4-week mark. Given the absence of any published data on the clinical characteristics of this group of children with CC, we systematically clinically evaluated these children using an evidence-based approach that included assessment for pertussis.20 This approach included using a priori definitions of diagnosis and cessation of cough, contemporaneously related to the treatment to reduce the many possible biases29 when ascribing aetiology in evaluating paediatric CC.
Of those with CC at day 28 who were reviewed by a pulmonologist, we identified 55 (47.0%) children with PBB and 44 (37.6%) children with chronic RI, most of which were new diagnoses and some of which are serious (eg, bronchiectasis). Irrespective of the diagnosis, early identification to avoid long-term adverse sequelae and undue child and family burden is important when cough is persistent.10 11 Importantly, we found that the proportion of those with a new chronic lung disease was similar in the group with <7 days of cough to that with >28 days at the point of ED presentation (table 2). This supports our assertion that children with cough >4 weeks should be clinically assessed as a child with CC rather than at the 8-week time point.
We found that PBB was the predominant cause of CC post-ARI. It is beyond the scope of this article to discuss all the causes of CC in children but our study’s findings are similar to that found in an Australian study involving 346 children newly referred for a CC.10 Our study is not entirely comparable as the duration of cough at enrolment in that cohort was substantially longer (median of 16–18 weeks).10 Our data are in contrast to a recent UK study30 that identified pertussis in 20% of children aged 5–15 years with cough duration of >2 weeks (mean 5 weeks); the authors did not specify other diagnoses. In our study, only one child was diagnosed with pertussis at review.
The limitations of our study include the large proportion of children who were screened but not enrolled and/or the likely high number of children presenting to ED outside of research nurse hours who were not screened. This places constraints on the generalisability of the study. Approximately, 21% of participants enrolled were LTFU and we could not confirm cough persistence. However, we considered it reasonable to assume that those who did not continue were less likely to have CC, particularly given the known burden CC places on families10 11 and the opportunity for a child to be reviewed by a pulmonologist. Previous analyses suggested that LTFU was associated with a milder illness.17 Finally, we included children with cough of >2 weeks at the time of ED presentation and this may have resulted in an overestimation of CC following ARI. However, these children comprised 16% of the analysable cohort and 36% of these children still had CC at day 28. Inclusion of these children also provided the opportunity to examine cough management in ED and the duration of illness following discharge. Finally, our study was based in a tertiary centre and cannot be readily extrapolated to primary care.
Despite the limitations, our study’s findings were based on children systematically evaluated when they had CC post-ED. On the basis of our findings of a high proportion with a new chronic illness, our study suggests that when CC is present post-ARI, these children warrant further attention. Discharge planning should include counselling parents to represent for appropriate physician review and consideration of underlying lung disease if their child continues to cough.
Acknowledgments
The authors gratefully acknowledge the following people and departments for their assistance in this study: the RCH Emergency Department and Paediatric Emergency Research Unit; the Respiratory Physicians (particularly Prof Alan Isles, A/Prof Brent Masters, Dr Danielle Wurzel and Dr Nitin Kapur), Respiratory Scientists and administration staff at the Queensland Children’s Respiratory Centre; the Medical Records staff at the Royal Children’s Hospital and members of the Cough Asthma and Airways Research Group and Respiratory infection Outreach Research Teams, particularly Ben Arnold, Daniel Arnold, Simon Foster, Kate Shackleton and Clementine Shevill.
References
Footnotes
Contributors KO’G conceived the study idea, formulated the research questions, wrote the study protocol and standard operating procedures and was responsible for the overall implementation of the study. She wrote the final draft of the manuscript. BJD contributed to the study protocol, participant recruitment and follow-up, and participated in writing of the the first draft of the manuscript. ABC contributed to the study protocol, study implementation and made a major contribution to the manuscript. NP contributed to the design of the study protocol and study implementation in the Emergency Department and reviewed and approved the final manuscript. JA contributed to design of the study protocol and study implementation in the Emergency Department and reviewed and approved the final manuscript. JMM contributed to design of the study protocol and study implementation in the Queensland Children’s Respiratory Centre and reviewed and approved the final manuscript. VG was responsible for the majority of the child reviews and follow-ups in the Queensland Children’s Respiratory Centre and reviewed and approved the final manuscript.
Funding This study was funded by Queensland Children’s Medical Research Institute/Queensland Children’s Health Foundation Program Grant. BJD was supported by a NHMRC Post-Graduate Scholarship (1075467). K-AO’G is supported by a NHMRC Career Development Fellowship (1045157) and Queensland Government Smart Futures Fellowship. VG is supported by a NHMRC Post-Graduate Scholarship (1075119). ABC is supported by NHMRC Practitioner Fellowship 1058213.
Competing interests None declared.
Ethics approval The study protocol was approved by the ethics committees of the Queensland Children’s Health Services (HREC/11/QRCH/83), The University of Queensland (2012000700) and the Queensland University of Technology (1400000057).
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Data from this study will be made available on request with the appropriate human research ethics committee clearances.