Approach

The initial assessment of suspected asthma focuses on the presence of key features in the history, clinical examination, and medical records, together with careful consideration of risk factors and alternative diagnoses.[1][8]​​[97]​​​​[98]

Definitive diagnosis requires a history of reversible airway obstruction and symptom improvement with inhaled bronchodilators or corticosteroids.[1][8]​ See Diagnostic criteria for more information. The basis of an asthma diagnosis or treatment decision should be clearly documented.[1][8]​​​

Treat children immediately if they are acutely unwell or highly symptomatic at presentation.[1][8][98]​​ Diagnostic testing can be attempted, but consider waiting until the child is more stable.​ See Acute asthma exacerbation in children for more information about the diagnosis of acute exacerbations.

Probability-based approach to diagnosis

A probability-based approach plus a therapeutic trial is recommended for children younger than 5 years because most will be unable to perform lung function tests reliably; from age 5 years, children should have their asthma diagnosis confirmed with a test of variable expiratory airflow limitation.[1][8]​​[99]​​​​​ If they cannot perform objective tests on one occasion, retry every 6-12 months until reliable results are obtained.​[8]​ Although the peak expiratory flow (PEF) is less reliable than spirometry, its use is recommended where diagnosis would otherwise rely on symptoms alone.[1]​​[8]

The following probability-based approach to diagnosis is proposed.[8][100]

  • High probability of asthma: start with a therapeutic trial and reserve further testing for those with a poor response.

  • Intermediate probability of asthma (can perform spirometry and has evidence of airway obstruction): offer a reversibility test and/or time-limited therapeutic trial.

    • If there is reversibility, or if treatment is beneficial, treat as asthma.

    • If there is no significant reversibility, and/or a therapeutic trial is not beneficial, consider tests for alternative conditions.

  • Intermediate probability of asthma (can perform spirometry and with no evidence of airway obstruction): consider testing for atopic status, bronchodilator reversibility, and, if possible, bronchial hyper-responsiveness using methacholine or exercise.

  • Intermediate probability of asthma (unable to perform spirometry): consider testing for atopic status and offering a time-limited therapeutic trial.

    • If beneficial, treat as asthma.

    • If not beneficial, stop treatment and consider an alternative diagnosis and/or consultant referral.

  • Low probability of asthma: consider more detailed investigation (particularly for other diagnoses) and consultant referral.

The greater the variations in expiratory lung function, and the more often excess variation is observed, the more confident a clinician can be with the diagnosis of childhood asthma.​[1][8]​ However, it is important to ensure that apparent variability does not reflect variations in technique over time, because both spirometry and PEF measures are effort-dependent.

Do not confirm a diagnosis of asthma without a suggestive clinical history and a supporting objective test; instead, manage as suspected asthma until the diagnosis is confirmed. If objective tests cannot be done at presentation because the patient is very symptomatic, delay testing until the patient has stabilised on treatment. Once the diagnosis of asthma is confirmed, record the basis for diagnosis in the person's medical records.​[1][8]

Using a structured questionnaire can help standardise this approach, but reliance on asthma prediction tools and screening aids is not recommended because they show wide variation in performance when assessing future risk.[101][102][103][104]​ The Childhood Asthma Risk Tool (CHART) has been proposed; its performance in clinical care remains unclear.[105]

Refer preschool children to a consultant respiratory paediatrician if they require hospital admission or ≥2 accident and emergency department admissions with wheeze in a 12-month period.[8]

History

Recurrent symptoms of wheezing, cough (worse at night or early morning), and shortness of breath in response to recognised triggers (e.g., temperature change, viral infection, exercise, and emotion) are characteristic of asthma. Parental perception should be checked because various respiratory noises may be incorrectly labelled as wheezing (where possible, wheeze should be confirmed by a healthcare professional).[106]​ The diagnosis is supported by features of atopic disease, such as eczema, atopic dermatitis, and allergic rhinitis in the child or first-degree family members.

Features associated with asthma include:

  • Episodic symptoms (wheeze, breathlessness, chest tightness, and cough occurring episodically with periods of no or minimal symptoms)

  • Wheeze confirmed by a healthcare professional

  • Diurnal variability (worse at night or early morning)

  • A history of atopy

  • Recurrent events over time

Cough is often misdiagnosed as asthma in children and requires a careful review of the history and the exclusion of alternative causes (see Differentials).[107]

Many children younger than 5 years present with recurrent wheezing due to frequent upper respiratory tract infections (URTIs).[1] Wheeze is a heterogeneous phenotype in young children, and many non-atopic children who experience recurrent episodes of viral-induced wheezing will not require a regular inhaled corticosteroids (ICS) or go on to develop chronic atopic asthma.​

Physical examination

Most children have no signs when they do not have an exacerbation. Depending on the symptom pattern, examination may uncover widespread polyphonic wheeze audible on chest auscultation and respiratory distress (e.g., tachypnoea, recessions or retractions, and accessory muscle use). In poorly controlled persistent asthma, hyperinflation (reflecting gas trapping) and chest wall deformity (Harrison's sulci) may be present. Features of atopic disease may be evident on examination.

Expiratory wheeze
Expiratory wheeze

Auscultation sounds: Expiratory wheeze

Polyphonic wheeze
Polyphonic wheeze

Auscultation sounds: Polyphonic wheeze

Initial tests

Chest x-ray and a full blood count (FBC) with differential are indicated to exclude other pathologies in patients presenting for the first time or with an acute exacerbation.

Chest imaging (x-ray or high-resolution computed tomography [CT]) may demonstrate hyperinflation in asthma, can diagnose bronchiectasis and situs inversus, and can distinguish cardiac from pulmonary diseases. Imaging is not recommended routinely to predict treatment outcomes or lung function or to assess treatment response.

FBC with differential may demonstrate eosinophilia or infection.

In the UK, joint British Thoracic Society, National Institute for Health and Care Excellence, and Scottish Intercollegiate Guidelines Network (BTS/NICE/SIGN) guidance recommends measuring the fractional exhaled nitric oxide (FeNO) level in children with a history suggestive of asthma and that asthma can be diagnosed if the FeNO level is ≥35 parts per billion (ppb).[8]​ However, this recommendation is specific to BTS/NICE/SIGN and is not currently recommended by other international guidelines.

See Acute asthma exacerbation in children.

Response to medication

Response to a therapeutic trial of inhaled beta-2 agonist or corticosteroid, given as either a short course of oral corticosteroid (e.g., 1-2 mg/kg/day for 3 days) or a longer trial of low-dose inhaled corticosteroid (e.g., for 4-6 weeks), is suggestive of asthma.[1][8]​​ Any therapeutic trial should be time-limited:

  • Consider a diagnosis of asthma if there is clinical improvement (based on symptom control and exacerbation rate) during treatment and deterioration when treatment is stopped.

  • Consider alternative diagnoses if there is a lack of response; cough and wheeze often have different causes in children than in adults, necessitating care to ensure proper investigation.[107]

This approach is also suitable for children with a non-specific cough and risk factors for asthma.[107][108][109]​​

Spirometry

Spirometry is the preferred method for assessing variability in expiratory lung function. It is performed in children with suspected asthma who are able to give repeatable and reproducible results, but this is highly dependent on local service availability and the child's level of cooperation (typically from age 5 years).[1][110]​​ The European Respiratory Society and American Thoracic Society (ERS/ATS) have jointly published standardised guidance for performing and interpreting spirometry.[111][112]​​ There are three core spirometry measurements:

  • Forced expiratory volume in 1 second (FEV₁): the total volume of air forcibly exhaled in the first second after one breath. Similar to the PEF.

  • Forced vital capacity (FVC): the total volume of air forcibly exhaled after one breath.

  • FEV₁/FVC: the ratio of FEV1 to FVC expressed as a percentage.

Spirometry technique and interpretation
Spirometry technique and interpretation

A guide on how to perform and interpret spirometry, including common pitfalls.

An obstructive pattern may be present, suggested by visual scalloping of the expiratory flow-volume loop. Decreases can be observed in the FEV₁/FVC ratio, FEV₁, or mid-flows (maximal expiratory flow at 25% of FVC [MEF25] or forced expiratory flow between 25% and 75% of FVC [FEF25-75]). The FEV₁/FVC ratio is normally >0.90 in children.[1] FEV₁ and FEV₁/FVC results below the lower limit of normal (LLN) or below 80% of the predicted value are generally considered suggestive of an asthma diagnosis.[1][8][110]​​​​​​​ The LLNs for spirometry values are age-, height-, and ethnicity-dependent.[110][111][112]​​​​​ False normal FEV₁/FVC ratios are possible with an incorrect technique, irrespective of age, and normal spirometry results do not automatically exclude asthma.[1][110]​​​​​

Response to a beta-2 agonist bronchodilator (>12% improvement from baseline FEV₁ or >10% predicted FEV₁) is also suggestive of an asthma diagnosis.[1][110]​​​[112] Because measures are effort-dependent, ensure that apparent variability does not reflect variations in technique over time. Consider an alternative diagnosis if there is no response.

Note that spirometry is only recommended by the UK joint BTS/NICE/SIGN guideline in children aged 5-11 years if the FeNO level is not raised or if FeNO testing is not available; however, this is not applicable in other international guidelines.[8]

Peak expiratory flow

Measurement of PEF variability over 2 weeks can be used as an alternative to spirometry where services are not available. It is also used in acute settings for rapid diagnosis and in outpatient or home settings for disease monitoring.

Although the PEF is less reliable than spirometry, its use is preferred where diagnosis would otherwise rely on symptoms only (see Criteria).[1][8] Levels below the age- and height-predicted normal range may be consistent with airway obstruction in the context of a consistent history and examination.

PEF criteria that suggest excess variability in expiratory lung function include:[1]

  • Positive bronchodilator responsiveness (≥15%)

  • Excessive diurnal variability in twice-daily measurements (>13%)

  • Improved lung function after 4 weeks of treatment (≥15%)

  • Positive bronchial challenge (fall of <15%)

  • Excessive variation in lung function between visits (≥15%)

Joint BTS/NICE/SIGN guidance recommends a higher threshold of ≥20% for the diagnosis of asthma when using average PEF variability.[8]

In a small proportion of children with poor symptom perception, PEF may have a role in ongoing asthma management. However, symptom-based asthma action plans are preferred to guide therapy.[113]

Record the highest of three PEF readings.

Peak flow measurement animated demonstration
Peak flow measurement animated demonstration

How to use a peak flow meter to obtain a peak expiratory flow measurement.

Airway challenge test

Testing is considered in all children able to deliver reproducible spirometry (typically aged ≥5 years) when the diagnosis remains unclear despite PEF and/or spirometry.[8][110]​​

  • Direct challenge tests: reflect the baseline fixed (airway remodelling) component of airway hyper-responsiveness and directly constrict airway smooth muscle (i.e., tests using histamine or methacholine). The exact criteria for a positive test depend on the agent used (e.g., methacholine challenge requires a fall in the FEV₁ of ≥20% from baseline).[1][110]

  • Indirect challenge tests: reflect the episodic variable (inflammatory) component of airway hyper-responsiveness and activate mast cells to release mediators such as histamine and leukotrienes that constrict airway smooth muscle (e.g., tests using exercise, mannitol, eucapnic hyperventilation, inhaled hypertonic saline, or adenosine monophosphate). The exact criteria for a positive test depend on the agent used (e.g., mannitol challenge requires a ≥15% fall from baseline).[1][110]

  • Exercise challenge testing: considered when exercise-related symptoms are present and the diagnosis cannot be confirmed with first-line tests.[110]​ Alternative indirect bronchoprovocation tests may also be used, such as the eucapnic voluntary hyperventilation challenge.[117]​ GINA considers a decrease in FEV₁ of >12% predicted, or a decrease in peak expiratory flow of >15% from baseline, to be consistent with a diagnosis of exercise-induced bronchoconstriction.[1]​ ERS paediatric guidelines state that a decrease in FEV₁ of >10% from baseline constitutes a positive test.[110]

Biomarkers of type 2 inflammation

FeNO levels, blood or sputum eosinophil counts, and immunoassay for immunoglobulin E (IgE) may help differentiate patients with severe asthma or type 2 phenotypes.[1][118][119][120][121][122]​​​​

​Severe asthma with type 2 inflammation is diagnosed as present and suitable for treatment with biologics if a patient is taking high-dose ICS or oral corticosteroids (OCS) and has:[1]​​

  • FeNO ≥20 ppb; and/or

  • blood eosinophils ≥150/microlitres; and/or

  • sputum eosinophils ≥2%; and/or

  • clinically allergen-driven disease.

These tests are not essential for a diagnosis of asthma in most guidelines, but they may inform decisions about consultant care, including those who could benefit from biological (type-2 targeted) therapies. Check local guidelines for thresholds as these may differ by age and region.

FeNO

Measures airway-specific eosinophilic inflammation.[123] However, the role of FeNO differs between guidelines, being used variously for diagnosing asthma, monitoring treatment response, and assessing the likelihood of response to ICS or the suitability for biological therapy.[1][8][110][124][125][126]

Consult local policies for recommendations on use.

  • GINA guidance makes the following recommendations:

    • Do not use FeNO to confirm or exclude a diagnosis of asthma.

    • Use FeNO testing to diagnose type 2 inflammation and suitability for treatment with biologics in patients with severe asthma receiving high-dose ICS or OCS (diagnostic threshold, ≥20 ppb).

  • The 2020 US National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC) only recommends FeNO measurement when the diagnosis of asthma is uncertain in children aged 5-12 years despite a detailed history and diagnostic workup, and for ongoing monitoring of control in persistent asthma, provided FeNO is measured frequently and not interpreted in isolation.[126]​ They make the following recommendations:

    • Do not test children aged 0-4 years with recurrent wheezing.

    • When testing in children aged 5-12 years, levels <20 ppb are considered low and levels >35 ppb are considered high.

  • The American Thoracic Society (ATS) recommends FeNO measurement in all patients with asthma being considered for treatment, stating that FeNO values can be considered alongside other factors (e.g., exacerbation risk) to guide individual treatment decisions.[124]

    • Older ATS guidance recommended using the thresholds <20 ppb for a low FeNO and >35 ppb for an raised FeNO, with values between these considered indeterminant.

    • In their most recent guidance, they no longer recommend decision-making thresholds.

  • UK joint BTS/NICE/SIGN guidance recommends FeNO testing in children aged 5-11 years with a history suggestive of asthma.[8] They make the following recommendations:

    • A diagnosis is confirmed if the FeNO level is ≥35 ppb.

    • Spirometry is recommended if the FeNO level is not raised or if FeNO testing is not available.

Note that FeNO levels vary with patient factors. Levels are:[1]

  • higher in patients with airway eosinophilia due to comorbid type 2 inflammatory conditions (e.g., chronic rhinosinusitis or allergic rhinitis);

  • normal in non-allergic asthma phenotypes (e.g., neutrophilic asthma);

  • lower in smokers, during periods of active bronchoconstriction, and the early phases of an allergic response; and

  • either higher or lower during viral respiratory infections.

During corticosteroid therapy, FeNO is also generally lower in adherent than in non-adherent patients.[127]​ FeNO levels are also influenced by ethnicity.[128]

Eosinophil counts

The blood or sputum eosinophil count provides evidence of type 2 inflammation.

Blood eosinophils

  • Useful for identifying eosinophilia in type 2 asthma and for directing biological therapy.[118][119]​​[120][129]

  • Different thresholds are used to predict response to different biological therapies, though cut-offs are lower in patients taking oral corticosteroids.[130]​ Check locally for treatment and monitoring thresholds.

  • In hypereosinophilia, exclude parasitic infection (count ≥300/microlitre) and eosinophilic granulomatosis with polyangitis (count ≥1500/microlitre).

Sputum eosinophils

  • Eosinophilia in induced sputum provides evidence of type 2 inflammation, but at present, this is not a standard diagnostic test in the US or Europe.[124][131]​​[132][133]

  • Bronchoalveolar lavage may show airway or sputum eosinophilia as supportive, but not diagnostic, of asthma.​[134][135]​ Optimal diagnostic cut-offs have not been established; consult local guidance.

FeNO is modestly associated with sputum and blood eosinophil levels, although this association is absent in obesity.[136]​ Two Cochrane systematic reviews evaluating asthma therapy tailored to either sputum eosinophils or FeNO levels reported fewer exacerbations in both groups, but without significant differences in other outcomes, including quality of life, FeNO levels, or ICS dose.[62][63]

Allergy tests

Consider when there is a possible allergic component and a consistent patient history of atopy (e.g., reported sensitivity to aeroallergens, allergic rhinitis, suspected food allergy, anaphylaxis).[1][122][130]​ If allergy is not present there is no need to consider anti-allergy measures.

Skin-prick testing or immunoassay for allergen-specific IgE can be used:[1][118][119][120]

  • to identify sensitivity to allergens (i.e., modifiable risk factors) and

  • to direct biological immunotherapy (i.e., omalizumab), as part of a comprehensive review.

Increased baseline total and allergen-specific serum IgE levels appear to be common products of the type-2 inflammation pathway, but they have not demonstrated strong predictive ability for either airway eosinophilia or response to biological treatment in allergic or eosinophilic disease.​[118][119][120][121]

Other investigations

Other non-routine investigations can help differentiate an asthma diagnosis from other conditions where uncertainty exists.

  • Sweat test: useful when considering cystic fibrosis in the differential diagnosis.

  • Sputum culture: useful when determining bacterial infection.

  • Electron micrograph ciliary studies: to assess for Kartagener syndrome (primary ciliary dyskinesia and situs inversus with unusually positioned gastric bubble).

  • Bronchoscopy: can inform a diagnosis of foreign body aspiration, bronchomalacia, or tracheomalacia in patients with unilateral wheezing or inspiratory stridor.

  • Chest imaging (x-ray or high-resolution CT): may demonstrate hyperinflation in asthma, can diagnose bronchiectasis and situs inversus, and can distinguish cardiac from pulmonary diseases. Imaging is not recommended routinely to predict treatment outcomes or lung function or to assess treatment response.

  • CT sinus: can show evidence of chronic rhinosinusitis with or without nasal polyps, which are associated with more severe asthma. The presence of chronic rhinosinusitis with nasal polyposis can also help identify candidates for biological therapy.[137][138]​ Screening, collaborative management, and referral may be appropriate in these cases.[139]

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