Airborne fungal cell fragments in homes in relation to total fungal biomass.

Fungal exposure may induce respiratory symptoms. The causative agents are compounds in the fungal cell wall. Fragments of microbes may be present in air samples but are not measurable using conventional spore counting or by the determination of viable organisms. This study assesses the proportion of fungal cell biomass and endotoxin in different particle size fractions in air samples from homes. Air samples were collected from 15 homes using a cyclone sampler, collecting particles in three aerodynamic size fractions: <1.0, 1.0-1.8, and >1.8 µm. N-Acetylhexosaminidase (NAHA) was determined as a marker of fungal cell biomass. Endotoxin was determined using the Limulus amebocyte lysate method. NAHA and endotoxin in the size range <1.0 µm comprised up to 63% (mean 22.7%) and 96.3% (mean 22.6%) of the total concentrations, respectively. There were significant relationships between the amounts of NAHA and endotoxin in the total amount and in the size fraction >1.8 µm but not in the smaller fractions. The results demonstrate significant amounts of fungal cell biomass and endotoxin in particles <1.0 µm. Homes with reported mold damage had a lower concentration of NAHA in particles <1.0 µm than homes without mold damage. To assess airborne exposure for diagnostic and preventive purposes, measurement techniques that include this fraction should be considered.

In vitro and in vivo reactivity to fungal cell wall agents in sarcoidosis.

Sarcoidosis is an inflammatory disease. Epidemiological and treatment studies suggest that fungi play a part in the pathogenesis. The aim of this work was to study the effect of fungal cell wall agents (FCWA) on the in vitro secretion of cytokines from peripheral blood monocytes from subjects with sarcoidosis and relate the results to fungal exposure at home and clinical findings. Subjects with sarcoidosis (n=22) and controls (n=20) participated. Peripheral blood mononuclear cells were stimulated with soluble or particulate ß-glucan (S-glucan, P-glucan), chitin or lipopolysaccharide (LPS), whereafter tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and IL-12 were measured. The severity of sarcoidosis was determined using a chest X-ray-based score. Serum cytokines (IL-2R, IL-6, IL-10 and IL-12) were determined. To measure domestic fungal exposure, air in the bedrooms was sampled on filters. N-acetylhexosaminidase (NAHA) on the filters was measured as a marker of fungal cell biomass. The induced secretion of cytokines was higher from peripheral blood mononuclear cells (PBMC) from subjects with sarcoidosis. P-glucan was more potent than S-glucan inducing a secretion. Chitin had a small effect. Among subjects with sarcoidosis there was a significant relation between the spontaneous PBMC production of IL-6, IL-10 and IL-12 and the NAHA levels at home. The P-glucan induced secretion of IL-12 was related to the duration of symptoms at the time of diagnosis. Their X-ray scores were related to an increased secretion of cytokines after stimulation with LPS or P-glucan. Subjects with sarcoidosis have a higher reactivity to FCWA in vitro and to home exposure. The influence of FCWA on inflammatory cells and their interference with the inflammatory defense mechanisms in terms of cytokine secretion could be important factors for the development of sarcoidosis.

[Feasibility of a screening programme for lung cancer among workers previously heavily exposed to asbestos]. / Valutazione di un programma per la diagnosi precoce di cancro polmonare negli ex esposti ad asbesto.

BACKGROUND: We evaluated the feasibility and costs of a screening programme with spiral CT for the early diagnosis of lung cancer among workers previously heavily exposed to asbestos. METHODS: We invited 2000 workers, 1165 (58%) of whom accepted. Women and individuals with incomplete information were excluded; 1119 subjects (mean age, 57 years) entered the main analysis. Subjects with non-calcified lung nodules and/or dubious pleural plagues (No=338) entered a post-screening diagnostic protocol based on radiological follow-up. RESULTS: Twenty-five biopsies were performed (13 pulmonary, 9 pleural, 3 combined) revealed 5 cases of lung cancer (including 1 in stage IA). The positive predictive value of the screening test was low (31%) despite its known high sensitivity (100%) and specificity (99%). Incidence of lung cancer was similar to that registered among male residents of the Veneto Region aged 55 to 59 years. The cost of the programme was Euro 1,000 per screened subject and Euro 245,000 per diagnosis (total cost, Euro 1,181,310). The total radiation dose administered to healthy subjects was about 1,100 mSv (220 mSv per lung cancer diagnosis). CONCLUSIONS: This screening programme was ineffective due to the low participation rate, the small number of diagnoses, low predictive value, and high costs.

Exposure to hydrogen peroxide and eye and nose symptoms among workers in a beverage processing plant.

OBJECTIVES: Two cross-sectional studies were undertaken on workers in a beverage processing plant to investigate the association between low H(2)O(2) exposure and symptoms of irritation (2005 study) and to investigate the effect of wearing respiratory protection (2006 study). METHODS: The study comprised 69 workers exposed to H(2)O(2) in sterile chambers and 65 unexposed controls. The exposure was assessed from measurements and work task information from employment records. The severity of work-related symptoms was evaluated using questionnaires. Data were analyzed by the Student's t-test, multiple linear regression and analysis of variance for repeated measures of symptoms. RESULTS: Symptoms of eye, nose and throat irritation were significantly (P < 0.001) more severe among exposed workers compared to controls. Exposure values were occasionally above American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value-time-weighted average (TLV-TWA) in the sterile chambers. The relationship between the severity of symptoms and the number of entrances in the chambers was significant (P < 0.0001) in 2005 but not in 2006, when respirators were used during work in the sterile chamber. No differences were found between exposed who entered a sterile chamber in 2005 but not in 2006 and exposed who entered a sterile chamber both in 2005 and 2006. This suggests that respirators provided an efficient protection and that the irritative effects of exposure to H(2)O(2) in 2005 did not disappear after 1 year. CONCLUSIONS: The source of risk was exposure in the sterile chamber, even though the time of exposure was generally only approximately 30 min. To ensure complete worker protection, there is a need for a short-term exposure limit for H(2)O(2) in addition to the existing ACGIH TLV-TWA value.

Moldy environments and toxic pneumonitis.

Exposure to organic dusts might cause an acute reaction with influenza like symptoms (toxic pneumonitis). Although it is well known that endotoxin, which is often present in organic dusts, may cause this reaction, there is no information about fungal cell wall agents as causative agents. The capacity of different fungal cell wall agents to induce an acute inflammation was evaluated in animal inhalation experiments. Guinea pigs were exposed to an aerosol of endotoxin, molds, and different fungal cell wall agents (FCWA) in a continuous flow exposure chamber, and the number of free lung cells was determined 24 h thereafter. Endotoxin caused a dose-dependent increase in the number of neutrophils and macrophages. None of the other agents tested caused a neutrophil response. The results suggest that toxic pneumonitis in environments with organic dusts is caused by the presence of inhaled endotoxin. Although no effect from FCWA was found, it is well known that this inhalation under chronic conditions will cause lung disease, particularly granulomatous pneumonitis.

Lung and other cancer site mortality in a cohort of Italian cotton mill workers.

BACKGROUND: Several studies report a lower than expected mortality in lung cancer among workers exposed to organic dust. Recent studies also reported a decreased risk for cancer at other sites. OBJECTIVES: To evaluate the mortality from lung and other cancer sites in cotton mill workers. MATERIAL AND METHODS: A cohort of 3961 Italian cotton mill workers was divided into those working with carding (exposed to high levels of endotoxin-containing cotton dust) and other tasks, which generally have lower exposure. Standardised mortality ratios (SMRs), with 95% confidence intervals (CI), were calculated using death rates of the regional general population as a reference. Cancer mortality was analysed in relation to the length of employment in the two task groups. An internal analysis was also performed through Poisson regression. RESULTS: Among workers in carding departments, lung cancer SMRs were 1.88 (CI: 0.69 to 4.08), 1.01 (CI: 0.20 to 2.94) and 0.22 (CI: 0.00 to 1.24), respectively, for <6, 6-12 and >12 years of employment (chi(2) for trend = 5.45; p<0.05). A significant (p = 0.04) trend was confirmed by Poisson regression. No reduced risks were found for other forms of cancer, nor for those working with other tasks. CONCLUSIONS: The results support previous reports that a high and prolonged exposure to cotton dust and other endotoxin-containing organic dusts is related to a lower risk of lung cancer. There was no indication of a reduced risk for other forms of cancer.

Muscularity and adiposity in addition to net acid excretion as predictors of 24-h urinary pH in young adults and elderly.

OBJECTIVE: In patients with nephrolithiasis, an inverse relationship between 24-h urinary pH (24h-UpH) and body weight has been reported. Whether body composition indices and 24h-UpH are similarly associated in healthy subjects needs investigation. DESIGN: Cross-sectional, retrospective analysis. SETTING: Dortmund, Germany and Gothenburg, Sweden. SUBJECTS: Healthy young adults (18-23 years; n=117) and elderly (55-75 years; n=85) having a mean body mass index (BMI) of 22.80+/-3.4 and 25.3+/-3.9 kg/m2, respectively. METHODS: Anthropometric data, 24h-UpH, and 24-h urinary excretion rates of net acid (NAE), creatinine, and urea were determined. After adjusting for urea (reflecting protein intake), renal creatinine output was used as a biochemical marker for muscularity. The BMI served as a marker of adiposity. RESULTS: NAE, body weight, and BMI were significantly (P<0.05) higher, and height and creatinine significantly lower in the elderly, whereas body-surface area (BSA) was not different. Step-wise multiple regression analysis using BSA-corrected urinary variables revealed NAE as the primary predictor of 24h-UpH (with R2 values of 0.64 and 0.68 in young adults and elderly, respectively, P<0.0001), followed by urea (P<0.0001), creatinine (P<0.05), and BMI (P<0.05 for the young adults and P=0.12 for the elderly). These associations were negative for NAE and BMI, and positive for urea and creatinine. CONCLUSIONS: Muscularity (i.e. creatinine adjusted for urea) and particularly in the group of young adults, adiposity (i.e. BMI) proved to be modest, but significant predictors of 24h-UpH. Future research should focus on more obese subjects in whom insulin resistance and particular kidney functions should also be examined to further substantiate the role of obesity in low-urine pH-associated conditions, for example, nephrolithiasis.

(1-->3)-beta-D-glucan does not induce acute inflammation after nasal deposition.

To assess if (1-->3)-beta-D-glucan, a microbial cell wall agent normally present in pollen, has the ability to produce pollenlike response, sensitive persons received a nasal deposition of two doses of (1-->3)-beta-D-glucan. The percentage of eosinophils and amount of eotaxin were measured in nasal lavage 30 minutes and 24 hours after challenge. No effect could be demonstrated. The absence of an inflammatory response after (1-->3)-beta-D-glucan application confirms earlier findings in inhalation studies.

Slight respiratory irritation but not inflammation in mice exposed to (1-->3)-beta-D-glucan aerosols.

Airway irritation effects after single and repeated inhalation exposures to aerosols of beta-glucan (grifolan) were investigated in mice. In addition, the effects on serum total immunoglobulin E (IgE) production and histopathological inflammation in the respiratory tract were studied. The beta-glucan aerosols provoked slight sensory irritation in the airways, but the response was not concentration dependent at the levels studied. Slight pulmonary irritation was observed after repeated exposures. No effect was found on the serum total IgE levels, and no signs of inflammation were seen in the airways 6 h after the final exposure. The results suggest that, irrespective of previous fungal sensitization of the animals, inhaled beta-glucan may cause symptoms of respiratory tract irritation but without apparent inflammation. Respiratory tract irritation reported after inhalation of fungi may not be entirely attributed to beta-glucan.

Mould exposure at home relates to inflammatory markers in blood.

Living in damp buildings has been associated with airway symptoms, suspected to be due to inflammatory reactions. The relationship between home exposure to mould and signs of inflammation was, therefore, studied. Nonsmoking subjects with a high (G-high, > 4.0 ng x m(-3), n = 17) or low (G-low, < 2.0 ng x m(-3), n = 18) amount of airborne beta(1 --> 3)-D-glucan, an indicator of mould biomass, in the home were recruited. Blood samples were analysed for granulocytic enzymes, T-cell subsets and the secretion of cytokines from in vitro incubated peripheral blood mononuclear cells (PBMCs). In the G-high group, the proportion of cytotoxic T-cells (CD8+S6F1+) was lower and secretion of tumour necrosis factor-alpha from PBMCs higher than in the G-low group. There were no significant differences in secretion of interferon gamma and interleukin (IL)-4 from PBMCs between the two groups. Among nonatopic subjects, the ratio between interferon gamma and IL-4 was significantly higher in the G-high group than in the G-low group and was related to the amount of beta(1 --> 3)-D-glucan in the home. No significant differences were found regarding secretion of IL-10 or IL-Ibeta from PBMCs, eosinophil cationic protein or myeloperoxidase in serum, or differential cell counts in blood. The effects found on inflammatory markers in relation to beta(1 --> 3)-D-glucan in the home suggest upregulation of some parts of the inflammatory/immunological system due to mould exposure.

Work related symptoms among sewage workers: a nationwide survey in Sweden.

AIMS: To assess the risk for work related symptoms among sewage workers in Sweden using a postal questionnaire. METHODS: All municipalities in Sweden were contacted and asked to provide addresses of sewage workers and controls. Controls were recruited among other municipal workers not exposed to sewage, such as workers in drinking water plants and gardeners. A questionnaire was sent to the subjects and after two reminders, the response rate was 74% among sewage workers and 59% among controls. RESULTS: Significantly increased risks for airway symptoms, chronic bronchitis, and toxic pneumonitis, as well as central nervous system symptoms such as headache, unusual tiredness, and concentration difficulties were found among the sewage workers compared with controls. Furthermore, an increased risk for non-specific work related gastrointestinal symptoms was found among the sewage workers; an increased risk for joint pains, related to pains in more than four joints but not with loading, was also found. CONCLUSIONS: The results of this questionnaire survey show an increased risk for airway, gastrointestinal, and general symptoms such as joint pains and central nervous system symptoms among sewage workers. Clinical investigations are needed to determine the cause of the reported symptoms among sewage workers, and further field studies are required to assess the causal agents.

Microbial cell wall product contamination of bedding may induce pulmonary inflammation in rats.

To test the hypothesis that airborne microbial cell wall components could induce an inflammatory response in the lungs, measurements were made of the amounts of bacterial endotoxin and (1-->3)-beta-D-glucan in laboratory animal bedding materials. Groups of rats were exposed by inhalation to airborne endotoxin, (1-->3)-beta-D-glucan or a combination of the two for 5 weeks. The results demonstrated that measurable amounts of endotoxin and (1-->3)-beta-D-glucan could be detected in the different bedding materials. In contrast to animals at delivery, those kept on bedding for 5 weeks showed moderate inflammatory reactions in the lung. These were most pronounced among animals exposed to endotoxin and (1-->3)-beta-D-glucan. The results suggest that further studies need to be undertaken to elucidate the role of microbial cell wall products in the development of inflammatory lung responses among research animals.

Effects after inhalation of (1-->3)-beta-D-glucan in healthy humans.

BACKGROUND AND AIM: This study was performed to assess the effects of an exposure to a pure (1-->3)-beta-D-glucan, a cell wall component of fungi, plants and certain bacteria. METHODS: Twenty-one healthy subjects inhaled saline or (1-->3)-beta-D-glucan suspended in saline in a random, double-blind, cross-over design. They were examined before exposure and 24 and 72h afterwards with spirometry, blood sampling and collection of induced sputum. Differential cell counts and eosinophilic cationic protein (ECP) were determined in blood and sputum, and myeloperoxidase (MPO), tumour necrosis factor-alpha (TNF-alpha), and interleukin (IL)-8 and IL-10 were determined in sputum supernatants. TNF-alpha was determined after cultivation of blood mononuclear cells. RESULTS: In sputum, inhalation of saline caused a significant increase in ECP and TNF-alpha. (1-->3)-beta-D-Glucan inhalation caused a further increase in these cytokines, although not statistically significantly different from the increase induced by inhalation of saline alone. In blood, the number of eosinophils was significantly decreased 72 h after the challenge with (1-->3)-beta-D-glucan. This effect was not found after the inhalation of saline alone. TNF-alpha production from stimulated blood mononuclear cells was significantly decreased 72 h after the (1-->3)-beta-D-glucan inhalation as compared with the increase induced by saline inhalation. CONCLUSIONS: The results suggest that (1-->3)-beta-D-glucan causes a different type of response as compared with inflammatory agents such as bacterial endotoxin that cause a neutrophil-dominated inflammatory response.

Moderate alcohol consumption and urinary excretion of magnesium and calcium.

The aim of this study was to evaluate the magnesium (Mg) status of male subjects consuming moderate amounts of alcohol (n = 14) in comparison with that of a group of non-consumers of alcohol (n = 10). Plasma ionized Mg levels and total erythrocyte Mg content were determined as well as the excretion of Mg in urine before and after an oral loading test. Intake of Mg via food and water was estimated using a one-week dietary records. The results showed a significantly higher, alcohol dose-related excretion of Mg and Ca (calcium) in the urine after the oral Mg load among consumers of alcohol. Although the study is based on a small number of subjects with differences in smoking habits, it is suggested that alcohol consumption even in moderate amounts could contribute to Mg deficiency.

Healthy subjects express differences in clinical responses to inhaled lipopolysaccharide that are related with inflammation and with atopy.

BACKGROUND: Endotoxin and its purified derivative LPS are important contaminants of both domestic and occupational environments that have been related to airway diseases. A body of data suggests that there is considerable interindividual variability in LPS sensitivity. OBJECTIVE: The aim of the study was to relate the individual clinical responses to inhaled LPS with the inflammatory process and the atopic status. METHODS: Fifteen healthy subjects were challenged each week by inhalation with saline solution or LPS (0.5, 5, or 50 microg). The systemic response was defined by the increase in body temperature, blood neutrophilia, acute-phase proteins (C-reactive protein and LPS-binding protein [LBP]), and E-selectin. The LPS-induced airway response was defined as the increase in airway responsiveness and related to the cell count and concentration of TNF-alpha, myeloperoxidase, and eosinophil cationic protein in induced sputum. The atopic status was defined as an increase in IgE or a positive skin prick test result. RESULTS: Subjects (n = 7) with a significant increase in body temperature had a larger increase in the systemic inflammatory response (blood neutrophilia; P <.01) and in blood concentrations of C-reactive protein (P <.02) and LBP (P <.01). Subjects with a significant increase in airway responsiveness (n = 8) had an increase in the sputum concentration of eosinophil cationic protein (P <.01). The amplitude of the systemic response (increase in body temperature [P <.001], blood neutrophilia [P <.02], and rise in LBP [P <.05] and decrease in FEV(1) [P <.01]) were inversely associated with the atopic status, suggesting a link between atopy and LPS responsiveness. CONCLUSIONS: The clinical response to LPS occurs systemically or locally and is associated with inflammation. The atopic status was inversely related to the systemic inflammation.

Inhalation of (1-->3)-beta-D-glucan causes airway eosinophilia.

BACKGROUND: Moulds are present in a variety of environments and aerosols of fungal spores are generated when mouldy materials are handled. Molds contain (1-->3)-beta-D-glucan, a polyglucose which is present in the cell wall of fungi, certain bacteria and plants. AIM: This study was undertaken to investigate the cellular inflammatory response in the lung after inhalation of (1-->3)-beta-D-glucan and bacterial endotoxin. METHODS: Guinea pigs were exposed daily to an aerosol of pure (1-->3)-beta-D-glucan and pure endotoxin for five weeks. Lung lavage and lung interstitial cell preparations were done and the inflammatory cells counted. Histological sections were prepared from the trachea. RESULTS: There was an increase in eosinophil numbers in lung lavage, lung interstitium, and the airway epithelium of animals exposed to (1-->3)-beta-D-glucan. In animals simultaneously exposed to endotoxin, there was no increase in eosinophils. In the lung interstitium, (1-->3)-beta-D-glucan exposure caused an increase in lymphocytes, which was not found after endotoxin exposure. Endotoxin exposure caused an increase in neutrophils and macrophages in lung lavage, which was not found after (1-->3)-beta-D-glucan exposure. CONCLUSIONS: The results support previous findings that (1-->3)-beta-D-glucan causes a different response in the airways as compared to endotoxin. Endotoxin modulated the increase in eosinophils caused by (1-->3)-beta-D-glucan exposure, suggesting a complex interaction between the microbial cell wall components.