| 1. |
- Amaral, Andre F. S., et al.
(författare)
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Chronic airflow obstruction and ambient particulate air pollution
- 2021
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Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 76:12, s. 1236-1241
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Tidskriftsartikel (refereegranskat)abstract
- Smoking is the most well-established cause of chronic airflow obstruction (CAO) but particulate air pollution and poverty have also been implicated. We regressed sex-specific prevalence of CAO from 41 Burden of Obstructive Lung Disease study sites against smoking prevalence from the same study, the gross national income per capita and the local annual mean level of ambient particulate matter (PM2.5) using negative binomial regression. The prevalence of CAO was not independently associated with PM2.5 but was strongly associated with smoking and was also associated with poverty. Strengthening tobacco control and improved understanding of the link between CAO and poverty should be prioritised.
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| 2. |
- Amaral, Andre F. S., et al.
(författare)
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Interaction between gas cooking and GSTM1 null genotype in bronchial responsiveness : results from the European Community Respiratory Health Survey
- 2014
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Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 69:6, s. 558-564
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Tidskriftsartikel (refereegranskat)abstract
- Background Increased bronchial responsiveness is characteristic of asthma. Gas cooking, which is a major indoor source of the highly oxidant nitrogen dioxide, has been associated with respiratory symptoms and reduced lung function. However, little is known about the effect of gas cooking on bronchial responsiveness and on how this relationship may be modified by variants in the genes GSTM1, GSTT1 and GSTP1, which influence antioxidant defences. Methods The study was performed in subjects with forced expiratory volume in one second at least 70% of predicted who took part in the multicentre European Community Respiratory Health Survey, had bronchial responsiveness assessed by methacholine challenge and had been genotyped for GSTM1, GSTT1 and GSTP1-rs1695. Information on the use of gas for cooking was obtained from interviewer-led questionnaires. Effect modification by genotype on the association between the use of gas for cooking and bronchial responsiveness was assessed within each participating country, and estimates combined using meta-analysis. Results Overall, gas cooking, as compared with cooking with electricity, was not associated with bronchial responsiveness (beta=-0.08, 95% CI -0.40 to 0.25, p=0.648). However, GSTM1 significantly modified this effect (beta for interaction=-0.75, 95% CI - 1.16 to -0.33, p=4x10(-4)), with GSTM1 null subjects showing more responsiveness if they cooked with gas. No effect modification by GSTT1 or GSTP1-rs1695 genotypes was observed. Conclusions Increased bronchial responsiveness was associated with gas cooking among subjects with the GSTM1 null genotype. This may reflect the oxidant effects on the bronchi of exposure to nitrogen dioxide.
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| 3. |
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| 4. |
- Amaral, Andre F. S., et al.
(författare)
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Tuberculosis associates with both airflow obstruction and low lung function : BOLD results
- 2015
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 46:4, s. 1104-1112
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Tidskriftsartikel (refereegranskat)abstract
- In small studies and cases series, a history of tuberculosis has been associated with both airflow obstruction, which is characteristic of chronic obstructive pulmonary disease, and restrictive patterns on spirometry. The objective of the present study was to assess the association between a history of tuberculosis and airflow obstruction and spirometric abnormalities in adults. The study was performed in adults, aged 40 years and above, who took part in the multicentre, cross-sectional, general population-based Burden of Obstructive Lung Disease study, and had provided acceptable post-bronchodilator spirometry measurements and information on a history of tuberculosis. The associations between a history of tuberculosis and airflow obstruction and spirometric restriction were assessed within each participating centre, and estimates combined using meta-analysis. These estimates were stratified by high- and low/middle-income countries, according to gross national income. A self-reported history of tuberculosis was associated with airflow obstruction (adjusted odds ratio 2.51, 95% CI 1.83-3.42) and spirometric restriction (adjusted odds ratio 2.13, 95% CI 1.42-3.19). A history of tuberculosis was associated with both airflow obstruction and spirometric restriction, and should be considered as a potentially important cause of obstructive disease and low lung function, particularly where tuberculosis is common.
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| 5. |
- Burney, Peter, et al.
(författare)
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Prevalence and Population-Attributable Risk for Chronic Airflow Obstruction in a Large Multinational Study
- 2021
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 203:11, s. 1353-1365
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: The Global Burden of Disease program identified smoking and ambient and household air pollution as the main drivers of death and disability from chronic obstructive pulmonary disease (COPD).Objectives: To estimate the attributable risk of chronic airflow obstruction (CAO), a quantifiable characteristic of COPD, due to several risk factors.Methods: The Burden of Obstructive Lung Disease study is a cross-sectional study of adults, aged ≥40, in a globally distributed sample of 41 urban and rural sites. Based on data from 28,459 participants, we estimated the prevalence of CAO, defined as a postbronchodilator FEV1-to-FVC ratio less than the lower limit of normal, and the relative risks associated with different risk factors. Local relative risks were estimated using a Bayesian hierarchical model borrowing information from across sites. From these relative risks and the prevalence of risk factors, we estimated local population attributable risks.Measurements and Main Results: The mean prevalence of CAO was 11.2% in men and 8.6% in women. The mean population attributable risk for smoking was 5.1% in men and 2.2% in women. The next most influential risk factors were poor education levels, working in a dusty job for ≥10 years, low body mass index, and a history of tuberculosis. The risk of CAO attributable to the different risk factors varied across sites.Conclusions: Although smoking remains the most important risk factor for CAO, in some areas, poor education, low body mass index, and passive smoking are of greater importance. Dusty occupations and tuberculosis are important risk factors at some sites.
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| 6. |
- Imboden, Medea, et al.
(författare)
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Epigenome-wide association study of lung function level and its change
- 2019
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 54:1
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Tidskriftsartikel (refereegranskat)abstract
- Previous reports link differential DNA methylation (DNAme) to environmental exposures that are associated with lung function. Direct evidence on lung function DNAme is, however, limited. We undertook an agnostic epigenome-wide association study (EWAS) on pre-bronchodilation lung function and its change in adults.In a discovery-replication EWAS design, DNAme in blood and spirometry were measured twice, 6-15 years apart, in the same participants of three adult population-based discovery cohorts (n=2043). Associated DNAme markers (p<5×10-7) were tested in seven replication cohorts (adult: n=3327; childhood: n=420). Technical bias-adjusted residuals of a regression of the normalised absolute β-values on control probe-derived principle components were regressed on level and change of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and their ratio (FEV1/FVC) in the covariate-adjusted discovery EWAS. Inverse-variance-weighted meta-analyses were performed on results from discovery and replication samples in all participants and never-smokers.EWAS signals were enriched for smoking-related DNAme. We replicated 57 lung function DNAme markers in adult, but not childhood samples, all previously associated with smoking. Markers not previously associated with smoking failed replication. cg05575921 (AHRR (aryl hydrocarbon receptor repressor)) showed the statistically most significant association with cross-sectional lung function (FEV1/FVC: pdiscovery=3.96×10-21 and pcombined=7.22×10-50). A score combining 10 DNAme markers previously reported to mediate the effect of smoking on lung function was associated with lung function (FEV1/FVC: p=2.65×10-20).Our results reveal that lung function-associated methylation signals in adults are predominantly smoking related, and possibly of clinical utility in identifying poor lung function and accelerated decline. Larger studies with more repeat time-points are needed to identify lung function DNAme in never-smokers and in children.
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| 7. |
- Jansson, Christer, et al.
(författare)
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Testing bronchodilator responsiveness
- 2019
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Ingår i: European Respiratory Journal. - : EUROPEAN RESPIRATORY SOC JOURNALS LTD. - 0903-1936 .- 1399-3003. ; 54:6
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Tidskriftsartikel (övrigt vetenskapligt)
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| 8. |
- Knox-Brown, Ben, et al.
(författare)
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Small airways obstruction and its risk factors in the Burden of Obstructive Lung Disease (BOLD) study : a multinational cross-sectional study
- 2023
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Ingår i: The Lancet Global Health. - : Elsevier. - 2214-109X. ; 11:1, s. E69-E82
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Tidskriftsartikel (refereegranskat)abstract
- Background: Small airways obstruction is a common feature of obstructive lung diseases. Research is scarce on small airways obstruction, its global prevalence, and risk factors. We aimed to estimate the prevalence of small airways obstruction, examine the associated risk factors, and compare the findings for two different spirometry parameters.Methods: The Burden of Obstructive Lung Disease study is a multinational cross-sectional study of 41 municipalities in 34 countries across all WHO regions. Adults aged 40 years or older who were not living in an institution were eligible to participate. To ensure a representative sample, participants were selected from a random sample of the population according to a predefined site-specific sampling strategy. We included participants' data in this study if they completed the core study questionnaire and had acceptable spirometry according to predefined quality criteria. We excluded participants with a contraindication for lung function testing. We defined small airways obstruction as either mean forced expiratory flow rate between 25% and 75% of the forced vital capacity (FEF25-75) less than the lower limit of normal or forced expiratory volume in 3 s to forced vital capacity ratio (FEV3/FVC ratio) less than the lower limit of normal. We estimated the prevalence of pre-bronchodilator (ie, before administration of 200 mu g salbutamol) and post-bronchodilator (ie, after administration of 200 mu g salbutamol) small airways obstruction for each site. To identify risk factors for small airways obstruction, we performed multivariable regression analyses within each site and pooled estimates using random-effects meta-analysis.Findings: 36 618 participants were recruited between Jan 2, 2003, and Dec 26, 2016. Data were collected from participants at recruitment. Of the recruited participants, 28 604 participants had acceptable spirometry and completed the core study questionnaire. Data were available for 26 443 participants for FEV3/FVC ratio and 25 961 participants for FEF25-75. Of the 26 443 participants included, 12 490 were men and 13 953 were women. Prevalence of pre-bronchodilator small airways obstruction ranged from 5% (34 of 624 participants) in Tartu, Estonia, to 34% (189 of 555 participants) in Mysore, India, for FEF25-75, and for FEV 3/FVC ratio it ranged from 5% (31 of 684) in Riyadh, Saudi Arabia, to 31% (287 of 924) in Salzburg, Austria. Prevalence of post-bronchodilator small airways obstruction was universally lower. Risk factors significantly associated with FEV 3/FVC ratio less than the lower limit of normal included increasing age, low BMI, active and passive smoking, low level of education, working in a dusty job for more than 10 years, previous tuberculosis, and family history of chronic obstructive pulmonary disease. Results were similar for FEF25-75, except for increasing age, which was associated with reduced odds of small airways obstruction.Interpretation: Despite the wide geographical variation, small airways obstruction is common and more prevalent than chronic airflow obstruction worldwide. Small airways obstruction shows the same risk factors as chronic airflow obstruction. However, further research is required to investigate whether small airways obstruction is also associated with respiratory symptoms and lung function decline.
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| 9. |
- Kubler, Andre, et al.
(författare)
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Cathepsin K Contributes to Cavitation and Collagen Turnover in Pulmonary Tuberculosis
- 2016
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 213:4, s. 618-627
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Tidskriftsartikel (refereegranskat)abstract
- Cavitation in tuberculosis enables highly efficient person-to-person aerosol transmission. We performed transcriptomics in the rabbit cavitary tuberculosis model. Among 17 318 transcripts, we identified 22 upregulated proteases. Five type I collagenases were overrepresented: cathepsin K (CTSK), mast cell chymase-1 (CMA1), matrix metalloproteinase 1 (MMP-1), MMP-13, and MMP-14. Studies of collagen turnover markers, specifically, collagen type I C-terminal propeptide (CICP), urinary deoxypyridinoline (DPD), and urinary helical peptide, revealed that cavitation in tuberculosis leads to both type I collagen destruction and synthesis and that proteases other than MMP-1, MMP-13, and MMP-14 are involved, suggesting a key role for CTSK. We confirmed the importance of CTSK upregulation in human lung specimens, using immunohistochemical analysis, which revealed perigranulomatous staining for CTSK, and we showed that CTSK levels were increased in the serum of patients with tuberculosis, compared with those in controls (3.3 vs 0.3 ng/mL; P = .005).
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| 10. |
- Lara-Cerón, Jesús A., et al.
(författare)
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Ultrasound-assisted synthesis of organotin compounds and their application as luminescent dye in silk fibroin scaffolds
- 2020
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Ingår i: Inorganica Chimica Acta. - : Elsevier BV. - 0020-1693. ; 505
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we report the green synthesis of four luminescent organotin compounds 1–4 derived from amino acid Schiff bases (1: Naph-Trp-SnPh2, 2: Naph-Tyr-SnBu2, 3: Naph-Tyr-SnPh2, 4: Naph-Phe-SnPh2), obtained by ultrasound-assisted synthesis in short time (~20 min) and good yields (>95%). The molecular structure proposed in solution (1H and 119Sn NMR) was confirmed by X-ray diffraction study for compound 1 where the tin atom resides in trigonal bipyramid geometry. Luminescent silk fibroin scaffolds (SF 1–4) were elaborated with organotin compounds by freeze-drying technique. Photophysical properties of organotin compounds and scaffolds were obtained in solid state, observing bathochromic behaviors in tyrosine derived compounds, suggesting that the tyrosine produce supramolecular interactions across the –OH group that change the fluorescent properties. Scaffolds 1–4 were characterized by FTIR, XDR, TG/DTG, and SEM analysis. In addition, cytotoxic analysis of SF 1 presents high cellular viability, which could be applied as a scaffold in tissue engineering.
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