Asthma Phenotyping and Immune Mechanisms

Asthma is now recognised as a complex syndrome encompassing multiple clinical phenotypes and mechanistic endotypes rather than a single disorder. Clinical phenotyping stratifies patients by observable characteristics such as symptom frequency, lung function variability and response to therapy, while endotyping seeks to define the underlying immunological and molecular pathways. Central to many asthmatic endotypes is type 2 inflammation, an immune pattern driven by T helper 2 cells and innate lymphoid cells releasing interleukins IL-4, IL-5 and IL-13. This process promotes eosinophil recruitment, mucus hypersecretion and airway remodelling. Conversely, non-type 2 endotypes may involve neutrophilic inflammation, Th17 responses and structural cell–mediated pathways independent of classic type 2 cytokines. Advances in high-throughput technologies—such as transcriptomics, proteomics and metabolomics—have facilitated the discovery of novel biomarkers and key regulatory networks, improving the precision of diagnostics and guiding targeted therapies. An integrated understanding of both local airway and systemic immune processes has underscored causal relationships between peripheral blood immune signatures and tissue-specific drivers. The global burden of asthma, particularly in resource-limited settings, highlights the need for accessible biomarkers and stratified treatment algorithms. Emerging biological agents that intercept specific cytokines, receptors or alarmins offer promise for personalised control of severe asthma, reducing exacerbations and reliance on systemic corticosteroids. Continued elucidation of intercellular communication, genetic modifiers and epithelial-immune interactions will be essential to refine endotype-directed interventions and improve long-term outcomes.

Research from Nature Portfolio

Recent studies have illuminated the genetic regulation of mucus plugging in severe asthma by examining a common variant in the gene encoding intelectin-1. Investigators demonstrated that IL-13 induction of intelectin-1 in a subset of mucus-secreting epithelial cells enhances binding to the MUC5AC mucin, promoting mucostasis and airway obstruction. Loss of intelectin-1 expression, due to a protective polymorphism, reduced mucus viscosity and plug formation in type 2-high patients. This work identifies intelectin-1 both as a biomarker predicting susceptibility to mucus plugging and as a potential target to alleviate airway occlusion in severe eosinophilic asthma.

Asthma Phenotyping and Immune Mechanisms publication trend

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

Technical terms

Phenotype: observable clinical presentation of asthma determined by measurable features such as symptom patterns, lung function and biomarker profiles.

Endotype: distinct mechanistic subtype of asthma defined by specific pathobiological pathways rather than clinical appearance.

Type 2 inflammation: immune response driven by T helper 2 cells and type 2 cytokines (such as IL-4, IL-5 and IL-13) leading to eosinophilic airway inflammation.

Eosinophil: a type of white blood cell central to allergic inflammation and airway damage in type 2 asthma.

Polymorphism: genetic variation at a single DNA locus among individuals that may influence disease susceptibility or severity.

Transcriptome: complete set of RNA transcripts produced by the genome in a given cell or tissue, reflecting gene‐expression patterns.

References

1. A common polymorphism in the Intelectin-1 gene influences mucus plugging in severe asthma. Nature Communications (2024).
2. Integrated study of systemic and local airway transcriptomes in asthma reveals causal mediation of systemic effects by airway key drivers. Genome Medicine (2023).
3. Current Understanding of Asthma Pathogenesis and Biomarkers. Cells (2022).
4. Molecular Targets for Biological Therapies of Severe Asthma. Frontiers in Immunology (2020).