Asthma is the clearest example in the inflammatory catalogue of a diagnosis that describes a symptom pattern rather than a mechanism. Two donors can both carry the label and sit at opposite ends of the type 2 axis, with different blood eosinophil counts, different cytokine tone and opposite responses to every targeted therapy on the market. Recruiting on the diagnosis alone is how asthma cohorts end up with variance that swamps the effect being measured.
The endotype split is the first thing to specify
Contemporary asthma research divides the population by inflammatory endotype rather than by severity alone. Type 2 high disease is characterized by eosinophilic airway inflammation, raised blood eosinophils, elevated fractional exhaled nitric oxide and frequently atopy. Type 2 low disease shows neutrophilic or paucigranulocytic inflammation, tends to present later, is more associated with obesity and smoking, and responds poorly to the therapies that transformed type 2 high disease.
Blood eosinophil count is the single most useful annotation because it is measured routinely, it is available in almost every clinical record, and it stratifies the population along the axis that matters. It should be treated as a continuous variable rather than dichotomised, since the thresholds used clinically are pragmatic rather than biological.
| Endotype | Blood signature | Typical associations | Research use |
|---|---|---|---|
| Type 2 high, allergic | Raised eosinophils, raised total IgE, sensitisation | Earlier onset, atopic comorbidity | Type 2 cytokine biology, allergen-driven mechanisms |
| Type 2 high, non-allergic | Raised eosinophils, IgE not elevated | Later onset, nasal polyposis common | Eosinophilic biology without allergic drive |
| Type 2 low, neutrophilic | Neutrophil predominant, eosinophils low | Obesity, smoking, later onset | Non-type-2 mechanisms, an under-served research area |
| Paucigranulocytic | Neither raised | Often milder or well controlled | Comparator arm within the diagnosis |
Severity and control are different variables and both get recorded as one
Severity describes the treatment intensity required to maintain control. Control describes current symptom burden. A donor on high-dose inhaled corticosteroid and a long-acting bronchodilator with no symptoms is severe and controlled. A donor on low-dose therapy with frequent symptoms is mild and uncontrolled. These produce different circulating profiles and are routinely collapsed into a single severity field.
Recording treatment step alongside a control measure separates them, and both are normally in the clinical record already.
Related product
Disease-state PBMCs. PBMCs from donors with a documented diagnosis, across 24 autoimmune and inflammatory indications.
Inhaled and systemic corticosteroid exposure differ enormously
Inhaled corticosteroid is delivered to the airway with limited systemic exposure at standard doses, so its effect on circulating cells is modest compared with oral therapy. Oral corticosteroid, whether maintenance or a recent exacerbation course, suppresses circulating eosinophils markedly and shifts lymphocyte counts within days.
A donor sampled shortly after an oral steroid burst can have a blood eosinophil count that misrepresents their underlying endotype completely, which is the most common way an asthma cohort gets misclassified. Time since the last oral corticosteroid course belongs in the required fields.
Biologic therapy defines what the sample can still answer
Targeted biologics in severe asthma include anti-immunoglobulin E, anti-interleukin 5 and anti-interleukin 5 receptor agents, interleukin 4 receptor alpha blockade and thymic stromal lymphopoietin blockade. Each removes a different part of the type 2 axis, and anti-interleukin 5 receptor therapy in particular depletes circulating eosinophils almost entirely.
That has an obvious consequence. A donor on eosinophil-depleting therapy cannot support an eosinophil-based readout, and their blood eosinophil count no longer describes their endotype. These donors remain valuable for pharmacodynamic work and for studying the residual compartment, provided the agent and duration are recorded.
Comorbidity travels with the endotypes
Allergic rhinitis, chronic rhinosinusitis with nasal polyposis and atopic dermatitis cluster with type 2 high disease, while obesity, gastro-oesophageal reflux and obstructive sleep apnoea cluster with type 2 low disease. Because these comorbidities carry their own circulating signatures, the endotype and the comorbidity profile are partly confounded by nature.
The practical response is to record comorbidity rather than attempt to exclude it, since an asthma cohort with no comorbidity is not representative of the population any therapy will be used in.
What cryopreserved material supports here
Type 2 and type 1 cytokine production on stimulation, memory T cell subset distribution, innate lymphoid cell frequencies, monocyte subsets and signalling capacity under cytokine challenge all work from cryopreserved mononuclear cells. Direct eosinophil and basophil functional work does not, because granulocytes are largely removed by the density gradient separation used to prepare mononuclear cells and those populations tolerate freezing poorly.
Specifying an asthma cohort
OrganaBio supplies disease-state donor material across 24 autoimmune and inflammatory indications for research use, covering discovery, drug screening and biomarker work, with a post-thaw viability specification above 80 percent. Donor-matched plasma, serum and PBMCs from the same donor are available, which most suppliers cannot provide. Donor selection can be scoped by disease state, HLA genotype, age, sex, ethnicity, blood type, CMV and EBV status, BMI and smoking status, all subject to availability.
For this indication the parameters worth naming are blood eosinophil count with the date it was measured, atopy and total IgE status, treatment step, time since any oral corticosteroid course, current biologic agent with duration, smoking status and body mass index.
High-resolution NGS HLA genotyping is performed across HLA-A, HLA-B, HLA-C, HLA-DR, HLA-DQ and HLA-DP, and KIR genotyping is included in donor characterization. Where a design needs the same donor sampled more than once, the repeat-collection program covers eligible donors and is not a blanket guarantee for every donor or request.
Related material: what a mononuclear cell preparation contains, how HLA typing resolution is reported, and the cryopreserved PBMC format.
Frequently asked questions
Why is blood eosinophil count the most useful annotation?
Because it is measured routinely, sits in almost every clinical record, and stratifies the population along the type 2 axis that determines mechanism and treatment response. Treat it as a continuous variable, since clinical thresholds are pragmatic rather than biological.
How does recent oral corticosteroid affect endotype assignment?
It suppresses circulating eosinophils markedly within days, so a count taken during or shortly after a course will understate the true endotype. Use a count from a stable period and record when it was taken.
Can donors on anti-interleukin 5 therapy support eosinophil work?
No. Anti-interleukin 5 receptor therapy depletes circulating eosinophils almost entirely, and their eosinophil count no longer describes their endotype. Those donors remain useful for pharmacodynamic work and for the residual compartment.
Are severity and control the same variable?
No. Severity reflects the treatment intensity needed to maintain control; control reflects current symptom burden. A donor can be severe and controlled or mild and uncontrolled. Record treatment step and a control measure separately.
Is type 2 low asthma worth sourcing?
It is arguably the more under-served research population, since it responds poorly to existing type 2 directed therapies. It associates with obesity, smoking and later onset, so comparators should be matched on body mass index and smoking status.
Why exclude eosinophil functional assays from cryopreserved material?
Granulocytes are largely removed by the density gradient separation used to prepare mononuclear cells, and they tolerate freezing poorly. Those questions need a different sample type.
What viability specification applies to this material?
Disease-state donor material carries a post-thaw viability specification above 80 percent. That figure applies to the disease-state line specifically and is not carried across from healthy donor products.
Can this material be used for clinical manufacturing?
No. Disease-state donor material is supplied for research use covering discovery, drug screening and biomarker work. Material intended for further manufacturing is a separate cGMP scope with its own agreement and documentation requirements.
Talk to OrganaBio
Sourcing an asthma cohort?
Donor selection can be scoped by disease state, HLA genotype and donor characteristics, subject to availability, and donor-matched plasma, serum and PBMCs are available from the same donor. Tell us the parameters your protocol needs and the scientific team will confirm what can be supplied.
