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Lung Lavage Granulocyte Patterns and Clinical Phenotypes in Children with Severe, Therapy-Resistant Asthma
W Gerald Teague1, Monica G Lawrence2, Debbie-Ann T Shirley1
1Child Health Research Center, Division of Respiratory Medicine, Allergy, and Immunology, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Va.
Insights
Severe asthma in children is often poorly controlled. Bronchoalveolar lavage (BAL) revealed distinct granulocyte patterns and pathogens, offering new targets for treating refractory pediatric asthma.
Area of Science:
- Pediatric Pulmonology
- Asthma Research
- Immunology
Background:
- Severe pediatric asthma frequently involves exacerbations despite high-dose corticosteroid treatment.
- Underlying causes like refractory lung inflammation and infections in children with severe asthma are not well understood.
Purpose of the Study:
- To identify prevalent granulocyte patterns in children with severe asthma.
- To detect potential pathogens as targets for improved asthma treatment strategies.
Main Methods:
- 126 children with severe asthma underwent bronchoscopy with bronchoalveolar lavage (BAL).
- BAL analysis included cell counts, differential, bacterial/viral studies, spirometry, and blood tests for eosinophils and IgE.
- Outcomes were compared across four distinct BAL granulocyte patterns.
Main Results:
- Pauci-granulocytic BAL was most common (52%), associated with less airflow limitation and enterovirus detection.
- Isolated neutrophilia BAL showed more bacterial pathogens than pauci-granulocytic BAL.
- Mixed granulocytic BAL was linked to higher prednisone use, eosinophilia, and allergen sensitization.
Conclusions:
- Distinct BAL granulocyte patterns and infectious agents in severe pediatric asthma correlate with unique phenotypic features.
- Findings suggest potential for pathway-specific treatment revisions, including anti-TH2 therapies for eosinophilic infiltration (32%) and antibiotics for bacterial pathogens (12%).
Background:
Children with severe asthma have frequent exacerbations despite guidelines-based treatment with high-dose corticosteroids. The importance of refractory lung inflammation and infectious species as factors contributing to poorly controlled asthma in children is poorly understood.
Objective:
To identify prevalent granulocyte patterns and potential pathogens as targets for revised treatment, 126 children with severe asthma underwent clinically indicated bronchoscopy.
Methods:
Diagnostic tests included bronchoalveolar lavage (BAL) for cell count and differential, bacterial and viral studies, spirometry, and measurements of blood eosinophils, total IgE, and allergen-specific IgE. Outcomes were compared among 4 BAL granulocyte patterns.
Results:
Pauci-granulocytic BAL was the most prevalent granulocyte category (52%), and children with pauci-granulocytic BAL had less postbronchodilator airflow limitation, less blood eosinophilia, and less detection of BAL enterovirus compared with children with mixed granulocytic BAL. Children with isolated neutrophilia BAL were differentiated by less blood eosinophilia than those with mixed granulocytic BAL, but greater prevalence of potential bacterial pathogens compared with those with pauci-granulocytic BAL. Children with isolated eosinophilia BAL had features similar to those with mixed granulocytic BAL. Children with mixed granulocytic BAL took more maintenance prednisone, and had greater blood eosinophilia and allergen sensitization compared with those with pauci-granulocytic BAL.
Conclusions:
In children with severe, therapy-resistant asthma, BAL granulocyte patterns and infectious species are associated with novel phenotypic features that can inform pathway-specific revisions in treatment. In 32% of children evaluated, BAL revealed corticosteroid-refractory eosinophilic infiltration amenable to anti-TH2 biological therapies, and in 12%, a treatable bacterial pathogen.
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