What factors influence prognosis in children with acute cough and respiratory tract infection in primary care?BMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e6212 (Published 20 September 2012) Cite this as: BMJ 2012;345:e6212
- Gail Hayward, academic clinical fellow1,
- Matthew Thompson, senior clinical scientist1,
- Alastair D Hay, general practitioner and reader2
- 1Department of Primary Care Health Sciences, Oxford University, Oxford OX1 2ET, UK
- 2Centre for Academic Primary Care, School of Social and Community Medicine, University of Bristol, Bristol, UK
- Correspondence to: G Hayward
- Accepted 30 July 2012
Cough is the commonest reason for preschool children to see a general practitioner,1 with primary care costs conservatively estimated at £31 million (€38.4 million; $50.3 million) a year for this age group alone.2 Acute cough has been shown to last longer than two weeks in a quarter of preschool children, and up to 12% of children could have deterioration in their condition necessitating reconsultation or complications, including pneumonia.3
Primary care clinicians attempt to balance the need to reduce unnecessary antibiotic prescriptions with the prevention of complications from respiratory tract infections. However, recent guidance from the National Institute for Health and Clinical Excellence4 acknowledged that a key driver for increased antibiotic prescriptions is clinical uncertainty in identifying those children most likely to develop complications or who need hospital care for respiratory infections—that is, those at risk of poorer prognosis. This uncertainty is evident from the wide variation in prescribing rates between individual clinicians, general practices, and countries.5 6 7
What is the evidence of uncertainty?
We researched this question using a literature review (box).
Search strategy for literature review
We designed a literature review to answer the following questions:
Which factors predict (future) poor prognosis in children presenting to primary care with acute cough and respiratory tract infection?
Which factors are associated (in the present) with diagnosis of pneumonia?
We performed a systematic literature search of Medline from inception to January 2012 using the following search strategy:
respiratory tract infection [MeSH Terms] OR respiratory infection* OR rti OR lrti OR urti OR lri OR uri OR chest infection* OR cough OR dyspnoea OR congestion OR (lung consolidation) OR (lobar pneumonia) OR (difficult breath*) OR respiration disorder*
child* OR schoolchild* OR preschool* OR pediatric* OR paediatric* OR parent OR parents OR parental OR mother OR father OR mom OR dad OR mum OR caregiver OR guardian OR carer OR infant OR infancy
primary care OR family practice OR general practice OR family medicine OR community healthcare OR primary healthcare OR ambulatory care
asthma OR malaria OR tuberculosis
We searched reference lists of identified articles.
We included primary studies and systematic reviews in paediatric populations in primary care settings. Where none were found, we included studies conducted in emergency departments. We excluded studies of children with asthma, chronic cough, cystic fibrosis, or tuberculosis, and studies in countries not classified as high income by the Organisation for Economic Co-operation and Development, where the disease spectrum is different and thus less relevant to primary care in high income countries.
Factors predicting poor prognosis in children with cough and respiratory tract infections presenting to primary care
We found no systematic reviews, and only two primary studies, which derived and then attempted to validate a clinical rule to predict complications of acute cough.8 Presence of fever and chest signs increased the probability of complications (defined as deterioration in condition due to illness, treatment, or hospital admission) from 10%, to a post-test probability of 40%. However, when this prediction rule was validated in a different population in the United Kingdom, these clinical features were not associated with complications.9
Factors associated with pneumonia
Clinical symptoms and signs
We did not find any systematic reviews, but did find one study that recruited children aged 16 years or less presenting to primary care as well as emergency departments and outpatient settings with an acute illness.10 This prospective study identified 16 cases of pneumonia (presence of infiltrate in chest radiograph) from a cohort of 3981 patients. The combination of dyspnoea and the clinician’s impression that “something was wrong” had a sufficient negative predictive value (100%) to rule out pneumonia but insufficiently high positive predictive value (5.3%) to rule it in. We also found a further 12 studies that were based in emergency departments, mainly with small sample sizes and higher prevalence of pneumonia than would be typically expected in primary care (table⇓).11 12 13 14 15 16 17 18 19 20 21 22 A history of fever, and clinical signs of tachypnoea, fever, abnormal respiratory examination findings, and hypoxaemia were associated with pneumonia, and were most useful when absent to help rule out pneumonia.
However, almost all of the studies used appearance of pneumonia in chest radiographs as the reference diagnostic test, and therefore included only those children needing a chest radiograph to investigate a clinical suspicion of pneumonia. This is problematic for two reasons: firstly, changes in radiographs do not necessarily correlate with clinical outcomes, and secondly, the populations do not represent the children presenting to general practice with respiratory tract infection, where chest radiographs are rarely used.
Six trials derived clinical prediction rules for pneumonia (table). However, very few of the rules have been externally validated by further prospective studies; in the only study where this was attempted, significantly lower sensitivity and negative predictive value were noted.11 Without (at least) external validation, where a study’s findings are checked in a different population, clinical prediction rules are not “fit for purpose” for routine clinical care, because their diagnostic value has often been found to be overly optimistic.
The difficulty in creating reliable prediction rules could be partly due to the nature of the clinical signs and symptoms involved; sensitive clinical features (such as fever) are not unique to pneumonia but occur in many acute infections. By contrast, highly specific signs, such as crackles, are only present in a subset of patients. Furthermore, inter-observer agreement about presence or absence of signs is poor.23 Respiratory rate is frequently not measured by general practitioners,24 could be inaccurate when measured over short periods, and varies widely under both normal physiological conditions and in the presence of fever.25 Moreover, the lower prevalence of pneumonia in primary care, compared with the emergency department, is likely to enhance the diagnostic value of the absence of these symptoms and signs in ruling out pneumonia, albeit at the cost of also reducing their positive predictive value.
Ultimately, many clinicians will base their judgment of illness severity on the general appearance of the child. This approach is supported by systematic reviews of clinical predictors of serious infection in children in whom, in primary care settings, the clinician’s assessment of general appearance is the most useful predictor.26 27
C reactive protein
We found no studies assessing the extent to which C reactive protein can predict prognosis in children with acute cough and respiratory infection. In terms of diagnosis, children with raised concentrations of inflammatory markers would be expected to have a greater risk of bacterial pneumonia. A systematic review28 including eight studies (1230 patients) suggested that children with bacterial pneumonia were more likely to have concentrations of C reactive protein exceeding 35-60 mg/L (1 mg/L=9.52 nmol/L) than those with non-bacterial infections (odds ratio 2.58, 95% confidence interval 1.2 to 5.55). However, only one of these studies recruited patients from primary care settings,29 and this study found no association between C reactive protein and bacterial pneumonia.
There is increasing recognition of the mixed viral and bacterial aetiology of a significant proportion of paediatric patients with pneumonia, and the potential interactions between viral and bacterial pathogens that worsen clinical illness.29 30 Therefore, distinguishing bacterial from viral aetiology might be less important for both diagnosis and prognosis of pneumonia.
If levels of C reactive protein did predict children at higher risk of complications in primary care, it would be important to determine their added value over other diagnostic tools (for example, pulse oximetry), as well as acceptability to parents, feasibility and cost in primary care settings, and the potential for over-medicalising largely self-limiting illnesses.
Pulse oximeters are now widely available in general practice, although devices suitable for very young children are more costly. We found no studies that assessed whether decreased oxygen saturations predict poorer prognosis in children with cough and respiratory infection. We found one systematic review31 that included three studies from high income countries and assessed the prevalence of hypoxaemia in children under age 5 years presenting with acute lower respiratory infection to either outpatient or emergency departments. The prevalence of hypoxaemia (in children diagnosed with bronchiolitis and pneumonia) was between 6% and 19%. More recently, oxygen saturation has been assessed in addition to clinical symptoms and signs in three prospective cohort studies.19 20 22 The studies showed positive predictive values of 10-14% and negative predictive values of 96-97% for saturations less than 92% (reported in two studies), and positive likelihood ratios for pneumonia ranging from 2.40 to 3.06 for saturations less than 93%. However, a case-control study failed to show a significant association between oxygen saturation and chest radiograph changes consistent with pneumonia in 803 children under 2 years old.32
Is ongoing research likely to provide relevant evidence?
We searched the UK Clinical Research Network Study Portfolio (http://public.ukcrn.org.uk/search) and the international clinical trials registry platform on 22 June 2012 for prognostic studies of respiratory tract infection in children and identified two relevant studies. The TARGET study (www.targetstudy.org.uk/) is a prospective cohort study that will assess the prognostic use of symptoms, signs, bacteriology, and virology to predict poor prognosis in children aged up to 16 years presenting to primary care with acute cough. The Happy Audit (www.happyaudit.org) aims to study the incidence of respiratory tract infections among patients in European general practice and carry out research based on audit registration to explore the existing use of diagnostic tools in patients with respiratory tract infections.
What should we do in the light of the uncertainty?
We found little evidence to support general practitioners in identifying children at greatest risk of complications when presenting to primary care with cough and respiratory tract infection. We therefore focused on the evidence available to assist clinicians to form a diagnosis of pneumonia. The limited evidence from primary care settings supports the “rule out” value of two clinical features: the absence of a clinician’s subjective impression that the child is unwell, and the absence of difficult or laboured breathing. Evidence from emergency department settings suggests that the absence of individual or combined symptoms and signs, including raised respiratory rate, chest signs, fever (or history of fever), and general unwell appearance can rule out the presence of pneumonia, and that their presence should increase clinical suspicion of pneumonia. In view of the diagnostic value of these signs in the emergency department setting, general practitioners should consider using these clinical features when assessing children attending primary care for whom they have some concerns, or are working in settings (for example, out of hours) where continuity and prior knowledge of the patient and their family are more limited. In practice, the decision to prescribe antibiotics or arrange admission for a child with acute cough and respiratory infection will be guided not only by these clinical features but also by parental concern,26 previous medical problems, and the ability to use careful safety-netting.
Recommendations for further research
Population: Children attending primary care with acute cough
Intervention and comparator: Presence versus absence of abnormal symptoms and signs
Outcome: Significant illness, deterioration or hospital admission for lower respiratory tract infection (for example, bronchiolitis, pneumonia, or empyema) needing oxygen, intravenous fluids, or antibiotics in a defined period after recruitment
Population: Children attending primary care with acute cough
Intervention and comparator: Presence versus absence of co-isolation of bacteria and viruses from upper respiratory tract throat swabs available as rapid or point of care tests
Outcome: Prolonged and more severe symptoms
Cite this as: BMJ 2012;345:e6212
This is one of a series of occasional articles that highlight areas of practice where management lacks convincing supporting evidence. The series adviser is David Tovey, editor in chief, the Cochrane Library. To suggest a topic for this series, please email us at.
Contributors: All authors contributed to data interpretation, drafting, revising, and final approval of the manuscript before publication. MT is guarantor for the project.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; ADH is chief investigator and principal investigator of the Bristol centre of the TARGET study; MT is the principal investigator of the Oxford centre of the TARGET study, funded by a grant from the Department of Health’s National Institute for Health Research Programme Grants for Applied Research; no other relationships or activities that could appear to have influenced the submitted work.
Provenance and peer review: Not commissioned; externally peer reviewed.