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Biomedical subjects

Torben Sigsgaard

Publications and source records attributed to Torben Sigsgaard.

At least 19 recordsLinked to original sources
PubMed2005

A single exposure to organic dust of non-naïve non-exposed volunteers induces long-lasting symptoms of endotoxin tolerance.

BACKGROUND: Work with occupational levels of organic dust is associated with a chronic inflammatory response that must somehow be controlled. Endotoxin tolerance has previously been described in vitro and animal studies as a mechanism that modifies the threshold at which response occurs. OBJECTIVE: We investigated the response of non-naïve, currently non-exposed persons to a single exposure of organic dust in a swine confinement building. METHODS: We exposed 16 non-naïve persons in a swine confinement building with low-to-moderate representative levels of organic dust and characterized their acute immune response. RESULTS: Under work-like 3-hour exposure conditions, non-naïve volunteers developed an inflammatory response documented by an increase in interleukin-6 (IL-6) in bronchoalveolar lavage (BAL) from 3.1 to 6.1 pg/ml and visual indices of bronchial inflammation. Similarly, serum IL-6 increased with a peak 3 h after exposure. Tumor necrosis factor (TNF)-alpha was not detected in BAL, and serum TNF-alpha was reduced from 3.7 pg/ml at baseline to less than 2 pg/ml within 3 h after exposure, and remained decreased until 2 weeks after exposure. This is a cardinal marker for immune suppression which was confirmed by other markers: reduction in HLA-DR expression on alveolar macrophages and CD14 expression on blood monocytes. CONCLUSION: We report findings that suggest that long-lasting endotoxin tolerance and immune suppression may be induced by a brief exposure to organic dust concentrations in the medium-low range of occupational levels.

Adult↗
PubMed2005

Respiratory allergy in agricultural workers: recent developments.

PURPOSE OF REVIEW: To review recent evidence on the relationship between occupational exposure to allergens and asthmagens, and risk for developing allergy and asthma and the role of modifying factors in farmers and farm workers. RECENT FINDINGS: Recent studies identified agents that have not been associated with allergy or asthma in farming populations before. The most intriguing findings, however, are those that suggest that the development of atopy and asthma might be influenced by exposure to pathogen associated molecular patterns (PAMPs), including endotoxin. SUMMARY: The adverse and potentially protective effects of microbial exposures in the farm environment are discussed. Recent findings indicate that it is very likely that the protective effect of exposure to PAMPs such as endotoxin is not limited to childhood age. The protective effects that probably developed during childhood can still be observed at adult age. Furthermore, it even seems likely that exposures at adult age (in occupational environments), which stimulate the innate immune system, have an effect on allergy, independently of childhood exposure. It is hypothesized that reversal of atopy might occur as a result of high exposure to endotoxins and other PAMPs.

Agricultural Workers' Diseases↗
PubMed2005

Phthalates in indoor dust and their association with building characteristics.

In a recent study of 198 Swedish children with persistent allergic symptoms and 202 controls without such symptoms, we reported associations between the symptoms and the concentrations of n-butyl benzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP) in dust taken from the childrens' bedrooms. In the present study we examined associations between the concentrations of different phthalate esters in the dust from these bedrooms and various characteristics of the home. The study focused on BBzP and DEHP because these were the phthalates associated with health complaints. Associations have been examined using parametric and nonparametric tests as well as multiple logistic regression. For both BBzP and DEHP, we found associations between their dust concentrations and the amount of polyvinyl chloride (PVC) used as flooring and wall material in the home. Furthermore, high concentrations of BBzP (above median) were associated with self-reported water leakage in the home, and high concentrations of DEHP were associated with buildings constructed before 1960. Other associations, as well as absence of associations, are reported. Both BBzP and DEHP were found in buildings with neither PVC flooring nor wall covering, consistent with the numerous additional plasticized materials that are anticipated to be present in a typical home. The building characteristics examined in this study cannot serve as complete proxies for these quite varied sources. However, the associations reported here can help identify homes where phthalate concentrations are likely to be elevated and can aid in developing mitigation strategies.

Case-Control Studies↗
PubMed2004

Ex vivo induction of cytokines by mould components in whole blood of atopic and non-atopic volunteers.

We investigated the time-course release of IL-1beta and IL-8 protein as well as the steady state mRNA level of their genes in human whole blood after stimulation with LPS, beta-1,3-D-glucan and mould extracts. We compared the response of 10 non-atopic and 10 atopic individuals. In parallel, cytokine protein release and the corresponding steady state mRNA level was determined by the standard ELISA and real-time on-line RT-PCR methods, respectively. Glucan induced the highest level of IL-1beta mRNA and protein release after 3 h. IL-8 was induced at 3 h after glucan, but not after LPS, induction, which indicates different induction pathways. At the time-points found to elicit the optimal cytokine response significantly higher basal cytokine mRNA levels and significantly lower LPS induced cytokine mRNA levels were observed in the non-atopic group. Generally, mould components induced cytokine mRNA steady state to lower levels in the atopics compared to the non-atopics. In contrast, no differences were found between the two groups in their capacity to induce cytokine protein release. These findings persisted after correction for the percentage of mononuclear cells. The data supported our hypothesis that "exhaustion" of the atopic immune system elicits lower basal cytokine mRNA levels and that analysis of cytokine gene expression has the potential to differentiate between non-atopic and atopic individuals.

Antigens, Fungal↗
PubMed2004

Working Group report 1: tools for the diagnosis of organic dusts-induced disease.

This paper describes the outcomes of the discussion of Working Group 1. The tasks of the workgroup were to: i) review current methods for the clinical diagnosis of organic dust induced disease, and ii) suggest how further research in this field should proceed. The working group proceeded on the paradigm that for diagnosis specific and precise tests are needed, where outcomes can be related to the risk for disease. The different methods available for the investigation of individuals and groups exposed to organic dusts are summed and graded according to scientific or diagnostic values. Many of the tools should be used in experimental research only, but can be used diagnostically for evaluation during follow up of patients when treated or removed from exposure. These techniques may also be employed for investigations of outbreaks, however, only after comparison with a proper control group. Future research should focus on associations between markers of inflammation and symptoms or clinical outcomes and dose-response relationships both for short-term and long-term health effects.

Airway Obstruction↗
PubMed2004

Endotoxins isolated from the air of a Danish paper mill and the relation to change in lung function: an 11-year follow-up.

BACKGROUND: A decline in lung function has been associated with farming, cotton spinning, and work in the animal feed industry. The aim of the study was to reveal if loss of lung function was associated to work at a paper mill. METHODS: Ninety-seven male paper workers (PW), and 55 control workers were examined. Hygiene samples included total dust, endotoxins, and microorganisms. Interview, pulmonary function testing, and skin prick test (SPT) were performed and yearly decline in lung function was calculated. RESULTS: The exposure for endotoxin (LPS) ranged from Median (Max-Min) 69 (370-6) EU/m3, in the wet-end of the paper machines to 6 (19-16) in the pulping area. The lung function decline among the controls was comparable to the decrements among the maintenance and repair workers at the paper factory, around 51-54 and 37-38 ml/year among smokers' and non-smokers, respectively. After adjustment for baseline FEV1, the variables associated to an increased loss of FEV1 were age smoking and cough. For FVC we found an inverse relation between exposure and yearly decline. CONCLUSION: No increase in loss of lung function is seen among workers exposed to up to 200 EU/m3 of LPS.

Air Pollutants, Occupational↗
PubMed2004

Exposure to work-related levels of swine dust up-regulates CD106 on human alveolar macrophages.

BACKGROUND: Exposure to dust from swine confinement buildings, causes an inflammatory response. Monocyte recruitment to the murine lung after instillation of lipopolysaccharide (LPS) has been shown to partially depend on CD106/VCAM1. We wanted to determine whether this can be confirmed in man. METHODS: Non-naïve persons bearing personal air samples were exposed for 3 hr in a swine confinement building, and were bronchoscopied before and after exposure. Blood samples were taken at the time of bronchoscopy. Expression of adhesion molecules on leukocytes was investigated by flow cytometry in bronchoaveloar lavage (BAL) and blood. RESULTS: Expression of CD106 on alveolar macrophages, but not on neutrophils or T cells in BAL or blood, was up-regulated in proportion to the amount of LPS that individuals were exposed. CONCLUSIONS: This argues for requirement of CD106 during inflammatory recruitment of monocytes to the human lung.

Air Pollutants, Occupational↗
PubMed2004

IgE sensitization to bacterial and fungal biopesticides in a cohort of Danish greenhouse workers: the BIOGART study.

BACKGROUND: The use of biopesticides in agriculture may implicate new risks of work-related allergic reactions. METHODS: Sera were tested from the BIOGART project, a longitudinal respiratory health study among >300 Danish greenhouse workers. IgE was measured by enzyme immunoassay (EIA) with extracts of biopesticide products containing Bacillus thuringiensis (BT) or Verticillium lecanii (Vert). RESULTS: Many sera had detectable IgE to BT (23-29%) or Vert (9-21%). IgE titers from the 2- and 3-year follow-up (n=230) were highly correlated, with discordant results in <15%. IgE titers to different BT, or to different Verticillium products were also significantly correlated (both r >0.70), whereas IgE anti-BT and anti-Verticillium showed no correlation at all. CONCLUSIONS: Exposure to these microbial biopesticides may confer a risk of IgE-mediated sensitization. In future research there is a need to identify allergenic components in the preparations, perform studies on non-exposed controls and analyze the relation between sensitization and health parameters.

Adult↗
PubMed2004

The association between asthma and allergic symptoms in children and phthalates in house dust: a nested case-control study.

Global phthalate ester production has increased from very low levels at the end of World War II to approximately 3.5 million metric tons/year. The aim of the present study was to investigate potential associations between persistent allergic symptoms in children, which have increased markedly in developed countries over the past three decades, and the concentration of phthalates in dust collected from their homes. This investigation is a case-control study nested within a cohort of 10,852 children. From the cohort, we selected 198 cases with persistent allergic symptoms and 202 controls without allergic symptoms. A clinical and a technical team investigated each child and her or his environment. We found higher median concentrations of butyl benzyl phthalate (BBzP) in dust among cases than among controls (0.15 vs. 0.12 mg/g dust). Analyzing the case group by symptoms showed that BBzP was associated with rhinitis (p = 0.001) and eczema (p = 0.001), whereas di(2-ethylhexyl) phthalate (DEHP) was associated with asthma (p = 0.022). Furthermore, dose-response relationships for these associations are supported by trend analyses. This study shows that phthalates, within the range of what is normally found in indoor environments, are associated with allergic symptoms in children. We believe that the different associations of symptoms for the three major phthalates-BBzP, DEHP, and di-n-butyl phthalate-can be explained by a combination of chemical physical properties and toxicologic potential. Given the phthalate exposures of children worldwide, the results from this study of Swedish children have global implications.

Air Pollution, Indoor↗
PubMed2004

Occupational asthma diagnosis in workers exposed to organic dust.

The clinical evaluation of newly developed asthma in an adult should always include consideration of his occupational environment, since an abundance of different exposures, which are known causes of asthma, occur in workplaces. Two types of occupational asthma (OA) are distinguished, by whether they appear after a latency period: 1)Immunological OA, characterised by a latency period, caused by high and low-molecular-weight agents, with or without an IgE mechanism 2) Non-immunological, i.e. irritant induced asthma. The first step of the clinical evaluation is to confirm a diagnosis of asthma. Second step is to find out if there is a temporo-spatial distribution of symptoms and lung function that are indicative of OA. Third step is to determine if the disease at hand is an IgE or a non-IgE mediated disease. Last step is a challenge test that can be either unspecific, in order to assess the responsiveness of the lung, or specific challenge test, especially for the non-IgE mediated OA. The depth of clinical evaluation may vary from a situation in which a classical history confirms the clinical symptoms in e.g. a baker with confirmed allergy towards well-known allergens and a characteristic pattern in serial measurements of lung function, to more elaborate investigations in a situation with no or unknown allergen. In the latter situation, a specific challenge test might be necessary in order to find the offending agent. Finally, challenge tests are important in order to distinguish a causal relation from unspecific hyperresponsiveness in persons with pre-existing asthma. In these situations, extended sick leave and challenge tests can be the only way to find the answer.

Adult↗
PubMed2003

Respiratory symptoms and ex vivo cytokine release are associated in workers processing herring.

OBJECTIVE: To determine the prevalence of respiratory symptoms among workers processing herring and assess ex vivo cytokine release in response to agents at their workplace. METHODS: We applied a questionnaire, and performed skin prick testing and pulmonary investigations in 36 workers at two herring factories, using 31 municipal workers as controls. In a whole blood assay (WBA), venous blood from the subjects was incubated with lipopolysaccharide (LPS), beta(1,3)-glucan or sterile-filtered, fish constituents such as skin and rinsing water. We determined the IL-1beta and IL-8 release in the plasma by chemiluminescence ELISA. RESULTS: Among smoking fish-factory workers the forced vital capacity (FVC) was higher (per cent predicted 92.0 vs 85.0; P=0.028) than among municipal workers. Fish rinsing water induced WBA IL-8 release to higher levels than LPS and glucan. Among non-smokers the induced IL-1beta release for rinsing water ( P=0.007) and the IL-8 release for skin ( P=0.001) and meat ( P=0.003) were higher in fish-factory workers than in municipal workers. The IL-1beta release for rinsing water ( P=0.028) and skin ( P=0.041) was higher among non-smokers than among smokers, and so was the IL-8 release for rinsing water ( P=0.008). CONCLUSIONS: Assessing the cytokine release by use of the WBA we identified substances in the occupational environment with a pro-inflammatory potential comparable to that of LPS. The cytokine release for fish constituents was highest among non-smoking fish-factory workers. The results suggest a priming effect of the work exposure.

Adult↗
PubMed2003

Plasma C3d levels of young farmers correlate with respirable dust exposure levels during normal work in swine confinement buildings.

Work in swine confinement buildings leads to an inflammatory response and may be associated with increased levels of acute phase proteins. We compared the inflammatory response of a control group of young former farm workers with age-matched former farm workers who had previously developed the lower airway symptoms of wheeze, cough, tightness of the chest during work in swine confinement buildings, and because of these symptoms had stopped work. Both groups were subjected to an experimental exposure in a swine confinement building for 3 hours. Complement activation and acute phase proteins were measured in blood samples and broncho-alveolar lavage. Plasma C3d levels correlated with respirable dust, significantly so for individual cases and for the whole cohort. Plasma C3, fibrinogen and alpha (1) -acid glycoprotein peaked 1 and 6 h after exposure start, mannan-binding lectin, C-reactive protein and alpha(1)-antitrypsin peaked after 2 h. Surfactant protein D (SP-D) and alpha (2) -macroglobulin were downregulated. In lavage, only SP-D, alpha (2)-macroglobulin and fibronectin were detected. FEV(1), FVC, TLC and FEV(25-75) did not vary during exposure. There was complement activation in response to respiratory dust, more so amongst cases than in the control group. Acute exposure, with work related levels of organic dust containing endotoxin, leads to a weak systemic inflammatory response.

Adult↗
PubMed2002

Selenium serum and urine is associated to mild asthma and atopy. The SUS study.

To examine the associations between selenium (Se) status, asthma, bronchial hyperresponsiveness (BHR), and atopy in 154 male subjects (72 with mild asthma, 41 with BHR and 41 with no respiratory symptoms) aged 18 (range 17-22) years. Each subject underwent a medical interview and FEV1 and FVC were recorded. Histamine bronchial reactivity (Yan method) was measured, skin prick test (inhalant allergens) was performed and Se in urine and serum was analysed (AOAC modified fluometric method). Se in serum 74.04 (10.58) micrograms/L (mean (SD)) was lower in subjects with asthma and the logarithm of the ratio of Se in serum (microgram/L) and urine standardised to creatinine excretion (ng/mg creatinine) 0.748 (0.096) (mean (SD)) was lower in subjects with asthma and atopy compared to subjects with no allergic symptoms 77.79 (10.16) micrograms/L and 0.808 (0.111) respectively (p < 0.05). In subjects with asthma atopy was significantly associated to urine Se 0.24 (0.73) (beta (SE)) (p < 0.05). Subjects with BHR had the same Se status as subjects with no respiratory symptoms and heavy smokers had a lower concentration of Se in serum 73.80 (9.56) micrograms/L than non-smokers 78.16 (10.74) micrograms/L (p < 0.05), Se status was associated to asthma and smoking. Measuring Se in urine might add further information to possible relations between Se status, atopy and asthma.

Adolescent↗
PubMed2002

Determinants of wood dust exposure in the Danish furniture industry.

This paper investigates the relation between wood dust exposure in the furniture industry and occupational hygiene variables. During the winter 1997-98 54 factories were visited and 2362 personal, passive inhalable dust samples were obtained; the geometric mean was 0.95 mg/m(3) and the geometric standard deviation was 2.08. In a first measuring round 1685 dust concentrations were obtained. For some of the workers repeated measurements were carried out 1 (351) and 2 weeks (326) after the first measurement. Hygiene variables like job, exhaust ventilation, cleaning procedures, etc., were documented. A multivariate analysis based on mixed effects models was used with hygiene variables being fixed effects and worker, machine, department and factory being random effects. A modified stepwise strategy of model making was adopted taking into account the hierarchically structured variables and making possible the exclusion of non-influential random as well as fixed effects. For woodworking, the following determinants of exposure increase the dust concentration: manual and automatic sanding and use of compressed air with fully automatic and semi-automatic machines and for cleaning of work pieces. Decreased dust exposure resulted from the use of compressed air with manual machines, working at fully automatic or semi-automatic machines, functioning exhaust ventilation, work on the night shift, daily cleaning of rooms, cleaning of work pieces with a brush, vacuum cleaning of machines, supplementary fresh air intake and safety representative elected within the last 2 yr. For handling and assembling, increased exposure results from work at automatic machines and presence of wood dust on the workpieces. Work on the evening shift, supplementary fresh air intake, work in a chair factory and special cleaning staff produced decreased exposure to wood dust. The implications of the results for the prevention of wood dust exposure are discussed.

Air Pollutants, Occupational↗