Introduction

Asthma is an incredibly common and chronic airway condition which affects greater than 12% of the population, with approximately 160,000 people per year receiving an asthma diagnosis. Children diagnosed with asthma often grow out of the condition, however it can return later in life, with the highest prevalence in the 16 to 20-year-old age group. It is important for this condition to be identified and managed appropriately, as poorly controlled asthma can cause significant morbidity and can be fatal.

Epidemiology

  • Incidence: 800.00 cases per 100,000 person-years
  • Peak incidence: 6-15 years
  • Sex ratio: 1:1
Condition Relative
incidence
Asthma in children1
Bronchiolitis0.63
Inhaled foreign body0.002
Cystic fibrosis0.0003
<1 1-5 6+ 16+ 30+ 40+ 50+ 60+ 70+ 80+

Aetiology

Asthma is a complex respiratory condition which is likely multi-factorial, with a number of environmental and genetic influences resulting in the condition.

Genetic factors
  • Family history
    • Those with a family history of asthma or other atopic conditions are far more likely to also develop asthma, more commonly in childhood than adulthood
    • Twin studies have estimated that genetic factors may contribute >75% of the risk variance
  • Sex
    • Childhood asthma tends to be more common in males
    • However, this gender predominance tends to even out once in adulthood

Pre and peri-natal factors
  • Poor maternal asthma control
    • In pregnant mothers, poor asthma control increases the likelihood of the offspring developing asthma
    • Therefore, it is imperative to ensure adequate control during pregnancy
  • Maternal smoking
    • Pre-natal exposure to maternal smoking is an established risk factor for developing asthma
    • In-utero exposure is associated with greater likelihood of more severe childhood asthma and persistence to adulthood
  • Prematurity
    • Fetal prematurity is a risk factor for developing asthma
    • The shorter the gestational duration, the greater the risk

Environmental factors
  • Exposure to allergens
    • The exposure to indoor allergens (particularly dust mites, animal proteins and fungi) is related to development of asthma in children
    • Sensitisation to these allergens is important in the pathophysiological processes which lead to asthma development
  • Respiratory infections
    • Respiratory infections, both viral and bacterial, are known to be triggers for acute exacerbations of asthma
    • It is unclear at this point whether respiratory infections are a cause, a marker of susceptibility, or a trigger for asthma (or potentially, all of the above)
    • Infection with respiratory syncitial virus (RSV) in early life has been particularly implicated, and is predictive of development of asthma in later childhood
    • The theory has been proposed that lower respiratory tract infection promotes sensitisation to aeroallergens
  • Exposure to passive smoking
    • Passive smoking increases the risk of allergic sensitisation and therefore the development of asthma
    • In children exposed to passive smoking, it increases the frequency and severity of symptoms, particularly increasing the likelihood of a severe asthma exacerbation

Pathophysiology

Asthma is a condition characterised by variable airflow limitation and airway hyper-responsiveness in response to a number of stimuli. With ongoing inflammation, it can eventually result in permanent airway remodelling and therefore limitations in the reversibility of airflow limitation.

Variable airflow limitation
  • A key feature of asthma is that the airflow limitation is variable and reversible
  • The airflow obstruction is as a result of three factors: smooth muscle constriction, mucous production, and bronchial inflammation
  • Smooth muscle constriction
    • Accounts for many of the rapid changes in airflow limitation
    • Due to the direct effects of contractile agonists released from inflammatory cells (e.g. mast cells, eosinophils)
    • The basis for bronchodilator therapy via beta-agonists is due to the direct relaxation of airway smooth muscle cells and therefore airway dilation
  • Bronchial inflammation
    • Inflammation results from IgE-dependent release of mediators from mast cells
    • Such mediators include histamine, tryptase, leukotrienes and prostaglandins
    • These mediators directly cause stimulation and contraction of airway smooth muscle, resulting in further bronchoconstriction
    • With ongoing inflammation, it results in further oedema and therefore worsened airflow limitations
  • Mucous production
    • Mucous hypersecretion, somewhat as a result from ongoing inflammation, leads to further airflow limitations
    • May result in formation of mucous plugs which further block small airways and reduce further airflow

Airway hyper-responsiveness
  • Bronchial hyper-responsiveness manifests as an exaggerated constrictor response to a variety of stimuli
  • This accounts for the sudden onset in clinical symptoms when triggered by stimuli such as cold air or irritants in the air
  • The mechanism of airway hyper-responsiveness is multifactorial, including due to inflammation, dysfunctional neuroregulation, and structural airway changes

Airway remodelling
  • Although asthma is characteristically described as a variable and reversible airflow limitation, overtime airway remodelling can mean that airway limitation is only partially reversible
  • Due to ongoing inflammation, it can result in permanent structural changes
  • Such changes include thickening of the sub-basement membrane, sub-epithelial fibrosis, airway smooth muscle cell hypertrophy and hyperplasia, and mucous gland hyperplasia and subsequent hypersecretion

Clinical features

Asthma typically presents as recurrent episodes of wheezing, coughing, and shortness of breath. However, the most common symptom of childhood asthma is coughing alone, and some children may present with this as the sole complaint.

Symptoms
  • Cough
    • A nocturnal cough should raise suspicion for asthma, particularly if it lasts for >3 weeks or if triggered by particular seasons or allergens
    • Typically dry and non-productive in nature
    • Infrequently may be productive of clear or white sputum
  • Shortness of breath
    • This occurs usually on exertion or on exposure to triggers (e.g. cold air, tobacco smoke, crying, exercise)
    • May accompany wheeze and cough during an exacerbation, but is rarely solely present

Signs
  • Wheeze
    • In over 60%, wheezing does not persist into late childhood
    • Typically expiratory, however in severe airway obstruction may be inspiratory also
    • Usually polyphonic (variable pitch)
    • Can typically be heard without use of a stethoscope, but for some the wheeze may be subtle
    • The NICE guidelines note to be aware in the case of normal examination findings, as asthma is episodic and therefore signs may not be present at time of examination
  • Silent chest
    • In severe asthma exacerbations, the wheeze may disappear and no airway sounds may be heard, termed a 'silent chest'
    • This is a medical emergency, as the airway obstruction is so significant that no airflow is occurring
  • Increased work of breathing
    • Tachypnoea
    • Use of accessory muscles of respiration (e.g. abdominal breathing, intercostal/suprasternal/costal margin retractions, sternocleidomastoid contraction resulting in head bobbing)
    • Nasal flaring
    • Sitting in forward posture

Severe asthma exacerbation
  • There are a number of clinical features which, when present, may suggest a severe or critical episode of asthma
  • These include:
    • Altered mental state (e.g. confusion, drowsiness)
    • Maximal work of breathing accessory muscle use/recession
    • Exhaustion
    • Significant tachycardia
    • Unable to talk
    • Silent chest (note: wheeze is typically a poor predictor of severity)

Investigations

There are a number of investigations available to confirm a suspected asthma diagnosis, however the utility of these will depend on the age of the child. In a child less than 5-years-old, the NICE guidelines recommend treating symptoms based on a clinical diagnosis without any investigations, and then to carry out testing if symptoms are still present at 5-years-old.

If a child is unable to perform the following tests once aged 5-years old, the NICE guidelines recommend trying to complete the tests again every 6-12 months whilst continuing to treat based on a clinical diagnosis. It is important to consider referral to a specialist if investigations cannot be performed repeatedly, or if treatment is not resulting in a clinical improvement.

Spirometry
  • The NICE guidelines suggest offering spirometry to children aged over 5-years-old if a diagnosis of asthma is being considered
  • A forced expiratory volume in 1 second to forced vital capacity (FEV1:FVC) ratio of less than 70% is suggestive of obstructive airway disease
  • Bronchodilator reversibility
    • To be classified as asthma, obstructive airway disease needs to show an element of reversibility, and therefore testing with bronchodilators is necessary
    • For children aged 5 to 16-years-old, an improvement in FEV1 of >12% is suggestive of asthma
    • For children aged 17 years-old and older, an improvement in FEV1 of >12%, plus an increase in volume of >200mL, is suggestive of asthma

Fraction exhaled nitric oxide
  • This can be considered in children aged 5 to 16-years-old if there is diagnostic uncertainty after initial investigations (e.g. normal spirometry, presence of negative bronchodilator reversibility)
    • A fraction exhaled nitric oxide level of greater than 35 parts per billion (ppb) is suggestive of asthma

Peak expiratory flow
  • Peak expiratory flow can be completed at home or at the bedside using a portable tool, and this tool should remain consistent throughout testing (as in, a patient should not use multiple peak expiratory flow meters)
  • The NICE guidelines suggest monitoring peak flow variability for 2-4 weeks if there is any diagnostic uncertainty
  • Greater than 20% variability is considered a positive test, suggestive of asthma
  • After diagnosis and treatment, peak expiratory flow can also be used as an indicator of treatment effect and a marker of clinical improvement/deterioration

Differential diagnosis

In the early years of life (less than 5-years-old), confirmatory testing for asthma is virtually impossible, therefore other causes of the clinical symptoms need to be considered, particularly if there is failure to respond to medical treatment. Typically, as cough is the most common presenting feature, causes of a chronic cough in children should be considered highly.

Viral induced wheeze
  • Similarities
    • Both can present with wheeze
    • Both may have a cough
    • Asthma may be exacerbated by a viral infection, and viral induced wheeze similarly presents with a viral infection
  • Differences
    • Viral induced wheeze tends to occur in children under the age of 3-years-old, whereas asthma tends to occur in children over this age
    • Prior to diagnosis, asthma tends to present with a regular daily wheeze (with periods of worsening at times), whereas viral induced wheeze tends to occur in singular or intermittent episodes initiated by a viral infection
    • Children with asthma tend to present with interval symptoms (e.g. regular cough/wheeze at night or early morning, and/or with exercise), whereas this is not as common with viral-induced wheeze

Bronchiolitis
  • Similarities
    • Both more common in childhood
    • Both associated with exposure to tobacco smoke
    • Both will have evidence of a polyphonic wheeze on auscultation
    • May be recurrent episodes
  • Differences
    • Children with bronchiolitis will typically have a prodrome of rhinorrhoea, cough and intermittent fever, followed by wheezing and tachypnoea
    • In bronchiolitis, the child may present otherwise unwell with fevers, fatigue and/or reduced feeding

Protracted bacterial bronchitis
  • Similarities
    • Both can present with wheeze
    • Cough is typical in both
  • Differences
    • Bronchitis will characteristically have a moist and productive cough, whereas the cough in asthma is typically dry
    • Sputum culture or bronchoalveolar lavage will isolate a bacteria, commonly Haemophilus influenzae, Streptococcus pneumoniae or Moraxella catarrhalis
    • Will not respond to inhaled or oral steroid therapy

Inhaled foreign body
  • Similarities
    • Both may present with cough and wheeze
    • Child will be otherwise well with no signs of infective disease e.g. absence of fever, fatigue, malaise
    • An episode of asthma and inhalation of a foreign body can both appear with sudden onset and deterioration
    • A chronic inhaled foreign body similarly can cause recurrent episodes of wheeze
  • Differences
    • Inhaled foreign bodies typically cause an inspiratory stridor, rather than an expiratory wheeze
    • May present with choking

Cystic fibrosis
  • Similarities
    • Both can present with wheeze, cough and shortness of breath
    • Asthma and cystic fibrosis can co-exist
    • Wheeze, cough and breathlessness may worsen with a concurrent respiratory tract infection in both
  • Differences
    • Cough is typically moist and productive
    • In children with cystic fibrosis, they may present with poor growth/failure to thrive
    • May also have foul-smelling or greasy stools, and/or chronic diarrhoea

Structural airway abnormality
  • Similarities
    • Tracheomalacia/bronchomalacia and asthma both can present with cute episodes of wheeze, dyspnoea and cough
    • Both typically more common in children
  • Differences
    • Broncho/tracheomalacia tend to be characterised by expiratory stridor or monophonic expiratory wheeze
    • Non-responsive to inhaled or oral steroids or bronchodilators
    • More common in first two years of life, asthma tends to present from after 2-years-old

Management

NICE released guidance on the management of asthma in 2017. These followed on quickly from the 2016 British Thoracic Society (BTS) guidelines. Given previous precedents where specialist societies or Royal colleges eventually default/contribute to NICE, we have followed the NICE guidance for the notes and questions.

Children aged 5-16 with asthma are now managed in a very similar way to adults

Children and young people aged 5 to 16

NICE do not follow the stepwise approach of the previous BTS guidelines. However, to try to make the guidelines easier to follow we've added our own steps:

StepNotes
1

Newly-diagnosed asthma
Short-acting beta agonist (SABA)
2

Not controlled on previous step
OR
Newly-diagnosed asthma with symptoms >= 3 / week or night-time waking
SABA + paediatric low-dose inhaled corticosteroid (ICS)
3SABA + paediatric low-dose ICS + leukotriene receptor antagonist (LTRA)
4SABA + paediatric low-dose ICS + long-acting beta agonist (LABA)

In contrast to the adult guidance, NICE recommend stopping the LTRA at this point if it hasn't helped
5SABA + switch ICS/LABA for a maintenance and reliever therapy (MART), that includes a paediatric low-dose ICS
6SABA + paediatric moderate-dose ICS MART

OR consider changing back to a fixed-dose of a moderate-dose ICS and a separate LABA
7SABA + one of the following options:
  • increase ICS to paediatric high-dose, either as part of a fixed-dose regime or as a MART
  • a trial of an additional drug (for example theophylline)
  • seeking advice from a healthcare professional with expertise in asthma


Children aged less than 5 years

Clearly, it can be difficult to definitively diagnose asthma in young children. NICE acknowledge the greater role for clinical judgement in this age group.

Again, the stepwise approach is our own rather than NICE's:

StepNotes
1

Newly-diagnosed asthma
Short-acting beta agonist (SABA)
2

Not controlled on previous step
OR
Newly-diagnosed asthma with symptoms >= 3 / week or night-time waking
SABA + an 8-week trial of paediatric MODERATE-dose inhaled corticosteroid (ICS)

After 8-weeks stop the ICS and monitor the child's symptoms:
  • if symptoms did not resolve during the trial period, review whether an alternative diagnosis is likely
  • if symptoms resolved then reoccurred within 4 weeks of stopping ICS treatment, restart the ICS at a paediatric low dose as first-line maintenance therapy
  • if symptoms resolved but reoccurred beyond 4 weeks after stopping ICS treatment, repeat the 8‑week trial of a paediatric moderate dose of ICS
3SABA + paediatric low-dose ICS + leukotriene receptor antagonist (LTRA)
4Stop the LTRA and refer to an paediatric asthma specialist

Other points

Maintenance and reliever therapy (MART)
  • a form of combined ICS and LABA treatment in which a single inhaler, containing both ICS and a fast-acting LABA, is used for both daily maintenance therapy and the relief of symptoms as required
  • MART is only available for ICS and LABA combinations in which the LABA has a fast-acting component (for example, formoterol)

It should be noted that NICE does not advocate changing treatment in patients who have well-controlled asthma simply to adhere to the latest guidance.

Table showing examples of inhaled corticosteroid doses

Frustratingly, the definitions of what constitutes a low, moderate or high-dose ICS have also changed. In contrast to the BTS guidelines NICE also have different definitions for adults and children. For children:
  • <= 200 micrograms budesonide or equivalent = paediatric low dose
  • 200 micrograms - 400 micrograms budesonide or equivalent = paediatric moderate dose
  • > 400 micrograms budesonide or equivalent= paediatric high dose.

Prognosis

Childhood asthma is commonly grown out of, with three our of four school-aged children outgrowing the condition by adulthood. In those who do not fully outgrow the condition, approximately 50% of children will have markedly improved or become asymptomatic by early adulthood. Those with childhood onset asthma, as compared to adult onset asthma, are far more likely to experience a complete remission from the condition.

Predictors of persistent asthma
  • Atopy
    • Presence of concurrent allergic rhinitis and/or atopic dermatitis
  • Low lung function
    • Significantly decreased peak expiratory flow and/or reduced FEV1:FVC ratio
  • Higher airway hyper-responsiveness
  • Sensitisation and exposure to indoor allergens
    • Three-fold increased risk of persistent asthma

Long-term effect on lung function
  • Although asthma can be grown out of, asthma in early childhood does result in slight decrements in pulmonary function compared to those who have never experienced asthma
  • Those at higher risk of long-term airway damage include those children with poor adherence to treatment, those with poorly controlled asthma, and those with recurrent severe exacerbations requiring hospital admission
  • Features of poorly controlled asthma include:
    • 3+ days per week with symptoms, or
    • 3+ days per week requiring use of a bronchodilator for symptomatic relief, or
    • 1+ night per week awakening due to asthma symptoms
  • These decrements are persistent throughout childhood and adolescence, and can sometimes persist to adulthood also
  • Decrements include reduced peak forced expiratory volume in one second (FEV1), or an early decline in lung function in adulthood (therefore more susceptible to chronic lung conditions)
  • However, these decrements are not associated with an increased mortality risk

Mortality
  • Well-controlled childhood asthma does not cause an increased risk of mortality compared to that of the general population
  • Poorly controlled asthma (e.g. inadequate medical therapy, poor compliance) and recurrent severe exacerbations increase the risk of mortality if not managed appropriately
  • In the UK, on average, 3 people die from a severe asthma attack per year
  • These children should certainly be referred to a specialist to reduce the morbidity and mortality