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Occupational risk for Crohn's disease: A two-center study

Digestive and Liver Disease, In Press, Corrected Proof, Available online 5 August 2016, Available online 5 August 2016

Abstract

Background

Occupational factors have been suggested as possible elements in the etiology of Crohn's disease, although evidences have not been fully obtained.

Aims

This study is to investigate possible associations between occupation and development of Crohn's disease.

Methods

This prospective study was carried out in two major hospitals during January 2010 and December 2014. Demographic and clinical data were collected for the calculation of standard incidence ratios and 95% confidence intervals by occupation.

Results

A total of 401 patients with Crohn's disease were recruited into this study. Participants were distributed into 8 major occupational groups, among which “professionists” (17.7%), “service and sales” (18.7%) and “unclassified individuals” (mainly students) (20.2%) took up the most proportions. Increased standard incidence ratios were found in “service and sales” (2.526 ± 0.135, 95% CI: 1.939–3.290), “professionists” (4.216 ± 0.142, 95% CI: 3.194–5.565), and most significantly, in “administrative staffs” (5.476 ± 0.170, 95% CI: 3.926–7.639). In contrast, decreased standard incidence ratios for Crohn's disease were observed in the category of “workers in agriculture, forestry, animal husbandry, fishery and water conservancy” (0.088 ± 0.146, 95% CIs: 0.066–0.117).

Conclusion

Occupational elements are implicated in the likelihood of development of Crohn's disease.

Keywords: Crohn's disease, Incidence, Inflammatory bowel disease, Occupation, Socioeconomic.

1. Introduction

The incidence and prevalence of Crohn's disease (CD) have been globally increasing during recent decades [1]. Atypical symptoms (abdominal pain, diarrhea and fever) as well as severe complications including bowel obstruction, gastrointestinal fistula and bleeding indicate its emergence as a systemic and life-threatening disease. The nature of relapse and recurrence of CD results in major socioeconomic burden and significant decline in quality of life [2].

Unfortunately, the etiology of CD has not been fully revealed, although extensive studies have suggested that genetic susceptibility, disturbed immune responses and diminished diversity of commensal microbiota affected by environmental elements collectively contribute to the development of CD [3].

Environmental factors such as smoking, diet, stress, geographical and social status are assumed to be involved in the regulation of commensal microbiota, and further participate in the host immune responses and even epigenetic modifications [4]. Current evidences support an essential role of environmental elements in the pathogenesis of CD.

Previous studies have reported increased risks for Crohn's disease among population in certain occupations [5], [6], [7], and [8]. It is possible that occupation related to education and socioeconomic status, and thereby affecting the risk of developing CD in multiple ways. However, deep analysis towards the possible role of occupational exposure in the likelihood of CD is still obscure. Association between specific occupation and the standard incidence ratio of CD is awaiting investigation as well. Moreover, current knowledge related to CD epidemiology is overwhelmingly based on reports from Western population. Data from Asia-Pacific region would provide an insight into the role of occupational factors in the likelihood of CD, and be helpful to understand the influence of such disease on work productivity and quality of life from globally public-healthcare perspectives.

In present study, we will recruit patients diagnosed as Crohn's disease from two major tertiary hospitals in China. We will observe the occupational distribution, compare the clinical features among different occupational groups, and calculate specific occupational risks for the development of CD in homogeneous Chinese population.

2. Materials and methods

2.1. Patient recruitment

This is a two-center prospective study performed in Nanjing Drum Tower Hospital and Jinling Hospital. Both hospitals are major tertiary healthcare facilities located in southeastern China and receive patients from across the nation. Patients were recruited from the multi-disciplinary outpatient clinic of inflammatory bowel disease (IBD) at the two hospitals between January 2010 and December 2014. Demographic information was collected by a self-reporting form, and disease-related data including CDAI (Crohn's disease activity index) score, Montreal classification and extra-intestinal manifestations were assessed and recorded by a physician at the clinic.

Patients were eligible if they were diagnosed as Crohn's disease verified by clinical manifestations, radiologic, endoscopic, and histopathologic evidences. Patients that were unwilling to participate in current study would be excluded.

2.2. Occupation classification

According to the “Dictionary of Occupation in CHINA”[9], all enrolled patients were assigned into one of eight major occupation groups, including executives (GBM0), professionists (GBM1/2), administrative staffs (GBM3), service and sales (GBM4), workers in agriculture, forestry, animal husbandry, fishery and water conservancy (GBM5), workers in industry and manufacturing (GBM6–9), soldiers (GBM X) and unclassified occupations (GBM Y). Each major occupation was further classified into several sub-categories (Table 1).

Table 1

Category of occupations.a

 

Occupation code Occupation description
GBM0 Executives of government agencies, companies and social institutions
GBM1/2 Professionists (scientists, engineers, doctors, teachers, lawyers, journalists, economists, artists, architects, IT specialists, accountings, etc.)
GBM3 Administrative staffs (secretaries, office assistants, firemen, postmen, polices, city managers, etc.)
GBM4 Service and sales (salesmen, cicerones, restaurant and hotel receptionists, self-employers, etc.)
GBM5 Workers in agriculture, forestry, animal husbandry, fishery and water conservancy
GBM6–9 Workers in industry and manufacturing
GBM X Soldiers
GBM Y Unclassified occupations (unemployed, students, etc.)

a According to the Dictionary of Occupation in CHINA (China Labour and Social Security Publishing House, 2015 edition. ISBN: 9787516722039).

2.3. Statistical analysis

The standard incidence ratio (SIR) of Crohn's disease in each occupation group was calculated according to the Woolf's method [10] described in previous publication [8]. An odds ratio was considered significant if its confidence limits do not include unity. A significance level of p = 0.05 was chosen in risk calculation. Ninety-five percent confidence intervals (95% CIs) were calculated assuming a Poisson distribution [5]. Data regarding the employee distribution in each occupation group were retrieved from the 2014 annual report of the National Bureau of Statistics of CHINA [11]. The SIRs in population (control group) was particularly collected from population in Nanjing that has been reported in our previous publication [12].

All statistical tests were performed with SPSS software (SPSS for Windows, version 13.0, SPSS, Chicago, IL). Continuous variables were described as mean ± SD, and categorical variables were presented as percentages.

2.4. Ethical statement

This prospective study was approved by both of the Ethics Committee of Nanjing Drum Tower Hospital and Jinling Hospital. A written informed consent was obtained from each enrolled patient.

3. Results

3.1. Occupational distribution of patients with Crohn's disease

Between January 2010 and December 2014, a total of 401 patients with Crohn's disease were enrolled into this study. Fig. 1 demonstrated the occupational distribution of patients with CD. Among them, “professionists” (GBM1/2), “service and sales” (GBM4) and “unclassified individuals” (mainly “students”) (GBM Y) were the most frequent major occupations, with a proportion of 17.7%, 18.7% and 20.2% respectively. “Workers in industry and manufacturing” (GBM6–9), “workers in agriculture, forestry, animal husbandry, fishery and water conservancy” (GBM5) and “administrative staffs” (GBM3) took up 15.0%, 14.0% and 12.2% of enrolled patients, respectively. The other two types of major occupations, including “executives” (GBM0) and “soldiers” (GBM X), only represented 1% of patients with CD.

gr1

Fig. 1

Occupational distribution of patients with Crohn's disease. A total of 401 patients with Crohn's disease were divided into 8 major occupation groups. Internal pie chart represented group name (percentage). External pie chart represented sub-categories of each major occupation.

 

Further analysis of sub-categories of occupation found that “farmers” (11.2%), “industrial workers” (7.0%), “office assistants” (5.0%) and “salesmen” (5.0%) were the most common types of patients with CD. Occupations that took up 3.5–5.0% included “self-employers” (4.5%), “teachers” (4.2%), “engineers” (3.7%), “secretaries” (3.5%) and “manufacturing workers” (3.5%). Fig. 1 illustrated the composition of general and sub-categories of occupations in patients with CD.

3.2. Clinical characteristics among major occupational groups

We next collected the demographic and clinical features of all participants in different occupational groups (Table 2). Middle-aged pattern ranging between 30 and 45 years old was observed in all groups except unclassified group that was mainly consisted of much younger students. Male predominance was found in all groups, resulting in a male prevalence of 67.3% in total. Relatively low BMI ranging between 17.1 and 21.7 (mean value 19.3 ± 3.41) was observed in all groups as well, suggesting that malnutrition was common in patients with CD. CDAI score was ranging between 100 and 180 points among groups, leading to a mean CDAI score of 136.9 ± 64.2 points in total.

Table 2

Clinical features of patients with Crohn's disease in different occupational groups.

 

Occupation code GBM0 GBM1/2 GBM3 GBM4 GBM5 GBM6–9 GBM X GBM Y Total
Number of patients (%) 6 (1.50%) 71 (17.7%) 49 (12.2%) 75 (18.7%) 56 (14.0%) 60 (15.0%) 3 (0.75%) 81 (20.2%) 401 (100%)
Age (years) 42.8 ± 11.2 36.1 ± 11.1 35.4 ± 9.84 33.3 ± 8.29 42.3 ± 11.0 36.8 ± 11.6 38.0 ± 16.5 20.4 ± 5.35 33.4 ± 11.9
Gender (male, %) 6 (100%) 44 (62.0%) 32 (65.3%) 63 (84.0%) 30 (53.6%) 43 (71.7%) 3 (100%) 49 (60.5%) 270 (67.3%)
BMI (kg/m2) 19.3 ± 3.23 20.2 ± 3.29 19.7 ± 3.51 19.9 ± 3.76 19.1 ± 3.29 19.6 ± 2.96 21.7 ± 2.72 17.1 ± 3.10 19.3 ± 3.41
CDAI score 179.5 ± 41.7 141.4 ± 80.4 164.3 ± 56.0 131.5 ± 84.5 127.7 ± 49.1 158.7 ± 17.7 100.0 ± 70.7 129.5 ± 60.7 136.9 ± 64.2
Disease location
 L1 (ileal) 1 (16.7%) 24 (33.8%) 22 (44.9%) 26 (34.7%) 21 (37.5%) 32 (53.3%) 2 (66.7%) 23 (28.4%) 151 (37.7%)
 L2 (colonic) 2 (33.3%) 10 (14.1%) 14 (28.6%) 11 (14.7%) 16 (28.6%) 10 (16.7%) 1 (33.3%) 22 (27.2%) 86 (21.4%)
 L3 (ileocolonic) 3 (50.0%) 37 (52.1%) 13 (26.5%) 38 (50.7%) 19 (33.9%) 18 (30.0%) 0 36 (44.4%) 164 (40.9%)
 +L4 (upper GI) 2 (33.3%) 4 (5.63%) 1 (2.04%) 2 (2.67%) 3 (5.36%) 6 (10.0%) 0 3 (3.70%) 21 (5.23%)
Disease behavior
 B1 (inflammatory) 1 (16.7%) 27 (38.0%) 18 (36.7%) 30 (40.0%) 16 (28.6%) 27 (45.0%) 0 44 (54.3%) 163 (40.6%)
 B2 (stricturing) 4 (66.7%) 37 (52.1%) 23 (46.9%) 32 (42.7%) 23 (41.1%) 22 (36.7%) 3 (100%) 25 (30.9%) 169 (42.1%)
 B3 (penetrating) 1 (16.7%) 7 (9.86%) 8 (16.3%) 13 (17.3%) 17 (30.3%) 11 (18.3%) 0 12 (14.8%) 69 (17.2%)
 +P (perianal) 2 (33.3%) 26 (36.6%) 26 (53.1%) 27 (36.0%) 11 (19.6%) 20 (33.3%) 2 (66.7%) 35 (43.2%) 347 (86.5%)
Extra-intestinal manifestationsa 3 (50.0%) 37 (52.1%) 24 (49.0%) 31 (41.3%) 37 (66.1%) 30 (50.0%) 1 (33.3%) 46 (56.8%) 209 (52.1%)

a Extra-intestinal manifestations include anemia, thrombocytosis, oral ulcer, arthralgia, erythema nodosum and sclerosing cholangitis, etc.

According to the Montreal classification of Crohn's disease, L3 (ileocolonic) and B2 (stricturing) were the most frequent disease location and behavior in all patients. Upper gastrointestinal lesion was found in 5.23% of patients, while perianal involvement was observed in majority of patients (86.5%). Nevertheless, no statistical difference was found between occupational groups. More than half of participants demonstrated extra-intestinal manifestations, mainly including anemia (25.4%), oral ulcer (23.4%), thrombocytosis (11.2%) and arthralgia (13.7%) (Table 2).

3.3. Occupational risk for Crohn's disease

Standard incidence ratio of CD in all 8 major occupations was calculated. The values of odds ratio (OR), standard error (SE) and 95% CIs were listed in Table 3. Increased SIRs for CD were observed in “service and sales” (GBM4) (2.526 ± 0.135, 95% CI: 1.939–3.290). More significant elevation of SIRs for CD were found in “professionists” (GBM1/2) and “administrative staffs” (GBM3), with an OR value of 4.216 and 5.476, respectively.

In contrast, decreased SIRs for CD were observed in GBM5 (0.088 ± 0.146, 95% CIs: 0.066–0.117), i.e., “workers in agriculture, forestry, animal husbandry, fishery and water conservancy” were less likely to develop Crohn's disease. No statistical significance was found in other occupational groups (Table 3).

Table 3

Standardized incidence ratio of Crohn's disease in different occupations.

 

Odds ratio Standard error 95% CIs Conclusion
GBM0 0.939 0.422 0.411–2.145 ns*
GBM1/2 4.216 0.142 3.194–5.565 High risk
GBM3 5.476 0.170 3.926–7.639 High risk
GBM4 2.526 0.135 1.939–3.290 High risk
GBM5 0.088 0.146 0.066–0.117 Low risk
GBM6–9 0.975 0.144 0.736–1.293 ns
GBM X 3.579 0.632 0.969–11.51 ns
GBM Y 1.410 0.129 0.085–2.326 ns

* ns, not significant.

4. Discussion

Current study has clearly demonstrated that certain occupations are carrying significantly increased or decreased risk of the likelihood of CD in Chinese population. This study has suggested an involvement of occupation in the development of Crohn's disease.

Herein, we summarize our main findings in present study. (1) Patients with CD are widely distributed in various occupations. The prevalence of Crohn's disease is highest in “students”, “service and sales”, and “professionists”. Specific occupation analysis reveals that “farmers”, “industrial workers”, “office assistants” and “salesmen” exhibit higher incidence of Crohn's disease. (2) Middle-aged pattern with male predominance is observed in all occupational groups. Malnutrition with relatively active disease status is frequent in all groups as well. Perianal involvement and extra-intestinal manifestation are common in CD patients, with no statistical difference between occupational groups. (3) SIR calculation discovers that “administrative staffs”, “professionists” and “service and sales” expose to significantly higher risk for the development of Crohn's disease, in contrast to “workers in agriculture, forestry, animal husbandry, fishery and water conservancy” that were less likely to develop Crohn's disease.

Recently, occupational factors have been suggested as possible elements in the pathogenesis of Crohn's disease. The possible underlying mechanism includes job exposure (such as smoking environment), diet habit, fast pace of work and stressful working style. All these elements could influence the diversity and bioactivity of commensal microbiota, which further participates in host immune responses [13], [14], and [15].

Previous investigations have reported certain occupations that were associated with increased or decreased likelihood of CD. However, consistent result has not been achieved yet. Sonnenberg et al. reported open-air workplace and physical exercise as protective factors compared to air-conditioning workplace and irregular shift working as harmful factors of IBD [8]. In contrast, this hypothesis was not supported by Boggild et al., who discovered that “sedentary work” was the only risk factor of IBD [16]. Sonnenberg et al. recently found that “white collar workers” exposed to higher risk of mortality compared to “blue collar workers” presumably due to different education level and working environment [6]. However, Li et al. found that occupation and education level exert minor effect on the likelihood of CD development [5]. Bernstein et al. also concluded that patients with IBD are not of a higher socioeconomic status [17].

It is too early to conclude whether results from current study are in conformity with results of previous studies, since occupational category and ethnic characteristics vary dramatically between studies. Besides, it remains a challenge to evaluate and precisely quantify all these elements in different occupational groups. Therefore, we were currently unable to investigate the impact of these elements on the occupational risk of the development of Crohn's disease.

Furthermore, current evidences regarding the occupational risk for CD are primarily obtained from Western population, such as United States, Germany, Sweden and Denmark. Our report could fill an Asia-Pacific gap in this field. We believe a more comprehensive knowledge towards the association between occupation and risk of CD development could assist to define a global “healthy IBD patterns of work” [4], including the recognition and prevention of hazardous elements in working environment, assessment of working quality and productivity, identification of IBD fitness for work, and eventually the establishment of integrated management strategy for IBD workers in individual occupational settings. We expect these actions would support IBD patients to solve work-related problems, enhance their social competences, and ultimately improve their quality of life.

We are aware of our limitations in this study. First, this is an observational study without follow-up data. Therefore, it is impossible to evaluate the response to social supports or therapeutic interventions in different occupational groups. Second, this is a two-center instead of population-based study. The occupational composition in Chinese community could be theoretically changing during the study period. However, sub-group analysis would divide the experimental group and therefore reduce the statistical power of our study. Also, we were unable to calculate the SIRs for each sub-categories of occupation due to inadequate sample size in sub-groups. Future multiple-center study with larger recruitment of patients within a shorter study period would be more precisely to calculate the occupational risk for the development of Crohn's disease. Third, current study contains no information about specific occupational exposure such as chemical and smoking, therefore it fails to identify specific agents that should be prevented from working environment.

In conclusion, occupation is implicated in the likelihood of development of Crohn's disease in homogeneous Chinese population. Future population-based studies are expected to identify specific occupational risk factors for Crohn's disease, and clarify the causative mechanism of occupation in Crohn's disease.

Conflict of interest

None declared.

Funding

This study was supported by the grant from the National Natural Science Foundation of China (No. 81372364) (W. Guan), the Natural Science Foundation of Jiangsu Province (No. BK 20160114) (S. Liu) and the Fundamental Research Funds for the Central Universities (No. 021414380169) (S. Liu).

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Footnotes

a Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China

b Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China

Corresponding author at: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan RD, Nanjing 210002, China.

⁎⁎ Corresponding author at: Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan RD, Nanjing 210008, China.