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- Aldonyte, Ruta, et al.
(författare)
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Circulating monocytes from healthy individuals and COPD patients.
- 2003
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 4:1, s. 11-11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic obstructive pulmonary disease (COPD) is characterized by incompletely reversible airflow obstruction associated with inflammation in which monocytes/macrophages are the predominant inflammatory cells. The only known genetic factor related to COPD is inherited PiZZ deficiency of alpha1-antitrypsin (AAT), an inhibitor of serine proteases. Methods: We investigated the basal and LPS-stimulated release of pro-inflammatory molecules from blood monocytes isolated from age and gender matched healthy (n = 30) and COPD (n = 20) individuals with and without AAT deficiency. Results: After 18 h of cell culture the basal release of MMP-9 was 2.5-fold, p < 0.02 greater, whereas IL-8 was 1.8-fold (p < 0.01) lower from COPD patient monocytes than from controls. LPS-stimulated release of IL-6 and MCP-1 was greater from COPD patient's monocytes relative to controls, while activation of control cells resulted in enhanced secretion of ICAM-1 and MMP-9 compared to COPD patients. Independent of disease status, monocytes from PiZZ AAT carriers released less TNFalpha (by 2.3-fold, p < 0.03). Conclusions: The basal and LPS-stimulated secretion of specific pro-inflammatory molecules from circulating monocytes differs between healthy and COPD subjects. These findings may be valuable for further studies on the mechanisms involved in recruitment and activation of inflammatory cells in COPD.
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- Bakker, M. Els, et al.
(författare)
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Assessment of Regional Progression of Pulmonary Emphysema With CT Densitometry
- 2008
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Ingår i: Chest. - : Elsevier BV. - 1931-3543 .- 0012-3692. ; 134:5, s. 931-937
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lung densitometry is an effective method to assess overall progression of emphysema, but generally the location of the progression is not estimated. We hypothesized that progression of emphysema is the result of extension from affected areas toward less affected areas in the lung. To test this hypothesis, a method was developed to assess emphysema severity at different levels in the lungs in order to estimate regional changes. Methods: Fifty subjects with emphysema due to alpha(1)-antitrypsin deficiency (AATD) [AATD deficiency of phenotype PiZZ (PiZ) group] and 16 subjects with general emphysema (general emphysema without phenotype PiZZ [non-.PiZ] group) were scanned with CT at baseline and after 30 months. Densitometry was performed in 12 axial partitions of equal volumes. To indicate predominant location, craniocaudal locallity was defined as the slope in the plot of densities against partitions. Regional progression of emphysema was calculated after volume correction, and its slope identifies the area of predominant progression. The hypothesis was tested by investigating the correlation between predominant location and predominant progression. Results: As expected, the PiZ patients showed more basal emphysema than the non-PiZ group (craniocaudal locality, -40.0 g/L vs -6.2 g/L). Overall progression rate in PiZ patients was lower than in non-PiZ subjects. A significant correlation was found between craniocaudal locality and progression slope in PiZ subjects (R = 0.566, p < 0.001). In the non-PiZ group, no correlation was found. Conclusions: In the PiZ group, the more emphysema is distributed basally, the more progression was found in the basal area. This finding suggests that emphysema due to AATD spreads out from affected areas. (CHEST 2008; 134:931-937)
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- Basil, Nawfal, et al.
(författare)
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Severe alpha-1-antitrypsin deficiency increases the risk of venous thromboembolism
- 2021
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Ingår i: Journal of Thrombosis and Haemostasis. - : John Wiley & Sons. - 1538-7933 .- 1538-7836. ; 19:6, s. 1519-1525
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Tidskriftsartikel (refereegranskat)abstract
- Background: Severe alpha-1-antitrypsin deficiency (AATD), phenotype PiZZ, is associated with increased risk of liver disease and chronic obstructive pulmonary disease (COPD), but the risk of venous thromboembolism (VTE) is unknown. Our aim was to evaluate the risk of VTE in individuals with severe AATD compared with control subjects from the general population.Methods: Individuals with severe AATD (n = 1577) were recruited from the Swedish national AATD register. Control subjects (n = 5969) were selected from the OLIN (Obstructive Lung Disease in Northern Sweden) studies, that include a random general population sample. Longitudinal data on VTE and diagnoses were obtained from the Swedish National Patient Registry. Associations were analyzed using multivariable Cox regression.Results: At inclusion, 46% of the AATD individuals and 53% of the controls were never-smokers. COPD was present in 46% of the AATD individuals compared with 4% of the controls. During a median follow-up of 18 years, 116 (7%) of the AATD individuals and 89 (1%) of the control subjects developed VTE, unadjusted hazard ratio 6.5 (95% confidence interval 4.9–8.6). Risk factors for incident VTE were male gender, age, COPD, cancer, and liver disease. Adjusting for these factors, the AATD individuals had a significantly higher risk of incident VTE, adjusted hazard ratio 4.2 (95% confidence interval 2.9–6.2) as compared with the controls.Conclusion: Subjects with severe AATD have considerably increased risk of developing VTE compared with the general population, even after accounting for risk factors. This calls for optimized risk factor management and clinical follow-up of this patient group.
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- Bernspång, Elisabeth, et al.
(författare)
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CT lung densitometry in young adults with alpha-1-antitrypsin deficiency
- 2011
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 105:1, s. 74-79
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Tidskriftsartikel (refereegranskat)abstract
- Background: Severe (PiZZ) and moderate (PiSZ) alpha-1-antitrypsin (AAT) deficiency predispose to lung emphysema, especially in smokers. We hypothesized that multi-slice computed tomography (CT) might be superior to pulmonary function tests (PFT) to detect lung emphysema in AAT-deficient individuals at the age of 32 years. Methods: A subgroup of PiZZ and PiSZ individuals identified during the Swedish newborn screening programme in 1972-74 underwent multi-slice CT and PFT at the age of 32 years. From the CT scans the percentile density at 15% (PD15) and the relative area below -910 Hounsfield Units (RA(-910) HU) were calculated. The results of PFT and CT were compared between the AAT-deficient individuals and an age-matched control group. Results: Twenty-five PiZZ, 11 PiSZ and 17 PiMM individuals participated in the study. All Pi subgroups had normal lung function. The mean PD15 was 81 (SD 22) g/L in the PiZZ individuals, 96 (SD 35) g/L in the PiSZ individuals and 79 (SD 17) g/L in the PiMM individuals (ns), and the RA-910 were 30 (SD 18)%, 24 (SD 20)%, and 32 (SD 18)%, respectively (ns). For the never-smoker subgroups, in the PiZZ (n = 23), PiSZ (n = 8) and PiMM (n = 12), the mean PD15 were 95 (SD 35) g/L, 81 (SD 22) g/L, and 75 (SD 12) g/L, respectively (ns). PD15 was significantly correlated to CT derived lung size (r = -0.72; p < 0.001). Conclusions: CT densitometry revealed no signs of emphysema and no differences between the AAT-deficient individuals identified by neonatal screening and age-matched control subjects.
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- Bernspång, Elisabeth, et al.
(författare)
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Lung function in 30-year-old alpha-1-antitrypsin-deficient individuals.
- 2009
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 103, s. 861-865
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Alpha-1-antitrypsin (AAT) deficiency increases the risk of emphysema, especially in smokers. In 1972-1974, all 200,000 Swedish new-born infants were screened for AAT deficiency and individuals with severe (PiZZ) and moderate (PiSZ) deficiency have been followed-up regularly. The aim of the present study was to examine their lung function at the age of 30years, comparing them to a group of age-matched control subjects (PiMM) recruited from the general population, and to compare current smokers with never-smokers. METHOD: Static and dynamic spirometry, including TLC, FRC, RV, VC, FEV(1,)K(CO) and D(L,CO), was performed for all participants. All values were expressed as percentages of the expected values. FEV(1)/VC was expressed both as percentage of the expected value and in absolute numbers. RESULTS: Four of 60 PiZZ, none of 19 PiSZ and 9 of 33 PiMM participating individuals were current smokers. All Pi groups had a normal mean FEV(1). The mean (SD) FEV(1)/VC ratio was 75% (7.4) in the PiZZ smokers and 84% (5.5) in the PiZZ never-smokers (p<0.01). The mean (SD) K(CO) was 81 (13) in the PiZZ smokers and 99 (14) in the PiZZ never-smokers (p<0.05). CONCLUSION: AAT-deficient individuals identified by neonatal screening have normal lung function at the age of 30. The PiZZ smokers had changes in lung function that may be signs of early emphysema.
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| 10. |
- Bernspång, Elisabeth, et al.
(författare)
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Respiratory symptoms and lung function in 30-year-old individuals with alpha-1-antitrypsin deficiency.
- 2007
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 101, s. 1971-1976
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Individuals with severe alpha-1-antitrypsin (AAT) deficiency have a well-known risk of developing emphysema but it is not known at which age the first symptoms occur and lung function declines. The aim of this study was to examine the prevalence of smoking, respiratory symptoms and lung function at the age of 30 in AAT-deficient individuals (PiZ and PiSZ) identified by neonatal screening. Material and methods: One hundred and seven PiZ, 45 PiSZ and 197 control subjects (PiMM) filled in a questionnaire regarding smoking habits and symptoms. Ninety PiZ, 40 PiSZ and 84 control subjects underwent spirometry including FEV1 and FVC. Results: Twenty-one percent of PiZ, 23% of PiSZ and 34% of PiMM subjects had smoked at some time (p < 0.05). Sixty-five percent of PiZ, 55% of PiSZ and 35% of PiMM ever-smokers reported shortness of breath on exertion (p < 0.05 PiZ vs PiMM). The mean FEV1, was 101% predicted (95% CI 98-104) in PiZ, 101% predicted (95% CI 97-106) in PISZ, and 96% predicted (95% 93-98) in PiMM individuals (p < 0.05). There was no difference in mean FEV1 when comparing ever- and neversmokers in the different Pi groups separately. Conclusion: At the age of 30, the AAT-deficient individuals in this cohort report more symptoms than the control subjects. Smoking is less common in the cohort compared to controls. Their lung function is normal.
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