Advancing Asthma Research Through Biomarker Discovery

Photo Credit: CDC/ Margaret A. Parsons

Asthma affects more than 25 million Americans, yet this single diagnostic label encompasses a remarkably heterogeneous collection of airway diseases with distinct inflammatory mechanisms, triggers, and therapeutic responses.¹ The recognition that “asthma is not one disease” has transformed research approaches, driving the search for biomarkers that can identify specific disease endotypes, predict exacerbation risk, and guide personalized treatment selection. Asthma is one of the core conditions supported by our respiratory & metabolic conditions biospecimen portfolio.

High-quality biospecimens with comprehensive clinical characterization — and, where appropriate, linkable genomic annotation — serve as essential tools in asthma biomarker discovery. These datasets help researchers unravel disease heterogeneity and develop precision medicine approaches that move beyond a traditional one-size-fits-all treatment paradigm.

Understanding Asthma Heterogeneity

Asthma heterogeneity manifests across multiple dimensions, each influencing biomarker selection, study design, and therapeutic response interpretation.

Clinical Phenotypes

• Allergic asthma (triggered by environmental allergens)
• Non-allergic asthma (triggered by irritants, exercise, stress)
• Adult-onset asthma
• Childhood-onset asthma
• Exercise-induced bronchoconstriction
• Aspirin-exacerbated respiratory disease
• Occupational asthma

Severity Classification

• Intermittent asthma
• Mild persistent asthma
• Moderate persistent asthma
• Severe asthma
• Severe asthma with frequent exacerbations

Inflammatory Endotypes

• Type 2 high (eosinophilic) asthma
• Type 2 low (non-eosinophilic) asthma
• Neutrophilic asthma
• Paucigranulocytic asthma

This heterogeneity explains why some patients respond dramatically to inhaled corticosteroids while others derive minimal benefit, and why therapeutic advances like biologics benefit only specific patient subsets.² Biomarker discovery enables precision matching of patients to therapies and supports more efficient clinical trial enrollment and endpoint selection.

Key Biomarker Categories in Asthma Research

Type 2 Inflammation Biomarkers

The most clinically advanced asthma biomarkers identify Type 2 high inflammation:

• Blood eosinophil count: widely used marker predicting response to inhaled corticosteroids and several biologics
• Fractional exhaled nitric oxide (FeNO): non-invasive measure of airway inflammation, often elevated in Type 2 high asthma
• Serum IgE: total and allergen-specific IgE levels that guide anti-IgE therapy selection
• Serum periostin: matricellular protein associated with Type 2 inflammation and airway remodeling

Cytokine and Inflammatory Mediators

Plasma and serum biospecimens enable measurement of immune mediators such as:

• IL-4, IL-5, IL-13 (Type 2 cytokines)
• IL-17 (Type 17 inflammation)
• TNF-α, IL-6 (general inflammation)
• Thymic stromal lymphopoietin (TSLP)
• IL-33

These mediators function both as biomarkers and therapeutic targets addressed by biologic therapies.³

Genomic and Transcriptomic Markers

Access to whole blood and PBMCs supports:

• Gene expression profiling for molecular endotype identification
• Genetic risk scores for asthma susceptibility
• Pharmacogenomic variants associated with treatment response
• Epigenetic markers linked to disease development and severity

Novel Protein Biomarkers

Emerging protein biomarkers under investigation include:

• Club cell secretory protein (CC16)
• Surfactant proteins
• Matrix metalloproteinases
• Chitinases and chitinase-like proteins

The Value of Comprehensive Clinical Annotation

For asthma biomarker discovery, biospecimens must be paired with detailed clinical data to support phenotype and endotype assignment, covariate control, and outcome correlation.

Disease Characterization

• Confirmed asthma diagnosis (with spirometry)
• Age at diagnosis
• Asthma severity classification
• Exacerbation frequency and severity
• Hospitalization history
• ICU admissions requiring intubation

Pulmonary Function

• FEV1 and FVC measurements
• FEV1/FVC ratio
• Bronchodilator reversibility
• Peak expiratory flow variability
• Lung volumes and diffusion capacity (when available)

Allergic Sensitization

• Skin prick test results
• Specific IgE measurements
• Environmental allergen exposures (as collected/approved by protocol)

Treatment History

• Inhaled corticosteroid dose and duration
• Long-acting beta-agonist use
• Leukotriene modifiers
• Biologic therapies (omalizumab, mepolizumab, benralizumab, dupilumab, tezepelumab)
• Oral corticosteroid use and requirements
• Bronchial thermoplasty

Comorbidities

• Allergic rhinitis
• Chronic rhinosinusitis with nasal polyps
• Gastroesophageal reflux disease
• Obesity
• Obstructive sleep apnea

When these data elements are linkable to specimen timepoints — and complemented by genomic annotation where appropriate — biomarker studies can better distinguish true endotype signals from confounding effects of medications, comorbidities, or disease duration.

Biospecimen Types for Asthma Biomarker Research

Plasma and Serum

Plasma and serum are ideal for measuring:

• Eosinophil-derived proteins (eosinophil cationic protein, major basic protein)
• Inflammatory cytokines and chemokines
• IgE levels (total and specific)
• Periostin and other remodeling-associated proteins
• Metabolomic profiles

For assay development, validation panels, or inter-lab harmonization at scale, bulk plasma can support method standardization alongside patient-matched study specimens.

Whole Blood

Whole blood is essential for:

• Complete blood count with differential (eosinophil count)
• DNA extraction for genetic studies
• RNA isolation for gene expression profiling
• Flow cytometry of circulating leukocytes (method-dependent)

PBMCs

PBMCs are valuable for:

• Immune cell phenotyping
• T cell subset analysis (Th2, Th17, regulatory T cells)
• B cell characterization
• Functional assays of immune responses
• Single-cell RNA sequencing

Where deeper mechanistic immune work is required, immune subsets such as CD3+ T cells and CD56+ NK cells can support targeted functional assays and immune correlates research.

Current Frontiers in Asthma Biomarker Research

Biologic Therapy Selection

A major application of asthma biomarkers is guiding selection among multiple biologic options:

• High eosinophils + elevated IgE: consider anti-IgE therapy
• High eosinophils: consider anti-IL-5 pathway biologics
• Type 2 high inflammation: consider anti-IL-4Rα pathway approaches
• Broader phenotype coverage (including Type 2 low): consider upstream epithelial alarmin targets such as TSLP

Biospecimens enabling measurement of these markers support both therapeutic development and clinical decision-making.

Exacerbation Risk Prediction

Identifying patients at high risk for severe exacerbations enables preventive interventions. Biomarkers under investigation include:

• Blood eosinophil count trajectories
• FeNO levels
• Inflammatory cytokine patterns
• Gene expression signatures
• Metabolomic profiles

Treatment Response Biomarkers

Beyond baseline stratification, biomarkers that change with treatment provide insight into therapeutic efficacy, dose optimization, adherence, and the development of resistance.

Longitudinal biospecimen collections capturing pre-treatment, on-treatment, and post-treatment timepoints enable investigation of dynamic biomarker changes. Learn about our longitudinal collection capabilities.

Access to Specific Asthma Populations

Certain patient populations are particularly valuable for biomarker discovery and validation:

Severe Asthma Patients

• Persistent symptoms despite high-intensity treatment
• Frequent exacerbations
• Oral corticosteroid dependence
• High-value for testing novel biomarkers and therapeutics

Treatment-Naïve Patients

• Newly diagnosed asthma
• No prior controller medication use
• Useful for understanding baseline disease biology

Biologic-Treated Patients

• Matched pre- and post-treatment samples
• Responder vs non-responder characterization
• Mechanisms of therapeutic benefit

Specific Endotypes

• High eosinophilic asthma
• Neutrophilic asthma
• Paucigranulocytic asthma
• Type 2 low asthma

Sanguine’s network across the United States supports access to diverse asthma populations with confirmed diagnoses and detailed clinical characterization. For targeted cohorts, see prospective collection services.

Ensuring Quality in Asthma Biospecimen Research

Asthma research biospecimens should meet rigorous standards to ensure clinical relevance and analytical reliability.

Confirmed Diagnoses

• Spirometry demonstrating variable airflow limitation
• Bronchodilator reversibility or bronchial hyperresponsiveness
• Exclusion of COPD and other conditions
• Not suspected asthma without objective confirmation

Standardized Collection

• Consistent collection protocols
• Controlled timing relative to exacerbations (study-dependent)
• Standardized processing methods
• Appropriate storage conditions

Ethical Compliance

• IRB approval
• Informed patient consent
• HIPAA-compliant de-identification
• ISO-certified quality systems

Learn about our quality & compliance standards.

Real-World Impact of Asthma Biomarkers

Biomarker-guided treatment is transforming asthma care:

Case Example 1: Eosinophil-Guided Therapy

A patient with severe asthma and blood eosinophil count >300 cells/μL demonstrates excellent response to anti-IL-5 pathway biologic therapy, achieving exacerbation reduction and improved quality of life. Without biomarker guidance, this targeted therapy might not have been selected.

Case Example 2: Preventing Over-Treatment

A patient with predominantly Type 2 low asthma and low eosinophil count shows poor response to escalating inhaled corticosteroid doses. Biomarker profiling guides de-escalation of corticosteroids and investigation of alternative diagnoses or triggers.

The Future of Asthma Biomarkers

Emerging directions in asthma biomarker research include:

Multi-Omics Integration

• Combining genomics, transcriptomics, proteomics, and metabolomics
• Systems biology approaches to disease understanding
• Artificial intelligence for pattern recognition

Point-of-Care Biomarkers

• Rapid bedside assessment
• Real-time treatment decisions
• Monitoring during exacerbations

Environmental Biomarkers

• Interaction between patient biology and environmental exposures
• Personalized trigger identification
• Pollution and allergen exposure integration

Microbiome Markers

• Airway and gut microbiome characterization
• Relationship to disease phenotype
• Therapeutic targeting of dysbiosis

Conclusion

Asthma biomarker discovery is revolutionizing our understanding of airway disease heterogeneity and enabling precision medicine approaches that improve patient outcomes. High-quality biospecimens with comprehensive clinical characterization and, where appropriate, genomic annotation serve as essential tools for:

• Identifying disease endotypes
• Guiding biologic therapy selection
• Predicting exacerbation risk
• Understanding treatment response mechanisms
• Developing novel therapeutics

Access to well-characterized asthma biospecimens from patients with confirmed diagnoses, detailed phenotyping, and longitudinal follow-up accelerates discovery and clinical translation. Whether your research focuses on inflammatory mechanisms, therapeutic biomarker development, or precision medicine implementation, premium-quality asthma biospecimens from study design to receipt of samples provide the foundation for impactful discovery. Explore our full respiratory & metabolic conditions biospecimen portfolio for related conditions.

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References

1. Centers for Disease Control and Prevention. Asthma Data, Statistics, and Surveillance. Accessed December 2024.
2. Kuruvilla ME, Lee FE, Lee GB. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol. 2019;56(2):219-233. doi:10.1007/s12016-018-8712-1
3. Cahill KN, Katz HR, Cui J, et al. KIT inhibition by imatinib in patients with severe refractory asthma. N Engl J Med. 2017;376(20):1911-1920. doi:10.1056/NEJMoa1613125