Objective: To develop and validate a prediction model for airflow obstruction (AO) in older Chinese.Methods.Design: Multivariable logistic regression analysis in large population cohort of Chinese... Show moreObjective: To develop and validate a prediction model for airflow obstruction (AO) in older Chinese.Methods.Design: Multivariable logistic regression analysis in large population cohort of Chinese aged >50 years.Participants: Model development: 8762 Chinese aged >= 50 years were selected from the early phase recruits to the Guangzhou Biobank Cohort Study (GBCS) (recruited from September 2003 to May 2006). Internal validation: 100 bootstrap samples drawn with replacement from the development sample. External validation: 8395 Chinese aged >= 50 years from later phase GBCS (recruited from September 2006 to January 2008).Outcomes: AO was defined by a forced expiratory volume in 1 s/forced vital capacity ratio < lower limits of normal.Results: 839 (9.6%) and 764 (9.1%) individuals had AO in the development and temporal validation samples respectively. The predictors in the prediction model included sex, age, body mass index groups, smoking status, presence of respiratory symptoms, and history of asthma. Model development and validation was stratified by sex. Model performance including calibration (calibration-in-the-large -0.017 vs. -0.157; and calibration slope 0.88 vs. 1.02), discrimination (C-statistic 0.72 vs. 0.63 with 95% confidence interval 0.69-0.75 vs. 0.62-0.73) and clinical usefulness (decision curve analysis) in the external temporal validation sample were more satisfactory in men than that in women. Prediction models with risk thresholds (13% in men and 7% in women) and easy-to-use nomograms were developed to assess the probability of AO.Conclusion: The diagnostic models based on readily available epidemiologic and clinical information with satisfactory performance can assist physicians to identify older individuals at high risk of AO and may improve the efficiency of spirometry for active case finding. Further validation beyond the Chinese population is warranted. Show less
Human blood monocytes are divided into populations based on the differential expression of CD14 and CD16 receptors: CD14 (+) CD16(classical), CD14 (+) CD16 (+) (intermediate), and CD14(-)CD16(+) ... Show moreHuman blood monocytes are divided into populations based on the differential expression of CD14 and CD16 receptors: CD14 (+) CD16(classical), CD14 (+) CD16 (+) (intermediate), and CD14(-)CD16(+) (non-classical). Given their functional differences and their role in pathogenesis of chronic obstructive pulmonary disease (COPD), monocyte profiling is of clinical interest. Here we investigated blood monocyte subsets in clinically stable COPD patients with alpha1-antitrypsin (AAT) deficiency (PiZZ, n = 7) and with normal AAT variant (PiMM, n = 7). Peripheral whole blood was collected in sodium heparin tubes and incubated with LPS (from E. coli; 1 mu g/ml) or placebo for 6 h at 37 degrees C, 5% CO2. To profile monocyte subsets we performed flow cytometry analysis based on HLA-DR and CD14/CD16 staining. HLA-DR + subsets of cells did not differ between PiZZ and PiMM COPD, and healthy controls (n = 7), used as a reference. Monocyte profiling, which express the CD14 and CD16, but not the HLA-DR (HLA-DR-) showed that intermediate monocytes subset was lowest in PiZZ group, and almost totally disappeared from blood treated with LPS. The non-classical subset was almost absent in PiZZ patients independently of LPS treatment. Recent studies demonstrate that non-classical monocytes exhibit a unique ability to protect the vascular endothelium under both homeostatic and inflammatory conditions whereas intermediate monocytes are recruited at a later stage of inflammation, and are associated with secretion of cytokines/chemokines and wound healing. Evident alterations in blood monocyte subsets together with a partial reduction of AAT levels, an important anti-inflammatory protein, can be key factors for the early manifestation of emphysema in some PiZZ AATD carriers. Show less
Boland, M.R.S.; J.F.M. van boven; Kruis, A.L.; Chavannes, N.H.; Molen, T. van der; Goossens, L.M.A.; Rutten-van Molken, M.P.M.H. 2016
BACKGROUND: Bronchial dimensions measured in CT images generally do not take inspiration level into consideration. However, some studies showed that the bronchial membrane is distensible with... Show moreBACKGROUND: Bronchial dimensions measured in CT images generally do not take inspiration level into consideration. However, some studies showed that the bronchial membrane is distensible with airway inflation. Therefore, re-examination of the elasticity of bronchi is needed. PURPOSE: To assess the influence of respiration on bronchial lumen area (defined as distensibility) in different segmental bronchi and to explore the correlations between distensibility and both lung function and emphysema severity. MATERIAL AND METHODS: In 44 subjects with COPD related to alpha-1-antitrypsin deficiency (AATD), bronchial lumen area was measured in CT images, acquired at different inspiration levels. Measurements were done at matched locations in one apical and two basal segmental airways (RB1, RB10 and LB10). Airway distensibility was calculated as lumen area difference divided by lung volume difference. RESULTS: Bronchial lumen area in the lower lobes (RB10 and LB10) correlated positively with FEV(1)%predicted (p=0.027 for RB10; and p=0.037 for LB10, respectively). Lumen area is influenced by respiration (p=0.006, p=0.045, and, p=0.005 for RB1, RB10 and LB10, respectively). Airway distensibility was different between upper and lower bronchi (p<0.001), but it was not correlated with lung function. CONCLUSION: Lumen area of third generation bronchi is dependent on inspiration level and this distensibility is different between bronchi in the upper and lower lobes. Therefore, changes in lumen area over time should be studied whilst accounting for the lung volume changes, in order to estimate the progression of bronchial disease while excluding the effects of hyperinflation. Show less
Background: Severe (PiZZ) and moderate (PiSZ) alpha-1-antitrypsin (AAT) deficiency predispose to lung emphysema, especially in smokers. We hypothesized that multi-slice computed tomography (CT)... Show moreBackground: Severe (PiZZ) and moderate (PiSZ) alpha-1-antitrypsin (AAT) deficiency predispose to lung emphysema, especially in smokers. We hypothesized that multi-slice computed tomography (CT) might be superior to pulmonary function tests (PFT) to detect lung emphysema in AAT-deficient individuals at the age of 32 years. Methods: A subgroup of PiZZ and PiSZ individuals identified during the Swedish newborn screening programme in 1972-74 underwent multi-slice CT and PFT at the age of 32 years. From the CT scans the percentile density at 15% (PD15) and the relative area below -910 Hounsfield Units (RA(-910) HU) were calculated. The results of PFT and CT were compared between the AAT-deficient individuals and an age-matched control group. Results: Twenty-five PiZZ, 11 PiSZ and 17 PiMM individuals participated in the study. All Pi subgroups had normal lung function. The mean PD15 was 81 (SD 22) g/L in the PiZZ individuals, 96 (SD 35) g/L in the PiSZ individuals and 79 (SD 17) g/L in the PiMM individuals (ns), and the RA-910 were 30 (SD 18)%, 24 (SD 20)%, and 32 (SD 18)%, respectively (ns). For the never-smoker subgroups, in the PiZZ (n = 23), PiSZ (n = 8) and PiMM (n = 12), the mean PD15 were 95 (SD 35) g/L, 81 (SD 22) g/L, and 75 (SD 12) g/L, respectively (ns). PD15 was significantly correlated to CT derived lung size (r = -0.72; p < 0.001). Conclusions: CT densitometry revealed no signs of emphysema and no differences between the AAT-deficient individuals identified by neonatal screening and age-matched control subjects. (C) 2010 Elsevier Ltd. All rights reserved, Show less
BACKGROUND: The exact prevalence and etiology of exertional dyspnea in the clinical course of acute pulmonary embolism (PE) have not yet been established. METHODS: A large cohort of consecutive... Show moreBACKGROUND: The exact prevalence and etiology of exertional dyspnea in the clinical course of acute pulmonary embolism (PE) have not yet been established. METHODS: A large cohort of consecutive patients diagnosed with acute PE was subjected to a dyspnea questionnaire and invited for cardiopulmonary work-up including the 6-min walk test, spirometry and echocardiography. The prevalence, severity, determinants and underlying diseases of exertional dyspnea were evaluated. RESULTS: Of the registered 877 patients, 259 (30%) had died and 11 (1.3%) were excluded for geographical reasons. From the remaining 607 patients, 217 reported exertional dyspnea (36%; 95% CI 32-40%) 3.6 +/- 1.7 years after the PE. In 76% this dyspnea had developed or worsened after the acute PE. 421 patients completed the cardiopulmonary work-up. Cardiopulmonary comorbidity (OR 12; 95% CI 6.5-20), advanced age (OR 1.02 per year; 95% CI 1.01-1.03), higher BMI (OR 1.06 per kg/m(2); 95% CI 1.01-1.1) and a smoking history (OR 1.6; 95% CI 1.02-2.6) were identified as independent predictors of exertional dyspnea. A pre-defined dyspnea explaining diagnosis could be established in all patients with exertional dyspnea. In only 4 patients, this diagnosis was directly correlated to the acute PE. Increased severity of dyspnea was associated with decreased exercise performance (p < 0.001) and a higher number of dyspnea-related diagnoses (p < 0.001). CONCLUSION: Exertional dyspnea is a frequent symptom in the long term clinical course of acute PE. More severe dyspnea results in decreased exercise capacity and increased burden of cardiopulmonary comorbidity. This dyspnea is likely to be unrelated to the past thromboembolic event in the vast majority of patients. Show less
Gestel, Y.R.B.M. van; Flu, W.J.; Kuijk, J.P. van; Hoeks, S.E.; Bax, J.J.; Sin, D.D.; Poldermans, D. 2010
Introduction: There is increasing evidence that non-invasive imaging modalities such as ultrasonography may be able to detect subclinical atherosclerotic lesions, and as such may be useful tools... Show moreIntroduction: There is increasing evidence that non-invasive imaging modalities such as ultrasonography may be able to detect subclinical atherosclerotic lesions, and as such may be useful tools for risk-stratification. However, the clinical relevance of these observations remains unknown in patients with COPD. Therefore we investigated the association between COPD and carotid wall intima-media thickness (IMT) in patients undergoing vascular surgery and its relationship with mortality in these patients. Methods: Carotid wall IMT was measured in 585 patients who underwent lower extremity, aortic aneurysm or stenosis repair. Primary study endpoint was increased carotid wall IMT which was defined as IMT >= 1.25 mm. Secondary study endpoints included total and cardiovascular mortality over a mean follow-up of 1.5 years. Results: Thirty-two percent of patients with mild COPD and 36% of the patients with moderate/severe COPD had increased carotid wall IMT, while only 23% had an increased carotid wall IMT in patients without COPD (p < 0.01). COPD was independently associated with an increased carotid wall IMT (OR 1.60; 95% Cl 1.08-2.36). Among patients with COPD, increased carotid wall IMT was associated with an increased risk of total (HR, 3.18 95% CI 1.93-5.24) and cardiovascular mortality (HR 7.28, 95% Cl 3.76-14.07). Conclusions: COPD is associated with increased carotid wall IMT independent of age and smoking status. Increased carotid wall IMT is associated with increased total and cardiovascular mortality in patients with COPD suggesting that carotid wall measurements may be a good biomarker for morbidity and mortality in these patients. (C) 2009 Elsevier Ltd. All rights reserved. Show less
