I recently had the honor of hosting an educational session on biologics for asthma control — a topic that was new to me as a respiratory therapist. The mechanisms, pathways, and drug names can be complex, so I turned to writing as a way to deepen my understanding and make sense of the information. If this blog helps your understanding, please comment!

Asthma is no longer seen as a single disease but rather an umbrella term for multiple conditions that may appear similar but have distinct underlying mechanisms. This evolving perspective has revolutionized asthma management, emphasizing the importance of identifying phenotypes (clinical presentations) and endotypes (biological pathways) to guide more precise treatments. Today, managing asthma involves much more than simply prescribing albuterol.

Phenotypes vs. Endotypes: The Key to Precision Treatment

Asthma phenotypes categorize patients based on observable characteristics, such as age of onset, allergen sensitivity, or comorbid conditions. Some common asthma phenotypes include:

• Allergic asthma — Early-onset, often associated with IgE-mediated allergies.
• Late-onset eosinophilic asthma — Typically non-allergic, driven by eosinophilic inflammation.
• Aspirin-exacerbated respiratory disease (AERD) — Triggered by aspirin or NSAIDs.
• Obesity-related asthma — More common in adults, often without clear signs of inflammation.

While phenotypes help clinicians describe asthma presentations, endotypes provide deeper insight into the biological mechanisms driving the disease. The two primary endotypes are:

• T2-high asthma — Driven by Type 2 inflammation, involving eosinophils, IgE, and cytokines such as IL-4, IL-5, and IL-13.
• T2-low asthma — Characterized by neutrophilic or paucigranulocytic inflammation, often linked to infections, pollution, or metabolic factors like obesity.

Understanding which endotype a patient has allows for more effective, targeted treatment strategies.

The Role of T2 Inflammation in Severe Asthma

T2 inflammation is present in 55–70% of patients with severe asthma and plays a major role in airway inflammation and obstruction. This process begins when allergens or irritants activate the immune system, leading to:

1. TSLP activation — The cytokine thymic stromal lymphopoietin (TSLP) initiates T2 inflammation by triggering immune responses.
2. T-helper type 2 (Th2) and innate lymphoid cells (ILC2) activation — These cells release cytokines such as IL-4, IL-5, and IL-13, driving inflammation.
3. Eosinophilic airway inflammation and mucus overproduction — IL-5 supports eosinophil growth, while IL-13 contributes to mucus hypersecretion and airway remodeling.

Common biomarkers for T2-high asthma include:

• Elevated blood eosinophil count (AECs) (e.g., AEC ≥150–300 cells/μL for biologic therapy eligibility)
• Increased FeNO (fractional exhaled nitric oxide) (≥25 ppb)
• Elevated IgE levels or positive allergen-specific IgE tests

These biomarkers help identify candidates for biologic therapies targeting specific pathways in T2 inflammation.

Non-T2 Inflammation: The Less Understood Pathway

Unlike T2-high asthma, T2-low asthma lacks eosinophilic inflammation and does not respond well to corticosteroids or biologics targeting IL-4, IL-5, or IgE. Instead, neutrophilic or paucigranulocytic inflammation is often involved, driven by factors such as:

• Infections or pollution exposure — Triggering immune responses dominated by neutrophils.
• Obesity or metabolic factors — Affecting airway function without classic inflammation.
• Smoking-related airway remodeling — Leading to fixed obstruction and poor bronchodilator response.

T2-low asthma can be challenging to treat, as traditional asthma therapies are less effective. Tezepelumab (Tezspire) is the only biologic currently available that does not require biomarker testing and has shown efficacy in both T2-high and T2-low asthma.

Biologic Therapies: Matching the Right Treatment to the Right Patient

Biologic therapies have revolutionized asthma management by targeting specific inflammatory pathways. When considering a biologic, healthcare professionals should evaluate the patient’s:

• FDA-indicated phenotype (eosinophilic asthma, allergic asthma, or OCS-dependent asthma)
• Biomarkers (AECs, FeNO, IgE, allergen sensitivity)
• Comorbid conditions (e.g., nasal polyps, atopic dermatitis, eosinophilic esophagitis)
• Dosing preferences and adherence potential

Effectiveness and Selection of Biologic Therapies

The effectiveness of biologic therapies varies depending on the patient’s underlying asthma phenotype and endotype.

When Is a Patient a Candidate for Biologic Therapy?

A patient with persistent symptoms despite high-dose inhaled therapy would be considered a candidate for biologic therapy. Key indicators for biologic therapy in severe asthma include:

1. Frequent Exacerbations — Two or more asthma exacerbations per year requiring systemic corticosteroids suggest poor control and a need for a targeted approach.
2. High Oral Corticosteroid (OCS) Use — Patients who rely on long-term OCS therapy may benefit from biologics as a steroid-sparing option.
3. Elevated Biomarkers — Blood eosinophil count (AEC), FeNO, IgE levels, and allergen sensitivity help determine the best biologic choice.
4. Poor Lung Function (FEV1 Reduction) — A low FEV1 despite appropriate inhaled therapy suggests uncontrolled inflammation.
5. Comorbidities That Worsen Asthma — Conditions like nasal polyps and chronic rhinosinusitis may indicate a need for biologic therapy.

By addressing these factors, healthcare professionals can better determine the right biologic therapy for each patient.

Closing Thoughts and Call to Action

Severe asthma management has evolved significantly, moving from a generalized treatment approach to a more precise, biomarker-driven strategy. By identifying phenotypes and endotypes, selecting the most appropriate biologic therapy, and incorporating shared decision-making, healthcare professionals can provide more effective, personalized care.

As research continues to advance, staying informed about emerging treatments and best practices is crucial. Consider attending asthma-focused conferences, engaging in professional development, and following the latest clinical guidelines. The more we learn, the better we can support our patients in achieving optimal asthma control and improving their quality of life.