Phenotyping and Management Strategies in Severe Asthma

Severe asthma represents a heterogeneous condition characterised by recurrent exacerbations, persistent airflow limitation and an often-intractable symptom burden despite high-dose inhaled therapies. Advances in clinical and molecular phenotyping have revealed distinct patient subgroups defined by inflammatory patterns, biomarker profiles and comorbidities. Endotyping, which links mechanistic pathways to observable traits, has facilitated the development of targeted biologic agents and guided personalised management. Cluster-based approaches integrate clinical data, pulmonary function, airway inflammation and omics-derived signatures to delineate eosinophilic, neutrophilic, mixed granulocytic and paucigranulocytic subtypes. Management strategies now encompass biomarker-driven corticosteroid adjustment, biologic therapies directed at interleukin-5, interleukin-4 receptor α or immunoglobulin E, and non-pharmacological interventions such as bronchial thermoplasty for refractory phenotypes. Real-world cohorts and randomised trials continue to refine treatment algorithms by linking specific endotypes to drug response, highlighting the global imperative to tailor interventions and improve outcomes in this high-risk population.

Research from Nature Portfolio

Recent studies have applied high-dimensional immunoprofiling to children with life-threatening asthma admitted to intensive care. Plasma cytokine analysis coupled with gene expression in neutrophils uncovered two discrete endotypes distinguished by differential cytokine abundance and inflammatory signalling pathways. One subgroup exhibited elevated interleukins and toll-like receptor pathway activation, whereas the other showed relatively muted cytokine expression but a higher subsequent exacerbation risk. These findings underscore the need for stratified therapeutic approaches even in paediatric critical care settings and point towards alternative anti-inflammatory regimens for specific endotypes.

Phenotyping and Management Strategies in Severe Asthma publication trend

The graph below shows the total number of articles in phenotyping and management strategies in severe asthma across all publications each year (not limited to Nature Index journals).

Technical terms

Phenotype: Observable clinical and biological traits of asthma, including symptom patterns and inflammatory cell profiles.

Endotype: A subtype defined by distinct underlying pathophysiological mechanisms.

Biomarker: A measurable indicator of disease activity or therapeutic response, such as blood eosinophil count or exhaled nitric oxide.

Type 2 inflammation: An immune response driven by interleukins IL-4, IL-5 and IL-13, often associated with eosinophilic airway pathology.

Cluster analysis: A statistical method to group patients by similarity across multiple clinical and molecular variables.

References

1. Cluster analysis of plasma cytokines identifies two unique endotypes of children with asthma in the pediatric intensive care unit. Scientific Reports (2023).
2. Multidimensional endotyping in patients with severe asthma reveals inflammatory heterogeneity in matrix metalloproteinases and chitinase 3–like protein 1. Journal of Allergy and Clinical Immunology (2016).
3. Statistical Cluster Analysis of the British Thoracic Society Severe Refractory Asthma Registry: Clinical Outcomes and Phenotype Stability. PLOS ONE (2014).