Increased risk of eosinophilic esophagitis with poor environmental quality as measured by the Environmental Quality Index.

Geographic differences in eosinophilic esophagitis (EoE) prevalence suggest the possibility that environmental exposures contribute to EoE pathogenesis. We aimed to examine the association between environmental quality and risk of EoE, using the Environmental Quality Index (EQI), which provides quantification of environmental quality in five domains: air, land, water, built, and sociodemographic for all counties in the United States. To do this, we performed a case-control study in a large pathology database. EoE cases were defined by ≥15 eosinophils per high-power field with other pathologic diagnoses excluded; controls did not have EoE. The pathology data were geocoded and linked with the EQI by county of residence. Logistic regression was used to estimate odds ratio (OR and 95% confidence interval [CI]) of EoE with overall EQI and for each domain, after adjusting for sex, age, and proportion minority race or ethnicity at the county level (higher EQI score indicates worse environmental quality). Of 29,802 EoE cases and 593,329 controls analyzed, odds of EoE were highest in the worst quintile of EQI (OR 1.25; 95% CI: 1.04-1.50), which was largely explained by poor scores in the water domain (OR: 1.33; 1.17-1.50). Conversely, odds of EoE were reduced with higher scores in the air domain (OR: 0.87, 0.74-1.03) and land domain (OR 0.87; 0.76-0.99). Poor EQI, mostly reflected by poor water quality, was associated with increased odds of EoE, while poor air and land quality were inversely associated with EoE. Additional work to identify specific water pollutants that may have an etiologic role in EoE may be warranted.

Associations between gastric histopathology and the occurrence of colonic polyps.

AIM: Compromise of the gastric acid barrier may facilitate bacterial invasion of the lower intestinal tract and promote the development of colonic neoplasia. Our study aimed to test the associations between histopathological abnormalities of the upper and lower gastrointestinal tract in patients undergoing bidirectional endoscopy. METHOD: The Inform Diagnostics database is a national electronic repository of histopathological records of patients distributed throughout the USA. A case-control study of 302 061 patients, 163 168 of whom had colonic polyps, evaluated whether the occurrence of colonic polyps was influenced by the presence of the following gastro-oesophageal diagnoses: gastric Helicobacter pylori infection, gastric intestinal metaplasia, fundic gland polyps and gastric hyperplastic polyps. The influence of individual diagnoses on the occurrence of colonic polyps was expressed as odds ratios with their 95% confidence intervals. RESULTS: The odds ratio for tubular adenomas being associated with gastric H. pylori was 1.53 (1.49-1.58), with intestinal metaplasia 1.65 (1.59-1.71), with fundic gland polyps 1.49 (1.45-1.54) and with gastric hyperplastic polyps 1.85 (1.75-1.96). The odds ratio for sessile serrated polyps being associated with gastric H. pylori was 1.03 (0.96-1.10), with intestinal metaplasia 1.21 (1.13-1.30), with fundic gland polyps 1.79 (1.69-1.89) and with gastric hyperplastic polyps 1.52 (1.35-1.71. CONCLUSION: A diminished gastric acid barrier function, which occurs in various upper gastrointestinal diseases associated with lowered gastric acid output, may promote the development of colonic neoplasia.

Decreased risk for microscopic colitis and inflammatory bowel disease among patients with reflux disease.

AIM: Previous studies have found an increased risk for microscopic colitis (MC) associated with proton pump inhibitors. In patients with ulcerative colitis (UC) or Crohn's disease (CD), proton pump inhibitors have been associated with an increased risk for IBD flares and impaired outcomes. The aim of this study was to test the epidemiological associations between gastro-oesophageal reflux disease (GERD) and MC, UC or CD in a large database. METHOD: The Miraca Life Sciences Database is a national electronic repository of histopathological records of patients distributed throughout the entire USA. A case-control study evaluated whether the presence of Barrett's metaplasia, erosive oesophagitis on endoscopy or histological signs of reflux oesophagitis, clinical diagnosis of GERD or any GERD type affected the occurrence of MC, UC or CD among 228 506 subjects undergoing bidirectional endoscopy. Multivariate logistic regression analyses were used to calculate ORs and their 95% CI for the risk of MC, UC or CD associated with various types of GERD and were adjusted for age, sex and presence of Helicobacter pylori. RESULTS: The analysis revealed an inverse relationship between GERD and different types of inflammatory bowel disease. The inverse relationships applied similarly to MC (mean = 0.62, 95% CI: 0.58-0.66), UC (mean = 0.89, 95% CI: 0.81-0.97) and CD (mean = 0.76, 95% CI: 0.69-0.85). It also applied to different forms of GERD, with a trend towards more pronounced inverse relationships associated with Barrett's metaplasia or erosive oesophagitis than clinical diagnosis of GERD. CONCLUSION: Gastro-oesophageal reflux disease is inversely associated with all forms of inflammatory bowel disease, such as MC, UC, or CD.

Quantification of the duodenal eosinophil content in adults: a necessary step for an evidence-based diagnosis of duodenal eosinophilia.

BACKGROUND: The normal content of eosinophils in the adult duodenum remains undefined. Therefore, there is no foundation for evidence-based criteria to diagnose eosinophilic duodenitis. AIM: This study aimed at: (1) establishing the range of the eosinophil density in the mucosa of the duodenum of normal adults, and (2) determining the biopsy-based prevalence of isolated eosinophilic duodenitis in a large population of adults. METHODS: We counted intact eosinophils in three separate high-power fields (hpf area = 0.237 mm2 each) with the highest densities of eosinophils from the duodenal biopsy specimens of 370 consecutive adults (60% women) with no history of small intestinal disease and a normal duodenal histology. From a large database we also extracted patients with a diagnosis of elevated duodenal eosinophilia and reviewed their biopsies and clinical history. RESULTS: The mean eosinophil count for the 370 patients was 8.2 eos/hpf with a standard deviation of ± 6.3. Twenty-seven of the 370 had eosinophil counts outside the 95% range, which was calculated as: mean + 1.96 × SD = 20.4 eos/hpf. In a database of 458 668 adult subjects, 31 patients (6.8/100 000) had elevated duodenal eosinophilia; 21 of these had other gastrointestinal organs involved by eosinophilia, suggesting eosinophilic gastroenteritis. No significant association between duodenal eosinophilia and any specific symptom was observed. CONCLUSIONS: This study suggests that in this diverse US population, a cut-off count of 20 eos/hpf would be useful to separate patients with normal from those with elevated duodenal eosinophilic infiltrations. The clinical implications of duodenal eosinophilia, particularly when it is not an expression of eosinophilic gastroenteritis, remain to be established.

The ethnic distribution of sessile serrated polyps in the United States is inversely associated with Helicobacter pylori prevalence.

AIM: Little is known about the epidemiology of sessile serrated polyps (SSP). Our study aimed to investigate the influence of Helicobacter pylori gastritis and patient demographic characteristics (age, gender, ethnicity) on the prevalence of SSP using a large national database of patients undergoing bi-directional endoscopy. METHOD: De-identified patient data were extracted from the Miraca Life Sciences electronic database of histopathological reports. Using multivariate logistic regression analysis, the influence of H. pylori gastritis and demographic characteristics on the occurrence of SSP were expressed as odds ratios (OR) with their 95% confidence intervals (CI). RESULTS: The total study population comprised 228 506 subjects, of whom 28 890 carried a diagnosis of H. pylori gastritis and 11 285 SSP. Age (OR 4.35, 95% CI: 3.82-4.96), female gender (0.92, 0.88-0.95) and H. pylori gastritis (0.94, 0.88-0.99) exerted the strongest influence on the occurrence of SSP. In comparison with the population comprising Caucasians and African Americans, SSP were less common among subjects of Hispanic (0.67, 0.62-0.73), East Asian (0.59, 0.50-0.69), Indian (0.43, 0.27-0.64) or Middle Eastern descent (0.61, 0.41-0.87). All these ethnic subgroups were also characterized by a higher prevalence of H. pylori than the comparison group. A low prevalence of H. pylori was significantly associated with a high prevalence of SSP (R2  = 0.82, P < 0.001). CONCLUSION: The prevalence of SSP within the United States is characterized by a marked ethnic variation. The inverse correlation between the prevalence of H. pylori and SSP suggests that gastric infection with H. pylori may be partly responsible for the observed ethnic distribution of SSP.

Demographic and socioeconomic influences on Helicobacter pylori gastritis and its pre-neoplastic lesions amongst US residents.

BACKGROUND: Gastric infection with Helicobacter pylori (Hp) can lead to chronic inactive gastritis, atrophy and intestinal metaplasia. AIMS: To investigate in a cross-sectional study these changes among different socioeconomic and ethnic groups within the USA. METHODS: We used the Miraca Life Sciences database, an electronic depository of clinicopathological records from patients distributed throughout the USA, to extract data from 487 587 patients who underwent oesophago-gastro-duodenoscopy with biopsy between 1/2008 and 12/2014. We then classified patients into ethnic and socioeconomic categories using previously validated algorithms, as well as ZIP code-based information derived from the 2011-2012 US Census. RESULTS: The prevalence of Hp increased significantly until the age-group 40-49, before it leveled off and started a gradual decrease. The prevalence of chronic inactive gastritis, atrophy, and intestinal metaplasia increased significantly with age. The prevalence of Hp, chronic inactive gastritis, intestinal metaplasia, and atrophy decreased significantly with the percentage of Whites per ZIP code. The prevalence of all four diagnoses also decreased significantly with rising levels of income or college education. Hp, chronic inactive gastritis, atrophy and intestinal metaplasia were more common among Hispanics and the influence of income or college education less pronounced than in the entire population. Hp, chronic inactive gastritis, atrophy, and intestinal metaplasia were also more common among East-Asians, Hp and atrophy decreasing with rising income but remaining unaffected by levels of college education. CONCLUSION: Ethnicity and socioeconomic factors influence the occurrence of Hp gastritis, and its progression to chronic inactive gastritis, atrophy or intestinal metaplasia.

The influence of Helicobacter pylori on the ethnic distribution of Barrett's metaplasia.

BACKGROUND: Environmental risk factors associated with ethnicity may contribute to the occurrence of Barrett's metaplasia. AIM: To investigate the interaction between ethnicity and Helicobacter pylori infection in the occurrence of Barrett's metaplasia among patients undergoing oesophago-gastro-duodenoscopy. METHODS: The Miraca Life Sciences Database is an electronic repository of histopathological patient records. A case-control study evaluated the influence of age, gender, ethnicity and histological diagnosis of H. pylori on the occurrence of Barrett's metaplasia. RESULTS: The total study population comprised 596 479 subjects, of whom 76 475 harboured a diagnosis of Barrett's metaplasia. Male sex, age and H. pylori infection in declining order exerted the strongest influence on the occurrence of BM. In comparison with the population comprising Caucasians and African Americans, Barrett's metaplasia was less common among subjects of African (OR = 0.09, 95% CI = 0.01-0.43), Middle Eastern (0.26, 0.20-0.34), East Asian (0.35, 0.31-0.40), Indian (0.39, 0.32-0.47), Hispanic (0.62, 0.59-0.64) or Jewish descent (0.50, 0.45-0.54), but more common among subjects of Northern European descent (1.14, 1.03-1.26). With the exception of Jews and Northern Europeans, all other ethnic subgroups were characterised by a higher prevalence of H. pylori than the comparison group. A low prevalence of H. pylori was significantly associated with a high prevalence of Barrett's metaplasia (R2 = 0.82, P < 0.001), as well as dysplasia or oesophageal adenocarcinoma (R2 = 0.81, P < 0.001). CONCLUSION: Our analysis reveals an inverse relationship between the prevalence of Barrett's metaplasia and H. pylori gastritis among different ethnic groups within the United States.

Differences in the socio-economic distribution of inflammatory bowel disease and microscopic colitis.

AIM: Inflammatory bowel disease (IBD) and microscopic colitis are characterized by different geographical distributions across the USA. In this cross-sectional study we utilized demographic and socio-economic information associated with individual ZIP codes to further delineate the epidemiological characteristics of the two diseases. METHOD: A total of 813 057 patients who underwent colonoscopy between 2008 and 2014 were extracted from an electronic database of histopathology reports. The prevalence of patients with IBD or microscopic colitis was expressed as percentage of the population associated with specific demographic (age, sex, ethnicity) and socio-economic characteristics (population size, housing value, annual income, tertiary education). RESULTS: Both diseases were more common among subjects from ZIP codes with predominantly White residents and less common among subjects from ZIP codes with predominantly non-White residents such as Black, Hispanic and Asian. These ethnic variations were more pronounced in microscopic colitis than IBD. Markers of affluence, such as average residential house value and annual income, were positively associated with IBD and negatively with microscopic colitis. The prevalence of both diseases was positively correlated with tertiary education. CONCLUSION: The occurrence of both IBD and microscopic colitis is influenced by environmental risk factors. The differences in the demographic, ethnic and socio-economic distributions of the two diseases suggest that different sets of risk factors affect the two diseases and that their aetiology is unrelated.

Prospective assessment of serum periostin as a biomarker for diagnosis and monitoring of eosinophilic oesophagitis.

BACKGROUND: Periostin is highly expressed in eosinophilic oesophagitis (EoE), but has not been extensively studied as a non-invasive biomarker. AIM: To assess whether serum periostin distinguished EoE from controls at baseline, had utility for monitoring treatment response, or was associated with IL-13 levels. METHODS: This was a sub-analysis of a prospective cohort study of adults undergoing out-patient upper endoscopy. Incident cases of EoE were diagnosed per consensus guidelines. Controls were subjects with either GERD or dysphagia without EoE. EoE patients were treated with swallowed/topical steroids and had repeat endoscopy/biopsy. Serum periostin levels for cases and controls were compared at baseline, and pre/post-treatment levels were compared for cases. Serum IL-13 and tissue expression of periostin were also assessed. RESULTS: A total of 61 incident EoE cases and 87 controls were analysed. Despite a marked increase in tissue periostin expression in cases, the median baseline serum periostin level was only slightly higher in cases than controls (22.1 ng/mL vs. 20.7; P = 0.04); there was no change in post-treatment levels. There was also no difference in serum periostin for cases by histologic response or atopic status. There was a strong trend towards higher serum IL-13 levels in cases in the highest periostin quartile (57.1 pg/mL vs. 2.6; P = 0.07). CONCLUSIONS: Serum periostin levels were similar in cases and controls, and there were no changes post-treatment. Given elevated IL-13 levels in the EoE patients with the highest periostin levels, future studies could explore periostin as a biomarker in EoE, perhaps in the setting of anti-IL-13 therapy.

Oesophageal signet ring cell carcinoma as complication of gastro-oesophageal reflux disease.

BACKGROUND: Signet ring cell carcinoma occurs as a histological variant of oesophageal adenocarcinoma. AIM: In a cross-sectional study, to pursue the hypothesis that oesophageal signet ring cell cancers constitute a complication of gastro-oesophageal reflux disease. METHODS: In a large national database of histopathology records, we accumulated 91 802 patients with Barrett's oesophagus (BE), 2817 with oesophageal nonsignet ring adenocarcinoma (EAC) and 278 with oesophageal signet ring cell carcinoma (SRC). The three groups were compared with respect to their clinical and demographic characteristics, as well as socio-economic risk factors (associated with patients' place of residence). RESULTS: About 9% of all oesophageal adenocarcinomas harboured features of signet ring cell carcinoma. Patients with oesophageal adenocarcinoma and signet ring cell carcinoma were characterised by almost identical epidemiological patterns. Patients with either cancer type were slightly older than those with Barrett's oesophagus (EAC 68.0, SRC 66.7 vs. BE 63.7 years), and both showed a striking male predominance (EAC and SRC 85% vs. BE 67%). Both cancer types were associated with a similar set of alarm symptoms, such as dysphagia, pain and weight loss. The distribution by race (Whites vs. Blacks) and socio-economic parameters, such as levels of college education and family income, were similar among the three groups of patients. CONCLUSIONS: Signet ring cell carcinoma is a rare variant of oesophageal adenocarcinoma with similar epidemiological characteristics. The reasons why a minority of reflux patients progress to develop signet ring cell carcinoma, rather than the usual type of oesophageal adenocarcinoma, remain unknown.

Seasonal variation in detection of oesophageal eosinophilia and eosinophilic oesophagitis.

BACKGROUND: Seasonal variation has been reported in diagnosis of eosinophilic oesophagitis (EoE), but results are not consistent across studies and there are no national-level data in the USA. AIM: To determine if there is seasonal variation in diagnosis of oesophageal eosinophilia and EoE in the USA, while accounting for factors such as climate zone and geographic variation. METHODS: This was a cross-sectional study using a USA national pathology database. Patients with oesophageal eosinophilia (≥15 eosinophils per high-power field) comprised the primary case definition and were compared to those with normal oesophageal biopsies. We calculated the crude and adjusted odds of oesophageal eosinophilia by season, as well as by day of the year. Sensitivity analyses were performed using more restrictive case definitions of EoE, and after stratification by climate zone. RESULTS: Exactly, 14 524 cases with oesophageal eosinophilia and 90 459 normal controls were analysed. The adjusted odds of oesophageal eosinophilia were higher in the late spring and summer months, with the highest odds in July (aOR: 1.13; 95% CI: 1.03-1.24). These findings persisted with increasing levels of oesophageal eosinophilia, as well as across EoE case definitions. Seasonal variation was strongest in temperate and cold climates, and peak diagnosis varied by climate zone. CONCLUSIONS: There is a mild but consistent seasonal variation in the diagnosis of oesophageal eosinophilia and EoE, with cases more frequently diagnosed during summer months. These findings take into account climate and geographic differences, suggesting that aeroallergens may contribute to disease development or flare.

The coeliac stomach: gastritis in patients with coeliac disease.

BACKGROUND: Lymphocytic gastritis (LG) is an uncommon entity with varying symptoms and endoscopic appearances. This condition, as well as two forms of H. pylori-negative gastritis [chronic active gastritis (CAG) and chronic inactive gastritis (CIG)], appears to be more common in patients with coeliac disease (CD) based on single-centred studies. AIM: To compare the prevalence of LG, CAG and CIG among those with normal duodenal histology (or nonspecific duodenitis) and those with CD, as defined by villous atrophy (Marsh 3). METHODS: We analysed all concurrent gastric and duodenal biopsy specimens submitted to a national pathology laboratory during a 6-year period. We performed multiple logistic regression to identify independent predictors of each gastritis subtype. RESULTS: Among patients who underwent concurrent gastric and duodenal biopsy (n = 287,503), the mean age was 52 and the majority (67%) were female. Compared to patients with normal duodenal histology, LG was more common in partial villous atrophy (OR: 37.66; 95% CI: 30.16-47.03), and subtotal/total villous atrophy (OR: 78.57; 95% CI: 65.37-94.44). CD was also more common in CAG (OR for partial villous atrophy 1.93; 95% CI: 1.49-2.51, OR for subtotal/total villous atrophy 2.42; 95% CI: 1.90-3.09) and was similarly associated with CIG (OR for partial villous atrophy 2.04; 95% CI: 1.76-2.35, OR for subtotal/total villous atrophy 2.96; 95% CI: 2.60-3.38). CONCLUSIONS: Lymphocytic gastritis is strongly associated with coeliac disease, with increasing prevalence correlating with more advanced villous atrophy. Chronic active gastritis and chronic inactive gastritis are also significantly associated with coeliac disease. Future research should measure the natural history of these conditions after treatment with a gluten-free diet.

Helicobacter-negative gastritis: a distinct entity unrelated to Helicobacter pylori infection.

BACKGROUND: Helicobacter-negative gastritis is diagnosed when no organisms are detected in a gastric mucosa with typical features of Helicobacter gastritis (Hp-gastritis). If Helicobacter-negative gastritis consisted mostly of 'missed' Helicobacter infections, its prevalence should represent a constant percentage of these infections in a population, and their clinico-epidemiological features would overlap. AIM: To compare the epidemiologic patterns of Hp-positive and Hp-negative gastritis. METHODS: From a pathology database, we extracted demographic, clinical and histopathological data from patients with gastric biopsies (1.2008-12.2013). We allocated patients to high (≥12%) and low (≤6%) H. pylori prevalence regions defined by ZIP code-based data. The prevalence of H. pylori-positive and -negative gastritis by sex, age and state were expressed as a per cent of the total study population stratified accordingly. RESULTS: Of 895 323 patients, 10.6% had Hp-gastritis and 1.5% Helicobacter-negative gastritis. Hp-gastritis, but not Helicobacter-negative gastritis, was more common in males than females (OR 1.17, 95% CI: 1.16-1.19). While Hp-gastritis was more prevalent in high than in low-prevalence areas (OR 3.65, 95% CI: 3.57-3.74), Helicobacter-negative gastritis was only minimally affected by the underlying H. pylori prevalence (1.7% vs. 1.5%). The age-specific prevalence of Hp-gastritis peaked in the 4th to 5th decades; Helicobacter-negative gastritis exhibited a low and relatively flat pattern. The geographic distribution of H. pylori-positive and -negative gastritis showed no significant correlation. Intestinal metaplasia was found in 13.0% of patients with Hp-gastritis and in 6.1% of those with Helicobacter-negative gastritis (OR 0.43, 95% CI: 0.40-0.47). CONCLUSION: These data suggest that Helicobacter-negative gastritis is, in the vast majority of cases, a nosologically and epidemiologically distinct entity that deserves further investigation.