Janet M. Hughes

Provocation-challenge studies in shrimp-sensitive individuals☆

Thirty individuals with history of immediate, objective, adverse reactions after shrimp ingestion underwent double-blind, placebo-controlled shrimp-food challenges. All individuals who did not exhibit a positive response (reproduction of objective symptoms) were administered an open challenge of 16 whole cooked shrimp. Positive challenge responses occurred in 9/30 subjects (30%); six of these subjects experienced a positive response during the double-blind phase. Of the 21 remaining subjects, 12 experienced generalized pruritus as their only symptom, whereas nine subjects had completely negative challenge responses. All placebo challenges were negative. Although a positive skin test was strongly associated with challenge symptoms (p less than 0.001), the shrimp prick skin test titration end points were not different among the challenge groups. The serum shrimp RAST percent was significantly higher in the positive challenge group (p less than 0.02). Mean levels of shrimp-specific serum IgG, IgA, and IgM levels were not different among the challenge groups. Although no single immunologic variable could be consistently used to identify subjects more likely to exhibit a positive challenge response, the composite of a positive shrimp prick skin test and elevated serum shrimp-specific IgE (RAST percent label bound greater than 11%) demonstrated a correct predictive value of 87% in this group of shrimp-sensitive subjects.

Crystalline silica exposure, radiological silicosis, and lung cancer mortality in diatomaceous earth industry workers

BACKGROUND The role of silicosis as either a necessary or incidental condition in silica associated lung cancer remains unresolved. To address this issue a cohort analysis of dose-response relations for crystalline silica and lung cancer mortality was conducted among diatomaceous earth workers classified according to the presence or absence of radiological silicosis. METHODS Radiological silicosis was determined by median 1980 International Labour Organisation system readings of a panel of three “B” readers for 1809 of 2342 white male workers in a diatomaceous earth facility in California. Standardised mortality ratios (SMR) for lung cancer, based on United States rates for 1942–94, were calculated separately for workers with and without radiological silicosis according to cumulative exposures to respirable crystalline silica (milligrams per cubic meter × years; mg/m3-years) lagged 15 years. RESULTS Eighty one cases of silicosis were identified, including 77 with small opacities of ⩾1/0 and four with large opacities. A slightly larger excess of lung cancer was found among the subjects with silicosis (SMR 1.57, 95% confidence interval (CI) 0.43 to 4.03) than in workers without silicosis (SMR 1.19, 95% CI 0.87 to 1.57). An association between silica exposure and lung cancer risk was detected among those without silicosis; a statistically significant (p = 0.02) increasing trend of lung cancer risk was seen with cumulative exposure, with SMR reaching 2.40 (95% CI 1.24 to 4.20) at the highest exposure level (⩾5.0 mg/m3-years). A similar statistically significant (p = 0.02) dose-response gradient was observed among non-silicotic subjects when follow up was truncated at 15 years after the final negative radiograph (SMR 2.96, 95% CI 1.19 to 6.08 at ⩾5.0 mg/m3-years), indicating that the association among non-silicotic subjects was unlikely to be accounted for by undetected radiological silicosis. CONCLUSIONS The dose-response relation observed between cumulative exposure to respirable crystalline silica and lung cancer mortality among workers without radiological silicosis suggests that silicosis is not a necessary co-condition for silica related lung carcinogenesis. However, the relatively small number of silicosis cases in the cohort and the absence of radiographic data after employment limit interpretations.

Asbestos exposure, asbestosis, and asbestos-attributable lung cancer.

The study was designed to test the hypothesis that the risk of lung cancer from asbestos exposure is confined to persons with radiographic evidence of pulmonary fibrosis. Occupational and smoking histories were obtained from 271 patients with a confirmed diagnosis of primary lung cancer and 678 referents (279 with other respiratory disease and 399 with cardiac disease). Histories were reviewed blind to assess the timing, duration, and probability of exposure to asbestos. To allow for a lag between asbestos exposure and the development of lung cancer, subjects were classified by the time they had spent in an occupation entailing definite or probable exposure more than 15 years before diagnosis. The presence and extent of fibrosis was assessed blindly from chest radiographs by three readers and scored for small opacities with the ILO 1980 International Classification of Radiographs of the Pneumoconioses. 93 (34-3%) cases had worked in an occupation with definite or probable asbestos exposure compared with 176 (25.8%) referents (crude odds ratio for lung cancer 1-49, 95% Cl 1.09-2.04). After adjustment for age, sex, smoking history, and area of referral, the odds ratio (95% Cl) was 2.03 (1 00-4.13) in the subgroup of 211 with a median ILO score for small parenchymal opacities of 1/0 or more, and 1 56 (1.02-2.39) in the 738 with a score of 0/1 or less (ie, those without radiological evidence of pulmonary fibrosis). These results suggest that asbestos is associated with lung cancer even in the absence of radiologically apparent pulmonary fibrosis. (Lancet 1995;345:1074-8)

Immunologic evaluation of shrimp-allergic individuals

Thirty-three individuals with a history of immediate hypersensitivity reactions after shrimp ingestion and 29 nonshrimp-sensitive control subjects were evaluated for evidence of crustacea-specific immunity by skin prick test titration end point, RAST, and ELISA, with extracts of shrimp, crab, crayfish, and lobster. Individuals were categorized as either atopic or nonatopic on the basis of history and skin test reactivity to common inhalant allergens. Most (28/33) shrimp-sensitive subjects had positive skin prick tests to shrimp extract, whereas skin tests were negative in 27/29 control subjects. Eighty-one percent of atopic and 41% of nonatopic shrimp-sensitive subjects had elevated shrimp-RAST ratios. The RAST ratios of atopic individuals were significantly higher than ratios of nonatopic individuals, and there was a significant correlation between shrimp-RAST ratios and historical clinical symptom scores. RAST determinations of all control subjects were negative. Shrimp-sensitive subjects also had significantly elevated serum levels of shrimp-specific IgG and IgA as compared to control individuals. Both IgG and IgA shrimp-specific reactivity demonstrated a significant positive correlation with shrimp-RAST ratios. These studies indicate that IgE-mediated, type I mechanisms, detected by positive shrimp skin tests and RASTs, appear to be operative in crustacea-sensitive individuals, particularly those with concurrent respiratory allergy. Although the role of shrimp-specific IgG and IgA antibodies in the immunopathogenesis of crustacea allergy remains unclear, such antibodies appear to represent increased immunologic recognition of shrimp allergens/antigens in shrimp-sensitive subjects.

Follow up study of workers exposed to man made mineral fibres.

A survey of workers in seven man made mineral fibre (MMMF) production plants, the subject of a previous report, was conducted, with other blue collar workers serving as regional comparisons. Based on the median reading of chest radiographs by five readers, a low prevalence of small opacities, all at the 1/0 and 1/1 profusion levels, was again found: for workers with MMMFs, 23/1435 (1.6%); for comparison workers, 2/305 (0.7%). Spirometric measurements indicated generally healthy populations, and were not related to presence of opacities. Ninety three per cent (21/23) of MMMF workers with opacities worked at the two plants with the highest exposures to fine fibres, resulting in a dose-response relation across plants. For one location, the prevalences of opacities for the MMMF and comparison workers were not significantly different (5.9% (13/220) v 3.1% (2/65)). No comparison x ray films were obtained for the MMMF plant with the highest prevalence (6.6%), so a second phase of the study was conducted, with pre-employment films from these two plants. On this second reading, the prevalence of opacities was lower; there were no significant differences between the two groups of films, and no relation between opacities and exposure indices. There was considerable inter and intrareader variability. These results indicate no adverse clinical, functional or radiographic signs of effects of exposure to MMMFs in these workers.