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Background & Aims: The association between atopic diseases and inflammatory bowel diseases (IBD) is unclear. We conducted a nationwide population-based study in Korea to investigate the effect of atopic diseases on the development of IBD., Methods: A total of 9,923,521 participants, who received a medical check-up in 2009, were included and followed through 2017. The presence of any atopic diseases, including atopic dermatitis (AD), allergic rhinitis (AR), and asthma, was evaluated. Patients who developed IBD, including Crohn's disease (CD) and ulcerative colitis (UC), were identified using claims data from National Health Insurance; the association between atopic diseases and the risk of IBD was evaluated using Cox proportional hazard models, and presented as adjusted hazard ratios (aHRs) with 95% CIs., Results: During a mean follow-up period of 7.3 years, 1419 patients (0.014%) developed CD and 5897 patients (0.059%) developed UC. The incidences of CD (per 100,000 person-years) were 3.756, 2.248, and 2.346 in patients with AD, AR, or asthma, respectively. The incidences of UC were 11.952, 9.818, and 9.358 in patients with AD, AR, or asthma, respectively. Multivariable analysis revealed that the aHRs for incident CD in patients with AD, AR, or asthma were 2.02, 1.33, and 1.60 (95% CIs, 1.118-3.663, 1.149-1.529, and 1.193-2.136, respectively) compared with controls. The risks of incident UC in patients with AD, AR, or asthma were 1.51, 1.32, and 1.29 (95% CIs, 1.082-2.104, 1.229-1.410, and 1.115-1.491, respectively) compared with controls. Moreover, an increase in the number of atopic diseases gradually increased the risk for CD and UC; for 1 or 2 or more atopic diseases, the aHRs for CD were 1.35 and 1.65 (95% CIs, 1.171-1.560 and 1.146-2.376), and the aHRs for UC were 1.30 and 1.49 (95% CIs, 1.211-1.392 and 1.249-1.774), respectively., Conclusions: Based on a nationwide population-based study in Korea, patients with any atopic disease, including AD, AR, or asthma, have an increased risk for CD and UC. The risk for IBD increases with the increase in the number of atopic diseases., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background Although occult hemoglobin in feces is universally valued as a screening tool for colorectal cancer (CRC), only few studies investigated the clinical meaning of fecal immunochemical test (FIT) in other diseases. We evaluated the clinical utility of FIT in patients with cardiovascular diseases (namely, ischemic stroke and myocardial infarction [MI]). Methods and Results Using the National Health Insurance database, participants (aged >50 years) with CRC screening records from 2009 to 2012 were screened and followed up. Subjects with a history of cardiovascular diseases and CRC were excluded. Ischemic stroke, MI, and other comorbidities were defined by International Classification of Diseases, Tenth Revision ( ICD-10 ), codes. Age, sex, smoking, alcohol consumption, regular exercise, diabetes mellitus, hypertension, dyslipidemia, and body mass index were adjusted in a multivariate analysis. A total of 6 277 446 subjects were eligible for analysis. During the mean 6.79 years of follow-up, 168 570 participants developed ischemic stroke, 105 983 developed MI, and 11 253 deaths were observed. A multivariate-adjusted model revealed that the risk of ischemic stroke was higher in the FIT-positive population (adjusted hazard ratio [HR], 1.09; 95% CI, 1.07-1.11). Similarly, FIT-positive subjects were at an increased risk of MI (adjusted HR, 1.09; 95% CI, 1.06-1.12). Moreover, increased all-cause mortality was observed in the FIT-positive population (adjusted HR, 1.15; 95% CI, 1.07-1.23). The increased risk remained consistent in the stratified analysis on anemia and CRC status. Conclusions Positive FIT findings were associated with ischemic stroke, MI, and mortality. Occult blood in feces may offer more clinical information than its well-known conventional role in CRC screening.

Background: Emerging data suggest that inflammatory bowel disease (IBD) and psoriasis are associated, sharing common genetic predispositions and immunological mechanisms. However, concrete data on psoriasis risk in IBD patients compared to the general population are limited., Objective: We investigated the risk of developing psoriasis in IBD patients compared to controls without IBD., Methods: Using the Korean National Health Insurance Database, patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) between 2005 and 2008 were age- and sex-matched 1:4 to non-IBD subjects from 2003 to 2018. IBD patients were defined by combining the International Classification of Diseases 10th revision code and at least one prescription of IBD-specific medications. Disease phenotypes, including psoriasis severity and psoriatic arthritis, were also identified. We investigated newly diagnosed psoriasis from 2009 to 2018. Incidence rates and risk of psoriasis were assessed with multivariate Cox regression models. Subgroup analyses for age and sex, and sensitivity analysis involving tumor necrosis factor (TNF) inhibitor-naïve patients were performed., Results: During nearly a decade of follow-up, 20,152 IBD patients were identified (14,619 [72.54%] UC and 5,533 [27.46%] CD). Among them, 439 patients were newly diagnosed with psoriasis (incidence rate of 217.68 per 100,000 person-years and 228.62 per 100,000 person-years for UC and CD, respectively). The psoriasis risk was higher in IBD patients than in the matched controls (adjusted hazard ratio, aHR, 2.95, 95% confidence interval, CI, 2.60-3.33). Moreover, IBD patients aged <30 years were at an increased risk (aHR 3.35, 95% CI 2.58-4.35), a trend that was unchanged across all psoriasis phenotypes. Sensitivity analysis of TNF inhibitor-naïve patients revealed consistent results., Conclusions: IBD patients were more likely to develop psoriasis compared to non-IBD subjects, including younger patients at an elevated risk regardless of TNF inhibitor use. This advocates the interplay between IBD and psoriasis; thus, inspection of cutaneous manifestation and dermatological consultation may be helpful in IBD patients at risk., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Anemia is a common manifestation of inflammatory bowel disease (IBD), but it remains unclear whether anemia is associated with the development of IBD. We assessed the risk of developing IBD in anemic patients, and stratified the results with respect to their hemoglobin concentrations. A population-based study was conducted using the National Healthcare Insurance Service database in South Korea. We included individuals over 20 years' old who participated in the national health screening program in 2009 (n = 9,962,064). Anemia was defined as a hemoglobin level less than 13 g/dL in men and less than 12 g/dL in women. We compared the rate of newly diagnosed IBD in anemic patients and non-anemic individuals. Newly diagnosed IBD was identified using both the ICD-10 medical code and specialized V codes for rare intractable diseases in South Korea. During the mean follow-up period of 7.3 years, the incidences of CD and UC in anemic patients were 2.89 and 6.88 per 100,000 person-years, respectively. The risk of CD was significantly higher in anemic patients than in non-anemic individuals [adjusted hazard ratio (aHR), 2.084; 95% confidence interval (CI), 1.769-2.455]. The risk of CD development was inversely proportional to the hemoglobin concentration. A J-curve relationship was observed between age and the risk of CD in anemic patients. The risk of CD in male anemic patients was significantly higher than that in female anemic patients (aHR, 1.432 vs. 1.240, respectively). By contrast, there was no statistically significant difference in the risk of developing UC in anemic and non-anemic individuals (aHR, 0.972; 95% CI, 0.880-1.073). This work indicates that anemia is related to the development of CD, and this risk was inversely proportional to the hemoglobin concentration., Competing Interests: The authors have declared that no competing interests exist.

Background and Aim: The relationship between inflammatory bowel disease (IBD) and idiopathic pulmonary fibrosis (IPF) remains unclear. We evaluated the risk for developing IPF in patients with IBD using a nationwide population-based study., Methods: Using claims data from the National Health Insurance service in Korea, patients with IBD, including Crohn's disease (CD) and ulcerative colitis (UC), were identified through both the 10th revision of the International Statistical Classification of Diseases and Related Health Problems and rare and intractable disease program codes from January 2010 to December 2013. We compared 38 921 IBD patients with age-matched and sex-matched individuals without IBD in a ratio of 1:3. Patients with newly diagnosed IPF were identified by both the 10th revision of the International Statistical Classification of Diseases and Related Health Problems and rare and intractable disease registration codes., Results: During a mean 4.9-year follow-up, the incidence of IPF in patients with IBD was 33.21 per 100 000 person-years. The overall risk of IPF was significantly higher in IBD patients than in non-IBD controls (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.20-2.20; P = 0.003). In patients with CD, the incidence (per 100 000 person-years) of IPF was 26.04; in controls, the incidence was 9.15 (HR, 2.89; 95% CI, 1.46-5.72; P = 0.002). The incidence of IPF in patients with UC tended to be higher than in controls (36.66 vs 26.54 per 100 000 person-years; 95% CI, 0.99-1.99; HR, 1.41; P = 0.066). The risk of developing IPF in patients with IBD was higher in male patients than in female patients (P = 0.093 in CD; P = 0.147 in UC by interaction analysis)., Conclusions: Patients with IBD, especially CD, have an increased risk of developing IPF., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: The relationships between lipid profiles and IBD remain elusive., Aim: To determine the association of IBD with serum lipid profiles., Methods: A nationwide population-based study was performed using claims data from the Korean National Healthcare Insurance service. A total of 9 706 026 subjects undergoing medical check-ups in 2009 were enrolled and followed up until 2016. Individuals who developed Crohn's disease (CD) or ulcerative colitis (UC) were identified during follow-up. Adjusted hazard ratio (aHR) by age, sex, body mass index, cigarette smoking, alcohol drinking, exercise, income and underlying comorbidities was calculated to define the impact of serum lipid profiles on developing IBD., Results: During a median follow-up of 7.3 years, IBD was detected in 7,058 (0.07%) individuals. Compared with the highest quartile of serum total cholesterol (TC) levels, lower TC levels were associated with higher incidence of CD (aHR: Q1, 2.52; Q2, 1.52; Q3, 1.27), but not UC. Lower serum LDL-C levels were associated with higher incidence of CD (aHR: Q1, 1.92; Q2, 1.47; Q3, 1.22), but not UC. Moreover, lower serum HDL-C levels were associated with higher incidence of CD (aHR: Q1, 2.49; Q2, 1.90; Q3, 1.43), but not UC. In contrast, lower serum triglyceride levels were associated with higher incidence of UC (aHR: Q1, 1.22; Q2, 1.19; Q3, 1.19), but not CD., Conclusions: Low serum TC, LDL-C and HDL-C levels were associated with CD. Low serum triglyceride levels were related to UC., (© 2019 John Wiley & Sons Ltd.)

Background: The incidence of inflammatory bowel disease (IBD) is increasing in Asia. Numerous risk factors associated with IBD development have been investigated., Aim: To investigate trends and environmental risk factors of Crohn's disease (CD) diagnosed in persons aged ≥ 40 years in South Korea., Methods: Using the National Health Insurance Service database, a total of 14060821 persons aged > 40 years who underwent national health screening in 2009 were followed up until December 2017. Patients with newly diagnosed CD were enrolled and compared with non-CD cohort. CD was identified according to the International Classification of Diseases 10th revision and the rare/intractable disease registration program codes from the National Health Insurance Service database. The mean follow-up periods was 7.39 years. Age, sex, diabetes, hypertension, smoking, alcohol consumption, regular exercise, body mass index, anemia, chronic kidney disease (CKD) and dyslipidemia were adjusted for in the multivariate analysis model., Results: During the follow-up, 1337 (1.33/100000) patients developed CD. Men in the middle-aged group (40-64 years) had a higher risk than women [adjusted hazard ratio (aHR) 1.46, 95% confidence interval (CI): 1.29-1.66]; however, this difference tended to disappear as the age of onset increases. In the middle-aged group, patients with a history of smoking [aHR 1.46, 95%CI: 1.19-1.79) and anemia (aHR 1.85, 95%CI: 1.55-2.20) had a significantly higher CD risk. In the elderly group (age, ≥ 65 years), ex-smoking and anemia also increased the CD risk (aHR 1.68, 95%CI: 1.22-2.30) and 1.84 (95%CI: 1.47-2.30, respectively). Especially in the middle-aged group, those with CKD had a statistically elevated CD risk (aHR 1.37, 95%CI: 1.05-1.79). Alcohol consumption and higher body mass index showed negative association trend with CD incidence in both of the age groups. [Middle-aged: aHR 0.77 (95%CI: 0.66-0.89) and aHR 0.73 (95%CI: 0.63-0.84), respectively] [Elderly-group: aHR 0.57 (95%CI: 0.42-0.78) and aHR 0.84 (95%CI 0.67-1.04), respectively]. For regular physical activity and dyslipidemia, negative correlation between CD incidences was proved only in the middle-aged group [aHR 0.88 (95%CI: 0.77-0.89) and aHR 0.81 (95%CI: 0.68-0.96), respectively]., Conclusion: History of cigarette smoking, anemia, underweight and CKD are possible risk factors for CD in Asians aged > 40 years., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest for this article., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: There is a growing evidence regarding an increased risk of inflammatory bowel disease (IBD) among patients with airway diseases., Aim: To investigate the influence of chronic obstructive pulmonary disease (COPD) on the risk of IBD., Methods: A nationwide, population-based study was conducted using data from the National Health Insurance Service database. A total of 1303021 patients with COPD and 6515105 non-COPD controls were identified. The COPD group was divided into the severe and the mild COPD group according to diagnostic criteria. The risk of IBD in patients with COPD compared to controls was analyzed by Cox proportional hazard regression models. The cumulative incidences of IBD were compared between the groups., Results: The COPD group had higher incidences of IBD compared to non-COPD controls (incidence rate, 9.98 vs 7.18 per 100000 person-years, P < 0.001). The risk of IBD in the COPD group was increased by 1.38 (adjusted hazard ratio (HR); 95%CI: 1.25-1.52). The incidence rate of IBD was higher in the severe COPD group than in the mild COPD group (12.39 vs 9.77 per 100000 person-year, P < 0.001). The severity of COPD was associated with an increased risk of IBD (adjusted HR 1.70 in severe COPD, 95%CI: 1.27-2.21 and adjusted HR 1.35 in mild COPD, 95%CI: 1.22-1.49)., Conclusion: The incidences of IBD were significantly increased in COPD patients in South Korea and the risk of developing IBD also increased as the severity of COPD increased., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts-of-interest related to this article., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Former cigarette smokers are at risk of developing ulcerative colitis (UC). However, the impact of smoking behavior on the occurrence of UC according to the amount smoked remains elusive. We aimed to determine the relationship between smoking behavior and the risk of UC development., Methods: We conducted a retrospective population-based cohort study using the National Health Insurance Service database in South Korea. From January 2009 to December 2012, 23,235,771 individuals over 18 years of age who underwent a national health examination were enrolled and followed until 2016. All study participants were divided into the following 3 groups: nonsmokers, former smokers, and current smokers. The primary endpoint was newly developed UC., Results: Compared with nonsmokers, the risk of UC development was significantly higher in former smokers [adjusted hazard ratio (aHR) 1.83; 95% confidence interval (CI) 1.73-1.95] but significantly lower in current smokers (aHR 0.92; 95% CI 0.87-0.98). Among current smokers, individuals who stopped smoking after the baseline evaluation had a significantly higher risk of UC development than those who continued to smoke (aHR 2.42; 95% CI 2.10-2.80). The risk of UC development among former smokers was significantly associated with smoking amount and duration. Among current smokers, however, the risk of UC development was not correlated with the cumulative lifetime smoking exposure. The preventive effect of current smoking on UC development was observed only in men (aHR 0.90; 95% CI 0.84-0.96)., Conclusions: Compared with nonsmokers, former smokers have a significantly higher risk of UC development that may be proportional to the cumulative smoking exposure.

Background/aims: The risk of herpes zoster (HZ) among patients with inflammatory bowel disease (IBD) remains unclear in terms of age and metabolic comorbidities, including diabetes mellitus, hypertension, or dyslipidemia. We conducted a nationwide population-based study to investigate the risk of HZ in patients with IBD., Methods: From 2010 to 2013, a retrospective study was performed using claims data in Korea. We compared the incidence of HZ between 30,100 IBD patients (10,517 Crohn’s disease [CD] and 19,583 ulcerative colitis [UC] patients) and 150,500 non-IBD controls matched by age and sex., Results: During a mean follow-up of 5.0 years, incidence rates of HZ (per 1,000 person-years) were 13.60, 14.99, and 9.19 in the CD, UC, and control groups, respectively. The risk of HZ was significantly higher in patients with CD (adjusted hazard ratio [HR], 2.13; p<0.001) and UC (adjusted HR, 1.40; p<0.001) than in the controls. The impact of CD on developing HZ was significantly more prominent in younger patients (adjusted HR, 2.61 for age <15, whereas 1.39 for age ≥60; interaction p=0.001) and in patients without metabolic comorbidities (adjusted HR, 2.24, whereas 1.59 in those with metabolic comorbidities; interaction p=0.015). Moreover, the impact of UC on developing HZ significantly increased in younger patients (adjusted HR, 2.51 in age <15, whereas 1.22 in age ≥60; interaction p=0.014) and patients without metabolic comorbidities (adjusted HR, 1.49 whereas 1.16 in those with metabolic comorbidities; interaction p<0.001)., Conclusions: IBD was associated with an increased risk of HZ, especially in younger patients without metabolic comorbidities.

Aim: To estimate the risk of end-stage renal disease (ESRD) in patients with inflammatory bowel disease (IBD)., Methods: From January 2010 to December 2013, patients with Crohn's disease (CD) and ulcerative colitis (UC) were identified, based on both the International Classification of Diseases, 10 th revision (ICD-10) and the rare, intractable disease registration program codes from the National Health Insurance (NHI) database in South Korea. We compared 38812 patients with IBD to age- and sex-matched non-IBD controls with a ratio of 1:3. Patients newly diagnosed with ESRD were identified with the ICD-10 code., Results: During a mean follow-up of 4.9 years, ESRD was detected in 79 (0.2%) patients with IBD and 166 (0.1%) controls. The incidence of ESRD in patients with IBD was 0.42 per 1000 person-years. Patients with IBD had a significantly higher risk of ESRD than controls [adjusted hazard ratio (HR) = 3.03; 95% confidence interval (CI): 1.77-5.20; P < 0.001]. The incidences (per 1000 person-years) of ESRD were 0.51 in patients with CD and 0.13 in controls, respectively (adjusted HR = 6.33; 95%CI: 2.75-14.56; P < 0.001). In contrast, the incidence of ESRD was similar between the UC and control groups (0.37 vs 0.37 per 1000 person-years; adjusted HR = 2.01; 95%CI: 0.90-4.51; P = 0.089)., Conclusion: The risk of ESRD was elevated in patients with CD, but not UC. Patients with CD should be monitored carefully for signs of renal insufficiency., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest.