EVALUATING THE CHILD

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Paediatric Respiratory Reviews 13 (2012) 135–138

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Paediatric Respiratory Reviews

Mini-Symposium: Recurrent Lower Respiratory Tract Infections

Evaluating the child with recurrent lower respiratory tract infections Paul L.P. Brand *, M.F. Paulien Hoving, Eric P. de Groot Princess Amalia Children’s Clinic, Isala Klinieken, PO Box 10400, 8000 GK Zwolle, the Netherlands

EDUCATIONAL AIMS: AFTER READING THIS ARTICLE, THE READER WILL BE: Able to discuss the limitations in currently available evidence on underlying causes of recurrent pneumonia in children Able to explain why asthma is not a common underlying cause of recurrent pneumonia in children Able to discuss the limitations of the differential approach towards evaluating children with recurrent pneumonia in one lobe vs different or multiple lobes Able to follow a pragmatic step-wise approach in evaluating children with recurrent pneumonia

A R T I C L E I N F O

S U M M A R Y

Keywords: Pneumonia Recurrent pneumonia Asthma Chest radiography

We review the limited available evidence on underlying causes of recurrent pneumonia in children, supplemented by our own clinical experience. Diagnosing recurrent pneumonia in children is difďŹ cult. Diagnostic confusion is possible with recurrent upper respiratory tract infections and asthma. In our series of children with recurrent pneumonia, we never identiďŹ ed asthma as an underlying cause. Because the frequency or severity of recurrent pneumonia does not always justify additional invasive investigations, the diagnostic work-up may be incomplete in a number of cases. This may help to explain why an underlying cause for recurrent pneumonia cannot be found in approximately 30% of cases. Finally, the paradigm that recurrent pneumonia in the same lung lobe has a differential diagnosis different from those recurring in multiple lobes was not borne out in our case series. A stepwise and pragmatic approach to evaluating children with recurrent lower respiratory tract infections is recommended. Ă&#x; 2011 Elsevier Ltd. All rights reserved.

Given the high prevalence of recurrent lower respiratory tract infections in children it is striking how little attention this clinical problem has received in medical literature to date. Only a handful of studies have examined the underlying causes of recurrent pneumonia in children,1–4 and in-depth reviews of the clinical approach to the child with such recurrent lower respiratory tract infections are even rarer.5,6 In this article, we will discuss the approach to diagnosis and management of children presenting with recurrent lower respiratory tract infections from a clinician’s point of view. This will be largely based on our own clinical experience and that of colleagues we discussed it with, because there is so little published evidence available.

generally unwell child in whom physical examination shows either laboured breathing or abnormal ďŹ ndings on chest auscultation (which may include bronchial or diminished breath sounds, or crackles).7 Pneumonia is extremely common, in particular in developing countries, in which it remains a major cause of child mortality. Death from pneumonia in children is rare in industrialized countries, but its incidence is high, affecting as much as 4% of children < 2 yrs of age, 2% of 5-9 yr old children, and 1% older children each year.5 Recurrent pneumonia is usually deďŹ ned as two or more episodes of pneumonia in a year, or 3 or more ever, and is thought to occur in 7-9% of all children with pneumonia.5,6 As a result, recurrent pneumonia is one of the most common reasons for referral to paediatric chest physicians, and a common presenting symptom in general paediatric practice as well.

THE SCOPE OF THE PROBLEM

CURRENT WISDOM

Pneumonia is described by the World Health Organization as an acute illness characterized by cough, fever, and tachypnoea in a

Published case series suggest that in most if not all cases of recurrent pneumonia an underlying cause can be identiďŹ ed, and that the diagnostic work-up is dependent on whether the recurrent pneumonias repeatedly occur in the same lung lobe, or affect multiple lobes or different areas in different episodes.1–6 The data on

INTRODUCTION

* Corresponding author. Tel.: +31 38 4245050; fax: +31 38 4247660. E-mail address: p.l.p.brand@isala.nl (Paul L.P. Brand). 1526-0542/$ – see front matter Ă&#x; 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.prrv.2011.02.005

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underlying causes comes from retrospective case series only,1–4 and the differential diagnostic approach dichotimized by consistent or variable pneumonia localization appears to be based more on logical reasoning (it does seem logical to assume that pneumonias recurring in the same location may be more likely due to a local factor than recurrent infections in different lung lobes) than on published research evidence. Prospective studies on the underlying causes of recurrent pneumonia have never been performed, and the usefulness of the proposed diagnostic approach to recurrent pneumonia has never been evaluated. Curiously, not a single study to date has formally examined diagnostic strategies in evaluating recurrent pneumonia in children. One striking finding is that the majority of causes of recurrent pneumonia in children are already known before the first episode of pneumonia occurs.4,8 For example, psychomotor retardation with feeding problems and gastroesophageal reflux and congenital heart disease are common causes of recurrent pneumonia in children, but these are already known when the child presents with recurrent pneumonia. In such cases, there is no need to pursue another underlying cause for recurrent pneumonia. In addition, a number of commonly reported underlying causes do not have very strict defining criteria (such as asthma in young children, or immunoglobulin subclass deficiency syndromes). Similarly, many ‘‘underlying conditions’’ do not usually present with recurrent pneumonia (such as asthma, airway malacia or vascular malformations) and it is therefore not always clear whether the presence of two conditions (recurrent pneumonia and the suspected underlying condition) in a child truly represent a causal relationship, or merely co-incide by chance. This might be particularly true for common conditions such as asthma. These considerations justify a certain degree of scepticism towards the established wisdom of diagnosing and managing children with recurrent pneumonia. In our own series of children with recurrent pneumonia, for example, we were unable to identify an underlying cause in as much as 30% of cases.8 Similar experiences have been reported to us by colleagues from Western Europe, Australia, and the United Kingdom (Drs Suzanne Terheggen, Dominic Fitzgerald, and David Spencer, personal communication). THE BASIC QUESTIONS In evaluating a child referred to paediatric (pulmonology) practice, we always ask ourselves five basic questions (Box 1).

Box 1. Five basic questions to address in evaluating a child with recurrent respiratory infections 1. Does this child have recurrent respiratory tract infections? (or does s/he have recurrent respiratory symptoms caused by another respiratory condition?) 2. Are the recurrent respiratory tract infections based in upper or lower airways? 3. Is there any involvement of other organ systems? 4. Are the frequency and severity of recurrent lower respiratory tract infections sufficient to warrant additional investigations? 5. Where in the lung(s) does each episode take place, and how does this help to plan further investigations?

viral wheeze in young children)12 and lower respiratory tract infections. If parents and physicians report the symptoms and signs listed in the right-hand column of this table, diagnostic confusion may arise between asthma and lower respiratory tract infections. When such a child is referred, taking a careful history focusing on the symptoms and signs differentiating the two conditions (Table 1) is usually helpful to distinguish between the two; if not, one can ask the parent to bring back the child to hospital for examination during the next episode. An experienced paediatrician should be able to distinguish an exacerbation of asthma (or viral induced wheeze) from a lower respiratory tract infection by only taking a history and performing a physical examination. Unfortunately, such a clear distinction may be difficult to less experienced medical personnel. A chest radiograph may then be taken to rule out pneumonia; however, there is a high degree of interobserver variability in the interpretation of chest films.8,13 In our own series, paediatricians or junior staff involved in the case were more likely to interpret non-specific signs on chest radiographs as infiltrates or consolidation than an independent radiologist examining the chest film without having seen the patient.8 Such ‘‘overcall’’ in interpreting chest radiographs by clinicians has been reported previously.14 In addition, it has been shown that asthma is being overdiagnosed in children with recurrent nonspecific respiratory symptoms.15,16 Such diagnostic confusion may partly explain why ‘‘asthma’’ is a commonly reported ‘‘underlying condition’’ in children with recurrent pneumonia.

Does this child have recurrent respiratory tract infections? This question may seem trite but it is not; numerous children referred for recurrent respiratory tract infections do in fact have asthma (or vice versa).8,9 In a study in primary paediatric care in Canada, for example, as much as 64% of young children with recurrent wheeze had been treated with antibiotics.10 Repeated courses of antibiotics for such episodes can then lead to an incorrect diagnosis of ‘‘recurrent lower respiratory tract infections’’. Similarly, numerous children with persistent bacterial bronchitis (chronic wet cough, clearing after a course of antibiotics) are being diagnosed as asthma.11 Table 1 shows similarities and differences between asthma (including episodic

Are the recurrent respiratory tract infections based in upper or lower airways? Another simple question, which may be difficult to answer. Upper and lower respiratory tract infections may coincide, or infections of the upper respiratory tract may descend and proceed into lower respiratory tract infections.17 Moreover, an exact anatomic border between upper and lower respiratory tract infections has not been uniformally established. Symptoms and signs may overlap considerably between upper and lower respiratory tract infections; patients from both categories may appear unwell, with fever, difficulty in breathing, and tachyp-

Table 1 Similarities and differences between asthma (including episodic viral wheeze in young children) and lower respiratory tract infections Asthma

Lower respiratory tract infection

Symptoms shared between the two conditions

History

Wheeze as the key symptom

Physical exam

Wheeze as key finding on physical exam Nonspecific Hyperinflation; airway wall thickening

Cough, tachypnoea, and being generally unwell as key symptoms Toxic appearance, tachypnoea, reduced or bronchial breath sounds, inspiratory crackles Nonspecific Lobar or patchy infiltrates or consolidation

Dyspnoea as presenting symptom fever (if asthma is triggered by viral respiratory infection) Retractions, nasal flaring, poor air entry Mucus rattles on auscultation Nonspecific; not helpful Increased interstitial or vascular markings; perihilar linear opacities, atelectasis

Lab tests Chest radiograph

P.L.P. Brand et al. / Paediatric Respiratory Reviews 13 (2012) 135–138

noea.18 The younger the child, the more upper respiratory tract infections are accompanied by general symptoms such as fever and appearing unwell, and the more difďŹ cult it may be to distinguish between upper and lower respiratory tract infections.19 Although tachypnoea appears to be a sensitive marker of pneumonia in children,7 it is not very speciďŹ c –more than half of the children presenting with a respiratory tract infection and tachypnoea have a normal chest radiograph.18 Although experienced clinicians should be able to diagnose pneumonia reliably in a child, diagnostic confusion with uncomplicated upper respiratory tract infections is a distinct possibility, in particular in young children. Clearly distinguishing between the two may require repeated examinations when the child is unwell. Is there any involvement of other organ systems? Answering this question may help in distinguishing certain underlying conditions. For example, cystic ďŹ brosis rarely presents with only recurrent lower respiratory tract infections; there usually is evidence of involvement of the digestive tract (malabsorption, poor weight gain, voluminous stools, meconium ileus). Similarly, the presence of serious infections in other organs (e.g., skin) may suggest certain types of immunodeďŹ ciencies, and chronic therapy-resistant upper airway symptoms (sinusitis, purulent ear discharge) raises the possibility of primary ciliary dyskinesia. Thus, the evaluation of children with recurrent pneumonia should not be focused only on the respiratory tract, but should also include a careful history and assessment of other organ involvement. Children presenting with only recurrent pneumonia without any other organ involvement are unlikely to have cystic ďŹ brosis, and this may help in deciding the order in which additional testing is being performed. Are the frequency and severity of recurrent lower respiratory tract infections sufďŹ cient to warrant additional investigations? Review articles on recurrent pneumonia present a wide range of possible underlying conditions, and recommend investigations to try and identify the underlying cause.5,6 Some of the proposed investigations are invasive and may require general anaesthesia (bronchoscopy, magnetic resonance imaging) or require relatively high doses of ionizing radiation (high resolution computed tomography). Because such investigations may be associated with adverse effects, a relatively high threshold to perform them is justiďŹ ed. The usual paradigm is that any child with 2 or more episodes of pneumonia within a year, or 3 or more in a lifetime, justiďŹ es investigations some of which may be invasive or potentially harmful.5,6 We have experienced numerous cases, however, where deviations from this paradigm were considered justiďŹ ed (Box 2). These examples illustrate the perhaps obvious point that the decision to proceed to further (invasive) investigations should be made carefully in each individual case, taking medical issues, parental views and concerns, and potential adverse effects into account. Where in the lung(s) does each episode take place, and how does this help to plan further investigations? Although reviews on the subject consistently express the logical notion that the differential diagnosis of recurrent pneumonia in the same lung lobe is different from recurrent pneumonia affecting different or multiple lung lobes, to our knowledge this assumption has never been tested in a study. In our own series of 62 children with recurrent pneumonia (39 of which had radiological conďŹ rmation of each pneumonia episode), we found some exceptions to this rule (Table 2).8 For example, 80% of children with humoral

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Box 2. Examples of cases of recurrent pneumonia in which we refrained from further (invasive) investigations: An 8-yr old child who had 3 episodes of confirmed pneumonia, with disease-free intervals lasting many years, and who recovered quickly and completely after a course of antibiotics. Both the child and the parents were unwilling to proceed to invasive investigations; A 3-yr old child who had 2 episodes of pneumonia one month apart, and had been completely well beforehand (and remained well afterwards). In retrospect, we considered this a single prolonged episode, and refrained from further testing A 2-yr old child with recurrent pneumonia, in whom screening of humoral immunity showed no abnormalities, who remained free from further infections during a 6-month trial of antibiotic maintenance therapy. This was diagnosed as slow maturation of humoral immunity, and further investigations were renounced An 18-month old child experiencing two episodes of pneumonia 11 months apart, who did not show up for a follow-up appointment, and who has not been taken to her general practitioner for respiratory symptoms ever since A 2-yr old with recurrent upper respiratory tract infections and otitis media, who had two episodes of pneumonia but no other infections. This was diagnosed by his paediatrician as delayed maturation of humoral immunity, and a wait-andsee policy was adopted

immunodeďŹ ciency had pneumonias recurring in the same lung lobe, whilst 20% of patients with conďŹ rmed structural lung abnormalities (such as airway stenosis or pulmonary sequestration) had recurrent pneumonias in different lung lobes. Apparently, although the initial approach to additional investigations may be guided by the localizations of the recurrent pneumonias, clinicians should bear in mind that this paradigm is a rule of thumb rather than an evidence-based clinical guideline. ASTHMA AS UN UNDERLYING CAUSE? Although asthma has been reported as a common and important underlying cause of recurrent pneumonia in children,1–6 our clinical experience does not support this. First, almost all children with asthma in our unit can be well controlled on inhaled corticosteroids alone,20 have normal lung function,21 and have few if any lower respiratory tract infections as a complication. Furthermore, even in series of children with very difďŹ cult asthma referred to tertiary specialized care, lower respiratory tract infections are not reported as a complication.22,23 Thus, if asthma is an underlying cause of recurrent pneumonia in children, this seems to be conďŹ ned to very unusual and complicated cases of asthma. We believe that it is more likely that patients with recurrent lower respiratory symptoms including cough and fever (‘‘pneumonia’’) and other nonspeciďŹ c respiratory complaints (such Table 2 Distribution of pneumonia localization in 39 children with radiologically conďŹ rmed recurrent pneumonias from a general hospital in the Netherlands8 Underlying abnormality

Pneumonia recurring in same lung lobe

Different lung lobes involved

Total

Anatomical abnormalities Middle lobe syndrome Bronchiectasis Humoral immune deďŹ ciency Congenital heart defect Psychomotor retardation Total

4 2 2 8 2 5 23

1 0 1 2 1 11 16

5 2 3 10 3 16 39

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as chestiness, difďŹ culty in breathing, dyspnoea, or noisy breathing) may be liberally labelled as having ‘‘asthma’’. In our series of 62 children with recurrent pneumonia, 8 children (13%) had had a doctor’s diagnosis of ‘‘asthma’’, but the diagnosis of either asthma or recurrent pneumonia was rejected in all these cases after critical review. This is likely due to the diagnostic confusion between asthma and recurrent pneumonia discussed above. CONCLUSIONS The questions and issues discussed in this review clearly indicate that the diagnosis of (recurrent) lower respiratory tract infections and their underlying cause are fraught with difďŹ culties. Differentiating between upper and lower respiratory tract infections is difďŹ cult, and diagnostic confusion with asthma is also distinctly possible. Many children with recurrent pneumonia do not need a full diagnostic work-up, either because their penumonia episodes are not frequent or severe enough, or because the lower respiratory infections simply cease to recur. These issues and controversies are particularly common in young children with delayed maturation of the humoral immune system. Based on these considerations, it may be expected that a clear underlying cause of recurrent pneumonia can not always be identiďŹ ed. This was indeed the case in our series;8 similar experiences have been reported to us by numerous colleagues from around the world. The ďŹ nding from the literature that an underlying cause (including ‘‘asthma’’) is identiďŹ ed in almost all cases of recurrent pneumonia is likely due to a combination of retrospective case series design, coincidental co-occurrence of two common disorders, and diagnoses of uncertainty. In a considerable proportion of children with recurrent pneumonia, no clear underlying cause can be identiďŹ ed. We recommend a stepwise and pragmatic approach to investigating the underlying cause of recurrent pneumonia in children, commencing with screening for humoral immunodeďŹ ciency and cystic ďŹ brosis (because this can be easily done without any harm to the patient), followed by thoracic imaging (CT scan), before proceeding to invasive procedures under general anaesthesia. Obviously, this should be preceded by a careful history and physical examination, preferrably during an episode of suspected pneumonia.

PRACTICE POINTS Asthma is not a common underlying cause of recurrent pneumonia in children Evaluating recurrent pneumonia in children begins by taking a careful history, an examination while the child is unwell, and conďŹ rmation that the child is truly experiencing recurrent pneumonia Screening for immunodeďŹ ciency and cystic ďŹ brosis are useful ďŹ rst steps in evaluating recurrent pneumonia, irrespective of the localization of the pneumonias Even after careful evaluation, an underlying cause may not be found in many children with recurrent pneumonia

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