Biomedical subjects

Kjell Larsson

Publications and source records attributed to Kjell Larsson.

At least 19 recordsLinked to original sources

PubMed2007

Effect of formoterol and salmeterol on IL-6 and IL-8 release in airway epithelial cells.

Beta(2)-adrenoceptors are widely distributed and occur on airway epithelial cells. The aim of this study was to find out whether the two long-acting beta(2)-agonists formoterol and salmeterol influence interleukin-6 (IL-6) and -8 (IL-8) release from airway epithelial cells in vitro. A549 cells and primary bronchial epithelial cells (PBEC) were stimulated with organic dust from pig barns. Non-stimulated and dust-stimulated cells were incubated for 24h with formoterol or salmeterol (10(-13)-10(-6)M) and the release of IL-6 and IL-8 into the medium was assessed by ELISA technique. Propranolol (10(-5)M) or sotalol (10(-3)M) were used to block the beta(2)-agonist mediated effects. Formoterol and salmeterol both induced enhancement of IL-6 and IL-8 release and added to the effect of organic dust. This enhanced release was blocked by a beta-blocker in PBEC but not in A549 cells. To our knowledge, this is the first time beta(2)-agonists have been shown to stimulate IL-6 release from airway epithelial cells. The results indicate different mechanisms of beta(2)-agonist action in bronchial and alveolar epithelial cells. Furthermore, our results indicate that A549 cells do not possess functional beta(2)-adrenoceptors.

Adrenergic beta-Agonists↗

PubMed2006

Interval training compared with continuous training in patients with COPD.

The aim of this study was to compare the effects of interval training (3-min intervals) with continuous training on peak exercise capacity (W peak), physiological response, functional capacity, dyspnoea, mental health and health-related quality of life (HRQoL) in patients with moderate or severe COPD. Sixty patients exercised twice weekly for 16 weeks after randomisation to interval- or continuous training. Target intensity was 80% of baseline W peak in the interval group (I-group) and 65% in the continuous group (C-group). Patients were tested by spirometry, ergometer cycle test, cardiopulmonary test and a 12 min walk test. Dyspnoea was measured by the dyspnoea scale from Chronic Obstructive Disease Questionnaire (CRDQ), mental health by Hospital Anxiety and Depression scale (HAD) and HRQoL by the Medical Outcomes Survey Short Form 36 (SF-36). After training, W peak, peak oxygen uptake (VO(2) peak) and exhaled carbon dioxide (VCO(2) peak) increased significantly in both groups, no significant differences between the groups. Minute ventilation (V(E) peak) increased only in the C-group. At identical work rates (isotime) VO(2), VCO(2) and V(E) were significantly more decreased in the I-group than in the C-group (p<0.05). Functional capacity, dyspnoea, mental health, and HRQoL improved significantly in both groups, no difference between the groups. Interval training and continuous training were equally potent in improving peak exercise capacity, functional exercise capacity, dyspnoea, mental health and HRQoL in patients with moderate or severe COPD. At isotime, the physiological response to training differed between the groups, in favour of the interval training.

Adult↗

PubMed2006

Peak exercise capacity estimated from incremental shuttle walking test in patients with COPD: a methodological study.

BACKGROUND: In patients with COPD, both laboratory exercise tests and field walking tests are used to assess physical performance. In laboratory tests, peak exercise capacity in watts (W peak) and/or peak oxygen uptake (VO2 peak) are assessed, whereas the performance on walking tests usually is expressed as distance walked. The aim of the study was to investigate the relationship between an incremental shuttle walking test (ISWT) and two laboratory cycle tests in order to assess whether W peak could be estimated from an ISWT. METHODS: Ninety-three patients with moderate or severe COPD performed an ISWT, an incremental cycle test (ICT) to measure W peak and a semi-steady-state cycle test with breath-by-breath gas exchange analysis (CPET) to measure VO2 peak. Routine equations for conversion between cycle tests were used to estimate W peak from measured VO2 peak (CPET). Conversion equation for estimation of W peak from ISWT was found by univariate regression. RESULTS: There was a significant correlation between W peak and distance walked on ISWT x body weight (r = 0.88, p < 0.0001). The agreement between W peak measured by ICT and estimated from ISWT was similar to the agreement between measured W peak (ICT) and W peak estimated from measured VO2 peak by CPET. CONCLUSION: Peak exercise capacity measured by an incremental cycle test could be estimated from an ISWT with similar accuracy as when estimated from peak oxygen uptake in patients with COPD.

Adult↗

PubMed2006

Bronchial responsiveness to leukotriene D4 is resistant to inhaled fluticasone propionate.

BACKGROUND: Inhaled corticosteroids are highly effective in asthma, reducing inflammatory markers and bronchial hyperresponsiveness. Cysteinyl-leukotrienes are major mediators of airway obstruction and display proinflammatory effects. Although the synthesis of leukotrienes is not affected by corticosteroid treatment, the influence of corticosteroids on the leukotriene pathway remains unresolved. OBJECTIVE: We investigated whether or not bronchial responsiveness to leukotriene (LT) D(4) is reduced by fluticasone propionate in subjects with asthma. METHODS: In 13 subjects with mild asthma, inhalation challenges with methacholine and LTD(4) were performed on consecutive days before and after 2 weeks of treatment with inhaled fluticasone 500 mug, twice daily, in a double-blind, randomized, placebo-controlled study with crossover design and 3 weeks of washout between periods. Exhaled nitric oxide was measured as a marker of corticosteroid responsiveness, and baseline urinary LTE(4) concentrations as an index of cysteinyl-leukotriene biosynthesis. RESULTS: Fluticasone produced a significant decrease in methacholine responsiveness, corresponding to 2.6-fold shift in the PD(20) FEV(1), and a significant reduction in the levels of exhaled nitric oxide. By contrast, bronchial responsiveness to LTD(4) in the same subjects was unaffected by fluticasone, as were urinary LTE(4) concentrations. CONCLUSION: These new data indicate that neither the biosynthesis nor the actions of leukotrienes appear to be sensitive to inhaled corticosteroids. CLINICAL IMPLICATIONS: The study provides mechanistic support for the additive therapeutic efficacy of antileukotrienes and inhaled corticosteroids in asthma.

Administration, Inhalation↗

PubMed2006

Two different training programmes for patients with COPD: a randomised study with 1-year follow-up.

PURPOSE: To compare the effects on exercise capacity and health related quality of life (HRQoL) of two exercise programmes; one programme including endurance training and one including only resistance training and callisthenics. A second purpose was to find out whether the severity of chronic obstructive pulmonary disease (COPD) affected the training response and whether the interventions had a long-term effect. METHODS: Sixty-three patients were stratified according to severity of COPD and randomised to two training groups. Group A had a mixed programme including endurance training. Group B had resistance training and callisthenics. All trained twice weekly for 8 weeks. A symptom-limited ergometer test, 12-min walking test, dynamic spirometry, blood gas analysis at rest and HRQoL were measured before and after the training period. Follow-up tests were conducted at 6 and 12 months after training. RESULTS: Forty-two patients fulfilled the trial. In group A (n=20) peak exercise capacity increased by 7W (P<0.001) and 12-min walking distance (12MWD) by 50 m (P<0.01), whereas group B (n=22) did not change in any of these variables. HRQoL did not change significantly in either group. Training response was similar in patients with moderate and severe disease. One year post-training 12MWD had returned to pre-training level in group A, and below pre-training level in group B (P<0.05). CONCLUSIONS: Exercise capacity in patients with severe and moderate COPD improved by intensive endurance training, two sessions a week for 8 weeks. The improvement was however small and HRQoL did not improve. Severity of illness did not affect response to training. The results indicated that the effects of a short endurance training intervention slowed down decline in baseline functional exercise capacity for 1 year.

Aged↗

PubMed2006

Quality of life and inflammatory markers in mild asthma.

STUDY OBJECTIVES: The aim of this study was to explore the relationship between quality of life and measures of asthma, such as lung function, reversibility to bronchodilation, exhaled nitric oxide (NO), and bronchial responsiveness to direct and indirect stimulus in patients with mild asthma in a primary care setting. PATIENTS AND MEASUREMENTS: Seventy-seven asthmatic patients not treated with glucocorticosteroids completed the Asthma Quality of Life Questionnaire. Spirometry was performed before and after bronchodilation, and bronchial challenges with methacholine and eucapnic dry air hyperventilation were conducted on separate days. NO in exhaled air and serum IgE were also analyzed. RESULTS: We found no correlation between quality of life and any of the other parameters. There was a significant covariation between exhaled NO and bronchial responsiveness to methacholine and dry air, and also between FEV(1) (percentage of predicted) and reversibility to a bronchodilator. The levels of exhaled NO were higher in the asthmatic subjects with atopy than in the nonatopic asthmatics. CONCLUSIONS: The measures used in our study do not reflect health-related quality of life in subjects with mild asthma. We conclude that in the clinical situation, quality of life and other measures of asthma provide complementary information.

Adolescent↗

PubMed2006

Effect of respirators equipped with particle or particle-and-gas filters during exposure in a pig confinement building.

OBJECTIVES: This study compared the protective effect of two respiratory protection devices during exposure in a pig confinement building. METHODS: Thirty-six healthy persons were exposed for 3 hours in the building, 12 without any protection, 12 with a particle-filter mask, and 12 with a mask filtering both particles and gases. Symptoms, body temperature, nasal lavage fluid, exhaled nitric oxide, and bronchial responsiveness to methacholine were assessed before and after the exposure. Pre- and postexposure urine and blood samples were collected. RESULTS: After the exposure, the participants with respirators reported fewer symptoms than those without. Wearing a mask also reduced the inflammatory response assessed with nasal lavage (cell concentration, interleukins 6 and 8) and peripheral blood (cell number). Lung function was significantly impaired only in the unprotected group; postexposure vital capacity and forced expiratory volume in 1 second showed a decrease of 3-4% from the preexposure levels (P=0.006 and P=0.002, respectively). Bronchial responsiveness (P<0.01) and body temperature (P<0.001) increased similarly in the three groups. Bronchial responsiveness to methacholine increased 2.7, 2.4, and 2.1 doubling concentration steps for those unprotected, those using a particle-filter mask, and those using a mask with particle and gas filters, respectively. The prostaglandin D2 metabolite, 9a, 11b-PGF2 increased significantly (P=0.003) only in those unprotected. CONCLUSIONS: Wearing a respirator in a pig confinement building reduces the inflammatory reaction but does not influence the increase in bronchial responsiveness, with no difference between the use of a particle-filter mask or a mask with a particle-gas filter combination.

Adult↗

PubMed2005

Effects of 5-lipoxygenase inhibitor zileuton on airway responses to inhaled swine house dust in healthy subjects.

BACKGROUND: Inhalation of swine house dust induces acute airway inflammation and increased bronchial responsiveness in healthy subjects. OBJECTIVE: The aim of the study was to investigate whether 5-lipoxygenase products such as leukotrienes may have a role in this reaction. METHODS: Twenty-three healthy subjects were randomised into two groups receiving treatment with either zileuton (600 mg) or placebo four times a day. After 5 days of treatment, all subjects were exposed for 3h in a swine barn. Bronchial responsiveness, exhaled nitric oxide (NO), and mediators in nasal lavage (NAL), blood and urine were measured before and after the exposure. RESULTS: The exposure induced an increased bronchial responsiveness to methacholine in both groups with 2-3 doubling concentration steps, no significant difference between treatments. Leukotriene E(4) in urine increased significantly following exposure in the placebo group from 37.3 (29.1-45.6) (mean (95% confidence interval)) ng/mmol creatinine to 47.7 (36.3-59.0) ng/mmol creatinine (P<0.05), but not in the zileuton group. The post-exposure increase of LTB(4) levels in NAL fluid was totally abolished in the zileuton group (P<0.05 vs. the placebo). The levels of exhaled NO increased significantly (P<0.01), two-fold in both groups. The PGD(2) metabolite 9alpha, 11beta-PGF(2) increased in placebo-treated subjects (P<0.01; P<0.05 vs. zileuton), strengthening mast cell participation. Neutrophil counts and levels of IL-6 in peripheral blood increased in both groups, with a significantly larger increase in zileuton treated subjects (P<0.05 and P<0.001, respectively compared to placebo). CONCLUSIONS: Pre-treatment with clinically recommended doses of the 5-lipoxygenase inhibitor zileuton did not affect the increase of bronchial reactivity induced by swine dust exposure. The intervention totally abolished the LTB(4) release in NAL fluid, but only partially inhibited the formation of leukotrienes as monitored by urinary levels. The enhanced increase of neutrophils and IL-6 in peripheral blood in the zileuton group, suggests that inhibition of 5-lipoxygenase may have pro-inflammatory effects.

Adult↗

PubMed2005

Interleukin-17A mRNA and protein expression within cells from the human bronchoalveolar space after exposure to organic dust.

BACKGROUND: In mice, the cytokine interleukin (IL)-17A causes a local accumulation of neutrophils within the bronchoalveolar space. IL-17A may thereby also contribute to an increased local proteolytic burden. In the current study, we determined whether mRNA for IL-17A is elevated and protein expression of IL-17A occurs locally in inflammatory cells within the human bronchoalveolar space during severe inflammation caused by organic dust. We also assessed the expression of the elastinolytic protease MMP-9 in this airway compartment. METHODS: Six healthy, non-smoking human volunteers were exposed to organic dust in a swine confinement, a potent stimulus of neutrophil accumulation within the human bronchoalveolar space. Bronchoalveolar lavage (BAL) fluid was harvested 2 weeks before and 24 hours after the exposure and total and differential counts were conducted for inflammatory BAL cells. Messenger RNA for IL-17A was measured using reverse transcript polymerase chain reaction-enzyme linked immunoassay (RT-PCR-ELISA). Intracellular immunoreactivity (IR) for IL-17A and MMP-9, respectively, was determined in BAL cells. RESULTS: The exposure to organic dust caused more than a forty-fold increase of mRNA for IL-17A in BAL cells. IL-17A immunoreactivity was detected mainly in BAL lymphocytes, and the number of these IL-17A expressing lymphocytes displayed an eight-fold increase, even though not statistically significant. The increase in IL-17A mRNA was associated with a substantial increase of the number of BAL neutrophils expressing MMP-9 immunoreactivity. CONCLUSION: Exposure to organic dust increases local IL-17A mRNA and because there is intracellular expression in BAL lymphocytes, this suggests that IL-17A protein can originate from lymphocytes within the human bronchoalveolar space. The fact that the increased IL-17A mRNA is associated with an increased number of MMP-9-expressing neutrophils is compatible with IL-17A increasing the local proteolytic burden through its neutrophil-accumulating effect.

Adult↗

PubMed2005

Exposure to organic dust causes activation of human plasma complement factors C3 and B and the synthesis of factor C3 by lung epithelial cells in vitro.

Exposure in swine confinement buildings induces an intense airway inflammation. Twenty-two volunteers, of whom eleven wore a half-mask, were exposed for 3 hr in a swine barn. Blood samples were drawn before and after exposure. The ratio C3b/totalC3 in plasma decreased from 6.8 to 5.0% (p = 0.02) without mask and from 6.6 to 5.9% (p = 0.01) with mask (p = 0.67 between groups). The ratio Bb/totalB decreased from 14.5 to 13.5% (p < 0.01) without and 14.6-13.3% (p = 0.09) with mask (p = 0.25 between groups). Epithelial cells (A549) incubated up to 24 hr with 0.1 mg/mL dust suspensions were analysed for C3, IL-6 and IL-8 secretion. Cumulative C3 synthesis of dust stimulated cell cultures was 43,000 pg/mL compared to 25,000 pg/mL in unstimulated cells. Cumulative dust-induced IL-6 and IL-8 secretion was 200 and 3000 pg/mL, respectively and below detection in unstimulated cells. The activation of complement in vivo and induced C3 synthesis by epithelial cells suggests a role of complement in the airway reaction to organic dust exposure.

Adult↗

PubMed2005

Noneosinophilic CD4 lymphocytic airway inflammation in menopausal women with chronic dry cough.

BACKGROUND: Chronic dry cough without dyspnea and wheezing is a well-known condition that is considered to be clinically overrepresented in women. The etiology and morphology remain unknown in many cases despite thorough investigations. DESIGN: To examine inflammatory cells and the lymphocyte profile in the lower airways and blood in women with chronic cough of unknown etiology. SETTING: University hospital department of respiratory medicine. PARTICIPANTS: Twenty-five otherwise healthy women with idiopathic cough and 11 age-matched healthy control women, all nonatopic nonsmokers. MEASUREMENTS: In order to characterize the cough, a careful standardized interview of the patients was made. Lung functions were tested. Cells were collected by BAL and analyzed for differential cell counts separate in the bronchial (first) wash and in the pooled peripheral washes (BAL fluid). The lymphocyte profile in BAL fluid and blood was characterized by dual-color flow cytometry. RESULTS: Eleven female patients formed a specific group with a history of a dry, nonproductive cough that always started in connection with an airway infection coinciding with menopause. Neither exercise, climate, nor seasonal change influenced the cough. BAL fluid contained an increased number of T (CD3+) lymphocytes: median. Seventy-three percent of T lymphocytes were T-helper lymphocytes (CD4+). A median of 57% of the BAL fluid T cells expressed HLA-DR activation marker compared with a median of 20% in the control subjects and in the other 14 included patients with chronic cough but with minor expectoration periodically (p < 0.001 and p < 0.0001, respectively). No differences between the groups were found in the blood. CONCLUSIONS: HLA-DR-activated CD4+ lymphocytic airway inflammation with a low number of eosinophils was identified in a group of nonsmoking, nonatopic otherwise healthy women patients with dry cough of life-long character. The disease appeared exclusively in connection to menopause.

Adult↗

PubMed2005

Salmeterol does not alter increased bronchial responsiveness caused by organic dust exposure.

BACKGROUND: Exposure in a swine house induces airway inflammation and increases bronchial responsiveness to methacholine in healthy subjects. STUDY OBJECTIVES: The aim was to investigate whether a long-acting beta2-agonist, salmeterol, alters the increased bronchial responsiveness induced in healthy subjects following exposure to organic dust in a swine barn. DESIGN AND SUBJECTS: The study includes three separate parts. In the first part (part 1), healthy subjects inhaled salmeterol (50 microg bid, n = 8) or placebo (n = 8) over 2 weeks. In part 2, healthy subjects inhaled one single dose of salmeterol (100 microg, n = 6) or placebo (n = 6) 1 h prior to exposure in a swine barn, which was followed by a bronchial methacholine challenge. In part 3, eight healthy individuals inhaled placebo or salmeterol (100 microg), 2 h or 8 h prior to a bronchial methacholine provocation, without being exposed in the swine barn. RESULTS: Exposure caused an increase of bronchial responsiveness to methacholine by 3.2 doubling concentration steps (25 to 75th percentiles, 2.8 to 4.1) and 2.6 doubling concentration steps (25 to 75th percentiles, 1.4 to 3.7) in the placebo and salmeterol groups (2 weeks), respectively, with no significant differences between the groups (p = 0.3; part 1). Similar results were obtained when salmeterol was administered as a single dose (part 2) prior to exposure. However, salmeterol significantly attenuated the bronchial responsiveness to methacholine by 1.2 doubling concentration steps (0.8 to 1.7) 8 h after inhalation (part 3). CONCLUSIONS: Salmeterol inhalation did not protect against the increased bronchial responsiveness induced in healthy subjects following exposure to organic dust when administered for 2 weeks or as a single dose prior to exposure. This lack of protection cannot be explained by homologous beta2-adrenoceptor desensitization. We hypothesize that exposure to organic material may alter the airway response to beta2-agonists.

Administration, Inhalation↗

PubMed2004

Influence of 8-bromo-cyclicAMP on interleukin -6 and -8 mRNA levels in A549 human lung epithelial cells exposed to organic dust: a time-kinetic study.

Exposure in a swine confinement building of previously unexposed subjects leads to an intense inflammatory reaction with increased number of inflammatory cells and mediators in the upper and lower respiratory tract. In vitro the organic dust induces cytokine release from respiratory epithelial cells. Whether the dust-induced release of IL-6 and IL-8 protein from A549 lung epithelial cells is a result of sustained mRNA expression during the 24 h exposure generally applied is unknown. Furthermore, it is not known if the previously demonstrated effects on basal and dust-induced IL-6 and IL-8 protein production by 8-bromo-cyclicAMP are time-dependent, since only cumulative effects are observed by measurement of cytokine release. In the present study reverse transcription- (RT-) PCR was applied to investigate expression of IL-6 and IL-8 mRNA in A549 cells exposed to organic dust in a time-kinetic manner. The dust increased IL-6 and IL-8 mRNA expression at all times tested (1 h-48 h). The IL-6 mRNA expression peaked at 1-1.5 h and was reduced with time, whereas the dust-induced IL-8 mRNA expression remained elevated. At 1-1.5 h, 8-bromo-cAMP stimulated basal and dust-induced IL-6 mRNA expression and attenuated dust-induced IL-8 mRNA expression by activation of protein kinase A- (PKA), as assessed with the PKA inhibitor H-89. On prolonged exposure (>3 h), the dust-induced IL-6 mRNA was PKA-dependently decreased, whereas at 17 h and longer the IL-8 mRNA expression induced by a dust-suspension with 8-bromo-cAMP was similar to, or enhanced, relative to the dust-induced IL-8 mRNA. Thus, 8-bromo-cAMP exerted opposite action on dust-induced IL-6 and IL-8 mRNA expression with time.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2004

Partial protection by respirators on airways responses following exposure in a swine house.

BACKGROUND: Exposure to swine dust leads to an intense airway inflammation and increased bronchial responsiveness. The purpose of the present study was to evaluate the effect of a respiratory protection device during exposure in a swine house. METHODS: Twenty-two subjects, 11 with a respirator, were exposed. Symptoms, body temperature, nasal lavage, and a bronchial metacholine challenge were performed before and 7 hr after exposure. For exposure assessment a nasal sampler was evaluated. RESULTS: The subjects with a respirator showed an attenuated inflammatory nasal response. An increase in bronchial responsiveness was observed in both groups, significantly greater in the unprotected group. The use of respirators reduced endotoxin exposure by more than 90% (assessed by nasal samplers). CONCLUSION: The use of a respirator attenuated the inflammatory response compared with an unprotected group. The minor effect on bronchial responsiveness suggests that gases and/or ultrafine particles may also be important factors.

Adult↗

PubMed2004

Airborne cat allergen reduction in classrooms that use special school clothing or ban pet ownership.

BACKGROUND: Allergens from furred animals are brought to school mainly via clothing of pet owners. Asthmatic children allergic to cat have more symptoms when attending a class with many cat owners, and some schools allocate specific resources to allergen avoidance measures. OBJECTIVE: The aim of the current study was to evaluate the effect of school clothing or pet owner-free classes compared with control classes on airborne cat allergen levels and to investigate attitudes and allergic symptoms among the children. METHODS: Allergen measurements were performed prospectively in 2 classes with school clothing, 1 class of children who were not pet owners, and 3 control classes during a 6-week period in 2 consecutive years. Portable pumps and petri dishes were used for collection of airborne cat allergen, and a roller was used for sampling on children's clothes. Cat allergen (Fel d 1) was analyzed with enzyme-linked immunoassay and immunostaining. Both years, questionnaires were administered to the children. RESULTS: We found 4-fold to 6-fold lower airborne cat allergen levels in intervention classes compared with control classes. Levels of cat allergen were 3-fold higher on clothing of cat owners than of children without cats in control classes. Pet ownership ban seemed less accepted than school clothing as an intervention measure. CONCLUSION: For the first time, it has been shown that levels of airborne cat allergen can be reduced by allergen avoidance measures at school by using school clothing or pet ownership ban, and that both measures are equally efficient. The clinical effect of these interventions remains to be evaluated.

Air↗

PubMed2004

Acute respiratory effects of exposure to ammonia on healthy persons.

OBJECTIVES: This study investigated the acute respiratory effects of low ammonia exposure on healthy persons. METHODS: Twelve healthy persons underwent sham or ammonia (5 and 25 ppm) exposure randomly in an exposure chamber on three occasions. The exposure duration was 3 hours, 1.5 hours resting (seated) and 1.5 hours exercising (50 W on a bicycle ergonometer). Symptoms were registered repeatedly before, during, and after the exposure on visual analogue scales. Bronchial responsiveness to methacholine, lung function, and exhaled nitric oxide (NO) were measured before and 7 hours after the exposure. In addition, nasal lavage was performed, and peripheral blood samples were drawn before and 7 hours after the exposure. RESULTS: All the symptom ratings increased significantly during 25-ppm ammonia exposure as compared with the control exposure. The cumulative dose of methacholine causing a 20% decrease in forced expiratory volume in 1 second was lower (<1 concentration step of methacholine) for the exposure than for a pretrial control challenge. However, no difference was found between the control and ammonia exposures (P=0.33). The ammonia exposure did not significantly influence lung function or the exhaled NO levels. The total cell or interleukin-8 concentration in nasal lavage fluid did not change. The total leucocyte concentration in peripheral blood increased significantly (P<0.001) after both the sham and ammonia exposure, mainly due to an increase in neutrophils (P<0.001). Ammonia exposure did not significantly alter complement factor 3b in plasma. CONCLUSIONS: During ammonia exposure in an exposure chamber, symptoms related to irritation and central nervous effects increase and are constant with no signs of adaptation. Ammonia inhalation does not cause detectable upper-airway inflammation or increased bronchial responsiveness to methacholine in healthy persons.

Adult↗

PubMed2003

Organic dust activates NF-kappaB in lung epithelial cells.

Exposure in swine confinement facilities induces airway inflammation in healthy subjects. The aim of the present study was to elucidate the role of nuclear factor (NF)-kappaB in the inflammatory response induced by organic dust. A human lung epithelial carcinoma cell line (A549) was transfected with reporter genes of the human IL-6 promoter or the NF-kappaB binding site fused to the luciferase reporter gene and stimulated with dust from a swine confinement building. Cytokine release in cell culture supernatants and luciferase activity was measured. The dust-induced the activities of the IL-6 promoter reporter gene and the NF-kappaB reporter gene in parallel with an increase in IL-6 and IL-8 release. The addition of pyrrolidinedithiocarbamate, a chemical NF-kappaB blocking agent, inhibited IL-6 and IL-8 secretion as well as the NF-kappaB reporter gene activity. Increasing the amount of IkappaB alpha led to inhibition of organic dust-induced IL-6 promoter and NF-kappaB reporter gene activities. Fluticasone inhibited the organic dust-induced NF-kappaB activation and IL-6 and IL-8 secretion. Finally, swine dust incubation of A549 cells resulted in a NF-kappaB DNA binding, which is composed of the NF-kappaB1 and RelA proteins. In conclusion, by interference at various levels we have shown that NF-kappaB plays a key role in the inflammatory response to organic dust.

Androstadienes↗

PubMed2003

Does living in a cold climate or recreational skiing increase the risk for obstructive respiratory diseases or symptoms?

OBJECTIVES: Respiratory symptoms and obstructive pulmonary diseases experienced during exercise and in cold weather were analysed in a large postal questionnaire study of a general adult population living in a cold climate. The aim of this study was to assess the prevalence of shortness of breath (SOB) during exercise, or in cold weather, and to find out if the risks (odds ratio=OR) for asthma, chronic bronchitis, or SOB during exercise, or in cold weather, were affected by recreational cross-country skiing, or by outdoor work in a cold climate. RESULTS: Of the 7937 invited persons, 84% responded; 876 of them were outdoor workers and 1497 were recreational cross-country skiers. Of the non-smoking responders, asthmatic subjects had the highest prevalence of SOB during exercise in cold weather (78%-82%), but allergic and bronchitic persons also had significantly higher prevalence rates (22%-38% and 27%-59%, respectively) than healthy persons (10%-19%). In all categories, the prevalence of SOB was significantly higher among current smokers than among ex- or non-smokers. Risk factor analysis revealed increased risks for respiratory conditions among those who had a family history of obstructive airway disease, or allergy. Skiers did not have a significantly increased risk for asthma, or respiratory symptoms. Among outdoor workers the risk for SOB during exercise in cold weather, OR 1.23 (CI 1.03-1.47), and for chronic bronchitis, OR 1.77 (CI 1.21-2.60), was higher than among indoor workers. CONCLUSIONS: In conclusion, the risk for chronic bronchitis and bronchitic symptoms was elevated among outdoor workers, but not among regular recreational cross-country skiers, and the risk for asthma was not significantly elevated by regular exercising, or by working in a cold climate.

Adult↗