School of Medicine and Health Sciences Poster Presentations

Title

Mixed immune response in Pediatric severe asthma

Poster Number

345

Document Type

Poster

Status

Research Fellow

Abstract Category

Clinical Specialties

Keywords

Severe Asthma, Children, Cytokines, Bronchoalveolar Lavage, Th1 Th2 Th17.

Publication Date

Spring 2018

Abstract

Rationale: Severe asthma account for 5-10% of all patients but >70% of healthcare cost. While the majority of asthma is thought to be driven by a Th2 immune response, recent data suggests Th1 and Th17 responses may play a role in severe asthma. Few studies have evaluated Broncho alveolar lavage (BAL) cytokines in pediatric severe asthma. In this pilot study, we hypothesize that children with severe asthma exhibit a mixed Th2 and Th1/Th17 response based on BAL cytokine profiling. Method: BAL samples and data were collected from children undergoing bronchoscopy for severe refractory asthma symptoms or chronic cough. MSD multiplex kits were used to measure Th1 (IFN-Y, IL-1β, TNF-α), Th2 (IL-5, IL-13, TSLP) and Th17 (IL-17A, IL21, IL-23, and IL-33) cytokines in BAL. Data collected included demographics, asthma history, serum IgE and eosinophils, BAL neutrophil and eosinophil count. Asthma severity was defined based on NAEPP criteria. BAL results and clinical characteristics were analyzed comparing severe asthma to non-severe asthma subjects. Results: A total of 22 children were included in this study of which 17 BAL samples were analyzed (77.2% male, median age 6.0 yrs (SED ±1.1), 72.7% African American). Overall, median FEV1 was 86% predicted (SED ±3.2), serum IgE 80IU/ml (SED ±145.8) and serum eosinophilia 0.34K/mcl. Children with severe asthma were older [10.0 vs. 2.0 years (p <0.001)], received a higher number of systemic steroid courses in the past year [3 vs. 2 (p= 0.05), and had a higher median BAL eosinophil (14 vs. 0% (p<0.001)]. After correcting for age, there was no increase in any BAL cytokine in severe vs. non-severe asthma. Unlike findings in non-severe asthma, there was a significant positive correlation in the severe asthma cohort between IL-13 and TNF-α (p= 0.003), IL-5 with Th17 (IL-23, IL-33) (p= 0.001 for both), and IL-13 with Th17 (IL-23, IL-33) (p=0.017, 0.023 respectively). Conclusion: In pediatric patients with severe asthma, BAL samples showed multiple correlations between Th1, Th2, and Th17 cytokines. This reflects a mixed immune response of different T-helper cells unique to severe asthma in children. This may help explain inadequate responses to current treatment measures, including steroids. Further studies are needed to evaluate mechanisms for this mixed response in epithelium, smooth muscle and sub-epithelial structures, which may lead to other therapeutic targets for severe, therapy resistant asthma.

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Mixed immune response in Pediatric severe asthma

Rationale: Severe asthma account for 5-10% of all patients but >70% of healthcare cost. While the majority of asthma is thought to be driven by a Th2 immune response, recent data suggests Th1 and Th17 responses may play a role in severe asthma. Few studies have evaluated Broncho alveolar lavage (BAL) cytokines in pediatric severe asthma. In this pilot study, we hypothesize that children with severe asthma exhibit a mixed Th2 and Th1/Th17 response based on BAL cytokine profiling. Method: BAL samples and data were collected from children undergoing bronchoscopy for severe refractory asthma symptoms or chronic cough. MSD multiplex kits were used to measure Th1 (IFN-Y, IL-1β, TNF-α), Th2 (IL-5, IL-13, TSLP) and Th17 (IL-17A, IL21, IL-23, and IL-33) cytokines in BAL. Data collected included demographics, asthma history, serum IgE and eosinophils, BAL neutrophil and eosinophil count. Asthma severity was defined based on NAEPP criteria. BAL results and clinical characteristics were analyzed comparing severe asthma to non-severe asthma subjects. Results: A total of 22 children were included in this study of which 17 BAL samples were analyzed (77.2% male, median age 6.0 yrs (SED ±1.1), 72.7% African American). Overall, median FEV1 was 86% predicted (SED ±3.2), serum IgE 80IU/ml (SED ±145.8) and serum eosinophilia 0.34K/mcl. Children with severe asthma were older [10.0 vs. 2.0 years (p <0.001)], received a higher number of systemic steroid courses in the past year [3 vs. 2 (p= 0.05), and had a higher median BAL eosinophil (14 vs. 0% (p<0.001)]. After correcting for age, there was no increase in any BAL cytokine in severe vs. non-severe asthma. Unlike findings in non-severe asthma, there was a significant positive correlation in the severe asthma cohort between IL-13 and TNF-α (p= 0.003), IL-5 with Th17 (IL-23, IL-33) (p= 0.001 for both), and IL-13 with Th17 (IL-23, IL-33) (p=0.017, 0.023 respectively). Conclusion: In pediatric patients with severe asthma, BAL samples showed multiple correlations between Th1, Th2, and Th17 cytokines. This reflects a mixed immune response of different T-helper cells unique to severe asthma in children. This may help explain inadequate responses to current treatment measures, including steroids. Further studies are needed to evaluate mechanisms for this mixed response in epithelium, smooth muscle and sub-epithelial structures, which may lead to other therapeutic targets for severe, therapy resistant asthma.