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)

• The Role of Eosinophil Granule Proteins in Asthma

  Asthma is a diverse inflammatory disease rather than a single condition with one biological pathway. In many people, particularly those with type 2 inflammation, eosinophils accumulate in the airways and release granule proteins that can injure the respiratory epithelium, amplify inflammation and worsen airway hyperresponsiveness.

  These proteins are increasingly relevant to precision respiratory medicine. They help explain why some patients experience frequent exacerbations, persistent mucus production or progressive loss of lung function, even when symptoms appear controlled between attacks. Their effects also connect laboratory findings with practical decisions about inhaled treatment and biologic therapy.

  For clinicians working across Australia, this science has relevance in metropolitan hospitals in Sydney, Melbourne and Brisbane, as well as regional services where access to induced sputum testing and specialist review may be limited. Understanding eosinophil biology can support more consistent assessment and better use of available therapies.

  Eosinophils And Type 2 Airway Inflammation

  Eosinophils are white blood cells involved in host defence and allergic inflammation. In asthma, cytokines such as interleukin-5 promote their production, survival and recruitment from the bloodstream into airway tissue. Chemokines, including eotaxin, then help direct eosinophils towards inflamed bronchial mucosa.

  Once activated, eosinophils can undergo piecemeal degranulation or release extracellular traps. These processes deliver concentrated inflammatory material into the airway environment. The result may include epithelial damage, increased sensitivity of airway smooth muscle and a cycle of inflammation that makes symptoms harder to control.

  Major Granule Proteins And Their Effects

  The best-characterised eosinophil granule proteins are major basic protein, eosinophil peroxidase, eosinophil cationic protein and eosinophil-derived neurotoxin. Major basic protein can disrupt epithelial cells and alter smooth muscle reactivity. Eosinophil peroxidase contributes to oxidative injury by generating reactive oxidant products in the presence of hydrogen peroxide and halides.

  Eosinophil cationic protein is strongly associated with cell toxicity and may impair epithelial integrity. Eosinophil-derived neurotoxin has ribonuclease activity and can influence innate immune signalling. These proteins do not act in isolation: their combined effects can increase mucus secretion, expose sensory nerves and intensify bronchial hyperresponsiveness.

  Airway Damage And Remodelling

  The airway epithelium forms a protective barrier against inhaled allergens, pollutants and infectious agents. Granule proteins can weaken this barrier, making it easier for irritants to reach deeper tissues. Damaged epithelial cells release alarm signals that stimulate additional immune responses, including the production of cytokines and chemokines.

  Repeated inflammation may contribute to airway remodelling, a process involving thickening of the reticular basement membrane, changes in smooth muscle mass and increased mucus gland activity. Eosinophil proteins are one part of this process, alongside mast cells, T-helper 2 lymphocytes, epithelial cytokines and structural airway cells. This helps explain why long-standing asthma can become less reversible over time.

  Biomarkers In Clinical Assessment

  Blood eosinophil counts are widely used as a practical marker of type 2 inflammation. They are easy to obtain and can help identify people more likely to respond to corticosteroids or selected biologic medicines. However, a single result may be affected by recent steroid use, infection, seasonal allergens and natural biological variation.

  Sputum eosinophils offer a closer measure of airway inflammation but require specialist laboratory expertise. Measuring granule proteins directly remains more common in research than routine care. In Australia, respiratory teams may need to interpret blood results alongside spirometry, fractional exhaled nitric oxide, exacerbation history and treatment adherence, especially when advanced testing is unavailable outside major centres.

  Relationship With Asthma Severity

  High eosinophil activity is often linked with exacerbation-prone disease, reduced lung function and a greater risk of emergency treatment. It may also be associated with adult-onset asthma, chronic rhinosinusitis with nasal polyps and sensitivity to aspirin or other non-steroidal anti-inflammatory medicines.

  The relationship is not absolute. Some patients with severe symptoms have little evidence of eosinophilic inflammation, while others with raised eosinophils may report modest day-to-day symptoms. Clinical interpretation therefore requires a broader view of airway phenotype, exposure history, comorbidities and the pattern of attacks over time.

  Implications For Treatment

  Inhaled corticosteroids remain central because they suppress several components of type 2 inflammation and reduce eosinophil survival. Regular use can lower airway eosinophilia and decrease the release of damaging granule proteins. Poor adherence, incorrect inhaler technique or ongoing exposure to triggers can make treatment appear ineffective when the underlying medicine has not been used consistently.

  For eligible patients with severe eosinophilic asthma, biologic therapies may target interleukin-5, the interleukin-5 receptor, immunoglobulin E or the interleukin-4 receptor pathway. Medicines such as mepolizumab, benralizumab and dupilumab are used within specialist frameworks, including Australia’s Pharmaceutical Benefits Scheme criteria. Their role is to reduce exacerbations and oral corticosteroid dependence, rather than simply improve an isolated laboratory value.

  Research Directions And Clinical Translation

  Current research is examining how granule proteins interact with airway nerves, epithelial repair mechanisms and the lung microbiome. Better assays may eventually distinguish active eosinophil degranulation from the mere presence of eosinophil cells. This could improve prediction of treatment response and identify patients at risk before a major flare.

  The field also highlights the value of coordinated care. Australian patients may move between general practice, hospital respiratory clinics and rural or remote health services, creating gaps in monitoring. Clear documentation of eosinophil results, exacerbations, inhaler use and biologic eligibility can make specialist decisions more consistent across these settings.

  The biology of eosinophil granule proteins provides a useful bridge between inflammation and patient outcomes. It clarifies how eosinophils can damage the airway, why type 2 biomarkers matter and how targeted treatment may reduce the burden of severe disease. The immediate practical step is to review each patient’s recent blood eosinophil count alongside exacerbation history, inhaler technique and corticosteroid exposure at the next asthma assessment.

  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)