Hypersensitivity pneumonitis and metalworking fluids contaminated by mycobacteria.

Metalworking fluids (MWF) are responsible for hypersensitivity pneumonitis (HP). The aim of the present study was to identify the antigen (Ag) responsible for MWF-associated HP, and to optimise serological diagnosis by definition of a threshold allowing discrimination between HP patients and asymptomatic exposed workers. 13 patients, who were workers at a car engine manufacturing plant, were suspected of MWF-associated HP. Microbial analysis of 83 used MWFs was carried out. Sera from 13 MWF-associated HP patients, 12 asymptomatic exposed workers and 18 healthy unexposed controls were tested to determine their immunological responses to three Ags, including Mycobacterium immunogenum. M. immunogenum was identified in 40% of used fluids by culture and confirmed by DNA sequencing. The threshold for differentiating MWF-associated HP patients from asymptomatic exposed workers was five arcs of precipitation (sensitivity 77% and specificity 92%), as determined by electrosyneresis (ES). Using ELISA methods with protein extract from M. immunogenum, a threshold leading to 92% sensitivity and 100% specificity was established. The detection of specific antibodies against M. immunogenum Ag at high levels in case sera suggests that M. immunogenum-contaminated MWF is responsible for MWF-associated HP. To discriminate MWF-associated HP patients from asymptomatic exposed workers, we suggest a five-arc threshold for ES and a 1.6-AU threshold for ELISA methods.

Exposure to occupational and environmental factors in myelodysplastic syndromes. Preliminary results of a case-control study.

We performed a case-control study of occupational and environmental risk factors in myelodysplastic syndromes (MDS) diagnosed at our institution, using the method of Siemiatycki. A control for each MDS case, matched for age, sex, and residence area was chosen. The questionnaire asked demographic data, medical history, and information on life-time environmental and occupational exposures. Occupational exposures were first assessed by job titles, then by evaluating exposure to a list of 70 chemicals, and the level and duration of exposure to those chemicals (exposure index). In the first 100 cases and controls analyzed, a significantly higher incidence of smokers or ex-smokers was seen in MDS cases (odds ratio, OR = 1.83, P = 0.03). A significant excess of MDS was found in male patients with jobs (or previous jobs) generally exposing to chemical compounds, including plant and machine operators and assemblers (odds ratio, OR = 3.73, P = 0.014) whereas, on the contrary, technicians and associate professionals were more often seen in controls (OR = 0.17, P = 0.002). In males, there was also a trend for more skilled agricultural workers and coal miners in MDS cases. In females, there was a non-significant trend for more professionals in controls. After adjusting for sex, age and smoking habits, significantly more frequent exposure to stone dusts (OR = 3.06, P = 0.011), and cereal dusts (OR = 2.27, P = 0.04) was found. There was also a trend for higher incidence of exposure to exhaust gases and nitro-organic explosives. In addition, significantly higher exposure indices to petrol and diesel derivatives (P = 0.03) and to fertilizers (P = 0.003) were seen in MDS cases, as compared to controls. No significant difference in exposure to other chemicals was seen between MDS cases and controls. These preliminary results of our study, which is accruing more cases, suggest, as two previously published case-control studies of risk factors in MDS, that exposure to some chemicals may be involved in the pathogenesis of MDS.

Therapy related myelodysplastic syndrome and leukemia with no "unfavourable" cytogenetic findings have a good response to intensive chemotherapy: a report on 15 cases.

We treated 15 patients with therapy related acute nonlymphocytic leukemia (tANLL) or therapy related myelodysplastic syndrome (tMDS) who had no rearrangements of chromosomes 5 and/or 7 or complex cytogenetic rearrangements by intensive chemotherapy. The median age was 43 years. Seven patients had one of the "specific" rearrangements of de novo ANLL (inv(16), t(8;21), t(15;17)or t(9;11)). Eight patients had a normal karyotype (4 cases) or single cytogenetic rearrangements not involving chromosomes 5 and 7: trisomy 8 (2 cases), t(1,2)(1 case), 20q deletion (1 case). All 7 patients with "specific" rearrangements had tANLL at presentation, without a preceding myelodysplastic phase. Seven of the 8 patients with a normal karyotype or other single cytogenetic rearrangements presented with tMDS, and the remaining patient with tANLL. Twelve patients achieved complete remission (CR), 2 had hypoplastic death and 1 had resistant disease. Median actuarial disease free interval (DFI) was 30 months. No significant prognostic factor for achieving CR was found. Significantly longer DFI was found in patients with "specific" chromosome rearrangements, compared to other karyotypes, and in patients who presented with tANLL, compared to those who presented with tMDS. Those 2 prognostic factors strongly correlated. In contrast to tANLL and tMDS with rearrangements of chromosomes 5 and/or 7 or complex karyotypes, patients with tANLL or tMDS who had other abnormal cytogenetic findings seem to achieved a high CR rate with intensive chemotherapy. tANLL with "specific" rearrangements achieved prolonged CR in many cases, whereas tMDS with other abnormal karyotypes generally had short CR, like their de novo counterparts.