| 11. |
- de Marco, Roberto, et al.
(författare)
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Risk Factors for Chronic Obstructive Pulmonary Disease in a European Cohort of Young Adults
- 2011
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 183:7, s. 891-897
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Few studies have investigated the factors associated with the early inception of chronic obstructive pulmonary disease (COPD). Objectives: We investigated COPD risk factors in an international cohort of young adults using different spirometric definitions of the disease. Methods. We studied 4,636 subjects without asthma who had prebronchodilator FEV1/FVC measured in the European Community Respiratory Health Survey both in 1991 to 1993 (when they were 20-44 yr old) and in 1999 to 2002. COPD was defined according to the Global Initiative for Chronic Obstructive Lung Disease fixed cut-off criterion (FEV1/FVC < 0.70), and two criteria based on the Quanjer and LuftiBus reference equations (FEV1/FVC less than lower limit of normal). COPD determinants were studied using two-level Poisson regression models. Measurements and Main Results: COPD incidence ranged from 1.85 (lower limit of normal [Quanjer]) to 2.88 (Global Initiative for Chronic Obstructive Lung Disease) cases/1,000/yr. Although about half of the cases had smoked less than 20 pack-years, smoking was the main risk factor for COPD, and it accounted for 29 to 39% of the new cases during the follow-up. Airway hyperresponsiveness was the second strongest risk factor (15-17% of new cases). Other determinants were respiratory infections in childhood and a family history of asthma, whereas the role of sex, age, and of being underweight largely depended on the definition of COPD used. Conclusions: COPD may start early in life. Smoking prevention should be given the highest priority to reduce COPD occurrence. Airway hyperresponsiveness, a family history of asthma, and respiratory infections in childhood are other important determinants of COPD. We suggest the need for a definition of COPD that is not exclusively based on spirometry.
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| 12. |
- Gómez Real, Francisco, et al.
(författare)
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Menstrual irregularity and asthma and lung function
- 2007
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 120:3, s. 557-564
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Tidskriftsartikel (refereegranskat)abstract
- Background: Oligomenorrhea was associated with more asthma (Respiratory Health in Northern Europe study), but a possible association with lung function has not been investigated previously. Objective: To investigate whether oligomenorrhea was related to lung function and asthma, and whether body mass index and physical activity modified associations. Methods: Women age 28 to 44 years (n = 1631) participating in the European Community Respiratory Health Survey were included. Women who were taking exogenous sex hormones, were pregnant, or had recently given birth were excluded. Results: Long or irregular menstrual cycles were reported by 313 women (19%). Oligomenorrhea was significantly associated with more asthma symptoms (odds ratio [OR], 1.76; 95% CI, 1.29-2.40), allergic asthma (OR, 2.46; 95% CI, 1.43-4.23), and lower forced vital capacity (FVC; adjusted difference, 63 mL; 95% CI, -124 to -1). When excluding women using asthma medication, very lean women, or women exercising daily, these associations remained significant. Effects of oligomenorrhea were additive to those of body mass index (BMI) on asthma and FVC. Asthma symptoms increased significantly with BMI. FVC and FEV1 increased with BMI until 25 kg/m2 and thereafter decreased with increasing BMI. Excluding women exercising daily, asthma symptoms increased significantly with decreasing physical activity (OR, 1.09; 95% CI, 1.001-1.19) per category of physical activity) independently of oligomenorrhea. Among women exercising daily, oligomenorrhea predicted very high risk for asthma symptoms (OR, 12.6; 95% CI, 3.7-43). Conclusion: Women with oligomenorrhea have reduced lung function and more asthma, particularly allergic asthma, independent of BMI and physical activity. Airways pathology may have not only a hormonal but also a metabolic component. Clinical implications: Women with oligomenorrhea should be investigated with regard to asthma and lung function. Underlying metabolic disturbance should be considered in asthma.
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| 13. |
- Gudbjartsson, Daniel F., et al.
(författare)
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Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:3, s. 342-347
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).
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| 14. |
- Hancock, Dana B, et al.
(författare)
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Genome-Wide Joint Meta-Analysis of SNP and SNP-by-Smoking Interaction Identifies Novel Loci for Pulmonary Function
- 2012
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 8:12, s. e1003098-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV1), and its ratio to forced vital capacity (FEV1/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV1 and FEV1/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest PJMA = 5.00×10−11), HLA-DQB1 and HLA-DQA2 (smallest PJMA = 4.35×10−9), and KCNJ2 and SOX9 (smallest PJMA = 1.28×10−8) were associated with FEV1/FVC or FEV1 in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.
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| 15. |
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| 16. |
- Krauss-Etschmann, Susanne, et al.
(författare)
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Of flies, mice and men : a systematic approach to understanding the early life origins of chronic lung disease
- 2013
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Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 68:4, s. 380-384
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Forskningsöversikt (refereegranskat)abstract
- Despite intensive research efforts, the aetiology of the majority of chronic lung diseases (CLD) in both, children and adults, remains elusive. Current therapeutic options are limited, providing only symptomatic relief, rather than treating the underlying condition, or preventing its development in the first place. Thus, there is a strong and unmet clinical need for the development of both, novel effective therapies and preventative strategies for CLD. Many studies suggest that modifications of prenatal and/or early postnatal lung development will have important implications for future lung function and risk of CLD throughout life. This view represents a fundamental change of current pathophysiological concepts and treatment paradigms, and holds the potential to develop novel preventative and/or therapeutic strategies. However, for the successful development of such approaches, key questions, such as a clear understanding of underlying mechanisms of impaired lung development, the identification and validation of relevant preclinical models to facilitate translational research, and the development of concepts for correction of aberrant development, all need to be solved. Accordingly, a European Science Foundation Exploratory Workshop was held where clinical, translational and basic research scientists from different disciplines met to discuss potential mechanisms of developmental origins of CLD, and to identify major knowledge gaps in order to delineate a roadmap for future integrative research.
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| 17. |
- Leynaert, Benedicte, et al.
(författare)
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Gender differences in prevalence, diagnosis and incidence of allergic and non-allergic asthma : a population-based cohort
- 2012
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Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 67:7, s. 625-631
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Tidskriftsartikel (refereegranskat)abstract
- Background Although women with severe non-allergic asthma may represent a substantial proportion of adults with asthma in clinical practice, gender differences in the incidence of allergic and non-allergic asthma have been little investigated in the general population. Methods Gender differences in asthma prevalence, reported diagnosis and incidence were investigated in 9091 men and women randomly selected from the general population and followed up after 8-10 years as part of the European Community Respiratory Health Survey. The protocol included assessment of bronchial responsiveness, IgE specific to four common allergens and skin tests to nine allergens. Results Asthma was 20% more frequent in women than in men over the age of 35 years. Possible under-diagnosis of asthma appeared to be particularly frequent among non-atopic individuals, but was as frequent in women as in men. The follow-up of subjects without asthma at baseline showed a higher incidence of asthma in women than in men (HR 1.94; 95% CI 1.40 to 2.68), which was not explained by differences in smoking, obesity or lung function. More than 60% of women and 30% of men with new-onset asthma were non-atopic. The incidence of non-allergic asthma was higher in women than in men throughout all the reproductive years (HR 3.51; 95% CI 2.21 to 5.58), whereas no gender difference was observed for the incidence of allergic asthma. Conclusions This study shows that female sex is an independent risk factor for non-allergic asthma, and stresses the need for more careful assessment of possible non-allergic asthma in clinical practice, in men and women.
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| 18. |
- Loth, Daan W, et al.
(författare)
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Genome-wide association analysis identifies six new loci associated with forced vital capacity
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46, s. 669-677
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Tidskriftsartikel (refereegranskat)abstract
- Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
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| 19. |
- Macsali, Ferenc, et al.
(författare)
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Early Age at Menarche, Lung Function, and Adult Asthma
- 2011
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 183:1, s. 8-14
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Hormonal and metabolic status appears to influence lung health in women, and there are findings suggesting that early menarche may be related to asthma, cardiovascular disease, diabetes, and breast cancer. Objectives: This study investigates whether age at menarche is related to adult lung function and asthma. Methods: Among participants in the European Community Respiratory Health Survey II, 3,354 women aged 27-57 years from random population samples in 21 centers responded to a questionnaire concerning women's health (1998-2002). Of these women, 2,873 had lung function measurements, 2,136 had measurements of bronchial hyperreactivity, and 2,743 had IgE measurements. Logistic, linear, and negative binomial regression analyses included adjustment for age, height, body mass index, education, smoking, family size, and center. Measurements and Main Results: FEV1 and FVC were lower and asthma was more common in women with early menarche. Women reporting menarche at age 10 years or less, as compared with women with menarche at age 13 years (reference category), had lower FEV1 (adjusted difference, -113 ml; 95% confidence interval [CI], -196 to -33 ml) and FVC (-126 ml; 95% CI, -223 to -28 ml); also lower FEV1 expressed as a percentage of the predicted value (-3.28%; 95% CI, -6.25 to -0.30%) and FVC expressed as a percentage of the predicted value (-3.63%; 95% CI, -6.64 to -0.62%). Women with early menarche more often had asthma symptoms (odds ratio, 1.80; 95% CI, 1.09-2.97), asthma with bronchial hyperreactivity (odds ratio, 2.79; 95% CI, 1.06-7.34), and higher asthma symptom score (mean ratio, 1.58; 95% CI, 1.12-2.21). Conclusions: Women with early menarche had lower lung function and more asthma in adulthood. This supports a role for metabolic and hormonal factors in women's respiratory health.
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| 20. |
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