Advancing Asthma Research Through Biomarker Discovery

Photo Credit: CDC/ Margaret A. Parsons

Asthma affects more than 25 million Americans. But that single label covers many different airway diseases, each with its own inflammatory mechanism, trigger, and treatment response.¹ Researchers now recognize that asthma isn’t one disease — it’s many. That shift has driven the search for biomarkers that can identify specific disease endotypes, predict exacerbation risk, and guide personalized treatment. Asthma is one of the core conditions supported by our respiratory & metabolic conditions biospecimen portfolio.

High-quality biospecimens with detailed clinical data — and, where appropriate, linkable genomic annotation — are essential tools for this work. They help researchers untangle disease heterogeneity and build precision medicine approaches that go beyond one-size-fits-all treatment.

Understanding Asthma Heterogeneity

Asthma heterogeneity shows up in several ways. Each one affects biomarker selection, study design, and how we interpret treatment response.

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 variation explains why some patients respond well to inhaled corticosteroids while others see little benefit. It’s also why biologic therapies only help certain patient subsets.² Biomarker discovery helps match patients to the right therapy, and it 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 let researchers measure 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 work as both biomarkers and treatment targets for 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 need detailed clinical data alongside them. This supports phenotype and endotype assignment, helps control for confounding factors, and links markers to outcomes.

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

Linking this data to specimen timepoints — and including genomic annotation where appropriate — helps biomarker studies separate true endotype signals from confounding effects. Those effects include medications, comorbidities, and 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 help standardize methods 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

For deeper mechanistic immune work, immune subsets like CD3+ T cells and CD56+ NK cells 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 that let researchers measure these markers support both drug 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 shift with treatment offer insight into how well a therapy is working, dose optimization, adherence, and resistance.

Longitudinal biospecimen collections — capturing pre-, on-, and post-treatment timepoints — let researchers track how biomarkers change over time. 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 gives researchers access to diverse asthma populations with confirmed diagnoses and detailed clinical data. For targeted cohorts, see prospective collection services.

Ensuring Quality in Asthma Biospecimen Research

Asthma research biospecimens should meet strict standards to ensure they’re clinically relevant and reliable to analyze.

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 a blood eosinophil count above 300 cells/μL responds well to anti-IL-5 pathway biologic therapy. They have fewer exacerbations and a better quality of life. Without biomarker guidance, doctors might never have chosen this targeted therapy.

Case Example 2: Preventing Over-Treatment

A patient with mostly Type 2 low asthma and a low eosinophil count responds poorly to higher inhaled corticosteroid doses. Biomarker profiling supports lowering the corticosteroid dose and prompts a look at other possible 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 changing how we understand airway disease heterogeneity. It’s enabling precision medicine approaches that improve patient outcomes. High-quality biospecimens with detailed clinical data — and, where appropriate, genomic annotation — are 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 — speeds up discovery and clinical translation. Whether your research focuses on inflammatory mechanisms, biomarker development, or precision medicine, premium-quality asthma biospecimens give you a strong foundation. That foundation spans from study design to sample delivery. Explore our full respiratory & metabolic conditions biospecimen portfolio for related conditions.

---

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