An investigation of the relationship between microbial and particulate indoor air pollution and the sick building syndrome.

The sick building syndrome has been the subject of research for approximately 10 years. Although it is often suggested that symptoms in office workers are due to circulating micro-organisms or particles, epidemiological studies investigating the relationship between them have been lacking. This cross-sectional study has combined medical and aerobiological assessments of offices in Great Britain and has found that, although airborne particulates and micro-organisms are unlikely to be the sole cause of the sick building syndrome, positive associations between symptom prevalence rates and levels of airborne viable bacteria and fungi within groups of buildings with similar ventilation systems, suggest a possible causal link that should be explored.

The effect of smoking on the development of allergic disease and specific immunological responses in a factory workforce exposed to humidifier contaminants.

The effects of smoking on the development of work related asthma and on the production of specific IgE and IgG antibodies to antigen from a contaminated humidifier are described for a sample of 258 workers from a printing factory. Current smoking was associated with low production of IgG antibody but with higher production of IgE antibody. No dose response for either antibody was found when numbers of cigarettes or pack-years smoked were considered. Work related asthma was detected in 12 workers by peak flow recordings. Six were current smokers and one was an ex-smoker. One subject with work related asthma had a high (and one a marginal) concentration of specific IgE to humidifier antigen.

Characterization of immunologically important antigens and allergens of Aspergillus fumigatus.

Using a variety of immunochemical methods, including quantitative immuno-electrophoretic techniques, combined with gel filtration and iso-electric focusing, and production of monospecific antisera for identification and affinity purification, 4 major components of Aspergillus fumigatus have now been partially characterized. Numbering of these was derived from a reference allergic bronchopulmonary aspergillosis (ABPA) self-crossed radio-immuno-electrophoresis pattern of reactivity. Two major intracellular/cytoplasmic, concanavalin A (Con A)-binding antigens, Ag 7 and Ag 13, of molecular weights 150-200 and 70 kilodaltons (kD), respectively, were confirmed to be of importance for both ABPA and aspergilloma in specific sandwich enzyme-linked immunosorbent assays. A rapidly released component, Ag 5, of molecular weight 35 kD, proved both antigenic and allergenic, with aspergilloma patients having especially high-titre IgG antibodies. The major allergenic component Ag 3, of molecular weight 24 kD by gel filtration and 18 kD by SDS-PAGE was, like Ag 5, relatively heat-labile and non-Con-A-binding. Interestingly, T cell clones have been identified which respond primarily to an 18-kD fraction.

Allergy to rats: quantitative immunoelectrophoretic studies of rat dust as a source of inhalant allergen.

The antigenic composition of an extract of rat dust, as a source of aeroallergens for rat-sensitive individuals, has been investigated and compared to the antigenic composition of rat saliva and urine. Of four main antigenic peaks identified by crossed immunoelectrophoresis, one antigenic peak (Ag 4) was demonstrated to be antigenically closely related to and with similar molecular weight (approximately 22 kd) and isoelectric point values as urinary prealbumin, already recognized as a major rat allergen. Ag 4 was present in all dusts studied and was also identified as a minor component of saliva. However, no component with the same electrophoretic mobility or physicochemical characteristics of the alpha 2-euglobulin of male rat urine that shares partial identity with the prealbumin was detected, even in dust collected from a male rat room. A second high molecular weight (greater than 200 kd) component, Ag 1, present in most of the dust extracts, could not be detected in either urine or saliva. Crossed immunoelectrophoresis and skin prick tests confirmed the allergenicity of both these antigens. Analysis of an air filter sample taken within a male rat room revealed significant amounts of the "prealbumin" component, and a monospecific antiserum to this component was used to quantitate levels in dusts collected from various locations. These findings suggest that a major inhalant allergen present in rat dust is closely related to urinary prealbumin but that this and other allergenic components may not be derived predominantly from rat urine or saliva but possibly from secretions originating from the skin of the animals and present in the fur.

Amoebae and humidifier fever.

One hundred and nineteen sera from workers at four different work sites exposed to different contaminated humidifiers were examined by the immunofluorescent antibody (IFA) technique for antibodies to the amoebae Acanthamoeba polyphaga and Naegleria gruberi. Twenty-five of the sera were from workers with humidifier fever (HF) and six from workers with work related asthma (WRA) shown to be due to the contaminated humidifiers. A positive IFA test was found to correlate precipitin reaction to humidifier antigen, but did not correlate with smoking habit, work related symptoms (detected by standard questionnaire) or with HF or WRA. Amoebae were identified in all humidifiers studied.

Antigens and allergens of Aspergillus fumigatus. I. Characterization by quantitative immunoelectrophoretic techniques.

Both the IgG (precipitinogen) and IgE combining components of Aspergillus fumigatus have been studied by quantitative immunoelectrophoretic techniques with sera of patients with allergic bronchopulmonary aspergillosis and specific rabbit antisera. Considerable batch-to-batch variation in biochemical properties and in immunologic (both antigenic and allergenic) activity was revealed in identically prepared culture-filtrate antigens of the same strain of A. fumigatus. Profiles of crossed immunoelectrophoresis/crossed radioimmunoelectrophoresis appeared to vary qualitatively; however, the differences in antigenicity and allergenicity were demonstrated by crossed-line immunoelectrophoretic techniques to be essentially quantitative rather than qualitative in nature. Both types of activity were concentrated in the protein fraction obtained by salt precipitation, and little activity remained in the predominantly polysaccharide supernatant that accounted for greater than 30% (dry weight) of the antigenic extract. Heat-stability studies demonstrated a varied pattern of denaturation. Certain allergenic components were stable to considerable heating, and the extracts so treated were still active on skin testing.

Factors affecting the development of precipitating antibodies in workers exposed to contaminated humidifiers.

A total of 601 sera from groups of workers exposed to heavily and moderately contaminated humidifiers respectively were examined by the double diffusion test for precipitating antibodies to humidifier extracts. Clinical information was obtained using a standardized questionnaire. Skin-prick tests to control, to three common inhalant antigens and to an extract from the humidifier were performed in 103 subjects exposed to a heavily contaminated humidifier. In this environment a strong inverse relationship between current smoking and precipitins was detected (P less than 0.001). Pack years smoked had no bearing on precipitin level. In the larger study there was a clear dose response effect of smoking on precipitins. The effect of smoking appeared to reverse within 3 years. Duration of exposure also had a major effect on the development of precipitins with a clear 'dose response' again being seen in the larger study. These relationships did not apply in the groups exposed to moderately contaminated humidifiers. Levels of airborne antigen were measured using a competitive ELISA inhibition assay and were found to be much lower in sites with moderately contaminated humidifiers than at sites with heavily contaminated humidifiers. Our results suggest that the airborne antigen level is crucial in determining the pattern and strength of precipitin response in smokers and non-smokers exposed to contaminated humidifiers.

Balkan (endemic) nephropathy.

The clinical and pathological features of Balkan (endemic) nephropathy are discussed and correlations of incidence with excess late summer and autumn rainfall outlined. Cultures of a strain of Penicillium verrucosum var. cyclopium isolated from maize collected in an endemic area were fed to rats and lesions were produced in the straight third segment of the proximal kidney tubules. Extensive degeneration and nuclear changes were seen and on prolonged feeding further nuclear enlargement (to greater than 6n) and the formation of multinucleate cells occurred. The relevance of these findings to the clinical disease in man, especially the occurrence of urinary tract tumours, and the evidence supporting mycotoxin involvement, are discussed.

An ultrastructural investigation of nephrotoxicity in rats induced by feeding cultures of Penicillium verrucosum var. cyclopium.

A renal tubular lesion was induced in male rats by giving them a culture homogenate or culture filtrate of Penicillium verrucosum var. cyclopium by gastric gavage for 20 days. The fungus was obtained from stored maize in an area of endemic nephropathy in Bulgaria. Changes in the proximal convoluted tubules were studied by light and electron microscopy. The lesion was confined to the pars recta in the outer stripe of the outer zone of the medulla. It consisted of degeneration and necrosis of epithelial cells, prominent karyomegaly, arrested mitotic divisions and production of binucleate and tetranucleate tubular cells. Two patterns of degeneration occurred with comparable frequency: a vesicular form with pyknotic nucleus and electron lucent degeneration. Nuclei of the epithelial cells in affected tubules contained segregated nucleoli. The necrotic cells were replaced by actively regenerating cells derived from adjacent viable epithelium. The similarity between the tubular lesions induced in rats and the changes found in patients with Balkan endemic nephropathy is discussed.

Balkan (endemic) nephropathy and a toxin-producing strain of Penicillium verrucosum var cyclopium: An experimental model in rats.

Cultures of an isolate of Penicillium verrucosum var. cyclopium, obtained from stored maize in an area of Balkan (endemic) nephropathy--Vratza, Bulgaria--has consistently induced renal tubular lesions when force-fed to rats for 20 days. The lesions, confined to the lower reaches of the proximal convoluted tublues (pars recta and junctional zone), closely resemble the tubular changes in patients with Balkan nephropathy. Preliminary evidence suggests that this nephrotoxin-producing strain of P. verrucosum var. cyclopium may be implicated in the aetiology of Balkan nephropathy.