| 1. |
- Sakornsakolpat, Phuwanat, et al.
(författare)
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Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 494-505
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 x 10-8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.
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| 2. |
- 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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| 3. |
- Knox-Brown, Ben, et al.
(författare)
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The association of spirometric small airways obstruction with respiratory symptoms, cardiometabolic diseases, and quality of life : results from the Burden of Obstructive Lung Disease (BOLD) study
- 2023
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Ingår i: Respiratory Research. - : BioMed Central (BMC). - 1465-9921 .- 1465-993X. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSpirometric small airways obstruction (SAO) is common in the general population. Whether spirometric SAO is associated with respiratory symptoms, cardiometabolic diseases, and quality of life (QoL) is unknown.MethodsUsing data from the Burden of Obstructive Lung Disease study (N = 21,594), we defined spirometric SAO as the mean forced expiratory flow rate between 25 and 75% of the FVC (FEF25-75) less than the lower limit of normal (LLN) or the forced expiratory volume in 3 s to FVC ratio (FEV3/FVC) less than the LLN. We analysed data on respiratory symptoms, cardiometabolic diseases, and QoL collected using standardised questionnaires. We assessed the associations with spirometric SAO using multivariable regression models, and pooled site estimates using random effects meta-analysis. We conducted identical analyses for isolated spirometric SAO (i.e. with FEV1/FVC ≥ LLN).ResultsAlmost a fifth of the participants had spirometric SAO (19% for FEF25-75; 17% for FEV3/FVC). Using FEF25-75, spirometric SAO was associated with dyspnoea (OR = 2.16, 95% CI 1.77–2.70), chronic cough (OR = 2.56, 95% CI 2.08–3.15), chronic phlegm (OR = 2.29, 95% CI 1.77–4.05), wheeze (OR = 2.87, 95% CI 2.50–3.40) and cardiovascular disease (OR = 1.30, 95% CI 1.11–1.52), but not hypertension or diabetes. Spirometric SAO was associated with worse physical and mental QoL. These associations were similar for FEV3/FVC. Isolated spirometric SAO (10% for FEF25-75; 6% for FEV3/FVC), was also associated with respiratory symptoms and cardiovascular disease.ConclusionSpirometric SAO is associated with respiratory symptoms, cardiovascular disease, and QoL. Consideration should be given to the measurement of FEF25-75 and FEV3/FVC, in addition to traditional spirometry parameters.
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| 4. |
- Abozid, Hazim, et al.
(författare)
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Prevalence of chronic cough, its risk factors and population attributable risk in the Burden of Obstructive Lung Disease (BOLD) study : a multinational cross-sectional study
- 2024
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Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 68
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Tidskriftsartikel (refereegranskat)abstract
- Background Chronic cough is a common respiratory symptom with an impact on daily activities and quality of life. Global prevalence data are scarce and derive mainly from European and Asian countries and studies with outcomes other than chronic cough. In this study, we aimed to estimate the prevalence of chronic cough across a large number of study sites as well as to identify its main risk factors using a standardised protocol and definition. Methods We analysed cross-sectional data from 33,983 adults (>= 40 years), recruited between Jan 2, 2003 and Dec 26, 2016, in 41 sites (34 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We estimated the prevalence of chronic cough for each site accounting for sampling design. To identify risk factors, we conducted multivariable logistic regression analysis within each site and then pooled estimates using random -effects metaanalysis. We also calculated the population attributable risk (PAR) associated with each of the identifed risk factors. Findings The prevalence of chronic cough varied from 3% in India (rural Pune) to 24% in the United States of America (Lexington,KY). Chronic cough was more common among females, both current and passive smokers, those working in a dusty job, those with a history of tuberculosis, those who were obese, those with a low level of education and those with hypertension or airflow limitation. The most influential risk factors were current smoking and working in a dusty job. Interpretation Our findings suggested that the prevalence of chronic cough varies widely across sites in different world regions. Cigarette smoking and exposure to dust in the workplace are its major risk factors.
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| 5. |
- 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 Publishing Group Ltd. - 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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| 6. |
- Houben-Wilke, Sarah, et al.
(författare)
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Revealing Methodological Challenges in Chronic Obstructive Pulmonary Disease Studies Assessing Comorbidities: A Narrative Review.
- 2019
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Ingår i: Chronic obstructive pulmonary diseases (Miami, Fla.). - : COPD Foundation. - 2372-952X. ; 6:2, s. 166-77
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Tidskriftsartikel (refereegranskat)abstract
- Beyond respiratory impairment, patients with chronic obstructive pulmonary disease (COPD) often suffer from comorbidities which are associated with worse health status, higher health care costs and worse prognosis. Reported prevalences of comorbidities largely differ between studies which might be explained by different assessment methods (objective assessment, self-reported assessment, or assessment by medical records), heterogeneous study populations, inappropriate control groups, incomparable methodologies, etc. This narrative review demonstrates and further evaluates the variability in prevalence of several comorbidities in patients with COPD and control individuals and discusses several shortcomings and pitfalls which need to be considered when interpreting comorbidity data. Like in other chronic organ diseases, the accurate diagnosis and integrated management of comorbidities is a key for outcome in COPD. This review highlights that there is a need to move from the starting point of an established index disease towards the concept of the development of multimorbidity in the elderly including COPD as an important and highly prevalent pulmonary component.
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| 7. |
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| 8. |
- Stolk, Jan, et al.
(författare)
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Randomised controlled trial for emphysema with a selective agonist of the gamma-type retinoic acid receptor
- 2012
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 40:2, s. 306-312
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Tidskriftsartikel (refereegranskat)abstract
- Palovarotene is an oral gamma-selective retinoid agonist. In animal emphysema models, palovarotene reduced inflammation, promoted structural repair and functional improvement. REPAIR (Retinoid treatment of Emphysema in Patients on the alpha(1)-antitrypsin International Registry), was an investigator-initiated, double-blind, placebo-controlled randomised study to assess the safety and efficacy of 5 mg.day(-1) palovarotene given for 1 year to 262 patients with severe alpha(1)-antitrypsin deficiency and emphysema confirmed by computed tomography. Change in volume-adjusted 15th percentile point lung density from baseline in 1 year was the primary endpoint; functional end-points were also regularly assessed. We randomly assigned 133 and 129 patients to placebo or palovarotene, respectively. Both groups were well matched for all baseline characteristics, including respiratory medications. 88% and 85% of patients completed 1 year of treatment with placebo and palovarotene, respectively. Palovarotene was generally well tolerated. In the study completers population, the placebo-corrected difference of lung density was -0.45 HU at week 28 (p=0.64) and -0.25 HU at week 52 (p=0.94). A nonsignificant treatment difference in most functional parameters of the lung in favour of the drug was observed over time suggesting potential pharmacological effects of palovarotene. Palovarotene 5 mg.day(-1) over 1 yr failed to show a significant benefit on lung density in moderate-to-severe emphysema secondary to severe alpha(1)-antitrypsin deficiency.
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