Search

Purpose Cluster analysis has been proposed to examine phenotypic heterogeneity in chronic obstructive pulmonary disease (COPD). The aim of this study was to use cluster analysis to define COPD phenotypes and validate them by assessing their relationship with mortality. Methods Male subjects with COPD were recruited to identify and validate COPD phenotypes. Seven variables were assessed for their relevance to COPD, age, FEV.sub.1 % predicted, BMI, history of severe exacerbations, mMRC, SpO.sub.2, and Charlson index. COPD groups were identified by cluster analysis and validated prospectively against mortality during a 4-year follow-up. Results Analysis of 332 COPD subjects identified five clusters from cluster A to cluster E. Assessment of the predictive validity of these clusters of COPD showed that cluster E patients had higher all cause mortality (HR 18.3, p < 0.0001), and respiratory cause mortality (HR 21.5, p < 0.0001) than those in the other four groups. Cluster E patients also had higher all cause mortality (HR 14.3, p = 0.0002) and respiratory cause mortality (HR 10.1, p = 0.0013) than patients in cluster D alone. Conclusion COPD patient with severe airflow limitation, many symptoms, and a history of frequent severe exacerbations was a novel and distinct clinical phenotype predicting mortality in men with COPD., Author(s): Chiung-Zuei Chen[sup.1] , Liang-Yi Wang[sup.2] , Chih-Ying Ou[sup.1] , Cheng-Hung Lee[sup.1] , Chien-Chung Lin[sup.1] , Tzuen-Ren Hsiue[sup.1] Author Affiliations: (1) Division of Chest Medicine, Department of Internal Medicine, National [...]

Anesthetized mechanically ventilated rats were analyzed after the administration of glibenclamide to determine the role of adenosine triphosphate (ATP)-sensitive K+ channels on microvascular circulation. Inhibition of ATP-sensitive K+ channels partially inhibited diaphragmatic microcirculation by blocking ATP-sensitive K+ channel activity. However, the effects of glibenclamide were altered by the administration of K-sensitive K+ channel agonists indicating the role of K+ channels in mediating diaphragmatic circulation.

Chen, Chang-Wen, Han-Yu Chang, and Tzuen-Ren Hsiue. Mechanism of adenosine-induced vasodilation in rat diaphragm microcirculation. Am J Physiol Heart Circ Physiol 279: H2210-H2217, 2000.--The mechanism of adenosineinduced vasodilation in rat diaphragm microcirculation was investigated using laser Doppler flowmetry. Adenosine ([10.sup.-5], 3.2 x [10.sup.-5], and [10.sup.-4] M), the nonselective adenosine agonist 5'-N-ethylcarboxamido-adenosine (NECA) ([10.sup.-8] - [10.sup.-7] M), the specific [A.sub.2A] agonist 2-p-(2-carboxyethyl)phenyl-amino-5' -N-ethyl carboxamidoadenosine (CGS-21680) ([10.sup.-8] - [10.sup.-7] M), and the adenosine agonist with higher [A.sub.1]-receptor affinity, R-[N.sup.6]-phenylisopropyladenosine (R-PIA) ([10.sup.-7], 3.2 X [10.sup.-7], and [10.sup.-6] M) elicited a similar degree of incremental[ increase of microcirculatory flow in a dose-dependent manner. The ATP-dependent potassium ([K.sub.ATP) channel blocker glibenclamide (3.2 x [10.sup.-6] M) significantly attenuated the vasodilation effects of these agonists. Adenosine-induced vasodilation could be significantly attenuated by the nonselective adenosine antagonist 8-(p-sulfophenyl)-theophy]line (3 x [10.sup.-5] M) or the selective [A.sub.2A] antagonist 4-(2-[7-amino-2-(2-furyl) [1,2,4] triazolo [2,3-a] [1,3,5] triazin-5-ylamino]ethyl) phenol (ZM-241385, 10-6 M), but not by the selective [A.sub.1] antagonist 8-cyclopentyl-l,3-dipropylxanthine (5 x [10.sup.-8] M). Adenylate cyclase inhibitor N-(cis-2-phenyl-cyclopentyl) azacyclotridecan-2-imine-hydrochloride (MDL-12330A, [10.sup.-5]M) effectively suppressed the vasodilator response of adenosine and forskolin. These results suggest that adenosine-induced vasodilation in rat diaphragm microcirculation is mediated through the stimulation of [A.sub.2A] receptors, which are coupled to adenylate cyclase activation and opening of the [K.sub.ATP] channel. blood flow; glibenclamide; laser Doppler flowmetry; skeletal muscle

Objective. Parental atopy and environmental exposures are recognized risk factors for childhood asthma. However, the relative contributions of specific risk factors and the overall contributions of indoor and outdoor exposures remain unexplored. This study was undertaken to identify risk factors, estimate the population attributable risk of each exposure, and compare the data for boys versus girls for physician-diagnosed asthma in Taiwanese schoolchildren. Methods. During a February to June 2001 cross-sectional national survey, 35 036 6- to 15-year-old schoolchildren were chosen from 22 elementary and 22 middle schools located within 1-km catchment areas of 22 air-monitoring stations in Taiwan. The main outcome measure was physician-diagnosed asthma, as reported by the parents. We investigated hereditary and indoor and outdoor environmental factors for childhood asthma by questionnaire. The adjusted prevalences of questionnaire-determined outdoor indicators were also compared with air-monitoring data. Results. Outdoor air pollutants were associated with parent-reported perceived ambient air pollution. Physician-diagnosed asthma was reported for 8.1% of the boys (1330 of 16 441) and 5.6% of the girls (894 of 16 056). The risk of physician-diagnosed asthma was significantly associated with parental atopy and perceived ambient air pollution in both sexes. The presence of visible cockroaches (odds ratio [OR]: 1.30; 95% confidence interval [CI]: 1.07-1.59), mold on walls at home (OR: 1.20; 95% CI: 1.01-141), and water damage (OR: 1.33; 95% CI: 1.02-1.70) were also associated with asthma in girls; however, only visible mold on walls at home was related to asthma in boys. Mutually adjusted analytical models produced statistically significant associations between any indoor factor and asthma in girls (OR: 1.24; 95% CI: 1.00-1.56) but not in boys (OR: 1.04; 95% CI: 0.87-1.25). For all hereditary and environmental factors, the total population attributable risk was 44.31% in boys and 60.61% in girls. Conclusions. Parental atopy contributed more to childhood asthma than indoor or outdoor environmental factors. Girls may be more susceptible to indoor factors than boys. Pediatrics 2003;112:e389-e395. URL: http://www. pediatrics.org/cgi/content/full/112/5/e389; children, asthma, environmental exposure, parental atopy, cockroaches, mold, water damage, air pollution, population attributable risk.