The role of metals in autoimmune vasculitis: epidemiological and pathogenic study.

BACKGROUND: A possible relationship between Silica (Si) exposure and antineutrophil cytoplasm antibodies (ANCA)-associated vasculitis has been reported. Furthermore, tuberculosis (TBC) has been frequently described in patients with silicosis, and TBC infection shares with ANCA-associated vasculitis the formation of granulomas. Therefore, an intriguing network including Silica, Vasculitis, TBC and ANCA might be hypothesized. The aim of this work was to further investigate these correlations using both epidemiological and pathogenic approaches. METHODS: Study I--epidemiological study. A case-control study to compare the occupational histories of 31 cases of biopsy proven vasculitis (18 pauci-immune crescentic glomerulonephritis, 9 microscopic polyangitis, 4 Wegener's granulomatosis) with those of 58 age, sex and residence-matched controls (affected by other kidney diseases), was performed. Occupational Health physicians designed an appropriate questionnaire in order to evaluate a wide spread of exposures and calculate their entity by the product of Intensity x Frequency x Duration. Study II--tuberculosis association. A case-control study to evaluate the frequency of a previous history of tuberculosis (TBC) in 45 patients with vasculitis and 45 controls were performed. Study III--ANCA positivity. A case-control study to evaluate the presence of ANCA was performed by testing blood samples of 64 people with previous professional exposure and 65 sex/age matched patients hospitalized in a General Medicine Unit. Furthermore, the same evaluation was made in a pilot study in 16 patients with ongoing or previous TBC. Study IV--experimental study. The oxygen free radicals (OFR) and IL-12 production (both involved in the pathogenesis of vasculitis) from human phagocytic cells stimulated with an amorphous (diatomaceous earth) and a crystalline (quartz) form of Si at the doses of 10 and 100 microg ml(-1) was evaluated. RESULTS: Study I--a positive history of exposure to Si resulted in significantly more present in cases (14/31 = 45%) than in controls (14/58 = 24%, P = 0.04, OR = 2.4) and no other significant exposure association was found (including asbestos, mineral oil, formaldehyde, diesel and welding fumes, grain and wood dust, leather, solvents, fungicides, bitumen, lead and paint). Study II--past TBC infection was significantly more present in patients with vasculitis (12/45 = 26%) than in controls (4/45 = 8%, P < 0.05). Study III--ANCA was present in 2/64 exposed people (vs. 0/65 controls, P = NS) and 0/16 patients with TBC. Study IV--both amorphous and crystalline Si forms represented a stimulus for OFR and IL-12 production, but quartz resulted as a greater inductor. CONCLUSIONS: We conclude that Si exposure might be a risk factor for ANCA-associated vasculitis, possibly enhancing endothelial damage by phagocyte generation of oxygen free radicals and Th1 differentiation by an excessive IL-12 phagocyte production. Frequency of TBC was significantly higher in vasculitis patients. ANCA was not frequent in the preliminary examination of people with previous professional exposure or patients with TBC, but the number of samples evaluated is too small to allow conclusions.

[Talcosis as an occupational disease. Case histories]. / La talcosi come malattia professionale. Contributo casistico.

The case are examined of 49 people (45 males, 4 females), mean age 60 exposed to the risk of talc inhalation in a talc processing and packing factory who were granted disability pensions by the Turin I.N.A.I.L. on the grounds of silicosis in 1975-86. Radiologically the cases presented small round patches in 28 subjects small irregular ones in 15 and large patches in 6. In functional terms, examination revealed ventilatory insufficiency that was primarily restrictive in 17 cases, obstructive in 11 and mixed in 21.

[Respiratory functional decline after 5 years in patients with silicosis and asbestosis]. / Declino funzionale respiratorio a 5 anni nei soggetti affetti da silicosi e asbestosi.

A retrospective study of 561 patients with silicosis and 234 with asbestosis was performed to assess whether lung function decline in five years is related to the type (restrictive or obstructive) and/or to the degree of initial damage. Based on lung function tests, three groups of patients were identified: NC with normal lung function tests, CR with restrictive impairment and CO with airway obstruction. The degree of impairment was classified as mild, moderate and severe. Patients were considered worse if five years later they presented a higher degree of impairment. The prevalence of CR was significantly higher in asbestosis, that of NC and CO in silicosis (p less than 0.01). Among subjects with normal starting lung function, 9% only developed CR or CO 5 years later. The prevalence of subjects with worsened lung function in the CR groups was significantly higher (p less than 0.001) in asbestotics (36%) than in silicotics (14%) and was closely related to starting functional impairment. In the CO group the prevalence of worsened subjects was significantly higher than in CR (p less than 0.001), similar in the two diseases and independent of starting lung impairment.

[Data on cellular subpopulations in bronchoalveolar lavage in silicosis and asbestosis patients. Case contribution]. / Dati sulle sottopopolazioni cellulari nel lavaggio broncoalveolare nei silicotici ed asbestosici. Contributo casistico.

Data on the cytology of BAL performed on 8 silicosis and 5 asbestosis patients with different degrees of radiological profusion and functional impairment are examined. The prevalently neutrophilic alveolitis reported in the literature in these forms of pneumoconiosis is confirmed, while differences were found between the percentage of lymphocyte subpopulations in the two diseases.

[Functional compromise of the small airways in subjects exposed to SiO2]. / Compromissione delle piccole vie aeree nei soggetti esposti a SiO2.

Aims of our study were: to evaluate small airway function of subjects with past or present silica dust exposure and normal spirometric values; to investigate whether small airway disease is related to radiographic signs of silicosis, to cumulative dust exposure (ES) and to cigarette smoking. Maximal expiratory flow at 50% (MEF50) and 25% (MEF25) of forced expired vital capacity were measured in 112 subjects, 69 with radiographic signs of silicosis, group I, and the remaining 43 with normal chest X-rays. Even if age and ES were significantly higher in group I, no significant difference in respiratory function tests and in prevalence of small airway disease was found between the two groups. In both groups small airway function was significantly negatively related to smoking habits, while it was independent of the other variables considered. Multiple regression analysis with MEF50 and MEF25 as dependent variables did not show any significant relationship. We conclude that small airway disease due to encroachment of bronchiolar walls by SiO2 deposition is masqued by the damage produced by cigarette smoking, even in the presence of radiographic signs of silicosis.

[Occupational asthma from the use of synthetic resins. Personal case histories and a review of the literature]. / L'asma professionale da impiego di resine sintetiche. Casistica personale e revisione della letteratura.

33 cases of occupational asthma in plastics workers encountered by Turin INAIL in 1971-85 are examined. Functional and immunological test data reveal the possibility of various asthmogenic mechanisms both immune and non-immune.

Serum angiotensin converting enzyme (ACE) in silicosis.

Circulating Angiotensin Converting Enzyme (ACE) level, chest X-rays and respiratory function tests were determined in 76 male patients with silicosis. Mean serum ACE in the patients was significantly higher than in 30 healthy controls (129.8 +/- 4 U/ml and 92.4 +/- 22.7 respectively), although individual values were in the normal range in about half of the patients. Enzyme levels were independent of silica dust exposure, X-ray changes, functional lung impairment, age, smoking habits, and presence of chronic obstructive pulmonary disease. However, patients with more severe radiological changes tended to have lower ACE values. Our data confirm that serum ACE level is frequently raised in silicosis, but does not give further information in the evaluation of the disease.