Diagnosing Childhood Asthma in Primary Care

Asthma is a chronic inflammatory disease of the airways, associated with widespread, variable outflow obstruction. Clinically, this manifests as^[1]:

• Wheeze
• Cough
• Difficulty breathing
• Chest tightness

The outflow obstruction reverses either spontaneously or with medication. The underlying inflammation is associated with bronchial hyper-responsiveness (BHR) or airway hyper-reactivity to a variety of stimuli (eg, environmental allergens and irritants).

Diagnosis of asthma in children is difficult because of the complex nature of the disorder in the young. Accurate diagnosis in primary care remains an important challenge.

Many people consider 'wheeze' synonymous with asthma, yet there are many different causes of wheeze in childhood and increasingly we recognise different 'phenotypes' of wheezing. These are usually determined retrospectively, as they depend on the pattern of symptoms over time:

• Episodes of wheezing, cough and difficulty breathing associated with viral upper respiratory tract infections (URTIs) with no persisting symptoms. Common in infants and preschool children (about 30% of children aged under 3 years)^[2]. Most, however, will have stopped having recurrent symptoms by school entry.
• Some children who wheezed early, will go on to develop wheezing with other triggers so that they develop interval symptoms, similar to older children with classical atopic asthma.
• Atopic asthma is more common in school-aged children; symptoms occur often with identifiable triggers and often alongside eczema or hay fever but, even in this age group, non-atopic asthma is as frequent as the atopic variant.

The diagnosis of asthma is clinically based without a single confirmatory diagnostic test, only corroboration of the diagnosis with changes in lung function or response to treatment. In the past, lung function testing was not possible before the age of about 5 years; however, several newer tests may enable testing somewhat earlier (eg, specific airways resistance, impulse oscillometry and measurements of residual volume), although none as yet has been fully evaluated.

Epidemiology^[3]

• The UK has one of the highest prevalences for childhood asthma internationally, with about 15% children affected^[4].
• The prevalence is 8-10 times higher in developed countries than in developing countries.
• The prevalence of 'any wheeze' over recent months (usually taken as within the previous year) amongst children has risen from about 10% in the 1960s to 20-30% in the 1990s. There is some evidence of a possible flattening of this rise from the late 1990s onwards. An increasing percentage of currently wheezing children also have a diagnosis of asthma^[3].
• Interestingly, there has been a decline in the prevalence of moderate-to-severe asthma in 13- to 14-year-olds in the UK. This can be explained in part by the delivery of more effective treatment - inhaled corticosteroids (ICS) primarily - but does not explain the concurrent decline in mild asthma in the same age range^[3].
• Children still die from asthma and there is still a significant morbidity associated with the disease, particularly severe childhood asthma, despite therapeutic advances.
• Prevalence is higher in lower socio-economic groups in urban areas.
• There are gender differences. Boys are affected more before puberty (three times greater prevalence). Prevalence is equal in adolescence but adult-onset asthma is more common in women^[5].
• The increasing prevalence of asthma is mirrored by the increasing prevalence of childhood obesity. Prospective studies suggest that obesity increases the risk of subsequent asthma (although the underlying mechanisms are unclear) but obesity also increases the clinical severity of asthma and reduces quality of life for children with asthma^[6].

Risk factors

There is a long list of possible risk factors, which includes:

• Personal history of atopy.
• Family history of asthma or atopy.
• Triggers (eg, allergens such as pollens, animal dander), dust, exercise, viruses, chemicals, weather changes, emotional factors, irritants and smoke^[7].
• Urban environment.
• Socio-economic stresses.
• Obesity^[5].
• Prematurity and low birth weight.
• Viral infections in early childhood.
• Maternal smoking.
• Passive as well as active smoking^[8].
• In vitro fertilisation.
• Early exposure to broad-spectrum antibiotics^[9].

Breast-feeding possibly confers protection^[10].

Risk factors for persistence of wheezing and asthma throughout childhood include^[1]:

• Age at presentation - those presenting aged younger than 2 years tend to have become asymptomatic by mid-childhood.
• Co-existing atopy is a risk factor for persistence of asthma.
• Family history of atopy, particularly maternal atopy.
• Sex - male sex is a risk factor for asthma in prepubertal children whilst female sex is a risk factor for persistence of asthma into adulthood. Girls are less likely to 'grow out' of their asthma.
• More severe and frequent wheezing episodes are associated with asthma persisting into adolescence.
• Abnormal lung function, both baseline airway function and increased airways responsiveness.

A simple tool has been validated for predicting asthma at school age in preschool children with wheeze or cough. The tool consists of ten predictors yielding a total score between 0 and 15: sex, age, wheeze without colds, wheeze frequency, activity disturbance, shortness of breath, exercise-related and aeroallergen-related wheeze/cough, eczema and parental history of asthma/bronchitis^[11].

Presentation^[4]

Clinical features that increase the probability of the diagnosis of asthma in children^[1]:

• More than one of the following symptoms - wheeze, cough, difficulty breathing, chest tightness, particularly if these symptoms:
• Are frequent and recurrent.
• Are worse at night and in the early morning.
• Occur in response to, or are worse after, exercise or other triggers, such as exposure to pets, cold or damp air, or with emotions or laughter.
• Occur apart from colds.
• Personal history of atopic disorder.
• Family history of atopic disorder.
• Widespread wheeze heard on auscultation.
• History of improvement in symptoms or lung function in response to adequate therapy.

Symptoms

When taking a history:

• Ask about typical symptoms:
  • Wheeze - very common, high-pitched, polyphonic and present in expiration. As severity increases, it may be present during expiration and inspiration. In the most severe episode, it may be completely absent. It must be distinguished from the inspiratory, monophonic noise of stridor which is associated with reduced or impaired upper airway patency. Note that parental understanding of wheeze may include whistling, squeaking or gasping sounds, or a different style, rate or timbre of breathing. Clarify what a patient or their parent means by wheeze.
  • Cough may be the only symptom in children (particularly with exercise-induced asthma and nocturnal asthma). The cough is usually dry and nonparoxysmal. The nocturnal cough of asthma usually occurs after midnight. About 10% of preschool children have chronic cough without wheeze at some time. Chronic cough on its own is a poor marker for asthma and one should always consider other diagnoses. Children with cough-predominant asthma should show improvement on a short trial of asthma medication and return of symptoms on discontinuation of treatment.
  • Chest tightness with or without other symptoms occurs, particularly with exercise and at night in asthma.
  • Breathlessness varies according to severity. Establish whether the child is able to play, run or walk. The most severe attacks are accompanied by breathlessness at rest, paucity of speech, agitation, feeding difficulties and attenuated cry (in infants). Children become drowsy and confused and, in adolescents particularly, symptoms develop late as severity increases.
• Identify triggers - eg, viral URTIs, cold air, dust, pets, pollen, change in weather, exercise.
• Ask about symptoms in the intervals between exacerbations.
• Establish what the pattern has been over time and the current frequency of acute episodes.
• Ask about atopic illnesses in the patient and their family.
• Check previous diagnoses, treatment and concordance with treatment.
• Check for previous emergency contacts with healthcare professionals with related symptoms.
• Note what impact there has been on the child's life and how much school has been missed.

Signs

Signs will vary according to the severity of asthma and the severity of any exacerbation. During episodes, check for:

• Widespread wheeze.
• Increased work of breathing.
• Pulse rate.
• Respiratory rate.
• Oxygen saturation.
• Peak expiratory flow rate (PEFR) - in children aged over 5 years.
• Response to bronchodilator therapy.

Between episodes, there may be no clinical signs but check for:

• Hyperexpansion and Harrison's sulci.
• Clues to other possible diagnoses.

Differential diagnosis^{[1, 4, 12]}

Investigations^{[1, 13]}

After the initial clinical assessment, it is usually possible to determine the relative likelihood of asthma in a particular child and the need for further investigations (although tests may only be needed if there is doubt about the diagnosis or significant disability from the disorder).

• High probability of asthma - move directly to a trial of treatment, the choice of which will be based on assessment of current asthma severity. Reassess in 2-3 months. Investigate further those who show a poor response to treatment or who have severe disease.
• Low probability of asthma - consider more detailed investigations and referral, particularly where an alternative diagnosis seems likely.
• Intermediate probability of asthma - in some and especially those aged under 4-5 years, there may be insufficient evidence to make a firm diagnosis. Approaches in this instance include:
  • Watchful waiting with review.
  • Trial of treatment with review - where beneficial, treat as asthma.
  • Spirometry and reversibility testing.

Spirometry

With older children with an intermediate probability of asthma, diagnostic tests such as PEFR and forced expiratory volume in one second (FEV1) can provide objective measures of airways obstruction but these may be normal between episodes of bronchospasm and provide poor discrimination with other conditions that also cause airways obstruction. Spirometry is usually possible from about 5 years of age, although there is wide variation and it is dependent on the child's co-operation and comprehension of the task.

Where there is evidence of airways obstruction, looking for changes in PEFR or FEV1 10 minutes after the use of a bronchodilator (reversibility usually taken as >12% subsequent improvement in lung function). Also, look for response to a treatment trial over a defined time period, as this adds further weight to the diagnosis of asthma.

Where no evidence of airways obstruction is found with spirometry, consider referral and testing for:

• Atopic status (skin tests*, blood eosinophilia or raised specific immunoglobulin E (IgE) to a cat, dog or mite).
• Bronchodilator reversibility.
• Bronchial hyper-responsiveness (with methacholine, exercise or mannitol)* - high negative predictive value (86-100%) but less useful as a positive predictive tool (55%).

(*These tests are not normally available within primary care.)

Radiology

CXRs should not be used as part of the initial work-up in primary care of children aged 0-6 years in the absence of a specific clinical indication^[1].

Indications for referral^[1]

These include:

• Diagnosis unclear or in doubt.
• Symptoms present from birth or a perinatal lung problem.
• Excessive vomiting/possetting.
• Severe URTI.
• Persistent wet cough.
• Family history of unusual chest disease.
• FTT.
• Nasal polyps.
• Unexpected clinical findings (eg, focal chest signs, abnormal cry or voice, dysphagia, stridor).
• Failure to respond to conventional treatment (especially corticosteroids above 400 micrograms/day). Vocal cord dysfunction can mimic steroid-refractory asthma.
• Frequent use of oral steroids.
• Parental concerns or anxiety.