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Biomedical subjects

T Sandström

Publications and source records attributed to T Sandström.

At least 19 recordsLinked to original sources
PubMed2006

Airway inflammation in iron ore miners exposed to dust and diesel exhaust.

The aim of the present study was to investigate if underground miners exposed to dust and diesel exhaust in an iron ore mine would show signs of airway inflammation as reflected in induced sputum. In total, 22 miners were studied, once after a holiday of at least 2 weeks and the second time after 3 months of regular work. Control subjects were 21 "white-collar" workers. All subjects completed a questionnaire regarding medical and occupational history, and underwent lung function testing and induced sputum collection. Total and differential cell counts and analyses of the fluid phase of the induced sputum were performed. Sampling of personal exposure to elemental carbon, nitrogen dioxide and inhalable dust was recorded. The average concentrations of inhalable dust, nitrogen dioxide and elemental carbon were 3.2 mg.m-3, 0.28 mg.m-3 and 27 microg.m-3, respectively. Miners had increased numbers of inflammatory cells, mainly alveolar macrophages and neutrophils, and increased concentrations of fibronectin, metalloproteinase-9 and interleukin-10 in induced sputum compared with controls. In conclusion, miners in an underground iron ore mine demonstrated persistent airway inflammation that was as pronounced after a 4-week holiday as after a 3-month period of work underground in the mine.

Adult↗
PubMed2006

Asthma during the primary school ages--prevalence, remission and the impact of allergic sensitization.

BACKGROUND: Childhood is the most important time for asthma development. The aims of this study were to study changes in prevalence of asthma and wheeze, remission of asthma and changes in risk factor pattern from age 7-8 to age 11-12 in a cohort of school children. METHODS: In 1996, 3525 children aged 7-8 years in northern Sweden were invited to participate in a parental expanded ISAAC questionnaire survey. The cohort has been followed prospectively with yearly follow-ups to age 11-12, with a 97% yearly response rate. Skin prick tests were conducted at age 7-8 and 11-12. RESULTS: The prevalence of physician-diagnosed asthma increased from 5.7% at age 7-8 to 7.7% at age 11-12. Life-time prevalence of wheeze was 34.7% at age 11-12. The remission of asthma was 10% yearly and inversely related to allergic sensitization. Relapses were common, and remission persisting throughout the observation period was 5% yearly. Allergic sensitization was associated with current asthma at age 7-8 [adjusted odds ratio (OR) 4.9 (95% confidence interval (CI) 3.3-7.3)] and when the children were 4 years older [OR 5.6 (3.9-8.2)]. A family history of asthma was associated with current asthma at age 7-8 [OR 3.0 (2.1-4.5)] and 11-12 (OR 2.8 [2.0-3.9]). Ever having lived with a cat was significantly negatively associated with current asthma. CONCLUSIONS: The prevalence of asthma increased continuously during the primary school ages. Among several significant risk factors, allergic sensitization and a family history of asthma were the most important. With increasing age many known risk factors lost significance. Remission was inversely related to allergic sensitization.

Age Distribution↗
PubMed2006

Airway antioxidant and inflammatory responses to diesel exhaust exposure in healthy humans.

Pulmonary cells exposed to diesel exhaust (DE) particles in vitro respond in a hierarchical fashion with protective antioxidant responses predominating at low doses and inflammation and injury only occurring at higher concentrations. In the present study, the authors examined whether similar responses occurred in vivo, specifically whether antioxidants were upregulated following a low-dose DE challenge and investigated how these responses related to the development of airway inflammation at different levels of the respiratory tract where particle dose varies markedly. A total of 15 volunteers were exposed to DE (100 microg x m(-3) airborne particulate matter with a diameter of <10 microm for 2 h) and air in a double-blinded, randomised fashion. At 18 h post-exposure, bronchoscopy was performed with lavage and mucosal biopsies taken to assess airway redox and inflammatory status. Following DE exposure, the current authors observed an increase in bronchial mucosa neutrophil and mast cell numbers, as well as increased neutrophil numbers, interleukin-8 and myeloperoxidase concentrations in bronchial lavage. No inflammatory responses were seen in the alveolar compartment, but both reduced glutathione and urate concentrations were increased following diesel exposure. In conclusion, the lung inflammatory response to diesel exhaust is compartmentalised, related to differing antioxidant responses in the conducting airway and alveolar regions.

Adult↗
PubMed2006

The economic value of anti-IgE in severe persistent, IgE-mediated (allergic) asthma patients: adaptation of INNOVATE to Sweden.

BACKGROUND: Severe allergic asthma patients may not be controlled even with guideline recommended care, including inhaled corticosteroids, long-acting beta-2 agonists, theophylline, oral steroids and anti-leukotrienes. They experience exacerbations requiring intensive healthcare use and which may be fatal. Omalizumab, a new monoclonal antibody for use in IgE-mediated allergic diseases, reduces exacerbations and daily symptoms in this patient population. The aim of this study is to estimate the cost effectiveness of adding omalizumab to optimized standard therapy (ST) in patients with severe persistent IgE-mediated (allergic) asthma. METHODS: A Markov model comparing lifelong ST with a treatment period of omalizumab add-on therapy followed by ST, was developed based on efficacy data from the INNOVATE trial (28 weeks, N = 419) and Swedish life table and cost data. This model assumes that patients are at risk of having an exacerbation every 2 weeks and are at risk of dying from a clinically significant severe asthma exacerbation. Patients in a steady-state of having no exacerbations are defined to be in an 'optimized asthma control' state. Resource use data and utilities were obtained from INNOVATE and from a UK observational study. Costs from a societal perspective include estimates for drugs, routine care, exacerbations and costs in added years of life; benefits are expressed in QALYs. The response to omalizumab was evaluated after 16 weeks of trial, and non-responders stopped taking omalizumab for the remaining time. RESULTS: Total lifetime discounted costs and QALYs on ST were 52,702 euros and 11.60. Omalizumab add-on therapy cost an additional 42,754 euros for 0.76 additional QALYs, resulting in an incremental cost-effectiveness ratio of 56,091 euros. A probabilistic sensitivity analysis indicates that the 95% CI around the ICER is [31,328 euros; 120,552 euros]. One-way analyses indicate that the results are sensitive to the exacerbation-related mortality rate, the time horizon and the discount rates. CONCLUSIONS: Based on the model and the assumptions used, our results suggest that omalizumab provides cost offsets, improves quality of life and may have an attractive ICER in treating the severe allergic asthma population.

Adult↗
PubMed2005

Increased expression of p38 MAPK in human bronchial epithelium after lipopolysaccharide exposure.

Bacterial endotoxin (lipopolysaccharides (LPS)) is normally present in the wall of Gram-negative bacteria and has potent pro-inflammatory properties. Exposure to LPS has been shown to induce neutrophilic airway inflammation in humans. The aim of this investigation was to study the early inflammatory responses to LPS exposure in human airway mucosa in vivo. In total, 15 healthy nonsmoking volunteers participated. Bronchoscopy was performed on two separate occasions, 3 h after saline inhalation and after inhalation of 50 mug LPS in saline. Endobronchial mucosal biopsy specimens were taken and stained immunohistochemically using a panel of monoclonal antibodies directed against mitogen-activated protein kinases (MAPKs), transcription factors, cytokines, adhesion molecules and inflammatory cells. Expression of p38 MAPK increased as a consequence of LPS exposure, as determined by both total epithelial staining and nuclear location. These two responses were strongly associated. Epithelial expression of interleukin-8 showed a tendency towards a significant increase after LPS compared to saline. Epithelial mast cell numbers were increased after LPS, whereas neutrophil numbers were unchanged. Inhalation of lipopolysaccharide induced activation of the bronchial epithelium, as demonstrated 3 h after exposure by increased expression of p38 mitogen-activated protein kinase and interleukin-8, and may represent early regulatory steps in the subsequent development of a neutrophilic bronchial inflammation.

Adult↗
PubMed2005

Altered protein tyrosine phosphorylation in asthmatic bronchial epithelium.

A disease-related, corticosteroid-insensitive increase in the expression of epidermal growth factor (EGF) receptor (EGFR) tyrosine kinase in asthmatic bronchial epithelium has been shown previously by the current authors. To determine whether this is associated with enhanced intracellular signalling, the aim of this study was to evaluate epithelial tyrosine phosphorylation. Bronchial biopsies were analysed for the presence of phosphotyrosine by immunohistochemistry. Bronchial epithelial cells were exposed to EGF, hydrogen peroxide or tumour necrosis factor-alpha in vitro for measurement of tyrosine phosphorylated signalling intermediates and interleukin (IL)-8 release. Phosphotyrosine was increased significantly in the epithelium of severe asthmatics when compared with controls or mild asthmatics; however, in mild asthma, phosphotyrosine levels were significantly decreased when compared with controls. There was no significant difference between phosphotyrosine levels before or after 8 weeks of treatment with budesonide. Stimulation of bronchial epithelial cells resulted in tyrosine phosphorylation of several proteins, including EGFR, Shc and p42/p44 mitogen-activated protein kinase. In the presence of salbutamol, a transient partial suppression of EGFR phosphorylation occurred, whereas dexamethasone was without effect. Neither salbutamol nor dexamethasone inhibited EGF-stimulated IL-8 release. These data indicate that regulation of protein tyrosine kinase activity is abnormal in severe asthma. The epidermal growth factor receptor and/or other tyrosine kinase pathways may contribute to persistent, corticosteroid-unresponsive inflammation in severe asthma.

Administration, Inhalation↗
PubMed2005

Inflammatory markers in bronchoalveolar lavage fluid from human volunteers 2 hours after hydrogen fluoride exposure.

Fluoride has been in focus as a possible causal agent for respiratory symptoms amongst aluminium potroom workers for several decades. Previously, using bronchoalveolar lavage (BAL), we demonstrated airway inflammation in healthy volunteers 24 hours after exposure to hydrogen fluoride (HF). The objective of the present study was to examine early lung responses to HF exposure. Bronchoscopy with BAL was performed 2 hours after the end of 1-hour exposure to HE Significant reductions in the total cell number and the number of neutrophils and lymphocytes were observed in bronchoalveolar portion (BAP), whereas there were no significant changes in the bronchial portion (BP). Significantly decreased concentrations of beta2-MG, IL-6 and total protein were found in both BAP and BP. Additionally, IL-8 was significantly reduced in BP, and ICAM-1 and albumin were present in lower concentrations in BAP. Lung function measurements were not affected by HF exposure. These reported effects are presumably transitory, as many were not present in the airways 24 hours after a similar HF exposure.

Administration, Inhalation↗
PubMed2004

Different airway inflammatory responses in asthmatic and healthy humans exposed to diesel.

Particulate matter (PM) pollution adversely affects the airways, with asthmatic subjects thought to be especially sensitive. The authors hypothesised that exposure to diesel exhaust (DE), a major source of PM, would induce airway neutrophilia in healthy subjects, and that either these responses would be exaggerated in subjects with mild allergic asthma, or DE would exacerbate pre-existent allergic airways. Healthy and mild asthmatic subjects were exposed for 2 h to ambient levels of DE (particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10) 108 microg x m(-3)) and lung function and airway inflammation were assessed. Both groups showed an increase in airway resistance of similar magnitude after DE exposure. Healthy subjects developed airway inflammation 6 h after DE exposure, with airways neutrophilia and lymphocytosis together with an increase in interleukin-8 (IL-8) protein in lavage fluid, increased IL-8 messenger ribonucleic acid expression in the bronchial mucosa and upregulation of the endothelial adhesion molecules. In asthmatic subjects, DE exposure did not induce a neutrophilic response or exacerbate their pre-existing eosinophilic airway inflammation. Epithelial staining for the cytokine IL-10 was increased after DE in the asthmatic group. Differential effects on the airways of healthy subjects and asthmatics of particles with a 50% cut-off aerodynamic diameter of 10 microm at concentrations below current World Health Organisation air quality standards have been observed in this study. Further work is required to elucidate the significance of these differential responses.

Adult↗
PubMed2004

Adjustable maintenance dosing with budesonide/formoterol compared with fixed-dose salmeterol/fluticasone in moderate to severe asthma.

BACKGROUND: Current asthma guidelines recommend that patients are educated to adjust their medication according to their asthma severity using physician-guided self-management plans. However, many patients take a fixed dose of their controller medication and adjust their reliever medication according to asthma symptoms. OBJECTIVES: This study examined whether asthma control improved if patients adjusted the maintenance dose of budesonide/formoterol (Symbicort Turbuhaler* 160/4.5 microg) according to asthma severity compared with traditional fixed dosing (FD) regimens. METHODS: Symptomatic patients with asthma (n = 658, mean symptom score 1.5, mean inhaled corticosteroids 735 microg/day, mean forced expiratory volume in 1 second [FEV(1)] 84% predicted) were randomised after 2 weeks' run-in to either: budesonide/formoterol adjustable maintenance dosing (AMD), budesonide/formoterol FD or salmeterol/fluticasone (Seretide Diskus dagger 50/250 microg) FD. In a 4-week double-blind period, both budesonide/formoterol AMD and FD groups received two inhalations twice daily (bid) and salmeterol/fluticasone FD patients received one inhalation bid. In the following 6-month open extension, both FD groups continued with the same treatment. Patients in the AMD group with well-controlled asthma stepped down to one inhalation bid; others continued with two inhalations bid. All AMD patients could increase to four inhalations bid for 7-14 days if symptoms worsened. All patients used terbutaline or salbutamol for symptom relief throughout. The primary variable was the odds of achieving a well-controlled asthma week (WCAW). RESULTS: The odds ratio for achieving a WCAW did not differ between the FD regimens; however, during the open period, budesonide/formoterol AMD increased the odds of achieving a WCAW vs. budesonide/formoterol FD (odds ratio 1.335; 95% CI: 1.001, 1.783; p = 0.049) despite a 15% reduction in average study drug use. Budesonide/formoterol AMD patients had a lower exacerbation rate over the study: 40% lower vs. salmeterol/fluticasone FD (p = 0.018); 32% lower vs. budesonide/formoterol FD (NS). During the double-blind period, there were no clinically relevant differences between the budesonide/formoterol FD and salmeterol/fluticasone FD groups. Budesonide/formoterol AMD patients used less reliever medication in the open extension: 0.58 vs. 0.92 occasions/day for budesonide/formoterol FD (p = 0.001) and 0.80 occasions/day for salmeterol/fluticasone FD (p = 0.011). CONCLUSIONS: Adjustable maintenance dosing with budesonide/formoterol provides more effective asthma control by reducing exacerbations and reliever medication usage compared with fixed-dose salmeterol/fluticasone.

Adolescent↗
PubMed2003

Ozone-induced bronchial epithelial cytokine expression differs between healthy and asthmatic subjects.

BACKGROUND: Ozone (O3) is a common air pollutant associated with adverse health effects. Asthmatics have been suggested to be a particularly sensitive group. OBJECTIVE: This study evaluated whether bronchial epithelial cytokine expression would differ between healthy and allergic asthmatics after ozone exposure, representing an explanatory model for differences in susceptibility. METHODS: Healthy and mild allergic asthmatic subjects (using only inhaled beta2-agonists prn) were exposed for 2 h in blinded and randomized sequence to 0.2 ppm of O3 and filtered air. Bronchoscopy with bronchial mucosal biopsies was performed 6 h after exposure. Biopsies were embedded in GMA and stained with mAbs for epithelial expression of IL-4, IL-5, IL-6, IL-8, IL-10, TNF-alpha, GRO-alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), fractalkine and ENA-78. RESULTS: When comparing the two groups at baseline, the asthmatic subjects showed a significantly higher expression of IL-4 and IL-5. After O3 exposure the epithelial expression of IL-5, GM-CSF, ENA-78 and IL-8 increased significantly in asthmatics, as compared to healthy subjects. CONCLUSION: The present study confirms a difference in epithelial cytokine expression between mild atopic asthmatics and healthy controls, as well as a differential epithelial cytokine response to O3. This O3-induced upregulation of T helper type 2 (Th2)-related cytokines and neutrophil chemoattractants shown in the asthmatic group may contribute to a subsequent worsening of the airway inflammation, and help to explain their differential sensitivity to O3 pollution episodes.

Adult↗
PubMed2003

Not 15 but 50% of smokers develop COPD?--Report from the Obstructive Lung Disease in Northern Sweden Studies.

BACKGROUND: The prevalence of chronic obstructive pulmonary disease (COPD) according to guidelines of today seems considerably higher than has been reported also in recent literature. AIM: To estimate the prevalence of COPD as defined by British Thoracic Society (BTS) criteria and the recent global initiative for chronic obstructive lung disease (GOLD) criteria. Further aims were to assess the proportion of underdiagnosis and of symptoms in subjects with COPD, and to study risk factors for COPD. METHODS: In 1996, 5892 of the Obstructive Lung Disease in Northern Sweden (OLIN) Study's first cohort could be traced to a third follow-up survey, and 5189 completed responses (88%) were received corresponding to 79% of the original cohort from December 1985. Of the responders, a random sample of 1500 subjects were invited to a structured interview and a lung function test, and 1237 of the invited completed a lung function test with acceptable quality. RESULTS: In ages >45 years, the prevalence of COPD according to the BTS guidelines was 8%, while it was 14% according to the GOLD criteria. The absolutely dominating risk factors were increasing age and smoking, and approximately a half of elderly smokers fulfilled the criteria for COPD according to both the BTS and the GOLD criteria. Family history of obstructive airway disease was also a risk factor, while gender was not. Of those fulfilling the BTS criteria for COPD, 94% were symptomatics, 69% had chronic productive cough, but only 31% had prior to the study been diagnosed as having either chronic bronchitis, emphysema, or COPD. The corresponding figures for COPD according GOLD were 88, 51, and 18%. CONCLUSIONS: In ages >45 years, the prevalence of COPD according to the BTS guidelines was 8%, and it was 14% according to the GOLD criteria. Fifty percent of elderly smokers had developed COPD. The large majority of subjects having COPD were symptomatic, while the proportion of those diagnosed as having COPD or similar diagnoses was small.

Aged↗
PubMed2003

Repeated daily exposure to 2 ppm nitrogen dioxide upregulates the expression of IL-5, IL-10, IL-13, and ICAM-1 in the bronchial epithelium of healthy human airways.

BACKGROUND: Repeated daily exposure of healthy human subjects to NO2 induces an acute airway inflammatory response characterised by neutrophil influx in the bronchial mucosa AIMS: To assess the expression of NF-kappaB, cytokines, and ICAM-1 in the bronchial epithelium. METHODS: Twelve healthy, young non-smoking volunteers were exposed to 2 ppm of NO2/filtered air (four hours/day) for four successive days on separate occasions. Fibreoptic bronchoscopy was performed one hour after air and final NO2 exposures. Bronchial biopsy specimens were immunostained for NF-kappaB, TNF-alpha, eotaxin, Gro-alpha, GM-CSF, IL-5, -6, -8, -10, -13, and ICAM-1 and their expression was quantified using computerised image analysis. RESULTS: Expression of IL-5, IL-10, IL-13, and ICAM-1 increased following NO2 exposure. CONCLUSION: Upregulation of the Th2 cytokines suggests that repeated exposure to NO2 has the potential to exert a "pro-allergic" effect on the bronchial epithelium. Upregulation of ICAM-1 highlights an underlying mechanism for leucocyte influx, and could also explain the predisposition to respiratory tract viral infections following NO2 exposure since ICAM-1 is a major receptor for rhino and respiratory syncytial viruses.

Adult↗
PubMed2003

The need for a focus on air pollution research in the elderly.

During recent years an increasing focus has been directed towards the adverse health effects associated with ambient air pollution. Elderly people appear to be particularly susceptible to the adverse effects involving the respiratory and cardiovascular systems, resulting in symptoms, exacerbations of disease and even mortality. From an epidemiological point of view it is essential to obtain a more detailed description and identification of factors associated with these health effects. Novel study designs are needed with complementary exposure and biomedical characterisation. Long-term prospective studies are required. A better understanding of the pathophysiological mechanisms is considered important and requires an interaction between epidemiological and mechanistic studies in elderly individuals with or without complementary diseases that put in them especially at risk. Generally a synergy between complementary disciplines is warranted to move this important research area forward, also including in vitro models of cell responses in the elderly, animal models of diseases of the elderly, together with controlled air pollution exposure studies identifying health-related events and mechanisms. The generation of an understanding of air pollution effects in the elderly, at an elevated level, is a prerequisite to substantially reducing the adverse health effects of this population group. At local, national and European Union levels, some steps have been taken to support the research in this area. A major focus on the adverse air pollution effects in the elderly requires a long-term commitment that still remains to be established.

Aged↗
PubMed2002

Increased ozone-induced airway neutrophilic inflammation in extracellular-superoxide dismutase null mice.

Extracellular-superoxide dismutase (EC-SOD) exists primarily in the tissue interstitium and the lung contains particularly large amounts of the enzyme. To determine the roles of EC-SOD and extracellularly formed superoxide radicals in the pulmonary response to the common air pollutant ozone, wild-type mice and mice lacking EC-SOD were exposed to 1.5 ppm ozone for 48 h. The exposure resulted in a marked neutrophilic inflammatory reaction observed both in the bronchoalveolar lavage fluid (BALF) and by histopathology of the lungs, which was much stronger in the mice lacking EC-SOD. Unlike the wild-type mice, the null mutants also showed increased levels of interleukin-6 in the BALF. The ozone exposure also resulted in increased airway mucosal permeability and cell damage as indicated by increased protein and lactate dehydrogenase in the BALF. There was, however, no difference between the two groups of mice.The results suggest that extracellular superoxide radicals are important inflammatory mediators in the pulmonary response to ozone, but in the present model, the radical and the infiltrating neutrophils contributed little to the pulmonary injury The data, together with previous findings, support a role for EC-SOD as a modulator of inflammatory reactions.

Air Pollutants↗