Applying Precision Medicine to the Heterogeneity of Asthma Attacks.

Abstract

The standard of care for management of asthma attacks has remained unchanged for 70 years, relying on a symptom-based, severity-stratified approach. Severe asthma attacks are defined by a worsening of asthma requiring oral corticosteroid (OCS) treatment for unresolved symptoms for at least 48 hours, decreased lung function, or both. The 1-size-fits-all strategy with OCS treatment overlooks the biological mechanisms driving attacks and may lead to suboptimal outcomes. Importantly, OCS-related toxicities lead to significant morbidity, and cumulative OCS use has been associated with increased mortality. Antibiotics, often used indiscriminately, also increase adverse events and antimicrobial resistance. Recent studies have highlighted the heterogeneity of asthma attacks across clinical, etiologic, and therapeutic dimensions. Biomarker-informed assessments using blood eosinophils, exhaled nitric oxide (Feno), and point-of-care microbial molecular testing have improved the evaluation of attacks. Observational studies and trials have explored biomarker-guided management to reduce OCS and antibiotic use, potentially improving outcomes. Distinct inflammatory and OCS response profiles were identified in patients receiving biologics, emphasizing the complexity of attacks and the importance of residual (untreated) type 2 inflammatory pathways. Studies of the airway microbiome revealed that microbial dysbiosis is associated with clinical and inflammatory clusters. Asthma attacks are complex episodes with diverse causes, endotypes, and phenotypes. Emerging evidence supports incorporating biomarkers (blood eosinophils, Feno, and microbial testing) into clinical assessment to refine management. Recent evidence expands our understanding of exacerbation mechanisms, highlighting the need for tailored management strategies. Recognizing asthma heterogeneity could shift care toward precision medicine, reducing OCS reliance and improving patient outcomes.