Clinical Review - Asthma in children

Section 1: Epidemiology and aetiology
Asthma in children causes repeated attacks of airway obstruction and intermittent symptoms of increased air-way responsiveness to triggering factors such as exercise, allergen exposure and viral infections.

A large-scale international study of asthma and allergy in childhood (ISAAC) found that the UK, Australia and New Zealand had among the highest prevalences, with 15 per cent of children affected.¹

Sequential asthma studies in the UK have detected an increase in asthma over the past 25 years. The increase appears to peak, and phase III of ISAAC has shown a fall in the prevalence, at least in some regions.

Asthma is more prevalent in children with a family history of atopy, and symptoms and exacerbations are provoked by a wide range of triggers including viral infections, indoor and outdoor allergens, exercise, tobacco smoke and poor air quality.

Studies have investigated various treatments in older children with classic allergic asthma, yet relatively few have considered the many young children who have a recurrent wheeze.

Many common treatments now have a good evidence base in older children, but gaps still exist, such as treatments for the most difficult and severe childhood asthma, and preschool wheeze.

Therapeutic advances include both new drugs and new licences for older drugs. Yet despite an increasing number of therapeutic options, children still die from asthma. There were 23 recorded deaths in 2002 in the UK.

Aetiology
Asthma is a complex immune-mediated multifactorial disease in older children; evidence for an inflammatory basis in preschool wheeze is less compelling.

There is a clear genetic component; more strongly inherited from the mother.²

Airway narrowing in asthma is a combination of bronchial smooth muscle constriction and obstruction of the lumen by airway wall oedema and inflammatory exudates. The relative contribution of these varies between children and between attacks in the same child.

An increasing body of evidence suggests that asthma is a complex disorder (a syndrome) and that different patterns of illness have different underlying pathogenesis.

Viral-associated wheeze
Episodic viral wheeze is common; 30-50 per cent of preschool children have at least one episode. Some young children with atopic asthma start with a pattern of episodic viral wheeze before more persistent features surface, but most of those with pure episodic viral wheeze tend to outgrow their symptoms as they get older.

Atopic asthma
Atopic asthma commonly presents as the school-aged child with episodic wheeze, cough and shortness of breath, often with identifiable non-viral triggers and other stigmata of atopy, such as eczema and hay fever.

Atopic asthma is more common than non-atopic asthma in childhood. As many as 85 per cent of school-aged children with asthma are atopic. This type of asthma is classically associated with infiltration of the airways by eosinophils and mast cells.

Cough variant asthma
One area of diagnostic difficulty in childhood asthma is chronic cough.

Cough is a common complaint in childhood; up to 10 per cent of preschool and early school-aged children have chronic cough without wheeze at some time.³ Isolated chronic dry cough is a poor marker of asthma and, without other typical features of asthma, in a community setting is most unlikely to be due to asthma.

Cough predominant or cough variant asthma undoubtedly does exist but is rare, even in a tertiary centre. This type of asthma is associated with bronchial hyper-responsiveness or reversible airways obstruction, both key features of asthma. Demonstrating these features can help to identify children with cough predominant asthma.

Section 2: Diagnosis

If there is one feature that consistently points to a diagnosis of asthma in children, it is wheeze. However, 'wheeze' is used by parents to describe a multipli-city of respiratory noises, such as whistling, squeaking or gasping,4 so always try to determine exactly what is meant.

Alternative diagnoses
There are many alternative diagnoses in wheezing children, including: structural abnormalities (characterised by a constant wheeze present from birth); a laryngeal problem (weak cry with or without stridor); congestive cardiac failure; GORD; bronchopulmonary dysplasia; immunodeficiency; cystic fibrosis; primary ciliary dyskinesia (persistent nasal discharge and otitis media); aspiration of foreign body; bronchiectasis (chronic wet cough); post-bronchiolitic wheeze (postviral wheeze) and obliterative bronchiolitis (hyperinflation and fine crackles).

Investigations
A diagnosis can usually be made by history and examination. In children old enough for spirometry, documentation of variable airflow obstruction is mandatory. Look for an acute response to a beta-2 agonist, or broncho-constriction to exercise.

A simple assessment of the extent of symptoms and variability of lung function using home peak flow recordings and symptom diaries over a month or so can be helpful.

If the diagnosis is in doubt or severe asthma persists despite common treatments, referral to a specialist clinic is needed.

History and examination in asthma

Section 3: Management
Management of asthma should involve a comprehensive treatment plan that includes avoidance of airborne allergens and irritant triggers, appropriate pharmacotherapy and asthma education programmes.

Key areas include acute asthma management plans, day-to-day 'preventer' treatments, monitoring for side-effects, and an emphasis on trying to achieve a normal level of functioning. For young children and those with atypical features, repeated review also provides an opportunity to revisit the diagnosis.

The British Thoracic Society/SIGN 2008 guideline recommends that all patients with asthma should have a written, individualised asthma management plan that includes clear and easy-to-follow instructions on acute management, as well as guidance on daily treatment and when to call emergency services.⁵

Long-term management
In atopic asthma, treatment follows a stepwise approach until control is achieved. Patients are then maintained on the lowest level of treatment that still achieves control. There should be regular attempts to reduce the level of treatment once control is achieved.⁵

Pharmacotherapy
Pharmacotherapy is based on the combination of treatments to relax smooth muscle and to reduce airway inflammation. The goal of pharmacotherapy is control of symptoms and prevention of exacerbations with a minimum of drug-related side-effects.

Treatment should be given in a stepwise approach according to the persistence, severity and/or frequency of the symptoms, and should take into account the presenting asthma phenotype. Children starting a new therapy should be monitored, and changes made where appropriate. Regular review allows therapy to be stepped up or down according to response.

The introduction of inhaled corticosteroids (ICS) has transformed the management of chronic asthma. Considerable benefit for all major clinical outcome measures is seen with low and moderate doses (beclometasone to 400 microgram/day or fluticasone to 200 microgram/day).

Beyond this, however, the dose-response curve is relatively flat in most children. Although side-effects are unlikely at doses of 400 microgram/day of beclometasone equivalent, they become apparent at the higher doses.^2,3

Practically, if a child seems to require higher doses of ICS than those recommended, the questions that need to be considered are:

• Is the diagnosis correct?
• Is the asthma genuinely severe?
• Are avoidable triggers present?
• Are concordance and the medication delivery device adequate?
• Are other treatments available that could be added to reduce the dose of ICS needed?

This will ensure that all treatment options are maximised and alternatives considered.

Drug delivery
To achieve optimum inhaled drug delivery for children with asthma, the correct device must be prescribed and education must be given on how to use it correctly.

Poor inhaler technique can result in the child swallowing more than 80 per cent of the drug. NICE has recently published guidance on recommended inhaler devices for children aged under five and for those aged between five and 15 years.6,7

Monitoring in primary care⁵
Routine clinical review on at least an annual basis:

• Symptomatic asthma control questionnaire: using directive questions such as the Asthma Control Test.
• Lung function, assessed by spirometry or by peak flow.
• Exacerbations.
• Oral corticosteroid use.
• Time off school since last assessment.
• Inhaler technique.
• Compliance, which can be assessed by reviewing prescription frequency.
• Bronchodilator reliance, assessed by reviewing prescription frequency, and possession of and use of self-management/personal action plan.

Section 4: Complications

Smoking
Passive exposure to tobacco smoke is one of the strongest risk factors for developing recurrent coughing/wheezing or asthma symptoms at any age during childhood. Maternal smoking during pregnancy results in impaired lung growth in the developing fetus.²

Avoiding tobacco smoke is therefore one of the most important factors in preventing asthma and other respiratory diseases. At every visit, the smoking habits of the family should be assessed and discussed.

Difficult-to-treat asthma
Problematic asthma - as indicated by frequent use of short-acting beta-2 agonists despite high-dose ICS treatment, or brittle asthma - may present atypically, be infrequent and yet life-threatening and nonresponsive to treatment. A comprehensive assessment and exclusion of other causes of asthma-like symptoms is needed.

Lack of compliance and unrecognised adverse environmental influences must be considered, as non-compliance is the most common cause of a poor response.

At the Royal Brompton, we use a staged difficult asthma protocol. This sorts out difficult asthma from the truly severe, therapy-resistant cases for whom modern molecular-based therapies may be appropriate.

When to refer

• Patient has reached step 4 of BTS/SIGN guideline.⁵ However, if the GP is unfamiliar with treatments that are added on to inhaled corticosteroids, an earlier referral is sensible; indeed most asthma specialist services will wish to receive referrals if 400 microgram/day of beclometasone or equivalent is not achieving control.⁵
• Features that point to another diagnosis/diagnosis unclear or in doubt.
• Symptoms present from birth.
• Excessive vomiting.
• Persistent wet or productive cough.
• Failure to thrive.
• Parental anxiety or need for reassurance.
• Concordance and drug delivery need careful assessment and expertise of specialist asthma nurse.
• Recurrent admission to hospital - suggests dangerous pattern of asthma.
• Particularly severe acute asthma, such as needing intravenous treatments or intensive care.
• Family history of unusual chest disease.

Resources
Information resources for patients

• Asthma UK (www.asthma.org.uk). Comprehensive information resource on asthma for parents and children, including chat rooms and information on educational holidays.
• Patient UK. Asthma (www.patient.co.uk/showdoc/23068680/). Provides information on what asthma is and on the different treatment options available.
• British Thoracic Society (www.brit-thoracic.org.uk). Provides a link to the updated guidelines on the management of asthma and the evidence behind the guidelines.

References

1. International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee. Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISSAC. Lancet 1998; 351: 1,225-32.

2. Townshend J, Hails S, Mckean M. Diagnosis of asthma in children and management. BMJ 2007; 335: 198-202.

3. Silverman M, ed. Childhood asthma and other wheezing disorders. 2nd ed. London: Hodder Arnold, 2002.

4. Cane RS, Ranganathan SC,McKenzie SA. What do parents of wheezy children understand by "wheeze"? Arch Dis Child 2000; 82: 327-32.

5. British Guideline on the Management of Asthma. British Thoracic Society Scottish Intercollegiate Guidelines Network. Thorax 2008; 63: iv1-iv121.

6. National Institute for Clinical Excellence. Guidance on the use of inhaler systems (devices) in children under the age of 5 years with chronic asthma. London: NICE, 2000.

7. National Institute for Health and Clinical Excellence. Inhaler devices for routine treatment of chronic asthma in older children (aged 5-15 years). London: NICE, 2002.

For an archive of all GP clinical reviews visit www.healthcarerepublic.com/clinical/GP