| 1. |
- Olin, Anna-Carin, 1960, et al.
(författare)
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Single breath N2-test and exhaled nitric oxide in men.
- 2006
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Ingår i: Respiratory medicine. - : Elsevier BV. - 0954-6111. ; 100:6, s. 1013-9
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Tidskriftsartikel (refereegranskat)abstract
- The N(2) slope is an index of inhomogeneous distribution of ventilation and has been suggested to be suited for early testing of chronic obstructive pulmonary disease (COPD) in smokers. The aim of the present study was to examine the association between the fraction of exhaled nitric oxide (FENO) and the N(2) slope in a random population of smoking and non-smoking men. Altogether 57 subjects were included in the study, 24 never-smokers, seven ex-smokers and 26 current smokers. Subjects were examined twice, in 1995 when they regarded themselves as healthy, and in a follow-up in 2001. Spirometry, N(2) slope and high-resolution computed tomography (HRCT) were performed in 1995 while the follow-up examination included also measurement of FENO. The FENO value was significantly lower and the N(2) slope higher in current smokers. In smokers but not in never- or ex-smokers FENO was correlated to the difference in N(2) slope between 1995 and 2001 (r(s)=0.49, P=0.01). We analysed the data by multiple linear regression adjusted for smoking, mild respiratory symptoms and inhaled steroids. There were significant associations between FENO and the N(2) slope both in 1995 and in 2001. The strongest association was found to exist with the change in N(2) slope during these years. Sixteen of the subjects could be classified as having COPD, six with mild and ten with moderate COPD. There was a trend for an increase in N(2) slope with increased severity of COPD; among subjects with no COPD the N(2) slope in 2001 was 2.3% N(2)/L, and those with mild and moderate COPD had 2.5% N(2)/L and 3.9% N(2)/L, respectively (P=0.0004). No such trend was seen for FENO (17.8, 15.5 and 20.3 parts per billion (ppb), respectively, P=0.8). The results show that FENO is associated with the N(2) slope, indicating that FENO reflects inflammatory changes in the peripheral airways of both non-smoking and smoking subjects.
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| 2. |
- Amin, Kawa, et al.
(författare)
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Relationship between inflammatory cells and structural changes in the lungs of asymptomatic and never smokers : a biopsy study
- 2003
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Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 58:2, s. 135-142
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A study was undertaken to investigate the relationship between inflammatory cells and structural changes in the mucosa of the airways in an epidemiological sample of a group of asymptomatic smokers (smokers who had never sought medical attention for respiratory problems) and in non-smoking subjects. METHODS: Bronchial biopsy specimens were taken from 29 smokers and 16 never smokers and stained with monoclonal antibodies HNL, EPO, AA1, CD68 in order to identify neutrophils, eosinophils, mast cells, and macrophages, respectively. The biopsy specimens were also stained with monoclonal antibodies to the cytokines interleukin (IL)-1beta and IL-8. Structural changes were identified by staining the biopsy specimens with antibodies to tenascin and laminin and by evaluating the condition of the epithelial layer. RESULTS: The numbers of all inflammatory cells and of cytokine staining cells were significantly increased in smokers. The thickness of the tenascin and laminin layers was increased in the smoking group and the integrity of the epithelial layer was significantly reduced. In smokers the epithelial integrity was negatively correlated with the number of eosinophils and macrophages. The thickness of the tenascin and laminin layers was positively correlated with AA1 and EPO positive cells only. CONCLUSION: High numbers of inflammatory cells are present in the bronchial mucosa of asymptomatic smokers which have a clear relationship with the impaired epithelial integrity. The increased thickness of the laminin and tenascin layers in these subjects was strongly related to the presence of eosinophils and mast cells, suggesting a role for these cells in tissue remodelling of the airways of smokers.
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| 3. |
- Andelid, Kristina, 1953, et al.
(författare)
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Myeloperoxidase as a marker of increasing systemic inflammation in smokers without severe airway symptoms
- 2007
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Ingår i: Respiratory medicine. - : Elsevier BV. - 0954-6111. ; 101:5, s. 888-95
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is increasing evidence of systemic inflammation in patients with chronic obstructive pulmonary disease (COPD), but there is very little information on the development of systemic inflammation in smokers without severe airway symptoms. In this longitudinal study, we examined whether smokers with mild or no airway symptoms develop signs of systemic inflammation by assessing inflammatory markers in blood over a 6-year period. METHODS: Forty smokers and 28 male never-smokers were investigated in 1995 (year 0) and 6 years later (year 6). At year 6, 11 smokers had stopped smoking (quitters); these subjects were analysed as a separate group. At year 0 and 6, we measured serum levels of myeloperoxidase (MPO), lysozyme and human neutrophil lipocalin (HNL), regarded as markers of activity in neutrophils plus monocyte-lineage cells, monocyte-lineage cells only and neutrophils only. RESULTS: All systemic markers of inflammation (MPO, HNL and lysozyme) were significantly higher in smokers than in never smokers at year 6. For MPO alone, smokers only displayed a unique pattern compared with the other groups; the concentration of MPO in blood increased among smokers during the 6-year period, and this increase was statistically significant compared with that observed in never-smokers. Even though quitters did not display any clear change in MPO, we observed a statistically significant negative correlation between the change in blood MPO and the duration of smoking cessation in this group. For HNL and lysozyme, the changes over time were similar in smokers and never-smokers, with no statistically significant difference compared with quitters. CONCLUSION: This study provides evidence that male smokers without severe airway symptoms develop an increasing systemic inflammation during a 6-year period. The study forwards both direct and indirect evidence that MPO may be an early marker of this systemic inflammation. However, our study also forwards indirect evidence that ongoing tobacco smoking may "drive" the level of systemic HNL and lysozyme. The origin of the increased MPO and its value as an easily measured predictor for future COPD deserves to be further evaluated.
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| 4. |
- Andelid, Kristina, 1953, et al.
(författare)
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Systemic cytokine signaling via IL-17 in smokers with obstructive pulmonary disease: a link to bacterial colonization?
- 2015
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Ingår i: International Journal of Chronic Obstructive Pulmonary Disease. - : Informa UK Limited. - 1178-2005. ; 10, s. 689-702
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Tidskriftsartikel (refereegranskat)abstract
- We examined whether systemic cytokine signaling via interleukin (IL)-17 and growth-related oncogene-alpha (GRO-alpha) is impaired in smokers with obstructive pulmonary disease including chronic bronchitis (OPD-CB). We also examined how this systemic cytokine signaling relates to bacterial colonization in the airways of the smokers with OPD-CB. Currently smoking OPD-CB patients (n=60, corresponding to Global initiative for chronic Obstructive Lung Disease [ GOLD] stage I-IV) underwent recurrent blood and sputum sampling over 60 weeks, during stable conditions and at exacerbations. We characterized cytokine protein concentrations in blood and bacterial growth in sputum. Asymptomatic smokers (n=10) and never-smokers (n=10) were included as control groups. During stable clinical conditions, the protein concentrations of IL-17 and GRO-alpha were markedly lower among OPD-CB patients compared with never-smoker controls, whereas the asymptomatic smoker controls displayed intermediate concentrations. Notably, among OPD-CB patients, colonization by opportunistic pathogens was associated with markedly lower IL-17 and GRO-alpha, compared with colonization by common respiratory pathogens or oropharyngeal flora. During exacerbations in the OPD-CB patients, GRO-alpha and neutrophil concentrations were increased, whereas protein concentrations and messenger RNA for IL-17 were not detectable in a reproducible manner. In smokers with OPD-CB, systemic cytokine signaling via IL-17 and GRO-alpha is impaired and this alteration may be linked to colonization by opportunistic pathogens in the airways. Given the potential pathogenic and therapeutic implications, these findings deserve to be validated in new and larger patient cohorts.
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| 5. |
- Andelid, Kristina, 1953, et al.
(författare)
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Systemic signs of neutrophil mobilization during clinically stable periods and during exacerbations in smokers with obstructive pulmonary disease
- 2015
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Ingår i: International Journal of Chronic Obstructive Pulmonary Disease. - : Informa UK Limited. - 1178-2005. ; 10, s. 1253-1263
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is still unclear whether signs of neutrophil mobilization in the blood of patients with chronic obstructive pulmonary disease represent true systemic events and how these relate to bacterial colonization in the airways. In this study, we evaluated these issues during clinically stable periods and during exacerbations in smokers with obstructive pulmonary disease and chronic bronchitis (OPD-CB). Methods: Over a period of 60 weeks for each subject, blood samples were repeatedly collected from 60 smokers with OPD-CB during clinically stable periods, as well as during and after exacerbations. Myeloperoxidase (MPO) and neutrophil elastase (NE) protein and mRNA, growth of bacteria in sputum, and clinical parameters were analyzed. Ten asymptomatic smokers and ten never-smokers were included as controls. Results: We found that, during clinically stable periods, neutrophil and NE protein concentrations were increased in smokers with OPD-CB and in the asymptomatic smokers when compared with never-smokers. During exacerbations, neutrophil and MPO protein concentrations were further increased in smokers with OPD-CB, without a detectable increase in the corresponding mRNA during exacerbations. However, MPO and NE protein and mRNA displayed positive correlations. During exacerbations, only increased neutrophil concentrations were associated with growth of bacteria in sputum. Among patients with low transcutaneous oxygen saturation during exacerbations, PaO2 (partial oxygen pressure) correlated with concentrations of MPO and NE protein and neutrophils in a negative manner. Conclusion: There are signs of systemic neutrophil mobilization during clinically stable periods and even more so during exacerbations in chronic obstructive pulmonary disease. In this condition, MPO and NE may share a cellular origin, but its location remains uncertain. Factors other than local bacteria, including hypoxemia, may be important for driving systemic signs of neutrophil mobilization.
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| 6. |
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| 7. |
- Ekberg-Jansson, Ann, 1960
(författare)
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Airway inflammation in "healthy" smokers. Relation to lung function and high resolution CT findings
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of the present study was to characterize the inflammatory pattern in "healthy"smokers and relate it to lung function, high resolution computed tomography (HRCT) findings and respiratory symptoms in order to identify smokers at risk to develop COPD. Subjects were recruited from a population study "Men born 1933 in Göteborg". Only smokers who considered themselves as healthy (n=58) were investigated. From the same population a random sample of healthy never-smokers (n=34) were recruited. All subjects underwent lung function tests, HRCT, and answered a questionnaire. Thirty smokers (30/58) and 18 never-smokers (18/34) accepted to undergo a bronchoscopy with bronchial lavage, bronchoalveolar lavage (BAL) and bronchial biopsies. The levels of neutrophil-associated soluble inflammatory markers e.g. human neutrophil lipocalin (HNL), were higher in smokers in both blood, bronchial lavage and BAL, as compared with never-smokers. Inflammatory markers in bronchial lavage and BAL were related to carbon monoxide transfer (DLCO) but not to forced expiratory volume in one second (FEV1). HRCT showed emphysematous changes in 25/57 smokers while only 1/32 never-smokers showed this. Such emphysematous changes in smokers were related to a decrease in transfer factor (DLCO/ VA) as well as to an increase in HNL in BAL. Smokers with emphysematous changes also had more alveolar macrophages in BAL as compared with smokers without changes. Bronchial biopsies were analysed according to some T cell subpopulations, in different compartments in never-smokers. In healthy never-smokers, an increased number of cytotoxic T cells (CD 8+) were found in the bronchial epithelium as compared with lamina propria. Also in smokers, the same gradient in bronchial biopsies was seen. Even if the number of CD8+ cells in lamina propria were not increased in smokers as compared with never-smokers, a relation between CD8+ cells and an impairment in FEV1 was demonstrated in smokers. In BAL in never-smokers, the proportion of different T cell activation markers were higher in BAL than in blood (e.g. HLA-DR, CD54+, CD69+). In BAL in smokers as compared with never-smokers, an increased proportion of CD8+ and decreased proportion of CD4+ T cells was seen. The CD4+/CD8+ ratio was also low. The occurrence of different respiratory symptoms in smokers who considered themselves as "healthy" were high. Smokers with symptoms had lower FEV1, FEV% and specific airway conductance (sGaw) as well as increased number of CD8+ cells in the bronchial biopsies as compared with smokers without symptoms. However, no relation between reported symptoms and soluble inflammatory markers in blood/BAL, emphysematous changes or lung function tests mainly reflecting the small airways, could be seen. In summary, smokers without any diagnosed pulmonary or bronchial disease, frequently report respiratory symptoms, have decreased lung function, emphysematous changes on HRCT and these findings are related to inflammatory markers in bronchial tissue and bronchial lavage, BAL and blood. Thus, "healthy" smokers have an inflammation in the bronchial mucosa suggesting early chronic obstructive pulmonary disease (COPD) or preclinical COPD.
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| 8. |
- Ekberg-Jansson, Ann, 1960, et al.
(författare)
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Bronchial mucosal mast cells in asymptomatic smokers relation to structure, lung function and emphysema
- 2005
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Ingår i: Respir Med. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 99:1, s. 75-83
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Tidskriftsartikel (refereegranskat)abstract
- The pathologic mechanisms of chronic obstructive pulmonary disease (COPD) most certainly involves neutrophil granulocytes, cytotoxic T-cells, macophages and mast cells. The aim of this study was to investigate the relation between the number of mast cells in different compartments in bronchial biopsies of central proximal airways to structural changes, lung function tests and emphysema detected by high resolution computed tomography (HRCT). Twenty nine asymptomatic smoking and 16 never-smoking men from a population study were recruited. Central bronchial biopsies were stained to identify mast cells by immunohistochemistry. The number of mast cells in the epithelium, lamina propria and smooth muscle as well as epithelial integrity and thickness of the tenascin and laminin layer were determined. Smokers had increased numbers of mast cells in all compartments (P<0.001). Structural changes were correlated to mast cell numbers with the closest associations to mast cell numbers in the smooth muscle [epithelial integrity (R(S)=-0.48, P=0.008), laminin layer (R(S)=0.63, P=0.0002), tenascin layer (R(S)=0.40, P=0.03)]. Similar correlations between mast cells and lung function tests were seen [functional residual capacity (FRC) (R(S)=0.60, P=0.0006), total lung capacity (TLC) (R(S)=0.44, P=0.02) and residual volume (RV) (R(S)=0.41, P=0.03)]. No correlations could be detected between mast cells and FEV1 or to emphysema. Smoking is associated with an increase of mast cells in all compartments of the bronchial mucosa, including smooth muscle, and this is related to altered airway structure and function.
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| 9. |
- Ekberg-Jansson, Ann, 1960, et al.
(författare)
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Budesonide inhaler device switch patterns in an asthma population in Swedish clinical practice (ASSURE)
- 2015
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Ingår i: International journal of clinical practice. - : Blackwell Publishing Ltd. - 1368-5031. ; 69:10, s. 1171-1178
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Tidskriftsartikel (refereegranskat)abstract
- Background Dry powder inhaler (DPI) device switch in asthma treatment could potentially increase with the entrance of new devices. We examined the switch patterns of budesonide (BUD) DPI analogues available in Sweden. Methods This observational real-life study linked primary healthcare medical records data from the Västra Götaland region to national Swedish registries, and included asthma patients (ICD-10-CM J45) prescribed BUD in a multidose DPI. Index date: first dispense of BUD DPI. Switch date: prescription of another BUD DPI device. Study outcomes (switch vs. non-switch) were exacerbations and prescription of short-acting β2-agonists. Study period was 1 July 2005 to 31 October 2013. Results Overall, 15,169 asthma patients were on treatment with BUD DPI; 1178 (7.35%) switched to another BUD DPI during the study. Pair-wise 1:1 matching of switchers vs. non-switchers resulted in two groups of 463 patients each (mean age 36 years, 55% female patients). A 25% higher exacerbation rate was seen postswitch (0.40 vs. 0.32; p = 0.047). Switchers were 4.5 year younger and had lower medication possession rate than non-switchers. Switch without primary healthcare visit did not differ between groups regarding consultations and exacerbations (no visit 4.96 and 0.90; visit 4.29 and 0.77, respectively). However, patients without primary healthcare visit at switch had significantly more outpatient hospital visits (2.01 vs. 0.81; p < 0.001). Conclusions Considering the low switch rate, asthma patients and physicians in Swedish general practice seem reluctant to switch to another BUD DPI device. Switch, especially without primary healthcare visit, was associated with decreased asthma control resulting in higher exacerbation rate and more outpatient hospital visits. © 2015 John Wiley & Sons Ltd.
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| 10. |
- Ekberg-Jansson, Ann, 1960, et al.
(författare)
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Inflammatoriska mekanismer vid KOL
- 2006
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Ingår i: In: Kroniskt obstruktiv lungsjukdom KOL. Larsson K, ed.. ; Kapitel 2:3, s. 77-93
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Tidskriftsartikel (refereegranskat)
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