C

O
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H
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-D
O
N
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 SECTION 2. CHILDREN 5 YEARS AND
YOUNGER

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Chapter 6.

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Diagnosis and
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management of asthma
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in children
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5 years and younger

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 6.1. DIAGNOSIS
KEY POINTS

• Recurrent wheezing occurs in a large proportion of children 5 years and younger, typically with viral upper
respiratory tract infections. It is difficult to discern when this is the initial presentation of asthma.
• Previous classifications of wheezing phenotypes (episodic wheeze and multiple-trigger wheeze; or transient
wheeze, persistent wheeze and late-onset wheeze) do not appear to identify stable phenotypes, and their clinical
usefulness is uncertain. However, emerging research suggest that more clinically relevant phenotypes will be
described and phenotype-directed therapy possible.
• A diagnosis of asthma in young children with a history of wheezing is more likely if they have:
o Wheezing or coughing that occurs with exercise, laughing or crying, or in the absence of an apparent respiratory
infection
o A history of other allergic disease (eczema or allergic rhinitis), allergen sensitization or asthma in first-degree

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relatives

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o Clinical improvement during 2–3 months of low-dose inhaled corticosteroid (ICS) treatment plus as-needed

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short-acting beta2 agonist (SABA) reliever, and worsening after cessation.

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ASTHMA AND WHEEZING IN YOUNG CHILDREN

R
O
Asthma is the most common chronic disease of childhood and the leading cause of childhood morbidity from chronic
PY
disease as measured by school absences, emergency department visits and hospitalizations.750 Asthma often begins in
O
C
early childhood; in up to half of people with asthma, symptoms commence during childhood.751 Onset of asthma is
T

earlier in males than females.752-754

O
N
O

No intervention has yet been shown to prevent the development of asthma or modify its long-term natural course. Atopy
-D

is present in the majority of children with asthma who are over 3 years old, and allergen-specific sensitization (and
L

particularly multiple early-life sensitizations) is one of the most important risk factors for the development of asthma.755
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Viral-induced wheezing
AT
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Recurrent wheezing occurs in a large proportion of children aged 5 years or younger. It is typically associated with upper
D

respiratory tract infections (URTI), which occur in this age group around 6–8 times per year.756 Some viral infections
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(respiratory syncytial virus and rhinovirus) are associated with recurrent wheeze throughout childhood. Wheezing in this
H
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age group is a highly heterogeneous condition, and not all wheezing indicates asthma. A large proportion of wheezing
R

episodes in young children is virally induced whether the child has asthma or not. Therefore, deciding when wheezing
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with a respiratory infection is truly an isolated event or represents a recurrent clinical presentation of childhood asthma
O
C

may be difficult.754,757 In children aged under 1 year, bronchiolitis may present with wheeze. It is usually accompanied by
other chest signs such as crackles on auscultation.

Wheezing phenotypes
In the past, two main classifications of wheezing (called ‘wheezing phenotypes’) were proposed:
• Symptom-based classification:758 this was based on whether the child had only episodic wheeze (wheezing during
discrete time periods, often in association with URTI, with symptoms absent between episodes) or multiple-trigger
wheeze (episodic wheezing with symptoms also occurring between these episodes, e.g., during sleep or with
triggers such as activity, laughing, or crying).
• Time trend-based classification: this system was initially based on retrospective analysis of data from a cohort
study.754 It included transient wheeze (symptoms began and ended before the age of 3 years); persistent wheeze
(symptoms began before the age of 3 years and continued beyond the age of 6 years), and late-onset wheeze
(symptoms began after the age of 3 years). These general patterns have been confirmed in subsequent studies
using unsupervised statistical approaches.759,760

170 6. Diagnosis and management of asthma in children 5 years and younger

 However, prospective allocation of individual children to these phenotypes has been challenging in ‘real-life’ clinical
situations, and the clinical usefulness of these, and other, classification and asthma prediction systems remain a subject
of active investigation. For example, one study conducted in a research setting with high medication adherence found
that daily ICS treatment reduced exacerbations in pre-school children characterized as ‘sensitization with indoor pet
exposure’ or ‘multiple sensitization with eczema’, but not among those characterized as ‘minimal sensitization’ or
‘sensitization with tobacco smoke exposure’.761

CLINICAL DIAGNOSIS OF ASTHMA

It may be challenging to make a confident diagnosis of asthma in children 5 years and younger, because episodic
respiratory symptoms such as wheezing and cough are also common in children without asthma, particularly in those
aged 0–2 years,762,763 and it is not possible to routinely assess airflow limitation or bronchodilator responsiveness in this
age group. A probability-based approach, based on the pattern of symptoms during and between viral respiratory
infections,764 may be helpful for discussion with parents/caregivers (Box 6-1 & 2). This allows individual decisions to be
made about whether to give a trial of controller treatment. It is important to make decisions for each child individually, to

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avoid either over- or under-treatment.

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Box 6-1. Probability of asthma diagnosis in children 5 years and younger

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N
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Symptoms suggestive of asthma in children 5 years and younger

As shown in Boxes 6-1, 6-2 and 6-3, an asthma diagnosis in children 5 years and younger can often be based on:
• Symptom patterns (recurrent episodes of wheeze, cough, breathlessness (typically manifested by activity
limitation), and nocturnal symptoms or awakenings)
• Presence of risk factors for development of asthma, such as family history of atopy, allergic sensitization, allergy
or asthma, or a personal history of food allergy or atopic dermatitis
• Therapeutic response to controller treatment.
• Exclusion of alternate diagnoses.

6. Diagnosis and Management of asthma in children 5 years and younger 171

 Box 6-1 is a schematic figure showing the estimated probability of an asthma diagnosis765,766 in children aged 5 years or
younger who have viral-induced cough, wheeze or heavy breathing, based on the pattern of symptoms.
Many young children wheeze with viral infections; it may be difficult to decide when a child should be given controller
treatment. The frequency and severity of wheezing episodes and the temporal pattern of symptoms (only with viral colds
or also in response to other triggers) should be taken into account. Any controller treatment should be viewed as a
treatment trial, with follow up scheduled after 2–3 months to review the response. Review is also important since the
pattern of symptoms tends to change over time in a large proportion of children.
A diagnosis of asthma in young children is therefore based largely on recurrent symptom patterns combined with a
careful clinical assessment of family history and physical findings with careful consideration of the differential diagnostic
possibilities. A positive family history of allergic disorders, or the presence of atopy or allergic sensitization provide
additional predictive support, as early allergic sensitization increases the likelihood that a wheezing child will develop
persistent asthma.755

Box 6-2. Features suggesting a diagnosis of asthma in children 5 years and younger

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Feature Characteristics suggesting asthma

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Cough • Recurrent or persistent non-productive cough that may be worse at night

IS
or accompanied by wheezing and breathing difficulties

D
R
• Cough occurring with exercise, laughing, crying or exposure to tobacco

O
smoke, particularly in the absence of an apparent respiratory infection
PY
O
Wheezing • Recurrent wheezing, including during sleep or with triggers such as activity,
C

laughing, crying or exposure to tobacco smoke or air pollution

T
O
N

Difficult or heavy breathing or • Occurring with exercise, laughing, or crying

O

shortness of breath
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Reduced activity • Not running, playing or laughing at the same intensity as other children;
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tires earlier during walks (wants to be carried)

AT

Past or family history • Other allergic disease (atopic dermatitis or allergic rhinitis, food allergy).
M

Asthma in first-degree relative(s)

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Therapeutic trial with low-dose ICS • Clinical improvement during 2–3 months of low-dose ICS treatment and
H

(Box 6-6, p.183) plus as-needed SABA

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worsening when treatment is stopped

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See list of abbreviations (p.10).

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Wheeze
C

Wheeze is the most common and specific symptom associated with asthma in children 5 years and younger. Wheezing
occurs in several different patterns, but a wheeze that occurs recurrently, during sleep, or with triggers such as activity,
laughing, or crying, is consistent with a diagnosis of asthma. Clinician confirmation is important, as parents/caregivers
may describe any noisy breathing as ‘wheezing’.767 Some cultures do not have a word for wheeze.
Wheezing may be interpreted differently based on:
• Who observes it (e.g., parent/caregiver versus the health care provider)
• The environmental context (e.g,. high income countries versus areas with a high prevalence of parasites that
involve the lung)
• The cultural context (e.g., the relative importance of certain symptoms can differ between cultures, as can the
diagnosis and treatment of respiratory tract diseases in general).

172 6. Diagnosis and management of asthma in children 5 years and younger

 Box 6-3. Questions that can be used to elicit features suggestive of asthma

• Does your child have wheezing? Wheezing is a high-pitched noise which comes from the chest and not the throat.
Use of a video questionnaire,768 or asking a parent/caregiver to record an episode on a smartphone if available
can help to confirm the presence of wheeze and differentiate from upper airway abnormalities.
• Does your child wake up at night because of coughing, wheezing, or difficult breathing, heavy breathing, or
breathlessness?
• Does your child have to stop running, or play less hard, because of coughing, wheezing or difficult breathing,
heavy breathing, or shortness of breath?
• Does your child cough, wheeze or get difficult breathing, heavy breathing, or shortness of breath when laughing,
crying, playing with animals, or when exposed to strong smells or smoke?
In children with respiratory symptoms, additional features may help to support the diagnosis of asthma
• Has your child ever had eczema, or been diagnosed with allergy to foods?

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• Has anyone in your family had asthma, hay fever, food allergy, eczema, or any other disease with breathing

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problems?

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Cough

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Cough due to asthma is generally non-productive, recurrent and/or persistent, and is usually accompanied by wheezing

O
episodes and breathing difficulties. Allergic rhinitis may be associated with cough in the absence of asthma. A nocturnal
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cough (when the child is asleep) or a cough that occurs with exercise, laughing or crying, in the absence of an apparent
O
respiratory infection, supports a diagnosis of asthma. The common cold and other respiratory illnesses including
C
T

pertussis are also associated with coughing. Prolonged cough in infancy, and cough without cold symptoms, are
O
N

associated with later parent/caregiver-reported physician-diagnosed asthma, independent of infant wheeze.

O

Characteristics of cough in infancy may be early markers of asthma susceptibility, particularly among children with
-D

maternal asthma.769
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Breathlessness
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Parents/caregivers may also use terms such as ‘difficult breathing’, ‘heavy breathing’, or ‘shortness of breath’.
M

Breathlessness that occurs during exercise and is recurrent increases the likelihood of the diagnosis of asthma. In
D

infants and toddlers, crying and laughing are equivalent to exercise in older children.
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Activity and social behavior

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Physical activity is an important trigger of asthma symptoms in young children. Young children with poorly controlled
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asthma often abstain from strenuous play or exercise to avoid symptoms, but many parents/caregivers are unaware of
O

such changes in their children’s lifestyle. Engaging in play is important for a child’s normal social and physical
C

development. For this reason, careful review of the child’s daily activities, including their willingness to walk and play, is
important when assessing a potential asthma diagnosis in a young child. Parents/caregivers may report irritability,
tiredness and mood changes in their child as the main problems when asthma is not well controlled.

TESTS TO ASSIST IN DIAGNOSIS

While no tests specifically and definitively diagnose asthma with certainty, in children 5 years and younger, the following
are useful adjuncts.

Therapeutic trial
A trial of treatment for at least 2–3 months with as-needed SABA and regular low-dose ICS may provide some guidance
about the diagnosis of asthma (Evidence D). Response should be evaluated by symptom control (daytime and night-
time), and the frequency of wheezing episodes and exacerbations. Marked clinical improvement during treatment, and

6. Diagnosis and Management of asthma in children 5 years and younger 173

 deterioration when treatment is stopped, support a diagnosis of asthma. Due to the variable nature of asthma in young
children, a therapeutic trial may need to be repeated in order to be certain of the diagnosis.

Tests for allergic sensitization

Sensitization to allergens can be assessed using either skin prick testing or allergen-specific immunoglobulin E. Allergic
sensitization is present in the majority of children with asthma once they are over 3 years of age; however, absence of
sensitization to common aeroallergens does not rule out a diagnosis of asthma. Allergic sensitization is the best
predictor for development of persistent asthma.770

Chest X-ray
Radiographs are rarely indicated; however, if there is doubt about the diagnosis of asthma in a wheezing or coughing
child, a plain chest X-ray may help to exclude structural abnormalities (e.g., congenital lobar emphysema, vascular ring)
chronic infections such as tuberculosis, an inhaled foreign body, or other diagnoses. Other imaging investigations may
be appropriate, depending on the condition being considered.

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Lung function testing

TR
Due to the inability of most children 5 years and younger to perform reproducible expiratory maneuvers, lung function

IS
D
testing, bronchial provocation testing, and other physiological tests do not have a major role in the diagnosis of asthma

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at this age. However, by 5 years of age, many children are capable of performing reproducible spirometry if coached by

O
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an experienced technician and with visual incentives.
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Exhaled nitric oxide
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O

Measurement of fractional concentration of exhaled nitric oxide (FeNO) is not widely available for most children in this
N
O

age group and currently remains primarily a research tool. FeNO can be measured in young children with tidal breathing,
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and normal reference values have been published for children aged 1–5 years.771 In pre-school children with recurrent
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coughing and wheezing, an elevated FeNO recorded 4 weeks from any URTI predicted physician-diagnosed asthma at
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school age,772 and increased the odds for wheezing, asthma and ICS use by school age, independent of clinical history
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and presence of specific IgE.773

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Risk profiles
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A number of risk profile tools aimed at identifying which wheezing children aged 5 years and younger are at high risk of
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developing persistent asthma symptoms have been evaluated for use in clinical practice. However, these tools have
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shown limited performance for clinical practice. Only three prediction tools have been externally validated (Asthma
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Predictive Index774 from Tucson, USA, Prevention and Incidence of Asthma and Mite Allergy (PIAMA) index675 from the
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Netherlands, and Leicester tool775 from the UK), and a systematic review has shown that these tools have poor
predictive accuracy, with variation in sensitivity and positive predictive value.776 Larger predictive studies using more
advanced statistical methods, and with objective measurements for asthma diagnosis, are probably needed to propose a
practical tool in clinical care to predict persistent asthma in recurrent wheezers in infancy and pre-school age. The role of
these tools is to help identify children at greater risk of developing persistent asthma symptoms, not as criteria for the
diagnosis of asthma in young children. Each tool demonstrates different performance characteristics with varying criteria
used to identify risk.777

174 6. Diagnosis and management of asthma in children 5 years and younger

DIFFERENTIAL DIAGNOSIS
A definite diagnosis of asthma in this young age group is challenging but has important clinical consequences. It is
particularly important in this age group to consider and exclude alternative causes that can lead to symptoms of wheeze,
cough, and breathlessness before confirming an asthma diagnosis (Box 6-4).762

Box 6-4. Common differential diagnoses of asthma in children 5 years and younger

Condition Typical features

Recurrent viral respiratory Mainly cough, runny congested nose for <10 days; no symptoms between infections
tract infections
Gastroesophageal reflux Cough when feeding; recurrent chest infections; vomits easily especially after large
feeds; poor response to asthma medications

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Foreign body aspiration Episode of abrupt, severe cough and/or stridor during eating or play; recurrent chest

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infections and cough; focal lung signs

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IS
Pertussis Protracted paroxysms of coughing, often with stridor and vomiting

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Persistent bacterial Persistent wet cough; poor response to asthma medications

O
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bronchitis
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Tracheomalacia Noisy breathing when crying or eating, or during upper airway infections (noisy inspiration
C
T

if extrathoracic or expiration if intrathoracic); harsh cough; inspiratory or expiratory

O
N

retraction; symptoms often present since birth; poor response to asthma medications
O
-D

Tuberculosis Persistent noisy respirations and cough; fever unresponsive to normal antibiotics;
enlarged lymph nodes; poor response to bronchodilators or inhaled corticosteroids;
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contact with someone who has tuberculosis

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AT

Congenital heart disease Cardiac murmur; cyanosis when eating; failure to thrive; tachycardia; tachypnea or
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hepatomegaly; poor response to asthma medications

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Cystic fibrosis Cough starting shortly after birth; recurrent chest infections; failure to thrive
H

(malabsorption); loose greasy bulky stools

IG
R

Primary ciliary dyskinesia Cough and recurrent chest infections; neonatal respiratory distress, chronic ear infections
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and persistent nasal discharge from birth; poor response to asthma medications; situs
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inversus occurs in about 50% of children with this condition

C

Vascular ring Persistently noisy breathing; poor response to asthma medications

Bronchopulmonary Infant born prematurely; very low birth weight; needed prolonged mechanical ventilation
dysplasia or supplemental oxygen; difficulty with breathing present from birth
Immune deficiency Recurrent fever and infections (including non-respiratory); failure to thrive
See list of abbreviations (p.10).

6. Diagnosis and Management of asthma in children 5 years and younger 175

Key indications for referral of a child 5 years or younger for further diagnostic investigations or therapeutic
decisions
Any of the following features suggest an alternative diagnosis and indicate the need for further investigations:
• Failure to thrive
• Neonatal or very early onset of symptoms (especially if associated with failure to thrive)
• Vomiting associated with respiratory symptoms
• Continuous wheezing
• Failure to respond to asthma medications (inhaled ICS, oral steroids or SABA)
• No association of symptoms with typical triggers, such as viral URTI
• Focal lung or cardiovascular signs, or finger clubbing
• Hypoxemia outside context of viral illness.

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176 6. Diagnosis and management of asthma in children 5 years and younger

 6.2. ASSESSMENT AND MANAGEMENT

KEY POINTS

• The goals of asthma management in young children are similar to those in older patients:
o To achieve good control of symptoms and maintain normal activity levels
o To minimize the risk of asthma flare-ups, impaired lung development and medication side-effects.
• Wheezing episodes in young children should be treated initially with inhaled SABA, regardless of whether the
diagnosis of asthma has been made. However, for initial episodes of wheeze in children <1 year in the setting of
infectious bronchiolitis, SABAs are generally ineffective.
• A trial of low-dose ICS treatment should be given if the symptom pattern suggests asthma, alternative diagnoses
have been excluded and respiratory symptoms are uncontrolled and/or wheezing episodes are frequent or severe.

• Response to treatment should be reviewed before deciding whether to continue it. If the response is absent or

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incomplete, reconsider alternative diagnoses.

U
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TR
• The choice of inhaler device should be based on the child’s age and capability. The preferred device is a pressurized
metered dose inhaler and spacer, with face mask for <3 years and mouthpiece for most children aged 3–5 years.

IS
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Children should be switched from a face mask to mouthpiece as soon as they are able to demonstrate good

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technique.

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• Review the need for asthma treatment frequently, as asthma-like symptoms remit in many young children.
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GOALS OF ASTHMA MANAGEMENT

O
N

As with other age groups, the goals of asthma management in young children are:
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• To achieve good control of symptoms and maintain normal activity levels

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• To minimize future risk; that is to reduce the risk of flare-ups, maintain lung function and lung development as
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close to normal as possible, and minimize medication side-effects.

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AT

Maintaining normal activity levels is particularly important in young children because engaging in play is important for
M

their normal social and physical development. It is important to also elicit the goals of the parent/caregiver, as these may
D

differ from conventional medical goals.

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The goals of asthma management are achieved through a partnership between the parent/caregiver and the health
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professional team, with a cycle of:

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• Assess (diagnosis, symptom control, risk factors, inhaler technique, adherence, parent preference)
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• Adjust treatment (medications, non-pharmacological strategies, and treatment of modifiable risk factors)
• Review response including medication effectiveness and side-effects. This is carried out in combination with:
Education of parent/caregiver, and child (depending on the child’s age)
• Skills training for effective use of inhaler devices and encouragement of good adherence
• Monitoring of symptoms by parent/caregiver
• A written personalized asthma action plan.

ASSESSMENT OF ASTHMA

What does ‘asthma control’ mean?

Asthma control means the extent to which the manifestations of asthma are controlled, with or without treatment. 29,69 It
has two components (Box 6-5, p.178): the child’s asthma status over the previous four weeks (current symptom control),
and how asthma may affect them in the future (future risk). In young children, as in older patients, both symptom control

6. Diagnosis and management of asthma in children 5 years and younger 177

 and future risk should be monitored (Evidence D). The rationale for this is described on p.40.

Assessing asthma symptom control

Defining satisfactory symptom control in children 5 years and younger depends on information derived from family
members and carers, who may be unaware either of how often the child has experienced asthma symptoms, or that their
respiratory symptoms represent uncontrolled asthma. Few objective measures to assess symptom control have been
validated for children <4 years. The Childhood Asthma Control Test can be used for children aged 4–11 years.91 The
Test for Respiratory and Asthma Control in Kids (TRACK) is a validated questionnaire for parent/caregiver completion
for preschool-aged children with symptoms consistent with asthma; it includes both symptom control and courses of
systemic corticosteroids in the previous year.95 However, children with no interval symptoms can still be at risk of
exacerbations.
Box 6-5 shows a working schema for assessing asthma control in children ≤5 years, based on current expert opinion. It
incorporates assessment of symptoms; the child’s level of activity and their need for reliever/rescue treatment; and

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assessment of risk factors for adverse outcomes (Evidence D).

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Box 6-5. GINA assessment of asthma control in children 5 years and younger

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A. Symptom control Level of asthma symptom control

D
R
Well Partly

O
In the past 4 weeks, has the child had: Uncontrolled
controlled controlled
Daytime asthma symptoms for more than a few minutes, Yes No PY
O
C
more than once a week?
T
O

Any activity limitation due to asthma? (Runs/plays less Yes No

None 1–2 3–4
N

than other children, tires easily during walks/playing?)

O

of these of these of these

-D

SABA reliever medication needed* more than once a week?Yes No

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Any night waking or night coughing due to asthma? Yes No

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B. Future risk for poor asthma outcomes

AT
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Risk factors for asthma exacerbations within the next few months
D
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• Uncontrolled asthma symptoms

H

• One or more severe exacerbations (ED attendance, hospitalization, or course of OCS) in previous year
IG

The start of the child’s usual ‘flare-up’ season (especially if autumn/fall)

R

•
PY

• Exposures: tobacco smoke; indoor or outdoor air pollution; indoor allergens (e.g., house dust mite, cockroach,
O

pets, mold), especially in combination with viral infection778

C

• Major psychological or socio-economic problems for child or family

• Poor adherence with ICS medication, or incorrect inhaler technique
• Outdoor pollution (NO2 and particles)111
Risk factors for persistent airflow limitation
• Severe asthma with several hospitalizations
• History of bronchiolitis
Risk factors for medication side-effects
• Systemic: Frequent courses of OCS, high-dose and/or potent ICS (see Box 6-7, p.184
• Local: moderate-to high-dose or potent ICS; incorrect inhaler technique; failure to protect skin or eyes when using
ICS by nebulizer or spacer with face mask

See list of abbreviations (p.10). * Excludes reliever taken before exercise. Before stepping up treatment, ensure that the child’s symptoms are due to
asthma, and that the child has good inhaler technique and good adherence to existing treatment.

178 6. Diagnosis and management of asthma in children 5 years and younger

Assessing future risk of adverse outcomes
The relationship between symptom control and future risk of adverse outcomes, such as exacerbations (Box 6-5, p.178),
has not been sufficiently studied in young children. Although exacerbations may occur in children after months of
apparently good symptom control, the risk is greater if current symptom control is poor. Preschool children at high risk of
asthma (based on modified API) who were treated with daily low-dose ICS experienced fewer days with asthma
symptoms and a reduced risk of exacerbations than those receiving placebo.779
The future risk of harm due to excessive doses of inhaled or systemic corticosteroids must also be avoided. This can be
minimized by ensuring that the prescribed treatment is appropriate and reduced to the lowest dose that maintains
satisfactory symptom control and minimizes exacerbations. The child’s height should be measured and recorded at least
yearly, as growth velocity may be lower in the first 1–2 years of ICS treatment,132 and poorly controlled asthma can affect
growth.131 The minimum effective dose of ICS to maintain good asthma control should be used. If decreased growth
velocity is seen, other factors should be considered, including poorly controlled asthma, frequent use of oral
corticosteroids (OCS), and poor nutrition, and referral should be considered.

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If ICS is delivered through a face-mask or nebulizer, the skin on the nose and around the mouth should be cleaned

U
shortly after inhalation in order to avoid local side-effects such as steroid rash (reddening and atrophy).

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TR
IS
MEDICATIONS FOR SYMPTOM CONTROL AND RISK REDUCTION

D
R
Choosing medications for children 5 years and younger

O
PY
Good control of asthma can be achieved in the overwhelming majority of young children with a pharmacological
O
intervention strategy.780 This should be developed in a partnership between the family/carer and the health care provider.
C
T

As with older children and adults, medications comprise only one component of asthma management in young children;
O
N

other key components include education, skills training for inhaler devices and adherence, non-pharmacological
O

strategies including environmental control where appropriate, regular monitoring, and clinical review (see later sections in
-D

this chapter).
L
IA

When recommending treatment for a young child, both general and individual questions apply (Box 3-3, p.52).
ER

• What is the ‘preferred’ medication option at each treatment step to control asthma symptoms and minimize future
AT

risk? These decisions are based on data for efficacy, effectiveness and safety from clinical trials, and on
M

observational data. Studies suggest that consideration of factors such as allergic sensitization and/or peripheral
D
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blood count may help to better identify which children are more likely to have a short-term response to ICS.781
H

However, further studies are needed to assess the applicability of these findings in a wider range of settings,
IG
R

particularly in areas where blood eosinophilia may reflect helminth infection rather than asthma or atopy.
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• How does this individual child differ from other children with asthma, in terms of:
O
C

o Response to previous treatment

o Preferences of the parent/caregiver (goals, beliefs and concerns about medications)
o Practical issues (cost, inhaler technique and adherence)?
The following treatment recommendations for children of 5 years of age or younger are based on the available evidence
and on expert opinion. Although the evidence is expanding it is still rather limited as most clinical trials in this age group
have not characterized participants with respect to their symptom pattern, and different studies have used different
outcomes and different definitions of exacerbations.
A stepwise treatment approach is recommended (Box 6-6, p.183), based on symptom patterns, risk of exacerbations and
side-effects, and response to initial treatment. Generally, treatment includes the daily, long-term use of low-dose ICS
treatment to keep asthma well controlled, and reliever medications for as-needed symptom relief. The choice of inhaler
device is also an important consideration (Box 6-8, p.185).

6. Diagnosis and management of asthma in children 5 years and younger 179

Which children should be prescribed regular controller treatment?
Intermittent or episodic wheezing of any severity may represent an isolated viral-induced wheezing episode, an episode
of seasonal or allergen-induced asthma, or unrecognized uncontrolled asthma. The initial treatment of wheezing is
identical for all of these – a SABA every 4–6 hours as needed until symptoms disappear, usually within 1 to 7 days.
Further treatment of the acute wheezing episodes themselves is described below (see Acute asthma exacerbations in
children 5 years and younger, p.187). However, uncertainty surrounds the addition of other medications in these
children, especially when the nature of the episode is unclear. In general, the following principles apply.
• If the history and symptom pattern suggest a diagnosis of asthma (Box 6-2, p.172; Box 6-3, p.173) and respiratory
symptoms are uncontrolled (Box 6-5, p.178) and/or wheezing episodes are frequent (e.g., three or more episodes
in a season), regular controller treatment (usually maintenance low-dose ICS) should be initiated (Step 2, Box 6-6,
p.183) and the response evaluated (Evidence D). Regular ICS treatment may also be indicated in a child with less
frequent, but more severe episodes of viral- induced wheeze (Evidence D).
• If the diagnosis of asthma is in doubt, and inhaled SABA therapy or courses of antibiotics need to be repeated
frequently, e.g., more than every 6–8 weeks, a trial of regular ICS treatment should be considered to confirm

TE
whether the symptoms are due to asthma (Evidence D). Referral for specialist opinion should also be considered

U
IB
at this stage.

TR
IS
It is important to discuss the decision to prescribe controller treatment and the choice of treatment with the child’s

D
parents or caregivers. They should be aware of both the relative benefits and risks of the treatments, and the importance

R
of maintaining normal activity levels for their child’s normal physical and social development. Although effects of ICS on

O
PY
growth velocity are seen in pre-pubertal children in the first 1–2 years of treatment, this is not progressive or cumulative,
O
and the one study that examined long-term outcomes showed a difference of only 0.7% in adult height.132,782 Poorly
C
controlled asthma itself adversely affects adult height.131
T
O
N

Treatment steps to control asthma symptoms and minimize future risk for children 5 years and younger
O
-D

Asthma treatment in young children follows a stepwise approach (Box 6-6), with medication adjusted up or down to
L

achieve good symptom control and minimize future risk of exacerbations and medication side-effects. The need for
IA
ER

controller treatment should be re-assessed regularly.

AT

Before considering a step-up of controller treatment

M
D

If symptom control is poor and/or exacerbations persist despite 3 months of adequate controller therapy, check the
TE

following before any step up in treatment is considered.

H
IG

• Confirm that the symptoms are due to asthma rather than a concomitant or alternative condition (Box 6-4, p.176).
R

Refer for expert assessment if the diagnosis is in doubt.

PY

• Check and correct inhaler technique.

O
C

• Confirm good adherence with the prescribed dose.

• Consider trial of one of the other treatment options for that step, as many children may respond to one of the
options.
• Enquire about risk factors such as allergen or tobacco smoke exposure (Box 6-5, p.178).

180 6. Diagnosis and management of asthma in children 5 years and younger

ASTHMA TREATMENT STEPS FOR CHILDREN AGED 5 YEARS AND YOUNGER

STEP 1: As-needed inhaled short-acting beta2-agonist (SABA)

Preferred option: as-needed inhaled short-acting beta2-agonist (SABA)

All children who experience wheezing episodes should be provided with inhaled SABA for relief of symptoms (Evidence
D), although it is not effective in all children. See Box 6-8 (p.185) for choice of inhaler device. Use of SABA for the relief
of symptoms on average more than twice a week over a 1-month period indicates the need for a trial of low-dose ICS
treatment. Initial episodes of wheeze in children <1 year often occur in the setting of infectious bronchiolitis, and this
should be managed according to local bronchiolitis guidelines. SABAs are generally ineffective for bronchiolitis.783
Other options
Oral bronchodilator therapy is not recommended due to its slower onset of action and higher rate of side-effects,

TE
compared with inhaled SABA (Evidence D).

U
IB
For children with intermittent viral-induced wheeze and no interval symptoms, particularly those with underlying atopy

TR
(positive for modified API) in whom inhaled SABA medication is not sufficient, intermittent high-dose ICS may be

IS
considered649,784,785 (see Management of worsening asthma and exacerbations, p.187), but because of the risk of side-

D
effects, this should only be considered if the physician is confident that the treatment will be used appropriately.

R
O
PY
STEP 2: Initial controller treatment plus as-needed SABA O
C

Preferred option: regular daily low-dose ICS plus as-needed SABA

T
O
N

Regular daily, low-dose ICS (Box 6-7, p.184) is recommended as the preferred initial treatment to control asthma in
O

children 5 years and younger (Evidence A).779,786-788 This initial treatment should be given for at least 3 months to
-D

establish its effectiveness in achieving good asthma control.

L
IA
ER

Other options
AT

In young children with persistent asthma, regular treatment with a leukotriene receptor antagonist (LTRA) modestly
M

reduces symptoms and need for oral corticosteroids compared with placebo.789 However, for young children with
D

recurrent viral- induced wheezing, a review concluded that neither regular nor intermittent LTRA reduces OCS-requiring
TE

exacerbations (Evidence A).790 A further systematic review found that in preschool children with asthma or recurrent
H
IG

wheezing, daily ICS was more effective in improving symptom control and reducing exacerbations than regular LTRA
R

monotherapy.791 Parents/caregivers should be counselled about the potential adverse effects of montelukast on sleep
PY

and behavior, and health professionals should consider the benefits and risks of side effects before prescribing; the FDA
O
C

has required a boxed warning about these problems.236

For preschool children with asthma characterized by frequent viral-induced wheezing and interval asthma symptoms, as-
needed (prn)792 or episodic ICS793 may be considered, but a trial of regular daily low-dose ICS should be undertaken
first. The effect on exacerbation risk seems similar for regular daily low-dose and episodic high-dose ICS.788 See also
Initial home management of asthma exacerbations, p.188.
If good asthma control is not achieved with a given therapy, trials of the alternative Step 2 therapies are recommended
prior to moving to Step 3.781

6. Diagnosis and management of asthma in children 5 years and younger 181

 STEP 3: Additional controller treatment, plus as-needed SABA and consider specialist referral

If 3 months of initial therapy with a low-dose ICS fails to control symptoms, or if exacerbations continue to occur, check
the following before any step up in treatment is considered.
• Confirm that the symptoms are due to asthma rather than a concomitant or alternative condition (Box 6-4,
p.176).
• Check and correct inhaler technique. Consider alternative delivery systems if indicated.
• Confirm good adherence with the prescribed dose.
• Enquire about risk factors, such as exposure to allergens or tobacco smoke (Box 6-5, p.178).
Preferred option: medium-dose ICS (double the ‘low’ daily dose)
Doubling the initial low dose of ICS may be the best option (Evidence C). Assess response after 3 months. The child
should be referred for expert assessment if symptom control remains poor and/or flare-ups persist, or if side-effects of
treatment are observed or suspected.

TE
U
Other options

IB
TR
Addition of a LTRA to low-dose ICS may be considered, based on data from older children (Evidence D). The relative

IS
cost of different treatment options in some countries may be relevant to controller choices for children. See note above

D
about the FDA warning for montelukast. 236

R
O
Not recommended
PY
O
There are insufficient data about the efficacy and safety of ICS-LABA in children <4 years old to recommend their use. A
C

short-term (8 week) placebo-controlled study did not show any significant difference in symptoms between combination
T
O

fluticasone propionate-salmeterol versus fluticasone propionate alone; no additional safety signals were noted in the
N

group receiving LABA.794

O
-D
L

STEP 4: Continue controller treatment and refer for expert assessment

IA
ER

Preferred option: refer the child for expert advice and further investigation (Evidence D).
AT
M

If doubling the initial dose of ICS fails to achieve and maintain good asthma control, carefully reassess inhaler technique
D

and medication adherence as these are common problems in this age group. In addition, reassess and address control
TE

of environmental factors where relevant, and reconsider the asthma diagnosis.

H
IG

Other options
R
PY

The best treatment for this population has not been established. If the diagnosis of asthma has been confirmed, options
O

to consider, with specialist advice, are:

C

• Further increase the dose of ICS for a few weeks until the control of the child’s asthma improves (Evidence D).
Monitor for side-effects.
• Add LTRA (data based on studies in older children, Evidence D). Benefits, and risks of side effects, should be
considered, as described previously. 236
• Add long-acting beta agonist (LABA) in combination with ICS; data based on studies in children ≥4 years of age
• Add a low dose of oral corticosteroid (for a few weeks only) until asthma control improves (Evidence D); monitor
for side-effects.
• Add intermittent high-dose ICS at onset of respiratory illnesses to the regular daily ICS if exacerbations are the
main problem (Evidence D).
The need for additional controller treatment should be re-evaluated at each visit and maintained for as short a period as
possible, taking into account potential risks and benefits. Treatment goals and their feasibility should be reconsidered
and discussed with the child’s family/carer.

182 6. Diagnosis and management of asthma in children 5 years and younger

Box 6-6. Personalized management of asthma in children 5 years and younger

TE
U
IB
TR
IS
D
R
O
PY
O
C
T
O
N
O
-D
L
IA
ER
AT
M
D
TE
H
IG
R
PY
O
C

See list of abbreviations (p.10). For ICS doses in children, see Box 6-7, p.184

t
 Box 6-7. Low daily doses of inhaled corticosteroids for children 5 years and younger

This is not a table of equivalence, but instead, suggestions for ‘low’ total daily doses for the ICS treatment
recommendations for children aged 5 years and younger in Box 6-6 (p.183), based on available studies and product
information. Data on comparative potency are not readily available, particularly for children, and this table does NOT
imply potency equivalence. The doses listed here are the lowest approved doses for which safety and effectiveness
have been adequately studied in this age group.
Low-dose ICS provides most of the clinical benefit for most children with asthma. Higher doses are associated with an
increased risk of local and systemic side-effects, which must be balanced against potential benefits.
Low total daily dose (mcg)
Inhaled corticosteroid
(age-group with adequate safety and effectiveness data)
BDP (pMDI, standard particle, HFA) 100 (ages 5 years and older)
BDP (pMDI, extrafine particle, HFA) 50 (ages 5 years and older)

TE
Budesonide nebulized 500 (ages 1 year and older)

U
IB
Fluticasone propionate (pMDI, standard particle, HFA) 50 (ages 4 years and older)

TR
IS
Fluticasone furoate (DPI) Not sufficiently studied in children 5 years and younger)

D
Mometasone furoate (pMDI, standard particle, HFA) 100 (ages 5 years and older)

R
O
Ciclesonide (pMDI, extrafine particle, HFA) Not sufficiently studied in children 5 years and younger
PY
O
BDP : beclometasone dipropionate. For other abbreviations see p.10. In children, pMDI should always be used with a spacer
C
T
O

REVIEWING RESPONSE AND ADJUSTING TREATMENT

N
O

Assessment at every visit should include asthma symptom control and risk factors (Box 6-5, p.178), and side-effects.
-D

The child’s height should be measured every year, or more often. Asthma-like symptoms remit in a substantial proportion
L

of children of 5 years or younger,795-797 so the need for continued controller treatment should be regularly assessed
IA
ER

(e.g,. every 3–6 months) (Evidence D). If therapy is stepped-down or discontinued, schedule a follow-up visit 3–6 weeks
AT

later to check whether symptoms have recurred, as therapy may need to be stepped-up or reinstituted (Evidence D).
M

Marked seasonal variations may be seen in symptoms and exacerbations in this age-group. For children with seasonal
D
TE

symptoms whose daily long-term controller treatment is to be discontinued (e.g., 4 weeks after their season ends), the
H

parent/caregiver should be provided with a written asthma action plan detailing specific signs of worsening asthma, the
IG

medications that should be initiated to treat it, and when and how to contact medical care.
R
PY
O

CHOICE OF INHALER DEVICE

C

Inhaled therapy constitutes the cornerstone of asthma treatment in children 5 years and younger. General information
about inhaler devices, and the issues that should be considered, are found in Chapter 3.3 (p.98) and in Box 3-21 (p.99).
These include, first, choosing the right medication(s) for the child to control symptoms, allow normal activity, and reduce
the risk of severe exacerbations; considering which delivery device is available; whether they can use it correctly after
training; and, if more than one type of inhaler device is available, their relative environmental impact.
For children aged 5 years and younger, a pressurized metered-dose inhaler (pMDI) with a valved spacer (with or without
a face mask, depending on the child’s age) is the preferred delivery system798 (Box 6-8, p.185) (Evidence A). This
recommendation is based on studies with beta2-agonists. The spacer device should have documented efficacy in young
children. The dose delivered may vary considerably between spacers, so consider this if changing from one spacer to
another.
The only possible inhalation technique in young children is tidal breathing. The optimal number of breaths required to
empty the spacer depends on the child’s tidal volume, and the dead space and volume of the spacer. Generally, 5–10
breaths will be sufficient per actuation. The way a spacer is used can markedly affect the amount of drug delivered:

184 6. Diagnosis and management of asthma in children 5 years and younger

 • Spacer size may affect the amount of drug available for inhalation in a complex way depending on the drug
prescribed and the pMDI used. Young children can use spacers of all sizes, but theoretically a lower volume
spacer (<350 mL) is advantageous in very young children.
• A single pMDI actuation should be delivered at a time, with the inhaler shaken in between. Multiple actuations into
the spacer before inhalation may markedly reduce the amount of drug inhaled.
• Delay between actuating the pMDI into the spacer and inhalation may reduce the amount of drug available. This
varies between spacers, but to maximize drug delivery, inhalation should start as soon as possible after actuation.
If a health care provider or a carer is giving the medication to the child, they should actuate the pMDI only when
the child is ready and the spacer is in the child’s mouth.
• If a face mask is used it must be fitted tightly around the child’s mouth and nose, to avoid loss of drug.
• Ensure that the valve is moving while the child is breathing through the spacer.
• Static charge may accumulate on some plastic spacers, attracting drug particles and reducing lung delivery. This
charge can be reduced by washing the spacer with detergent (without rinsing) and allowing it to air dry, but it may

TE
re-accumulate over time. Spacers made of anti-static materials or metals are less subject to this problem. If a

U
IB
patient or health care provider carries a new plastic spacer for emergency use, it should be regularly washed with

TR
detergent (e.g., monthly) to reduce static charge.

IS
• Nebulizers, the only viable alternative delivery systems in children, are reserved for the minority of children who

D
R
cannot be taught effective use of a spacer device. If a nebulizer is used for delivery of ICS, it should be used with

O
a mouthpiece to avoid the medication reaching the eyes. If a nebulizer is used, follow local infection control
procedures.
PY
O
C
T
O

Box 6-8. Choosing an inhaler device for children 5 years and younger
N
O

Age Preferred device Alternate device

-D
L

0–3 years Pressurized metered dose inhaler plus Nebulizer with face mask
IA
ER

dedicated spacer with face mask

AT

4–5 years Pressurized metered dose inhaler plus Pressurized metered dose inhaler plus dedicated spacer
M

dedicated spacer with mouthpiece with face mask or nebulizer with mouthpiece or face mask
D

See list of abbreviations (p.10).

TE
H
IG
R
PY
O
C

6. Diagnosis and management of asthma in children 5 years and younger 185

ASTHMA SELF-MANAGEMENT EDUCATION FOR CARERS OF YOUNG CHILDREN
Asthma self-management education should be provided to family members and carers of wheezy children 5 years and
younger when wheeze is suspected to be caused by asthma. An educational program should contain:
• A basic explanation about asthma and the factors that influence it
• Training about correct inhalation technique
• Information on the importance of the child’s adherence to the prescribed medication regimen
• A written asthma action plan.
Crucial to a successful asthma education program are a partnership between patient/carer and health care providers,
with a high level of agreement regarding the goals of treatment for the child, and intensive follow-up (Evidence D).30

Written asthma action plans

Asthma action plans should be provided for the family/carers of all children with asthma, including those aged 5 years
and younger (Evidence D). Action plans, developed through collaboration between an asthma educator, the health care

TE
provider and the family, have been shown to be of value in older children,799 although they have not been extensively

U
IB
studied in children of 5 years and younger. A written asthma action plan includes:

TR
• A description of how the parent or caregiver can recognize when symptom control is deteriorating

IS
D
• The medications to administer

R
• When and how to obtain medical care, including telephone numbers of services available for emergencies

O
PY
(e.g., doctors’ offices, emergency departments and hospitals, ambulance services and emergency pharmacies).
Details of treatments that can be initiated at home are provided in the following section, Part C: Management of
O
C
worsening asthma and exacerbations in children 5 years and younger, p.187.
T
O
N
O
-D
L
IA
ER
AT
M
D
TE
H
IG
R
PY
O
C

186 6. Diagnosis and management of asthma in children 5 years and younger

 6.3. MANAGEMENT OF WORSENING ASTHMA AND EXACERBATIONS IN CHILDREN 5 YEARS
AND YOUNGER

KEY POINTS

Symptoms of exacerbation in young children

• Early symptoms of exacerbations in young children may include increased symptoms; increased coughing,
especially at night; lethargy or reduced exercise tolerance; impaired daily activities including feeding; and a
poor response to reliever medication.
Home management in a written asthma action plan
• Give a written asthma action plan to parents/caregivers of young children with asthma so they can recognize
an impending severe attack, start treatment, and identify when urgent hospital treatment is required.
• Initial treatment at home is with inhaled short-acting beta2-agonist (SABA), with review after 1 hour or earlier.

TE
• Parents/caregivers should seek urgent medical care if the child is acutely distressed, lethargic, fails to respond

U
to initial bronchodilator therapy, or is worsening, especially in children <1 year of age.

IB
TR
• Medical attention should be sought on the same day if inhaled SABA is needed more often than 3-hourly or for

IS
more than 24 hours.

D
R
• There is no compelling evidence to support parent/caregiver-initiated oral corticosteroids.

O
Management of exacerbations in primary care or acute care facility
PY
O
• Assess severity of the exacerbation while initiating treatment with SABA (2–6 puffs every 20 minutes for first
C
hour) and oxygen (to maintain saturation 94–98%).
T
O

• Recommend immediate transfer to hospital if there is no response to inhaled SABA within 1–2 hours; if the
N
O

child is unable to speak or drink, has a respiratory rate >40/minute or is cyanosed, if resources are lacking in
-D

the home, or if oxygen saturation is <92% on room air.

L
IA

• Consider oral prednisone/prednisolone 1–2 mg/kg/day for children attending an Emergency Department (ED)
ER

or admitted to hospital, up to a maximum of 20 mg/day for children aged 0–2 years, and 30 mg/day for
AT

children aged 3–5 years, for up to 5 days; or dexamethasone 0.6 mg/kg/day for 2 days. If there is failure of
M

resolution, or relapse of symptoms with dexamethasone, consideration should be given to switching to

D

prednisolone.
TE
H

Arrange early follow-up after an exacerbation

IG

Children who have experienced an asthma exacerbation are at risk of further exacerbations. Arrange follow-up
R

•
PY

within 1–2 days of an exacerbation and again 1–2 months later to plan ongoing asthma management.
O
C

DIAGNOSIS OF EXACERBATIONS
A flare-up or exacerbation of asthma in children 5 years and younger is defined as an acute or sub-acute deterioration in
symptom control that is sufficient to cause distress or risk to health, and necessitates a visit to a health care provider or
requires treatment with systemic corticosteroids. In pediatric literature, the term ‘episode’ is commonly used, but
understanding of this term by parents/caregivers is not known
Early symptoms of an exacerbation may include any of the following:
• Onset of symptoms of respiratory tract infection
• An acute or sub-acute increase in wheeze and shortness of breath
• An increase in coughing, especially while the child is asleep
• Lethargy or reduced exercise tolerance
• Impairment of daily activities, including feeding
• A poor response to reliever medication.

6. Diagnosis and management of asthma in children 5 years and younger 187

 In a study of children aged 2–5 years, the combination of increased daytime cough, daytime wheeze, and night-time
beta2-agonist use was a strong predictor at a group level of an imminent exacerbation (1 day later). This combination
predicted around 70% of exacerbations, with a low false positive rate of 14%. In contrast, no individual symptom was
predictive of an imminent asthma exacerbation.800
Upper respiratory symptoms frequently precede the onset of an asthma exacerbation, indicating the important role of
viral URTI in precipitating exacerbations in many, although not all, children with asthma. In a randomized controlled trial
of acetaminophen versus ibuprofen, given for pain or fever in children with mild persistent asthma, there was no
evidence of a difference in the subsequent risk of flare-ups or poor symptom control.781

INITIAL HOME MANAGEMENT OF ASTHMA EXACERBATIONS

Initial management includes an action plan to enable the child’s family members and carers to recognize worsening
asthma and initiate treatment, recognize when it is severe, identify when urgent hospital treatment is necessary, and
provide recommendations for follow up (Evidence D). The action plan should include specific information about

TE
medications and dosages and when and how to access medical care.

U
IB
Need for urgent medical attention

TR
IS
Parents/caregivers should be advised to seek medical attention immediately if:

D
• The child is acutely distressed

R
O
• The child’s symptoms are not relieved promptly by inhaled bronchodilator

PY
• The period of relief after doses of SABA becomes progressively shorter
O
• A child younger than 1 year requires repeated inhaled SABA over several hours.
C
T
O

Initial treatment at home

N
O
-D

Inhaled SABA via a mask or spacer, and review response

L

The parent/caregiver should initiate treatment with two puffs of inhaled SABA (200 mcg salbutamol [albuterol] or
IA
ER

equivalent), given one puff at a time via a spacer device with or without a facemask (Evidence D). This may be repeated
a further two times at 20-minute intervals, if needed. The child should be observed by the family/carer and, if improving,
AT

maintained in a restful and reassuring atmosphere for an hour or more. Medical attention should be sought urgently if
M
D

any of the features listed above apply; or on the same day if more than 6 puffs of inhaled SABA are required for
TE

symptom relief within the first 2 hours, or if the child has not recovered after 24 hours.
H
IG

Family/carer-initiated corticosteroids
R
PY

Although practiced in some parts of the world, the evidence to support the initiation of oral corticosteroid (OCS)
O

treatment by family/carers in the home management of asthma exacerbations in children is weak.801-805 Preemptive
C

episodic high-dose nebulized ICS may reduce exacerbations in children with intermittent viral triggered wheezing.788
However, because of the high potential for side-effects, especially if the treatment is continued inappropriately or is
given frequently, family-administered high-dose ICS should be considered only where the health care provider is
confident that the medications will be used appropriately, and the child is closely monitored for side-effects (see p.191).
Leukotriene receptor antagonists
In children aged 2–5 years with intermittent viral wheezing, one study found that a short course of an oral LTRA (for 7–
20 days, commenced at the start of an URTI or the first sign of asthma symptoms) reduced symptoms, health care
utilization and time off work for the carer.806 In contrast another study found no significant effect with LTRA vs placebo
on episode-free days (primary outcome), OCS use, health care utilization, quality of life or hospitalization in children with
or without a positive Asthma Predictive Index (API). However, activity limitation and a symptom trouble score were
significantly improved, particularly in children with a positive API.807 Parents/caregivers should be counseled about the
FDA warning about risk of adverse effects on sleep and behavior with montelukast.236

188 6. Diagnosis and management of asthma in children 5 years and younger

 Box 6-9. Management of acute asthma or wheezing in children 5 years and younger

TE
U
IB
TR
IS
D
R
O
PY
O
C
T
O
N
O
-D
L
IA
ER
AT
M
D
TE
H
IG
R
PY
O
C

See list of abbreviations (p.10).

6. Diagnosis and management of asthma in children 5 years and younger 189

PRIMARY CARE OR HOSPITAL MANAGEMENT OF ACUTE ASTHMA EXACERBATIONS IN CHILDREN 5 YEARS
OR YOUNGER

Assessment of exacerbation severity

Conduct a brief history and examination concurrently with the initiation of therapy (Box 6-9, p.189). The presence of any
of the features of a severe exacerbation listed in Box 6-10 are an indication of the need for urgent treatment and
immediate transfer to hospital (Evidence D). Oxygen saturation from pulse oximetry of <92% on presentation (before
oxygen or bronchodilator treatment) is associated with high morbidity and likely need for hospitalization; saturation of
92–95% is also associated with higher risk.672 The FDA has issued a caution about potential overestimation of oxygen
saturation by pulse oximetry in people with dark skin color.654 Agitation, drowsiness and confusion are features of
cerebral hypoxemia. A quiet chest on auscultation indicates minimal ventilation, insufficient to produce a wheeze.
Several clinical scoring systems such as PRAM (Preschool Respiratory Assessment Measure) and PASS (Pediatric
Asthma Severity Score) have been developed for assessing the severity of acute asthma exacerbations in children.808

TE
U
Box 6-10. Initial assessment of acute asthma exacerbations in children 5 years and younger

IB
TR
Symptoms Mild Severe*

IS
D
Altered consciousness No Agitated, confused or drowsy

R
O
Oximetry on presentation (SaO2)** >95% <92%
PY
O
Speech† Sentences Words
C
T
O

Pulse rate <100 beats/minute >180 beats/minute (0–3 years)

N
O

>150 beats/minute (4–5 years)

-D

Respiratory rate ≤40/minute >40/minute

L
IA
ER

Central cyanosis Absent Likely to be present

AT

Wheeze intensity Variable Chest may be quiet

M
D

See list of abbreviations (p.10). *Any of these features indicates a severe asthma exacerbation. **Oximetry before treatment with oxygen or
TE

bronchodilator. Note FDA caution about potential overestimation of oxygen saturation with pulse oximetry in people with dark skin color.654 †
H

The developmental stage and usual capability of the child must be taken into account.
IG
R
PY

Indications for immediate transfer to hospital

O
C

Children with features of a severe exacerbation that fail to resolve within 1–2 hours despite repeated dosing with inhaled
SABA must be referred to hospital for observation and further treatment (Evidence D). Other indications are respiratory
arrest or impending arrest; lack of supervision in the home or doctor’s office; and recurrence of signs of a severe
exacerbation within 48 hours (particularly if treatment with OCS has already been given). In addition, early medical
attention should be sought for children with a history of severe life-threatening exacerbations, and those aged less than
2 years, as the risk of dehydration and respiratory fatigue is increased (Box 6-12, p.191).

190 6. Diagnosis and management of asthma in children 5 years and younger

Emergency treatment and initial pharmacotherapy
Oxygen
Treat hypoxemia urgently with oxygen by face mask to achieve and maintain percutaneous oxygen saturation 94–98%
(Evidence A). Note the FDA caution above about potential overestimation of oxygen saturation in people with dark skin
color. To avoid hypoxemia during changes in treatment, children who are acutely distressed should be treated
immediately with oxygen and SABA (2.5 mg of salbutamol or equivalent diluted in 3 mL of sterile normal saline)
delivered by an oxygen-driven nebulizer (if available). This treatment should not be delayed, and may be given before
the full assessment is completed. Transient hypoxemia due to ventilation/perfusion mismatch may occur during
treatment with SABAs.

Box 6-11. Indications for immediate transfer to hospital for children 5 years and younger

Immediate transfer to hospital is indicated if a child ≤5 years with asthma has ANY of the following:

TE
• At initial or subsequent assessment

U
o Child is unable to speak or drink

IB
TR
o Cyanosis

IS
o Respiratory rate >40 per minute

D
R
o Oxygen saturation <92% when breathing room air

O
o Silent chest on auscultation
PY
O
• Lack of response to initial bronchodilator treatment
C

Lack of response to 6 puffs of inhaled salbutamol [albuterol] (2 separate puffs, repeated 3 times) over 1–2 hours
T

o
O
N

o Persisting tachypnea* despite three administrations of inhaled SABA, even if the child shows other clinical signs
O

of improvement
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• Social environment that limits delivery of acute treatment, or parent/caregiver unable to manage acute asthma at
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home
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During transfer to hospital, continue to give inhaled SABA, oxygen (if available) to maintain saturation 94–98%, and
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give systemic corticosteroids (see Box 6-9, p.189)

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See list of abbreviations (p.10). *Normal respiratory rates: <60 breaths/minute in children 0–2 months; <50 breaths/minute in children 2–12 months;
<40 breaths/minute in children 1–5 years.
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Inhaled bronchodilator therapy

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The initial dose of inhaled SABA may be given by a pMDI with spacer and mask or mouthpiece or an air-driven
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nebulizer; or, if oxygen saturation is low, by an oxygen-driven nebulizer (as described above). For most children, pMDI
plus spacer is favored as it is more efficient than a nebulizer for bronchodilator delivery809 (Evidence A), and nebulizers
can spread infectious particles. The initial dose of SABA is two puffs of salbutamol (100 mcg per puff) or equivalent,
except in acute, severe asthma when six puffs should be given. When a nebulizer is used, a dose of 2.5 mg salbutamol
solution is recommended, and infection control procedures should be followed. The frequency of dosing depends on the
response observed over 1–2 hours (see below).
For children with moderate-severe exacerbations and a poor response to initial SABA, nebulized ipratropium bromide
may be added every 20 minutes for 1 hour only.809

Magnesium sulfate
The role of magnesium sulfate is not established for children 5 years and younger, because there are few studies in this
age group. Nebulized isotonic magnesium sulfate may be considered as an adjuvant to standard treatment with
nebulized salbutamol and ipratropium in the first hour of treatment for children ≥2 years old with acute severe asthma

6. Diagnosis and management of asthma in children 5 years and younger 191

 (e.g. oxygen saturation <92%, Box 6-10, p.190), particularly those with symptoms lasting <6 hours.810 Intravenous
magnesium sulfate in a single dose of 40–50 mg/kg (maximum 2 g) by slow infusion (20–60 minutes) has also been
used.811

Assessment of response and additional bronchodilator treatment

Children with a severe asthma exacerbation must be observed for at least 1 hour after initiation of treatment, at which
time further treatment can be planned.
• If symptoms persist after initial bronchodilator: a further 2–6 puffs of salbutamol (depending on severity) may be
given 20 minutes after the first dose and repeated at 20-minute intervals for an hour. Consider adding 1–2 puffs of
ipratropium. Failure to respond at 1 hour, or earlier deterioration, should prompt urgent admission to hospital,
addition of nebulized ipratropium, and a short-course of oral corticosteroids (Evidence D).
• If symptoms have improved by 1 hour but recur within 3–4 hours: the child may be given more frequent doses of
bronchodilator (2–3 puffs each hour), and oral corticosteroids should be given. The child may need to remain in
the emergency department, or, if at home, should be observed by the family/carer and have ready access to

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emergency care. Children who fail to respond to 10 puffs of inhaled SABA within a 3–4 hour period should be

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referred immediately to hospital (Evidence D).

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• If symptoms resolve rapidly after initial bronchodilator and do not recur for 1–2 hours: no further treatment may be

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required. Further SABA may be given every 3–4 hours (up to a total of 10 puffs/24 hours) and, if symptoms persist

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beyond 1 day, other treatments including inhaled and/or oral corticosteroids are indicated (Evidence D), as

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outlined below.
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Box 6-12.Initial emergency department management of asthma exacerbations in children 5 years and younger
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O
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Therapy Dose and administration

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Supplemental oxygen Delivered by face nasal prongs or mask, as indicated to maintain oxygen saturation at 94–
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98%
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Short-acting beta2- 2–6 puffs of salbutamol [albuterol] by spacer, or 2.5 mg by nebulizer, every 20 minutes for
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agonist (SABA) first hour*, then reassess severity. If symptoms persist or recur, give an additional 2–3 puffs
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per hour. Admit to hospital if >10 puffs required in 3–4 hours.

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Systemic Give initial dose of oral prednisolone (1–2 mg/kg up to a maximum 20 mg for children
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corticosteroids <2 years old; 30 mg for children 2–5 years)

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OR, intravenous methylprednisolone 1 mg/kg 6-hourly on day 1

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Additional options in the first hour of treatment

Ipratropium bromide Consider adding 1–2 puffs of ipratropium bromide by pMDI and spacer
For children with moderate-severe exacerbations with a poor response to initial SABA,
give nebulized ipratropium bromide 250 mcg every 20 minutes for 1 hour only

Magnesium sulfate Consider nebulized isotonic magnesium sulfate (150 mg) 3 doses in the first hour of
treatment for children aged ≥2 years with severe exacerbation (Box 6-10, p.190)

See list of abbreviations (p.10). *If inhalation is not possible an intravenous bolus of terbutaline 2 mcg/kg may be given over 5 minutes, followed by
continuous infusion of 5 mcg/kg/hour812 (Evidence C). The child should be closely monitored, and the dose should be adjusted according to clinical
improvement and side-effects. See below for additional and ongoing treatment, including maintenance ICS. If a nebulizer is used, follow infection control
procedures.

192 6. Diagnosis and management of asthma in children 5 years and younger

Additional treatment
When treatment in addition to SABA is required for an exacerbation, the options available for children in this age group
include ICS; a short course of oral corticosteroid; and/or LTRA (see p.188). However, the clinical benefit of these
interventions – particularly on endpoints such as hospitalizations and longer-term outcomes – has not been impressive.
Maintain current controller treatment (if prescribed)
Children who have been prescribed maintenance therapy with ICS, LTRA or both should continue to take the prescribed
dose during and after an exacerbation (Evidence D).
Inhaled corticosteroids
For children not previously on ICS, an initial dose of ICS twice the low daily dose indicated in Box 6-7 (p.184) may be
given and continued for a few weeks or months (Evidence D). Some studies have used high-dose ICS (1600 mcg/day,
preferably divided into four doses over the day and given for 5–10 days) as this may reduce the need for
OCS.649,784,785,813,814 Addition of ICS to standard care (including OCS) does not reduce risk of hospitalization but reduces

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length of stay and acute asthma scores in children in the emergency department.815 However, the potential for side-

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effects with high-dose ICS should be taken into account, especially if used repeatedly, and the child should be

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monitored closely. For those children already on ICS, doubling the dose was not effective in a small study of mild-

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moderate exacerbations in children aged 6–14 years,816 nor was quintupling the dose in children aged 5–11 years with

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good adherence. This approach should be reserved mainly for individual cases, and should always involve regular

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follow-up and monitoring of adverse effects (Evidence D).
Oral corticosteroids
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For children with severe exacerbations, a dose of OCS equivalent to prednisolone 1–2 mg/kg/day, with a maximum of
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20 mg/day for children under 2 years of age and 30 mg/day for children aged 2–5 years, is currently recommended
N

(Evidence A),817 although several studies have failed to show any benefits when given earlier (e.g. by parents or
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caregivers) during periods of worsening wheeze managed in an outpatient setting (Evidence D).801-804,818,819 A meta-
analysis demonstrated a reduced risk of hospitalization when oral corticosteroids were administered in the emergency
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department, but no clear benefit in risk of hospitalization when given in the outpatient setting.820 A course of 3–5 days is
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sufficient in most children of this age, and can be stopped without tapering (Evidence D), but the child must be reviewed
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after discharge (as below) to confirm they are recovering.

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In children discharged from the emergency department, an intramuscular corticosteroid may be an alternative to a
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course of OCS for preventing relapse,681 but the risk of long-term adverse effects must be considered. There is
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insufficient evidence to recommend intramuscular over oral corticosteroids.681

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Regardless of treatment, the severity of the child’s symptoms must be carefully monitored. The sooner therapy is started
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in relation to the onset of symptoms, the more likely it is that the impending exacerbation may be clinically attenuated or
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prevented.

Discharge and follow up after an exacerbation

Before discharge, the condition of the child should be stable (e.g., he/she should be out of bed and able to eat and
drink without problems).
Children who have recently had an asthma exacerbation are at risk of further exacerbations and require follow up. The
purpose is to ensure complete recovery, to establish the cause of the exacerbation, and, when necessary, to establish
appropriate maintenance treatment and adherence (Evidence D).

6. Diagnosis and management of asthma in children 5 years and younger 193

 Prior to discharge from the emergency department or hospital, family/carers should receive the following advice and
information (all are Evidence D).
• Instruction on recognition of signs of recurrence and worsening of asthma. The factors that precipitated the
exacerbation should be identified, and strategies for future avoidance of these factors implemented.
• A written, individualized action plan, including details of accessible emergency services
• Careful review of inhaler technique
• Further treatment advice explaining that:
o SABAs should be used on an as-needed basis, but the daily requirement should be recorded to ensure it is
being decreased over time to pre-exacerbation levels.
o ICS has been initiated where appropriate (at twice the low initial dose in Box 6-7 (p.184) for the first month
after discharge, then adjusted as needed) or continued, for those previously prescribed controller medication.
• A supply of SABA and, where applicable, the remainder of the course of oral corticosteroid, ICS or LTRA

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• A follow-up appointment within 1–2 days and another within 1–2 months, depending on the clinical, social and

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practical context of the exacerbation.

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T
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N
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194 6. Diagnosis and management of asthma in children 5 years and younger

 SECTION 2. CHILDREN 5 YEARS AND YOUNGER

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Chapter 7.

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Primary prevention
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of asthma in children
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KEY POINTS

• The development and persistence of asthma are driven by gene–environment interactions. For children, a ‘window
of opportunity’ to prevent asthma exists in utero and in early life, but intervention studies are limited.
• With regard to allergen avoidance strategies aimed at preventing asthma in children:
o Strategies directed at a single allergen have not been effective in reducing the incidence of asthma
o Multifaceted strategies may be effective, but the essential components have not been identified.
• Current recommendations for preventing asthma in children, based on high-quality evidence or consensus, include:
o Avoid exposure to environmental tobacco smoke during pregnancy and the first year of life.
o Encourage vaginal delivery.
o Where possible, avoid use of broad-spectrum antibiotics during the first year of life.
• Breast-feeding is advised, not for prevention of allergy and asthma, but for its other positive health benefits).

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FACTORS CONTRIBUTING TO THE DEVELOPMENT OF ASTHMA IN CHILDREN

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Asthma is a heterogeneous disease whose inception and persistence are driven by gene–environment interactions that

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are not yet fully understood. The most important of these interactions may occur in early life and even in utero. There is

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consensus that a ‘window of opportunity’ exists during pregnancy and early in life when environmental factors may

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influence asthma development. Multiple environmental factors, both biological and sociological, may be important in the

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development of asthma. Data from studies investigating the role of environmental risk factors for the development of
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asthma support further research on prevention strategies focusing on nutrition, allergens (both inhaled and ingested),
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pollutants (particularly environmental tobacco smoke), microbes, and psychosocial factors.

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‘Primary prevention’ refers to preventing the onset of disease. This chapter focuses on primary prevention in children.
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See p.116 and review articles49 for strategies for preventing occupational asthma.
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FACTORS ASSOCIATED WITH INCREASED OR DECREASED RISK OF ASTHMA IN CHILDREN

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Nutrition of mother and baby

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Maternal diet
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A large body of research investigating the development of allergy and asthma in children has focused on the mother’s
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diet during pregnancy. Current evidence does not clearly demonstrate that ingestion of any specific foods during
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pregnancy increases the risk for asthma. However, a study of a pre-birth cohort observed that maternal intake of foods
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commonly considered allergenic (peanut and milk) was associated with a decrease in allergy and asthma in the
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offspring.821 Similar data have been shown in a very large Danish National birth cohort, with an association between
ingestion of peanuts, tree nuts and/or fish during pregnancy and a decreased risk of asthma in the offspring.822,823
Epidemiological studies and randomized controlled trials on maternal dietary intake of fish or long-chain polyunsaturated
fatty acids during pregnancy showed no consistent effects on the risk of wheeze, asthma or atopy in the child.824-827
Dietary changes during pregnancy are therefore not recommended for prevention of allergies or asthma.
Maternal obesity and weight gain during pregnancy
Data suggest that maternal obesity and weight gain during pregnancy pose an increased risk for asthma in children. A
meta-analysis828 showed that maternal obesity in pregnancy was associated with higher odds of ever asthma or wheeze
or current asthma or wheeze; each 1 kg/m2 increase in maternal body-mass index (BMI) was associated with a 2% to
3% increase in the odd of childhood asthma. High gestational weight gain was associated with higher odds of ever
asthma or wheeze. However, no recommendations can be made at present, as unguided weight loss in pregnancy
should not be encouraged.

196 7. Primary prevention of asthma

Breastfeeding
Despite the existence of many studies reporting a beneficial effect of breastfeeding on asthma prevention, results are
conflicting,829 and caution should be taken in advising families that breastfeeding will prevent asthma.830 Breastfeeding
decreases wheezing episodes in early life; however, it may not prevent development of persistent asthma (Evidence D).
Regardless of any effect on development of asthma, breastfeeding should be encouraged for all of its other positive
benefits (Evidence A).
Timing of introduction of solids
Beginning in the 1990s, many national pediatric agencies and societies recommended delay of introduction of solid food,
especially for children at a high risk for developing allergy. However, meta-analyses have found no evidence that this
practice reduces the risk of allergic disease (including asthma).831 In the case of peanuts, early introduction may prevent
peanut allergy in high risk infants.831

Dietary supplements for mothers and/or babies

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Vitamin D

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Intake of vitamin D may be through diet, dietary supplementation or sunlight. A systematic review of cohort, case control

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and cross-sectional studies concluded that maternal dietary intake of vitamin D, and of vitamin E was associated with

D
lower risk of wheezing illnesses in children.832 This was not confirmed in two randomized controlled trials (RCTs) of

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vitamin D supplementation in pregnancy, which compared standard-dose with high-dose vitamin D; however, a

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significant effect was not disproven.833,834 When the results from these two trials were combined, there was a 25%
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reduction of risk of asthma/recurrent wheeze at ages 0–3 years.835 The effect was greatest among women who
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maintained 25(OH)vitamin D levels of at least 30 ng/mL from the time of study entry through delivery, suggesting that
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sufficient levels of Vitamin D during early pregnancy may be important in decreasing risk for early life wheezing
N

episodes,835 although in both trials, no effects of vitamin D supplementation on the development of asthma and recurrent
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wheeze were evident at the age of 6 years.836

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Fish oil and long-chain polyunsaturated fatty acids

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Systematic reviews of cohort studies about maternal dietary intake of fish or seafood during pregnancy824,837 and of
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RCTs on maternal dietary intake of fish or long-chained polyunsaturated fatty acids during pregnancy824 showed no
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consistent effects on the risk of wheeze, asthma or atopy in the child. One study demonstrated decreased
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wheeze/asthma in preschool children at high risk for asthma when mothers were given a high-dose fish oil supplement
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in the third trimester;838 however ‘fish oil’ is not well defined, and the optimal dosing regimen has not been established.
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Probiotics
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A meta-analysis provided insufficient evidence to recommend probiotics for the prevention of allergic disease (asthma,
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rhinitis, eczema or food allergy).839

Inhalant allergens
Sensitization to indoor, inhaled aeroallergens is generally more important than sensitization to outdoor allergens for the
presence of, and/or development of, asthma. While there appears to be a linear relationship between exposure and
sensitization to house dust mite,840,841 the relationship for animal allergen appears to be more complex.829 Some studies
have found that exposure to pet allergens is associated with increased risk of sensitization to these allergens,842,843 and
of asthma and wheezing.844,845 By contrast, other studies have demonstrated a decreased risk of developing allergy with
exposure to pets.846,847 Analyses of data from large populations of school-age children from birth cohorts in Europe have
found no association between pets in the homes early in life and higher or lower prevalence of asthma in children.848,849
For children at risk of asthma, dampness, visible mold and mold odor in the home environment are associated with
increased risk of developing asthma.850 Overall, there are insufficient data to recommend efforts to either reduce or
increase pre-natal or early-life exposure to common sensitizing allergens, including pets, for the prevention of allergies
and asthma.

7. Primary prevention of asthma 197

 Birth cohort studies provide some evidence for consideration. A meta-analysis found that studies of interventions
focused on reducing exposure to a single allergen did not significantly affect asthma development, but that multifaceted
interventions such as in the Isle of Wight study,851 the Canadian Asthma Primary Prevention Study,852 and the
Prevention of Asthma in Children study853 were associated with lower risk of asthma diagnosis in children younger than
5 years.854 Two multifaceted studies that followed children beyond 5 years of age demonstrated a significant protective
effect both before and after the age of 5 years.851,855 The Isle of Wight study has shown a continuing positive benefit for
early-life intervention through to 18 years of age;856 however, it remains unclear which components of the intervention
contributed to the effects reported, and the precise mechanism of these effects.
Treatment with grass pollen sublingual allergen immunotherapy (SLIT) for 3 years did not reduce the incidence of
asthma diagnosis (primary outcome) in a large randomized double-blind placebo-controlled trial in children aged 5–12
years with grass-allergic rhinoconjunctivitis, but asthma symptoms and asthma medication use were reduced. At
present, SLIT for children with grass allergic rhinoconjunctivitis is not recommended for asthma prevention.857 Additional
studies are needed.

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Pollutants

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Maternal smoking during pregnancy is the most direct route of pre-natal environmental tobacco smoke exposure.858 A

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meta-analysis concluded that prenatal smoking had its strongest effect on young children, whereas postnatal maternal

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smoking appeared only to affect asthma development in older children.859 Exposure to outdoor pollutants, such as living

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near a main road, is associated with increased risk of asthma.860,861 A 2019 study suggested that up to 4 million new

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pediatric asthma cases (13% of the global incidence) may be attributable to exposure to traffic-related air pollution.862
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Prenatal NO2, SO2, and PM10 exposures are associated with an increased risk of asthma in childhood,863 but it is
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difficult to separate effects of prenatal and postnatal exposure.
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Microbial effects
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The ‘hygiene hypothesis’, and the more recently coined ‘microflora hypothesis’ and ‘biodiversity hypothesis’,864 suggest
that human interaction with microbiota may be beneficial in preventing asthma. For example, there is a lower risk of
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asthma among children raised on farms with exposure to stables and consumption of raw farm milk than among children
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of non-farmers.865 The risk of asthma is also reduced in children whose bedrooms have high levels of bacterial-derived
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lipopolysaccharide endotoxin.866,867 Similarly, children in homes with ≥2 dogs or cats are less likely to be allergic than
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those in homes without dogs or cats.847 Exposure of an infant to the mother’s vaginal microflora through vaginal delivery
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may also be beneficial; the prevalence of asthma is higher in children born by cesarean section than those born
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vaginally.868,869 This may relate to differences in the infant gut microbiota according to their mode of delivery.870
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Respiratory syncytial virus infection is associated with subsequent recurrent wheeze, and preventative treatment of
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premature infants with monthly injections of the monoclonal antibody, palivizumab, (prescribed for prophylaxis of
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respiratory syncytial virus) is associated with a reduction in recurrent wheezing in the first year of life.871 However, a
sustained effect has not been definitively demonstrated. Although the risk of parent-reported asthma with infrequent
wheeze was reduced at 6 years, there was no impact on doctor-diagnosed asthma or lung function.872 Thus, the long-
term effect of palivizumab in the prevention of asthma remains uncertain.

Medications and other factors

Antibiotic use during pregnancy and in infants and toddlers has been associated with the development of asthma later in
life,873 although not all studies have shown this association.874 Intake of the analgesic, paracetamol (acetaminophen),
may be associated with an increased risk of asthma in both children and adults,875 although exposure during infancy
may be confounded by use of paracetamol for respiratory tract infections.875 Frequent use of paracetamol by pregnant
women has been associated with increased risk of asthma in their children.876
There is no evidence that vaccinations increase a child’s risk of developing asthma.

198 7. Primary prevention of asthma

Psychosocial factors
The social environment to which children are exposed may also contribute to the development and severity of asthma.
Maternal distress during pregnancy877 or during the child’s early years878 has been associated with an increased risk of
the child developing asthma.

Obesity
A meta-analysis of 18 studies found that being either overweight or obese was a risk factor for childhood asthma and
wheeze, particularly in girls.483 In adults, there is evidence suggesting that obesity affects the risk of asthma, but that
asthma does not affect the risk of obesity.879,880

ADVICE ABOUT PRIMARY PREVENTION OF ASTHMA

Based on the results of cohort and observational studies,881 and a GRADE-based analysis conducted for the Allergic
Rhinitis and its Impact on Asthma (ARIA) guidelines,829 parents/caregivers enquiring about how to reduce the risk of

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their children developing asthma can be provided with the advice summarized in Box 7-1.

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Possibly the most important factor is the need to provide a positive, supportive environment for discussion that

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decreases stress, and which encourages families to make choices with which they feel comfortable.

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Box 7-1. Advice about primary prevention of asthma in children 5 years and younger

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Parents/caregivers enquiring about how to reduce the risk of their child developing asthma can be provided with the
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following advice:
O
N

• Children should not be exposed to environmental tobacco smoke during pregnancy or after birth.
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• Identification and correction of Vitamin D insufficiency in women with asthma who are pregnant, or planning
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pregnancy, may reduce the risk of early life wheezing episodes.

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• Vaginal delivery should be encouraged where possible.

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• The use of broad-spectrum antibiotics during the first year of life should be discouraged.
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Breastfeeding is advised, not for prevention of allergy or asthma, but for its other positive health benefits.
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7. Primary prevention of asthma 199