Epidemiology of Lung Function and Chronic Obstructive Pulmonary Disease

Spirometry is a technique to evaluate the pulmonary ventilatory function and is a reflection of several forces implied in lung volumes. The lung volume is dependent on the elastic recoil of the lungs and chest wall and the muscular efforts of the chest wall, diaphragm, an

Clopidogrel use is associated with an increased prevalence of cerebral microbleeds in a stroke-free population: the Rotterdam study.

Although clopidogrel reduces the incidence of atherothrombotic events, its use is associated with an increased risk of major bleeding. Cerebral microbleeds (CMBs) are indicative of subclinical microangiopathy in the brain and may prelude symptomatic intracerebral hemorrhage. We examined the association between use of clopidogrel and CMBs in persons without a history of stroke. We performed a cross-sectional analysis using data from the Rotterdam Study, a prospective population-based cohort of persons aged 45 years and older. Among 4408 stroke-free individuals who underwent brain magnetic resonance imaging for the detection of CMBs, we identified 121 ever-users and 4287 never-users of clopidogrel before magnetic resonance imaging. We used multiple logistic regression to analyze the association between clopidogrel and CMBs with adjustment for age, sex, cardiovascular risk factors, and common cardiovascular medication. Users of clopidogrel had a higher prevalence of CMBs (odd ratio 1.55, 95% CI 1.01 to 2.37) than nonusers and more often had a high number (> 4) of CMBs (odds ratio 3.19, 95% CI 1.52 to 6.72). Clopidogrel use was associated with a significantly higher prevalence of deep or infratentorial CMBs (odd ratio 1.90, 95% CI 1.05 to 3.45). Among clopidogrel users, we were unable to demonstrate differences in the prevalence of CMBs by indication of prescription, history of coronary heart disease, or common genetic variants in CYP2C19. In stroke-free individuals, clopidogrel use was associated with a higher prevalence and higher number of CMBs. Whether this association is causal requires confirmation in prospective studies, especially given the small number of participants taking clopidogrel and the possibil

Prevalence of pulmonary hypertension in the general population

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Susceptibility to chronic mucus hypersecretion, a genome wide association study

Background: Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations. Methods: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and meta-analysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (≥20 pack-years). Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP). Results: A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25x10-6, OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression of SATB1 (4.3x10 -9) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture. Conclusions: Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH

β-adrenoceptor blockers and pulmonary function in the general population: The Rotterdam Study

Aim β-adrenoceptor blockers have been used with caution in patients with obstructive lung diseases such as asthma or chronic obstructive pulmonary disease (COPD), due to the potentially increased airway reactivity and risk of bronchial obstruction. Cardioselective β-adrenoceptor blockers have a more beneficial profile than non-cardioselective β-adrenoceptor blockers and can be safely prescribed to patients with both cardiovascular disease and COPD. We hypothesized that cardioselective β-adrenoceptor blockers also affect pulmonary function. Methods This study was performed within the Rotterdam Study, a prospective population-based cohort study. Effects of cardioselective and non-cardioselective β-adrenoceptor blockers on pulmonary function were analysed using regression techniques with multivariable adjustment for potential confounders. Results Current use of non-cardioselective β-adrenoceptor blockers was significantly associated with a lower forced expiratory volume in 1 s (FEV1) of -198 ml (95% CI -301, -96), with a lower forced vital capacity (FVC) of -223 ml (95% CI -367, -79) and with a decreased FEV 1: FVC of -1.38% (95% CI -2.74, -0.13%). Current use of cardioselective β-adrenoceptor blockers was significantly associated with a lower FEV1 of -118 ml (95% CI -157, -78) and with a lower FVC of -167 ml (95% CI -222, -111), but did not affect FEV1: FVC. After exclusion of patients with COPD, asthma and heart failure the effects of cardioselective β-adrenoceptor blockers remained significant for FEV 1 (-142 ml [95% CI -189, -96]) and for FVC (-176 ml [95% CI -236, -117]). Conclusion In our study both non-cardioselective and cardioselective β-adrenoceptor blockers had a clinically relevant effect on both FEV 1 and FVC. In contrast to cardioselective β-adrenoceptor blockers, use of non-cardioselective β-adrenoceptor blockers was associated with a significantly lower FEV1: FVC

Chronic obstructive pulmonary disease and lipid core carotid artery plaques in the elderly: The Rotterdam study

Rationale: Chronic obstructive pulmonary disease (COPD) is an independent risk factor for ischemic stroke and the risk increases with severity of airflow limitation. Even though vulnerable carotid artery plaque components, such as intraplaque hemorrhage and lipid core, place persons at high risk for ischemic events, the plaque composition in patients with COPD has never been explored. Objectives: To investigate the prevalence of carotid wall thickening, the different carotid artery plaque components, and their relationship with severity of airflow limitation in elderly patients with COPD. Methods: This cross-sectional analysis was part of the Rotterdam Study, a prospective population-based cohort study performed in subjects aged 55 years and older. Diagnosis of COPD was confirmed by spirometry. Participants with carotid wall intima-media thickness greater than or equal to 2.5 mm on ultrasonography underwent high-resolution magnetic resonance imaging for characterization of carotid plaques. Data were analyzed using logistic regression. MeasurementsandMainResults:COPDcases(n = 253)hadatwofold increasedrisk (odds ratio, 2.0; 95%confidence interval, 1.44-2.85;P < 0.0001) of presentation with carotid wall thickening on ultrasonography compared with control subjects with a normal lung function (n = 920). Moreover, the risk increased significantly with severity of airflow limitation. On magnetic resonance imaging, vulnerable lipid core plaques were more frequent in COPD cases than in control subjects (odds ratio, 2.1; 95% confidence interval, 1.25-3.69; P = 0.0058). Conclusions: Carotid artery wall thickening is more prevalent in patients with COPD than in control subjects. In elderly subjects with carotid wall thickening, COPD is an independent predictor for the presence of a lipid

Chronic obstructive pulmonary disease and cerebral Microbleeds the Rotterdam study

Rationale: Chronic obstructive pulmonary disease (COPD) is a common, complex multisystem disease in the elderly with multiple comorbidities that significantly impact morbidity and mortality. Although cerebral small-vessel disease is an important cause of cognitive decline and age-related disability, it is a poorly investigated potential systemic manifestation of patients with COPD. Objectives: To examine whether COPD relates to the development and location of cerebral microbleeds, a novel marker of cerebral small-vessel disease. Methods: Cross-sectional and longitudinal analyses were part of the Rotterdam Study, a prospective population-based cohort study in subjects aged greater than or equal to 55 years. Diagnosis of COPD was confirmed by spirometry. Cerebral microbleeds were detected using high-resolution magnetic resonance imaging (MRI). Measurements and Main Results: Subjects with COPD (n = 165) had a higher prevalence of cerebral microbleeds compared with subjects with normal lung function (n = 645) independent of age, sex, smoking status, atherosclerotic macroangiopathy, antithrombotic use, total cholesterol, triglycerides, and serum creatinin (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.152.47; P = 0.007). Regarding the specific microbleed location, subjects with COPD had a significantly higher prevalence of microbleeds in deep or infratentorial locations (OR, 3.3; 95% CI, 1.975.53; P , 0.001), which increased with severity of airflow limitation and are suggestive of hypertensive or arteriolosclerotic microangiopathy. Furthermore, in longitudinal analysis restricted to subjects without microbleed at baseline,COPDwas an independent predictor of incident cerebral microbleeds in deep or infratentorial locations (OR, 7.1;95%CI, 2.1 24.5; P = 0.002). Conclusions: Our findings are compatible with COPD causing an increased risk of the development of cerebral microbleeds in deep or infratentorial locations. Copyrigh

Prothrombotic genetic risk factors are associated with an increased risk of liver fibrosis in the general population: The Rotterdam Study

Background & Aims The coagulation system is known to be involved in fibrogenesis in patients with liver disease. We investigated whether common genetic prothrombotic risk factors are associated with an increased risk of fibrosis in the general population. Methods This investigation was part of the Rotterdam Study, an ongoing, population-based cohort study. Liver stiffness (LS) was measured using transient elastography (Fibroscan®) and associated with single nucleotide polymorphisms determining blood group type and presence of the Factor V Leiden (FVL) mutation or prothrombin G20210A gene variant. Results Reliable LS measurements and genetic data were obtained from 1055 Caucasian participants. LS ≥8.0 kPa, suggestive of clinically relevant fibrosis, was observed in 101 subjects (9.6%). Presence of FVL or prothrombin G20210A was independently associated with an increased risk of LS ≥8.0 kPa (OR 2.09, 95%CI 1.07-4.07, p = 0.03). Combination of blood group type non-O and the FVL mutation or prothrombin G20210A variant resulted in an even higher risk of LS ≥8.0 kPa (OR 3.36, 95%CI 1.50-7.56, p = 0.003). Presence of the FVL mutation or prothrombin G20210A variant in participants with blood group non-O was associated with a predicted probability of 14.3% (7.7-23.8) of LS ≥8.0 kPa. Conclusions Participants carrying the FVL mutation or prothrombin G20210A variant have an increased risk of clinically relevant liver fibrosis, which is even higher in blood group type non-O carriers. The fact that genetic prothrombotic risk factors are associated with an increased risk of liver fibrosis suggests that coagulation plays an important role in fibrogenesis in the general population