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1.
Artigo em Inglês | MEDLINE | ID: mdl-33775898

RESUMO

BACKGROUND & AIMS: Diet is thought to play a role in the development of inflammatory bowel disease (IBD), though the relationship between gluten intake and risk of IBD has not been explored. The aim of this study was to determine the relationship between gluten intake and risk of incident Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We performed a prospective cohort study of 208,280 US participants from the Nurses' Health Study (NHS; 1986-2016), NHSII (1991-2017), and Health Professionals Follow-up Study (1986-2016) who did not have IBD at baseline or celiac disease, and who completed semi-quantitative food frequency questionnaires. We used Cox proportional hazards modeling to estimate the risk of IBD according to quintiles of cumulative average energy-adjusted dietary gluten intake over follow-up period. RESULTS: We documented 337 CD cases and 447 UC cases over 5,115,265 person-years of follow-up. Dietary gluten intake was not associated with risk of IBD. Compared to participants in the lowest quintile of gluten intake, the adjusted hazard-ratios and 95% confidence intervals (CI) for participants in the highest quintile of gluten intake were 1.16 (95% CI: 0.82-1.64; Ptrend = 0.41) for CD and 1.04 (95% CI: 0.75-1.44; Ptrend = 0.64) for UC. Adjusting for primary sources of gluten intake did not materially change our estimates. CONCLUSIONS: In three large adult US prospective cohorts, gluten intake was not associated with risk of CD or UC. Our findings are reassuring at a time when consumption of gluten has been increasingly perceived as a trigger for chronic gastrointestinal diseases.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33280139

RESUMO

BACKGROUND: Although immune-mediated diseases (IMDs) including inflammatory bowel diseases (IBDs) are known to cluster, to what extent this is due to common environmental influences is unknown. AIM: To examine the incidence of IBD in individuals with another IMD. METHODS: We used data from the prospective Nurses' Health Study II cohort (1995-2017) to examine the effect of diagnoses of several common IMDs on subsequent risk of Crohn's disease (CD) or ulcerative colitis (UC) using Cox proportional hazards models, adjusting for detailed diet and lifestyle confounders. RESULTS: We documented 132 cases of CD and 186 cases of UC over 2 016 163 person-years of follow-up (median age at IBD diagnosis 50 years). Compared to participants with no history of IMD, the HRs of CD for those with 1 and ≥ 2 IMDs were 2.57 (95% CI 1.77-3.74) and 2.74 (95% CI 1.36 to 5.49), respectively (Ptrend  < 0.0001). This association was only modestly attenuated by adjustment for environmental risk factors (HR 2.35 and 2.46, respectively). The risk of UC was not increased, with multivariable-adjusted HRs of 1.22 (95% CI 0.85-1.76) and 1.33 (95% CI 0.67-2.65) for those with 1 and ≥ 2 IMDs, respectively, compared to those with none (Ptrend 0.16) (Pheterogeneity comparing CD and UC 0.037). Asthma, atopic dermatitis, psoriasis and rosacea were individually associated with higher risk of CD (HR ranging from 2.15 to 3.39) but not UC. CONCLUSIONS: Individuals with one or more IMDs are at an increased risk for CD but not UC.

5.
Inflamm Bowel Dis ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33089863

RESUMO

BACKGROUND: The effect of immunosuppressive treatment for immune-mediated diseases on risk of the novel coronavirus disease 2019 (COVID-19) has not been established. We aimed to define the effect of targeted biologic and immunomodulator therapy on risk of COVID-19 in a multi-institutional cohort of patients with inflammatory bowel disease (IBD). METHODS: We identified patients 18 years and older who received care for IBD at Partners Healthcare between January 2019 and April 2020. The primary outcome was development of COVID-19 defined as a positive polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2. Multivariable regression models were used to examine the effect of immunosuppression on risk of COVID-19 and its outcomes. RESULTS: In a cohort of 5302 IBD patients, 39 (0.7%) developed COVID-19. There was no difference in age, sex, or race between IBD patients with and without COVID-19. The rate of COVID-19 was similar between patients treated with immunosuppression (0.8%) compared with those who were not (0.64%; P = 0.55). After adjusting for age, sex, race, and comorbidities, use of immunosuppressive therapy was not associated with an increased risk of COVID-19 (odds ratio, 1.73; 95% confidence interval, 0.82-3.63). The presence of obesity was associated with a higher risk of COVID-19 (odds ratio, 8.29; 95% confidence interval, 3.72-18.47). There were 7 hospitalizations, 3 intensive care unit stays, and 1 death. Older age and obesity but not immunosuppressive treatment were associated with severe COVID-19 infection. CONCLUSIONS: The use of systemic immunosuppression was not associated with an increased risk of COVID-19 in a multi-institutional cohort of patients with IBD.

6.
Inflamm Bowel Dis ; 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32812048

RESUMO

BACKGROUND: The development of chromoendoscopy (CE) and high definition endoscopy (HDE) has improved detection of subtle colonic dysplasia in patients with inflammatory bowel diseases (IBDs). The role of random biopsies for dysplasia surveillance is unclear. METHODS: We reviewed patients with IBD who underwent a CE or HDE colonoscopy and had colonic dysplasia detected. Detection of dysplasia was classified as either visible or random and graded as low grade dysplasia (LGD), high grade dysplasia (HGD), or indefinite for dysplasia. Multivariable regression adjusted for relevant confounders examined the predictors of dysplasia detectable on random biopsies alone. RESULTS: The study included 300 patients (203 ulcerative colitis, 97 Crohn's disease with colonic involvement) contributing 442 colonoscopies; the mean disease duration was 24.5 years; 7.2% had primary sclerosing cholangitis (PSC). Three hundred sixty-two colonoscopies (82%) had only visible dysplasia, 52 (12%) had only random dysplasia, and 28 (6%) had both visible and random dysplasia. Longer disease duration (odds ratio, 1.04; 95% CI, 1.01-1.07), active inflammation (odds ratio, 2.89; 95% CI, 1.26-6.67), and concomitant PSC (odds ratio, 3.66; 95% CI, 1.21-11.08) were associated with detecting dysplasia on random biopsies compared with visible lesions. Patients with random dysplasia (21%) or both random and visible dysplasia (21%) were more likely to undergo surgical resection compared with those with only visible dysplasia (5%; P < 0.001) and have subsequent development of colorectal cancer (15%, 7%, 1%, respectively; P < 0.0001). CONCLUSION: Nearly one fifth of dysplasia detected in patients with IBD was found on random biopsies. Patients with high risk characteristics may benefit from continuing the practice of random biopsies during surveillance examinations.

7.
Gastroenterology ; 159(3): 873-883.e1, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32389666

RESUMO

BACKGROUND & AIMS: Inflammation is a potential mechanism through which diet modulates the onset of inflammatory bowel disease. We analyzed data from 3 large prospective cohorts to determine the effects of dietary inflammatory potential on the risk of developing Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We collected data from 166,903 women and 41,931 men in the Nurses' Health Study (1984-2014), Nurses' Health Study II (1991-2015), and Health Professionals Follow-up Study (1986-2012). Empirical dietary inflammatory pattern (EDIP) scores were calculated based on the weighted sums of 18 food groups obtained via food frequency questionnaires. Self-reported CD and UC were confirmed by medical record review. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We documented 328 cases of CD and 428 cases of UC over 4,949,938 person-years of follow-up. The median age at IBD diagnosis was 55 years (range 29-85 years). Compared with participants in the lowest quartile of cumulative average EDIP score, those in the highest quartile (highest dietary inflammatory potential) had a 51% higher risk of CD (HR 1.51; 95% CI 1.10-2.07; Ptrend = .01). Compared with participants with persistently low EDIP scores (at 2 time points, separated by 8 years), those with a shift from a low to high inflammatory potential of diet or persistently consumed a proinflammatory diet had greater risk of CD (HR 2.05; 95% CI 1.10-3.79 and HR 1.77; 95% CI 1.10-2.84). In contrast, dietary inflammatory potential was not associated with the risk of developing UC (Ptrend = .62). CONCLUSIONS: In an analysis of 3 large prospective cohorts, we found dietary patterns with high inflammatory potential to be associated with increased risk of CD but not UC.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32142939

RESUMO

BACKGROUND & AIMS: It is not clear whether a healthy lifestyle affects mortality of patients with inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We collected data form the Nurses' Health Study (1986-2014), Nurses' Health Study II (1991-2015), and Health Professionals Follow-up Study (1986-2014), which assess lifestyles with serial questionnaires. We estimated joint and individual associations between 5 healthy lifestyle factors after IBD diagnosis (never smoking, body mass index 18.5-24.9 kg/m2, vigorous physical activity in the highest 50% with non-zero value, alternate Mediterranean diet score ≥4, and light drinking [0.1-5.0 g/d]) and mortality using Cox proportional hazards models. RESULTS: We documented 83 deaths in 363 patients with CD during 4741 person-years and 80 deaths in 465 patients with UC during 6061 person-years. The median age of IBD diagnosis was 55 y. Compared to patients with IBD with no healthy lifestyle factors, patients with IBD with 3-5 healthy lifestyle factors had a significant reduction in all-cause mortality (hazard ratio [HR], 0.29; 95% CI, 0.16-0.52; Ptrend < .0001). This reduction was significant in patients with CD (Ptrend = .003) as well as in patients with UC (Ptrend = .0003). Individual associations were more than 25 pack-years (HR, 1.92; 95% CI, 1.24-2.97; Ptrend < .0001), physical activity (HR according to quintiles, 0.55-0.31; Ptrend = .001), Mediterranean diet (HR, 0.69; 95% CI, 0.49-0.98), and alcohol consumption (HR0.1-5 g/d 0.61; 95% CI, 0.39-0.95 vs HR>15 g/d 1.84; 95% CI, 1.02-3.32). The findings did not change when we adjusted for family history of IBD, immunomodulator use, and IBD-related surgery. CONCLUSIONS: In an analysis of data from 3 large cohort studies, we associated adherence to a healthy lifestyle with reduced mortality in patients with CD or UC.

9.
Gastroenterology ; 158(6): 1574-1583.e2, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31926169

RESUMO

BACKGROUND & AIMS: Microscopic colitis shares pathogenetic mechanisms with inflammatory bowel disease (IBD). We studied the association between microscopic colitis and risk of incident IBD using data from a nationwide cohort study. METHODS: We conducted a prospective cohort study of all adults who received a diagnosis of microscopic colitis from 1990 through 2017 in Sweden and risk of incident IBD. Cases of microscopic colitis (n= 13,957) were identified through Systematized Nomenclature of Medicine codes from the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study, which included gastrointestinal pathology reports from all of Sweden's 28 centers. Individuals with microscopic colitis were matched to 5 general population controls (n = 66,820) and to unaffected siblings (n =13,943). Cox regression was used to estimate adjusted hazard ratio (aHRs) and 95% confidence intervals (CIs). RESULTS: Through December of 2017, we identified 323 incident cases of ulcerative colitis (UC) and 108 incident cases of Crohn's disease (CD) in patients with microscopic colitis compared with 94 UC and 42 CD cases in population comparators. Mean times from diagnosis of microscopic colitis to diagnosis of CD was 3.3 ± 3.2 years and to diagnosis of UC was 3.2 ± 3.5 years. In multivariable models, microscopic colitis was associated with an aHR of 12.6 (95% CI 8.8-18.1) for CD, 17.3 (95% CI 13.7-21.8) for UC, and 16.8 (95% CI 13.9-20.3) for IBD. The 10-year absolute excess risks of CD and UC were 0.9 (95% CI 0.7-1.1) and 2.6 (95% CI 2.2-2.9) percentage points, respectively. In sensitivity analyses, comparing patients with microscopic colitis with their unaffected siblings, the aHRs of CD and UC were 5.4 (95% CI 3.2-9.2) and 9.4 (95% CI 6.4-13.8), respectively. CONCLUSIONS: In a population-based study in Sweden, we found a significant increase in risk of incident IBD among patients with microscopic colitis. Future studies should focus on potential mechanisms underlying these observed associations.


Assuntos
Colite Microscópica/epidemiologia , Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Adulto , Idoso , Biópsia/estatística & dados numéricos , Estudos de Casos e Controles , Colite Microscópica/complicações , Colite Microscópica/patologia , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/etiologia , Colite Ulcerativa/patologia , Colo/patologia , Doença de Crohn/diagnóstico , Doença de Crohn/etiologia , Doença de Crohn/patologia , Feminino , Seguimentos , Humanos , Incidência , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Sistema de Registros/estatística & dados numéricos , Fatores de Risco , Suécia/epidemiologia
10.
Clin Gastroenterol Hepatol ; 18(11): 2491-2499.e3, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31857243

RESUMO

BACKGROUND & AIMS: Microscopic colitis is one of the most common causes of chronic diarrhea in older populations. We investigated all-cause and cause-specific mortality in patients with microscopic colitis. METHODS: We conducted a nationwide cohort study of all cases of microscopic colitis (n = 14,333) diagnosed from 1990 through 2017 in Sweden. Cases of microscopic colitis were identified using SNOMED codes from gastrointestinal histopathology reports collected from Sweden's 28 pathology departments. Each case of microscopic colitis was matched to 5 population comparators (n = 68,700). Mortality data were ascertained from Sweden's cause of death register. We used Cox proportional hazards modeling to estimate adjusted hazard ratios (aHRs) and 95% CIs. RESULTS: Through December of 2017, we confirmed 3014 deaths in patients with microscopic colitis (27.4/1000 person-years) and 12,534 deaths in matched population comparators (23.3/1000 person-years). This corresponded to a 10-year absolute risk difference of 3.4% (95% CI, 2.1%-4.6%) and an aHR of 1.17 (95% CI, 1.12-1.22). However, further adjustment of models for comorbidity burden reduced the relative risk of death for patients with microscopic colitis (aHR, 0.98; 95% CI, 0.94-1.02). In analyses of cause-specific death, microscopic colitis was associated with an increased risk of gastrointestinal-related death (aHR, 1.68; 95% CI, 1.38-2.05) and infection-related death (aHR, 1.42 ; 95% CI, 1.11-1.83), but not cancer-related death (aHR, 0.83; 95% CI, 0.76-0.91) or cardiovascular-related death (aHR, 1.02; 95% CI, 0.96-1.10). CONCLUSIONS: In a nationwide cohort study in Sweden, we found that patients with microscopic colitis were at increased risk of death. However, the increase appears to be related to higher burden of comorbidities in this population.

11.
Clin Gastroenterol Hepatol ; 18(8): 1890-1892, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31404664

RESUMO

Crohn's disease (CD) and ulcerative colitis (UC) are heterogeneous. With availability of therapeutic classes with distinct immunologic mechanisms of action, it has become imperative to identify markers that predict likelihood of response to each drug class. However, robust development of such tools has been challenging because of need for large prospective cohorts with systematic and careful assessment of treatment response using validated indices. Most hospitals in the United States use electronic health records (EHRs) that warehouse a large amount of narrative (free-text) and codified (administrative) data generated during routine clinical care. These data have been used to construct virtual disease cohorts for epidemiologic research as well as for defining genetic basis of disease states or discrete laboratory values.1-3 Whether EHR-based data can be used to validate genetic associations for more nuanced outcomes such as treatment response has not been examined previously.

12.
Dig Dis Sci ; 65(1): 111-118, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31367882

RESUMO

BACKGROUND: Factors associated with interval colorectal cancer (CRC) development in the inflammatory bowel disease (IBD) population remain unclear. AIMS: Among a cohort of patients with interval CRC, we aimed to evaluate IBD characteristics, colonoscopy quality indicators, and surveillance guideline adherence. METHODS: We performed a retrospective review of IBD- and non-IBD-associated interval CRCs diagnosed between January 2007 and December 2014 within a large US healthcare system. We evaluated risk factors for CRC among patients with IBD. We assessed adherence to surveillance guidelines according to the American Society for Gastrointestinal Endoscopy (IBD surveillance) and the US Multi-Society Task Force on Colorectal Cancer (polyp surveillance). We compared colonoscopy quality measures between patients with and without IBD. RESULTS: Among 5345 cases of colonic adenocarcinoma, we detected 15 IBD-associated cases of interval CRC and 230 non-IBD-associated cases of interval CRC. Compared to patients without IBD, IBD patients were younger (54.5 vs. 70.4 years; p < 0.0001) and experienced a shorter interval between index colonoscopy and CRC diagnosis (20.7 vs. 35.1 months; p = 0.0009). Fifty three percent (8/15) of interval CRCs in IBD patients were detected within surveillance guidelines. All IBD patients with interval CRC detected after guideline surveillance interval had high-risk features, including active inflammation, previous low-grade or indefinite dysplasia, multiple pseudopolyps on index colonoscopy, or a first-degree relative with CRC. There were no differences in colonoscopy quality measures between patients with and without IBD. CONCLUSIONS: This study stresses the importance of strict short-interval surveillance for IBD patients with high-risk features, including active inflammation on index colonoscopy.


Assuntos
Adenocarcinoma/diagnóstico , Pólipos Adenomatosos/diagnóstico , Colite Ulcerativa/diagnóstico , Pólipos do Colo/diagnóstico , Colonoscopia/normas , Neoplasias Colorretais/diagnóstico , Doença de Crohn/diagnóstico , Detecção Precoce de Câncer/normas , Fidelidade a Diretrizes/normas , Guias de Prática Clínica como Assunto/normas , Adenocarcinoma/epidemiologia , Pólipos Adenomatosos/epidemiologia , Adulto , Idoso , Colite Ulcerativa/epidemiologia , Pólipos do Colo/epidemiologia , Neoplasias Colorretais/epidemiologia , Doença de Crohn/epidemiologia , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Indicadores de Qualidade em Assistência à Saúde/normas , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia
13.
Clin Gastroenterol Hepatol ; 18(4): 984-986, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31254673

RESUMO

The critical role of the gut microbiome in microscopic colitis (MC) is evident by the observation that fecal diversion is associated with resolution of mucosal inflammation while restoration of fecal stream is associated with recurrence of disease.1 Characterization of the composition and function of the gut microbiome in MC therefore could provide insights into disease pathogenesis.

16.
Am J Gastroenterol ; 114(1): 127-134, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30181535

RESUMO

OBJECTIVE: Microscopic colitis is a common cause of chronic watery diarrhea among the elderly. Although the prevalence of celiac disease appears to be higher in patients with microscopic colitis, the relationship between dietary gluten intake and risk of microscopic colitis among individuals without celiac disease has not been explored. METHODS: We conducted a prospective study of 160,744 US women without celiac disease enrolled in the Nurses' Health Study (NHS) and the NHSII. Dietary gluten intake was estimated using validated food frequency questionnaires every 4 years. Microscopic colitis was confirmed through medical records review. We used Cox proportional hazard modeling to estimate the multivariable-adjusted hazard ratio (HR) and 95% confidence interval (CI). RESULTS: We documented 219 incident cases of microscopic colitis over more than 20 years of follow-up encompassing 3,716,718 person-years (crude incidence rate: 5.9/100,000 person-years) in NHS and NHSII. Dietary gluten intake was not associated with risk of microscopic colitis (Ptrend = 0.88). Compared to individuals in the lowest quintile of energy-adjusted gluten intake, the adjusted HR of microscopic colitis was 1.18 (95% CI: 0.77-1.78) for the middle quintile and 1.03 (95% CI: 0.67-1.58) for the highest quintile. Additional adjustment for primary dietary sources of gluten including refined and whole grains did not materially alter the effect estimates (All Ptrend ≥ 0.69). The null association did not differ according to lymphocytic or collagenous subtypes (Pheterogeneity = 0.72) and was not modified by age, smoking status, or body mass index (All Pinteraction ≥ 0.17). CONCLUSIONS: Dietary gluten intake during adulthood was not associated with risk of microscopic colitis among women without celiac disease.


Assuntos
Doença Celíaca , Colite Ulcerativa/epidemiologia , Glutens/administração & dosagem , Adulto , Estudos de Coortes , Colite Ulcerativa/etiologia , Colite Ulcerativa/patologia , Comportamento Alimentar , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Prevalência , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários , Estados Unidos/epidemiologia , Saúde da Mulher
17.
Clin Gastroenterol Hepatol ; 17(12): 2523-2532.e1, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30529732

RESUMO

BACKGROUND & AIMS: Obesity promotes intestinal inflammation and might contribute to the pathogenesis of inflammatory bowel disease. We examined the association between obesity and risk of microscopic colitis in a prospective cohort study. METHODS: We collected data from 192,101 women enrolled in the Nurses' Health Study (NHS) (from 1986 through 2014) or the NHSII (from 1991 through 2015). Anthropomorphic and lifestyle information were self-reported biennially. Obesity was defined using body mass index (BMI). Microscopic colitis was confirmed by review of medical records. We used Cox proportional hazard models to estimate adjusted hazard ratios (aHRs) and 95% CIs. RESULTS: Among the participants in the NHS and NHSII, we confirmed 244 cases of microscopic colitis during 4,223,868 person-years of follow-up evaluation. Higher BMI was associated inversely with risk of microscopic colitis (Ptrend < .001). Compared with women with BMIs ranging from 18.5 to 20.9 kg/m2, the aHRs were 0.61 (95% CI, 0.41-0.91) for overweight women (BMI, 25-29.9 kg/m2) and 0.50 (95% CI, 0.32-0.79) for obese women (BMI ≥ 30 kg/m2). The aHR for each 5-kg/m2 increase in BMI was 0.79 (95% CI, 0.69-0.90). Weight gain since early adulthood (age, 18 y) also was associated inversely with risk of microscopic colitis (Ptrend = .001). The aHR for each 10-kg weight gain since early adulthood was 0.85 (95% CI, 0.77-0.94). The associations were not modified by age, cohort, physical activity, or smoking status (all Pinteraction ≥ .26). CONCLUSIONS: Unlike many other immune- and metabolic-related disorders, obesity and weight gain since early adulthood were associated with a lower risk of microscopic colitis, based on an analysis of participants in the NHS and NHSII.


Assuntos
Colite Microscópica/epidemiologia , Obesidade/epidemiologia , Ganho de Peso , Adulto , Índice de Massa Corporal , Estudos de Coortes , Feminino , Inquéritos Epidemiológicos , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Risco
18.
Gastroenterology ; 155(6): 1764-1775.e2, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30144433

RESUMO

BACKGROUND & AIMS: Microscopic colitis is a chronic inflammatory disorder of the colon primarily affecting postmenopausal women. However, the relation between hormonal determinants, including reproductive and menopausal factors, and risk of microscopic colitis has yet to be characterized. METHODS: We collected data from 227,766 women who participated in the Nurses' Health Study (NHS) and the NHSII without a baseline history of microscopic colitis. Reproductive and menopausal factors were assessed in 1988 in the NHS and 1989 in the NHSII and updated biennially. Cases of microscopic colitis were confirmed through review of pathology records. We used Cox proportional hazards modeling to estimate hazard ratios and 95% confidence intervals. RESULTS: Through 2014 in the NHS and 2015 in the NHSII, we confirmed 275 incident cases of microscopic colitis over 5,147,282 person-years. Compared with never use, current use of menopausal hormone therapy was associated with increased risk of microscopic colitis (multivariable-adjusted hazard ratio 2.64; 95% confidence interval 1.78-3.90). The risk increased with longer duration of use (P for trend < .0001) and decreased after discontinuation (P for trend = .002). The association did not differ according to disease subtype (P for heterogeneity = .34). Similarly, ever use of oral contraceptives was associated with increased risk of microscopic colitis (multivariable-adjusted hazard ratio 1.57; 95% confidence interval 1.16-2.13). There were no associations between age at menarche, parity, age at first birth, age at menopause, or menopause type and incident microscopic colitis. CONCLUSIONS: In 2 large prospective cohort studies, we observed an association between exogenous hormone use and incident microscopic colitis. Further studies are needed to determine the mechanisms underlying these associations.


Assuntos
Colite Microscópica/induzido quimicamente , Anticoncepcionais Orais/efeitos adversos , Terapia de Reposição de Estrogênios/efeitos adversos , Adulto , Idoso , Colite Microscópica/epidemiologia , Feminino , Inquéritos Epidemiológicos , Humanos , Incidência , Menopausa , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , História Reprodutiva , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo
19.
Inflamm Bowel Dis ; 24(8): 1840-1848, 2018 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-29718226

RESUMO

Background: Despite a high nonresponse rate, predictors of response to anti-tumor necrosis factor (anti-TNF) therapy in ulcerative colitis (UC) remain limited. We aim to determine clinical and genetic predictors of primary nonresponse (PNR) and durable response (DR) to anti-TNF therapy in a large prospective UC cohort. Methods: Using the Illumina Immunochip, candidate polymorphisms associated with clinical outcomes of PNR and DR were separately evaluated and combined into weighted genetic risk scores. Combined genetic and clinical multivariable models for PNR and DR were compared with clinical predictive models using area under the receiver operating characteristic (AUROC) curves. Models were internally (DR) or externally (PNR) validated. Multivariable logistic regression was utilized to assess the association of genetic risk scores with infliximab levels and antibodies. Results: Of 231 patients, 28 (12%) experienced PNR and 120 (52%) experienced DR. There was no significant difference in clinical features between primary nonresponders and responders. Eight alleles were associated with PNR. A combined clinical-genetic model (AUROC, 0.87) more accurately predicted PNR compared with a clinical-only model (AUROC, 0.57; P < 0.0001). In an external cohort of 131 patients, increasing tertiles of PNR genetic risk score correlated with increased risk of PNR (P = 0.052). Twelve candidate loci were associated with DR. Genetic risk score quartiles for DR demonstrated a strong dose-response relationship in predicting treatment duration. Genetic risk scores for PNR and DR were not associated with infliximab levels or antibody formation. Conclusion: Genetic polymorphisms enhance prediction of PNR and DR to anti-TNF therapy in patients with UC.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Variantes Farmacogenômicos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/uso terapêutico , Adolescente , Adulto , Boston , Feminino , Marcadores Genéticos , Testes Genéticos , Genótipo , Humanos , Infliximab/uso terapêutico , Modelos Logísticos , Masculino , Análise Multivariada , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Curva ROC , Sistema de Registros , Fumar/epidemiologia , Resultado do Tratamento , Adulto Jovem
20.
J Crohns Colitis ; 12(5): 559-567, 2018 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-29370359

RESUMO

Background: Long-term data on the influence of smoking on risk of microscopic colitis are limited. We therefore sought to examine and characterize the association between smoking and risk of incident microscopic colitis in two large prospective cohorts of women. Methods: We conducted a prospective study of 231015 women enrolled in the Nurses' Health Study [NHS] and NHSII. Information regarding smoking, other lifestyle factors and medications were collected biennially from 1976 to 2012 in NHS and from 1989 to 2013 in NHSII. Incident cases of microscopic colitis were confirmed through physician medical record review. We used Cox proportional hazards modelling to examine the association between smoking and risk of microscopic colitis. Results: We documented 166 incident cases of microscopic colitis over 6122779 person-years of follow up. Compared to non-smokers, the multivariable-adjusted hazard ratio [HR] for microscopic colitis was 2.52 (95% confidence interval [CI] 1.59-4.00) amongst current smokers and 1.54 [95% CI 1.09-2.17] amongst past smokers. The risk increased with higher pack-years of smoking [p trend = 0.001] and diminished following smoking cessation [p trend = 0.017]. Current smoking appeared to be more strongly associated with risk of collagenous colitis [HR 3.68; 95% CI 1.94-6.97] than lymphocytic colitis [HR 1.71; 95% CI 0.83-3.53]. Conclusion: In two large prospective cohort studies, we observed an association between current smoking and risk of microscopic colitis. Risk of microscopic colitis appeared to increase with higher pack-years and diminish following smoking cessation. Future studies focused on characterizing the biological mechanisms underlying these associations are warranted.


Assuntos
Colite Colagenosa/epidemiologia , Colite Linfocítica/epidemiologia , Fumar/epidemiologia , Adulto , Feminino , Inquéritos Epidemiológicos , Humanos , Incidência , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Abandono do Hábito de Fumar/estatística & dados numéricos , Estados Unidos/epidemiologia
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