Occupational and environmental risk factors of the myelodysplastic syndromes in the North of France

Aetiological factors of the myelodysplastic syndromes (MDS) are largely unknown, with the exception of alkylating agents, ionizing radiation and benzene. Some other risk factors have been suggested by the few epidemiological studies reported (solvents, ammonia, exhaust gases, metals, pesticides, alcohol). We performed a case-control study to assess the relationship between occupational or environmental factors and MDS. Two hundred and four patients with newly diagnosed MDS, and 204 sex- and age-matched controls were included. Medical history, demographic data, lifetime exposure and hobbies were obtained. Qualitative and quantitative exposure to chemical and physical hazards were evaluated with the patients and reviewed by a group of experts in occupational exposure. The median age was 70 years and 62% of the patients were men. In univariate analyses, we found relationships between MDS and smoking habits, gardening, occupations such as health professionals, technical and sale representatives, machine operators, agricultural workers, textile workers, qualitative occupational exposures (exposed/non-exposed) to oil, solvents, ammonia, pesticides, fertilizers, cereal dusts, contact with poultry or livestock and infective risk, and lifetime cumulative exposure to solvents, oil, textile dust and infective risk. The main risk factors of MDS determined by multivariate analyses (conditional logistic regression) were, being an agricultural worker [odds ratio (OR) = 3.66; 95% confidence interval (CI) 1.9-7.0], textile operator (OR = 3.66; 95% CI 1.9-7.9), health professional (OR = 10.0; 95% CI 2.1-48.7), commercial and technical sale representative (OR = 4.45; 95% CI 1.4-14.6), machine operator (OR = 2.69; 95% CI 1.2-6.0), living next to an industrial plant (OR = 2.45; 95% CI 1.5-4.1), smoking (OR = 1.74; 95% CI 1.1-2.7) and lifetime cumulative exposure to oil (OR = 1.1; 95% CI 1.0-1.2). Further studies should be performed to assess specific exposures more precisely and it would be of interest to develop a map of haematological malignancies according to industrial background.     

Occupational risk factors for the development of systemic lupus erythematosus

OBJECTIVE: There have been few studies of occupational exposures and systemic lupus erythematosus (SLE). We examined the association between the risk of SLE and occupational exposures (mercury, solvents, and pesticides), specific jobs (ever worked in teaching, healthcare, and cosmetology), and working night or rotating shifts. METHODS: Patients with recently diagnosed SLE (n = 265) were recruited through 4 university based and 30 community based rheumatology practices in North Carolina and South Carolina, USA. Controls (n = 355) were identified through driver's license records and were frequency matched to patients by age, sex, and state. Data collection included an in-person interview with detailed farming and work histories. RESULTS: Associations were seen with self-reported occupational exposure to mercury (OR 3.6, 95% CI 1.3, 10.0), mixing pesticides for agricultural work (OR 7.4, 95% CI 1.4, 40.0), and among dental workers (OR 7.1, 95% CI 2.2, 23.4). Although these associations were fairly strong and statistically significant, the prevalence of these exposures was very low and thus these estimates are based on a small number of exposed cases and controls. Weaker associations were seen between SLE and shift work (OR 1.6, 95% CI 0.99, 2.7) and among healthcare workers with patient contact (OR 1.7, 95% CI 0.99, 2.9). There was no association of SLE with use of solvents or among teachers or cosmetologists. CONCLUSION: This study reveals the potential contribution of occupational exposures to the development of SLE, and highlights some exposures and experiences that should be examined in other studies using more extensive exposure assessment techniques and in experimental studies of autoimmunity.     

The risk of asthma in relation to occupational exposures: a case-control study from a Swedish city.

The purpose of this study was to estimate the risk of adult asthma in relation to certain occupational exposures. The study was designed as a case-control study in G?teborg, including 321 subjects with asthma, born between 1926 and 1970. Controls (n=1,459) were randomly selected from the same area from registers of the 1986 population. Questionnaire information was collected in 1996, and included occupational exposures and smoking habits. Odds ratios were calculated for exposure before asthma onset, stratified by sex and age-class. The highest risks for asthma were associated with exposure to grain dust (odds ratio (OR) 4.2, 95% confidence interval (CI) 1.6-10.7) and flour dust (OR 2.8, 95% CI 1.1-7.2). Among males, significantly increased risks were observed after exposure to flour dust, welding fumes, man-made mineral fibres, and solvents. Among females, increased risks for asthma were associated with exposures to paper dust and textile dust. In logistic regression models controlling for age, smoking, sex and interacting exposures, increased risks were seen for welding fumes (OR 2.0, 95% CI 15-3.4), man-made mineral fibres (OR 2.6, 95% CI 1.4-7.3) and solvents (OR 2.2, 95% CI 1.2-3.2). The fraction of asthma attributed to occupational exposures after adjusting for sex, smoking and age was 11% (95% CI 7-14%). In conclusion, exposure to welding fumes, man-made mineral fibres, solvents and textile dust is associated with increased risk for asthma.     

Hairy cell leukaemia, occupation, and smoking

Summary The roles of farm practices, occupational exposures to organic solvents, and ionizing radiation in the risk of hairy cell leukaemia (HCL) were examined in a French hospital-based multicentre case-control study including 291 cases (229 men and 62 women) and 541 controls (425 men and 116 women). No positive association was observed with occupations involving exposure to organic solvents or with self-declared exposures to solvents, but a significant association with self-reported exposure to petrol or diesel was found for men (OR =1–5 CI95% [1–0–2–1]). No association with ionizing radiation was detected. Agriculture employment gave an odds ratio of 1–7 (CI95% [11–2–4]) for men and 2–7 (CI95% [1–1–6–7]) for women. Among men, the association seems to affect farmers rather than agricultural workers. Self-declared exposure to pesticides or bovine cattle breeding was related to HCL risk in both genders. Finally, a significant negative association with smoking was observed in men, with an inverse exposure-risk relationship odds ratios of 0–6, 0–5 and 0–2, respectively, for cumulative consumptions of <10, 10–23 and 24 pack-years), contrasting with an odds ratios clearly <1 in women.     

Case-control study of risk factors of myelodysplastic syndromes according to World Health Organization classification in a Chinese population

Risk factors of mydelodysplastic syndromes (MDS) remain largely unknown. We conducted a hospital-based case-control study consisting of 403 newly diagnosed MDS patients according to World Health Organization classification and 806 individually gender and age-matched patient controls from 27 major hospitals in Shanghai, China, to examine relation of lifestyle, environmental, and occupational factors to risk of MDS. The study showed that all MDS (all subtypes combined) risk factors included anti tuberculosis drugs [odds ratio (OR)(adj) = 3.15; 95% confidence interval (CI) = 1.22-8.12] as an independent risk factor, benzene (OR(adj) = 3.73; 95% CI = 1.32-10.51), hair dye use (OR = 1.46; 95% CI = 1.03-2.07), new building and renovations (OR = 1.69; 95% CI = 1.11-2.00), pesticides (OR = 2.16; 95% CI = 1.22-3.82), and herbicides (OR = 5.33; 95% CI = 1.41-20.10) as relative risk factors. Risk factors of MDS subtype refractory cytopenia with multiple dysplasia (RCMD) were benzene (OR(adj) = 5.99; 95% CI = 1.19-30.16) and gasoline (OR(adj) = 11.44; 95% CI = 1.31-100.03) as independent risk factors, and traditional Chinese medicines (OR = 2.17; 95% CI = 1.15-4.07), pesticides (OR = 2.92; 95% CI = 1.37-6.25), and herbicides (OR = 12.00; 95% CI = 1.44-99.67) as relative risk factors. Smoking tobacco was significantly associated with refractory anemia with excess of blasts (RAEB) (OR(adj) = 2.43; 95% CI = 1.02-5.77). Education is shown as an independent protective factor against all MDS (OR(adj) = 0.90; 95% CI = 0.83-0.99) and RCMD (OR(adj) = 0.89; 95% CI = 0.79-0.99). These findings suggest that multiple modifiable behavioral, environmental, and occupational factors play a role in MDS etiology, and various MDS subtypes may have different susceptibility.     

Childhood agricultural and adult occupational exposures to organic dusts in a population-based case-control study of systemic lupus erythematosus

Organic dust exposure can influence the development and symptoms of immune-related diseases such as atopy and asthma, but has rarely been examined in relation to systemic autoimmunity. The present analyses explore the association of lifetime farm and occupational organic dust exposures with systemic lupus erythematosus (SLE) in recently diagnosed patients (n = 265) compared with controls (n = 355) frequency matched by age, sex and state. Questionnaire data included childhood farm residence, childhood and adult experience with specific crops, and adult work in textiles, hog or poultry processing and paper or furniture manufacture. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression models including age, sex, state, race, education and silica exposure. Overall childhood or adult farm contact and childhood farm residence were not associated with SLE. Farm contact with livestock was inversely associated with SLE (OR = 0.55, 95% CI 0.35, 0.88). This effect was most pronounced among those with childhood farm residence and both childhood and adult livestock exposure (OR = 0.19; 95% CI 0.06, 0.63), but was difficult to separate from adult exposure to grains or corn. Other adult occupational exposures were not associated with SLE risk overall, regardless of childhood farm residence or livestock exposure, although an inverse association was seen among non-smokers (OR = 0.59; 95% CI 0.33, 1.1), particularly for textile work (OR = 0.34; 95% CI 0.19, 0.64). These exploratory findings support the development of studies to specifically investigate the effects of organic dust exposure on SLE risk, with particular attention to exposure assessment and characterization of demographics, smoking and other occupational exposures.     

Occupational silica and solvent exposures and risk of systemic lupus erythematosus in urban women

OBJECTIVE: To assess the risk of systemic lupus erythematosus (SLE) associated with occupational exposure to silica dust and organic solvents in an urban population. METHODS: Women with SLE were identified through both community screening and hospital databases in 4 predominantly African American neighborhoods in Boston. Female control patients were volunteers from the same communities and were screened for the absence of connective tissue disease. Demographic factors, smoking history, and a detailed occupational history, including exposures to specific chemicals, were obtained by in-person interviews. The exposure assessment was based on independent evaluation of the occupational history by 2 reviewers who were blinded to each subject's disease status. The risks associated with exposure to silica and solvents were analyzed using multivariate conditional logistic regression models, adjusted for potential confounders. RESULTS: Ninety-five patients and 191 age- and race-matched controls were included in this analysis. Exposure to silica for longer than 1 year was associated with SLE (odds ratio [OR] 4.3, 95% confidence interval [95% CI] 1.7-11.2). An exposure-response effect was seen for longer duration of exposures to silica (P for trend = 0.01). The association between occupational exposure to organic solvents and SLE was not statistically significant (OR 1.04, 95% CI 0.34-3.2). CONCLUSION: Silica exposure from a variety of industrial occupations in urban areas is associated with an increased risk of SLE. A longer duration of exposure to silica dust is associated with greater risks. This study provides further impetus for additional research into the influence of modifiable exposures on the pathogenesis of SLE.     

Systemic autoimmune disease mortality and occupational exposures

OBJECTIVE: To generate hypotheses regarding occupational exposures that may cause systemic autoimmune diseases. METHODS: Based on examination of US death certificates, we identified deaths in 26 states for which a cause was listed as rheumatoid arthritis (RA) (n = 36,178), systemic lupus erythematosus (SLE) (n = 7,241), systemic sclerosis (n = 5,642), or other systemic autoimmune disease (n = 4,270). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to estimate associations between occupation and death from any systemic autoimmune disease, and from RA, SLE, and systemic sclerosis, specifically. Additionally, we estimated risks associated with occupational exposures, which were assigned using job-exposure matrices. RESULTS: A broad array of occupations was associated with death from systemic autoimmune diseases, including several of a priori interest. Farming occupation was associated with death from any systemic autoimmune disease (OR 1.3 [95% CI 1.2-1.4]), and increased risk was also seen with occupational exposure to animals and pesticides. Several industrial occupations were associated with death from any systemic autoimmune disease, including mining machine operators (OR 1.3 [95% CI 1.1-1.5]), miscellaneous textile machine operators (OR 1.2 [95% CI 1.0-1.4]), and hand painting, coating, and decorating occupations (OR 1.8 [95% CI 1.0-2.9]). These occupations were also significantly associated with death from the specific autoimmune diseases examined. Certain occupations entailing exposure to the public, such as teachers, were associated with systemic autoimmune disease-related death, whereas others, such as waiters and waitresses, were not. CONCLUSION: Our results suggest that death from systemic autoimmune diseases may be associated with occupational exposures encountered in farming and industry. The hypotheses generated in this study provide leads for future research on determinants of these diseases.     

Occupational risk factors and asthma among health care professionals

RATIONALE: Recent U.S. data suggest an increased risk of work-related asthma among health care workers, yet only a few specific determinants have been elucidated. OBJECTIVES: To evaluate associations of asthma prevalence with occupational exposures in a cross-sectional survey of health care professionals. METHODS: A detailed questionnaire was mailed to a random sample (n=5,600) of all Texas physicians, nurses, respiratory therapists, and occupational therapists with active licenses in 2003. Information on asthma symptoms and nonoccupational asthma risk factors obtained from the questionnaire was linked to occupational exposures derived through an industry-specific job-exposure matrix. MEASUREMENTS: There were two a priori defined outcomes: (1) physician-diagnosed asthma with onset after entry into health care ("reported asthma") and (2) "bronchial hyperresponsiveness-related symptoms," defined through an 8-item symptom-based predictor. MAIN RESULTS: Overall response rate was 66%. The final study population consisted of 862 physicians, 941 nurses, 968 occupational therapists, and 879 respiratory therapists (n=3,650). Reported asthma was associated with medical instrument cleaning (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.34-3.67), general cleaning (OR, 2.02; 95% CI, 1.20-3.40), use of powdered latex gloves between 1992 and 2000 (OR, 2.17; 95% CI, 1.27-3.73), and administration of aerosolized medications (OR, 1.72; 95% CI, 1.05-2.83). The risk associated with latex glove use was not apparent after 2000. Bronchial hyperresponsiveness-related symptoms were associated with general cleaning (OR, 1.63; 95% CI, 1.21-2.19), aerosolized medication administration (OR, 1.40; 95% CI, 1.06-1.84), use of adhesives on patients (OR, 1.65; 95% CI, 1.22-2.24), and exposure to a chemical spill (OR, 2.02; 95% CI, 1.28-3.21). CONCLUSIONS: The contribution of occupational exposures to asthma in health care professionals is not trivial, meriting both implementation of appropriate controls and further study.     

Occupational risk factors for sarcoidosis in African-American siblings

OBJECTIVES: To determine whether certain occupations and occupationally related exposures were associated with a history of sarcoidosis in African-American siblings. METHODS: We collected occupational data from 921 African Americans in 273 sibships that had been identified through a sarcoidosis case. Among the 648 siblings of sarcoidosis index cases enrolled, 30 (4.6%) also had a history of sarcoidosis. A detailed job history was obtained for any job held for > or = 6 months throughout the subject's life. RESULTS: Having a usual occupation in education (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.07 to 4.44), in metal machining (OR, 7.47; 95% CI, 1.19 to 47.06), and ever working in metalworking, not elsewhere classified (OR, 2.05; 95% CI, 1.14 to 3.70) were associated with increased sarcoidosis risk. Occupations ever held in the transportation services industry (OR, 12.71; 95% CI, 1.32 to 122.56) and usual occupations in the retail trade industry (OR, 0.49; 95% CI, 0.27 to 0.88) also were associated with sarcoidosis risk. Specific occupational exposures that were associated with sarcoidosis included titanium (OR, 3.15; 95% CI, 1.02 to 9.68) and vegetable dust (OR, 1.82; 95% CI, 1.01 to 3.27), and indoor exposure to high humidity (OR, 1.51; 95% CI, 1.13 to 2.02), water damage (OR, 1.50; 95% CI, 1.11 to 2.03), or musty odors (OR, 1.78; 95% CI, 1.32 to 2.40) for > 1 year. CONCLUSION: Individuals who work in occupations with potential metal exposures or in workplaces with high humidity may be at an increased risk for sarcoidosis, but the complexity of occupationally related exposures makes it difficult to identify specific agents by using job titles as a surrogate for exposure. A more detailed exposure assessment of such jobs, along with the incorporation of genetic risk factors, should help to uncover the complex etiology of sarcoidosis.     

Occupational transmission of hepatitis C in healthcare workers and factors associated with seroconversion: UK surveillance data

The study aims were to describe a case series of occupationally acquired hepatitis C (HCV) infections in UK healthcare workers and examine factors associated with transmission using exposure data reported to the Health Protection Agency between July 1997 and December 2007. Fifteen reported cases of documented HCV seroconversion occurred after percutaneous exposure, the majority from hollow-bore needles used in the source patient's vein or artery and contaminated with blood or blood-stained fluid. The seroconversion rate was 2.2% (14/626). In multivariable analysis of healthcare workers with percutaneous exposure to blood or blood-stained fluid, we demonstrate that blood sampling procedures (odds ratio [OR], 5.75; 95% CI, 1.33-24.91; P = 0.01) and depth of injury (OR for deep vs superficial injury, 21.99; 95% CI, 2.02-239.61; P = 0.02) are independently associated with a greater risk of HCV seroconversion. This is the first UK study of occupationally acquired HCV in healthcare workers. It has reinforced our knowledge of risk factors for HCV transmission. Most of these exposures and transmissions were preventable. Healthcare employers should provide regular education on the risks of occupational exposure and prevention through standard infection control procedures. They should ensure the availability of effective prevention measures and facilitate prompt reporting and adequate follow-up of exposures.     

Occupational exposure to solvents and gender-related risk of systemic sclerosis: a metaanalysis of case-control studies

OBJECTIVE: In 2001 a metaanalysis reported an excess risk of systemic sclerosis (SSc) related to solvents exposure. The magnitude of risk varied among studies and sources of heterogeneity have not been investigated due to a lack of statistical power. We conducted a new metaanalysis to identify features associated with the magnitude of SSc risk in patients exposed to solvents. METHODS: We searched 4 databases (Medline, Pascal, Pascal Biomed, Francis). Inclusion criteria were: case-control study, occupational exposure to solvents (OES) assessed by questionnaire and summarized to "any solvent" or "any organic solvent," SSc defined by the American College of Rheumatology or the consultant's criteria. The quality of studies within this metaanalysis was scored according to the Newcastle-Ottawa scale. Odds ratios (OR) were adjusted for the "publication bias" and validated by a sensitivity analysis. Subgroup analyses investigated the effect of gender, quality of studies, and the type of controls. RESULTS: Among 11 studies (1291 patients and 3435 controls), 9 involved a majority of women (76.2 to 100%), while 2 involved men only. The risk of SSc associated with OES was variable among studies (p for heterogeneity = 0.01) and overrepresentation of higher OR values in smaller studies (p = 0.003) suggested "publication bias." SSc was associated with OES (OR 2.4; 95% CI 1.7-3.4; p < 0.0001), including after adjusting for bias (OR 1.8; 95% CI 1.2-2.5; p = 0.002). The relative risk was higher (p = 0.03) in men (OR 3.0; 95% CI 1.9-4.6; p < 0.0001) than in women (OR 1.8; 95% CI 1.5-2.1; p < 0.0001). CONCLUSION: Whereas SSc affects women predominantly, among subjects with occupational exposure to solvents, men are at higher risk than women for the disease.     

Risk factors and cumulative incidence of anaemia among HIV-infected injection drug users

Risk factors for anaemia and cumulative incidence of anaemia were examined in a longitudinal cohort study of 622 injection drug users (IDUs) (8885 visits) in Baltimore, Maryland, from 1988 to 2000. At enrollment, 19.6% subjects were anaemic (16.1% of men and 30.5% of women, P<0.0001) and 8.4% had microcytic anaemia (6.7% of men and 14.0% of women, P=0.006). Cumulative incidence of anaemia was 82.2% (87.9% of men and 100% of women, P<0.0001) during a median of 7.5 years follow-up. Factors associated with anaemia included age (per 5 year increase, odds ratio (OR)=1.22; 95% confidence interval (CI): 1.10, 1.36), female gender (OR=1.62; 95% CI: 1.16, 2.27), CD4+ lymphocyte count <200 cells/microl (OR 1.85; 95% CI: 1.52, 2.24), weight loss (OR 1.55; 95% CI: 1.26, 1.91), oral thrush (OR 1.53; 95% CI: 1.21, 1.94), Mycobacterium avium complex infection (OR 1.30; 95% CI: 1.04, 1.64), and zidovudine use (OR 1.24; 95% CI: 1.04, 1.48). Higher body mass index (OR 0.92; 95% CI: 0.88, 0.95) and marijuana use (OR 0.75; 95% CI: 0.61, 0.92) were associated with a lower risk of anaemia. The cumulative incidence of anaemia is high among IDUs, and women are at highest risk of anaemia.     

Familial pulmonary fibrosis is the strongest risk factor for idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a lethal lung disorder of unknown etiology. The disease is likely the result of complex interactions between genetic and environmental factors. Evidence suggests that certain environmental factors, such as cigarette smoking and metal dust exposures, or comorbidities like gastroesophageal reflux, and type 2 diabetes mellitus (DM2) may increase risk to develop IPF. Substantial uncertainty remains, however, regarding these and other putative risk factors for IPF. In this study we performed a case-control analysis including 100 patients with IPF and 263 controls matched for age sex and place of residence. We used a structured questionnaire to identify potential risk factors for IPF, including environmental and occupational exposures as well as the relevance of family history of pulmonary fibrosis. The multivariate analysis revealed that family history of pulmonary fibrosis [OR = 6.1, CI95% 2.3-15.9; p < 0.0001] was strongly associated with increased risk of IPF. Actually, 20% of the cases reported a parent or sibling with pulmonary fibrosis. Gastroesophageal reflux [OR = 2.9, CI: 1.3-6.6; p = 0.007], former cigarette smoking [OR = 2.5, CI: 1.4-4.6, p = 0.003], and past or current occupational exposure to dusts, smokes, gases or chemicals [OR = 2.8, CI: 1.5-5.5; p = 0.002] were also associated with the disease. Despite being a significant risk factor on univariate analysis DM2 was not significant in multivariate analysis. These findings indicate that family history of pulmonary fibrosis is a strong risk factor for IPF. Also, we confirmed that occupational exposures, gastroesophageal reflux and former smoking increase the risk for this disease.     

A case control etiologic study of sarcoidosis: environmental and occupational risk factors

Past research suggests that environmental factors may be associated with sarcoidosis risk. We conducted a case control study to test a priori hypotheses that environmental and occupational exposures are associated with sarcoidosis. Ten centers recruited 706 newly diagnosed patients with sarcoidosis and an equal number of age-, race-, and sex-matched control subjects. Interviewers administered questionnaires containing questions regarding occupational and nonoccupational exposures that we assessed in univariable and multivariable analyses. We observed positive associations between sarcoidosis and specific occupations (e.g., agricultural employment, odds ratio [OR] 1.46, confidence interval [CI] 1.13-1.89), exposures (e.g., insecticides at work, OR 1.52, CI 1.14-2.04, and work environments with mold/mildew exposures [environments with possible exposures to microbial bioaerosols], OR 1.61, CI 1.13-2.31). A history of ever smoking cigarettes was less frequent among cases than control subjects (OR 0.62, CI 0.50-0.77). In multivariable modeling, we observed elevated ORs for work in areas with musty odors (OR 1.62, CI 1.24-2.11) and with occupational exposure to insecticides (OR 1.61, CI 1.13-2.28), and a decreased OR related to ever smoking cigarettes (OR 0.65, CI 0.51-0.82). The study did not identify a single, predominant cause of sarcoidosis. We identified several exposures associated with sarcoidosis risk, including insecticides, agricultural employment, and microbial bioaerosols.     

Risk factors for anaemia in human immunodeficiency virus/hepatitis C virus-coinfected patients treated with interferon plus ribavirin

The most frequent and the most troublesome adverse effect of interferon plus ribavirin-based therapy is anaemia. The aim of this analysis was to determine the incidence and risk factors of anaemia (Hb < 10 g/dL) in human immunodeficiency virus/hepatitis C virus (HCV)-coinfected patients receiving anti-HCV therapy. We reviewed all cases of anaemia occurring among 416 patients participating in a randomized, controlled 48-week trial comparing peginterferon (peg-IFN) alpha 2b plus ribavirin with interferon alpha-2b plus ribavirin. Univariate and multivariate analyses were used to identify links with antiretroviral treatments, HCV therapy and clinical and laboratory findings. Sixty-one (15.9%) of the 383 patients who received at least one dose of anti-HCV treatment developed anaemia. In multivariate analysis the risk of anaemia was significantly associated with zidovudine (OR, 3.27 95% CI, 1.64-6.54, P = 0.0008) and peg-IFN (OR, 2.35; 95% CI, 1.16-4.57, P = 0.0179). The risk of anaemia was lower in patients with higher baseline haemoglobin levels (OR, 0.35 95% CI, 0.26-0.49, P < 0.0001) and in patients receiving protease inhibitor-based antiretroviral therapy (OR, 0.51 95% CI, 0.30-0.86, P = 0.0114). Zidovudine discontinuation could help to avoid anaemia associated with anti-HCV therapy.     

Glutathione S-transferase M null homozygosity and risk of systemic lupus erythematosus associated with sun exposure: a possible gene-environment interaction for autoimmunity

OBJECTIVE: Multiple genetic factors modulate predisposition to systemic lupus erythematosus (SLE). The glutathione S-transferase (GST) genes GSTM1, GSTT1, and GSTP1 catalyze metabolic pathways for the excretion of reactive oxygen species that may be generated by cellular oxidative stress induced by ultraviolet radiation in sunlight. We hypothesized that risk of SLE associated with occupational sun exposure is modulated by GSTM1, GSTT1, and GSTP1 genotypes. METHODS: DNA samples and occupational history were collected from 243 cases and 298 controls in the Carolina Lupus Study, a population based case-control study of patients with recently diagnosed SLE. RESULTS: There was no independent association between SLE and presence of the homozygous null GSTM1 or GSTT1 genotype, the homozygous Val/Val or heterozygous Val/Ile GSTP1 genotype, or occupational sunlight exposure. The prevalence of Ro autoantibodies was significantly increased among Caucasians with the GSTM1 null genotype (OR 2.6, 95% CI 1.0, 6.8), but was somewhat weaker among African-Americans (OR 1.5, 95% CI 0.7, 3.5). In the combined analysis of occupational sunlight exposure and GSTM1 genotype, the effect of sun exposure among Caucasians varied depending on GSTM1 genotype. There was a 3-fold increased risk (OR 3.1, 95% CI 0.9, 10.8) of SLE associated with 24 or more months' occupational sun exposure among Caucasians with the GSTM1 null genotype, but sun exposure was not associated with risk among GSTM1 positive Caucasians (OR 0.6, 95% CI 0.3, 1.5). The interaction was statistically significant (p = 0.028). CONCLUSION: Our results suggest that GSTM1 homozygous null genotype may modify the effect of occupational sun exposure on the risk of SLE in caucasians.     

Maternal and paternal environmental risk factors, metabolizing GSTM1 and GSTT1 polymorphisms, and congenital heart disease

Congenital heart defects (CHDs) are the most prevalent of all birth malformations arising from the complex interplay of environmental exposures and genes. Modifiable environmental risk factors are still largely unknown, especially for paternal exposure. The aim of the present study was to examine the association between the environmental exposures of both parents and CHD risk and to explore the modification effect of metabolizing gene polymorphisms in children who lack the genetic capacity to produce the glutathione S-transferase (GST) GSTM1 and GSTT1 enzymes. A total of 330 parents of a child with CHD and 330 parents of a child without any congenital malformations were compared in terms of lifestyle habits and toxicant exposure. GST gene polymorphisms were investigated in 180 patients with CHD (104 males, age 4.9 ± 5.8 years). Paternal smoking (≥15 cigarettes/day) was significantly associated with CHD risk (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.3 to 3.5, p = 0.002). Both maternal (OR 2.6, 95% CI 1.6 to 4.2, p <0.0001) and paternal (OR 2.5, 95% CI 1.6 to 3.8, p <0.0001) occupational/environmental exposures increased the risk of CHD. Also, a significant additive risk (OR 4.5, 95% CI 2.5 to 8.3, p <0.0001) was found when both parents were exposed to toxicants. Both maternal (OR 3.6, 95% CI 1.1 to 11.2, p = 0.03) and paternal (OR 3.3, 95% CI 1.0 to 10.8, p = 0.03) exposure to toxicants increased the CHD risk in children who carried the combined null GST genotypes. The effect for the combined null GST genotypes was also stronger (OR 6.5, 95% CI 1.5 to 28.0) when both parents were exposed. In conclusion, paternal smoking and exposure to toxicants for both parents affect the risk of children with CHD. Polymorphisms in GST genes can modify a person's risk of toxicant exposure-induced disease.     

Asthma severity and exposure to occupational asthmogens

RATIONALE: Severe asthma is a public health problem with limited information regarding preventable causes. Although occupational exposures have been implicated as important risk factors for asthma and asthma exacerbations, associations between occupational exposures and asthma severity have not been reported. OBJECTIVE: To examine associations between occupational exposures and asthma severity. METHODS: The Epidemiological Study on the Genetics and Environment of Asthma combines a case-control study with a family study of relatives of patients with asthma. Adult patients (n = 148) were recruited in chest clinics and control subjects without asthma (n = 228) were population-based. Occupational exposures to nonasthmogenic irritants and asthmogens (classified as "any asthmogen" including three broad groups: high-molecular-weight agents, low-molecular-weight agents, and mixed environments) were assessed by an asthma-specific job exposure matrix. Asthma severity was defined from an 8-grade clinical score (frequency of attacks, persistent symptoms, and hospitalization). Patients with severe (score >or= 2) and mild asthma were compared with control subjects using nominal logistic regression. MAIN RESULTS: Significant associations were observed between severe adult-onset asthma and exposure to any occupational asthmogen (odds ratio [OR], 4.0; 95% confidence interval [CI], 2.0-8.1), high-molecular-weight agents (OR, 3.7; CI, 1.3-11.1), low-molecular-weight agents (OR, 4.4; CI, 1.9-10.1), including industrial cleaning agents (OR, 7.2; CI, 1.3-39.9), and mixed environments (OR, 7.5; CI, 2.4-23.5). No significant associations were found between nonasthmogenic irritants and asthma severity, nor between asthmogens and childhood-onset asthma or mild adult-onset asthma. CONCLUSIONS: Our results suggested a strong deleterious role of occupational asthmogens in severe asthma. Clinicians should consider occupational exposures in patients with moderate to severe asthma.     

Incidence and risk factors of aplastic anemia in Latin American countries: the LATIN case-control study

Background

Associations between aplastic anemia and numerous drugs, pesticides and chemicals have been reported. However, at least 50% of the etiology of aplastic anemia remains unexplained.

Design and Methods

This was a case-control, multicenter, multinational study, designed to identify risk factors for agranulocytosis and aplastic anemia. The cases were patients with diagnosis of aplastic anemia confirmed through biopsy or bone marrow aspiration, selected through an active search of clinical laboratories, hematology clinics and medical records. The controls did not have either aplastic anemia or chronic diseases. A total of 224 patients with aplastic anemia were included in the study, each case was paired with four controls, according to sex, age group, and hospital where the case was first seen. Information was collected on demographic data, medical history, laboratory tests, medications, and other potential risk factors prior to diagnosis.

Results

The incidence of aplastic anemia was 1.6 cases per million per year. Higher rates of benzene exposure (≥30 exposures per year) were associated with a greater risk of aplastic anemia (odds ratio, OR: 4.2; 95% confidence interval, CI: 1.82–9.82). Individuals exposed to chloramphenicol in the previous year had an adjusted OR for aplastic anemia of 8.7 (CI: 0.87–87.93) and those exposed to azithromycin had an adjusted OR of 11.02 (CI 1.14–108.02).

Conclusions

The incidence of aplastic anemia in Latin America countries is low. Although the research study centers had a high coverage of health services, the underreporting of cases of aplastic anemia in selected regions can be discussed. Frequent exposure to benzene-based products increases the risk for aplastic anemia. Few associations with specific drugs were found, and it is likely that some of these were due to chance alone.