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Occupational mortality from inflammatory bowel disease in the United States 1991–1996
THE AMERICAN JOURNAL OF GASTROENTEROLOGY © 2001 by Am. Coll. of Gastroenterology Published by Elsevier Science Inc.
Vol. 96, No. 4, 2001 ISSN 0002-9270/01/$20.00 PII S0002-9270(01)02310-3
Occupational Mortality From Inflammatory Bowel Disease in the United States 1991–1996 Claudia Cucino, M.D., and Amnon Sonnenberg, M.D., M.Sc. Department of Veterans Affairs Medical Center, and The University of New Mexico, Albuquerque, New Mexico
OBJECTIVE: The occupational distribution of inflammatory bowel disease (IBD) may help to shed light on its yet unknown etiology. The U.S. vital statistics offer the opportunity to study cause of death by occupation and industry. METHODS: The numbers of deaths from Crohn’s disease and ulcerative colitis were retrieved from the computerized 1991–1996 data files of the National Center for Health Statistics. Deaths were grouped by gender, ethnicity, disease type, occupation, and industry. Mortality by occupation and industry were expressed as proportional mortality ratio (PMR), adjusted for gender and ethnicity. RESULTS: Between 1991 and 1996, 2399 subjects died from Crohn’s disease and 2419 subjects died from ulcerative colitis. Significant correlations were found between the PMR values of ulcerative colitis and Crohn’s disease regarding their distribution by occupation, r ⫽ 0.36 and p ⬍ 0.05, as well as by industry, r ⫽ 0.37, p ⬍ 0.01. IBD mortality by occupation was significantly reduced among farmers (PMR: 70, 95% confidence interval [CI]: 42–97), mining machine operators (31, 95% CI: 0 –74), and laborers (71, 95% CI: 45–98). A nonsignificant increase was found among sales persons (117, 95% CI: 95–139) and secretaries (122, 95% CI: 83–161). IBD mortality by industry was significantly reduced in agricultural production of livestock (39, 95% CI: 1–78), mining (46, 95% CI: 9 – 83), grocery stores (55, 95% CI: 17–94), and work in private households (64, 95% CI: 30 –97). A nonsignificant increase was found in food production (128, 95% CI: 74 –182), investment and insurance business (137, 95% CI: 77–198), and administration (122, 95% CI: 81–163). CONCLUSIONS: IBD mortality is low in occupations associated with manual work and farming and relatively high in sedentary occupations associated with indoor work. Crohn’s disease and ulcerative colitis show a similar distribution. (Am J Gastroenterol 2001;96:1101–1105. © 2001 by Am. Coll. of Gastroenterology)
INTRODUCTION Epidemiology deals with the distribution and variation of disease among different populations or subgroups of a single population. By comparing the patterns of disease distri-
bution with the patterns of potential health determinants, epidemiologists hope to obtain insight about risk factors and mechanisms that contribute to the occurrence of the disease (1). The occurrence of inflammatory bowel disease (IBD) has been analyzed extensively with respect to its demographical, socioeconomic, occupational, temporal, and geographical distribution, to shed light on its yet unknown etiology (2). Certain occupational groups have been previously identified as having higher risks of suffering from IBD. It has been shown that both types of IBD tend to affect the higher social classes more frequently than the lower social classes, and white collar employees are affected more frequently than blue collar employees (3– 6). The present study analyzes the occupational mortality from Crohn’s disease and ulcerative colitis in the United States during 6 consecutive yr. Data files of the National Center of Health Statistics of the United States offer a unique source to study death causes, broken down by occupation of the deceased.
MATERIALS AND METHODS The numbers of deaths from Crohn’s disease and ulcerative colitis were retrieved from the computerized 1991–1996 data files of the National Center for Health Statistics. Deaths were grouped by gender, ethnicity (whites and nonwhites), primary cause of death, occupation, and industry. Cause of death was coded according to the ninth revision of the International Classification of Diseases (ICD). The ICD code 556 represented ulcerative colitis, and the ICD code 555 (including the subcodes 5550, 5551, 5552 and 5559) represented Crohn’s disease. Industries and occupations were classified according to the index of the U.S. Bureau of the Census (7). For the purpose of the present analysis, data from the 6 consecutive yr 1991 to 1996 were pooled and analyzed together. Mortality from Crohn’s disease or ulcerative colitis per each industrial and occupational group were expressed as proportional mortality ratios (PMR) using the method of indirect standardization (8, 9). The number of deaths from all ICD codes 1–999 per individual industry (or occupation) was expressed as proportion of all deaths in all industries. These industry-specific (or occupation-specific)
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Table 1. US Mortality From Crohn’s Disease and Ulcerative Colitis, 1991–1996 Sum Mean age (SD) Men Women Whites Nonwhites
All Deaths
Crohn’s Disease
Ulcerative Colitis
13,539,945 (100%) 71.6 6,918,638 (51%) 6,621,307 (49%) 11,634,400 (86%) 1,888,510 (14%)
2,399 (100%) 66.3 (17.2) 937 (39%) 1,462 (61%) 2,212 (92%) 187 (8%)
2,419 (100%) 71.4 (17.7) 1,071 (44%) 1,348 (56%) 2,200 (91%) 219 (9%)
proportions were then multiplied by the sum of all deaths from Crohn’s disease, to obtain the expected number of deaths from Crohn’s disease in each industrial (or occupational) group. This calculation was carried out separately for each 10-yr age group of white and nonwhite men, as well as, white and nonwhite women. The sum of deaths from Crohn’s disease expected in each race- and sex-specific group represented the overall expected number of deaths (EXP) per industry (or occupation). The ratio of observed (OBS) over expected number of deaths corresponded to PMR, the value being given in percent: PMR ⫽ OBS/EXP. It indicated whether the observed mortality from ICD code 555 in a particular industry (or occupation) lay above or below the average expected value of 100%. Similar calculations were carried out for ulcerative colitis. The calculations yielded age-, race-, and sex-standardized PMR values. The SE of the PMR value was calculated as the PMR value divided by the square root of the observed deaths: SE ⫽ PMR/公OBS. The 95% confidence interval (CI) of each PMR value was then calculated as CI ⫽ PMR ⫾ 1.96 ⫻ SE. A PMR value was considered statistically significant if its 95% CI did not include unity or 100%. The industrial and occupational distributions of mortality from Crohn’s disease were compared with those of ulcerative colitis using a least-square regression analysis of the PMR values. The overall death rates from Crohn’s disease and ulcerative colitis among men were compared to those among women using the odds ratio (OR) and its 95% CI. Similarly, the odds ratio and its 95% CI were used to compare the rates among whites and nonwhites.
(95% CI: 1.76 –2.00) for Crohn’s disease and OR ⫽ 1.62 (95% CI: 1.48 –1.76) for ulcerative colitis. The initial list of industry types contained 254 separate codes. Mortality from Crohn’s disease and ulcerative colitis were distributed among 143 and 144 different industries, respectively; the frequencies varying between one and 143 deaths per industry. In 1703 cases of Crohn’s disease and 1812 cases of ulcerative colitis, the type of industry was not stated. In the subsequent analyses, related industries were lumped together to condense the original list to a smaller list of only 60 industries with larger average case numbers per industry. For instance, “National Security,” “Army,” “Air Force,” “Navy,” “Marines,” “Coast Guard,” “Armed Forces not otherwise specified,” and “National Guard” were lumped together as “Military.” Similarly, “Metal mining,” “Coal mining,” “Oil” and “gas extraction,” and “Nonmetallic mining and quarrying” were grouped together as “Mining.” The original list of occupations contained a total of 517 different codes. Mortality from Crohn’s disease and ulcerative colitis were distributed among 174 and 154 different occupations, respectively; their frequencies ranging between one and 173. In 1704 cases of Crohn’s disease and 1759 cases of ulcerative colitis, the occupation was not stated. In the majority of instances, the PMR values of Crohn’s disease and ulcerative colitis showed the same trend. The PMR values of Crohn’s disease smaller or greater than 100% were generally associated with PMR values of ulcerative colitis behaving in the same way. This pattern applied
RESULTS From 1991 to 1996 the overall number of deaths in the United States was 13.5 million. In less than 0.04% of deaths, Crohn’s disease and ulcerative colitis were listed as primary cause of death (Table 1). Mortality was of similar order of magnitude in Crohn’s disease as ulcerative colitis. Subjects dying from Crohn’s disease were on the average 5.4 yr younger than those dying from other causes (t ⫽ 15.270, df ⫽ 2,398, p ⫽ 0.000), and subjects dying from ulcerative colitis were on the average 0.2 yr younger (t ⫽ 0.585, df ⫽ 2,418, p ⫽ 0.56). Women were more frequently affected than men by both types of IBD, the odds ratio being 1.63 (95% CI: 1.54 –1.71) for Crohn’s disease and 1.31 (95% CI: 1.23–1.39) for ulcerative colitis. Both types of IBD were also more common in whites than nonwhites, OR ⫽ 1.91
Figure 1. Correlation between proportional mortality ratio (PMR) of Crohn’s disease and ulcerative colitis distributed by industry. n ⫽ 60; p ⬍ 0.01; r ⫽ 0.37.
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Occupational Mortality of IBD
Figure 2. Correlation between proportional mortality ratio (PMR) of Crohn’s disease and ulcerative colitis distributed by occupation. n ⫽ 22; p ⬍ 0.05; r ⫽ 0.36.
similarly to the distributions of Crohn’s disease and ulcerative colitis by industry and occupation, a concordant behavior of both diseases being observed in 60% of industries and 73% of occupations. In Figure 1, the PMR values of Crohn’s disease by industry were plotted against those of ulcerative colitis. Each dot represents a different industry type. The two distributions of Crohn’s disease and ulcerative colitis correlated positively with each other. In Figure 2, the PMR values of Crohn’s disease by occupation were plotted against those of ulcerative colitis. Each dot represents a different occupational group. The analysis was restricted to the 22 largest occupations with 10 or more deaths each. Again, the distributions of Crohn’s disease and ulcerative colitis correlated positively with each other. Because of their similar industrial and occupational distributions, in subsequent analyses Crohn’s disease and ulcerative colitis were lumped together to further increase the number of cases available for each industrial and occupational category. Table 2 contains the industrial distribution of mortality
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from IBD. Besides all significant associations, the table lists all industries whose PMR values differed from the average value by 15% or more. Four industries were associated with statistically reduced PMR values. These included “Agricultural production,” “Mining,” “Grocery stores,” and “Private households.” None of the 60 broad industrial groups were associated with a significant elevation of the PMR above 100%. A nonsignificant increase was seen, for instance, in “Food products,” “Investment, insurance,” “Administration,” and “Military.” Table 3 contains the occupational distribution of mortality from IBD. Besides all significant associations, the table lists all occupations whose PMR values differed from the average value by 15% or more. Four occupations were associated with statistically reduced PMR values. These included: “Farmers,” “Farm workers,” “Mining machine operators,” and “Laborers.” None of the various occupational groups were associated with any significant elevation of the PMR above 100%. However, the number of deaths among “Sales persons” and “Secretaries” appeared higher than expected. In general, the occupational and industrial distribution seemed to corroborate each other, as the occupations matched similar types of industry with a similar PMR value. For instance, “Agriculture” as well as “Farmers” or “Farm workers” were all associated with a significantly reduced PMR. So were “Mining” and “Mining machine operators” or “Private households” and “Homemaker.”
DISCUSSION The vital statistics were used to analyze the industrial and occupational distributions of mortality from IBD in the United States between 1991 and 1996. The industrial and occupational distributions for Crohn’s disease and ulcerative colitis were similar. Both diseases occurred less frequently in industries or occupations associated with agriculture, mining, and work in private households. The IBD
Table 2. Distribution of Inflammatory Bowel Diseases by Industry Industry
PMR
95% Confidence Interval
Observed
Expected
Agricultural productions, crops Agricultural productions, livestock* Other agricultural services Mining* Food products Radio and TV services Stores Grocery stores* Motor vehicles stores and gas dealers Eating and drinking places Investment, insurance Private households* Administrations Military
76 39 76 46 128 142 132 55 162 74 137 64 122 136
45–106 1–78 1–150 9–83 74–182 76–208 98–166 17–94 94–230 45–104 77–198 30–97 81–163 69–203
24 4 4 6 22 18 58 8 22 25 20 14 35 16
32 10 5 13 17 13 44 14 14 34 15 22 29 12
PMR ⫽ proportional mortality ratio. * Significant at p ⬍ 0.05 level.
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Table 3. Distribution of Inflammatory Bowel Disease by Occupation Occupation Registered nurses Sales persons Secretaries Bookkeepers, accounting, and auditing clerks Cleaners and servants (private household) Cooks Janitors and cleaners Farmers (except horticultural) Farm workers* Groundskeepers and gardeners (except farm) Mining machine operators* Truck drivers Laborers* Homemakers
PMR
95% Confidence Interval
Observed
Expected
63 117 122 84 75 68 66 70 26 132 31 77 71 94
26–101 95–139 83–161 36–132 35–114 23–113 27–106 42–97 0–76 2–263 0–74 41–113 45–98 84–104
11 111 38 12 14 9 11 25 1 4 2 18 28 342
17 95 31 14 19 13 17 36 4 3 6 23 39 364
PMR ⫽ proportional mortality ratio. * Significant at p ⬍ 0.05 level.
mortality was also low among janitors, cleaners, and laborers in general. It tended to be increased in industries or occupations associated with food production, investment and insurance, administration, and work as sales persons or secretaries. In discussing the relevance of the present findings, several potential limitations of using occupational mortality data need to be considered. The data deal only with instances of Crohn’s disease and ulcerative colitis resulting in death. Because the case fatality rate of IBD is ⬍5%, the population of the present study may represent a select group of patients with a particularly severe course (10). There is no evidence, however, to suggest that severe and mild forms of IBD are characterized by a different type of epidemiology (11). Because the vital statistics capture the entire U.S. population, the number of cases included in the present analysis is relatively large in comparison with other epidemiological studies of these two rare diseases. The inclusion of all deaths in the United States works against various other types of selection bias, like the analysis of data from one single geographical region or from one referral center serving a more affluent or indigent patient clientele. In many instances, no industry or occupation code was available, or the occupations recorded at the time of death frequently reflected the period of last or longest employment. As some subjects change their occupation several times during lifetime, previous or other types of occupational exposure go unnoticed. An occupation can show an unduly high mortality not because of its hazardous influence but because its less demanding working conditions attract chronically ill subjects (12). Vice versa, IBD mortality may seem artificially low among occupations that attract especially healthy persons. Such potential bias could impress as protection from IBD, for instance, among manual or bluecollar workers and laborers. Similar distributions as reported here, however, were previously observed in the occupational statistics from other countries (13, 14). Because some of the previous statistics dealt with disability claims of IBD
patients who became unable to pursue their initial employment, they seemed less likely to have been influenced by an underlying selection bias in favor of sedentary or against manual occupations (6, 13). Another type of bias may be introduced by relatives who provide imprecise descriptions or choose more prestigious occupations to honor the deceased. Lastly, similar work environments are nowadays associated with many different industries and occupations. For instance, working at a computer terminal or in an air-conditioned office may characterize completely unrelated types of industry, such as health care, publishing, or energy production. Recent assimilation of various work environments to one ubiquitous form would tend to counteract the influence of occupational and industrial exposure and bias the results toward the null hypothesis. Despite such potential limitations the data show a fairly consistent pattern. Agricultural production and all farming occupations were associated with a strong protective influence against IBD. The same variation emerged from the analyses of the data broken down by industry, occupation, and disease type. Similar patterns were observed in most of the previous studies that dealt with the occupational distribution of IBD (3–5, 13–15). It is interesting to note that this epidemiological behavior known primarily from European data sets accumulated 10 to 20 yr ago pertains similarly to the present U.S. population as well. Crohn’s disease and ulcerative colitis are known to affect primarily the urban and well-educated populations of the northern hemisphere characterized by economic affluence and westernized lifestyle (16 –18). It has remained an enigma what type of protection is conferred by a rural milieu. As opposed to urban a rural environment may involve less sanitation or more exposure to zoonoses. Other investigators have speculated about the protective influences of less sanitation or early exposure to helminths that primes the immune system and mitigates subsequent inflammatory responses (19 –21). In addition to farmers, laborers, and persons employed in mining were also characterized by a low mortality from IBD. These
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patterns could reflect a generally low occurrence of IBD among the less educated, lower social classes, or it could indicate that some of the working conditions associated with manual labor exert a protective influence. In conclusion, the present study of the industrial and occupational distributions of IBD mortality reveals low rates among farmers and manual labors and relatively high rates associated with sedentary and administrative work. These data also indicate that the risks, delineated primarily in European statistics from 10 to 20 yr ago, still shape the current IBD epidemiology and that they apply similarly to U.S. and European populations. The occurrence of both Crohn’s disease and ulcerative colitis must be influenced by environmental risk factors. Such risk factors could exert a protective or aggressive influence, and the exposure to these factors is related to the type of work selected or performed.
ACKNOWLEDGMENT A. S. was supported by a grant from the Centers for Disease Control and Prevention in Atlanta, GA. Reprint requests and correspondence: Amnon Sonnenberg, M.D., M.Sc., Department of Veterans Affairs Medical Center 111F, 1501 San Pedro Drive SE, Albuquerque, NM 87108. Received June 30, 2000; accepted Oct. 6, 2000.
REFERENCES 1. Last JM (ed). A dictionary of epidemiology, 3rd ed. New York: Oxford University Press, 1983. 2. Sandler RS. Epidemiology of inflammatory bowel disease. In: Targan SR, Shanahan F, eds. Inflammatory bowel disease: From bench to bedside. Baltimore: Williams & Wilkins, 1994: 5–32. 3. Bonnevie O. A socio-economic study of patients with ulcerative colitis. Scand J Gastroent 1967;2:129 –36. 4. Rogers BHG, Clark LM, Kirshner JB. The epidemiologic and demographic characteristics of inflammatory bowel disease: An analysis of a computerized file of 1,400 patients. J Chron Dis 1971;24:743–53. 5. Keighley A, Miller DS, Hughes AO, Langman MJS. The demographic and social characteristics of patients with Crohn’s disease in the Nottingham area. Scand J Gastroent 1976;11:293– 6.
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6. Sonnenberg A. Disability from inflammatory bowel disease among employees in West Germany. Gut 1989;30:367–70. 7. U.S. Bureau of the Census. Classified index of industries and occupations. 1990 Census of Population and Housing, 1st ed. Washington: U.S. Government Printing Office, April 1992. 8. Office of Population Censuses, and Surveys. Occupational mortality. The Registrar General’s decennial supplement for Great Britain, 1979 – 80:1982– 83. Series DS no. 6. Part I (commentary). London: Her Majesty’s Stationery Office, 1986:8 –11. 9. Kahn HA, Sempos CT. Statistical methods in epidemiology. New York: Oxford University Press 1989:95–105. 10. Ekbom A, Helmick CG, Zack M, et al. Survival and causes of death in patients with inflammatory bowel disease: A population-based study. Gastroenterology 1992;103:954 – 60. 11. Carbonnel F, Macaigne G, Beaugerie L, et al. Crohn’s disease severity in familial and sporadic cases. Gut 1999;44:91–5. 12. Wyke RJ, Edwards FC, Allan RN. Employment problems and prospects for patients with inflammatory bowel disease. Gut 1988;29:1229 –35. 13. Sonnenberg A. Occupational distribution of inflammatory bowel disease among German employees. Gut 1990;31:1037– 40. 14. Bøggild H, Tu¨chsen F, Ørhede E. Occupation, employment status and chronic inflammatory bowel disease in Denmark. Int J Epidemiol 1996;25:630 –7. 15. Sonnenberg A. Occupational mortality of inflammatory bowel disease. Digestion 1990;46:10 – 8. 16. Sandler RS. Epidemiology. In: Targan SR, Shanahan F, eds. Inflammatory bowel disease: From bench to bedside. Baltimore: Williams & Wilkins 1994:5–31. 17. Calkins BM. Inflammatory bowel disease. In: Everhart JE, ed. Digestive diseases in the United States: Epidemiology and impact. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Washington, DC: US Government Printing Office, 1994; NIH publication no. 94 –1447;511–544. 18. Sonnenberg A. Inflammatory bowel disease. In: Johanson JF, ed. Digestive disease: Risk factors and prevention. Philadelphia, New York: Lippincott–Raven, 1997:67– 89. 19. Gent AE, Hellier MD, Grace RH, et al. Inflammatory bowel disease and domestic hygiene in infancy. Lancet 1994;343: 766 –7. 20. Duggan AE, Usmani I, Neal KR, et al. Appendectomy, childhood hygiene, Helicobacter pylori status, and risk of inflammatory bowel disease. A case control study. Gut 1998;43: 494 – 8. 21. Christ AD, Sonnenberg A, Wenger M, et al. Is there a relationship between helminthic infection and chronic inflammatory bowel disease? Gastroenterology 2000;118:A1337.
Vol. 96, No. 4, 2001 ISSN 0002-9270/01/$20.00 PII S0002-9270(01)02310-3
Occupational Mortality From Inflammatory Bowel Disease in the United States 1991–1996 Claudia Cucino, M.D., and Amnon Sonnenberg, M.D., M.Sc. Department of Veterans Affairs Medical Center, and The University of New Mexico, Albuquerque, New Mexico
OBJECTIVE: The occupational distribution of inflammatory bowel disease (IBD) may help to shed light on its yet unknown etiology. The U.S. vital statistics offer the opportunity to study cause of death by occupation and industry. METHODS: The numbers of deaths from Crohn’s disease and ulcerative colitis were retrieved from the computerized 1991–1996 data files of the National Center for Health Statistics. Deaths were grouped by gender, ethnicity, disease type, occupation, and industry. Mortality by occupation and industry were expressed as proportional mortality ratio (PMR), adjusted for gender and ethnicity. RESULTS: Between 1991 and 1996, 2399 subjects died from Crohn’s disease and 2419 subjects died from ulcerative colitis. Significant correlations were found between the PMR values of ulcerative colitis and Crohn’s disease regarding their distribution by occupation, r ⫽ 0.36 and p ⬍ 0.05, as well as by industry, r ⫽ 0.37, p ⬍ 0.01. IBD mortality by occupation was significantly reduced among farmers (PMR: 70, 95% confidence interval [CI]: 42–97), mining machine operators (31, 95% CI: 0 –74), and laborers (71, 95% CI: 45–98). A nonsignificant increase was found among sales persons (117, 95% CI: 95–139) and secretaries (122, 95% CI: 83–161). IBD mortality by industry was significantly reduced in agricultural production of livestock (39, 95% CI: 1–78), mining (46, 95% CI: 9 – 83), grocery stores (55, 95% CI: 17–94), and work in private households (64, 95% CI: 30 –97). A nonsignificant increase was found in food production (128, 95% CI: 74 –182), investment and insurance business (137, 95% CI: 77–198), and administration (122, 95% CI: 81–163). CONCLUSIONS: IBD mortality is low in occupations associated with manual work and farming and relatively high in sedentary occupations associated with indoor work. Crohn’s disease and ulcerative colitis show a similar distribution. (Am J Gastroenterol 2001;96:1101–1105. © 2001 by Am. Coll. of Gastroenterology)
INTRODUCTION Epidemiology deals with the distribution and variation of disease among different populations or subgroups of a single population. By comparing the patterns of disease distri-
bution with the patterns of potential health determinants, epidemiologists hope to obtain insight about risk factors and mechanisms that contribute to the occurrence of the disease (1). The occurrence of inflammatory bowel disease (IBD) has been analyzed extensively with respect to its demographical, socioeconomic, occupational, temporal, and geographical distribution, to shed light on its yet unknown etiology (2). Certain occupational groups have been previously identified as having higher risks of suffering from IBD. It has been shown that both types of IBD tend to affect the higher social classes more frequently than the lower social classes, and white collar employees are affected more frequently than blue collar employees (3– 6). The present study analyzes the occupational mortality from Crohn’s disease and ulcerative colitis in the United States during 6 consecutive yr. Data files of the National Center of Health Statistics of the United States offer a unique source to study death causes, broken down by occupation of the deceased.
MATERIALS AND METHODS The numbers of deaths from Crohn’s disease and ulcerative colitis were retrieved from the computerized 1991–1996 data files of the National Center for Health Statistics. Deaths were grouped by gender, ethnicity (whites and nonwhites), primary cause of death, occupation, and industry. Cause of death was coded according to the ninth revision of the International Classification of Diseases (ICD). The ICD code 556 represented ulcerative colitis, and the ICD code 555 (including the subcodes 5550, 5551, 5552 and 5559) represented Crohn’s disease. Industries and occupations were classified according to the index of the U.S. Bureau of the Census (7). For the purpose of the present analysis, data from the 6 consecutive yr 1991 to 1996 were pooled and analyzed together. Mortality from Crohn’s disease or ulcerative colitis per each industrial and occupational group were expressed as proportional mortality ratios (PMR) using the method of indirect standardization (8, 9). The number of deaths from all ICD codes 1–999 per individual industry (or occupation) was expressed as proportion of all deaths in all industries. These industry-specific (or occupation-specific)
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Table 1. US Mortality From Crohn’s Disease and Ulcerative Colitis, 1991–1996 Sum Mean age (SD) Men Women Whites Nonwhites
All Deaths
Crohn’s Disease
Ulcerative Colitis
13,539,945 (100%) 71.6 6,918,638 (51%) 6,621,307 (49%) 11,634,400 (86%) 1,888,510 (14%)
2,399 (100%) 66.3 (17.2) 937 (39%) 1,462 (61%) 2,212 (92%) 187 (8%)
2,419 (100%) 71.4 (17.7) 1,071 (44%) 1,348 (56%) 2,200 (91%) 219 (9%)
proportions were then multiplied by the sum of all deaths from Crohn’s disease, to obtain the expected number of deaths from Crohn’s disease in each industrial (or occupational) group. This calculation was carried out separately for each 10-yr age group of white and nonwhite men, as well as, white and nonwhite women. The sum of deaths from Crohn’s disease expected in each race- and sex-specific group represented the overall expected number of deaths (EXP) per industry (or occupation). The ratio of observed (OBS) over expected number of deaths corresponded to PMR, the value being given in percent: PMR ⫽ OBS/EXP. It indicated whether the observed mortality from ICD code 555 in a particular industry (or occupation) lay above or below the average expected value of 100%. Similar calculations were carried out for ulcerative colitis. The calculations yielded age-, race-, and sex-standardized PMR values. The SE of the PMR value was calculated as the PMR value divided by the square root of the observed deaths: SE ⫽ PMR/公OBS. The 95% confidence interval (CI) of each PMR value was then calculated as CI ⫽ PMR ⫾ 1.96 ⫻ SE. A PMR value was considered statistically significant if its 95% CI did not include unity or 100%. The industrial and occupational distributions of mortality from Crohn’s disease were compared with those of ulcerative colitis using a least-square regression analysis of the PMR values. The overall death rates from Crohn’s disease and ulcerative colitis among men were compared to those among women using the odds ratio (OR) and its 95% CI. Similarly, the odds ratio and its 95% CI were used to compare the rates among whites and nonwhites.
(95% CI: 1.76 –2.00) for Crohn’s disease and OR ⫽ 1.62 (95% CI: 1.48 –1.76) for ulcerative colitis. The initial list of industry types contained 254 separate codes. Mortality from Crohn’s disease and ulcerative colitis were distributed among 143 and 144 different industries, respectively; the frequencies varying between one and 143 deaths per industry. In 1703 cases of Crohn’s disease and 1812 cases of ulcerative colitis, the type of industry was not stated. In the subsequent analyses, related industries were lumped together to condense the original list to a smaller list of only 60 industries with larger average case numbers per industry. For instance, “National Security,” “Army,” “Air Force,” “Navy,” “Marines,” “Coast Guard,” “Armed Forces not otherwise specified,” and “National Guard” were lumped together as “Military.” Similarly, “Metal mining,” “Coal mining,” “Oil” and “gas extraction,” and “Nonmetallic mining and quarrying” were grouped together as “Mining.” The original list of occupations contained a total of 517 different codes. Mortality from Crohn’s disease and ulcerative colitis were distributed among 174 and 154 different occupations, respectively; their frequencies ranging between one and 173. In 1704 cases of Crohn’s disease and 1759 cases of ulcerative colitis, the occupation was not stated. In the majority of instances, the PMR values of Crohn’s disease and ulcerative colitis showed the same trend. The PMR values of Crohn’s disease smaller or greater than 100% were generally associated with PMR values of ulcerative colitis behaving in the same way. This pattern applied
RESULTS From 1991 to 1996 the overall number of deaths in the United States was 13.5 million. In less than 0.04% of deaths, Crohn’s disease and ulcerative colitis were listed as primary cause of death (Table 1). Mortality was of similar order of magnitude in Crohn’s disease as ulcerative colitis. Subjects dying from Crohn’s disease were on the average 5.4 yr younger than those dying from other causes (t ⫽ 15.270, df ⫽ 2,398, p ⫽ 0.000), and subjects dying from ulcerative colitis were on the average 0.2 yr younger (t ⫽ 0.585, df ⫽ 2,418, p ⫽ 0.56). Women were more frequently affected than men by both types of IBD, the odds ratio being 1.63 (95% CI: 1.54 –1.71) for Crohn’s disease and 1.31 (95% CI: 1.23–1.39) for ulcerative colitis. Both types of IBD were also more common in whites than nonwhites, OR ⫽ 1.91
Figure 1. Correlation between proportional mortality ratio (PMR) of Crohn’s disease and ulcerative colitis distributed by industry. n ⫽ 60; p ⬍ 0.01; r ⫽ 0.37.
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Figure 2. Correlation between proportional mortality ratio (PMR) of Crohn’s disease and ulcerative colitis distributed by occupation. n ⫽ 22; p ⬍ 0.05; r ⫽ 0.36.
similarly to the distributions of Crohn’s disease and ulcerative colitis by industry and occupation, a concordant behavior of both diseases being observed in 60% of industries and 73% of occupations. In Figure 1, the PMR values of Crohn’s disease by industry were plotted against those of ulcerative colitis. Each dot represents a different industry type. The two distributions of Crohn’s disease and ulcerative colitis correlated positively with each other. In Figure 2, the PMR values of Crohn’s disease by occupation were plotted against those of ulcerative colitis. Each dot represents a different occupational group. The analysis was restricted to the 22 largest occupations with 10 or more deaths each. Again, the distributions of Crohn’s disease and ulcerative colitis correlated positively with each other. Because of their similar industrial and occupational distributions, in subsequent analyses Crohn’s disease and ulcerative colitis were lumped together to further increase the number of cases available for each industrial and occupational category. Table 2 contains the industrial distribution of mortality
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from IBD. Besides all significant associations, the table lists all industries whose PMR values differed from the average value by 15% or more. Four industries were associated with statistically reduced PMR values. These included “Agricultural production,” “Mining,” “Grocery stores,” and “Private households.” None of the 60 broad industrial groups were associated with a significant elevation of the PMR above 100%. A nonsignificant increase was seen, for instance, in “Food products,” “Investment, insurance,” “Administration,” and “Military.” Table 3 contains the occupational distribution of mortality from IBD. Besides all significant associations, the table lists all occupations whose PMR values differed from the average value by 15% or more. Four occupations were associated with statistically reduced PMR values. These included: “Farmers,” “Farm workers,” “Mining machine operators,” and “Laborers.” None of the various occupational groups were associated with any significant elevation of the PMR above 100%. However, the number of deaths among “Sales persons” and “Secretaries” appeared higher than expected. In general, the occupational and industrial distribution seemed to corroborate each other, as the occupations matched similar types of industry with a similar PMR value. For instance, “Agriculture” as well as “Farmers” or “Farm workers” were all associated with a significantly reduced PMR. So were “Mining” and “Mining machine operators” or “Private households” and “Homemaker.”
DISCUSSION The vital statistics were used to analyze the industrial and occupational distributions of mortality from IBD in the United States between 1991 and 1996. The industrial and occupational distributions for Crohn’s disease and ulcerative colitis were similar. Both diseases occurred less frequently in industries or occupations associated with agriculture, mining, and work in private households. The IBD
Table 2. Distribution of Inflammatory Bowel Diseases by Industry Industry
PMR
95% Confidence Interval
Observed
Expected
Agricultural productions, crops Agricultural productions, livestock* Other agricultural services Mining* Food products Radio and TV services Stores Grocery stores* Motor vehicles stores and gas dealers Eating and drinking places Investment, insurance Private households* Administrations Military
76 39 76 46 128 142 132 55 162 74 137 64 122 136
45–106 1–78 1–150 9–83 74–182 76–208 98–166 17–94 94–230 45–104 77–198 30–97 81–163 69–203
24 4 4 6 22 18 58 8 22 25 20 14 35 16
32 10 5 13 17 13 44 14 14 34 15 22 29 12
PMR ⫽ proportional mortality ratio. * Significant at p ⬍ 0.05 level.
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Table 3. Distribution of Inflammatory Bowel Disease by Occupation Occupation Registered nurses Sales persons Secretaries Bookkeepers, accounting, and auditing clerks Cleaners and servants (private household) Cooks Janitors and cleaners Farmers (except horticultural) Farm workers* Groundskeepers and gardeners (except farm) Mining machine operators* Truck drivers Laborers* Homemakers
PMR
95% Confidence Interval
Observed
Expected
63 117 122 84 75 68 66 70 26 132 31 77 71 94
26–101 95–139 83–161 36–132 35–114 23–113 27–106 42–97 0–76 2–263 0–74 41–113 45–98 84–104
11 111 38 12 14 9 11 25 1 4 2 18 28 342
17 95 31 14 19 13 17 36 4 3 6 23 39 364
PMR ⫽ proportional mortality ratio. * Significant at p ⬍ 0.05 level.
mortality was also low among janitors, cleaners, and laborers in general. It tended to be increased in industries or occupations associated with food production, investment and insurance, administration, and work as sales persons or secretaries. In discussing the relevance of the present findings, several potential limitations of using occupational mortality data need to be considered. The data deal only with instances of Crohn’s disease and ulcerative colitis resulting in death. Because the case fatality rate of IBD is ⬍5%, the population of the present study may represent a select group of patients with a particularly severe course (10). There is no evidence, however, to suggest that severe and mild forms of IBD are characterized by a different type of epidemiology (11). Because the vital statistics capture the entire U.S. population, the number of cases included in the present analysis is relatively large in comparison with other epidemiological studies of these two rare diseases. The inclusion of all deaths in the United States works against various other types of selection bias, like the analysis of data from one single geographical region or from one referral center serving a more affluent or indigent patient clientele. In many instances, no industry or occupation code was available, or the occupations recorded at the time of death frequently reflected the period of last or longest employment. As some subjects change their occupation several times during lifetime, previous or other types of occupational exposure go unnoticed. An occupation can show an unduly high mortality not because of its hazardous influence but because its less demanding working conditions attract chronically ill subjects (12). Vice versa, IBD mortality may seem artificially low among occupations that attract especially healthy persons. Such potential bias could impress as protection from IBD, for instance, among manual or bluecollar workers and laborers. Similar distributions as reported here, however, were previously observed in the occupational statistics from other countries (13, 14). Because some of the previous statistics dealt with disability claims of IBD
patients who became unable to pursue their initial employment, they seemed less likely to have been influenced by an underlying selection bias in favor of sedentary or against manual occupations (6, 13). Another type of bias may be introduced by relatives who provide imprecise descriptions or choose more prestigious occupations to honor the deceased. Lastly, similar work environments are nowadays associated with many different industries and occupations. For instance, working at a computer terminal or in an air-conditioned office may characterize completely unrelated types of industry, such as health care, publishing, or energy production. Recent assimilation of various work environments to one ubiquitous form would tend to counteract the influence of occupational and industrial exposure and bias the results toward the null hypothesis. Despite such potential limitations the data show a fairly consistent pattern. Agricultural production and all farming occupations were associated with a strong protective influence against IBD. The same variation emerged from the analyses of the data broken down by industry, occupation, and disease type. Similar patterns were observed in most of the previous studies that dealt with the occupational distribution of IBD (3–5, 13–15). It is interesting to note that this epidemiological behavior known primarily from European data sets accumulated 10 to 20 yr ago pertains similarly to the present U.S. population as well. Crohn’s disease and ulcerative colitis are known to affect primarily the urban and well-educated populations of the northern hemisphere characterized by economic affluence and westernized lifestyle (16 –18). It has remained an enigma what type of protection is conferred by a rural milieu. As opposed to urban a rural environment may involve less sanitation or more exposure to zoonoses. Other investigators have speculated about the protective influences of less sanitation or early exposure to helminths that primes the immune system and mitigates subsequent inflammatory responses (19 –21). In addition to farmers, laborers, and persons employed in mining were also characterized by a low mortality from IBD. These
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patterns could reflect a generally low occurrence of IBD among the less educated, lower social classes, or it could indicate that some of the working conditions associated with manual labor exert a protective influence. In conclusion, the present study of the industrial and occupational distributions of IBD mortality reveals low rates among farmers and manual labors and relatively high rates associated with sedentary and administrative work. These data also indicate that the risks, delineated primarily in European statistics from 10 to 20 yr ago, still shape the current IBD epidemiology and that they apply similarly to U.S. and European populations. The occurrence of both Crohn’s disease and ulcerative colitis must be influenced by environmental risk factors. Such risk factors could exert a protective or aggressive influence, and the exposure to these factors is related to the type of work selected or performed.
ACKNOWLEDGMENT A. S. was supported by a grant from the Centers for Disease Control and Prevention in Atlanta, GA. Reprint requests and correspondence: Amnon Sonnenberg, M.D., M.Sc., Department of Veterans Affairs Medical Center 111F, 1501 San Pedro Drive SE, Albuquerque, NM 87108. Received June 30, 2000; accepted Oct. 6, 2000.
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6. Sonnenberg A. Disability from inflammatory bowel disease among employees in West Germany. Gut 1989;30:367–70. 7. U.S. Bureau of the Census. Classified index of industries and occupations. 1990 Census of Population and Housing, 1st ed. Washington: U.S. Government Printing Office, April 1992. 8. Office of Population Censuses, and Surveys. Occupational mortality. The Registrar General’s decennial supplement for Great Britain, 1979 – 80:1982– 83. Series DS no. 6. Part I (commentary). London: Her Majesty’s Stationery Office, 1986:8 –11. 9. Kahn HA, Sempos CT. Statistical methods in epidemiology. New York: Oxford University Press 1989:95–105. 10. Ekbom A, Helmick CG, Zack M, et al. Survival and causes of death in patients with inflammatory bowel disease: A population-based study. Gastroenterology 1992;103:954 – 60. 11. Carbonnel F, Macaigne G, Beaugerie L, et al. Crohn’s disease severity in familial and sporadic cases. Gut 1999;44:91–5. 12. Wyke RJ, Edwards FC, Allan RN. Employment problems and prospects for patients with inflammatory bowel disease. Gut 1988;29:1229 –35. 13. Sonnenberg A. Occupational distribution of inflammatory bowel disease among German employees. Gut 1990;31:1037– 40. 14. Bøggild H, Tu¨chsen F, Ørhede E. Occupation, employment status and chronic inflammatory bowel disease in Denmark. Int J Epidemiol 1996;25:630 –7. 15. Sonnenberg A. Occupational mortality of inflammatory bowel disease. Digestion 1990;46:10 – 8. 16. Sandler RS. Epidemiology. In: Targan SR, Shanahan F, eds. Inflammatory bowel disease: From bench to bedside. Baltimore: Williams & Wilkins 1994:5–31. 17. Calkins BM. Inflammatory bowel disease. In: Everhart JE, ed. Digestive diseases in the United States: Epidemiology and impact. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Washington, DC: US Government Printing Office, 1994; NIH publication no. 94 –1447;511–544. 18. Sonnenberg A. Inflammatory bowel disease. In: Johanson JF, ed. Digestive disease: Risk factors and prevention. Philadelphia, New York: Lippincott–Raven, 1997:67– 89. 19. Gent AE, Hellier MD, Grace RH, et al. Inflammatory bowel disease and domestic hygiene in infancy. Lancet 1994;343: 766 –7. 20. Duggan AE, Usmani I, Neal KR, et al. Appendectomy, childhood hygiene, Helicobacter pylori status, and risk of inflammatory bowel disease. A case control study. Gut 1998;43: 494 – 8. 21. Christ AD, Sonnenberg A, Wenger M, et al. Is there a relationship between helminthic infection and chronic inflammatory bowel disease? Gastroenterology 2000;118:A1337.