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| 4. |
- 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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| 5. |
- 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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| 7. |
- 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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| 8. |
- 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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| 9. |
- 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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| 11. |
- Bernspång, Elisabeth, et al.
(författare)
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The liver in 30-year-old individuals with alpha(1)-antitrypsin deficiency.
- 2009
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 44:11, s. 1349-1355
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE. Severe (PiZZ) alpha(1)-antitrypsin (AAT) deficiency is a risk factor for liver disease, i.e. juvenile cirrhosis in infancy, and cirrhosis and hepatoma in adulthood. Little is known about the risk of liver disease in individuals with moderate (PiSZ) AAT deficiency. To investigate the natural course of AAT deficiency, a cohort of PiZZ and PiSZ individuals identified by the Swedish National neonatal screening programme in 1972-74 is followed regularly. The aim of this study was to compare liver function in this cohort with healthy control subjects aged 30 years. MATERIAL AND METHODS. Blood samples were obtained from 89 PiZZ, 40 PiSZ, and 84 control subjects (PiMM), and plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl (GT) transpeptidase were analysed. RESULTS. The mean values of all liver enzymes were within the normal range in all Pi subgroups. However, the mean AST was higher in the PiZZ and PiSZ subgroups than in the PiMM subgroup (p < 0.001), and the mean ALT was higher in the PiZZ individuals than in the controls (p < 0.05), while GT did not differ significantly among the Pi subgroups. The PiZZ women taking oral contraceptives had higher mean AST and ALT (p < 0.01) and GT (p < 0.05) than the control women taking oral contraceptives. CONCLUSIONS. At the age of 30 years, PiZZ and PiSZ individuals have normal plasma levels of the transaminases AST and ALT, although they are significantly higher than those in healthy control subjects. Use of oral contraceptives seems to influence liver enzymes in PiZZ women.
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| 14. |
- Carter, Richard I., et al.
(författare)
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The fibrinogen cleavage product A alpha-Val(360), a specific marker of neutrophil elastase activity in vivo
- 2011
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Ingår i: Thorax. - : BMJ. - 1468-3296 .- 0040-6376. ; 66:8, s. 686-691
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Tidskriftsartikel (refereegranskat)abstract
- Background Alpha-1-antitrypsin (A1AT) deficiency is the only recognised genetic risk factor for chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality worldwide. Since A1AT is the major inhibitor of neutrophil elastase (NE), this enzyme has become widely implicated in the pathogenesis of COPD in general; however, there is currently no specific biomarker for its pre-inhibition activity. Such a biomarker should be a measure of elastase-specific COPD disease activity with the potential to assess early targeted therapeutic intervention, in contrast to traditional and non-specific disease severity markers such as forced expiratory volume in 1 s. Methods In pilot studies, plasma A alpha-Val(360) and markers of neutrophil activation were measured in 95 subjects with a range of A1AT concentrations. A alpha-Val(360) and sputum elastase activity were also measured in a further seven PiZ A1AT-deficient subjects over the course of an acute exacerbation. Finally, A alpha-Val(360) was measured in plasma from subjects randomised to receive A1AT replacement or placebo in the EXACTLE trial. Results The plasma concentrations of A alpha-Val(360) and A1AT related exponentially, consistent with previous theoretical and in vitro experimental data. L-233 (an intracellular NE inhibitor) blocked generation of A alpha-Val(360) and subsequent A1AT/NE complex formation. A alpha-Val(360) was related to the spirometric severity of lung disease in A1AT deficiency, to sputum elastase activity in acute exacerbations and was decreased in subjects receiving A1AT replacement therapy (while remaining constant in those receiving placebo). Conclusions A alpha-Val(360) represents the first specific footprint of pre-inhibition NE activity and is a potential biomarker of disease activity and progression in subjects with elastase-dependent COPD.
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| 16. |
- Diaz, Sandra, et al.
(författare)
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Hyperpolarized (3)He apparent diffusion coefficient MRI of the lung: Reproducibility and volume dependency in healthy volunteers and patients with emphysema.
- 2008
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Ingår i: Journal of Magnetic Resonance Imaging. - : Wiley. - 1522-2586 .- 1053-1807. ; 27, s. 763-770
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To measure the apparent diffusion coefficient (ADC) of hyperpolarized (HP) (3)He gas using diffusion weighted MRI in healthy volunteers and patients with emphysema and examine the reproducibility and volume dependency. MATERIALS AND METHODS: A total of eight healthy volunteers and 16 patients with emphysema were examined after inhalation of HP (3)He gas mixed with nitrogen (N(2)) during breathhold starting from functional residual capacity (FRC) in supine position. Coronal diffusion-sensitized MR images were acquired. Each subject was imaged on three separate days over a seven-day period and received two different volumes (6% and 15% of total lung capacity [TLC]) of HP (3)He each day. ADC maps and histograms were calculated. The mean and standard deviation (SD) of the ADC at different days and volumes were compared. RESULTS: The reproducibility of the mean ADC and SD over several days was good in both healthy volunteers and patients (SD range of 0.003-0.013 cm(2)/second and 0.001-0.009 cm(2)/second at 6% and 15% of TLC for healthy volunteers, and a SD range of 0.001-0.041 cm(2)/second and 0.001-0.011 cm(2)/second, respectively, for patients). A minor but significant increase in mean ADC with increased inhaled gas volume was observed in both groups. CONCLUSION: Mean ADC and SD of HP (3)He MRI is reproducible and discriminates well between healthy controls and patients with emphysema at the higher gas volume. This method is robust and may be useful to gain new insights into the pathophysiology and course of emphysema. J. Magn. Reson. Imaging 2008. (c) 2008 Wiley-Liss, Inc.
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| 17. |
- Diaz, Sandra, et al.
(författare)
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Progression of Emphysema in a 12-month Hyperpolarized (3)He-MRI Study Lacunarity Analysis Provided a More Sensitive Measure than Standard ADC Analysis(1).
- 2009
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Ingår i: Academic Radiology. - : Elsevier BV. - 1878-4046 .- 1076-6332. ; 16:6, s. 700-707
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE AND OBJECTIVES: Inhaled hyperpolarized (3)He magnetic resonance (MR) imaging has been used to measure alveolar size in patients with emphysema. The aim of this study was to test the hypothesis that (3)He MR images could be used to develop a biomarker of emphysema progression. MATERIALS AND METHODS: Twelve healthy controls and 18 patients with emphysema (eight current smokers, 10 ex-smokers) were imaged at baseline and 6 and 12 months. An additional nine subjects with alpha-1 antitrypsin deficiency (four with emphysema, six without symptoms) were also imaged at baseline and at 6 months. Each subject was imaged at two lung volumes: functional residual capacity (FRC) and FRC plus 15% of total lung capacity. Means and standard deviations of apparent diffusion coefficients (ADCs) were calculated from coronal images of the entire lung and correlated with pulmonary function test results. The lacunarity hypothesis was tested and calculated from the data using a range of 2x2 x 2 to 6x6 x 6 voxels, and the average was calculated. RESULTS: There was no change in the mean ADC at either lung volume in any subject over the 6- or 12-month period. FRC and residual volume increased over the 12 months, suggesting air trapping. The lacunarity of images collected at FRC increased at 6 and 12 months in smokers only (P=.063 and P=.023, respectively). CONCLUSIONS: The mean ADC calculated from MR images of the lungs with helium was not sufficiently sensitive to detect changes over a 12-month period. However, lacunarity captured more of the spatial information in the images and detected emphysema progress in the smokers.
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| 18. |
- Diaz, Sandra, et al.
(författare)
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Validity of apparent diffusion coefficient hyperpolarized He-3-MRI using MSCT and pulmonary function tests as references
- 2009
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Ingår i: European Journal of Radiology. - : Elsevier BV. - 1872-7727 .- 0720-048X. ; 71:2, s. 257-263
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To compare apparent diffusion coefficient (ADC) measurements from hyperpolarized (HP) helium (He-3)-magnetic resonance imaging (MRI) with quantitative data from multislice Computed Tomography (CT) (MSCT) of the whole lungs and pulmonary function tests (PFT). Materials and methods: Twenty-seven subjects, 22 with established emphysema and 5 with preclinical emphysema defined by PFT criteria, were examined with Hp He-3-MRI and MSCT. Mean age was 55 (+/- 12) years, 18 female and 9 male. Mean ADC from He-3-MRI was compared with emphysema index (EI), 15th percentile and mean lung density (MLD) values from MSCT. Both mean ADC and MSCT data were compared to PFT, especially percent of predicted diffusing capacity of carbon monoxide (%predicted DLCO), using Pearson's correlation test. Results: Mean ADC and standard deviation values were 0.392 +/- 0.119 cm(2)/s for the established emphysema group and 0.216 +/- 0.046 for the pre-clinical emphysema group. MSCT values for the established emphysema group and pre-clinical emphysema group were: EI (%) 11 +/- 12 and 0.4 +/- 0.6, respectively; 15th percentile (Hounsfield Units (HU)), -956 +/- 25 and -933 +/- 13, respectively and MLD (HU) -877 +/- 20 and -863 +/- 15, respectively. Correlations between mean ADC and El and 15th percentile were both r=0.90 and for MLD r=0.59. There was higher correlation between mean ADC and %predicted DLCO (r=0.90) than between El and %predicted DLCO (r=0.76). Conclusion: Hp He-3-MRI correlates well with density measurements from MSCT and agrees better than MSCT with %predicted DLCO which is the PFT most related to emphysema. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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| 19. |
- Dirksen, A., et al.
(författare)
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Exploring the role of CT densitometry: a randomised study of augmentation therapy in alpha(1)-antitrypsin deficiency
- 2009
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 33:6, s. 1345-1353
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Tidskriftsartikel (refereegranskat)abstract
- Assessment of emphysema-modifying therapy is difficult, but newer outcome measures offer advantages over traditional methods. The EXAcerbations and Computed Tomography scan as Lung End-points (EXACTLE) trial explored the use of computed tomography (CT) densitometry and exacerbations for the assessment of the therapeutic effect of augmentation therapy in subjects with alpha(1)-antitrypsin (alpha(1)-AT) deficiency. In total, 77 subjects (protease inhibitor type Z) were randomised to weekly infusions of 60 mg.kg(-1) human alpha(1)-AT (Prolastin (R)) or placebo for 2-2.5 yrs. The primary end-point was change in CT lung density, and an exploratory approach was adopted to identify optimal methodology, including two methods of adjustment for lung volume variability and two statistical approaches. Other end-points were exacerbations, health status and physiological indices. CT was more sensitive than other measures of emphysema progression, and the changes in CT and forced expiratory volume in 1 s were correlated. All methods of densitometric analysis concordantly showed a trend suggestive of treatment benefit (p-values for Prolastin (R) versus placebo ranged 0.049-0.084). Exacerbation frequency was unaltered by treatment, but a reduction in exacerbation severity was observed. In patients with alpha(1)-AT deficiency, CT is a more sensitive outcome measure of emphysema-modifying therapy than physiology and health status, and demonstrates a trend of treatment benefit from alpha(1)-AT augmentation.
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| 22. |
- Hiller, Adriana Maria, et al.
(författare)
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Cancer risk in severe alpha-1-antitrypsin deficiency
- 2022
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 60:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Severe alpha-1-antitrypsin deficiency (AATD), phenotype PiZZ, is a risk factor for pulmonary emphysema and liver disease, but its effect on cancer risk is unknown. Our aim was to evaluate the risk and the risk factors for incident cancer in PiZZ individuals compared with the general population with known smoking habits.METHODS: A longitudinal study of PiZZ individuals (n=1595) from the Swedish National AATD Register, and controls (n=5999) from Swedish population-based cohorts. Data on cancer and mortality were obtained by cross-linkage with national registers. Individuals who had undergone lung transplantation (n=10) and those with a cancer diagnosis within 5 years prior to inclusion (n=63) were excluded. The risk factors for developing cancer were analysed using proportional hazards and Fine-Gray regression models, adjusting for age, sex, smoking habits and the presence of liver disease.RESULTS: The median follow-up time was 17 years (interquartile range 11 years) for the whole study population. The incidence rates of hepatic and non-hepatic cancer per 1000 person-years were 1.6 (95% CI 1.1-2.3) and 8.5 (95% CI 7.2-10.0), respectively, for the PiZZ individuals, and 0.1 (95% CI 0.04-0.2) and 6.6 (95% CI 6.0-7.1), respectively, for the controls. The adjusted hazard ratios for hepatic and for non-hepatic cancer were 23.4 (95% CI 9.9-55.4) and 1.3 (95% CI 1.1-1.5), respectively, in the PiZZ individuals compared with the controls.CONCLUSION: These results suggest that individuals with severe AATD may have an increased risk of developing both hepatic and non-hepatic cancer, compared with the general population.
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| 23. |
- Hiller, Adriana Maria, et al.
(författare)
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Cancer risk in severe alpha-1-antitrypsin deficiency: the importance of early identification
- 2022
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 60:5
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Tidskriftsartikel (refereegranskat)abstract
- Background Severe alpha-1-antitrypsin deficiency (AATD), phenotype PiZZ, is a risk factor for pulmonary emphysema and liver disease, but its effect on cancer risk is unknown. Our aim was to evaluate the risk and the risk factors for incident cancer in PiZZ individuals compared with the general population with known smoking habits. Methods A longitudinal study of PiZZ individuals (n=1,595) from the Swedish National AATD Register, and controls (n=5,999) from Swedish population-based cohorts. Data on cancer and mortality were obtained by cross-linkage with national registers. Individuals who had undergone lung transplantation (n=10) and those with a cancer diagnosis within five years prior to inclusion (n=63) were excluded. The risk factors for developing cancer were analyzed using proportional hazards and Fine-Gray regression models, adjusting for age, sex, smoking habits and the presence of liver disease. Results The median follow-up time was 17 years (IQR 11) for the whole study population. The incidence rate of hepatic and non-hepatic cancer per 1,000 person-years was 1.6 (95% CI 1.1-2.3) and 8.5 (95% CI 7.2-10.0) for the PiZZ individuals, and 0.1 (95% CI 0.04-0.2) and 6.6 (95% CI 6.0-7.1) for the controls, respectively. The adjusted hazard ratios (HR) for hepatic and for non-hepatic cancer were 23.4 (95% CI 9.9-55.4) and 1.3 (95% CI 1.1-1.5) respectively, in the PiZZ individuals compared with the controls. Conclusion These results suggest that individuals with severe alpha-1-antitrypsin deficiency may have an increased risk of developing both hepatic and non-hepatic cancer, compared with the general population.
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| 24. |
- Hiller, Adriana-Maria, et al.
(författare)
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Decline in FEV1 and hospitalized exacerbations in individuals with severe alpha-1 antitrypsin deficiency
- 2019
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Ingår i: International Journal of COPD. - 1178-2005. ; 14, s. 1075-1083
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Tidskriftsartikel (refereegranskat)abstract
- Background and aim: The value of the forced expiratory volume in one second (FEV1) is useful in the diagnosis and prognosis of chronic obstructive pulmonary disease (COPD). Previous studies on lung function in individuals with severe alpha-1 antitrypsin deficiency (AATD) have shown a variable annual decline in FEV1 (∆FEV1). The aim of this study was to analyze ∆FEV1 and to identify risk factors for ∆FEV1 in individuals with severe AATD.Material and methods: Data on smoking habits, symptoms, results of lung function tests and exacerbations were obtained from the Swedish AATD Register and the Swedish National Patient Register (SNPR). The ∆FEV1 was analyzed by random-effects modeling and adjusted for age and FEV1 at baseline.Results: One hundred and four (9%) current smokers, 539 (48%) ex-smokers and 489 (43%) never-smokers were included in the study and followed-up from 1991 to 2016. A total of 584 (52%) individuals with severe AATD had COPD at inclusion. The median (IQR) annual severe exacerbation rate was 0.66 (1.4). The adjusted mean ∆FEV1 was significantly higher in the current smokers compared with the ex-smokers and never-smokers (70 [95% CI 56–83] vs 42 [95% CI 36–48] and 32 [95% CI 25–38) mL·yr−1,], in the middle–aged individuals compared with the young individuals (48 [95% CI 41–55] vs 32 [95% CI 18–45] mL·yr−1,), in the individuals with respiratory symptoms at inclusion compared with the asymptomatic individuals (46 [95% CI 40–52] vs 30 [95% CI 22–38]mL·yr−1,), and in the individuals with frequent exacerbations compared with those with infrequent exacerbations (57 [95% CI 47–68] vs 27 [95% CI 17–37] mL·yr−1,).Conclusion: Active smoking, age, respiratory symptoms at baseline and repeated severe exacerbations of COPD are factors associated with an accelerated decline of lung function in individuals with severe AATD.
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