Phenotyping Responses to Systemic Corticosteroids in the Management of Asthma Attacks (PRISMA): Clinical and Translational Correlation to Point-Of-Care Biomarkers

RESEARCH BACKGROUND AND RATIONALE

Asthma attacks are loosely defined as symptom deterioration and/or lung function from baseline. In contrast, the more stringent classification of attack severity is based on the decision to treat: a severe episode requires ≥3 days of oral corticosteroids and/or hospitalization. Severe asthma attacks cause substantial morbidity, healthcare utilization, and avoidable deaths. Despite growing evidence of heterogeneity of mechanisms driving asthma attacks, the standard of care in acute asthma has not changed for 30 years. It consists of a 'one size fits all' treatment with oral corticosteroids and often antibiotics.

Data in a cross-sectional analysis of stable-state severe asthma showed the complementary and potentially additive value of blood eosinophils and FeNO. In this study of a cohort of patients with severe asthma proven to be highly adherent to high-intensity corticosteroid therapy, it was showed that blood eosinophils and FeNO non-suppression provide mechanistic information on two different immune compartments: blood eosinophils reflect the systemic pool of effector cells and circulating IL-5; whereas FeNO correlates with type-2 cytokine, chemokine, alarmin and eosinophilic inflammation in the airways.

In addition, epidemiological work investigating the annualized severe asthma attack rates in the control arm of randomized clinical trials showed additive value for baseline blood eosinophils and FeNO to predict asthma attacks. In those trial populations, a raised baseline FeNO (≥50 vs. <25 ppb) was associated with double the severe asthma attack rates for patients with similar blood eosinophilia (≥0.30×109/L). Further analyses revealed that the excess risk of asthma attacks conferred by both biomarkers was removed by type-2 targeted anti-inflammatory therapy.

In acute asthma, two studies have documented the heterogeneity of attacks. Still, treatment responses to acute systemic corticosteroid and antibiotic courses have not been related to the type-2 inflammatory phenotype and the presence of airway infection, respectively. Furthermore, evidence supporting acute point-of-care biomarker assessments is lacking, even though asthma attacks often present to general community practitioners and disproportionally affect isolated communities.