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Biomedical subjects

M Roponen

Publications and source records attributed to M Roponen.

10 recordsLinked to original sources
PubMed2006

Aspergillus fumigatus challenge increases cytokine levels in nasal lavage fluid.

Several studies have shown an association between exposure in moisture-damaged buildings and adverse health effects. There are several indicator microbes of moisture damage, but Aspergillus fumigatus is one of the best-documented molds provoking health problems in different occupational conditions. We assessed whether inhalation of a commercial A. fumigatus solution would affect cytokine levels (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, IL-4, IL-6, interferon [IFN]-gamma) in nasal lavage fluid (NAL) compared with that evoked by placebo challenge. Twenty-seven subjects were studied: 13 had occupational exposure in a moisture-damaged building, 4 were atopic, and 10 were considered as controls. In all the subjects, the IL-1beta levels were increased significantly both at 6 (p = 0.013) and 24 h (p = .005) after the A. fumigatus challenge compared to placebo. In subjects with previous occupational exposure in a moisture-damaged building, IL-4 concentrations were increased significantly both at 6 (p =.046) and 24 h (p =.008) after the A. fumigatus challenge compared with placebo. Furthermore, in the control group, TNF-alpha levels were significantly increased at 6 h after the A. fumigatus challenge compared to placebo (p = .028). Thus, these data show a link between markers of inflammation in NAL and experimental A. fumigatus challenge.

Adult↗
PubMed2006

Dust sampling methods for endotoxin - an essential, but underestimated issue.

Exposure to farming environment in early life has been associated with lower risk for allergic diseases possibly caused by increased exposure to endotoxin. The aims of this study were to compare the reproducibility of different sampling methods for endotoxin, and to determine whether environmental characteristics have different effect on endotoxin levels of different sample types. The reproducibility of sampling methods (bed dust, floor dust, vacuum cleaner dust bag dust, settled dust and air samples) was studied with repeated sampling (five visits during 1 year) in five farming and five urban homes. To examine determinants of endotoxin for different types of dust sample, sampling was conducted once in 12 farming and 17 urban homes. Endotoxin was analyzed using Limulus Amebocyte Lysate assay. Bed dust samples had the best reproducibility (intraclass correlation, ICC=66%), but the difference between farming and non-farming homes was not clear with this sample type. The reproducibility of floor (ICC=52%) and settled dust (ICC=51%) was moderate. With these sample types the difference between farming and non-farming homes was clear. Settled dust had some seasonal variation. Based on this study, the best compromise for sampling for endotoxin appears to be floor dust sample followed by bed and settled dust samples. Practical Implications Endotoxins have been widely measured, even though the validity of different sample types to reflect the endotoxin exposure level of an indoor environment is poorly known. This study shows that bed dust samples have the best reproducibility, but they do not reflect the differences in exposure due to environmental factors such as farming. Floor dust samples with moderate reproducibility may be the best choice for sampling of endotoxin in large field studies.

Air Pollution, Indoor↗
PubMed2005

Bacterial strains from moldy buildings are highly potent inducers of inflammatory and cytotoxic effects.

UNLABELLED: We aimed to identify inflammatory and cytotoxic potential of individual indoor air bacterial and fungal strains, as well as extracts of indoor air filter samples containing bacteria and fungi. Mouse RAW264.7 macrophages were exposed in vitro to four bacterial strains; Streptomyces californicus, Mycobacterium terrae, Bacillus cereus and Pseudomonas fluorescens, and three fungal strains; Penicillium spinulosum, Aspergillus versicolor and Stachybotrys chartarum. Furthermore, RAW264.7 macrophages were exposed to indoor air filter sample extracts representing 'low' (n = 21) and 'high' (n = 20) exposure to viable fungi or bacteria. Production of nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) as well as cell viability were measured after 24 h exposure. The results show that the bacterial strains induce more profound production of NO, TNF-alpha and IL-6 than the studied fungal strains. They also decrease the viability of mouse macrophages. Similarly, the indoor air filter samples with high concentration of bacteria induced a statistically significant increase in TNF-alpha and IL-6 production as well as a decrease in cell viability. Altogether, these results suggest that indoor air bacterial strains are potent inducers of inflammatory responses and thus possibly related to adverse health effects of the inhabitants. PRACTICAL IMPLICATIONS: There is abundant documentation of the association between building dampness and mold and adverse health effects on occupants, but the causal agents of the effects are still unclear. In order to reveal these causal links, experimental studies with in vitro and in vivo methods are needed. The present findings shed new light on studies of the microbial constituents of indoor air in moldy buildings responsible for adverse health effects. These results imply that bacteria should also be monitored in cases of suspected microbial contamination of indoor air.

Air Microbiology↗
PubMed2002

Comparison of inflammatory elements in nasal lavage and induced sputum following occupational exposure to moldy-building microbes.

Inflammatory processes in the nasal air passages may reflect corresponding processes in the lower airways due to the similarities in histology of nasal mucosa and bronchi. The objective of the current study was to determine whether the levels of inflammatory markers in nasal lavage fluid could be used as predictors of lower respiratory tract inflammation after exposure to microbes in indoor air of moisture-damaged buildings. Differential cell count, immunochemically measured concentrations of proinflammatory cytokines (Interleukins [IL] IL-1, IL-4, IL-6, and tumor necrosis factor alpha [TNFalpha]) and nitric oxide (NO), assessed as nitrite, were analyzed from nasal lavage (NL) and induced sputum (IS) samples of the occupants (n = 60) working in moisture-damaged and reference school buildings. The measurements of inflammation markers in NL and IS sample pairs, collected on the same day, were compared. Although the levels of NO (p =.026) and IL-4 (p =.014) in NL predicted their levels in IS in a statistically significant manner, their predictive values (6.9% and 7.8%, respectively) were low. There was no significant correlation between the concentrations of the studied proinflammatory cytokines or differential cell counts in NL and IS samples. Our results indicate that measurement of inflammatory mediators in NL is not per se a reliable method to evaluate the inflammatory status of the lower airways after exposure to indoor air pollutants of moisture damaged building. It is possible that NL is a more sensitive indicator of direct exposure to different irritants in inhaled air than is IS. This may be a reflection of the role of nasal mucosa as the primary physicochemical barrier to inhaled air.

Adult↗
PubMed2002

Nitric oxide alone is an insufficient biomarker of exposure to microbes in a moisture-damaged building.

Several epidemiological studies have revealed a large variety of adverse health effects related to exposure to microbes in moisture damaged buildings. Recently some evidence has been reported for a biochemical linkage between microbial exposure and the respiratory symptoms suffered by the occupants. The objective of the current study was to evaluate the value of nitric oxide (NO) measurements in determining the inflammatory status of airways in inhabitants of problem buildings. NO was measured by a chemiluminescence analyzer from the exhaled air. In addition, NO was determined as its metabolite nitrite from nasal lavage (NL) and induced sputum (IS) samples and also via the expression of inducible nitric oxide synthase (iNOS) in the cells. Occupants of moisture-damaged and reference schools were studied. The sampling was performed at the end of the spring term, at the end of the summer vacation, during the winter term, and after a 1-wk winter holiday. No statistically significant differences in NO levels were detected between the studied groups or between exposure and vacation periods. iNOS was not detected from IS or NL samples of the exposed occupants. These results suggest that NO measurements alone are not sufficient to quantify airway inflammation when evaluating subjects exposed to microbes present in moisture-damaged buildings.

Air Pollution, Indoor↗
PubMed2001

Inflammatory responses in mice after intratracheal instillation of spores of Streptomyces californicus isolated from indoor air of a moldy building.

Microbial growth in buildings is associated with respiratory symptoms in the occupants. However, the specific effects of the microbes and the way they provoke clinical manifestations are poorly understood. In the current study, mice were exposed via intratracheal instillation to single doses of the spores of Streptomyces californicus, isolated from indoor air of a moisture-damaged building (2.2 x 10(7), 1.1 x 10(8), and 3.3 x 10(8) spores), or lipopolysaccharide (50 microg). Inflammation and toxicity in lungs were evaluated 24 h later. The time course of the effects was explored with the dose of 1.1 x 10(8) spores for up to 7 days. The microbial spores elevated proinflammatory cytokine (i.e., TNFalpha and IL-6) levels in bronchoalveolar lavage fluid (BALF) and in serum in a dose- and time-dependent manner and evoked expression of inducible nitric oxide synthase in BAL cells. Both TNFalpha and IL-6 responses peaked at 6 h after instillation, but TNFalpha leveled off more quickly than IL-6. The cytokine surge was followed by inflammatory cell recruitment into airways. Moreover, the spores increased dose- and time-dependently total protein, albumin, hemoglobin, and lactate dehydrogenase concentrations in BALF during the first 24 h. Histopathological examination of lungs confirmed the inflammatory changes. With the exception of macrophage and lymphocyte numbers, all parameters returned to control level at 7 days. In summary, these observations indicate that the spores of S. californicus are capable of provoking an acute inflammation in mouse lungs and can cause cytotoxicity. Thus, S. californicus can be considered as a species with potential to cause adverse health effects in occupants of moisture-damaged buildings.

Air Microbiology↗
PubMed2001

Differences in inflammatory responses and cytotoxicity in RAW264.7 macrophages induced by Streptomyces Anulatus grown on different building materials.

Streptomyces anulatus, an indicator microbe of mold in buildings, was grown on different building materials in order to study the impact of growth conditions on the ability of the spores of this microbe to induce toxicity and inflammatory responses. The microbes were grown for 2 months on sterilized and unsterilized wood, chipboard, concrete, plaster board and mineral wool in tight glass vessels under humid conditions. The highest microbial spore concentration was detected on the sterilized mineral wool followed by the sterilized plaster board and the unsterilized mineral wool. Mouse RAW264.7 macrophages were exposed in vitro for 24 h to the spores of S. anulatus and the production of the inflammatory mediators, nitric oxide (NO), tumor necrosis factor alpha (TNF alpha), interleukin-6 (IL-6), interleukin-10 (IL-10) and cytotoxicity, were measured. The dose equivalent to 5 x 10(5) spores/ml of medium was used to compare the different materials. The most intense production of NO (11.6 microM), TNF alpha (560 pg/ml) and IL-6 (2800 pg/ml) in macrophages was induced by the spores grown on sterilized plaster board. They also caused the greatest loss of cell viability (39%). The spores grown on sterilized concrete induced significant production of NO (1.5 microM) and decreased cell viability (22%), and the spores grown on unsterilized and sterilized mineral wool increased production of NO (4.1 microM and 0.8 microM, respectively). The spores did not stimulate production of the anti-inflammatory cytokine IL-10. These results indicate that the ability of S. anulatus to induce inflammatory responses and cytotoxicity in macrophages is dependent on the growth conditions provided by different building materials.

Air Pollution, Indoor↗
PubMed2001

Inflammatory mediators in nasal lavage, induced sputum and serum of employees with rheumatic and respiratory disorders.

Exposure to microbes present in mould-damaged buildings has been linked to increased frequency of various inflammatory diseases. The current study examined differences in inflammatory mediators in nasal lavage (NAL), induced sputum (IS) and serum of occupants with rheumatic or respiratory disorders and their controls, all working in the same moisture-damaged building. Exhaled nitric oxide (NO) measurements, lung function tests, skin-prick tests and health data collection by questionnaire were performed. Concentrations of NO, interleukin (IL)-1, IL-4, IL-6 and tumour necrosis factor-alpha in NAL, IS and serum (excluding NO and IL-1) of the subjects were measured during an occupational exposure period and the vacation period without such exposure. The concentrations of IL-4 in NAL fluid were significantly higher among all occupants during the working period (geometric mean 8.5 microg x mL(-1), range 0-206.5 microg x mL(-1)), as compared to that during vacation (0.4 microng x mL(-1) range 0-3.7 pg x mL(-1)) (p = 0.008). Absence from the work environment also significantly diminished reporting of symptoms. IL-4 levels in the serum of case subjects were significantly higher than in controls. Moreover, employees with respiratory symptoms had markedly higher exhaled NO values than their controls (p = 0.028). In summary, these data suggest that mediators in nasal lavage samples reflect the occupational exposure to moulds, whereas possible indicators of existing disorders are detectable in serum.

Adult↗
PubMed1999

Nitric oxide and proinflammatory cytokines in nasal lavage fluid associated with symptoms and exposure to moldy building microbes.

Epidemiological data indicate that living or working in a moldy building is associated with increased risk of respiratory symptoms and disease related to inflammatory reactions, but biochemical evidence linking cause and effect is still scarce. The staff working in a mold-contaminated school, and a reference group without such exposure, were studied. Nasal lavage was performed and health data were collected with a questionnaire at the end of the spring term, after a 2.5-mo summer vacation, and at the end of the fall term. Here we show that concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and nitric oxide (NO) in nasal lavage fluid were significantly higher in the exposed than in the control subjects at the end of the first exposure period. These inflammatory mediators decreased to reference group concentrations during the period when there was no exposure and the production of NO and IL-6 increased again during the reexposure in the fall term. Reports of cough, phlegm, rhinitis, eye irritation, and fatigue paralleled the changes in the measured inflammatory markers. These results point to an association between inflammatory markers in the nasal lavage fluid, the high prevalence of respiratory symptoms among the occupants, and chronic exposure to molds in the indoor environment.

Adult↗