Speaker's Highlight

• Don Sin University of British Columbia, St. Paul Hospital (Canada)
  Kenneth R. Chapman Toronto General Hospital Research Institute (Canada)
• Parameswaran Nair McMaster University (Canada)
  Carolyn Calfee UCSF (U.S.A.)
• Gregory P. Downey University of Colorado School of Medicine (U.S.A.)
  David A. Schwartz University of Colorado School of Medicine (U.S.A.)
• Neil Schluger Tuberculosis Control Branch, California Department of Public Health (U.S.A.)
  Nick Kim Critical Care & Sleep Medicine, University of California San Diego (U.S.A.)
• Nicola Hananiah Baylor College of Medicine (U.S.A.)
  Jae-Joon Yim Seoul National University College of Medicine (Republic of Korea)
• Koichiro Asano Tokai University School of Medicine (Japan)
  Diahn-Warng Perng Taipei Veterans General Hospital (Taiwan)
• Konstantinos Kostikas University of Ioannina (Greece)
  Karin Klooster University Medical Center Groningen (Kingdom of the Netherlands)

• Sputum Eosinophils Predict Treatment Response in Severe Asthma

  Severe asthma affects a small but significant proportion of Australians, with estimates suggesting around 5 to 10 percent of the 2.8 million people living with asthma experience difficult-to-control disease. The condition places a heavy burden on patients, families, and the healthcare system, particularly during high-risk periods such as the bushfire season, when smoke and fine particulate matter trigger acute exacerbations across regional New South Wales, Victoria, and South Australia.

  In recent years, respiratory medicine has moved away from a uniform step-up strategy toward a phenotype-driven approach. Identifying specific patterns of airway inflammation allows clinicians to match individual patients with the therapies most likely to deliver clinical benefit. Among the biomarkers available, sputum eosinophils have emerged as one of the most informative markers of type 2 airway disease.

  Sputum eosinophil counts offer a direct window into the lower airway, reflecting the cellular environment that drives symptoms, exacerbations, and airflow limitation in many people with severe asthma. When measured alongside clinical assessment, lung function, and other biomarkers, they help stratify patients and predict who is likely to respond to targeted treatments.

  Biomarker	Source	Clinical Strengths	Practical Limitations
  Sputum eosinophils	Induced sputum	Direct measurement of lower airway inflammation; high specificity for type 2 phenotype	Requires induction and trained lab processing; not universally available
  Blood eosinophils	Peripheral blood	Easy to obtain; widely available; standardised reference ranges	Indirect surrogate; affected by recent corticosteroid use and diurnal variation
  Fractional exhaled nitric oxide	Exhaled breath	Non-invasive; rapid result	Influenced by smoking, inhaled steroids, and infection
  Serum periostin	Blood sample	Reflects IL-13 driven inflammation	Limited availability in Australian laboratories; modest predictive value

  The Biology of Eosinophilic Airway Inflammation

  Eosinophils are granulocyte white blood cells that migrate to airway tissue in response to type 2 cytokines such as interleukin-5, interleukin-4, and interleukin-13. Once activated, they release granule proteins that damage epithelium, promote mucus hypersecretion, and contribute to airway hyperresponsiveness.

  In patients with severe asthma, persistent eosinophilic airway disease is associated with frequent exacerbations, fixed airflow obstruction, and reduced corticosteroid responsiveness compared with non-eosinophilic phenotypes. Understanding this biology helps explain why a patient with high sputum eosinophils often responds well to therapies that specifically deplete eosinophils or block their recruitment.

  Measuring Sputum Eosinophils in Clinical Practice

  Sputum is usually collected through spontaneous expectoration or hypertonic saline induction, then processed in a specialised laboratory to separate cellular components from fluid. Differential cell counts quantify the proportion of eosinophils, neutrophils, and other inflammatory cells. A sputum eosinophil percentage above 2 to 3 percent is generally considered elevated and supportive of an eosinophilic phenotype.

  In Australia, sputum induction is offered at major teaching hospitals including the Royal Melbourne Hospital, the John Hunter Hospital in Newcastle, and Princess Alexandra Hospital in Brisbane. Smaller regional centres typically rely on partnerships with tertiary labs or send samples through courier services. Standardised processing remains a challenge, and quality depends heavily on operator training and laboratory protocol.

  Predictive Value for Corticosteroid Response

  Patients with elevated sputum eosinophils typically show greater clinical improvement with systemic and inhaled corticosteroids, including reductions in exacerbation frequency and improvements in lung function. Conversely, patients with low sputum eosinophils often derive limited benefit and may instead experience side effects without meaningful gains.

  This observation underpins steroid-sparing strategies that aim to taper oral corticosteroids in selected patients. In a real-world Australian cohort followed at the Royal Adelaide Hospital, optimising inhaled therapy while monitoring sputum eosinophils helped reduce average maintenance prednisone doses over a 12-month period without loss of asthma control.

  Guiding Biologic Therapy Selection

  Biologics targeting type 2 inflammation have transformed severe asthma management. Anti-IL-5 agents such as mepolizumab, benralizumab, and reslizumab deplete eosinophils or block their survival signals. Dupilumab blocks the shared receptor component of IL-4 and IL-13, while omalizumab addresses IgE-mediated pathways.

  High baseline sputum eosinophils predict stronger responses to anti-IL-5 biologics, with greater reductions in exacerbation rates and oral corticosteroid requirements. This predictive signal is particularly important under Australia's Pharmaceutical Benefits Scheme, where subsidy for these expensive therapies depends on documented evidence of eosinophilic inflammation. Specialists at the Woolcock Institute in Sydney have reported that combining sputum and blood eosinophil data improves confidence when applying for PBS-subsidised biologic therapy.

  Integrating Sputum and Peripheral Markers

  Sputum eosinophils correlate moderately with blood eosinophils, but the relationship is imperfect. Some patients have elevated sputum eosinophils despite normal peripheral counts, particularly those using maintenance oral corticosteroids. Conversely, blood eosinophilia can occur without significant airway eosinophilia, especially during infection or allergic flares. Many Australian respiratory physicians now use a tiered approach: blood eosinophils and FeNO as first-line screening, with sputum induction reserved for unclear cases, biologic selection decisions, and ongoing monitoring.

  Combining sputum eosinophils with fractional exhaled nitric oxide and serum IgE gives a fuller picture of type 2 inflammation. In practice, the biomarker panel is tailored to the individual clinical context. Telemedicine collaborations between metropolitan specialists and rural GPs offer one route to broaden access for patients living in regional Queensland and Western Australia.

  Translating Evidence into Australian Care

  Real-world implementation requires investment in training, infrastructure, and standardised protocols. Few Australian centres outside major tertiary hospitals currently have access to high-quality sputum cytometry, and transport logistics can compromise sample integrity for patients living in regional areas.

  The Australasian Severe Asthma Registry provides an additional layer of evidence, capturing how biomarker-guided therapy performs across diverse Australian settings. As protocols become more standardised and reimbursement frameworks evolve, sputum eosinophils are likely to play a larger role in everyday severe asthma care across the country, helping clinicians select the right biologic, taper steroids safely, and reduce the burden of unpredictable exacerbations for thousands of Australians.

  For clinicians working with patients who have exhausted standard therapies, the practical takeaway is clear: where sputum induction is feasible, it sharpens biologic selection, supports safer steroid tapering, and reduces preventable exacerbations. As protocols mature and reimbursement frameworks adapt, this decades-old biomarker is quietly regaining relevance in modern severe asthma care across Australia.

  Richard Russell Nuffield Department of Clinical Medicine, University of Oxford (United Kingdom)
• Mona Bafadhel King’s College London (United Kingdom)
  David Jackson Guy’s and St Thomas’ Hospital, King’s College London (United Kingdom)
• James Chalmers University of Dundee (United Kingdom)
  David Price University of Aberdeen (United Kingdom)