| 1. |
- Olin, Anna-Carin, 1960, et al.
(author)
-
Single breath N2-test and exhaled nitric oxide in men.
- 2006
-
In: Respiratory medicine. - : Elsevier BV. - 0954-6111. ; 100:6, s. 1013-9
-
Journal article (peer-reviewed)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.
|
|
| 2. |
- Andelid, Kristina, 1953, et al.
(author)
-
Myeloperoxidase as a marker of increasing systemic inflammation in smokers without severe airway symptoms
- 2007
-
In: Respiratory medicine. - : Elsevier BV. - 0954-6111. ; 101:5, s. 888-95
-
Journal article (peer-reviewed)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.
|
|
| 3. |
- Ekberg-Jansson, Ann, 1960, et al.
(author)
-
Bronchial mucosal mast cells in asymptomatic smokers relation to structure, lung function and emphysema
- 2005
-
In: Respir Med. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 99:1, s. 75-83
-
Journal article (peer-reviewed)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.
|
|
| 4. |
- Ekberg-Jansson, Ann, 1960, et al.
(author)
-
Inflammatoriska mekanismer vid KOL
- 2006
-
In: In: Kroniskt obstruktiv lungsjukdom KOL. Larsson K, ed.. ; Kapitel 2:3, s. 77-93
-
Journal article (peer-reviewed)
|
|
| 5. |
- Plymoth, Amelie, et al.
(author)
-
Protein expression patterns associated with progression of chronic obstructive pulmonary disease in bronchoalveolar lavage of smokers
- 2007
-
In: Clin Chem. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 53:4, s. 636-44
-
Journal article (peer-reviewed)abstract
- BACKGROUND: We modeled the expression of proteins in baseline bronchoalveolar lavage (BAL) samples from asymptomatic 60-year-old lifelong current smokers or healthy never-smokers, who were reevaluated after 6 to 7 years to record clinical outcome. METHODS: Applying a technology toolbox consisting of replicate 2-dimensional gel separations, image annotation, and mass spectrometry identification, we catalogued a global set of proteins that were differentially expressed in individuals by presence, absence, and intensity scores. RESULTS: By use of multivariate analysis, we selected a subset of proteins that accurately separated smokers from never-smokers based on composite scoring. Follow-up after 6 to 7 years identified a group of individuals who had progressed to chronic obstructive pulmonary disease (COPD), Global Initiative for Chronic Obstructive Lung Disease stage 2. The baseline BAL samples of these eventual COPD patients shared a distinct protein expression profile that could be identified using partial least-squares discriminant analysis. This pattern was not observed in BAL samples of asymptomatic smokers free of COPD at 6- to 7-year follow-up. CONCLUSIONS: Our model suggests that certain patterns of protein expression occurring in the airways of long-term smokers may be detected in smokers susceptible to a progression of COPD disease, before disease is clinically evident.
|
|
| 6. |
- Plymoth, Amelie, et al.
(author)
-
Rapid proteome analysis of bronchoalveolar lavage samples of lifelong smokers and never-smokers by micro-scale liquid chromatography and mass spectrometry
- 2006
-
In: Clin Chem.. - : Oxford University Press (OUP). ; 52:4, s. 671-679
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The aim of this study was to determine whether relative qualitative and quantitative differences in protein expression could be related to smoke exposure or smoke-induced airway inflammation. We therefore explored and characterized the protein components found in bronchoalveolar lavage (BAL) fluid sampled from either lifelong smokers or never-smokers. METHODS: BAL fluid samples obtained by bronchoscopy from 60-year-old healthy never-smokers (n = 18) and asymptomatic smokers (n = 30) were analyzed in either pooled or individual form. Initial global proteomic analysis used shotgun digestion approaches on unfractionated BAL fluid samples (after minimal sample preparation) and separation of peptides by gradient (90-min) liquid chromatography (LC) coupled with on-line linear ion trap quadropole mass spectrometry (LTQ MS) for identification and analysis. RESULTS: LTQ MS identified 481 high- to low-abundance proteins. Relative differences in patterns of BAL fluid proteins in smokers compared with never-smokers were observed in pooled and individual samples as well as by 2-dimensional gel analysis. Gene ontology categorization of all annotated proteins showed a wide spectrum of molecular functions and biological processes. CONCLUSIONS: The described method provides comprehensive qualitative proteomic analysis of BAL fluid protein expression from never-smokers and from smokers at risk of developing chronic obstructive pulmonary disease. Many of the proteins identified had not been detected in previous studies of BAL fluid; thus, the use of LC-tandem MS with LTQ may provide new information regarding potentially important patterns of protein expression associated with lifelong smoking.
|
|
| 7. |
- Vikgren, Jenny, 1957, et al.
(author)
-
Detection of mild emphysema by computed tomography density measurements
- 2005
-
In: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 46:3, s. 237-245
-
Journal article (peer-reviewed)abstract
- Purpose: To assess the ability of a conventional density mask method to detect mild emphysema by high- resolution computed tomography ( HRCT), to analyze factors influencing quantification of mild emphysema, and to validate a new algorithm for detection of mild emphysema. Material and Methods: Fifty- five healthy male smokers and 34 never- smokers, 61 - 62 years of age, were examined. Emphysema was evaluated visually, by the conventional density mask method, and by a new algorithm compensating for the effects of gravity and artifacts due to motion and the reconstruction algorithm. Effects of the reconstruction algorithm, slice thickness, and various threshold levels on the outcome of the density mask area were evaluated. Results: Forty- nine percent of the smokers had mild emphysema. The density mask area was higher the thinner the slice irrespective of the reconstruction algorithm and threshold level. The sharp algorithm resulted in increased density mask area. The new reconstruction algorithm could discriminate between smokers with and those without mild emphysema, whereas the density mask method could not. The diagnostic ability of the new algorithm was dependent on lung level. At about 90% specificity, sensitivity was 65 - 100% in the apical levels, but low in the rest of the lung. Conclusion: The conventional density mask method is inadequate for detecting mild emphysema, while the new algorithm improves the diagnostic ability but is nevertheless still imperfect.
|
|
