Exposure to Particles and Nitrogen Dioxide Among Workers in the Stockholm Underground Train System.

OBJECTIVES: Exposure to fine particles in urban air has been associated with a number of negative health effects. High levels of fine particles have been detected at underground stations in big cities. We investigated the exposure conditions in four occupational groups in the Stockholm underground train system to identify high-exposed groups and study variations in exposure. METHODS: PM1 and PM2.5 were measured during three full work shifts on 44 underground workers. Fluctuations in exposure were monitored by a real-time particle monitoring instrument, pDR, DataRAM. Qualitative analysis of particle content was performed using inductively coupled plasma mass spectrometry. Nitrogen dioxide was measured using passive monitors. RESULTS: For all underground workers, the geometric mean (GM) of PM1 was 18 µg/m3 and of PM2.5 was 37 µg/m3. The particle exposure was highest for cleaners/platform workers, and the GM of PM1 was 31.6 µg/m3 [geometric standard deviation (GSD), 1.6] and of PM2.5 was 76.5 µg/m3 (GSD, 1.3); the particle exposure was lowest for ticket sellers, and the GM of PM1  was 4.9 µg/m3 (GSD, 2.1) and of PM2.5 was 9.3 µg/m3 (GSD, 1.5). The PM1 and PM2.5 levels were five times higher in the underground system than at the street level, and the particles in the underground had high iron content. The train driver's nitrogen dioxide exposure level was 64.1 µg/m3 (GSD, 1.5). CONCLUSIONS: Cleaners and other platform workers were statistically significantly more exposed to particles than train drivers or ticket sellers. Particle concentrations (PM2.5) in the Stockholm underground system were within the same range as in the New York underground system but were much lower than in several older underground systems around the world.

Health effects of a subway environment in healthy volunteers.

Environmental particle exposure, often estimated as the particulate mass of particles with a diameter <10 microm, <2.5 microm or <1 microm (PM(10), PM(2.5) or PM(1)), is known to have a negative impact on the health of the population. Little is known about how the size and origin of particles influence the effects. We have previously shown that exposure to a road tunnel environment causes a cellular inflammatory response in the airways of healthy individuals. In the present study, our aim was to investigate potential airway health effects from exposure to a subway environment. 20 healthy volunteers were exposed to a subway and a control environment for 2 h, followed by measurements of lung function and the inflammatory response in the lower airways (bronchoscopy) and in the peripheral blood. No cellular response was found in the airways after exposure to the subway environment. In the blood, we found a statistically significant increase in fibrinogen and regulatory T-cells expressing CD4/CD25/FOXP3. Subway and road tunnel environments have similar levels of PM(10) and PM(2.5), whilst the concentrations of ultrafine particles, nitrogen monoxide and dioxide are lower in the subway. Although no cellular response was detected, the findings indicate a biological response to the subway environment. Our studies show that using gravimetric estimates of ambient particulate air pollution alone may have clear limitations in health-risk assessment.

Influence of herring (Clupea harengus) and herring fractions on metabolic status in rats fed a high energy diet.

AIM: Few dietary studies have looked beyond fish oil to explain the beneficial metabolic effects of a fish-containing diet. Our aim was to study whether addition of herring, or sub-fractions of herring, could counteract negative metabolic effects known to be induced by a high-fat, high-sugar diet. METHODS: Rats were given six different diets: standard pellets; high energy diet with chicken mince (HiE control); high energy diet with herring mince (HiE herring); and high energy diet with chicken mince and either herring oil (HiE herring oil), herring press juice, PJ (HiE PJ) or herring low molecular weight PJ (HiE LMW-PJ). Factors associated with the metabolic syndrome were measured. RESULTS: There were no differences in energy intake or body weight between the groups, but animals fed high energy diets had a higher body fat content compared with the pellet group, although not statistically significant in all groups. Mesenteric adipocyte size was smaller in the HiE herring oil group compared with the HiE control. Glucose clamp studies showed that, compared with the pellet group, the HiE control and HiE herring diets, but not the HiE herring oil diet, induced insulin resistance. Addition of herring or herring oil to the high energy diet decreased total cholesterol levels, triacylglycerols and the atherogenic index compared with the HiE control group. CONCLUSIONS: The results suggest that addition of herring or herring oil counteracts negative effects on blood lipids induced by a high energy diet. The lipid component of herring thus seems to be responsible for these beneficial effects.

Road tunnel air pollution induces bronchoalveolar inflammation in healthy subjects.

Traffic-related air pollution is associated with adverse respiratory effects. The aim of the present study was to investigate whether exposure to air pollution in a road tunnel causes airway inflammatory and blood coagulation responses. A total of 16 healthy subjects underwent bronchoscopy with bronchial mucosal biopsies and bronchoalveolar lavage (BAL) on two occasions, in random order: once at 14 h after a 2-h exposure to air pollution in a busy road tunnel, and once after a control day with subjects exposed to urban air during normal activities. Peripheral blood was sampled prior to bronchoscopy. The road tunnel exposures included particulate matter with a 50% cut-off aerodynamic diameter of 2.5 microm, particulate matter with a 50% cut-off aerodynamic diameter of 10 mum and nitrogen dioxide which had median concentrations of 64, 176 and 230 microg.m(-3), respectively. Significantly higher numbers of BAL fluid total cell number, lymphocytes and alveolar macrophages were present after road tunnel exposure versus control. Significantly higher nuclear expression of the transcription factor component c-Jun was found in the bronchial epithelium after exposure. No upregulation of adhesion molecules or cellular infiltration was present and blood coagulation factors were unaffected. In conclusion, exposure of healthy subjects to traffic-related air pollution resulted in a lower airway inflammatory response with cell migration, together with signs of an initiated signal transduction in the bronchial epithelium.

The development of emotional distress in 158 patients with recently diagnosed rheumatoid arthritis: a prospective 5-year follow-up study.

OBJECTIVES: To describe the development of emotional distress among patients with newly diagnosed rheumatoid arthritis (RA), and to explore for early predictors of elevated distress over time. METHODS: The study group consisted of 158 early RA patients (64% females) with mean age of 51.4 (SD = 12.7) years at disease onset. The patients were evaluated once a year for up to at least 4 years after baseline. Emotional distress was measured with the Symptom Checklist (SCL-90), disability with the Health Assessment Questionnaire (HAQ), pain with a visual analogue scale (VAS), and disease activity by an active joint count and erythrocyte sedimentation rate (ESR). Questions concerning social support were also included. RESULTS: Emotional distress decreased slowly for a majority of the patients. The change reached statistical significance in the third year from study start. A minority (12%) showed continuously high and increasing levels of distress. Measures of disease activity were poor predictors of distress. The best predictor of distress over time was distress at baseline. Other predictors were gender, age, civil status, and social support. CONCLUSIONS: Emotional distress tended to decrease for most patients in this cohort, but a minority showed continuously high levels. Patients at higher risk of developing emotional distress over time had higher levels of distress at baseline, were younger, more often female, and cohabiting, and experienced less social support.

Short-term infusion of interleukin-6 does not induce insulin resistance in vivo or impair insulin signalling in rats.

AIMS/HYPOTHESIS: Interleukin-6 has been implicated in the insulin resistance associated with obesity and impaired glucose tolerance. Previous studies in vitro have shown that IL-6 rapidly (1-2 h) impairs cellular insulin signalling and action through an increased expression of suppressor of cytokine signalling (SOCS)-3. In the present study, IL-6 or saline was infused in rats that were simultaneously in a state of hyperinsulinaemia. Muscle, liver and adipose tissue were excised after 2 h to examine potential effects on insulin signalling or gene expression. METHODS: The rats were infused with IL-6 or saline during a euglycaemic-hyperinsulinaemic clamp and the glucose infusion rate was measured after 90 to 120 min. Signal transducer and activator of transcription (STAT)3 phosphorylation and insulin-stimulated tyrosine phosphorylation of the insulin receptors and IRS were measured with immunoblotting and gene expression through real-time PCR. RESULTS: No inhibitory effect of IL-6 on insulin-stimulated whole-body glucose uptake was seen in spite of high circulating levels of IL-6 (0.85+/-0.08 nmol/l). Tyrosine phosphorylation of the insulin receptors and IRS was also unchanged in the liver, skeletal muscles and adipose tissue. However, tyrosine phosphorylation of STAT3 was increased in all tissues, showing that IL-6 signalling was activated. IL-6 mRNA tended to increase, while GLUT4, peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) and adiponectin gene expression were unchanged. CONCLUSIONS/INTERPRETATION: Infusion of IL-6 for 120 min in rats during euglycaemic-hyperinsulinaemic conditions did not alter the effect of insulin on whole-body glucose homeostasis, plasma adiponectin levels or insulin signalling in target tissues. Thus, the acute effects of IL-6, associated with SOCS-3 induction, do not lead to whole-body insulin resistance. These data further underscore the importance of the chronic, and potentially tissue-specific effects of IL-6 on insulin signalling and action.

Exhaled nitric oxide and bronchial responsiveness in healthy subjects exposed to organic dust.

Inhalation of organic dust from swine houses causes an intense inflammatory reaction in the respiratory tract, and increased bronchial responsiveness to methacholine in healthy subjects. The aims of the present study were to investigate whether exhaled nitric oxide (NO) is a marker of the inflammation caused by exposure to organic dust (swine dust), whether there is a relationship between an increase in exhaled NO and bronchial responsiveness, and also whether wearing a half-mask influences the airway reaction (assessed by exhaled NO) and the increased bronchial responsiveness. Thirty-three healthy nonatopic, nonsmoking subjects were exposed during 3 h of light work in a swine confinement building. Eleven of the subjects were wearing a half-mask and 22 were unprotected. Lung function, bronchial responsiveness and exhaled NO were measured before and after exposure. The provocative concentration causing a 20% fall in forced expiratory volume in one second fell by 2.7 (2.1-4.1) (median (25th-75th percentiles)) doubling concentration steps in subjects without a half-mask and by 1.5 (0.9-2.9) doubling concentration steps in subject wearing a mask. Exhaled NO increased from 7.5 (5.7-13.7) parts per billion (ppb) before to 13.4 (10.5-17.5) ppb after exposure in the unprotected group and was unaltered (8.3 (6.1-14.1) to 8.6 (6.6-14.6) ppb) in the group wearing a half-mask. There was no correlation between NO increase and provocative dose causing a 20% fall in the forced expiratory volume in one second decrease. In conclusion, bronchial responsiveness and exhaled nitric oxide increased after exposure to a swine confinement facility. Half-mask abolished the increase in exhaled nitric oxide levels, but influenced the increase in bronchial responsiveness to a minor extent. These results indicate that these two outcome measures reflect different aspects of airway inflammation induced by exposure to a farming environment.

Sodium cromoglycate attenuates pulmonary inflammation without influencing bronchial responsiveness in healthy subjects exposed to organic dust.

BACKGROUND: Inhalation of organic dust from a pig house induces airway inflammation and increases bronchial responsiveness to methacholine in healthy subjects. OBJECTIVE: To study whether sodium cromoglycate influences the airway inflammatory reaction and the increase in airway responsiveness induced by inhalation of organic dust. METHODS: Bronchoalveolar and nasal lavages, and bronchial methacholine challanges were performed and blood samples were drawn in 32 healthy subjects before and after exposure to dust in a pig farm. Sodium cromoglycate was inhaled (20 mg, twice a day) and administered intranasally (5.2 mg, twice a day) by 16 and a corresponding placebo was given to the other 16 healthy controls for two weeks prior to exposure. RESULTS: Exposure induced a significant increase in inflammatory cells and soluble components (pro-inflammatory cytokines, inflammatory mediators) in bronchoalveolar and nasal lavage fluid in both groups. The increase in neutrophils, interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha as well as myeloperoxidase and soluble intracellular adhesion molecule (ICAM)-1 in bronchoalveolar lavage (BAL) fluid was significantly reduced by treatment with sodium cromoglycate. Although sodium cromoglycate inhalation largely influenced a variety of inflammatory indices in bronchoalveolar lavage fluid it had no effect on the increase in bronchial responsiveness to methacholine. CONCLUSION: Sodium cromoglycate alters the airway inflammatory response to inhaled organic dust without influencing the dust-induced increase in bronchial responsiveness to methacholine.

Maternal endotoxemia results in obesity and insulin resistance in adult male offspring.

Events in utero appear to be important factors contributing to the development of somatic disorders at adult age. The aim of this study was to examine whether maternal immune challenge would be followed at adult age by metabolic and endocrine abnormalities in the offspring. Pregnant rats were given injections of either endotoxin (Escherichia coli lipopolysaccharide; 0.79 mg/kg, ip) or vehicle on days 8, 10, and 12 of gestation. Adult male offspring to lipopolysaccharide-exposed dams were heavier than controls (P < 0.05) and showed increased adipose tissue weights (P < 0.05), elevated food intake (P < 0.05), and increased circulating leptin (P < 0.01). The effect of insulin on glucose uptake was reduced, as measured by an euglycemic hyperinsulinemic clamp technique (P < 0.05). Serum levels of 17beta-estradiol and progesterone were elevated (P < 0.01 and P < 0.05, respectively). Baseline levels of corticosterone were normal, but the corticosterone response to stress was attenuated (P < 0.05), and hippocampal glucocorticoid receptor protein was up-regulated (P < 0.05). Female offspring were uninfluenced, except for increased testosterone levels (P < 0.05), increased baseline corticosterone levels (P < 0.05), and enlargement of heart and adrenals (P < 0.05). The results indicate that maternal endotoxemia leads to obesity, insulin resistance, and high serum levels of leptin in the adult male offspring. This study reports a novel animal model of obesity with features of the metabolic syndrome.

Preliminary report on the results of the second phase of a round- robin endotoxin assay study using cotton dust.

In an on-going endotoxin assay study, a two-part interlaboratory endotoxin assay study has been completed. The purpose of the study was to compare the variation in assay results between different laboratories, and, if the variation was high, to see if a common protocol would reduce the variation. In both parts of the study, membrane filters laden with the same approximate amount and type of cotton dust were sent for analysis to laboratories that "routinely" perform endotoxin analyses. First, each of these laboratories performed the analysis using the methodology common to its laboratory. In the second part of the study, membrane filters with cotton dust were again sent to the same laboratories where the analyses were performed as before but with a common extraction protocol. The preliminary results from the first phase of the study have been collected and showed that intra-laboratory variations were small, but large and significant interlaboratory variation was observed. The results were reported elsewhere. The preliminary results from the second part of the study consisting of the data currently collected are presented here. Again, intra-laboratory variations were small, but, also again, large and significant inter-laboratory variation was observed. However, in this part of the study, the range between the highest and lowest average results was narrower than in the first part of the study. Influence of the assay kit type was examined. The variation within assay kit type was small but significant differences in results were observed between assay kit types. The findings suggest that endotoxin concentration in samples can be ranked within laboratories, but not necessarily between laboratories. However, some of the variation between laboratories has been reduced by a common extraction protocol which suggests the possibility of further standardization that may lead to better comparability between laboratories.

Gram positive bacteria induce IL-6 and IL-8 production in human alveolar macrophages and epithelial cells.

BACKGROUND AND OBJECTIVE: Inhalation of dust from swine confinement buildings results in an acute inflammatory reaction in the respiratory tract. The dust has a high microbial content, dominated by Gram positive bacteria. The aim of the present study was to evaluate the significance of bacteria in the induction of IL-6 and IL-8 release from respiratory epithelial cells and alveolar macrophages. The results would give an indication to what extent the bacteria contribute to the toxic inflammation following exposure to swine dust. METHODS: Epithelial cells from a human lung carcinoma cell line (A549) and human alveolar macrophages obtained from healthy subjects by bronchoalveolar lavage, were stimulated with swine dust, LPS, one Gram negative and four Gram positive bacteria strains. The dose-response release of IL-6 and IL-8 were studied. In addition, a bacteria-free supernatant was prepared from each strain and used for stimulation. RESULTS: With a few exceptions, a dose-dependent IL-6 and IL-8 release was demonstrated from both cell types after stimulation with bacteria. In epithelial cells, Escherichia coli was the most potent bacteria at the highest concentration of 400 bacteria/cell regarding secretion of both IL-6 and IL-8 (P < 0.001), followed by Staphylococcus hominis and Staphylococcus lentus. In alveolar macrophages, S. lentus was the most potent strain (P < 0.001) in inducing cytokine release (P < 0.001), followed by S. hominis and E. coli concerning IL-6 secretion or Micrococcus luteus and E. coli with respect to IL-8 secretion (P < 0.001). Differences in potency between the various bacteria could be demonstrated, both within the two cell types as well as between the epithelial cells and macrophages. Bacteria-free supernatants were also able to induce cytokine release in both cell types. In macrophages the supernatants were even more potent stimuli than whole bacteria. CONCLUSIONS: The results indicate that bacteria or bacterial products could be an important contributing factor to the inflammatory reaction following exposure to swine dust.

Increase in interleukin-6 and fibrinogen in peripheral blood after swine dust inhalation.

OBJECTIVES: The inhalation of dust from swine confinement buildings causes inflammatory responses in the airways with a rise of interleukin-6 (IL-6). The purpose of this study was to confirm the increase in serum IL-6 after inhalation of swine dust and investigate a possible increase in plasma fibrinogen. METHODS: Eight healthy nonsmoking volunteers inhaled dust for 4 hours inside a swine confinement building. Inhalable dust and endotoxin were sampled. The concentrations of IL-6 and fibrinogen were determined in serum and plasma. RESULTS: The study showed a clear increase in the concentrations of IL-6 and fibrinogen after exposure. CONCLUSIONS: As fibrinogen is an important risk factor for ischemic heart disease, the increased concentration of fibrinogen among persons exposed to swine dust may increase the risk for this disease.

Airway responses in naive subjects to exposure in poultry houses: comparison between cage rearing system and alternative rearing system for laying hens.

BACKGROUND: Workers in the poultry industry have increased frequencies of respiratory health problems. The aim of the present study was to investigate acute health effects from exposure in poultry houses and to compare the health effects observed in a cage rearing system and the alternative "cage-less" rearing system for laying hens. METHODS: Thirty-four subjects were exposed for 3 hr in confined poultry houses. The subjects were randomized into three groups: one was exposed in a building with a cage rearing system and the two other groups were exposed in buildings with a cage-less system, with either young hens and fresh bedding material or with older hens and old bedding material. RESULTS: Inhalable dust levels were approximately 4 mg/m3 in the buildings with the cage-less system and 2 mg/m3 in the building with cage rearing system; the endotoxin concentration was approximately 100 ng/m3 in both systems. Bronchial responsiveness to methacholine increased approximately fivefold in all groups following exposure. The concentration of the proinflammatory cytokine interleukin-6 (IL-6) increased in nasal lavage fluid and in peripheral blood as a result of the exposure. The number of leukocytes in peripheral blood increased only in the groups exposed among loose laying hens. CONCLUSION: In the present study, we have demonstrated among previously non-exposed subjects, that 3-hr exposure in confined buildings for egg production induces an acute inflammatory reaction in the upper airways and increased bronchial responsiveness. There is a tendency towards stronger reactions in the groups exposed in the buildings with loose housing for laying hens.

Induction of insulin resistance by glucosamine reduces blood flow but not interstitial levels of either glucose or insulin.

To study the effects of a glucosamine infusion on skeletal muscle metabolism, microdialysis was performed in the medial femoral muscle in Sprague-Dawley rats during a euglycemic-hyperinsulinemic clamp (insulin infusion 18 mU x kg(-1) x min(-1)). During steady-state clamping conditions (70 min), an infusion of glucosamine (30 micromol x kg(-1) x min(-1)) or saline was given for 240 min. Blood flow was measured by the microsphere technique at the end of the clamp. An approximately 36% (P < 0.001) reduction in the glucose infusion rate was seen after 170 min in the glucosamine-treated rats compared with control rats. There were no significant differences in interstitial or plasma levels of either insulin or glucose between the two groups. Both interstitial (2.31 +/- 0.18 vs. 1.71 +/- 0.24 mmol/l, P < 0.05) and arterial plasma lactate concentrations (1.29 +/- 0.09 vs. 0.79 +/- 0.09 mmol/l, P < 0.01) were significantly higher in control rats compared with glucosamine-treated rats. Blood flow was significantly reduced in hind limb femoral muscles in the glucosamine-treated rats compared with control rats. The most pronounced reduction in blood flow was seen in the Soleus muscle (27.6 +/- 3.4 vs. 14.7 +/- 2.0 ml x 100 g(-1) x min(-1), P < 0.01). These results demonstrate that induction of insulin resistance by glucosamine results in a reduction of the blood flow rate as well as the uptake of glucose and the production of lactate in skeletal muscle. As a result of the inhibited glucose metabolism, the interstitial glucose concentration was unchanged despite the reduced blood flow after glucosamine administration. The data suggest the importance of regulation of blood flow by nonoxidative metabolism of glucose in resting muscle.

House dust induces IL-6 and IL-8 response in A549 epithelial cells.

The in vitro potency of house dust to induce cytokine response in A549 lung epithelial cells was studied. Dusts collected from carpet, bed, shelf and floor of a villa and an apartment by vacuuming were found to trigger the production of interleukin-8 (IL-8) and interleukin-6 (IL-6) in a dose-dependent manner, and the interleukin production was several-fold higher than of swine dust (used as a positive control). The IL-8 and IL-6 production of pure Escherichia coli lipopolysaccharide was significantly lower than of the dusts and a peptidoglycan-polysaccharide complex did not show any stimulatory effect at all. The lipopolysaccharide and peptidoglycan contents of the samples were determined by gas chromatography-tandem mass spectrometry analysis of, respectively, 3-hydroxy fatty acids and muramic acid; in addition, ergosterol was monitored for fungal biomass. The inflammatory properties of house dust upon inhalation may be reflected in its high potency to induce cytokine response in lung epithelial cells.

Induction of IL-8 production in human alveolar macrophages and human bronchial epithelial cells in vitro by swine dust.

BACKGROUND: Exposure to swine dust causes an intense airway inflammation with increased levels of interleukin 8 (IL-8) and predominantly neutrophils in the nasal and bronchoalveolar lavage fluids of healthy human subjects. It is not clear which components in the swine house environment are responsible for the airway reaction. The aim of the present study was to evaluate and compare the effect in vitro of swine dust components on human alveolar macrophages and bronchial epithelial cells. METHODS: Normal human bronchial epithelial cells (NHBE), human pulmonary epithelial carcinoma cell line (A549), and human alveolar macrophages were stimulated with swine dust, lipopolysaccharides (LPS; present in Gram negative bacteria), grain dust (swine feed components), and glucans (a structural component of fungi) in a dose response manner (1-100 micrograms/ml). RESULTS: Swine dust at a concentration of 100 micrograms/ml increased IL-8 production 20 fold in NHBE cells, 28 fold in A549 cells, and 15 fold in macrophages. LPS (100 micrograms/ml) stimulated all three cell types significantly, in macrophages to the same extent as swine dust, but in NHBE and A549 cells swine dust was 5-8 times as potent. Grain dust (100 micrograms/ml) had no effect in A549 cells and macrophages but not NHBE cells. Both glucans and grain dust were weaker stimuli than swine dust and LPS. The LPS content of swine dust solution was 2.16 (0.2) ng/100 micrograms and of grain dust was 0.53 (0.04) ng/100 micrograms. CONCLUSIONS: Swine dust is a strong stimulus for IL-8 production in both bronchial epithelial cells and human alveolar macrophages, whereas LPS has different potency in these cells.

Effect of rheumatoid arthritis on work status and social and leisure time activities in patients followed 8 years from onset.

OBJECTIVE: To evaluate the development of handicap in patients with rheumatoid arthritis (RA) followed 8 years from onset. METHODS: The study group consisted of 106 patients participating in a prospective early RA study. The mean duration of joint symptoms at inclusion was one year. The patients were assessed at least once annually. Disability was measured with the Health Assessment Questionnaire (HAQ) and emotional distress with a self-administered test (Symptom Checklist). Work status and different social measures were registered. A structured interview regarding work capacity, leisure time, and social activities was performed about 8 years after disease onset. RESULTS: Compared to study start, disease activity had decreased, emotional distress was unchanged, disability had increased somewhat, and radiographic changes had increased markedly. The prevalence of work disability at the end of the study was 37%. The majority of patients that eventually got disability pension had stopped working the first year after onset. Seventy-eight percent of the patients who continued to work had to adjust their work conditions to stay employed. The 3 most important predictors for work disability were higher HAQ at study start, lower educational level, and older age. Three-quarters of the patients had to alter leisure time activities and half of them were not satisfied with their recreation. Many patients experienced difficulties in their roles as spouse and parent. Higher levels of emotional distress were associated with these handicaps. CONCLUSION: In this cohort of patients with RA we found a high frequency of different types of handicaps at an early stage. Slightly more than 1/3 were work disabled. The majority had stopped working during the first year. Patients perceived handicaps in terms of changed leisure time activities, and difficulties performing different social roles were frequent. Patients with these handicaps felt more emotional distress.

Exposure of healthy volunteers to swine house dust increases formation of leukotrienes, prostaglandin D2, and bronchial responsiveness to methacholine.

BACKGROUND: Acute exposure of healthy subjects to swine house dust causes increased bronchial responsiveness to methacholine but no acute bronchoconstriction. The role of cysteinyl leukotrienes and mast cells in increased bronchial responsiveness is unclear. METHODS: Ten non-asthmatic subjects were exposed to swine dust for three hours while weighing pigs in a piggery. Urine was collected prior to and for up to 12 hours after entering the piggery and at the same times five days before and the day after exposure. As indices of whole body leukotriene production and mast cell activation, urinary levels of leukotriene E4 (LTE4) and 9 alpha, 11 beta-PGF2, the earliest appearing urinary metabolite of prostaglandin D2 (PGD2), were measured. Bronchial responsiveness to methacholine was determined five days before and the day after the exposure. RESULTS: Methacholine PD20FEV1 decreased from 1.32 mg (95% CI 0.22 to 10.25) before exposure to 0.38 mg (95% CI 0.11 to 1.3) after exposure (p < 0.01). Associated with the increase in bronchial responsiveness there was a significant mean difference between post- and prechallenge levels of LTE4 (difference 38.5 ng/mmol creatinine (95% CI 17.2 to 59.8); p < 0.01) and 9 alpha, 11 beta-PGF2 (difference 69 ng/mmol creatinine (95% CI 3.7 to 134.3); p < 0.05) on the day of exposure to swine dust. Swine dust exposure induced a 24-fold increase in the total cell number and a 12-fold increase in IL-8 levels in the nasal lavage fluid. The levels of LTB4 and LTE4 in nasal lavage fluid following exposure also increased 5.5-fold and 2-fold, respectively. CONCLUSIONS: The findings of this study indicate that cysteinyl leukotrienes and other mast cell mediators contribute to the development of increased bronchial responsiveness following inhalation of organic swine dust.

Effect of exposure to swine dust on levels of IL-8 in airway lavage fluid.

BACKGROUND: Inhalation of swine dust causes airway inflammation with influx of inflammatory cells, predominantly neutrophils, into the lungs. A study was undertaken to determine whether or not exposure to swine dust induces release of interleukin 8 (IL-8) into upper and lower airways and how this possible release is related to cellular influx. A further aim was to study the relationship between the inflammatory response and swine dust exposure. METHODS: Thirty one healthy, non-smoking, previously unexposed subjects were exposed to swine dust during three hours work in a swine house. Bronchoalveolar lavage (BAL) was performed two weeks before and 24 hours after the exposure (n = 16). Nasal lavage and acoustic rhinometry were carried out 1-2 hours before and seven hours after the start of the exposure (n = 31). Exposure measurements were performed with personal sampling equipment. RESULTS: The exposure led to 19-fold and 70-fold increases in the neutrophil concentrations in nasal lavage and BAL fluid, respectively (p < 0.001). In BAL, fluid macrophages, lymphocytes and eosinophils increased significantly. The IL-8 levels in BAL fluid increased from < 31.3 ng/l to 63 (43-109) ng/l (median (25-75th percentile), p < 0.001), and in nasal lavage fluid the concentrations increased from 144 (97-227) ng/l to 1064 (864-1437) ng/l (p < 0.001). IL-8 levels showed a significant correlation with the increase in neutrophils in the nasal lavage fluid but not in the BAL fluid. Acoustic rhinometry demonstrated significant swelling of the nasal mucosa. The air concentration of inhalable dust was 23.3 (20.0-29.3) mg/m3, endotoxin 1.3 (1.1-1.4) micrograms/m3, and muramic acid 0.99 (0.78-2.1) microgram/m3. CONCLUSIONS: The concentration of IL-8 increases in BAL fluid and nasal lavage fluid following exposure to swine dust and may be one of the chemoattractants contributing to the recruitment of neutrophils to the nasal cavity and the alveolar space.

CD8+ T cells from HIV type 1-seronegative individuals suppress virus replication in acutely infected cells.

CD8+ lymphocytes (CD8 cells) have been shown to inhibit replication of the human immunodeficiency virus (HIV) in vitro when cocultured with HIV-infected CD4+ lymphocytes (CD4 cells). This suppressive effect on HIV replication in experimentally infected CD4 cells has so far been demonstrated only for CD8 cells from HIV-seropositive individuals. In the present study we have investigated if CD8 cells from HIV-negative individuals can also suppress HIV replication in experimentally infected CD4 cells. Positively selected CD4 cells were infected with phenotypically different primary isolates of HIV type 1 and 2 (HIV-1 and HIV-2). Graded numbers of CD8 cells were added to the infected cultures. The T cells were activated by antibodies directed against the CD3 molecule or the T cell receptor. Culture supernatants were harvested for HIV p24 quantitation and the CD8 suppression of HIV replication was calculated by comparing p24 levels from parallel cultures in the presence or absence of CD8 cells from different donors. We show that CD8 cells from unexposed HIV-seronegative blood donors are able to control HIV-1 and HIV-2 replication in experimentally infected autologous CD4 cells. The antiviral activity of CD8 cells from and HIV-naive individual was reproducible over time and the suppressive effect was comparable to that seen with CD8 cells from HIV-positive individuals. The infected cells were not eliminated from the cultures. The suppressive effect of CD8 cells varied depending on the dose and biological phenotype of the virus used for infection. Thus, exposure to HIV in vivo is not a prerequisite for CD8 cells to exert a suppressive effect on HIV replication in acutely infected cells.