BACKGROUNDA study of occupational asthma among workers exposed to 4,4'-Diphenylmethane Diisocyanate (MDI).OBJECTIVETo demonstrate if serum concentrations of MDI-specific IgG or IgE are sensitive biological markers of disease or of MDI exposure.METHODSThe study group consisted of nine MDI-exposed workers and nine nonexposed workers. Air sampling for MDI and polymethylene polyphenyl isocyanate, occupational and medical histories, respiratory physical exams, pre- and postshift spirometry, and self-administered peak expiratory flow rates were performed. Serum specific IgE and IgG antibodies to an MDI-human serum albumin (HSA) conjugate were assayed by the radioallergosorbent test and the enzyme-linked immunosorbent assay, respectively, and compared to nine nonexposed laboratory controls.RESULTSNo definitive cases of occupational asthma were documented. The mean level of MDI-specific IgG was significantly greater among exposed workers compared to nonexposed workers and laboratory controls (p = 0.04). Mean levels of TDI and HDI-specific IgG were also increased.CONCLUSIONThis study demonstrates that serum concentrations of MDI-specific IgG appear to be a moderately sensitive biological marker of MDI exposure, but not an indicator of occupational asthma. Workers with IgG antibodies specific for one diisocyanate-HSA conjugate exhibit cross-reactivity to antigens prepared with other diisocyanates.

Two long-term cultured cell lines were established from BALB/c mouse axillary and cervical lymph nodes that exhibited a combination of functional, morphological, and phenotypic characteristics consistent only with high endothelial venule cells. Spleen lymphocytes selectively bound and migrated across the cell lines. On Matrigel, these cell lines formed tubules with lumens, a characteristic unique to endothelial cells. Morphologically the cells were 20–30 μm in diameter and exhibited contact inhibition. The cells were not myeloid in origin because they lacked sodium fluoride-inhibitable nonspecific esterase activity, myeloperoxidase activity, and F4/80 antigen. The cell line phenotypes were compared to high endothelial venule (HEV) cells in tissue sections. HEV cells in lymph node tissue sections expressed endoglin, PECAM-1, ICAM-1, VCAM-1, laminin, fibronectin, collagen IV, H2Kd, MECA 79, MECA 325, and vWF. The cell lines expressed endoglin, VCAM-1, fibronectin, and H2Kd. The cell line derived from cervical lymph nodes also expressed laminin and H2Dd. Neither cell line expressed collagen IV, IAd, ICAM-1, ICAM-2, dendritic cell antigen, or PECAM-1. They also did not express MECA antigens or intracellular vWF, consistent with reports of many cultured endothelial cells. To further substantiate cell line identification, antiserum generated against the cell lines bound specifically to HEV cells in frozen lymph node tissue sections and to both of the lymph node-derived cell lines but not control cell lines. Thus, the lymph node derived-cell lines expressed molecules found on HEV cellsin vivo and most importantly retained the functions of tubule formation, lymphocyte adhesion, and promotion of lymphocyte migration.

According to the International Narcotics Control Board, over 45,000 kg of morphine and 54,000 kg of codeine were ethically manufactured in 1986 at three facilities in the United States. Little information exists about possible adverse health effects associated with workplace exposure to opiate compounds in this industry. Because there are no specific federal standards for workplace exposure to narcotic dusts, exposure-control defaults to the nuisance dust standard (10 mg/m3, as an 8 hr time-weighted average). Narcotics manufacturing workers were evaluated for anti-morphine IgG before and 10 mo. after the implementation of an improved respiratory protection program (RPP). Significantly elevated IgG levels were measured before the improved RPP (P<0.005). After the improved RPP, a significant reduction was observed (P<0.001), suggesting that specific antibody levels could be used as biomarkers of exposure. Inhibition studies showed that the antibodies were specifically directed against morphine with some cross reactivity with morphine derivatives. Preliminary results are also shown which indicate that similar anti-morphine antibodies are present in the sera of intravenous heroin abusers. Elevated levels (P<5) of anti-morphine antibodies were detected in sera from heroin abusers, providing evidence that similar antibodies may be produced from non-occupational exposure to opiates. These finding have potentially far-reaching implications for addiction research and drug testing.

A 24-year-old white woman reported sexual intercourse-related pruritus, hives, wheezing, and dyspnea within 5 minutes after ejaculation. Systemic reactions (SRs) were prevented by use of condoms. Prick testing confirmed sensitization to five Sephadex G-100-separated fractions of her husband's seminal plasma. The intradermal end point threshold concentrations (ETC) were 10(-4) and 10(-1) micrograms of protein per milliliter to fractions 2 and 3, respectively. Leukocyte histamine release studies exhibited 100% release to fraction 2 and 37% release to fraction 3. A 2-day protocol of rapid immunotherapy (IT) was performed with subcutaneous incremental doses of human seminal plasma (HuSePl) fractions 2 and 3. The patient experienced an SR after receiving a cumulative dose of 38.55 micrograms of fraction 2 on day 1. On day 2, rapid IT with fraction 2 was administered until the patient experienced a mild SR after having received a cumulative dose of 102.8 micrograms. There was a one-log10 increase in the intradermal ETC to both fractions 2 and 3 at the end of day 2. IT was continued three times weekly for 4 months until the patient tolerated 100 micrograms doses of both fractions 2 and 3. At 4 months, coitus was resumed without SRs, and HuSePl IT was stopped. The intradermal ETC to fractions 1, 3, 4, and 5 was increased 6 months after cessation of HuSePl injections, but there was a one-log decrease in the ETC to fraction 2. Our experience demonstrated that systemic tolerance can be achieved by parenteral administration of selected HuSePl fractions. Partial immunologic desensitization of patients with anaphylactic sensitivity can be achieved.(ABSTRACT TRUNCATED AT 250 WORDS)

A cross-sectional medical evaluation was conducted to determine respiratory and dermatological effects of platinum salts sensitization among workers in a secondary refinery of precious metals. Fifteen of 107 current employees and eight (28%) of 29 former employees, who had been terminated from employment on average for 5 years because of respiratory symptoms, had positive skin reactivity to platinum salts. Platinum salts skin reactivity was significantly associated with average air concentrations of platinum salts in employees' present work area. Workers with positive platinum salts skin tests had significantly higher prevalences of reported rhinitis, asthma, and dermatitis than negative skin test workers. They also had increased bronchial response to cold air challenge and elevated levels of total serum IgE. Platinum salts sensitization was not associated with atopic tendency as measured by sensitivity to common aeroallergens, but was strongly associated with cigarette smoking status. The findings indicate that cigarette smoking may be a risk factor for the development of platinum salts allergy. The persistence of platinum salts sensitization and high prevalence of adverse health outcomes among former workers demonstrate the importance of regular medical monitoring so that sensitized workers can be removed from exposure before they develop long-term health problems.

An investigation of a platinum refinery operation consisted of an administered questionnaire, spirometry, skin prick testing with platinum salts and common aeroallergens, serum total IgE, radioallergosorbent test for platinum salts, and measurement of nonspecific airway hyperresponsiveness by cold air challenge testing. Among 136 employees examined, there were 107 current and 29 medically terminated workers; 23 (17 percent) subjects had a positive platinum salts prick skin test and 19 (14 percent) displayed a positive cold air challenge. RAST binding for platinum salts IgE antibodies showed a high level of agreement with platinum skin prick test results. A proportion (63 percent) of the population (74 current and 12 terminated workers) underwent repeat platinum skin testing one year later. Among current workers, there was conversion of the platinum skin test from negative to a positive test in five employees, with three conversions occurring in workers who showed only a positive cold air challenge test the year before. Platinum skin sensitivity, asthma symptoms, and nonspecific airway hyperresponsiveness persisted for years after termination of exposure in some medically terminated workers presumably because of a delay in removal from work of employees who became sensitized to platinum salts. It is suggested that proper surveillance for occupational asthma involves the use of several testing procedures. Prompt removal from work of individuals found to become sensitized to platinum salts is important in this industry.

Four groups of four Macaca fascicularis monkeys were administered 10 consecutive weekly subcutaneous injections of 2 mg aluminum hydroxide plus one of the following: 200 micrograms of phthalic anhydride (PA)-monkey serum albumin (PA-MSA, group 1); 200 micrograms of PA dissolved in ethanol-saline (EtOH-sal, group 2); 200 micrograms of MSA (group 3); or EtOH-sal alone (group 4). Direct intracutaneous tests to PA-MSA, PA-EtOH-sal, MSA, and EtOH-sal were applied at biweekly intervals throughout the course of the immunization. Serum-specific IgG to PA-MSA and specific IgE to PA-MSA were determined at 2-week intervals according to the ELISA and RAST methods, respectively. The prevalence of cutaneous sensitivity to PA-MSA in the PA-MSA-immunized group (group 1) was significantly greater after 4 and 6 (p less than 0.01) and 8 and 10 (p less than 0.05) weeks, compared with the other treatment groups. Significantly elevated (p less than 0.01) PA-MSA-specific IgG was also observed in monkeys in group 1 compared with the other treatment groups. No significant changes in PA-MSA RAST or total IgE were observed in any group during the study. These results indicate that parenteral sensitization to PA in subhuman primates requires the presence of new antigenic determinants formed by PA on protein carriers.

A cross-sectional evaluation was performed of workers in a steel foundry in which methylene diphenyldiisocyanate (MDI) was used as a component of a binder system used to make cores and molds. Preshift and postshift spirometry and clinical evaluations were performed on 26 currently exposed (group I), on six formerly exposed (group II), and on 14 nonexposed workers to MDI (group III). Serum samples were assayed for total antibody binding, specific IgG by ELISA, and specific IgE by the RAST method to MDI-human serum albumin (HSA). Symptoms compatible with occupational asthma were elicited from seven (27%) of 26 group I workers and from three of six group II workers. No symptoms were reported by group III workers. Intrashift change in FEV1 (a mean decrease of 0.049 L) in group I workers was significantly decreased compared to that in unexposed group III workers (a mean increase of 65 ml; p = 0.043). Specific IgG and total antibody responses to MDI-HSA were detected only in workers with current or former exposure to MDI. Only one worker was identified with IgE-mediated occupational asthma exhibiting a positive prick test and elevated RAST to MDI-HSA of 25.5% bound. In this occupational setting, polyclonal immune responses to MDI-HSA and clinical sensitization to MDI were demonstrated to occur.

We evaluated workers and performed an industrial hygiene assessment at a plant where raw eggs are processed into powdered egg yolk and whole egg. Egg dust levels in the packaging room straddled the American Conference of Governmental Industrial Hygienists' (ACGIH) exposure guideline of 10 mg/m3 for nuisance dust. We obtained medical histories from 25 workers, and performed physical examinations, spirometry, and serial determinations of peak expiratory flow rate (PEFR) by portable meter every 3 hrs (while awake) for 7 days. We defined symptomatic bronchial lability to be a decrement in PEFR on any one day of 20% or more of the day's maximum, with concurrent symptoms. Skin-prick tests and serum assays for specific IgE by the radioallergosorbent (RAST) method were performed to assess sensitivity to commercial egg proteins, egg protein fractions, and freshly prepared extracts of whole egg powder and yolk. We classified participants as definite cases of asthma if both the examining physician diagnosed asthma and symptomatic bronchial lability was demonstrated by serial PEFR determinations. Definite noncases of asthma were those participants in whom the physician did not diagnose asthma and in whom symptomatic bronchial lability was not demonstrated by PEFR. All five definite cases, compared to three of 16 definite noncases of asthma, had one or more positive skin-prick tests to egg proteins. Four of five cases, compared to 0 of 14 noncases, who had serum determinations, had an elevated RAST to one or more of the egg proteins. This study demonstrates that occupational asthma associated with IgE-mediated allergy to egg proteins occurs among workers exposed to inhaled egg proteins.

Six laboratory workers who were exposed to American cockroaches (AC) and German cockroaches (GC) while they were performing immunologic experiments were evaluated for cockroach hypersensitivity. Prick skin testing and RAST were performed with whole body extracts (1:20 wt/vol) of AC, brown-banded (BB), and GC species as well as hemolymph and fecal (F) extracts of AC. Three of six workers reported work-related nasal and ocular symptoms associated with xenografting and bleeding of cockroaches. All three symptomatic workers exhibited cutaneous reactivity to at least one cockroach antigen. Elevated RAST binding was observed in one of the three symptomatic workers. A nasal provocation to AC was positive in the most symptomatic worker at a provocative dose of 3.2 X 10(-3) mg causing a 50% decrease of nasal flow rate from baseline. After pretreatment with nasal cromolyn, the provocative dose causing a 50% decrease from baseline increased to 2.6 X 10(-1) mg. Nasal provocation with the same concentrations of AC were negative in two skin test negative subjects. RAST-inhibition studies demonstrated cross inhibition of the serum-specific IgE binding to AC-hemolymph by AC, GC, and BB whole body extracts. However, specific IgE binding to AC-F was inhibited by AC-F and AC but not by GC or BB whole body extracts, suggesting there was greater specificity of the F allergens. This study demonstrated that cockroach allergens elicit IgE-dependent upper respiratory sensitization in the workplace.

Twenty-five workers in an egg-processing factory were evaluated for respiratory sensitization to inhaled egg proteins by a physician evaluation, serial peak expiratory flow rate (PEFR) measurements for a 1-week period, and immunologic tests. Immunologic studies included skin prick tests, serum-specific IgE (RAST), and specific IgG (ELISA) to solutions prepared from commercial food allergens: factory-powdered egg white and yolk products and purified egg white fractions, including ovalbumin, ovomucoid, lysozyme, and conalbumin. Six workers had significant daily PEFR lability (greater than 20%) of whom five had associated cutaneous reactivity to at least one egg allergen. A diagnosis of "definite asthma" was established in five workers suspected by the physician of having asthma. These five workers exhibited significant decrements in daily PEFR that were accompanied by bronchial symptoms. Occupational asthma was diagnosed by the physician in four of the five latter workers. Definite asthma was significantly associated with both cutaneous reactivity to egg allergens (p less than 0.01) and RAST binding (p less than 0.01). Of eight workers with cutaneous reactivity to at least one egg reagent, four workers (50%) were positive to only purified egg white fractions. The highest levels of RAST binding were detected in four workers, and the best binding activity was to ovomucoid and ovalbumin fractions. Elevated specific IgG responses were significantly higher in egg-factory workers to whole egg (p less than 0.005), lysozyme (p less than 0.002), and conalbumin (p less than 0.002) allergens compared to responses of nonexposed control subjects. However, no differences in specific IgG were detected between symptomatic and asymptomatic workers.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid anhydride compounds are reactive chemicals that have been previously associated with immunoglobulin E (IgE) mediated occupational asthma. Twenty workers with exposure to himic anhydride powder used for the manufacture of a synthetic flame retardant were questioned about respiratory symptoms. The study was initiated after one individual from the plant developed asthma. A test for serum-specific IgE to human serum albumin conjugates of himic anhydride, phthalic anhydride, hexahydrophthalic anhydride and trimellitic anhydride was performed for seven workers with respiratory symptoms associated with himic anhydride exposure. Three of the seven symptomatic workers who reported wheezing at work exhibited elevated specific IgE to two or more acid anhydride-human serum albumin conjugates. Radioallergosorbent inhibition studies performed with sera containing high levels of himic anhydride-human serum albumin specific IgE from a symptomatic worker demonstrated cross-allergenicity between himic anhydride-human serum albumin and hexahydrophthalic anhydride-human serum albumin allergenic determinants. This study demonstrated that himic anhydride can elicit IgE-mediated sensitization in the workplace.

Evaluation (HHE), workers employed in a precious metal refinery exposed to platinum (Pt), palladium