Diagnosis of eosinophilic esophagitis in patients with dysphagia during the Coronavirus Disease 2019 (COVID-19) pandemic.

Background: The coronavirus disease 2019 (COVID-19) pandemic posed restrictions to many standard practices. Dysphagia is a common presentation of eosinophilic esophagitis (EoE) in adults, and biopsy via esophagogastroduodenoscopy (EGD) is required for diagnosis. We hypothesized that a diagnosis of EoE has declined during the pandemic. Objective: To investigate whether the COVID-19 pandemic influenced the likelihood of an EGD and an EoE diagnosis in patients with dysphagia. Methods: In this retrospective matched cohort study, we used the TriNetX US Collaborative Network to identify adult patients who presented with dysphagia to the emergency department (ED) during the year of and the year preceding the pandemic. Patients with a previous EoE diagnosis were excluded. The two cohorts were balanced for demographics, gastroesophageal reflux disease (GERD) diagnosis, obesity, H2 blockers and proton-pump inhibitors use, anemia, smoking, and alcohol use. The proportion of patients who received an EGD, and an EoE and a GERD diagnosis were contrasted up to 90 days from ED evaluation. Results: We identified 16,942 adult patients during the pandemic, and 16,942 adult patients the year preceding the pandemic who presented to the ED with a concern of dysphagia. During the 30-day follow-up period, no significant difference was observed in the proportion of patients who received an EGD during the pandemic versus the prepandemic period at 1, 7, and 30 days from ED evaluation. The proportion of patients who received an EoE diagnosis was not different, but slightly more patients received a GERD diagnosis during the pandemic versus prepandemic that was evident by day 30 (31.2% versus 30%; p ≤ 0.05). Conclusion: Our results revealed that the COVID-19 pandemic did not significantly impact diagnostic EGD and an EoE diagnosis.

Distinct Epithelial-Innate Immune Cell Transcriptional Circuits Underlie Airway Hyperresponsiveness in Asthma.

Rationale: Indirect airway hyperresponsiveness (AHR) is a highly specific feature of asthma, but the underlying mechanisms responsible for driving indirect AHR remain incompletely understood. Objectives: To identify differences in gene expression in epithelial brushings obtained from individuals with asthma who were characterized for indirect AHR in the form of exercise-induced bronchoconstriction (EIB). Methods: RNA-sequencing analysis was performed on epithelial brushings obtained from individuals with asthma with EIB (n = 11) and without EIB (n = 9). Differentially expressed genes (DEGs) between the groups were correlated with measures of airway physiology, sputum inflammatory markers, and airway wall immunopathology. On the basis of these relationships, we examined the effects of primary airway epithelial cells (AECs) and specific epithelial cell-derived cytokines on both mast cells (MCs) and eosinophils (EOS). Measurements and Main Results: We identified 120 DEGs in individuals with and without EIB. Network analyses suggested critical roles for IL-33-, IL-18-, and IFN-γ-related signaling among these DEGs. IL1RL1 expression was positively correlated with the density of MCs in the epithelial compartment, and IL1RL1, IL18R1, and IFNG were positively correlated with the density of intraepithelial EOS. Subsequent ex vivo modeling demonstrated that AECs promote sustained type 2 (T2) inflammation in MCs and enhance IL-33-induced T2 gene expression. Furthermore, EOS increase the expression of IFNG and IL13 in response to both IL-18 and IL-33 as well as exposure to AECs. Conclusions: Circuits involving epithelial interactions with MCs and EOS are closely associated with indirect AHR. Ex vivo modeling indicates that epithelial-dependent regulation of these innate cells may be critical in indirect AHR and modulating T2 and non-T2 inflammation in asthma.

Location of eosinophils in the airway wall is critical for specific features of airway hyperresponsiveness and T2 inflammation in asthma.

BACKGROUND: Eosinophils are implicated as effector cells in asthma, but the functional implications of the precise location of eosinophils in the airway wall is poorly understood. We aimed to quantify eosinophils in the different compartments of the airway wall and associate these findings with clinical features of asthma and markers of airway inflammation. METHODS: In this cross-sectional study, we utilised design-based stereology to accurately partition the numerical density of eosinophils in both the epithelial compartment and the subepithelial space (airway wall area below the basal lamina including the submucosa) in individuals with and without asthma and related these findings to airway hyperresponsiveness (AHR) and features of airway inflammation. RESULTS: Intraepithelial eosinophils were linked to the presence of asthma and endogenous AHR, the type that is most specific for asthma. In contrast, both intraepithelial and subepithelial eosinophils were associated with type 2 (T2) inflammation, with the strongest association between IL5 expression and intraepithelial eosinophils. Eosinophil infiltration of the airway wall was linked to a specific mast cell phenotype that has been described in asthma. We found that interleukin (IL)-33 and IL-5 additively increased cysteinyl leukotriene (CysLT) production by eosinophils and that the CysLT LTC4 along with IL-33 increased IL13 expression in mast cells and altered their protease profile. CONCLUSIONS: We conclude that intraepithelial eosinophils are associated with endogenous AHR and T2 inflammation and may interact with intraepithelial mast cells via CysLTs to regulate airway inflammation.