Asthma Management Handbook

Airway inflammation tests for diagnosis in adults

Recommendations

Do not routinely order induced sputum eosinophil count for all patients with suspected asthma. It is not necessary to demonstrate airway inflammation if the patient shows clinical features of asthma and there is a low probability that these are due to another cause.

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Measurement of exhaled nitric oxide is not recommended as a diagnostic test for asthma in routine clinical practice.

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available), with particular reference to the following source(s):

  • Dweik et al. 20111

More information

Induced sputum test for eosinophilia in adults and adolescents

Patients with untreated asthma usually have airway inflammation (eosinophilic and/or neutrophilic), but testing for this is not essential for making the diagnosis of asthma in clinical practice. Some types of asthma are not associated with eosinophilic airway inflammation. 

The induced sputum test is not a standard microbiology test. It is provided by specialised laboratories.

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Peripheral blood eosinophil count in adults and adolescents

White cell differential count on a peripheral blood sample is not currently recommended routinely in the investigation and management of asthma.

Two studies in severe asthma found that blood eosinophils correlated modestly with sputum eosinophil counts.2, 3 In severe asthma, higher blood eosinophil counts are associated with greater risk of poor symptom control and more frequent exacerbations.4 In patients with severe asthma, peripheral blood eosinophil count is important for predicting response to monoclonal antibody therapy and is a requirement for eligibility for some therapies.

Last reviewed version 2.0

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Exhaled nitric oxide (NO) testing in adults and adolescents

Measurement of the fraction of exhaled nitric oxide is not routinely used in Australian clinical practice, but is often used by respiratory physicians, severe asthma clinics and clinical asthma trials in both primary and secondary care to provide additional information about asthma phenotype that may help to inform treatment decisions.

The exhaled nitric oxide test is easy for patients to perform.

Roles in diagnostic investigation

In patients with symptoms that suggest asthma (e.g. wheeze, shortness of breath, variable cough), the finding of increased exhaled nitric oxide provides supportive evidence for an asthma diagnosis, but is not conclusive for several reasons:1

  • Some types of asthma (i.e. asthma without eosinophilic airway inflammation) are not associated with increased exhaled nitric oxide.
  • Patients treated with inhaled corticosteroids may have a normal exhaled nitric oxide level.
  • Exhaled nitric oxide may be elevated in other conditions (e.g. eosinophilic bronchitis, acute viral infection).
  • Exhaled nitric oxide may suppressed by other factors (cigarette smoke).

The predictive value of exhaled nitric oxide as a diagnostic test for asthma is higher than for peak expiratory flow and spirometry, and similar to that of bronchial challenge tests.1

Increased exhaled nitric oxide fraction not accurate as a single surrogate marker for airway eosinophilia in patients with asthma.5

There are several inflammatory phenotypes in asthma: eosinophilic, neutrophilic, mixed, and asthma with sputum cell counts within normal range (‘paucigranulocytic’). The exhaled nitric oxide fraction is commonly, but not always, associated with eosinophilic airway inflammation, but not with neutrophilic or paucigranulocytic asthma.5

Role in clinical management of asthma

In people with a clinical diagnosis of asthma, the exhaled nitric oxide test is useful for identifying those with asthma who are likely to experience a short-term symptomatic response to inhaled corticosteroids. However, there is no evidence at present that it is safe (with regard to risk of exacerbations) to withhold inhaled corticosteroids if exhaled nitric oxide is not elevated.

There is evidence from several studies in children with a diagnosis of asthma that exhaled nitric oxide can be used to adjust the dose of inhaled corticosteroids, leading to a reduction in exacerbation risk compared with guidelines-based adjustment, though not an improvement in symptom control.6 However, in adults, there was no significant difference in exacerbation risk with FeNO-based treatment adjustment compared with guidelines-based adjustment.7

Last reviewed version 2.0

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Impulse oscillometry in adults and adolescents

Impulse oscillometry is a noninvasive and rapid technique for measuring pulmonary function. Unlike spirometry, the test is easy to do and requires only passive cooperation by the patient, so it is suitable for small children. It is not used routinely in clinical practice, but is currently available in some tertiary referral centres.

Low-frequency impulse oscillometry (resistance at 5 Hz) measurements taken before and after administration of a bronchodilator correlate with spirometry (FEV1) in people with asthma and without asthma.8 Impulse oscillometry may be useful in identifying patients with asthma, and might possibly identify obstruction in the peripheral airways.9

This test is not used routinely in clinical practice because diagnostic cut-points are not well established yet.9 Australian normal values for adults without asthma have been developed.10

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References

  1. Dweik RA, Boggs PB, Erzurum SC, et al. An Official ATS Clinical Practice Guideline: Interpretation of Exhaled Nitric Oxide Levels (FeNO) for Clinical Applications. Am J Respir Crit Care Med. 2011; 184: 602-615. Available from: http://ajrccm.atsjournals.org/content/184/5/602.long
  2. Fowler SJ, Tavernier G, Niven R. High blood eosinophil counts predict sputum eosinophilia in patients with severe asthma. J Allergy Clin Immunol. 2015; 135: 822-4.e2. Available from: https://www.jacionline.org/article/S0091-6749(14)01370-0/abstract/
  3. ten Brinke A, Zwinderman AH, Sterk PJ et al. Factors associated with persistent airflow limitation in severe asthma. Am J Respir Crit Care Med. 2001; 164: 744-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/11549526/
  4. Fahy JV. Type 2 inflammation in asthma–present in most, absent in many. Nat Rev Immunol. 2015; 15: 57-65. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25534623/
  5. Korevaar DA, Westerhof GA, Wang J et al. Diagnostic accuracy of minimally invasive markers for detection of airway eosinophilia in asthma: a systematic review and meta-analysis. Lancet Respir Med. 2015; 3: 290-300. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25801413/
  6. Petsky HL, Kew KM, Chang AB. Exhaled nitric oxide levels to guide treatment for children with asthma. Cochrane Database Syst. Rev 2016; Issue 11: CD011439. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27825189/
  7. Petsky HL, Kew KM, Turner C, Chang AB. Exhaled nitric oxide levels to guide treatment for adults with asthma. Cochrane Database Syst. Rev 2016; 9: CD011440. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27580628/
  8. Nair A, Ward J, Lipworth BJ. Comparison of bronchodilator response in patients with asthma and healthy subjects using spirometry and oscillometry. Ann Allergy Asthma Immunol. 2011; 107: 317-322. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21962091
  9. Galant SP, Nickerson B. Lung function measurement in the assessment of childhood asthma: recent important developments. Curr Opin Allergy Clin Immunol. 2010; 10: 149-154. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20035221
  10. Newbury W, Crockett A, Newbury J. A pilot study to evaluate Australian predictive equations for the impulse oscillometry system. Respirology. 2008; 13: 1070-1075. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18699802