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Biomedical subjects

L C Grammer

Publications and source records attributed to L C Grammer.

At least 55 records · Page 3Linked to original sources

Hypersensitivity pneumonitis-like reaction among workers exposed to diphenylmethane [correction to piphenylmethane] diisocyanate (MDI).

Isocyanates are well documented as a cause of occupational asthma. A hypersensitivity pneumonitis type of reaction has also been reported but only in a few isolated cases. We investigated nine subjects who complained of respiratory and general symptoms related to workplace exposure. All the subjects had worked in a plant where a resin based on diphenylmethane diisocyanate (MDI) is used in the manufacture of woodchip boards. They underwent inhalation challenges using the MDI resin for progressively increasing periods of time on separate days. In eight subjects, exposure to subirritant amounts of MDI induced a pattern of reaction consistent with hypersensitivity pneumonitis, i.e., significant falls in both FEV1 and FVC associated with a rise in body temperature (> 38 degrees C) and an increase in blood neutrophils (> +2,500/mm3). Bronchoalveolar lavage, performed in two subjects 24 h after the end of challenge exposure, revealed an increase in lymphocytes and neutrophils. Specific immunoglobulin G (IgG) and IgE antibodies to MDI human serum albumin (HSA) conjugates were present in all subjects. We conclude that the MDI resin caused an hypersensitivity pneumonitis type of reaction in at least eight (4.7%) of the 167 potentially exposed workers employed in the plant. These findings indicate that in some workplaces, a hypersensitivity pneumonitis type of reaction may be a more frequent consequence of isocyanate exposure than is usually thought.

Adult↗

A clinical and immunologic study of workers with trimellitic-anhydride-induced immunologic lung disease after transfer to low exposure jobs.

The objective of the study was to determine the clinical and immunologic status of trimellitic anhydride (TMA) workers who have had immunologic lung diseases and who have been moved to lower exposure jobs. Twenty-nine consecutive workers with TMA-induced immunologic lung diseases who had been moved to low exposure jobs for more than 1 yr were studied retrospectively. Pulmonary symptoms were obtained by physician-administered questionnaire. Immunologic studies were performed using radioimmunoassay. Spirometry and chest film were obtained. Workers with late asthma (LA) (n = 3), late respiratory systemic syndrome (LRSS) (n = 8), or both LRSS and asthma rhinitis (A/R) (n = 6) had improved symptoms, improved pulmonary functions, and lower total antibody against TM-HSA. Five of the 12 workers with A/R had improved symptoms, improved pulmonary functions, and lower IgE against TM-HSA, whereas seven continued to have moderate to severe symptoms, abnormal pulmonary functions, and elevated IgE against TM-HSA. There were no chest film findings in any group that were definitely attributed to TMA. Although TMA workers with LA or LRSS improve when moved to lower exposure jobs, only half of workers with A/R improve; elevated IgE against TM-HSA appears to be a marker for the subpopulation of workers with A/R that does not improve.

Adult↗

The application of an asthma severity index in patients with potentially fatal asthma.

The asthma severity index (ASI) is proposed as a tool to monitor the course of patients with increased risk of asthma-related morbidity and mortality. The ASI is a weighted summary of the diagnostic features of potentially fatal asthma (PFA). Fifteen patients with PFA were evaluated with ASIs calculated for the intervals 1 year prior to and 1 year following management by our allergy-immunology service. In each patient, a reduction was noted in the ASI following management, which corresponded to a reduction in asthma events. The ASI will have utility in the evaluation of chronic asthma treatment and in patient education.

Adolescent↗

Hemorrhagic rhinitis. An immunologic disease due to hexahydrophthalic anhydride.

This is a descriptive study of six men who had been occupationally exposed to heated epoxy resin containing hexahydrophthalic anhydride (HHPA) who presented with rhinitis, nasal mucosal erosions, and significant epistaxis; three also had asthma. When they were removed from exposure to HHPA, the rhinitis symptoms, nasal erosions, and epistaxis resolved spontaneous. All six had high titers of IgG and IgE against HHP-HSA as determined by an enzyme-linked immunosorbent assay (ELISA). Other asymptomatic workers with similar HHPA exposure had ver low or negative titers of IgG and IgE against HHP-HSA. We conclude that these results are very suggestive of an immunologic mechanism being responsible for the rhinitis, nasal mucosal erosions, and epistaxis that occurred in the six described HHPA workers.

Adult↗

Algorithms for the diagnosis and management of idiopathic anaphylaxis.

A major approach to the prevention of anaphylaxis due to exposure to an allergen is avoidance of the allergens. In cases of idiopathic anaphylaxis (IA), the method of management must first be pharmacologic control of the acute episode of IA and then the prevention of recurrent episodes. The appropriate management requires diagnosis, classification, and immediate initiation of a treatment regimen that will control and then induce a remission in patients with IA of the frequent (F) type. The classification and management of IA are reviewed and algorithms are presented for initial and long-term management of patients with IA.

Algorithms↗

Exposure to TMXDI (meta) aliphatic isocyanate and TMI (meta) unsaturated aliphatic isocyanate. Clinical and immunological evaluation of 96 workers.

We evaluated 96 workers employed at facilities that manufacture or use TMXDI (meta) aliphatic isocyanate and TMI (meta) unsaturated aliphatic isocyanate. We used immunoglobulin (Ig) and IgG serum antibody enzyme-linked immunosorbent assay (ELISA) studies and a questionnaire designed to identify symptoms compatible with work-related syndromes such as asthma and hypersensitivity pneumonitis. There were no workers with immunologically induced disease due to TMI isocyanate or TMXDI isocyanate nor were there any workers whose questionnaires suggested new onset of asthma. Approximately 40% of workers experienced some irritant symptoms, mostly upper respiratory or ocular. One worker had low level IgE antibody against TMXDI-HSA but had no work-related respiratory symptoms. Very low-level IgG against TMI-HSA or TMXDI-HSA was present in 7% of workers, all of whom were in the high-exposure category.

Air Pollutants, Occupational↗

Immunologic specificity of IgG against trimellityl-human serum albumin in serum samples of workers exposed to trimellitic anhydride.

The specificity of immunoglobulin G (IgG) against trimellityl-human serum albumin (TM-HSA) in serum samples from 11 workers exposed to trimellitic anhydride (TMA) was characterized in this study. Levels of IgG against TM-HSA and HSA-conjugates of other acid anhydrides, phthalic anhydride (PA), maleic anhydride (MA), hexahydrophthalic anhydride (HHPA) and tetrachlorophthalic anhydride (TCPA) were estimated by enzyme-linked immunosorbent assay index. Inhibition studies using each of 5 HSA acid anhydride conjugates were performed on all 11 serum samples with IgG against TM-HSA, and on the three serum samples with highest IgG binding to P-HSA and M-HSA. The only conjugate capable of inhibiting TM-HSA was TM-HSA. Both P-HSA and TM-HSA were able to inhibit IgG bound to P-HSA, and all other anhydride conjugates were able to inhibit IgG bound to M-HSA to some degree. When using TM-HSA and the other anhydride-HSA conjugates to inhibit IgG against TM-HSA, cross-reactivity was not apparent. However, when using those same conjugates to inhibit IgG against P-HSA or M-HSA, cross-reactivity could be demonstrated in some serum samples. Thus TMA workers may have antibody that has some affinity for other anhydride-HSA conjugates, but this antibody cannot be demonstrated by inhibition studies of IgG against TM-HSA when using other acid anhydride-HSA conjugates. Further studies are needed to define the biologic relevance of these immunologic observations.

Adult↗

Occupational asthma caused by a prepolymer but not the monomer of toluene diisocyanate (TDI).

Isocyanates are the most common cause of occupational asthma. Isocyanate monomers and prepolymers are widely used in the manufacture of polyurethane compounds. However, prepolymers are generating increasing interest because of their lower volatility. No distinction has yet been made between asthmatic reactions caused by the monomers and the prepolymers of isocyanates, and asthmatic reactions caused by one type of isocyanate but not the other type have not been reported. We describe two wood-roof maintenance workers who developed asthma after being exposed to a varnish containing a prepolymer of toluene diisocyanate (TDI) with only small amounts of the monomer. Specific inhalation-challenge tests with the TDI monomer did not elicit significant airway obstruction, whereas exposure to the varnish and to the purified TDI prepolymer induced late asthmatic reactions. Specific antibodies against TDI monomer human serum albumin and TDI prepolymer human serum albumin conjugates could not be demonstrated. These observations demonstrate that isocyanate prepolymers can cause occupational asthma and that asthmatic reactions caused by isocyanate prepolymers, but not to the corresponding monomer, can occur in some exposed workers.

Adult↗

IgG subclass antibody against trimellitic anhydride in workers with and without immunologic lung diseases.

In a retrospective comparison of two worker cohorts with elevated total antibody against trimellitic anhydride (TMA) conjugated to human serum albumin (TM-HSA), IgG subclass antibodies against TMA were studied in 19 workers with and 12 workers without TMA-induced immunologic lung disease. The main outcome measures were ELISA index of IgG1, IgG2, IgG3, and IgG4 against TM-HSA. There were no statistically significant differences in levels of any IgG subclass between these two groups. Neither were there any statistically significant differences when workers without lung disease were compared with subgroups of workers with lung disease, such as late respiratory systemic syndrome (n = 8), asthma/rhinitis (n = 6), or both (n = 5). In TMA workers with elevated total antibody against TM-HSA, IgG subclasses against TM-HSA in workers with TMA-induced immunologic lung disease were not different from workers without disease.

Adult↗

Malignant idiopathic anaphylaxis: three additional cases and extended evaluation.

Northwestern University's Division of Allergy and Immunology (NUAI) has evaluated and treated 225 patients with idiopathic anaphylaxis (IA) over a period of 16 years. Four patients have been identified with malignant IA. The term "malignant" is used to identify those patients with the most severe form of IA that is resistant to standard therapy. The diagnosis of malignant IA is made in patients with IA whose controlling oral corticosteroid dose was not able to be reduced below 60 mg of prednisone (or its equivalent) every other day or 20 mg of prednisone (or its equivalent) every day without an exacerbation of IA. Presented here is the long-term evaluation of one patient as well as three additional patients with malignant IA managed by our service. At the time of this report we have had no deaths due to IA in patients treated with pharmacologic regimen.

Adrenal Cortex Hormones↗

A comparison of cutaneous testing and ELISA testing for assessing reactivity to ethylene oxide-human serum albumin in hemodialysis patients with anaphylactic reactions.

In five patients who have experienced anaphylaxis and in 29 patients who have not had such episodes during hemodialysis, we have performed two immunologic studies: cutaneous testing with ethylene oxide-human serum albumin (ETO-HSA) and ELISA for IgE against ETO-HSA. Four of five patients with reactions had positive cutaneous tests, whereas only one nonreactor had a positive skin test (p less than 0.0002). The same four of five patients with reactions also had positive ELISA results, whereas three nonreactors has positive ELISA results (p less than 0.003). In this group of patients, the positive predictive value of cutaneous testing (80%) is somewhat higher than that of ELISA testing (57%). However, the sensitivity, specificity, and negative predictive values are similar. We conclude that cutaneous testing with ETO-HSA probably offers a small advantage over IgE against ETO-HSA as determined by ELISA.

Anaphylaxis↗

Antibodies to toluene diisocyanate in patients with and without dialysis anaphylaxis.

In a majority of patients with anaphylaxis to dialysis, ethylene oxide has been identified as an etiologic agent. In a significant minority of patients sustaining such reactions, the antigen remains unidentified. Conflicting results have been published with regard to isocyanates as a possible antigen. The authors studied 19 hemodialysis patients with anaphylaxis in whom IgE against ethylene oxide-human serum albumin (ETO-HSA) was not identified (Group 1) and 25 peritoneal dialysis patients without anaphylaxis (Group 2). IgE against toluene diisocyanate-human serum albumin (TDI-HSA) was found in one patient in Group 1, and a similar incidence of IgG against TDI-HSA in Group 1 (16%) and Group 2 (12%) was noted. The results do not suggest that IgE against TDI-HSA is an important cause of dialysis anaphylaxis.

Anaphylaxis↗

Anaphylaxis during intrauterine insemination secondary to bovine serum albumin.

A case of anaphylaxis is reported after IUI with sperm processed in Tyrode's solution supplemented with BSA. The patient had a positive prick cutaneous test to BSA and also had specific IgE antibody against it. Repeat IUI using the patient's own blood serum instead of BSA for processing the sperm proceeded without incident. Clinicians should be aware of this rare, but not inconsequential, adverse effect of using xenogeneic proteins during IUI and other assisted reproductive techniques.

Adult↗

Clinical and serologic follow-up of four children and five adults with bird-fancier's lung.

We report the clinical and serologic findings in four children and five adults with chronic avian hypersensitivity pneumonitis. All subjects were treated with corticosteroids and bird exposure was reduced or eliminated. After a variable period, ranging from 6 months to 10 years, their clinical and serologic findings were reassessed. In terms of symptomatology, chest findings, and pulmonary functions, all four children improved and four adults improved, whereas one adult had a progressive clinical deterioration, ultimately resulting in her death 5 years later. In terms of serologic data, precipitating antibody tended to persist, and antibody to avian antigens, as determined by ELISA, remained positive, although the titer declined. We conclude that, while serologic positivity remains, the prognosis for children and adults with chronic avian hypersensitivity pneumonitis is very good, provided that irreversible damage has not already occurred at the time of diagnosis.

Adult↗

Clinical and immunologic evaluation of 37 workers exposed to gaseous formaldehyde.

Thirty-seven workers exposed to formaldehyde (F) were evaluated to determine whether any of their respiratory or ocular symptoms were mediated by an immunologic response to F. Because there has never been a case of defined immunologically mediated respiratory or ocular disease as a result of exposure to gaseous F, we used clinical and immunologic criteria developed for immunologic respiratory diseases that result from inhalational exposure to trimellitic anhydride. A clinical assessment included review of a medical summary of history, physical examination, chest x-ray films, and pulmonary function studies. Serologic assessment was made with an ELISA for IgE and IgG to F human serum albumin. The final evaluation for immunologically mediated disease was based on both the clinical and serologic assessments. None of the workers had IgE or IgG antibody to F-human serum albumin or an immunologically mediated respiratory or ocular disease caused by F; however, some of the workers appeared to experience irritant symptoms caused by workplace exposure to F or other irritant chemicals.

Adult↗

Resistance and allergy to recombinant human insulin.

Insulin allergy and antibody-mediated resistance may complicate therapy with animal insulins. We describe a 53-year-old man manifesting both resistance and persistent systemic allergy despite treatment with recombinant human insulin. Insulin resistance and symptoms of allergy appeared in this patient several months after initiating therapy with mixed beef-pork insulin, as is often the case. Symptoms initially improved, but persisted, and then worsened again, despite continuous human insulin therapy. Total insulin-binding capacity by Scatchard analysis, high plasma insulin-binding capacity, and specific anti-insulin antibody levels were consistent with an immunologic form of insulin resistance. Glucocorticoid therapy was required both to reduce allergic findings and to restore glycemic control. Although recently available human insulins may be less immunogenic than animal forms, immune responses to exogenous human insulin still may pose significant clinical problems.

Adult↗