Date of Award

January 2013

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Geoffrey L. Chupp

Subject Area(s)

Medicine

Abstract

IMPROVEMENT OF ASTHMA CONTROL AND INFLAMMATION IN PEDIATRIC PATIENTS UNDERGOING ADENOTONSILLECTOMY. Jonathan C Levin, Lisa Gagnon, David E Karas, and Geoffrey L Chupp. Section of Pulmonary and Critical Care, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.

Observational studies have suggested improvement in asthma control after adenotonsillectomy, but longitudinal studies that correlate the effect of the procedure on markers of airway inflammation with changes in asthma control are limited. We conducted a longitudinal, observational study on 130 pediatric patients undergoing adenotonsillectomy, including 66 with asthma and 64 control subjects. Asthma Control Test (ACT) scores, chitotriosidase (CHIT1) activity, and YKL-40 (CHI3L1) levels in the circulation were measured at the time of surgery and at a 6-month follow-up visit, and genotypes of chitinase family proteins were measured at baseline. Gene expression data was analyzed from blood, tonsil, and nasal epithelial tissue samples at baseline and in the blood at follow-up by microarray analysis. Mean ACT scores improved by 3 points (p< 0.001) after 6 months. 85% of children with poorly-controlled asthma demonstrated an increase in ACT score of at least 3 points or a decrease in Emergency Department/Urgent Care visits, oral corticosteroid courses, or rescue short acting bronchodilator usage. Serum chitinase activity decreased significantly in children with asthma (p< 0.01), but not in children without asthma (p= 0.83) undergoing tonsillectomy. Higher chitinase activity levels at baseline were associated with improved asthma control following surgery in all children with asthma (p< 0.01) and in the subgroup of children with poorly-controlled asthma (p< 0.05). Subjects with asthma had a higher allele frequency of the CHIT1 mutation (p< 0.02). Gene expression analysis identified a number of inflammatory genes differentially expressed in children who had improved asthma control that were not changed in children without improved control and control subjects. Of particular interest was SerpinB2, a plasmin activation inhibitor previously implicated in asthma, significantly downregulated after surgery compared to baseline in children with improved control. This data suggests that adenotonsillectomy improves asthma control by modulation of airway inflammation. Elevated serum chitinase activity may be a clinically useful determinant to identify patients with poorly-controlled asthma that will benefit from the procedure.

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