Investigations

Airway inflammation measures

Fractional exhaled nitric oxide

• a test that measures the amount of nitric oxide (NO) present on exhalation, usually expressed in parts per billion
• be aware that a person's current smoking status can lower FeNO levels both acutely and cumulatively (1)
  • however, a high level remains useful in supporting a diagnosis of asthma
• be aware that the results of spirometry and FeNO tests may be affected in people who have been treated with inhaled corticosteroids (the test results are more likely to be normal) (2)
• in adults, young people and children aged 5 to 16 with a history suggestive of asthma (2)
  • measure the blood eosinophil count or fractional exhaled nitric oxide (FeNO) level in adults with a history suggestive of asthma
    • diagnose asthma if the eosinophil count is above the laboratory reference range or the FeNO level is 50 ppb or more
  • in children aged 5 to 16
    • measure the FeNO level in children with a history suggestive of asthma
    • diagnose asthma if the FeNO level is 35 ppb or more

Blood/Serum Eosinophil Count

• eosinophilic asthma is often indicated by peripheral blood eosinophil counts that surpass specific benchmarks, such as >150 cells/μL, >300 cells/μL, or >400 cells/μL (3,4):
  • elevated counts are frequently linked to the severity of asthma exacerbations
  • is a discernible correlation between eosinophil counts in the sputum and blood
  • treatments like corticosteroids have been observed to reduce blood eosinophilia

NICE have included blood eosinophil count as an investigation in the diagnosis of asthma (5):

• "..the committee agreed that peripheral blood eosinophil counts could be part of the battery of tests used to establish a diagnosis of asthma, and that it could be useful as a rule-in test. They noted that peripheral blood eosinophil count is a simple measure to obtain, and it can be routinely collected in full-blood count in adults, although the need for venepuncture makes the test less easy to carry out in children..."
• "..concluded that peripheral blood eosinophils could be of use as a diagnostic test for asthma but noted that the current evidence did not support a specific cut-off for diagnosis. There are slight variations between the normal ranges quoted by different laboratories and their consensus view was that the upper limit of the relevant lab’s range should be used.."

NICE suggest a significant blood eosinophil count in the diagnosis of asthma is (2):

• if the eosinophil count is above the laboratory reference range when considering in adults and young people (aged over 16 years old)
• if the eosinophil count is more than 0.5 x 10⁹ per litre (500 cells/μL) in children aged 5 to 16 years

Lung function tests

Spirometry

• is an option for diagnosing asthma in adults, young people and children aged 5 to 16 with a history suggestive of asthma (2)
  • if asthma is not confirmed by eosinophil count or FeNO level, measure bronchodilator reversibility (BDR) with spirometry
    • diagnose asthma if the FEV₁ increase is 12% or more and 200 ml or more from the pre-bronchodilator measurement (or if the FEV₁ increase is 10% or more of the predicted normal FEV₁)
• is the preferred initial test (if available) to assess the presence and severity of airflow obstruction

Peak expiratory flow (PEF) variability

• is an option for diagnosing asthma in adults, young people and children aged 5 to 16 with a history suggestive of asthma (2)
  • if asthma is not confirmed by eosinophil count or FeNO level and spirometry is not available or it is delayed, measure peak expiratory flow (PEF) twice daily for 2 weeks
  • diagnose asthma if PEF variability (expressed as amplitude percentage mean) is 20% or more

Airway hyperreactivity measures

Direct bronchial challenge test

• is a test to measure airway responsiveness (bronchial responsiveness)
  • is performed by giving small increments of a bronchoconstrictor (most commonly methacholine) and measuring the FEV₁ after each dose until it falls by a predetermined amount (usually 20% from baseline)

Chest radiology

• undertaken after treatment of acute asthma attack has been initiated
• consider in any patient presenting atypically or with additional symptoms or signs
• in children, chest X-rays should be reserved for severe disease or clinical clues suggesting other conditions and need not be part of the initial diagnostic workup (1,6,7)

Skin prick testing

• measures the allergic response of an individual to certain specific allergens when a very small amount of the specific allergen is introduced into the skin (usually the inner forearm)

Serum IgE level

• been shown that it is predictive in asthma, and it may be used to differentiate between asthmatic and non-asthmatic individuals in conjunction with other biomarkers (8)

Reference:

1. British Thoracic Society (BTS)/Scottish Intercollegiate Guidelines Network (SIGN) 2019. British Guideline on the Management of Asthma. A national clinical guideline
2. NICE (November 2024). Asthma: diagnosis, monitoring and chronic asthma management (BTS, NICE, SIGN)
3. Hussain M, Liu G. Eosinophilic Asthma: Pathophysiology and Therapeutic Horizons. Cells. 2024 Feb 23;13(5):384
4. Hirano T, Matsunaga K. Measurement of Blood Eosinophils in Asthma and Chronic Obstructive Pulmonary Disease. Intern Med. 2023 Jan 1;62(1):21-25.
5. NICE (November 2024). Final Asthma: diagnosis,monitoring and chronic asthma management(update);[G] Evidence reviews for diagnostic accuracy of eosinophil blood count measures in the diagnosis of asthma.
6. Global Initiative For Asthma (GINA) 2023. Global strategy for asthma management and prevention
7. Kim H, Mazza J. Asthma. Allergy Asthma Clin Immunol. 2011;7 Suppl 1:S2
8. Ahmad Al et al. The predictive value of IgE as biomarker in asthma. J Asthma. 2008 Oct;45(8):654-63.