Progression of Difficult Wheeze to Persistent Asthma in Children: Ontogeny of Anatomic, Inflammatory, and Physiological Factors with Age
Saturday, March 3, 2018
South Hall A2 (Convention Center)
W. Gerald Teague, MD, Monica G. Lawrence, MD, Stephen Early, MD, John W. Steinke, PhD FAAAAI, Andrea Garrod, MD, Debbie-Ann Shirley, MD, Thomas J. Braciale, MD, PhD, Michael Ellwood, Larry Borish, MD FAAAAI
RATIONALE: Childhood asthma often progresses from an early life inception phase to an established syndrome by school-age. Few studies have addressed the ontogeny of lower respiratory and systemic markers of inflammation with maturation in children with difficult wheeze and asthma.

METHODS: 231 children spanning 3 months to 20 years of age wheeze and asthma resistant to guidelines-based treatment had bronchoscopy with BAL for granulocyte counts and pathogens in the lower respiratory air spaces, systemic markers of inflammation, and lung function.

RESULTS: Infants ≤ 12 months (n =15) had the highest prevalance of anatomic anomalies (73%), positive BAL pathogens (89%), and BAL neutrophilia (89%). Many children 1-5 years (n = 95) met criteria for asthma (53%), but anatomic anomalies were common (61%) with frequent BAL neutrophilia either isolated (41%) or with eosinophilia (10%), and prevalent BAL pathogens (56%). Children 6-11 years (n=73) primarily had asthma (96%), with heterogenous BAL granulocyte patterns, prevalent allergen sensitization (65%), blood eosinophilia (51%), airflow limitation (42%), and relatively fewer BAL pathogens (46%). Adolescents 12-18 years (n=48) mostly had asthma (96%), with the highest prevalence of pauci-granulocytic BAL (67%), the highest allergen sensitization (75%), lower blood eosinophilia (31%), the greatest prevalence of airflow limitation (56%), and few BAL pathogens (15%).

CONCLUSIONS: In children with problematic wheeze and asthma, common patterns of air space and systemic inflammation differ with maturation. In pre-school children anatomic anomalies and BAL neutrophilia with infection predominate, whereas by school-age children with asthma have heterogeneous air space granulocyte patterns informed by allergens, pathogens, and corticosteroid treatment.