Increased expression of pulmonary ACE2, the SARS-CoV-2 receptor, could contribute to increased infectivity of COVID-19 in patients with diabetes, but ACE2 expression has not been studied in lung ...tissue of subjects with diabetes. We therefore studied ACE2 mRNA and protein expression in lung tissue samples of subjects with and without diabetes that were collected between 2002 and 2020 from patients undergoing lobectomy for lung tumors. For RT-PCR analyses, samples from 15 subjects with diabetes were compared with 91 randomly chosen control samples. For immunohistochemical staining, samples from 26 subjects with diabetes were compared with 66 randomly chosen control samples. mRNA expression of ACE2 was measured by quantitative RT-PCR. Protein levels of ACE2 were visualized by immunohistochemistry on paraffin-embedded lung tissue samples and quantified in alveolar and bronchial epithelium. Pulmonary ACE2 mRNA expression was not different between subjects with or without diabetes. In contrast, protein levels of ACE2 were significantly increased in both alveolar tissue and bronchial epithelium of patients with diabetes compared with control subjects, independent of smoking, chronic obstructive pulmonary disease, BMI, renin-angiotensin-aldosterone system inhibitor use, and other potential confounders. To conclude, we show increased bronchial and alveolar ACE2 protein expression in patients with diabetes. Further research is needed to elucidate whether upregulation of ACE2 expression in airways and lungs has consequences on infectivity and clinical outcomes of COVID-19.
We evaluated the performance of the recently extended Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA version 5) in a Dutch prospective cohort, using a ...polygenic risk score (PRS) based on 313 breast cancer (BC)-associated variants (PRS
) and other, nongenetic risk factors.
Since 1989, 6522 women without BC aged 45 or older of European descent have been included in the Rotterdam Study. The PRS
was calculated per 1 SD in controls from the Breast Cancer Association Consortium (BCAC). Cox regression analysis was performed to estimate the association between the PRS
and incident BC risk. Cumulative 10-year risks were calculated with BOADICEA including different sets of variables (age, risk factors and PRS
). C-statistics were used to evaluate discriminative ability.
In total, 320 women developed BC. The PRS
was significantly associated with BC (hazard ratio HR per SD of 1.56, 95% confidence interval CI 1.40-1.73). Using 10-year risk estimates including age and the PRS
, other risk factors improved the discriminatory ability of the BOADICEA model marginally, from a C-statistic of 0.636 to 0.653.
The effect size of the PRS
is highly reproducible in the Dutch population. Our results validate the BOADICEA v5 model for BC risk assessment in the Dutch general population.
The aging population and its burden on health care systems warrant early detection of patients at risk of functional decline and mortality. We aimed to assess frailty transitions and its accuracy for ...mortality prediction in participants with impaired spirometry (Preserved Ratio Impaired Spirometry PRISm or chronic obstructive pulmonary disease COPD).
In participants from the population-based Rotterdam Study (mean age 69.1 ± 8.9 years), we examined whether PRISm (forced expiratory volume in 1 second FEV1/forced vital capacity FVC ≥ 70% and FEV1 < 80%) or COPD (FEV1/FVC < 70%) affected frailty transitions (progression/recovery between frailty states robust, prefrailty, and frailty, lost to follow-up, or death) using age-, sex- and smoking state-adjusted multinomial regression models yielding odds ratios (OR). Second, we assessed the diagnostic accuracy of frailty score for predicting mortality in participants with COPD using c-statistics.
Compared to participants with normal spirometry, participants with PRISm were more likely to transit from robust (OR 2.2 1.2-4.2, p < .05) or prefrailty (OR 2.6 1.3-5.5, p < .01) toward frailty. Participants with PRISm (OR 0.4 0.2-0.8, p < .05) and COPD (OR 0.6 0.4-1.0, NS) were less likely to recover from their frail state, and were more likely to progress from any frailty state toward death (OR between 1.1 and 2.8, p < .01). Accuracy for predicting mortality in participants with COPD significantly improved when adding frailty score to age, sex, and smoking status (90.5 82.3-89.8 vs 77.9 67.2-88.6, p < .05).
Participants with PRISm or COPD more often developed frailty with poor reversibility. Assessing physical frailty improved risk stratification for participants with impaired spirometry for predicting increased life years.
COPD is associated with an increased risk of cardiovascular morbidity and mortality, potentially by mechanisms of atherosclerosis. Insight into location-specific vulnerability to atherosclerosis in ...COPD, including intracranial arteries, is lacking. We aimed to investigate the relation between COPD and atherosclerosis in multiple vessel beds within a large population-based cohort study.
From 2003 to 2006, a random sample of 2187 elderly participants (mean age, 69.6 ± 6.8 years; 50.9% female; 11.7% COPD) from the population-based Rotterdam Study underwent computed tomography to quantify atherosclerotic coronary artery calcification (CAC), aortic arch calcification (AAC), extracranial carotid artery calcification (ECAC), and intracranial carotid artery calcification (ICAC). We investigated the association of COPD ratio of forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) < 70% with the presence of calcification and with calcification volumes in each vessel bed using logistic and linear regression, with adjustments for cardiovascular risk factors including smoking.
The prevalence of CAC, AAC and ECAC was significantly higher in subjects with COPD compared to those without. After adjusting for age and smoking, COPD remained associated with the presence of ECAC (odds ratio 1.46 95% confidence interval, 1.02–2.07, p = 0.037). COPD was significantly associated with larger calcification volumes in all four vessel beds in people in whom calcification was present.
The results of this study suggest that COPD plays a role in extracranial carotid artery atherosclerosis initiation and systemic atherosclerosis aggravation.
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•COPD is related to calcifications in the extracranial arteries.•COPD may affect atherosclerosis in various vessel beds differently.•COPD is related to arterial calcification independent of smoking.
ObjectivesPatients with chronic obstructive pulmonary disease (COPD) are at increased risk of cerebrovascular disease, which might be associated with decreases in cerebral blood flow. Since studies ...examining cerebral blood flow in COPD remain scarce and are limited by sample size, we aimed to study cerebral blood flow in participants with and without COPD.DesignObservational cohort study.SettingPopulation-based Rotterdam Study.Participants4177 participants (age 68.0±8.5 years; 53% females) with and without COPD.Predictor variableSpirometry and pulmonary diffusing capacity.Outcome measuresCerebral blood flow by two-dimensional phase-contrast cerebral MRI.ResultsCompared with subjects with normal spirometry (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥0.7 and FEV1 ≥80%), multivariable adjusted cerebral blood flow (mL/min) was preserved in subjects with COPD Global initiative for Chronic Obstructive Lung Disease (GOLD1) (FEV1/FVC <0.7 and FEV1 ≥80%), but significantly lower in subjects with COPD GOLD2-3 (FEV1/FVC <0.7 and FEV1 <80%), even after adjustment for cardiovascular comorbidities. In sex-stratified analyses, this difference in cerebral blood flow was statistically significant in women but not in men. Cerebral blood flow was lowest in subjects with FEV1, FVC and diffusion lung capacity for carbon monoxide % predicted values in the lowest quintile, even after adjustment for cardiovascular comorbidities and cardiac function.ConclusionWe observed a lowered cerebral blood flow in subjects with COPD GOLD2-3.
Increasing evidence suggests that sarcopenia and a higher systemic immune-inflammation index (SII) are linked with morbidity in patients with COPD. However, whether these two conditions contribute to ...all-cause mortality in middle-aged and older patients with COPD or asthma is unclear. Therefore, we investigated the association between sarcopenia, SII, COPD or asthma and all-cause mortality in a large-scale population-based setting.
Between 2009 and 2014, 4482 participants (aged >55 years; 57.3% female) from the population-based Rotterdam Study were included. COPD and asthma patients were diagnosed clinically and based on spirometry. Six study groups were defined according to the presence or absence of COPD or asthma and sarcopenia. Cox regression models were used to assess all-cause mortality in the study groups, adjusted for sex, age, body mass index, SII, smoking, oral corticosteroid use and comorbidities. In addition, all participants were categorised into sex-specific quartiles of SII, and mortality in these groups was compared.
Over a median follow-up of 6.1 years (interquartile range 5.0-7.2 years), 466 (10.4%) persons died. Independent of the presence of sarcopenia, participants with COPD had a higher risk of all-cause mortality (hazard ratio (HR) 2.13, 95% CI 1.46-3.12 and HR 1.70, 95% CI 1.32-2.18 for those with and without sarcopenia, respectively). Compared to lower SII levels, higher SII levels increased mortality risk even in people without sarcopenia, COPD or asthma.
Middle-aged and older people with COPD, higher SII levels or sarcopenia had an independently increased mortality risk. Our study suggests prognostic usefulness of routinely evaluating sarcopenia and SII in older people with COPD or asthma.
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