Overview
Definition:
Asthma biologic selection in pediatrics involves using targeted therapies, primarily monoclonal antibodies, to treat severe or uncontrolled asthma that is refractory to conventional inhaled corticosteroids and long-acting beta-agonists
This approach is guided by specific phenotypic characteristics of the child's asthma, such as eosinophilic inflammation or allergic sensitization.
Epidemiology:
Asthma is the most common chronic respiratory disease in children, affecting approximately 6-9% globally
Severe asthma accounts for 5-10% of childhood asthma cases
Phenotyping allows for more precise management of these complex cases, which are associated with higher healthcare utilization and poorer quality of life.
Clinical Significance:
Identifying distinct asthma phenotypes is crucial for optimizing treatment strategies
Phenotype-based selection of biologics offers a paradigm shift from a one-size-fits-all approach, leading to improved symptom control, reduced exacerbations, decreased oral corticosteroid dependence, and enhanced overall well-being in children with severe asthma
This is critical for residents preparing for DNB and NEET SS examinations.
Phenotypes And Biologic Targets
Allergic Asthma Type 2 High:
Characterized by elevated IgE, eosinophils, and atopy
Targeted by anti-IgE (omalizumab) and anti-IL-5/5R (mepolizumab, reslizumab, benralizumab).
Eosinophilic Asthma Type 2 High:
Defined by persistent sputum eosinophilia (>=300 cells/µL) or blood eosinophilia (>=400 cells/µL) independent of atopy
Targeted by anti-IL-5/5R agents.
Other Phenotypes:
Includes neutrophilic asthma and paucigranulocytic asthma, for which current biologic options are less established, though research is ongoing for other targets like TSLP.
Biologic Agents In Pediatrics
Omalizumab Anti Ige:
Indicated for moderate-to-severe persistent allergic asthma in children aged 6 years and older with sensitization to perennial allergens
Administered subcutaneously every 2-4 weeks
Dosage based on IgE levels and body weight.
Anti Il 5 Inhibitors:
Mepolizumab: Approved for severe eosinophilic asthma in children aged 12 years and older
Reslizumab: Approved for severe eosinophilic asthma in adults (less data in pediatrics)
Benralizumab: Approved for severe eosinophilic asthma in children aged 12 years and older
All administered subcutaneously every 4-8 weeks.
Anti Il 4 Receptor Alpha Inhibitors:
Dupilumab: Approved for moderate-to-severe atopic asthma in children aged 6 years and older with type 2 inflammation
Blocks both IL-4 and IL-13 signaling
Administered subcutaneously every 2-4 weeks.
Patient Selection And Assessment
Diagnostic Evaluation:
Confirm diagnosis of severe asthma
Assess for persistent symptoms despite optimal conventional therapy
Evaluate for type 2 inflammation markers: elevated IgE, blood/sputum eosinophilia, atopy (skin prick tests or specific IgE).
Exclusion Criteria:
Rule out alternative diagnoses or contributing factors such as poorly controlled rhinosinusitis, GERD, obesity, vocal cord dysfunction, or environmental exposures
Ensure adherence to prescribed inhaled therapies.
Monitoring Response:
Assess treatment response after 3-6 months using validated asthma control questionnaires (e.g., ACT/cACT), spirometry (FEV1), exacerbation rates, and oral corticosteroid reduction
Discontinue if no significant benefit is observed.
Management Considerations And Follow Up
Initiation And Dosing:
Biologics are typically initiated by a pediatric pulmonologist
Dosing is weight-based and/or IgE level-based for omalizumab, and fixed for IL-5 and IL-4/13 inhibitors
Ensure proper patient and caregiver education on administration and potential side effects.
Adverse Events:
Common side effects include injection site reactions
Anaphylaxis is rare but serious, particularly with omalizumab
Monitor for any new or worsening symptoms, including infections.
Long Term Management:
Continue with optimal conventional therapy alongside biologics
Regular follow-up with the pulmonologist is essential to monitor efficacy, safety, and potential need for dose adjustment or discontinuation
Consider transitioning to adult care when appropriate.
Key Points
Exam Focus:
Phenotype-based selection is key for severe pediatric asthma
Type 2 inflammation markers (IgE, eosinophils, atopy) guide choice of omalizumab, anti-IL-5, or anti-IL-4/13 agents
Know indications, age limits, and common administration routes for each biologic.
Clinical Pearls:
Always re-evaluate the patient and optimize conventional therapy before initiating biologics
Consider the burden of disease and patient preferences when discussing treatment options
Early identification of non-responders is crucial.
Common Mistakes:
Starting biologics without a clear phenotype or adequate trial of conventional therapy
Failing to monitor response adequately
Not excluding alternative diagnoses or exacerbating factors.