Immunologic aspects of granulomatous and interstitial lung diseases and of cystic fibrosis.
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Biomedical subjects
Publications and source records attributed to J N Fink.
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This case illustrates a comprehensive approach to assessing causality in a woman with apparent cognitive dysfunction, as measured by neuropsychological testing, and a 10-year history of occupational exposure to ethylene oxide. The analysis included a multidisciplinary examination of the patient, which took place several years after the termination of her exposure. In addition, all of the patient's prior medical and psychiatric records were reviewed, as were the records of her employer to ascertain her exposure history. Our evaluation revealed a pattern of neuropsychological findings not consistent with nervous system damage secondary to an organic effect of ethylene oxide. A more likely causal hypothesis is adopted: the patient's apparent cognitive dysfunction had a psychiatric etiology. This case also illustrates the potential impact of a patient's involvement in legal proceedings related to claims of neurocognitive dysfunction.
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Three patients are presented who ingested a health food known as "bee pollen" and who experienced an immediate allergic reaction. Examination revealed that the bee pollen contained dandelion pollen, which belongs to the Compositae family as does ragweed. In vivo and in vitro studies demonstrated that the patients were sensitive to several Compositae family members, rather than to insect-derived antigens. In addition, radioallergosorbent inhibition studies confirmed the suspected cross-reactivity between the health food and Compositae pollens. This study indicates that atopic individuals may experience anaphylaxis from ingestion of antigens in certain food stuffs that cross-react with pollens to which they are sensitive.
Antigens from Micropolyspora faeni, Saccharomonospora viridis, Thermoactinomyces candidus, T. sacchari and T. vulgaris were prepared by growing them on dialysate of trypticase soy broth. Sera from rabbits immunized with these antigens were used to study cross-reactivity between thermophilic actinomycetes by antigen-antibody crossed immunoelectrophoresis and by agar gel double diffusion. Mi. faeni and S. viridis showed some degree of cross-reaction, but both failed to show any cross reactivity with Thermoactinomyces species. Antigens from Thermoactinomyces cross-reacted with members within the genus, but no reactivity against S. viridis or M. faeni antisera was detected. Hence, the presence of antibodies to several thermophilic actinomycetes in the sera of patients may be attributed to the exposure of the individual to different thermophilic actinomycetes rather than to the antigenic cross-reactivity between the organisms.
This study was performed to determine whether the lung histological changes which occur in rabbits following intravenous injection of killed Bacilli Calmette-Guérin (BCG) are accompanied by measurable changes in pulmonary function. We measured pulmonary function in New Zealand white rabbits 3 weeks after intravenous injection of BCG and in normal rabbits. After a tracheostomy and carotid artery catheterization was performed, each anesthetized rabbit was placed in a body plethysmograph for pulmonary function testing. Following the measurements, the lungs were removed for weighing and histological evaluation. In the BCG-treated rabbits, the lung weight/body weight ratios were 152% greater, the pulmonary resistance was 104% higher, dynamic compliance was 45% lower, minute ventilation was 28% greater, and the delta AaPO2 gradient was 13 torr higher than in the normal control rabbits. Histological evaluation of the BCG-treated animals revealed diffuse pulmonary involvement with non-caseating granulomas.
Exocellular antigens from Micropolyspora faeni and Micropolyspora rectivirgula were prepared by growing them in a synthetic broth culture at 50 degrees C for 1 week under continuous shaking. The broth was separated from the organisms by filtration and the filtrate was dialyzed and freeze-dried. The cross-reactivity of these antigens were studied by antigen-antibody crossed-immunoelectrophoresis and the presence of similar antigens in different strains by tandem crossed-immunoelectrophoresis using rabbit anti-M. faeni and anti-M. rectivirgula sera. The results indicate that a number of antigenic components are common to the different strains of M. faeni and M. rectivirgula, while each strain demonstrates several specific antigenic determinants. Of the 26 clearly demonstrable precipitin arcs formed by crossed-immunoelectrophoresis, only 1 was detected in all the strains while 2 more were detected frequently. This study indicates that M. rectivirgula and M. faeni strains are not distinguishable from each other by morphological, biochemical or immunological criteria.
Serum IgA and IgG antibody activities against pigeon serum were measured in 16 symptomatic pigeon breeders, 20 asymptomatic pigeon breeders, and 3 normal subjects by radioimmunoassay. The IgA and IgG antibody activities against pigeon antigen of the group of patients with disease was significantly greater than those of patients in the asymptomatic and the control group. The overlap of results for the symptomatic and asymptomatic breeders limits the diagnostic value of these individual IgA or IgG antibody determinations. Bronchoalveolar fluid and serum samples from a smaller group of pigeon breeders who underwent lung lavage were available for studies of antibody activity against pigeon serum. Ten asymptomatic and 6 symptomatic breeders were available for study. Both IgG and IgA antibody activities were detected by radioimmunoassay in serum samples and bronchoalveolar fluid. The IgA antibody activity determined by the radioimmunoassay was higher in the respiratory secretions.
A family was recently studied in which two brothers with identical HLA serotypes had allergic bronchopulmonary aspergillosis. One of the two had a normal bronchogram. A field investigation of the family residence showed that a barn was the probable source of the organism causing disease in these patients. Immunologic characterization of the family members showed a broad spectrum of response to the environmental exposure.
Symptoms of hypersensitivity pneumonitis in three employees in an office building led to an investigation of their work environment. An open spray water air cooling system was implicated when inhalation challenge with the spray water caused acute illness in one of them. A questionnaire survey of the 4,023 co-workers identified 48 other suspect cases, and laboaratory studies confirmed hypersensitivity pneumonitis in three additional workers of this group. A significant change in pulmonary function, occurring only after exposure to the work environment, was the most useful laboratory finding and was found in five workers with no other pulmonary abnormalities, but not is asymptomatic workers or controls, since five of the six patients with hypersensitivy pneumonitis worked in offices cooled by the spray water system and since three had positive responses to inhalation challenge, use of the spray water system was discontinued. The affected workers improved after they were removed from the office complex.
In 5 patients with respiratory symptoms consistent with humidifier or air conditioner disease, a hypersensitivity pneumonitis, no identifiable organism was cultured from the humidifier water (HW). The water source to the humidifier or air conditioner was investigated for possible antigens which might explain the occurrence of the disease. Three subjects who lived in the same city supplied by Lake Michigan had increased IgG antibody activity against the city water supply when compared with another patient from a different city and a control subject. Both of the latter lived in cities with water supplied from Lake Michigan. Two of the 5 patients showed definite inhibition by concentrated tap water (TW) of IgG antibody against HW. The source of antigens in water was not determined but must be considered in cases of this type of hypersensitivity pneumonitis. A sixth case consistent with humidifier disease had Cephalosporium cultured from her HW. On gel diffusion there was a band of identity with her serum against Cephalosporium extract and her own HW, and by radioimmunoassay (RIA) there was over 50% inhibition of her IgG antibody activity against HW by Cephalosporium. No antibody against her city TW was demonstrated.
This study was designed to evaluate immunologic differences between aspergilloma (A) and allergic bronchopulmonary aspergillosis (ABPA), comparing the results to atopic and nonatopic control subjects. Humoral studies included skin tests with common inhalant antigens and Aspergillus fumigatus. Total and specific IgE and other immunologlobulin levels and serum precipitins were evaluated against A. fumigatus. Cellular immunity was studied with routine skin testing and phytohemaqglutinin-induced lymphocyte blast transformation. Antigen-induced blast transformation was also carried out with the use of serial dilutions of A. fumigatus. All patients with ABPA were atopic and had marked elevations of IgE. None of the patients were atopic and they had normal IgE levels. Immediate and late skin reactivity to A. fumigatus was low in control and A groups but high in 2 patients with ABPA. IgG antibody against A. fumigatus was generally greater in the ABPA group. Both ABPA and A had serum precipitating antibody against A. fumigatus. The atopic controls had elevated IgE levels and immediate skin test reactivity to A. fumigatus, and one also had weak serum precipitins against A. fumigatus. IgE antibody against A. fumigatus was generally higher in ABPA than A. ABPA and A patients had elevated stimulation indices (SI) to A. fumigatus. No stimulation could be detected with cells from control subjects. This study indicates that both T and B cell sensitization may play a role in the development of or as a response to aspergillus-related pulmonary disease.
Cases of the acquired form of angioedema have been recognized as a separate entity since 1972. Previously reported cases have been related to various hematologic malignancies. We have recently studied a patient with rectal carcinoma who manifests a complement pattern compatible with the acquired form of angioedema. No previous personal or family history of allergic disease or angioedema was present. Because the episodes of angioedema were laryngeal in location and required emergency intubation to maintain an adequate airway, a trial of danazol prophylaxis, which has been shown to be effective in hereditary angioedema, was undertaken. His beneficial response to this form of therapy is also documented.
The response of the adrenergic system of asthmatic subjects to exercise and the role of plasma catecholamines in exercise-induced asthma were investigated. Plasma levels of norepinephrine and epinephrine were measured at rest, during and after exercise in 7 asthmatic and 9 matched normal subjects. Exercise-induced bronchospasm occurred in all asthmatic subjects following exercise, while no significant change was observed in the normal subjects. The results showed that plasma levels of norepinephrine and epinephrine at rest and changes that occcurred during and after exercise were similar in both normal and asthmatic subjects. These data suggest that the adrenergic response of asthmatics to the same relative exercise stress as reflected in plasma catecholamine levels does not differ from that of normal subjects. It appears that changes in the circulating catecholamines do not play a significant role in the pathogenesis of exercised-induced asthma.
Seventy-five sera, including sera from 23 patients with aspergillosis, 17 with tuberculosis, asthma or carcinoma, and 35 normal controls, were studied for antibody activity against Aspergillus fumigatus by agar gel double diffusion (DD), counterimmunoelectrophoresis (CIE), indirect hemagglutination (IHA) and indirect immunofluorescence (IF). Metabolic antigens produced from a selected strain of A. fumigatus were used for DD, CIE and IHA, while slide cultures of the same organism were used for IF. The results indicated that sera from the patients with aspergillosis had high IHA and IF titers, while only 91 and 87% were positive for CIE and DD methods, respectively. IHA was more sensitive than DD and CIE, and IF was equally sensitive but had false-positive reactions. CIE was simple and fast, but had false-negative and occasionally false-positive results.
The plastics industry utilizes a number of organic chemicals which have the potential of producing pulmonary reactions, particularly in susceptible individuals. Five workers are reported who were involved in the production of epoxy resins and developed recurrent respiratory symptoms and physiologic abnormalities following exposure to tetrachlorophthalic anhydride (TCPA). Inhalation challenge with TCPA reproduced their symptoms and demonstrated both an immediate and late (4-6 hours) physiologic response. Although the clinical picture strongly suggested a hypersensitivity reaction, immunologic studies failed to demonstrate precipitating or specific IgE antibody. Avoidance of exposure resulted in resolution of symptoms; however, three of the five individuals had residual functional impairment.
Immunologic and inhalation challenge studies were performed on a patient engaged in bathtub refinishing who developed systemic and respiratory symptoms suggestive of hypersensitivity pneumonitis temporally related to his occupation. The refinishing process used a catalyst containing toluene diisocyanate, and all clinical features of the disorder were reproduced by challenge. No immunologic mechanism could be identified. A change of occupation resulted in complete relief of symptoms.