Inhibition of polymorphonuclear leukocyte chemiluminescence for detection of immune complexes in human sera.

An assay for the detection and quantitation of immune complexes is described. Experimental immune complexes or aggregated human gamma globulin (AHG) were incubated with polymorphonuclear leukocytes (PMN). After challenge of the PMN with opsonized zymosan, chemiluminescence was recorded in a scintillation spectrometer. A quantitative inhibition of chemiluminescence could be demonstrated by the interaction of PMN with immune complexes or AHG. Experimental immune complexes of bovine serum albumin-anti-bovine serum albumin were formed and tested by this assay, and immune complexes formed near antigen excess were best described by this technique. The technique was used to demonstrate immune complexes in the sera from patients with systemic lupus erythematosus, rheumatoid arthritis, and vasculitis. Immune complexes were quantitated by reference to a standard curve using AHG. By this technique, normal human sera had < 10 micrograms of AHG per milliliter of serum. Immune complexes at levels above this were detected in 9/15 patients with systemic lupus erythematosus, 18/30 patients with rheumatoid arthritis, and 2/5 patients with vasculitis. Therefore, this assay is a sensitive, simple method for measurement of circulating immune complexes in the sera of patients with certain connective tissue diseases.

Immunologic responses to inhaled cotton dust.

Byssinosis, a respiratory disease of workers on cotton, flax, and soft hemp, is classically characterized as shortness of breath, cough, and chest tightness on Mondays or the first day of return to work after a time off. Exposure to these vegetable dusts can also result in other respiratory diseases, and the term cotton dust-induced respiratory disease (CDIRD) is introduced. Although clinically characterized for more than a century, the underlying pathogenesis of CDIRD remains obscure. An allergic pathogenesis has been proposed. This article reviews previous and current research findings supporting this mechanism and raises the possibility that, in some individuals, CDIRD may be due to pre-existing or occupationally induced mold allergy.

Respiratory effects in toluene diisocyanate manufacture: a multidisciplinary approach.

A new plant manufacturing toluene diisocyanate (TDI) has provided a unique opportunity to investigate the effects of TDI vapor inhalation on respiratory health in a group of exposed workers who have been studied prior to the start of plant operation. In order to establish dose-response relationships and determine host factors, complete biologic monitoring, including pulmonary function and immunologic studies, has been performed concurrently with a comprehensive environmental monitoring program including continuous sampling for atmospheric concentrations of TDI. Study groups include workers with regular exposure to TDI in production jobs (83), workers with intermittent contact with this vapor, usually in maintenance (28), and a control group of workers employed outside the TDI area (55). This population is being followed for a period of 5 yr. The plant began operations in August 1973 with start-up procedures completed by the end of October. TDI spills occurred for numerous reasons, usually attributed to pump failure and resultant line blockage. Significant exposures also occurred in the drumming operation. The influence of these malfunctions is noted in the continuous monitoring data on atmospheric TDI concentrations which continue to reveal frequent excursions above the threshold limit value (TLV) of 0.02 ppm ceiling. These data are presented in relation to time and plant location. Although the first full year follow-up following initial exposure was not complete, certain preliminary clinical observations were made. A number of workers had episodes of acute respiratory symptoms related to single exposure to an irritant gas at work, usually either TDI or phosgene. It appears that two or three workers in the study population have become "clinically sensitized" to TDI and have been removed from regular TDI exposure. To date, the total number of workers who report the presence of recurring respiratory symptoms has not increased in comparison with the pre-exposure survey. Pulmonary function data after one full year of TDI exposure are not yet available. Pre- and post-shift ventilatory function studies do not indicate significant differences between the exposed and control groups. Selected individuals had carefully controlled inhalation challenge tests to monitored concentrations of TDI vapor under laboratory conditions. In workers suspected of having become "sensitized", immediate and/or late air flow obstruction was demonstrated and could be related to dose of inhaled TDI.

Function of lymphocytes and monocytes in silicosis.

The function of lymphocytes and monocytes was compared in a group of 18 ex-sandblasters with silicosis and 19 control subjects. Previously noted depressed lymphocytic proliferation in response to low concentrations of concanavalin A (ConA) in subjects with silicosis was not due to factors in the serum nor correctable by supplementation with allogeneic lymphocytes. Monocytes from the peripheral blood of the subjects with silicosis responded less to a chemotactic stimulus (zymosan-activated serum) than did monocytes from normal laboratory personnel; however, there was no difference in monocytic chemotaxis when groups of similar age were compared. There was a significant correlation between age and the monocytic response to chemotactic stimuli in the studied population (laboratory personnel, silicotic subjects, and age-matched control subjects). Overall, our data suggest subtle effects of silica on selected T-lymphocytic populations involved with responsiveness to the mitogen, concanavalin A, but no effects on monocytic function. Monocytic chemotaxis is unaffected by exposure to silica but is inversely related to age.

Incidence of serum precipitins against organic-dust antigens in different populations by counterimmunoelectrophoresis.

The incidence of serum antidust and antifungal precipitins was determined by counterimmunoelectrophoresis in 317 atopic and nonatopic subjects of three geographic areas (north central, southern, and western United States). The selected lyophilized crude antigens employed were from house dust, Micropolyspora faeni, Candida albicans, Alternaria tenuis, Aspergillus fumigatus, Puccinia coronata, Cantharellus cibarius, and Amborsia trifida. Antidust precipitins were detected with high frequency in atopic and nonatopic subjects of each geographic area (48 to 71 percent of different population subgroups). Precipitin reactions were generally intense and often multiple, in keeping with the marked heterogeneity of the crude dust antigen employed. Antidust precipitins were also present in serum fractions precipitated with ammonium sulfate and in IgG-rich fractions obtained by gel filtration (Sephadex G-200) and diethylaminoethyl-cellulose chromatography. Precipitins against crude somatic fungal and actinomycetic antigens were detected with considerably less frequency in all populations surveyed, considerably less frequency in all populations surveyed, and antiragweed precipitins were not detected. Our results suggest that prolonged environmental exposure to diverse, ubiquitous organic dusts results in a "normal" serum precipitating-antibody response. They also extend our previous finding of a high precipitin response against organic dusts in residents of the Gulf south area compared to other geographic areas.

Hypersensitivity pneumonitis and extrinsic asthma. An unusual association.

A farmer who had no prior history of pulmonary disease developed tightness in the chest of rapid onset, shortness of breath, fever, and pulmonary infiltration while farming. The symptoms of his disease worsened with repeated exposure to the dusty farm field but remitted after each of five hospitalizations. Provocative challenge with inhalation of a water-soluble extract of dust from the field reproduced both asthmatic and pneumonitic features of the disease, while administration of corticosteroids clinically controlled the entire process. The data suggest a common cause for asthma and pneumonitis in this patient.

Hypersensitivity pneumonitis.

Hypersensitivity pneumonitis represents a disease spectrum and not a single pulmonary disorder. Both acute and chronic forms of disease occur and presumably reflect different yet interrelated immune mechanisms of pathogenesis. The diagnosis of hypersensitivity pneumonitis, although often straightforward, may depend on the use of immunologic and microbiologic analyses with the aid of inhalation challenge testing. Finally, the immune pathway to disease expression is as yet undefined and may represent subtle changes in "suppressor" cell populations and their regulatory effects on immune effector cells.

Chronological assessment of asbestos exposure on cell composition in murine lung.

To elucidate immune pathogenic mechanisms in asbestosis, lung and spleen lymphoid cell populations were analyzed at defined time intervals (1, 2, 3, 6, and 12 weeks during exposure and 4, 24, and 48 weeks post-exposure) in asbestos-exposed and unexposed (control) mice. Polymorphonuclear leukocytes and macrophages were increased in the lung tissue histologic sections of asbestos-exposed mice compared to controls. No consistent changes were observed in percentages of lung or spleen helper, suppressor, or total lymphocyte populations after asbestos exposure. The numbers of B cells (identified by anti-IgG) in minced lung preparations of asbestos-exposed animals were increased after 12 weeks of exposure. There also was an increase in IgG production in asbestos-exposed mice after 12 weeks exposure and at 4 weeks post-exposure with a return to near baseline levels 24 and 48 weeks after initial exposure. Collectively, these studies demonstrate stimulatory effects of inhaled asbestos fibers on B cells and IgG production after 12 weeks of continuous inhalation of asbestos fibers in a dust generation chamber.

Reliability of cell counts and protein determinations in serial bronchoalveolar lavage procedures performed on healthy volunteers.

We measured the variability in volume, total cells, cell types, and proteins in the bronchoalveolar lavage fluid recovered from 10 volunteers (five smokers, five non-smokers) lavaged repeatedly over a three-year period. Thirty lavages were performed using a rigorously standardized approach. Differential counts on the cytospin preparations were performed by three independent readers and interobserver variability in the interpretation of these counts measured. Variability in interpreting the cellular counts was less in smokers than non-smokers and decreased as the number of cells of any particular type increased. Only one reader interpreting the mean percentage of cells recovered of one cell type (neutrophils) in only one smoking group, the nonsmokers, was significantly different from the other two. There was also considerable variability in bronchoalveolar lavage fluid total protein, albumin, IgG, and IgA. Expressing albumin and IgG as a percentage of total protein recovered and expressing IgA and albumin as a ratio in nonsmokers lessened the variability of these parameters. Mean and standard deviations of the cellular and protein concentrations showed that large differences in these parameters would be necessary in order to attribute these changes to changes in the underlying pulmonary status. Excessive variability in nearly all parameters in this group without recognized lung disease challenges the usefulness of this test in the clinical assessment of patients serially followed because of underlying lung disease.

Use of burn intensive care unit gymnasium as an adjunct to therapy.

One primary goal for patients with burns is to prevent loss in range of motion and function in the involved extremities. Because therapies were provided only on weekdays at our facility, the burn team designed a gymnasium that was built in the burn unit where patients can carry out their exercise programs after hours and on weekends. Patients assume responsibility to complete their occupational and physical therapy assignments, in addition to their other scheduled therapy sessions. The development of the burn intensive care unit gymnasium has increased the opportunity for patients to improve their range of motion and overall functional status. We have also noted that patients feel a greater sense of motivation and accomplishment when they are invited to take more control of their recovery. Assuming responsibility for their programs enables patients to achieve their goals, thus increasing their self-esteem after what is often a very devastating injury.

Effects of asbestos and beryllium on release of alveolar macrophage enzymes.

Rabbit alveolar macrophages were exposed in culture medium to asbestos, beryllium sulfate, and beryllium oxide. The specific activities of the lysosomal hydrolases, acid phosphatase beta-N-acetylglucosaminidase and beta-glucuronidase plus the glycolytic enzyme, phosphohexose isomerase were determined in the medium, whole-cell homogenates, mitochondrial fractions, and supernatant. These hydrolases increased significantly in the medium but not in the mitochondrial fraction of cells exposed to dusts. Asbestos and beryllium sulfate were highly cytotoxic for alveolar macrophages in vitro and the data suggested that these agents were not associated with an increase in enzyme synthesis but rather a direct cytotoxic effect at the macrophage membrane level. For induction of enzyme release in vitro, a higher concentration of beryllium oxide was needed when compared with asbestos and beryllium sulfate. The cytotoxicity and enzyme release induced by these agents may represent an important nonspecific mechanism by which they induce inflammation and perhaps local proliferation of fibroblasts.

Bronchial asthma. Mechanisms and management of a complex obstructive airway disease.

Airway hyperreactivity to physical, chemical, and pharmacologic stimuli is a hallmark of bronchial asthma. In patients with extrinsic (allergic) asthma, in whom an immunologic mechanism of the IgE type can be demonstrated, specific sensitivity develops to a variety of common environmental substances, including pollen, fungus spores, house dust mites, and animal danders. Persons with intrinsic asthma, in whom immunologic mechanisms are hard to demonstrate, often have chronic sinus disease and nasal polyps and manifest clinical intolerance to nonsteroidal antiinflammatory agents. Evaluation of asthma includes a history and complete physical examination, skin tests, radioallergosorbent tests, pulmonary function tests, blood gas determination, and inhalation challenge tests. Treatment is focused on environmental control, pharmacotherapy, and immunotherapy.