Unsedated transnasal endoscopy (TNE) is an alternative method of examining the esophageal mucosa in pediatric patients with eosinophilic esophagitis (EoE), reducing cost, time, and risk associated ...with frequent surveillance esophagogastroduodenoscopies (EGD). Adequacy of transnasal esophageal biopsies for the evaluation of eosinophilic esophagitis histologic scoring system (EoEHSS) has not yet been evaluated. We compared procedure times, endoscopic findings, and EoEHSS scoring for EoE patients undergoing TNE versus standard EGD. Sixty-six TNE patients and 132 EGD controls matched for age (mean age 14.0 years) and disease status (29.3% active) were included. Compared to patients undergoing standard EGD, patients undergoing TNE spent 1.94 h less in the GI suite (p < 0.0001), with comparable occurrence rates of all visual endoscopic findings and most EoEHSS components. TNE serves as a useful tool for long-term disease surveillance, and consideration should be given to its use in clinical trials for EoE.
Epithelial disruption in eosinophilic esophagitis (EoE) encompasses both impaired differentiation and diminished barrier integrity. We have shown that lysyl oxidase (LOX), a collagen cross-linking ...enzyme, is up-regulated in the esophageal epithelium in EoE. However, the functional roles of LOX in the esophageal epithelium remains unknown.
We investigated roles for LOX in the human esophageal epithelium using 3-dimensional organoid and air–liquid interface cultures stimulated with interleukin (IL)13 to recapitulate the EoE inflammatory milieu, followed by single-cell RNA sequencing, quantitative reverse-transcription polymerase chain reaction, Western blot, histology, and functional analyses of barrier integrity.
Single-cell RNA sequencing analysis on patient-derived organoids revealed that LOX was induced by IL13 in differentiated cells. LOX-overexpressing organoids showed suppressed basal and up-regulated differentiation markers. In addition, LOX overexpression enhanced junctional protein genes and transepithelial electrical resistance. LOX overexpression restored the impaired differentiation and barrier function, including in the setting of IL13 stimulation. Transcriptome analyses on LOX-overexpressing organoids identified an enriched bone morphogenetic protein (BMP) signaling pathway compared with wild-type organoids. In particular, LOX overexpression increased BMP2 and decreased the BMP antagonist follistatin. Finally, we found that BMP2 treatment restored the balance of basal and differentiated cells.
Our data support a model whereby LOX exhibits noncanonical roles as a signaling molecule important for epithelial homeostasis in the setting of inflammation via activation of the BMP pathway in the esophagus. The LOX/BMP axis may be integral in esophageal epithelial differentiation and a promising target for future therapies.
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What is a Severe Allergic Reaction? Kennedy, Katie; Capucilli, Peter; Alfaro, Maria Katerina ...
Journal of allergy and clinical immunology,
02/2020, Volume:
145, Issue:
2
Journal Article
Background & Aims: Epithelial disruption in eosinophilic esophagitis (EoE) encompasses both impaired differentiation and diminished barrier integrity. We have shown that lysyl oxidase (LOX), a ...collagen cross-linking enzyme, is up-regulated in the esophageal epithelium in EoE. However, the functional roles of LOX in the esophageal epithelium remains unknown. Methods: We investigated roles for LOX in the human esophageal epithelium using 3-dimensional organoid and air–liquid interface cultures stimulated with interleukin (IL)13 to recapitulate the EoE inflammatory milieu, followed by single-cell RNA sequencing, quantitative reverse-transcription polymerase chain reaction, Western blot, histology, and functional analyses of barrier integrity. Results: Single-cell RNA sequencing analysis on patient-derived organoids revealed that LOX was induced by IL13 in differentiated cells. LOX-overexpressing organoids showed suppressed basal and up-regulated differentiation markers. In addition, LOX overexpression enhanced junctional protein genes and transepithelial electrical resistance. LOX overexpression restored the impaired differentiation and barrier function, including in the setting of IL13 stimulation. Transcriptome analyses on LOX-overexpressing organoids identified an enriched bone morphogenetic protein (BMP) signaling pathway compared with wild-type organoids. In particular, LOX overexpression increased BMP2 and decreased the BMP antagonist follistatin. Finally, we found that BMP2 treatment restored the balance of basal and differentiated cells. Conclusions: Our data support a model whereby LOX exhibits noncanonical roles as a signaling molecule important for epithelial homeostasis in the setting of inflammation via activation of the BMP pathway in the esophagus. The LOX/BMP axis may be integral in esophageal epithelial differentiation and a promising target for future therapies.
We sought to evaluate the use of behavioral economics approaches to promote the carrying of epinephrine auto-injectors (EAIs) among adolescents with food allergies. We hypothesized that adolescents ...who receive frequent text message nudges (Intervention 1) or frequent text message nudges plus modest financial incentives (Intervention 2) would be more likely to carry their epinephrine than members of the usual care control group.
We recruited 131 adolescents ages 15 to 19 with a food allergy and a current prescription for epinephrine to participate in a cohort multiple randomized controlled trial. Participants were randomly assigned to participate in Intervention 1, Intervention 2, or to receive usual care. The primary outcome was consistency of epinephrine-carrying, measured as the proportion of checkpoints at which a participant could successfully demonstrate they were carrying their EAI, with photo-documentation of the device.
During Intervention 1, participants who received the intervention carried their EAI 28% of the time versus 38% for control group participants (P = .06). During Intervention 2, participations who received the intervention carried their EAI 45% of the time versus 23% for control group participants (P = .002).
Text message nudges alone were unsuccessful at promoting EAI-carrying but text message nudges combined with modest financial incentives almost doubled EAI-carriage rates among those who received the intervention compared with the control group. However, even with the intervention, adolescents with food allergies carried their EAI <50% of the time. Alternative strategies for making EAIs accessible to adolescents at all times should be implemented.
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