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Astma bij volwassenen: diagnose en monitoring in de eerste lijnPublished by: Werkgroep Ontwikkeling Richtlijnen Eerste Lijn (Worel)Last published: 2020Asthme chez l’adulte : diagnostic et surveillance en soins de santé primairesPublished by: Groupe de Travail Développement de recommmandations de première ligneLast published: 2020

Characteristic symptoms plus confirmed variable expiratory airflow limitation are required to make a diagnosis of asthma.[97]​ Clinicians should record the evidence underlying the diagnosis of asthma, as well as the patient's symptom severity, modifiable risk factors, and lung function.

If a patient presents with an acute exacerbation, refer to specific guidance. See Acute asthma exacerbation in adults.

History

Patients typically report recurrent episodes of dyspnea, chest tightness, wheezing, or coughing.

The medical history may identify allergen exposures that worsen the asthma, seasonal patterns, or other triggers (e.g., exercise). People with more severe asthma often have night-time symptoms that wake them from sleep or earlier in the morning than usual.

Differentials should be excluded.

Physical exam

The exam may be normal in patients with bronchial asthma. Examination of the nasal passages may reveal anterior nasal polyps or nasal congestion. Chest auscultation may reveal expiratory wheezes.

With more severe asthma, the wheezes may be audible without the use of a stethoscope.

In severe exacerbations, patients are continuously short of breath, they may use accessory muscles of respiration, and their lung examination may be silent.

Polyphonic wheeze
Polyphonic wheeze

Auscultation sounds: Polyphonic wheeze

Expiratory wheeze
Expiratory wheeze

Auscultation sounds: Expiratory wheeze

Initial tests in some patients with acute presentations

In patients presenting for the first time or with an acute exacerbation, chest x-ray and a complete blood count with differential are indicated to exclude other pathologies.

See Acute asthma exacerbation in adults.

Pulmonary function testing (PFT)

Characteristic symptoms together with confirmed variable expiratory airflow limitation are required to make a diagnosis of asthma.[97]​​​ The Global Initiative for Asthma (GINA) defines confirmed variable expiratory airflow limitation as documented excessive variability in lung function plus documented expiratory airflow limitation.[3]

Airflow limitation is demonstrated using PFTs (i.e., spirometry) that measure:

  • Forced expiratory volume at 1 second (FEV₁)

  • Forced vital capacity (FVC)

Adults without airflow limitation normally have an FEV₁/FVC ratio of >0.75 to 0.80.[3][98]

The diagnosis of asthma is confirmed by one or more tests confirming excessive variability in lung function.

A bronchodilator reversibility test may demonstrate reversibility of airflow obstruction to short-acting bronchodilator. GINA defines a bronchodilator reversibility test as positive if there is a ≥12% and ≥200 mL improvement in FEV₁ from baseline.[3]​ Note that the 2021 American Thoracic Society (ATS) and European Respiratory Society (ERS) technical standard recommends a slightly lower threshold of >10% improvement in the predicted FEV₁ or FVC.[99]

Normal PFT results are possible during periods of quiescence and do not exclude a diagnosis of asthma.

See Criteria.

Exercise-induced bronchoconstriction

Symptoms occur due to exercise in up to 90% of people with asthma; however, exercise-induced bronchoconstriction (EIB) is diagnosed based on changes in lung function after exercise, not symptoms.[2]

Guidelines from the American Thoracic Society (ATS) recommend:[100]

  • measuring the difference between the pre-exercise FEV₁ and the lowest FEV₁ value recorded within 30 minutes after exercise,

  • expressing this as a percentage of the pre-exercise value, and

  • diagnosing EIB if the percentage fall in FEV₁ after exercise is ≥10%.[100]

Objective assessment of EIB is particularly important in athletes as respiratory symptoms are poorly predictive of airway disease in this patient group.[101]

Peak expiratory flow (PEF)

PEF can be used as an alternative to spirometry for diagnosing asthma, and it is often beneficial in acute settings for rapid diagnosis and in outpatient or home settings for disease monitoring. However, PEF does not reflect the level of obstruction of the lung as accurately as the FEV₁ and FEV₁/FVC ratio. Accuracy depends on the patient's effort and technique.

PEF monitoring demonstrating diurnal variability (defined as [highest daily PEF - lowest daily PEF]/[highest daily PEF]) can be used to help diagnose asthma, especially occupational (work-related) asthma when spirometry is not available.[98]​ The diagnosis of asthma is supported if there is excessive variability in twice-daily PEF over 2 weeks. In adults, an average daily diurnal variability in PEF of >10% is considered excessive.[3]​ An increase in PEF by >20% from baseline after 4 weeks of treatment also indicates excessive variability.

Challenge tests

May be performed to support the diagnosis of asthma if PFT and PEF results do not show reversibility and variability.[102][103]

  • Direct challenge tests reflect the baseline fixed (airway remodeling) component of airway hyperresponsiveness and directly constrict airway smooth muscle (i.e., tests using histamine or methacholine).

  • Indirect tests reflect the episodic variable (inflammatory) component of airway hyperresponsiveness and activate mast cells to release mediators such as histamine and leukotrienes to constrict airway smooth muscle (e.g., tests using exercise, mannitol, eucapnic hyperventilation, inhaled hypertonic saline, or adenosine monophosphate).

Challenge tests are more resource-intensive than tests of bronchodilator reversibility.[98]

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).[3][104][105]

Skin-prick testing or immunoassay for allergen-specific immunoglobulin E (IgE) can be used to:[3][106][107][108]​​​

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

  • Direct biologic immunotherapy (i.e., omalizumab), as part of a comprehensive review

If allergy is not present there is no need to consider anti-allergy measures.

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 biologic treatment in allergic or eosinophilic disease.​[106][107][108][109]

Biomarkers of type 2 inflammation

Immunoassay for IgE, fractional exhaled nitric oxide (FeNO), and blood or sputum eosinophil counts may help differentiate patients with type 2 phenotypes.[3][104][106][107][108][109]​​​

Type 2 inflammation is defined as:[3]

  • FeNO ≥20 parts per billion (ppb); and/or

  • blood eosinophils ≥150/microliters; and/or

  • sputum eosinophils ≥2%; and/or

  • clinically allergen-driven disease.

These tests are not essential for a diagnosis of asthma, but they may inform decisions about specialist care, including those who could benefit from biologic (type 2-targeted) therapies. GINA recommends biologic therapy only for severe asthma and only after existing treatment has been optimized.[3]

FeNO

Measures airway-specific eosinophilic inflammation.[110]​ The main US guidelines differ in their guidance and only conditionally recommend FeNO testing.[3][111][112]​​ Levels >20 ppb generally considered evidence of type 2 inflammation.[3]

  • GINA states that the main role of FeNO is to help guide treatment decisions in patients with severe asthma.[3]

    • They do not recommend FeNO as a test for confirming or excluding a diagnosis of asthma, citing the overlap between FeNO levels among people with and without asthma.

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

  • The 2020 US National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC) recommends FeNO measurement:[111]

    • when the diagnosis of asthma is uncertain despite a detailed history and diagnostic workup

    • for ongoing monitoring of control in persistent asthma, provided FeNO is measured frequently and not interpreted in isolation.

    • provides thresholds for low, indeterminate, and high likelihood of eosinophilic airway inflammation and responsiveness to ICS (<25, 25-50, and >50 ppb, respectively).

  • 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.[112]​ However, they have not established decision-making thresholds.

High levels indicate that eosinophilic airways inflammation is likely, the phenotype is more likely to respond to ICS, and that the patient has allergic asthma or eosinophilic asthma.

Note that FeNO levels vary with patient factors. Levels are typically:[3]

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

  • normal in nonallergic 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.

In patients using corticosteroids, FeNO is also generally lower in adherent than in nonadherent patients.[113]

FeNO is modestly associated with sputum and blood eosinophil levels, although this association is lost in obesity.[114]​ 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 inhaled corticosteroid dose.[115][116]

Eosinophil count

Blood eosinophils

  • Useful for identifying eosinophilia in type 2 asthma and for directing biologic therapy.[106][107][108]

  • Elevated in the presence of a positive skin-prick test or elevated total IgE, but also in current smoking, allergic rhinitis, age ≤18 years, male sex, COPD, metabolic syndrome, and obesity.[117]

  • Different thresholds are used to predict response to different biologic therapies, though cutoffs are lower in patients taking oral corticosteroids.[105]​ Check locally for treatment and monitoring thresholds.

  • GINA recommends excluding parasitic infection by testing for strongyloides IgG if the eosinophil count is ≥300/μL and carefully excluding eosinophilic granulomatosis with polyangiitis if the eosinophil count is ≥1500/μL.

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.[98][112]​​[118][119]​​

FeNO is modestly associated with sputum and blood eosinophil levels, although this association is lost in obesity.[114]​ 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 inhaled corticosteroid dose.[115][116]

Imaging studies

Chest x-ray (CXR) and high-resolution CT (HRCT) are not routinely recommended for the diagnosis or management of asthma.[120]​ However, they may be performed to exclude alternative pulmonary and cardiac causes of dyspnea.[120]​ In asthma, HRCT typically demonstrates mosaic lung attenuation due to air trapping on expiration.[120]

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 biologic therapy.[121][122]​​ Screening, collaborative management, and referral may be appropriate in these cases.[123]

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