Asthma is a chronic disease with prominent heterogeneity in the pattern of underlying disease mechanisms, disease severity, clinical features, and responsiveness to specific treatments. Diagnosis of asthma is predominantly made with clinical history and examination. While the majority of asthmatic patients are controlled by standard pharmacological protocols of bronchodilators, a significant subgroup has very limited therapeutic options, representing a major unmet need. This limitation can be a probable result of underdiagnosis, misdiagnosis, or overdiagnosis of asthma.1
1) The usual diagnosis of asthma involves a very detailed history of similar issues in the family, lifestyle, medications, and exposure to allergens like pet hair, pollen, dust mites etc. The information of usual exacerbation timings and climatic conditions is also of importance.
2) If the symptoms are atypical to asthma, the physician most likely recommends X-ray imaging of the chest, sinus X-ray imaging, sputum analysis, and allergy tests to rule out similar pathologies.
1) Lung function testing by spirometry2:
● Most easily accessible test for diagnosis of asthma in a clinical setting.
● The presence of an obstructive picture, with a ratio of FEV1/FVC <70%, and associated reversibility following administration of bronchodilator is a strong indicator of asthma as a diagnosis.
● If an obstructive spirometry result is present; it is recommended that all adults aged 17 and over, should undergo a bronchodilator reversibility test. An improvement of ≥12% in FEV1 and an increase in ≥200 ml may be considered a positive test of reversible airflow obstruction.
● However, one of the key issues about the use of spirometry to help diagnose asthma is the absolute requirement for its correct usage and interpretation.3
● Interpretation of spirometry results varies even between specialist lung function laboratories, with a lack of standardisation in relation to definitions for the lower limit of normal.4
● Although confirmation of reversible airflow obstruction is as important for a diagnosis of asthma in children as in adults, the practical application of spirometry in children is even more of a challenge.
● In children below 17 years of age, the test being comfortable and co-operated for by children is rare.5
● Another critical issue for children is that when measured during stable disease, spirometry is frequently normal, even in those with severe disease.6
2) Use of exhaled nitric oxide:
● As the fundamental pathophysiology underlying asthma incorporates eosinophilic airway inflammation coupled with reversible airflow obstruction, exhaled nitric oxide is considered additive to measures of lung function as an indirect marker of airway inflammation.8
● If a value of 40 parts per billion (ppb) or higher is measured in a patient with suspected asthma, this is considered a positive result, and strongly supports asthma.9
3) Sputum eosinophil:
● In adult patients, the main use of sputum eosinophils has been to guide management and tailoring of therapy to achieve a reduction in exacerbations, rather than to make the diagnosis of asthma.10
4) Blood eosinophil:
● While interpreting blood eosinophils for asthma diagnosis, the very high counts (>500 cells/mcl) have a high certainty of an associated airway eosinophilia (not necessarily asthma), but for values <410 cells/mcl, the relationship between blood and airway eosinophils becomes less clear. In such cases, it is important to consider the overall clinical picture and all possible factors that might affect blood eosinophil counts.11
NICE guidelines (2017)12
a) For children under 5 with suspected asthma, treat symptoms based on observation and clinical judgement, and review the child regularly. If they still have symptoms when they reach 5 years, carry out objective tests.
If a child is unable to perform objective tests when they are aged 5:
● Continue to treat based on observation and clinical judgment
● Try doing the tests again every 6 to 12 months until satisfactory results are obtained
● Consider referral for specialist assessment if the child repeatedly cannot perform objective tests and is not responding to treatment.
b) Offer a FeNO test to adults (aged 17 and over) if a diagnosis of asthma is being considered.
Consider a FeNO level of 40 parts per billion (ppb) or more as a positive test. However, consider the effects of smoking on false-positive values.
c) Offer spirometry to adults, young people, and children aged 5 and over if a diagnosis of asthma is being considered. Consider a forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio of less than 70% (or below the lower limit of normal if this value is available) as a positive test for obstructive airway disease (obstructive spirometry).
A multifactorial approach is of utmost importance while diagnosing asthma, in order to avoid any misdiagnosis, underdiagnosis, and overdiagnosis. Consideration of lung function testing with spirometry along with FENO (fractional exhaled nitric oxide) can be helpful. Better diagnosis will help in planning the management efficiently.
1. Saglani, S., & Menzie-Gow, A. N. (2019). Approaches to asthma diagnosis in children and adults. Frontiers in pediatrics, 7, 148.
2. Saglani, S., & Menzie-Gow, A. N. (2019). Approaches to asthma diagnosis in children and adults. Frontiers in pediatrics, 7, 148.
3. Garcia‐Marcos, L., Edwards, J., Kennington, E., Aurora, P., Baraldi, E., Carraro, S., ... & van Sont, J. (2018). Priorities for future research into asthma diagnostic tools: A PAN‐EU consensus exercise from the European asthma research innovation partnership (EARIP). Clinical & Experimental Allergy, 48(2), 104-120.
4. Holt NR, Thompson BR, Miller B, Borg BM. Substantial variation exists in spirometry interpretation practices for airflow obstruction in accredited lung function laboratories across Australian and New Zealand. Intern Med J. (2018) 49:41–7. doi: 10.1111/imj.14047
5. Dombkowski, K. J., Hassan, F., Wasilevich, E. A., & Clark, S. J. (2010). Spirometry use among pediatric primary care physicians. Pediatrics, 126(4), 682-687.
6. Bush, A., Fleming, L., & Saglani, S. (2017). Severe asthma in children. Respirology, 22(5), 886-897.
7. Saglani, S., & Menzie-Gow, A. N. (2019). Approaches to asthma diagnosis in children and adults. Frontiers in pediatrics, 7, 148.
8. Dweik, R. A., Boggs, P. B., Erzurum, S. C., Irvin, C. G., Leigh, M. W., Lundberg, J. O., ... & American Thoracic Society Committee on Interpretation of Exhaled Nitric Oxide Levels (FENO) for Clinical Applications. (2011). An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. American journal of respiratory and critical care medicine, 184(5), 602-615.
9. Barnes, P. J., Dweik, R. A., Gelb, A. F., Gibson, P. G., George, S. C., Grasemann, H., ... & Zamel, N. (2010). Exhaled nitric oxide in pulmonary diseases: a comprehensive review. Chest, 138(3), 682-692.
10. Fleming, L., Tsartsali, L., Wilson, N., Regamey, N., & Bush, A. (2013). Longitudinal relationship between sputum eosinophils and exhaled nitric oxide in children with asthma. American journal of respiratory and critical care medicine, 188(3), 400-402.
11. van Bragt, J. J., Vijverberg, S. J., Weersink, E. J., Richards, L. B., Neerincx, A. H., Sterk, P. J., ... & Maitland-van der Zee, A. H. (2018). Blood biomarkers in chronic airways diseases and their role in diagnosis and management. Expert review of respiratory medicine, 12(5), 361-374.