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Biomedical subjects

T Sandström

Publications and source records attributed to T Sandström.

At least 37 records · Page 2Linked to original sources
PubMed2002

Effect of ozone on bronchial mucosal inflammation in asthmatic and healthy subjects.

Epidemiological studies suggestthat asthmatics are more affected by ozone than healthy people. This study tested three hypotheses (1) that short-term exposure to ozone induces inflammatory cell increases and up-regulation of vascular adhesion molecules in airway lavages and bronchial tissue 6 h after ozone exposure in healthy subjects; (2) these responses are exaggerated in subjects with mild allergic asthma; (3) ozone exacerbates pre-existent allergic airways inflammation. We exposed 15 mild asthmatic and 15 healthy subjects to 0.2 ppm of ozone or filtered air for 2 h on two separate occasions. Airway lavages and bronchial biopsies were obtained 6 h post-challenge. We found that ozone induced similar increases in bronchial wash neutrophils in both groups, although the neutrophil increase in the asthmatic group was on top of an elevated baseline. In healthy subjects, ozone exposure increased the expression of the vascular endothelial adhesion molecules P-selectin and ICAM- 1, as well as increasing tissue neutrophil and mast cell numbers. The asthmatics showed allergic airways inflammation at baseline but ozone did not aggravate this at the investigated time point. At 6 h post-ozone-exposure, we found no evidence that mild asthmatics were more responsive than healthy to ozone in terms of exaggerated neutrophil recruitment or exacerbation of pre-existing allergic inflammation. Further work is needed to assess the possibility of a difference in time kinetics between healthy and asthmatic subjects in their response to ozone.

Adult↗
PubMed2002

Ambient level of NO2 augments the inflammatory response to inhaled allergen in asthmatics.

Air pollution constitutes an important factor for asthma aggravation, and there is increased concern about respiratory health effects of common air pollutants. The purpose of this study was to examine how exposure to a high ambient concentration nitrogen dioxide (NO2) prior to a bronchial allergen challenge modulated the inflammatory response in the bronchi. Thirteen subjects with mild asthma and allergy were exposed at rest to either purified air or 500 microg x m 3 NO2 for 30 min, followed 4 h later by an allergen inhalation challenge. The exposures (NO2 or air) were performed in random order and at least 4 weeks apart. Lung function during NO2/air exposure and allergen challenge was measured by plethysmography, and then hourly by portable spirometry after exposures. Subjective symptoms were recorded during and after exposure. Bronchoscopy with bronchial wash (BW) and bronchoalveolar lavage (BAL) was performed 19 h after allergen challenge. NO2+allergen enhanced the percentage of neutrophils in both BW and BAL compared to air+allergen (BW 19 vs. 11, P=0.05; BAL 3 vs. 1, P=0.02 median values). The levels of eosinophil cationic protein (ECP) in BW was higher after NO2+allergen compared to air+allergen (90 vs. 3.6 microg/l; P=0.02, median values). There was no NO2-associated effect on symptoms or pulmonary function. These data suggest that ambient NO2 can enhance allergic inflammatory reaction in the airways without causing symptoms or pulmonary dysfunction.

Adult↗
PubMed2002

The effects of regular inhaled formoterol and budesonide on preformed Th-2 cytokines in mild asthmatics.

In a recent placebo-controlled study in mild atopic asthmatics, we observed a significant decrease in eosinophils in the bronchial submucosa, after 2 months oftreatment with inhaled formoterol and budesonide. Biopsy material from each treatment group; formoterol (24 microg bid), budesonide (400 microg b. i. d.) and placebo has been further assessed to investigatethe role of Th-2 cytokines by immunohistochemistry using Mabs to eosinophils as an index of inflammation, IL-4 and IL-5. Treatment with formoterol significantly reduced the number of eosinophils (EG2+) in the submucosa and epithelium, but this was not paralleled by changes in cytokine immunoreactivity In contrast, treatment with budesonide significantly reduced both the number of eosinophils (EG2+) and immunoreactivity for IL-4 and IL-5 in the submucosa. Thus, while budesonide has effects on cytokines involved in eosinophil recruitmentthis explanation does not apply tothe eosinopaenia observed with the long-acting beta2 adrenoreceptor agonist formoterol.

Administration, Inhalation↗
PubMed2001

Differences in basal airway antioxidant concentrations are not predictive of individual responsiveness to ozone: a comparison of healthy and mild asthmatic subjects.

The air pollutant ozone induces both airway inflammation and restrictions in lung function. These responses have been proposed to arise as a consequence of the oxidizing nature of ozone, depleting endogenous antioxidant defenses with ensuing tissue injury. In this study we examined the impact of an environmentally relevant ozone challenge on the antioxidant defenses present at the surface of the lung in two groups known to have profound differences in their antioxidant defense network: healthy control (HC) and mild asthmatic (MA) subjects. We hypothesized that baseline differences in antioxidant concentrations within the respiratory tract lining fluid (RTLF), as well as induced responses, would predict the magnitude of individual responsiveness. We observed a significant loss of ascorbate (ASC) from proximal (-45.1%, p <.01) and distal RTLFs (-11.7%, p <.05) in healthy subjects 6 h after the end of the ozone challenge. This was associated (Rs, -0.71, p <.01) with increased glutathione disulphide (GSSG) in these compartments (p =.01 and p <.05). Corresponding responses were not seen in asthmatics, where basal ASC concentrations were significantly lower (p <.01) and associated with elevated concentrations of GSSG (p <.05). In neither group was any evidence of lipid oxidation seen following ozone. Despite differences in antioxidant levels and response, the magnitude of ozone-induced neutrophilia (+20.6%, p <.01 [HC] vs. +15.2%, p =.01 [MA]) and decrements in FEV(1) (-8.0%, p <.01 [HC] vs. -3.2%, p <.05 [MA]) did not differ between the two groups. These data demonstrate significant differences between the interaction of ozone with RTLF antioxidants in MA and HC subjects. These responses and variations in basal antioxidant defense were not, however, useful predictive markers of group or individual responsiveness to ozone.

Adult↗
PubMed2001

Effects of budesonide and formoterol on NF-kappaB, adhesion molecules, and cytokines in asthma.

The asthmatic inflammatory response can be attenuated by corticosteroids and in part by beta(2)-agonists. We investigated if these effects are accompanied by a downregulation in nuclear factor kappa B (NF-kappaB), a transcription factor regulating many of the cytokine and adhesion molecule genes expressed in allergic inflammation. Bronchial biopsies were taken before and after 8 wk treatment with formoterol, budesonide, or placebo from atopic asthmatics. Biopsies were processed into glycol methacrylate and stained immunohistochemically for eosinophils (as an index of inflammation), activated and total NF-kappaB, adhesion molecules, and cytokines. After budesonide treatment there was a significant decrease in the number of submucosal cells staining for total NF-kappaB, granulocyte macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha), accompanied by a significant decrease in mucosal eosinophils and expression of vascular cell adhesion molecule-1 (VCAM-1) in the endothelium and interleukin-8 (IL-8) in the epithelium. After formoterol treatment there was a significant decrease in eosinophils and the epithelial expression of activated NF-kappaB, but these changes were not accompanied by reduced immunoreactivity for adhesion molecules or cytokines. We conclude that at least some of the therapeutic efficacy of inhaled corticosteroids is mediated through inhibition of NF-kappaB-regulated gene expression, whereas the reduction in airway eosinophilia by long-acting beta(2)-agonists probably operates through alternative pathways.

Administration, Topical↗
PubMed2001

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.

Adult↗
PubMed2001

Nitric oxide (NO) in exhaled air after experimental ozone exposure in humans.

We hypothesized that ozone, a common air pollutant, potent in producing airway inflammation, would increase the production of exhaled nitric oxide (NO). If so, measurement of exhaled NO could potentially be a valuable tool in population studies of air pollution effects. Eleven healthy non-smoking volunteers were exposed to 0.2 ppm ozone (O3) and filtered air for 2h on two separate occasions. Exhaled NO and nasal NO were measured before and on five occasions following the exposures. Changes in exhaled and nasal NO after ozone exposure were adjusted for changes after air exposure. There was a slight decrease in exhaled NO (-0.6; -3.1-1.2 ppb) (median and 95% confidence interval) and of nasal NO (-57; -173-75 ppb) directly after the ozone exposure. No significant changes in exhaled or nasal NO were however found 6 or 24 h after the exposure. Within the examined group, an O3 exposure level proven to induce an airway inflammation caused no significant changes in exhaled or nasal NO levels. Hence, the current study did not yield support for exhaled NO as a useful marker of ozone-induced oxidative stress and airway inflammation after a single exposure. This contrasts with data for workers exposed to repeated high peaks of ozone. The potential for exhaled NO as a marker of oxidative stress therefore deserves to be further elucidated.

Adult↗
PubMed2001

Incidence of physician-diagnosed asthma in adults--a real incidence or a result of increased awareness? Report from The Obstructive Lung Disease in Northern Sweden Studies.

Only limited data are available about the incidence of asthma based on longitudinal prospective studies. Further, the results from different studies on incidence vary considerably depending on the age composition of the cohorts under study, the used methods and the criteria for disease. Also among adults high incidence rates have been reported during recent years. The aim of this study was to examine to what extent the incidence of physician-diagnosed asthma could be explained by a real incidence of the disease, and to what extend by an increased diagnostic activity or altered diagnostic praxis. Another aim was to study risk factors for asthma based on incident cases. Three cross-sectional surveys have been performed in the same population sample living in the northern-most province of Sweden, Norrbotten. The first survey was performed in 1986, and 5698 subjects, 86% of those invited, responded to a postal questionnaire. Of these, 4754 subjects (83%) participated at the third survey in 1996. After exclusion of all subjects who had reported that they had asthma in 1986, or had been classified as having asthma in 1986, 68 men and 98 women (P=0.02) reported in 1996 that they had been diagnosed as having asthma by a physician. Thus, the cumulative incidence for the 10-year period was 3.2% among men and 4.5% among women. After correction for subjects who already in 1986 had reported symptoms common in asthma, or had been classified as having chronic bronchitis, 97 subjects with incident asthma remained, which corresponded to an annual incidence rate among men of 1.7 and among women of 2.9/1000 persons year(-1) (P=0.1). Clinical examinations confirmed asthma in a large majority of these 97 subjects. Significant risk factors were family history of asthma, both ex- and current smoking, and female sex. The socio-economic groups manual workers and assistant non-manual employees were associated with incident asthma, although not significantly. The increasing prevalence of asthma among adults during recent 10-20 years may to a considerable extent be explained by an increased diagnostic activity or altered diagnostic praxis. Use of different methods when measuring incidence may in part explain the extremely diverging incidence rates of asthma found in different studies.

Aged↗
PubMed2001

The effect of different concentrations of lactose powder on the airway function of adult asthmatics.

Lactose is widely used as a carrier of drugs in inhalation devices for asthmatic patients, but some clinicans have suspected that it may cause bronchoconstriction. Only a few studies have been done to examine this and the results are not uniform. This study was conducted to determine the effects of inhalation grade lactose delivered by Diskhaler on lung function and airway conductance in asthmatic subjects. The effect of five doses of lactose ranging from 6.25 mg to 100 mg and placebo were investigated using spirometry and constant volume plethysmography. Nineteen subjects (nine females) with stable asthma and a proven reversibility of at least 12% in forced expiratory volume in 1 sec (FEV) (compared to baseline) in the last 6 months, were included in this single-centre, randomized, placebo-controlled, double-blind, cross-over study. The subjects received placebo plus five doses of lactose on one study day and six doses of placebo on another study day. Both doses and study days were assigned in a random order, and intervals of 1 h were allowed between each dose and at least 36 h between study days. Specific airways conductance (sGaw) and FEV were measured periodically over the course of 1 h after each dose of lactose or placebo. Administration of lactose at four or eight times the concentration in the Diskus and Diskhaler dry powder inhalers did not result in any statistically significant changes in FEV1. sGaw also showed no statistical difference between lactose and placebo at 1 or 3 min post-dosing. Both placebo and lactose produced both dilatation and constriction of the airways in the same patients, with no consistency in direction and no dose-response relationship. No adverse effect of lactose on a rways conductance or FEV1 of stable asthmatic patients was found in this study when given at higher than normal clinical doses.

Adolescent↗
PubMed2001

Health effects of diesel exhaust emissions.

Epidemiological studies have demonstrated an association between different levels of air pollution and various health outcomes including mortality, exacerbation of asthma, chronic bronchitis, respiratory tract infections, ischaemic heart disease and stroke. Of the motor vehicle generated air pollutants, diesel exhaust particles account for a highly significant percentage of the particles emitted in many towns and cities. This review is therefore focused on the health effects of diesel exhaust, and especially the particular matter components. Acute effects of diesel exhaust exposure include irritation of the nose and eyes, lung function changes, respiratory changes, headache, fatigue and nausea. Chronic exposures are associated with cough, sputum production and lung function decrements. In addition to symptoms, exposure studies in healthy humans have documented a number of profound inflammatory changes in the airways, notably, before changes in pulmonary function can be detected. It is likely that such effects may be even more detrimental in asthmatics and other subjects with compromised pulmonary function. There are also observations supporting the hypothesis that diesel exhaust is one important factor contributing to the allergy pandemic. For example, in many experimental systems, diesel exhaust particles can be shown to act as adjuvants to allergen and hence increase the sensitization response. Much of the research on adverse effects of diesel exhaust, both in vivo and in vitro, has however been conducted in animals. Questions remain concerning the relevance of exposure levels and whether findings in such models can be extrapolated into humans. It is therefore imperative to further assess acute and chronic effects of diesel exhaust in mechanistic studies with careful consideration of exposure levels. Whenever possible and ethically justified, studies should be carried out in humans.

Animals↗
PubMed2001

Diesel exhaust enhances airway responsiveness in asthmatic subjects.

Particulate matter (PM) pollution has been associated with negative health effects, including exacerbations of asthma following exposure to PM peaks. The aim of the present study was to investigate the effects of short-term exposure to diesel exhaust (DE) in asthmatics, by specifically addressing the effects on airway hyperresponsiveness, lung function and airway inflammation. Fourteen nonsmoking, atopic asthmatics with stable disease, on continuous treatment with inhaled corticosteroids, were included. All were hyperresponsive to methacholine. Each subject was exposed to DE (particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10) 300 microg x m(-3)) and air during 1 h on two separate occasions. Lung function was measured before and immediately after the exposures. Sputum induction was performed 6 h, and methacholine inhalation test 24 h, after each exposure. Exposure to DE was associated with a significant increase in the degree of hyperresponsiveness, as compared to after air, of 0.97 doubling concentrations at 24 h after exposure (p < 0.001). DE also induced a significant increase in airway resistance (p=0.004) and in sputum levels of interleukin (IL)-6 (p=0.048). No changes were detected in sputum levels of methyl-histamine, eosinophil cationic protein, myeloperoxidase and IL-8. This study indicated that short-term exposure to diesel exhaust, equal to high ambient levels of particulate matter, is associated with adverse effects in asthmatic airways, even in the presence of inhaled corticosteroid therapy. The increase in airway responsiveness may provide an important link to epidemiological findings of exacerbations of asthma following exposure to particulate matter.

Adult↗
PubMed2000

The anti-inflammatory profile of inhaled corticosteroids combined with salmeterol in asthmatic patients.

Inhaled corticosteroid (ICS) therapy such as fluticasone propionate (FP) is effective in moderate-to-severe asthma, but for patients on ICS who still experience symptoms, treatment guidelines recommend either increasing the dose of ICS or adding a long-acting beta2-agonist such as salmeterol or formoterol. Several studies have now shown that adding salmeterol provides greater clinical benefit than increasing the dose of ICS, raising the question of whether salmeterol has an additive or complementary anti-inflammatory effect to that of ICS. Recent studies on bronchial biopsies and bronchoalveolar lavage from asthmatic patients treated with either salmeterol. FP or placebo in addition to low-dose ICS have demonstrated that addition of salmeterol produces independent or additional reductions in several pro-inflammatory cells, cytokines and cell adhesion molecules compared with FP. Such complementary anti-inflammatory effects may explain the improved control of asthma symptoms and exacerbations observed when salmeterol is added to low-dose ICS therapy, and may help to modify the long-term sequelae of asthma. These findings also indicate, contrary to earlier speculation, that salmeterol does not have a pro-inflammatory effect or mask persistent airway inflammation. This review presents the results of recent studies and suggests possible mechanisms for the additional antiinflammatory effects of salmeterol.

Administration, Inhalation↗
PubMed2000

Airway inflammation following exposure to diesel exhaust: a study of time kinetics using induced sputum.

The adverse health effects of particulate matter pollution are of increasing concern. In a recent bronchoscopic study in healthy volunteers, pronounced airway inflammation was detected following exposure to diesel exhaust (DE). The present study was conducted in order to evaluate the time kinetics of the inflammatory response following exposure to DE using induced sputum from healthy volunteers. Fifteen healthy nonsmoking volunteers were exposed to DE particles with a 50% cut-off aerodynamic diameter of 10 microm 300 microg x m(-3) and air for 1 h on two separate occasions. Sputum induction with hypertonic saline was performed 6 and 24 h after each exposure. Analyses of sputum differential cell counts and soluble protein concentrations were performed. Six hours after exposure to DE, a significant increase was found in the percentage of sputum neutrophils (37.7 versus 26.2% p=0.002) together with increases in the concentrations of interleukin-6 (12.0 versus 6.3 pg x mL(-1), p=0.006) and methylhistamine (0.11 versus 0.12 microg x L(-1), p=0.024). Irrespective of exposure, a significant increase was found in the percentage of sputum neutrophils at 24 as compared to 6 h, indicating that the procedure of sputum induction itself may change the composition of sputum. This study demonstrates that exposure to diesel exhaust induces inflammatory response in healthy human airways, represented by an early increase in interleukin-6 and methylhistamine concentration and the percentage of neutrophils. Induced sputum provides a safe tool for the investigation of the inflammatory effects of diesel exhaust, but care must be taken when interpreting results from repeated sputum inductions.

Adult↗
PubMed2000

Recombinant humanized mAb-E25, an anti-IgE mAb, in birch pollen-induced seasonal allergic rhinitis.

BACKGROUND: Allergic rhinitis is a common condition often requiring treatment. OBJECTIVE: We evaluated whether recombinant humanized (rhu)mAb-E25, a recombinant humanized construct of a murine antibody that binds to circulating IgE, could control symptoms and reduce intake of concomitant medication in seasonal allergic rhinitis (SAR) induced by birch pollen if given subcutaneously in a dose schedule predicted to reduce serum free IgE levels below 25 ng/mL. METHODS: We randomly assigned 251 adult subjects with a history of SAR and a positive skin test response to birch pollen to receive 300 mg of rhumAb-E25 or placebo given 2 or 3 times during the season, depending on baseline IgE levels. The primary efficacy variable was the subject's average daily nasal symptom severity score (sneezing, itching, runny, and stuffy nose) from diary data collected over the double-blind treatment period. Secondary efficacy variables included the average number of rescue antihistamine tablets per day, the proportion of days with any SAR medication use, and rhinoconjunctivitis-specific quality of life (QOL). RESULTS: Significant between-treatment differences in favor of rhumAb-E25 were observed in average daily nasal symptom severity scores, the average number of tablets of rescue antihistamines per day, the proportion of days with any SAR medication use, and all domains of QOL. Serum-free IgE levels were markedly lower in rhumAb-E25-treated subjects and were associated with clinical effectiveness. Recombinant humanized mAb-E25 was well tolerated. No anti-rhumAb-E25 antibodies were detected. CONCLUSION: Compared with placebo, rhumAb-E25 was safe and effective in controlling birch pollen-induced SAR symptoms, with less concomitant medication use and improved QOL. This study shows the therapeutic potential of anti-IgE antibody in SAR.

Adolescent↗
PubMed2000

Acute exposure to diesel exhaust increases IL-8 and GRO-alpha production in healthy human airways.

We have previously demonstrated that short-term exposure to diesel exhaust (DE) for 1 h induced a marked leukocytic infiltration in the airways of healthy human volunteers involving neutrophils, lymphocytes, and mast cells along with increases in several inflammatory mediators. We hypothesized that the leukocyte infiltration and the various inflammatory responses induced by DE were mediated by enhanced chemokine and cytokine production by resident cells of the airway tissue and lumen. To investigate this, 15 healthy human volunteers were exposed to diluted DE and air on two separate occasions for 1 h each in an exposure chamber. Fiberoptic bronchoscopy was performed 6 h after each exposure to obtain endobronchial biopsies and bronchial wash (BW) cells. Using reverse transcriptase/polymerase chain reaction enzyme-linked immunosorbent assay (RT-PCR ELISA), a novel and sensitive technique to quantify relative amounts of cytokine mRNA gene transcripts, and immunohistochemical staining with computer-assisted image analysis to quantify expression of cytokine protein in the bronchial tissue, we have demonstrated that DE enhanced gene transcription of interleukin-8 (IL-8) in the bronchial tissue and BW cells along with increases in IL-8 and growth-regulated oncogene-alpha (GRO-alpha) protein expression in the bronchial epithelium, and an accompanying trend toward an increase in IL-5 mRNA gene transcripts in the bronchial tissue. There were no significant changes in the gene transcript levels of interleukin-1B (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interferon gamma (IFN-gamma), and granulocyte macrophage colony-stimulating factor (GM-CSF) either in the bronchial tissue or BW cells after DE exposure at this time point. These observations suggest an underlying mechanism for DE-induced airway leukocyte infiltration and offer a possible explanation for the association observed between ambient levels of particulate matter and various respiratory health outcome indices noted in epidemiological studies.

Bronchoalveolar Lavage Fluid↗
PubMed1999

Altered lung antioxidant status in patients with mild asthma.

Lung lining fluid ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) concentrations are low in patients with mild asthma even though blood levels are normal or increased. These findings, along with the presence of increased amounts of oxidised glutathione in their airways, indicate that patients with asthma are subject to increased oxidative stress.

Antioxidants↗