Tag: Eosinophilic

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Comparison of clinical features in patients with eosinophilic esophagitis living in an urban and rural environment.

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Comparison of clinical features in patients with eosinophilic esophagitis living in an urban and rural environment.

Dis Esophagus. 2014 Jan 2;

Authors: Lee YJ, Redd M, Bayman L, Frederickson N, Valestin J, Schey R

Abstract
Eosinophilic esophagitis (EoE) has been associated with exposure to aeroallergens. Living in different locations (urban vs. rural) could potentially expose individuals to different environmental factors. Currently, there is limited data on the matter, and all was based on small population studies that did not exclude proton pump inhibitor (PPI)-responsive esophageal eosinophilia in their cohort. The primary aim of this study was to determine the prevalence of EoE in an urban versus rural population and compare demographic and clinical characteristics in patients that had been treated with high-dose PPI prior to diagnosis. Esophageal biopsies were obtained from a cohort of patients who presented with symptoms of dysphagia, odynophagia, globus sensation, and heartburn during a 10-year period. Only patients who had biopsies from the mid and distal esophagus with ?20 eosinophils per high-power field while on high-dose PPI treatment during endoscopy were included. Urban population was defined as >1000 people/square mile, and rural population was defined as ?1000 people/square mile (U.S. Census Bureau). Demographic data from each group was analyzed for age, sex, body mass index, duration of symptoms, and tobacco use. Chi-square analysis was used for frequencies with statistical significance defined as P???0.05. A total of 20?718 patients were identified and their records evaluated. From this cohort, 57 (0.28%) symptomatic patients (male/female: 39/18, mean age = 29.5 years) had biopsy-proven EoE (?20 eosinophils/hpf) while on PPI treatment. Of those EoE patients, 29 (50.9%) reported living in rural area versus 28 (49.1%) living in the urban area. The most common medical history components included asthma (12.3%), and the most common presenting symptoms included dysphagia (50.9%), heartburn (26.3%), and nausea/vomiting (22.8%). The average duration of symptoms, body mass index, and smoking habits did not differ between the groups. Dysphagia was significantly more prevalent in the urban population (37.9% vs. 64.3% P = 0.047), while heartburn and reflux were more prevalent in the rural population (37.9% vs. 14.3 P = 0.043). Asthma was prevalent in both populations without a significant difference (P = not significant). There is no residential variation in the incidence of EoE among patients with non-PPI-responsive esophageal eosinophilia. Dysphagia was more prevalent in the urban population, while heartburn and reflux symptoms were more prevalent in the rural environment. Further exploration of environmental factors and specific allergens may help explain the varying symptoms and causes of EoE.

PMID: 24382218 [PubMed – as supplied by publisher]

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Therapeutic Potential of ASP3258, a Selective Phosphodiesterase 4 Inhibitor, on Chronic Eosinophilic Airway Inflammation.

Therapeutic Potential of ASP3258, a Selective Phosphodiesterase 4 Inhibitor, on Chronic Eosinophilic Airway Inflammation.

Pharmacology. 2012;90(3-4):223-32

Authors: Kobayashi M, Kubo S, Shiraki K, Iwata M, Hirano Y, Ohtsu Y, Takahashi K, Shimizu Y

Abstract
We investigated and compared the pharmacological effects of a PDE4 inhibitor ASP3258 (3-[4-(3-chlorophenyl)-1-ethyl-7-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl] propanoic acid), with those of roflumilast, the most clinically advanced PDE4 inhibitor known. ASP3258 inhibited human PDE4A, 4B, 4C, and 4D with respective IC(50) values of 0.036, 0.050, 0.45, and 0.035 nmol/l, all approximately 3-6 times more potent than roflumilast. ASP3258 inhibited LPS-induced TNF-? production and PHA-induced IL-5 production in human whole blood cells with respective IC(50) values of 110 and 100 nmol/l, both approximately 10 times less potent than roflumilast. Repeatedly administered ASP3258 and roflumilast both suppressed chronic airway eosinophilia induced by repeated exposure to ovalbumin in Brown Norway rats with respective ED(50) values of 0.092 and 0.17 mg/kg. We also evaluated the toxicological profiles of ASP3258. Although PDE4 inhibitors induce emesis by mimicking the pharmacological action of an ?(2)-adrenoceptor antagonist, repeated administration of ASP3258 (3 mg/kg) had no such inhibitory effect on rats anesthetized with ?(2) – adrenoceptor agonist. PDE4 inhibitors are also known to induce vascular injury in rats. Although repeatedly administered ASP3258 (3 and 10 mg/kg) significantly increased plasma fibrinogen, a biomarker for toxicity, 1 mg/kg of ASP3258 did not. These results suggest that ASP3258 is an attractive PDE4 inhibitor for treating chronic eosinophilic airway inflammation due to asthma.

PMID: 23038661 [PubMed – in process]

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