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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 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: 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: The fecal immunochemistry test (FIT) has been proposed as a surrogate marker of intestinal inflammation. Psoriasis is a chronic inflammatory skin disease that is linked to underlying systemic inflammatory conditions, including inflammatory bowel disease. Methods: We investigated the association between occult blood in feces and the risk of psoriasis using data from the National Health Insurance System. This study was conducted involving 1,395,147 individuals who underwent health examinations from January 2009 to December 2012 and were followed up until the end of 2017. Results: The incidence of psoriasis (per 1,000 person-years) was 3.76 versus 4.14 (FIT-negative versus FIT-positive group) during a median follow-up of 6.68 years. In the multivariable-adjusted model, the hazard ratios for psoriasis were 1.03 for one positive FIT result, 1.12 for two positive FIT results, and 1.34 for three positive FIT results compared with negative FIT results. Conclusion: The risk of psoriasis was significantly increased in patients with positive FIT results compared to the FIT-negative population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Background and Aims: The impact of proteinuria and its severity on the incidence of inflammatory bowel disease (IBD) has not yet been studied. We aimed to determine the association between proteinuria measured by urine dipstick tests and the development of IBD. Methods: This nationwide population-based study was conducted using the Korean National Health Insurance Service (NHIS) database. A total of 9,917,400 people aged 20 years or older who had undergone a national health examination conducted by the NHIS in 2009 were followed up until 2017. The study population was classified into four groups—negative, trace, 1+, and ≥ 2+—according to the degree of proteinuria measured by the urine dipstick test. The primary endpoint was newly diagnosed IBD, Crohn's disease (CD), or ulcerative colitis (UC) during the follow-up period. Results: Compared with the dipstick-negative group, the incidence of CD significantly increased according to the degree of proteinuria (adjusted hazard ratio [aHR] with 95% confidence interval [CI], 1.01 [0.703–1.451], 1.515 [1.058–2.162], and 2.053 [1.301–3.24] in the trace, 1+, and ≥ 2+ dipstick groups, respectively; p for trend 0.007). However, there was no significant difference in the incidence of UC according to the degree of proteinuria (aHR with 95% CI, 1.12 [0.949–1.323], 0.947 [0.764–1.174], and 1.009 [0.741–1.373] in the trace, 1+, and ≥ 2+ dipstick groups, respectively; p for trend 0.722). In the subgroup analysis, dipstick-positive proteinuria independently increased the incidence of CD regardless of the subgroup. However, dipstick-positive proteinuria was associated with the risk of UC in those with diabetes mellitus and not in those without diabetes mellitus (aHR, 1.527 vs. 0.846; interaction p-value 0.004). The risk of CD was increased or decreased according to proteinuria changes but not associated with the risk of UC. Conclusion: Proteinuria, measured by the dipstick test, is strongly associated with the development of CD. [ABSTRACT FROM AUTHOR]

• Soluble Siglec–9 inhibited IκBα degradation and the DNA binding activity of NF–κB. • Soluble Siglec–9 prevented dextran sulfate sodium-induced murine colitis. • Soluble Siglec–9 alleviated chronic colitis in IL-10 deficient mice. Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a superfamily of immunoreceptors recognizing sialic acid. Siglec-9 has been shown to mediate inhibitory immune responses. The aim of this study was to evaluate the effect of a soluble form of Siglec-9 (sSiglec-9) on inflamed intestinal epithelial cells (IECs), murine macrophages, and experimental murine colitis models. COLO 205 human IECs and RAW 264.7 murine macrophages were pretreated with sSiglec-9 and then stimulated with TNF-α or lipopolysaccharides, respectively. The expression of proinflammatory cytokines such as IL-8 and TNF-α was measured using real-time RT-PCR and ELISA. To demonstrate the inhibitory effects of sSiglec-9 on the NF-κB pathway, IκBα phosphorylation/degradation was determined using western blotting and the DNA binding activity of NF-κB was evaluated using an electrophoretic mobility shift assay. Further, mouse models with dextran sulfate sodium-induced acute colitis and piroxicam-induced IL-10-/- chronic colitis were generated. Intraperitoneal injections of sSiglec-9 were performed, and body weight, colon length, and histopathologic findings were examined. sSiglec-9 suppressed IL-8 and TNF-α gene expression in stimulated COLO 205 and RAW 264.7 cells. sSiglec-9 inhibited IκBα phosphorylation/degradation and the DNA binding activity of NF-κB. sSiglec-9 injections significantly ameliorated weight loss, colon shortening, and the severity of intestinal inflammation in acute and chronic colitis mouse models. sSiglec-9 may inhibit NF-κB activation in IECs and macrophages and alleviate experimental colitis in mice, suggesting that sSiglec-9 is a potential therapeutic agent for the treatment of inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Background and Aims: It is not known whether inflammatory bowel disease (IBD) enhances the risk of Parkinson's disease (PD) or whether PD diagnosis is the result of increased health care use. We determined the risk of developing PD among patients with IBD in terms of health care and medication use. Methods: A nationwide population-based study was conducted using claims data from the Korean National Health care Insurance service. From 2010 to 2013, patients with Crohn's disease (CD) and ulcerative colitis (UC) were identified through both International Classification of Disease, Tenth Revision (ICD-10) and national rare intractable disease (RID) registration program codes. We compared 38,861 IBD patients with age and sex-matched non-IBD individuals at a ratio of 1:3. Patients with newly diagnosed PD were identified through both ICD-10 and RID codes. Results: The incidence of PD among patients with IBD was 49 per 100,000 person-years. The risk of developing PD in patients with IBD was significantly higher than controls even after adjustment for health care use (adjusted hazard ratio (aHR), 1.87; P < 0.001). Compared to controls, the risk of PD was significantly higher in patients with CD (aHR, 2.23; P = 0.023) and UC (aHR, 1.85; P < 0.001). Corticosteroid use showed a preventive effect on developing PD in patients with CD (aHR 0.08; P < 0.001), but not UC (aHR, 0.75; P = 0.213). Among 2110 patients receiving anti-tumor necrosis factor (anti-TNF), none of the treated patients experienced PD during 9950 person-years. Conclusion: Patients with IBD are at an increased risk of PD, regardless of health care use. Corticosteroid and anti-TNF use may prevent PD in patients with IBD. [ABSTRACT FROM AUTHOR]

Background and Aims: Inflammatory bowel disease (IBD) may be associated with anxiety and depression. The aim of this study was to evaluate the incidence of anxiety and depression in patients with IBD compared to the general population. Methods: A nationwide population-based cohort study was conducted using claims data from the National Healthcare Insurance service in Korea. We compared the incidence of anxiety and depression between 15,569 IBD patients and 46,707 non-IBD controls, age and sex matched at a ratio of 1:3. Results: During a mean follow-up of six years, IBD patients experienced significantly more anxiety (12.2% vs. 8.7%; p < 0.001) and depression (8.0% vs. 4.7%; p < 0.001) compared to controls. The curves showing cumulative incidences of anxiety and depression showed a steep rise within one year following a diagnosis of IBD, leading to lines with a constant slope. The hazard ratio (HR) for new onset anxiety following a diagnosis of Crohn's disease (CD) and ulcerative colitis (UC) was 1.63 and 1.60, respectively, compared to controls (p < 0.001). Compared to controls, the HR for developing depression after a diagnosis of CD and UC was 2.09 and 2.00, respectively (p < 0.001). The risks of anxiety and depression in patients with IBD were higher compared to controls, except in those with diabetes mellitus, hypertension, and dyslipidemia, or who required immunomodulators and biologics within one year of the IBD diagnosis. Conclusions: The risk of anxiety and depression increased after a diagnosis of IBD compared to the general population. [ABSTRACT FROM AUTHOR]

The association of diabetes with inflammatory bowel disease (IBD) remains unclear. The risk of diabetes in patients with IBD compared with non-IBD controls was investigated. Using the National Health Insurance database of South Korea, 8070 patients with IBD based on the International Classification of Disease 10th revision (ICD-10) codes and rare intractable disease codes for Crohn's disease (CD) and ulcerative colitis (UC) were compared with 40,350 non-IBD individuals (2010–2014). Newly diagnosed diabetes identified using ICD-10 codes and the prescription of anti-diabetic medication by the end of the follow-up period (2016) was investigated. During a mean follow-up of 5.1 years, the incidence of diabetes in patients with IBD was significantly higher compared with controls after adjusting for serum glucose levels and steroid use (23.19 vs. 22.02 per 1000 person-years; hazard ratio (HR), 1.135; 95% confidence interval (CI), 1.048–1.228). The risk of diabetes was significantly higher in patients with CD (HR, 1.677; 95% CI, 1.408–1.997), but not in UC (HR, 1.061; 95% CI, 0.973–1.156). The effect of IBD on the development of diabetes was significantly more prominent in younger patients (p < 0.001). Patients with CD are at a higher risk of diabetes. Regular monitoring for diabetes is recommended, even in younger CD patients who do not use steroid medication. [ABSTRACT FROM AUTHOR]