Workup of Severe Asthma

Chest. 2021 Dec;160(6):2019-2029. doi: 10.1016/j.chest.2021.07.008. Epub 2021 Jul 13.


A 56-year-old man has difficult-to-control asthma and a history of four exacerbations in the prior 12 months despite high-dose inhaled corticosteroids (ICS) and additional controller therapies. Is he suitable for more advanced therapeutic options? To address this query, we herein review the clinical assessment of a patient with suspected severe asthma and discuss factors contributing to poor asthma control and how biomarkers assist in disease investigation and stratification. The key components of our multidisciplinary approach are to confirm an asthma diagnosis and adherence to treatment, to assess any contributing comorbidities or confounding factors, and to stratify what type of asthma the patient has. The combination of spirometry and repeated measures of key biomarkers of type 2 airway inflammation-the blood eosinophil count and fractional exhaled nitric oxide-identifies whether poor disease control is driven by uncontrolled, ICS-resistant type 2 airway inflammation or ongoing airflow obstruction. A failure to elicit evidence of either suggests an alternative driver for the patient's symptoms, including chronic airway infection and non-asthma causes. Each phenotype represents a treatable trait that requires a specific targeted approach. Critically, steroids can cause harm, and their use should be guided by objective evidence of inflammation rather than symptoms alone. To conclude, after assessment of treatment adherence and exclusion of relevant comorbidities, the patient was found to have severe asthma with ICS-resistant type 2 airway inflammation. We will consider additional treatment options at our next appointment in part 2/2 of this How I Do It series.

Keywords: Feno; adherence; airways; asthma; biomarkers; eosinophils; exacerbations; multidisciplinary team; severe asthma; type 2 inflammation.

Publication types

  • Review

MeSH terms

  • Anti-Asthmatic Agents / therapeutic use*
  • Asthma / diagnosis*
  • Asthma / drug therapy*
  • Biomarkers / analysis
  • Comorbidity
  • Diagnosis, Differential
  • Diagnostic Imaging
  • Environmental Exposure
  • Humans
  • Medical History Taking
  • Respiratory Function Tests


  • Anti-Asthmatic Agents
  • Biomarkers