Elevated plasma TGF-β1 levels in patients with chronic obstructive pulmonary disease

SummaryBackgroundTransforming growth factor-β1 (TGF-β1), a multifunctional cytokine, has been implicated to be responsible for the increased deposition of extracellular matrix in the airways, and increased submucosal collagen expression in chronic obstructive pulmonary disease (COPD). We determined plasma TGF-β1 levels in patients with COPD and explored its association with common functional polymorphisms of TGF-β1 gene at C-509T and T869C in the development of COPD in a case–control study.MethodsStable COPD patients who were ever smokers, and age and pack-years smoked matched healthy controls (n = 205 in each group) were recruited for measurement of plasma TGF-β1 levels using commercially available ELISA kit, and genotyped at C-509T and T869C functional polymorphisms of TGF-β1 gene using polymerase chain reaction and restriction fragment length polymorphism (PCR–RFLP).ResultsCOPD patients had significantly elevated plasma TGF-β1 levels in comparison to healthy controls irrespective of the genotypes. Allele frequencies and genotype distributions at both polymorphic sites were not different among COPD patients or controls. TGF-β1 levels were inversely correlated (Pearson's correlation analysis) with FEV1 (% predicted) (p < 0.001) and FVC (% predicted) (p < 0.001).ConclusionThe findings of elevated plasma TGF-β1 levels in patients with COPD suggest that TGF-β1 may play a role in COPD pathogenesis. The C-509T and T869C functional polymorphisms of TGF-β1 gene do not represent a genetic predisposition to COPD susceptibility in Hong Kong Chinese patients

Hypoadiponectinemia is Related to Sympathetic Activation and Severity of Obstructive Sleep Apnea

Study Objectives: Hypoadiponectinemia is associated with cardiovascular morbidity and diabetes mellitus. We hypothesize that adiponectin may be downregulated in sleep apnea through various mechanisms, contributing to cardiometabolic risks. This study investigated the relationship between serum adiponectin and sleep disordered breathing and its potential determinants. Design: Cross-sectional study. Subjects and setting: Adult men without prevailing medical comorbidity from the sleep clinic in a teaching hospital. Measurements & Results: One hundred thirty-four men underwent polysomnography, with mean age of 43.9 (9.8) years, and median apnea-hypopnea index (AHI) of 17.1 (5.7, 46.6). Overnight urine samples for catecholamines and blood samples for analyses of insulin, glucose and adiponectin levels from fasting subjects were taken. Insulin resistance was estimated by homeostasis model assessment (HOMA-IR). Magnetic resonance imaging was performed to quantify the amount of abdominal visceral fat. Serum adiponectin level, adjusted for age, body mass index, and visceral fat volume, was significantly lower in subjects with severe obstructive sleep apnea (AHI ≥ 30) compared with those with an AHI of less than 30: 4.0 (3.1, 5.4) versus 5.4 (3.6, 7.9) ?g/mL, P = 0.039. After we adjusted for adiposity, adiponectin levels remained negatively correlated with AHI (P = 0.037), arousal index (P = 0.022), HOMA-IR/fasting insulin (P < 0.001), and urinary norepinephrine and normetanephrine (P < 0.008). In a multiple stepwise regression model, the independent determinants of adiponectin after adjustment for adiposity were HOMA-IR (P < 0.001) and urinary norepinephrine and normetanephrine (P = 0.037). Conclusions: Adiponectin was suppressed in subjects with severe obstructive sleep apnea, independent of obesity. Adiponectin levels were determined by insulin resistance and sympathetic activation, factors that may be totally or partially attributed to sleep disordered breathing.link_to_subscribed_fulltex

Computed tomographic evaluation of the role of craniofacial and upper airway morphology in obstructive sleep apnea in Chinese

Objectives: To evaluate the relationship between cephalometric parameters, upper airway morphological factors and obstructive sleep apnea (OSA) in Chinese subjects. Design: Polysomnogram (PSG) were performed and scored using standard criteria. Supine lateral cephalometric parameters and pharyngeal cross-sectional areas at the level of velopharynx (VA) and hypopharynx (HA) were measured from computed tomographic scans. The roles of these parameters and other anthropometric/demographic characteristics in OSA (apnea hypopnea index, AHI≥5) and their relationship with severity of OSA were explored by multiple logistic and multi-nominal regression analysis. Results: Ninety-two subjects, ranging from normal (n = 36), mild/moderate OSA (n = 34) to severe OSA (n = 22), were evaluated. Compared with normal subjects, OSA subjects were heavier (body mass index 27 vs. 24kg/m2 ) and older (47 vs. 42 years of age); had smaller VA size and VA to HA ratio, lower positioned hyoid bone, longer and thicker soft palate, and more retropositioned mandible relative to maxilia. After controlling for body mass index and age, subjects with severe OSA (AHI>30) had more retropositioned mandible relative to maxilla (odds ratio, OR 1.31, P = 0.044) and longer soft palate (OR 1.16, P = 0.01), while those with mild/moderate OSA had larger VA to HA ratio (OR 0.17, P = 0.018). Conclusions: Craniofacial factors and upper airway morphology contributed to severity of OSA in Chinese subjects. Having controlled for obesity, more retropositioned mandible was associated with more severe OSA. © 2003 Elsevier Ltd. All rights reserved.link_to_subscribed_fulltex