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04.03.19. (b) Evidence-Based Approach to the Child with Preschool Wheeze. ADCEP 2018

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Education & Practice Online First, published on June 30, 2017 as 10.1136/archdischild-2016-311254
Best practice
Fifteen-minute consultation: an
evidence-based approach to the
child with preschool wheeze
Renu Khetan,1 Matthew Hurley,1,2 Abraham Neduvamkunnil,1 Jayesh
Mahendra Bhatt1,3
1
Department of Paediatrics,
Nottingham Children's Hospital,
Nottingham, UK
2
Division of Child Health,
University of Nottingham,
Nottingham, UK
3
Nottingham Children’s
Hospital, National Paediatric
Ataxia Telangiectasia Clinic,
Nottingham, UK
Correspondence to
Dr Renu Khetan, Department
of Paediatrics, Nottingham
Children's Hospital, Nottingham,
NG 7, UK; ​Renu.​[email protected]​nuh.​
nhs.​uk
Received 17 July 2016
Revised 2 December 2016
Accepted 4 April 2017
To cite: Khetan R, Hurley M,
Neduvamkunnil A, et al.
Arch Dis Child Educ Pract
Ed Published Online
First: [please include Day
Month Year]. doi:10.1136/
archdischild-2016-311254
Abstract
Preschool wheeze is very common and
its prevalence is increasing. It consumes
considerable healthcare resources and has a
major impact on children and their families
due to significant morbidity associated with
acute episodes.History taking is the main
diagnostic instrument in the assessment of
preschool wheeze. Diagnosis and management
is complicated by a broad differential and
associations with many other diseases and
conditions that give rise to noisy breathing,
which could be misinterpreted as wheeze.
Several clinical phenotypes have been described
but they have limitations and do not clearly
inform therapeutic decisions. New insights in
aetiopathogenesis modify treatment options
and lay foundation for further research. An
understanding of the approach and available
evidence to assess and manage wheeze informs
best patient care and use of resources.Our
objective is to demonstrate a focused history,
examination and management options in a
preschool child with wheeze.
Definitions and classifications
Wheeze is a continuous high-pitched
sound (generated by bronchial wall vibrations that occurs when respiratory effort
exceeds that required to achieve maximal
airflow within the airway), with a musical
quality, emitting from the chest during
expiration. It can sometimes also be heard
during inspiration.1 2
Preschool wheeze is very common3 and
its prevalence is increasing.4 It consumes
high amounts of healthcare resources5
and has major impact on children and
their families due to significant morbidity
associated with acute episodes.
Several approaches have attempted to
classify preschool wheeze according to
its natural history—transient, persistent
and late-onset wheeze or other latent
classes.3–7 These classifications help
understanding the mechanisms and
natural history of preschool wheeze, but
do not help the clinician when faced with
a child in the clinic.
A European Task1 Force updated
recently8 proposed a pragmatic classification, based on symptoms which divides
preschool wheezing into episodic viral
wheeze (EVW, the most common clinical phenotype) and multitrigger wheeze
(MTW, a condition that resembles classical asthma) to support better therapeutic decisions. However, it has to be
acknowledged that there is intrapatient
variation and overlap in phenotype over
time, such that the phenotype can change
in up to 55% of the children, rendering
the distinction between EVW and MTW
unclear.
Risk factors of early wheeze
Risk factors for preschool wheeze are
summarised in figure 1. The heterogeneity
and complexity of preschool wheeze is
apparent with interactions with genetic,9
prenatal and perinatal exposure to environmental tobacco smoke and postnatal environmental factors such as viruses, bacteria,10
air pollution11 and allergic sensitisation.
Prematurity (<36 weeks) and intrauterine
growth restriction leads to abnormal lung
architecture (premodelling) and lung function.12 This in turn leads to prolonged
respiratory symptoms in infancy. These
factors activate the immune response and
allergic inflammatory cascade. Persistence
of triggers leads to airway remodelling and
persistence of wheeze.
Approach to preschool wheeze:
focussed history taking
Purpose
►► To confirm that the preschool child
has a wheezing disorder and that it is
bronchodilator responsive.
Khetan R, et al. Arch Dis Child Educ Pract Ed 2017;0:1–8. doi:10.1136/archdischild-2016-311254
1
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Best practice
Box 1
Figure 1 Risk factors for preschool wheeze.
►► To identify the pattern, severity of symptoms and possible
triggers.
►► To look for features suggestive of another diagnosis or
associated condition.
Why a careful history is so important
The diagnosis and management of wheeze in preschool
children is challenging because wheeze can be associated with many diseases and, unless the disorder has
been accurately identified, its management is as elusive
and imprecise.
Case history is summarised in box 1.
Presenting illness
General practitioner referral or emergency department attendance: history of episodes of wheeze (first
or recurrent) in a preschool child.
History of presenting illness
1. Confirm if it is really a wheeze or other upper or lower
airway noise.
►► Ask parents to demonstrate the noisy breathing or
you could demonstrate it to them to confirm or ask
them to bring a video in clinic.
►► Accurately identifying wheeze from the history
can be difficult since parents and healthcare
workers describe the term for a variety of
symptoms.13 Parent-reported wheeze should be
confirmed by a healthcare professional. There
may, however, be inter-observer differences14
among healthcare professionals.
►► Ask parents if they could feel vibrations or rattly
noise on the chest.
►► Ruttle, also known as ‘rattle’, is a low pitch noise
lacking any musical features. Parents may be able
to feel this noise as a vibration over the child’s
back. Ruttle may be related to excessive secretions
or to abnormal tone in the larger airway.15
►► Ask parents if they can localise the noisy breathing
(throat or upper chest)?
The differential diagnosis of upper airway noises is
summarised in box 2.
2
Case history
►► An 18-month old baby boy referred with history of
recurrent wheeze from the age of 9 months
►► Parents confirmed a whistling noise on breathing out
and had a video clip on their phone to confirm this.
His general practitioner also confirmed it on several
occasions. The wheeze was associated with shortness of
breath, which responded to salbutamol.
►► Following the first episode, he was admitted for
2 days and was treated with inhaled salbutamol. The
nasopharyngeal aspirate confirmed rhinovirus. He had
recurrent wheezy episodes almost every month; the
most recent hospital admission was for 10 days and
included paediatric intensive care.
►► On all these occasions he was given treatment
with prednisolone (in view of the very frequent and
severe nature of symptoms), oxygen and nebulised
bronchodilators. He remained symptom free in between
episodes, but whenever he had a cold, he seemed to get
very severe wheezing illness.
►► Systemic symptoms: There was no other significant
systemic history of note.
►► Allergies: He has frequent sneezing but no history of
runny nose without colds. He has moderate eczema.
There is no food allergy.
►► His parents do not smoke. His mother has a history of
asthma.
►► Birth history: He was born at full term with no neonatal
respiratory or bowel problems.
►► Examination: On previous examination, his weight and
height were on the 50th and 25th centiles, respectively.
There was no chest deformity; the chest was completely
clear on auscultation. There were no concerning features
on systemic examination.
►► Investigations: Baseline investigations were performed.
►► Treatment: He was commenced with inhaled fluticasone
via spacer. His symptoms improved, and there was a
decline in the need for attendance at the emergency
department and subsequent hospital admissions. He
was given a break from treatment over the summer and
was able to stay off inhaled fluticasone for the entire
summer.
2. Confirm whether or not it responds to salbutamol.
►► Wheeze indicates partial airway obstruction but
is not always because of bronchospasm. Airway
narrowing by secretions and airway wall oedema
will produce a wheeze, which does not respond to
bronchodilators. Airway malacia, fixed intrinsic or
extrinsic narrowing also leads to bronchodilatorunresponsive wheeze.
►► Reported noisy breathing that responds to
bronchodilator therapy is likely to be genuine
wheeze and to be caused, at least in part, by
constriction of airway smooth muscle.
3. Ask if there is history of shortness of breath with wheeze.
4. Ask if there is any associated history of cough.
Khetan R, et al. Arch Dis Child Educ Pract Ed 2017;0:1–8. doi:10.1136/archdischild-2016-311254
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Best practice
Box 2
Differential diagnosis
►► Upper airway disease—adenotonsillar hypertrophy,
rhinosinusitis, postnasal drip, subglottic stenosis,
laryngomalacia or vocal cord paresis.
►► Congenital or structural large airways disease—
complete cartilage rings, cysts, Webs, congenital or
acquired tracheomalacia.
►► Bronchial or tracheal compression—vascular rings and
sling, enlarged cardiac chamber, lymph nodes enlarged
by tuberculosis or lymphoma.
►► Endobronchial disease—foreign body or tumour.
►► Oesophageal or swallowing problems—reflux,
uncoordinated swallow, laryngeal cleft or
tracheoesophageal fistula.
►► Chronic bacterial infection—cystic fibrosis, primary
ciliary dyskinesia, persistent bacterial bronchitis or
immunodeficiency.
►► Miscellaneous—bronchopulmonary dysplasia or
pulmonary oedema.
►► Is it dry or wet or fruity or chesty?
►► Is it worse or noticeable at night?
5. Establish frequency, persistence and severity of episodes.
Ask history of onset, duration and progress of wheezy
episodes.
►► Is it the first episode or has there been recurrent
episodes?
►► If recurrent, how frequent and how were they
managed? Did they need hospital, paediatric
intensive care (PICU) or high dependency unit
admissions?
►► Is the wheeze episodic in nature and associated with
viral infections or is it multi-trigger in nature?
►► Has there been a change in the pattern of wheeze
over time?
6. Check if there was history of an initiating event.
►► Is there a history of bronchiolitis?
►► Young infants with episodic (viral) wheeze may
be difficult to distinguish from those with acute
bronchiolitis, not least because the definition used
for the clinical syndrome of bronchiolitis varies
in different parts of the world. In UK, Australia
and parts of Europe bronchiolitis is defined as
the presence of upper respiratory tract symptoms
with coryza and cough preceding the abrupt onset
of lower respiratory symptoms, with a variable
degree of respiratory distress, feeding difficulties
and hypoxia. On auscultation, there are
widespread crepitations. Wheeze may or may not
be present. In most of North America and parts of
Europe, the term bronchiolitis is generally applied
to all conditions involving expiratory wheeze and
evidence of a respiratory viral infection.16
►► Whether or not the initial episode is bronchiolitis
is less relevant, but recurrent wheezing is common
following initial infection with respiratory
syncytial virus (RSV) and other viruses.17 18
7. Check if there are any triggers.
►► Is there a virus identified in wheeze secondary to
upper respiratory infection?
►► Viral infections, particularly with RSV and human
rhinovirus, are the most common causes of
preschool wheezing.19
►► Does the child get symptoms with changes in
temperature, activity, feeding, laughter, crying,
dampness and thunderstorms?
►► These symptoms indicate underlying airway
hyper-responsiveness and would help categorise
as MTW. Viral infections are the most common
trigger for MTW but only viruses trigger
episodic viral wheeze and there are no interval
symptoms.
8. Check for interval symptoms.
►► Is there history of wheeze or noisy breathing or
cough when the child is completely well?
9. Exclude other cause of wheeze with a relevant systemic
history.
►► Is there history of vomiting or poor weight? May
raise concerns of gastro-oesophageal reflux disease.
►► Is there history of choking or chronic cough? May be
associated with foreign body aspiration.
►► Are there recurrent discharging ear infections,
persistent and/or early-onset (first few weeks of life)
rhinorrhoea? May raise concerns of primary ciliary
dyskinesia.
►► Is there history of chronic diarrhoea?
►► Is there history of serious, persistent, unusual and
recurrent infections? May raise concerns of primary
immunodeficiency.
►► Is there history of snoring, waking up in night or
sleep fragmentation? Consider obstructive sleep
apnoea.
10. Take a detailed allergy history.
►► Is there a personal history of atopy, that is, food
allergies, eczema or allergic rhinoconjunctivitis (hay
fever)?
►► Is there a family history of atopy, that is, allergic
rhinoconjunctivitis (hay fever), asthma or allergies?
►► Is there any history of smoking in household or
dampness in the house? Are there any pets?
Medical history
►► Current treatment
►► Response to previous treatments:Inhaled treatment—
which and changes made over period of time
►► Antibiotics: how many courses and how long
►► Oral steroids courses
Birth history
►► Neonatal respiratory problems—cough in the first few
weeks of life/poor weight gain (might point towards
primary ciliary dyskinesia or cystic fibrosis)
►► Neonatal bowel problems
The differential diagnosis of wheezing illness in
preschool children with suggested investigations is
summarised in table 1.
Khetan R, et al. Arch Dis Child Educ Pract Ed 2017;0:1–8. doi:10.1136/archdischild-2016-311254
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4
Cardiac abnormality
(particularly those causing left to
right shunt)
Postinfectious obliterative
bronchiolitis
Tracheomalacia/bronchomalacia
Primary ciliary dyskinesia
Cystic fibrosis
Immune deficiency
Viral infection
Gastro-oesophageal reflux with or
without aspiration
Inhaled foreign body
Wheeze with infections which are severe,
persistent, unusual or recurrent
Cough in the first weeks of life. Chronic diarrhoea due to
malabsorption leading to faltering growth (if pancreatic insufficient)
Chronically discharging ears and persistent and/or early-onset (first
few weeks of life) rhinorrhoea
History of trachea-oesophageal atresia and oesophageal atresia, harsh,
monophonic expiratory noise or noisy breathing
May be evidence of biventricular failure
(tachycardia, hepatomegaly and
Pulmonary crackles).
Previous adenovirus35 (most common antecedent) infection, prolonged
oxygen requirement, tachypnoea and crackles
Key clinical features
Likely viral or bacterial triggers
Clear history of viral trigger
Presence of interval symptoms as well as triggers other than viral
infections
Strong family history of atopy
Features of bronchiolitis—coryza, hyperinflation and basal crackles
Vomiting or poor weight gain. Symptoms such as coughing, mouth,
gagging when lying flat raises suspicion
Prior episode of coughing or choking (not always present).
Chronic cough
Wheeze in the first year of life
Episodic (viral) wheeze
Multitrigger wheeze
Inspiratory and expiratory images on high-resolution chest CT scan
Chest radiograph, ECG and echocardiogram
Most cases identified are now by newborn screening.
Sweat test
Chest radiograph to look for dextrocardia (present in 50%).
Ciliary studies
Flexible bronchoscopy
An inspiratory and expiratory chest radiograph when patient presents acutely can be difficult to
perform in preschool age group, a decubitus film may be helpful34; a history of a witnessed choking
episode combined with a sudden onset of respiratory symptoms remains the most important
indication for bronchoscopy.
To confirm and remove foreign body
Immunoglobulins, functional antibodies and T and B cells
Nasopharyngeal aspirate for immunofluoresence, PCR or viral culture
24 hours impedance and pH study. Contrast swallow, bronchoscopy for lipid laden macrophages
Nasopharyngeal aspirate
Thorough history and examination. Exclusion of other likely diagnoses
Thorough history and examination. Skin prick testing may be useful in
Multitrigger wheeze
Tests
Differential diagnosis of wheezing illness in preschool children with suggested investigations
Diagnosis
Table 1
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Best practice
Khetan R, et al. Arch Dis Child Educ Pract Ed 2017;0:1–8. doi:10.1136/archdischild-2016-311254
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Best practice
Box 3 Red flags—indications for referral to a
respiratory paediatrician
►►
►►
►►
►►
►►
►►
►►
►►
Diagnosis unclear or in doubt
Symptoms present from birth or perinatal lung problem
Excessive vomiting or posseting
Persistent wet or productive cough
Family history of unusual chest disease
Faltering growth
Nasal polyps
Unexpected clinical findings, focal signs, abnormal voice,
cry, dysphagia, finger clubbing
►► Inspiratory stridor
►► Failure to respond to treatment or frequent use of
steroids tablets
►► Parental anxiety or need for reassurance
Box 4 When to investigate?
►► Symptoms since birth
►► Airway obstruction is abnormally severe
►► Recovery is very slow or incomplete (resulting in
prolonged or repeated hospital admission in the first
few years of life)
►► Episodes continue in the absence of a viral infection
►► Parental anxiety
Physical examination
Aim
►► Identification of unusual or atypical features that would
suggest another underlying condition.
Examination and features suggestive of more complex
underlying disease:
►► Well/unwell
►► Growth: faltering growth
►► Abnormal voice/cry
►► ENT examination:
►► Inspiratory stridor
►► Rhinitis, nasal polys
►► Adenotonsillar hypertrophy
►► Skin examination: dry skin/eczema
►► Stigmata of chronic respiratory disease: (Any unexpected
clinical findings)
►► Abnormal shape of the chest
►► Finger clubbing
►► Focal signs
►► Systemic examination
Red flags—indications for referral to a respiratory
paediatrician is summarised in box 3.
Investigations
Most children do not require investigations.
Investigations are required if episodes are very
frequent and/or unusually severe (needing PICU
admission), resistant to therapy, accompanied by
unusual features or when there is doubt of the diagnosis.
These may include:
►► Chest X-ray to confirm that there is no evidence of
another diagnosis, for example, chronic lung disease,
when symptom free.
►► Cough swab if there is a history of wet cough.
►► Viral throat swab if current respiratory infection.
►► Skin prick test or specific IgE to allergens clearly identified
and acting as triggers for persistent wheeze to confirm
atopy.
‘When to investigate?’ is summarised in box 4.
Management
Non-pharmacological management
►► Smoking in parents of young children should be firmly
discouraged and smoking cessation interventions should
be offered. Tobacco smoke exposure increases the risk of
lower respiratory illness in children (by 70% in case of
maternal smoking).
►► Avoidance of inhaled allergens could be indicated in
MTW, although this could be expensive and challenging.
►► Multisession education of the families is desirable and
every opportunity should be taken to emphasise the
rationale for preventer and rescue treatment, spacer
technique and importance of compliance.
►► Personalised acute management plan and criteria to seek
urgent medical review should discussed and given in
writing to ‘particularly to those requiring critical care’.
Pharmacological treatment
Treatment of acute wheeze
The acute treatment of episodic wheeze is based on
extrapolation of those presenting with asthma, with
the exception that there is evidence that the use of oral
corticosteroids does not confer benefit20 21. However
there might be a subgroup of children with very severe
wheeze triggered by certain viruses and underlying
atopy where it might be justifiable to use oral corticosteroids during a very severe hospitalised episode.22
It is important that bronchodilator inhaler and
spacer technique are taught and reviewed and that
children have a written personalised management plan
for episodes of deterioration in terms of bronchodilator use and criteria for medical review.
Additional treatment options are continuing to be investigated with the recent finding that the acute use of azithromycin, commenced at presentation with respiratory tract
symptoms, significantly reduced the duration of symptoms.23 However, whether this should be widely adopted
or used in special groups (frequent or severe episodes)
is unclear. Another multicentre study showed a reduced
likelihood of severe illness in those children with recurrent severe wheezing who were treated with azithromycin
early in their illness.24 It is uncertain whether this effect is
immunologically, or microbiologically mediated.
Khetan R, et al. Arch Dis Child Educ Pract Ed 2017;0:1–8. doi:10.1136/archdischild-2016-311254
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Best practice
Figure 2 Approach to preschool wheeze.
Maintenance treatment
The evidence considering preventative/maintenance treatment is contradictory. For preventative strategies, a now
out-of-date Cochrane review found no evidence to support
low dose inhaled steroid and some evidence supporting
the use of high dose steroid, but only in those with mild
events.25 Two studies have since, however, demonstrated
no benefit of episodic use,26 27 except perhaps in a small
subgroup of children who were at high risk of going on
to establish asthma. In these children, inhaled steroids
appeared to reduce the severity of acute illnesses.
Evidence is accumulating to support the use of
modest doses of maintenance inhaled corticosteroid.28
6
For those infants experiencing severe or frequent
episodes, in particular for those requiring critical care,
it would seem reasonable to consider an 8-week trial
of low dose maintenance inhaled corticosteroids. It is
important that an open discussion be had with parents
clarifying the aims of treatment to reduce severity of
wheezing episodes, accepting that for periods when
the child is well that they will be receiving treatment
for which they will derive no benefit. It is equally
important that the success (or otherwise) of such an
approach be regularly reviewed.
The effects of montelukast, either given intermittently or as maintenance treatment, are disappointing
Khetan R, et al. Arch Dis Child Educ Pract Ed 2017;0:1–8. doi:10.1136/archdischild-2016-311254
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Best practice
Key messages
►► Epidemiological classification of wheeze does not help
in making therapeutic decisions.
►► Pragmatic clinical phenotypes (episodic viral wheeze
and multitrigger wheeze) can overlap and evolve.
►► Careful history is the most important tool in the
assessment of wheeze.
at the population level.29 However, there does appear
to be a small subgroup of children who derive benefit,
with an association with the 5/5 ALOX5 promoter genotype.30 Long-term use of corticosteroids used with the
aim modifying the natural history of preschool wheeze
appears not to be successful,26 31 32 neither is the use
of high- dose corticosteroid to reduce wheezing in the
months after RSV infection.33
Flow chart of ‘Approach to preschool wheeze’ is
summarised in figure 2.
Competing interests None declared.
Provenance and peer review Commissioned; externally peer reviewed.
© Article author(s) (or their employer(s) unless otherwise stated in the text of
the article) 2017. All rights reserved. No commercial use is permitted unless
otherwise expressly granted.
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Best practice
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Fifteen-minute consultation: an evidence-based
approach to the child with preschool wheeze
Renu Khetan, Matthew Hurley, Abraham Neduvamkunnil and Jayesh
Mahendra Bhatt
Arch Dis Child Educ Pract Ed published online June 30, 2017
Updated information and services can be found at:
http://ep.bmj.com/content/early/2017/06/29/archdischild-2016-311254
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