Publications

GIS mapping is a useful tool to study the spatial distribution of diseases and examine their association with geographic risk factors. Aim: We used GIS to determine spatial distribution of COPD in 22 rural villages spread across an area of 232 km 2 , and study the association between proximity to highways and prevalence of COPD. Methods: 3,592 randomly selected individuals were administered a respiratory health questionnaire and underwent pre and post bronchodilator spirometry (ndd Spirometer) according to the ATS/ERS standards. COPD was defined as post-bronchodilator FEV1/FVC Results: A significant cluster of COPD subjects were found residing 500m from the highway had a higher prevalence of COPD and this was strongly associated with the use of biomass fuel [OR: 1.46 (CI: 1.06-2.0); p Conclusion: Residing 500m from the highway and this was significantly associated with the use of biomass fuel.

Nitrosothiols (RS-NOs) are formed by interaction of nitric oxide (NO) with glutathione and may limit the detrimental effect of NO. Because NO generation is increased in airway inflammation, we have measured RS-NOs in exhaled breath condensate in patients with asthma, cystic fibrosis, or chronic obstructive pulmonary disease (COPD). We also measured exhaled NO and nitrite (NO2 −) in the same subjects. RS-NOs were detectable in exhaled breath condensate of all subjects. RS-NOs were higher in subjects with severe asthma (0.81 ± 0.06 μ M) when compared with normal control subjects (0.11 ± 0.02 μ M, p < 0.01) and with subjects with mild asthma (0.08 ± 0.01 μ M, p < 0.01). Elevated RS-NOs values were also found in patients with cystic fibrosis (0.35 ± 0.07 μ M, p < 0.01), in those with COPD (0.24 ± 0.04 μ M, p < 0.01) and in smokers (0.46 ± 0.09 μ M, p < 0.01). In current smokers there was a correlation (r = 0.8, p < 0.05) between RS-NOs values and smoking history (pack/year). We also found elevated concentrations of NO2 − in patients with severe asthma, cystic fibrosis, or COPD, but not in smokers or patients with mild asthma. This suggests that exhaled NO2 − is less sensitive than exhaled RS-NOs. This study has shown that RS-NOs are detectable in exhaled breath condensate of healthy subjects and are increased in patients with inflammatory airway diseases. As RS-NOs concentrations in exhaled breath condensate vary in the different airway diseases and increase with the severity of asthma, their measurement may have clinical relevance as a noninvasive biomarker of nitrosative stress.

Analyzing the kinematics of filamentary molecular clouds is a crucial step toward understanding their role in the star formation process. Therefore, we study the kinematics of 283 filament candidates in the inner Galaxy, that were previously identified in the ATLASGAL dust continuum data. The 13 CO(2 – 1) and C 18 O(2 – 1) data of the SEDIGISM survey (Structure, Excitation, and Dynamics of the Inner Galactic Inter Stellar Medium) allows us to analyze the kinematics of these targets and to determine their physical properties at a resolution of 30′′ and 0.25 km s −1 . To do so, we developed an automated algorithm to identify all velocity components along the line-of-sight correlated with the ATLASGAL dust emission, and derive size, mass, and kinematic properties for all velocity components. We find two-third of the filament candidates are coherent structures in position-position-velocity space. The remaining candidates appear to be the result of a superposition of two or three filamentary structures along the line-of-sight. At the resolution of the data, on average the filaments are in agreement with Plummer-like radial density profiles with a power-law exponent of p ≈ 1.5 ± 0.5, indicating that they are typically embedded in a molecular cloud and do not have a well-defined outer radius. Also, we find a correlation between the observed mass per unit length and the velocity dispersion of the filament of m ∝ σ v 2 . We show that this relation can be explained by a virial balance between self-gravity and pressure. Another possible explanation could be radial collapse of the filament, where we can exclude infall motions close to the free-fall velocity.

Precision medicine is a patient-specific approach that integrates all relevant clinical, genetic and biological information in order to optimise the therapeutic benefit relative to the possibility of side-effects for each individual. Recent clinical trials have shown that higher blood eosinophil counts are associated with a greater efficacy of inhaled corticosteroids (ICSs) in chronic obstructive pulmonary disease (COPD) patients. Blood eosinophil counts are a biomarker with potential to be used in clinical practice, to help target ICS treatment with more precision in COPD patients with a history of exacerbations despite appropriate bronchodilator treatment.The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 pharmacological treatment algorithms, based on the ABCD assessment, can be applied relatively easily to treatment-naive individuals at initial presentation. However, their use is more problematic during follow-up in patients who are already on maintenance treatment. There is a need for a different system to guide COPD pharmacological management during follow-up.Recent large randomised controlled trials have provided important new information concerning the therapeutic effects of ICSs and long-acting bronchodilators on exacerbations. The new evidence regarding blood eosinophils and inhaled treatments, and the need to distinguish between initial and follow-up pharmacological management, led to changes in the GOLD pharmacological treatment recommendations. This article explains the evidence and rationale for the GOLD 2019 pharmacological treatment recommendations.

The effect of body mass index (BMI) on outcomes after coronary artery revascularization remains controversial. We studied 1,203 patients who had multivessel coronary artery disease and underwent stenting (n = 599) or coronary artery bypass grafting (CABG; n = 604) in the Arterial Revascularization Therapies Study. Patients were assigned to 1 of 3 groups according to BMI: <25, 25 to 30, and >30 kg/m2. At 3-year follow-up, the incidence of death, cerebrovascular events, or myocardial infarction was similar for these BMI categories regardless of the revascularization technique used. Rates of repeat revascularization procedures were significantly higher among patients who had been randomized to stenting but were similar across BMI groups. For patients who had been randomized to undergo CABG, there was a significant decrease in repeat revascularization procedures in obese patients (p = 0.03). Among patients who underwent stenting, BMI had no effect on the 3-year combined end point of rate of major adverse cardiac or cerebrovascular events. Among patients who underwent CABG, major adverse cardiac or cerebrovascular event rates were significantly lower for patients who were obese (11%) or overweight (16%) compared with patients who had a normal BMI (24%; p = 0.008). Thus, in a large cohort of patients who had multivessel coronary artery disease and underwent surgical or percutaneous revascularization, BMI had no effect on 3-year outcome of those who underwent stenting. Conversely, among patients who underwent CABG, those who were overweight or obese had a significantly better outcome than did those who had a normal BMI with regard to survival without major adverse cardiac or cerebrovascular events, mainly due to lower rates of repeat revascularization procedures.

In this study we have evaluated the pharmacological profile of the muscarinic antagonist glycopyrrolate in guinea‐pig and human airways in comparison with the commonly used antagonist ipratropium bromide. Glycopyrrolate and ipratropium bromide inhibited EFS‐induced contraction of guinea‐pig trachea and human airways in a concentration‐dependent manner. Glycopyrrolate was more potent than ipratropium bromide. The onset of action (time to attainment of 50% of maximum response) of glycopyrrolate was similar to that obtained with ipratropium bromide in both preparations. In guinea‐pig trachea, the offset of action (time taken for response to return to 50% recovery after wash out of the test antagonist) for glycopyrrolate (t 1/2 [offset]=26.4±0.5 min) was less than that obtained with ipratropium bromide (81.2±3.7 min). In human airways, however, the duration of action of glycopyrrolate (t 1/2 [offset]&gt;96 min) was significantly more prolonged compared to ipratropium bromide (t 1/2 [offset]=59.2±17.8 min). In competition studies, glycopyrrolate and ipratropium bromide bind human peripheral lung and human airway smooth muscle (HASM) muscarinic receptors with affinities in the nanomolar range (K i values 0.5–3.6 n M ). Similar to ipratropium bromide, glycopyrrolate showed no selectivity in its binding to the M 1 –M 3 receptors. Kinetics studies, however, showed that glycopyrrolate dissociates slowly from HASM muscarinic receptors (60% protection against [ 3 H]‐NMS binding at 30 n M ) compared to ipratropium bromide. These results suggest that glycopyrrolate bind human and guinea‐pig airway muscarinic receptors with high affinity. Furthermore, we suggest that the slow dissociation profile of glycopyrrolate might be the underlying mechanism by which this drug accomplishes its long duration of action. British Journal of Pharmacology (1999) 127 , 413–420; doi: 10.1038/sj.bjp.0702573

No abstract is provided for this article.

Background The purpose of this pilot study was to identify biological risk factors for restenosis after percutaneous transluminal coronary angioplasty (PTCA) to predict the long-term outcome of PTCA before treatment. Methods and Results To investigate whether blood granulocytes and monocytes could determine luminal renarrowing after PTCA, several characteristics of these phagocytes were assessed before angioplasty in 32 patients who underwent PTCA of one coronary artery and who had repeat angiograms at 6-month follow-up. The plasma levels of interleukin (IL)-1β, tumor necrosis factor-α, IL-6, fibrinogen, C-reactive protein, and lipoprotein(a) before angioplasty were assessed as well. We found that the expression of the membrane antigens CD64, CD66, and CD67 by granulocytes was inversely associated with the luminal renarrowing normalized for vessel size (relative loss) at 6 months after PTCA, while the production of IL-1β by stimulated monocytes was positively associated with the relative loss. Next, these univariate predictors were corrected for the established clinical risk factors of dilation of the left anterior descending coronary artery and current smoking, which were statistically significant classic predictors in our patient group. Only the expression of CD67 did not predict late lumen loss independent of these established clinical risk factors. Multiple linear regression analysis showed that luminal renarrowing could be predicted reliably ( R 2 =.65; P &lt;.0001) in this patient group on the basis of the vessel dilated and only two biological risk factors that reflect the activation status of blood phagocytes, ie, the expression of CD66 by granulocytes and the production of IL-1β by stimulated monocytes. Conclusions The results of the present study indicate that activated blood granulocytes prevent luminal renarrowing after PTCA, while activated blood monocytes promote late lumen loss. To validate this new finding, further study in an independent patient group is required.

Currently, automated systems for quantitative analysis by intracoronary ultrasound (ICUS) are restricted to the detection of the lumen. The aim of this study was to determine the accuracy and reproducibility of a new semiautomated contour detection method, providing off-line identification of the intimal leading edge and external contour of the vessel in three-dimensional ICUS. The system allows cross-sectional and volumetric quantification of lumen and of plaque. It applies a minimum-cost algorithm and the concept that edge points derived from previously detected longitudinal contours guide and facilitate the contour detection in the cross-sectional images. A tubular phantom with segments of various luminal dimensions was examined in vitro during five catheter pull-backs (1 mm/sec), and subsequently 20 diseased human coronary arteries were studied in vivo with 2.9F 30 MHz mechanical ultrasound catheters (200 images per 20 mm segment). The ICUS measurements of phantom lumen area and volume revealed a high correlation with the true phantom areas and volumes (r = 0.99); relative mean differences were −0.65% to 3.86% for the areas and 0.25% to 1.72% for the volumes of the various segments. Intraobserver and interobserver comparisons showed high correlations (r = 0.95 to 0.98 for area and r = 0.99 for volume) and small mean relative differences (−0.87% to 1.08%), with SD of lumen, plaque, and total vessel measurements not exceeding 7.28%, 10.81%, and 4.44% (area) and 2.66%, 2.81%, and 0.67% (volume), respectively. Thus the proposed analysis system provided accurate measurements of phantom dimensions and can be used to perform highly reproducible area and volume measurements in three-dimensional ICUS in vivo.

No abstract is provided for this article.