Airway and Esophageal Eosinophils in Children With Severe Uncontrolled Asthma

Abstract

To examine the frequency of and correlation between esophageal and airway eosinophils in children with severe uncontrolled asthma (SUA).Researchers in the study included children with SUA according to international European Respiratory Society and American Thoracic Society guidelines who were referred for refractory respiratory symptoms to the Aerodigestive Center at Hassenfeld’s Children’s Hospital at New York University Langone Health from April 2015 to June 2017. All children had either poor symptom control despite use of high-dose inhaled corticosteroids with long-acting β-agonists medication or worsening of asthma control during attempts to taper those medications.This was a retrospective review of prospectively collected data on 24 children aged 2 to 16 years old (n = 24, 21 boys). All children had skin prick tests to food and/or aeroallergens. All subjects underwent triple endoscopy (sleep laryngoscopy, bronchoscopy with bronchoalveolar lavage [BAL] and endobronchial biopsy [EBB], and esophagogastroduodenoscopy with esophageal biopsy). Elevated BAL eosinophils were defined as >1% and neutrophils as >3.5%. Eosinophils in EBB were considered elevated if ≥1 per high-power field. Presence of 1 or more eosinophils per high-power field on esophagogastroduodenoscopy with esophageal biopsy was considered elevated. Airway eosinophils were defined as elevated BAL and/or elevated EBB eosinophils. Aerodigestive eosinophils were defined as the presence of elevated airway eosinophils and elevated esophageal eosinophils together.There was no difference at enrollment in gastrointestinal symptoms, previous diagnosis of reflux and allergy, and use of inhaled corticosteroids, long-acting β-agonists, and proton pump inhibitors between children with and without elevated esophageal eosinophils, airway eosinophils, and aerodigestive eosinophils. All patients with eosinophilic esophagitis (>15 eosinophils per high-power field) (n = 3) and 5 of 8 patients with reflux esophagitis (>5 eosinophils per high-power field) had elevated aerodigestive eosinophils, but only eosinophilic esophagitis correlated with gastrointestinal symptoms and food allergies. Elevated airway eosinophils were present in 71% of patients, and elevated esophageal eosinophils were present in 46% of patients. The number of eosinophils correlated between the BAL and EBB, which then correlated with esophageal eosinophils. Laryngomalacia, tracheal stenosis, or tracheomalacia were present in 4 patients. Over half had bacterial bronchitis on the basis of positive BAL culture results. All patients had BAL neutrophilia, which did not correlate with EBB or BAL eosinophils or the BAL culture.Children with SUA frequently have elevated airway and esophageal eosinophils, and there is a correlation between the airway and esophageal eosinophils.Reflux esophagitis has been strongly associated with increased airway hyperreactivity, and this study suggests that reflux esophagitis should be suspected even in asymptomatic severe asthmatics. Limitations include the small sample size and the low cutoff in defining elevated esophageal eosinophils, which could reduce the significance of this measure. Also, this study does not provide any specific implications for pathogenesis or how this would modify treatment of SUA. Collecting a larger sample size and potentially studying other eosinophil or inflammatory biomarkers would help to better characterize the role, if any, of aerodigestive eosinophils in SUA.