[Show abstract][Hide abstract] ABSTRACT: The objective of the present study was to establish multiethnic, all-age prediction equations for estimating stature from arm span in males and females. The arm span/height ratio (ASHR) from 13 947 subjects (40.9% females), aged 5-99 years, from nine centres (in China, Europe, Ghana, India and Iran) was used to predict ASHR as a function of age using the lambda, mu and sigma method. Z-scores for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC in 1503 patients were calculated using measured height and height calculated from arm span and age. ASHR varied nonlinearly with age, was higher in males than in females and differed significantly between the nine sites. The data clustered into four groups: Asia, Europe, Ghana and Iran. Average predicted FEV1, FVC and FEV1/FVC using measured or predicted height did not differ, with standard deviations of 4.6% for FEV1, 5.0% for FVC and 0.3% for FEV1/FVC. The percentages of disparate findings for a low FEV1, FVC and FEV1/FVC in patients, calculated using measured or predicted height, were 4.2%, 3.2% and 0.4%, respectively; for a restrictive pattern, there were 1.0% disparate findings. Group- and sex-specific equations for estimating height from arm span and age to derive predicted values for spirometry are clinically useful.
European Respiratory Journal 10/2014; 44:905-912. · 7.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Poor adherence to continuous positive airway pressure (CPAP) treatment in obstructive sleep apnea (OSA) adversely affects the effectiveness of this therapy. This randomized controlled trial (RCT) examined the efficacy of a brief motivational enhancement education program in improving adherence to CPAP treatment in OSA subjects.
Newly diagnosed OSA subjects were recruited into this RCT. The control group received usual advice on the importance of CPAP therapy and its care. Intervention group received usual care plus brief motivational enhancement education program directed at enhancing the subjects' knowledge, motivation and self-efficacy to use CPAP through the use of a 25-minute video, a 20-minute patient-centered interview and a 10-minute telephone follow up. Self-reported daytime sleepiness adherence-related cognitions and quality of life were assessed at 1 month and 3 months. CPAP usage data was downloaded at the completion of this 3-month study.
100 OSA subjects [mean±SD: age 52±10 years, Epworth Sleepiess Scales (ESS) 9±5, median Apnea Hypopnea Index of 29 (20, 53) events/hour] prescribed CPAP treatment were recruited. The intervention group had better CPAP use [higher daily CPAP usage by 2 hours/day (Cohen d=1.33, p<0.001), a four-fold increase in the number using CPAP for ≥70% of days with ≥4 hours per day (p<0.001)], and greater improvements in daytime sleepiness (ESS) by 2.2 units (p=0.001) and treatment self-efficacy by 0.2 unit (p=0.012) compared to the control group.
OSA subjects who received motivational enhancement education in addition to usual care were more likely to show better adherence to CPAP treatment, with greater improvements in treatment self-efficacy and daytime sleepiness.
[Show abstract][Hide abstract] ABSTRACT: Transplantation of mesenchymal stem cells (MSCs) holds great promise in the repair of cigarette smoke (CS)-induced lung damage in chronic obstructive pulmonary disease (COPD). As cigarette smoke leads to mitochondrial dysfunction, we therefore aimed to investigate the potential benefit of mitochondrial transfer from human-induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs) to CS-exposed airway epithelial cells in vitro and in vivo. Rats were exposed to 4% CS for one hour daily for 56 days. At day 29 and day 43, human iPSC-MSCs or adult bone marrow-MSCs (BM-MSCs) were administered intravenously to CS-exposed rats. CS-exposed rats exhibited severe alveolar destruction with a higher mean linear intercept (Lm) than sham air-exposed rats (p < 0.001) that was attenuated in the presence of iPSC-MSCs or BM-MSCs (p < 0.01). The attenuation of Lm value and the severity of fibrosis was greater in the iPSC-MSC-treated group than the BM-MSC-treated group (p<0.05). This might be contributed to the novel observation of mitochondrial transfer from MSCs to rat airway epithelial cells in lung sections exposed to CS. In vitro studies further revealed that transfer of mitochondria from iPSC-MSCs to bronchial epithelial cells (BEAS-2B) was more effective than from BM-MSCs with preservation of adenosine triphosphate contents. This distinct mitochondrial transfer occurred via the formation of tunneling nanotubes (TNT). Inhibition of TNT formation blocked mitochondrial transfer. Our findings indicate a higher mitochondrial transfer capacity of iPSC-MSCs than BM-MSCs to rescue CS-induced mitochondrial damage. iPSC-MSCs may thus hold promise for the development of cell therapy in COPD.
American Journal of Respiratory Cell and Molecular Biology 04/2014; · 4.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: ABSTRACT BACKGROUND Surfactant proteins play a key role in alveolar stability. We examined whether single nucleotide polymorphisms (SNPs) related to the surfactant protein genes are associated with severe influenza. METHODS In the first cohort, 12 SNPs related to surfactant protein genes were compared between Chinese patients with severe and mild A(H1N1)pdm09 infection, who were matched for age, sex and underlying risk conditions. The SNP rs1130866, which was significantly different between the two groups, was further genotyped in a second cohort of patients. Multivariate analysis was performed to control for confounding factors. The genotype frequencies were also compared with the general Han Chinese population. RESULTS This study consisted of 380 patients with A(H1N1)pdm09 infection. In the first cohort of 84 patients, the C allele of rs1130866, a SNP in the surfactant protein B gene (SFTPB), was significantly associated with severe disease (odds ratio[OR]=3.37, P=4.8×10-3), although the P value was 0.057 after Bonferroni correction. In the second cohort of 296 patients, the C/C genotype was confirmed to be associated with severe disease in the univariate analysis. Multivariate analysis of the second cohort showed that genotype C/C was an independent risk factor for severe A(H1N1)pdm09 infection (second cohort: OR=2.087, P=0.023). Comparing to the general Han Chinese population, C/C genotype was over-represented in patients with severe A(H1N1)pdm09 infection (OR=3.232, P=5.60×10-7). CONCLUSION SFTPB polymorphism is associated with severe influenza. The role of SFTPB in influenza warrants further studies.
[Show abstract][Hide abstract] ABSTRACT: Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH) during sleep, is increasingly recognized as an independent risk factor of cardiovascular diseases. OSA is associated with changes in the levels of circulating oxidative stress/inflammatory markers and dyslipidemia, supporting their mediating roles in cardiovascular pathogenesis. Our aims were to investigate the effect of IH on heart tissue using an IH-exposed rat model and to explore the potential mechanisms involved in the occurrence of cardiac damage. Male Sprague-Dawley rats were exposed to IH and intermittent normoxia as control and sacrificed after 2 or 4 weeks. IH for 4 weeks caused elevation in serum malondialdehyde and cytokine-induced neutrophil chemoattractant-1 and reduction in serum adiponectin levels. In contrast, cardiac oxidative stress and pro-inflammatory markers were suppressed while cardiac adiponectin and cholesterol levels were elevated after IH exposure for 4 weeks. In parallel, there was an increase in apoptosis in the heart of IH-exposed rats, demonstrated by elevations of Bax and cleaved caspase-3 protein and TUNEL staining. Cardiac damage was further evident with decreased arterial vessel and capillary densities, increased cardiac fibrosis, and the loss of troponin I. Our data demonstrated that IH exposure paradoxically caused systemic oxidative and inflammatory responses and cardioprotective responses, i.e., anti-oxidative and anti-inflammatory responses. Despite such a local compensatory protective mechanism, cardiac damage was observed that might be due to IH-induced cholesterol accumulation in the heart and caspase-dependent apoptosis.
Journal of physiology and biochemistry 10/2013; · 2.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The self-efficacy measure for sleep apnea (SEMSA) questionnaire was shown to be an effective tool to assess adherence-related cognitions on continuous positive airway pressure (CPAP) therapy in obstructive sleep apnea (OSA) subjects. SEMSA helps to solicit fundamental information for formulating strategies to promote CPAP adherence for better treatment outcomes. The objective of our study was to perform a linguistic and psychometric evaluation of a Chinese version of the SEMSA (SEMSA-C).
Data were obtained from 100 subjects in a randomized controlled trial (RCT) on CPAP education. Subjects were newly diagnosed of OSA and naïve to CPAP therapy.
A 26-item SEMSA-C was obtained by a rigorous linguistic validation process. Internal consistency was high with Cronbach α>0.88. One-week test-retest intraclass correlation coefficient (ICC) ranged from 0.70 to 0.82. Principal component factor analysis identified three of the same hypothesized factors (perceived risks, outcome expectancies, and treatment self-efficacy) as in the original version. CPAP adherence was associated with outcome expectancies and treatment self-efficacy at 3-month assessment. Further, SEMSA-C demonstrated an improvement in self-efficacy after CPAP use.
SEMSA-C shows similar psychometric properties as the original English version. It is a reliable and responsive instrument to measure perceived risks, outcome expectancies, and treatment self-efficacy in Chinese subjects with OSA.
[Show abstract][Hide abstract] ABSTRACT: Oxidative stress has been implicated in the pathogenesis of asthma. We aimed at investigating the biomarkers of oxidative stress, inflammation, and tissue damage in patients with asthma in acute exacerbation and remission. We recruited 18 asthmatics admitted to hospital with acute exacerbation and 18 healthy nonsmoking controls matched for age. We evaluated plasma levels of 8-isoprostane, C-reactive protein (CRP) and total matrix metalloproteinase- (MMP-) 9 by ELISA, and MMP-9 activity by zymographic analysis. Plasma levels of 8-isoprostane and CRP were significantly elevated in acute exacerbation and decreased in remission but remained significantly higher compared to healthy controls. The activities of pro-MMP-9 were also significantly higher in acute exacerbation and decreased in remission but remained significantly higher compared to healthy controls in parallel to plasma levels of total MMP-9. These data suggest that overproduction of MMP-9 along with highly elevated levels of oxidative stress and inflammation is implicated in asthma exacerbation and that measurements of these biomarkers can be a valid index in its management.
[Show abstract][Hide abstract] ABSTRACT: Intermittent hypoxia (IH) is a hallmark feature in obstructive sleep apnea (OSA) which is increasingly recognized as an independent risk factor for atherosclerosis. Oxidative stress, inflammation, and cell apoptosis are major pathological events initiating or accelerating atherogenesis. This study addressed whether IH would affect these proatherogenic factors in endothelial cells and the mechanistic pathways involved. EA.hy926 cells were exposed to intermittent normoxia or IH for different numbers of cycles (32, 64, or 96). IH exposure time-dependently raised cellular GSSG/GSH ratio, increased production of IL-6 and IL-8, and accelerated cell apoptosis and death, concurrent with activation of NF-κB and inhibition of Nrf2/HO-1 pathways. At 64 cycles, inhibition of NF-κB attenuated IH-induced cellular oxidative stress and accumulation of inflammatory cytokines in cell culture medium but aggravated IH-induced cell apoptosis, while stimulation of HO-1 suppressed IH-induced cellular oxidative stress and cell apoptosis without affecting accumulation of inflammatory cytokines in cell culture medium. We demonstrated that early stage of exposure to IH-induced oxidative and inflammatory stresses leading to acceleration of cell apoptosis via NF-κB and Nrf2/HO-1 pathways in endothelial cells, suggesting the potential mechanisms for IH-induced vascular pathogenesis, in resemblance to OSA.
Cell biochemistry and biophysics 12/2012; · 3.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Our recent study has indicated that Chinese green tea (Lung Chen), in which epigallocatechin-3-gallate (EGCG) accounts for 60% of catechins, protected cigarette smoke-induced lung injury. We now hypothesized that Lung Chen tea may also have potential effect on lung oxidative stress and proteases/anti-proteases in a smoking rat model. Sprague-Dawley rats were exposed to either sham air (SA) or 4% cigarette smoke (CS) plus 2% Lung Chen tea or water by oral gavage. Serine proteases, matrix metalloproteinases (MMPs) and their respective endogenous inhibitors were determined in bronchoalveolar lavage (BAL) and lung tissues by gelatin/casein zymography and biochemical assays. Green tea consumption significantly decreased CS-induced elevation of lung lipid peroxidation marker, malondialdehyde (MDA), and CS-induced up-regulation of neutrophil elastase (NE) concentration and activity along with that of α(1)-antitrypsin (α(1)-AT) and secretory leukoproteinase inhibitor (SLPI) in BAL and lung. In parallel, significant elevation of MMP-12 activity was found in BAL and lung of the CS-exposed group, which returned to the levels of SA-exposed group after green tea consumption but not CS-induced reduction of tissue inhibitor of metalloproteinase (TIMP)-1 activity, which was not reversed by green tea consumption. Taken together, our data supported the presence of local oxidative stress and protease/anti-protease imbalance in the airways after CS exposure, which might be alleviated by green tea consumption through its biological antioxidant activity.
Free Radical Research 05/2012; 46(9):1123-9. · 3.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Forced expiratory volume in 3 seconds (FEV(3)) and 6 seconds (FEV(6)) could complement FEV(1) and forced vital capacity (FVC) for detecting airflow obstruction.
To compare FEV(1)/ FEV(6) and FEV(3)/FVC with FEV(1)/FVC in the detection of airflow obstruction.
Previous lung function data were re-analysed to establish reference values for FEV(3) and FEV(6). Data from a separate cohort of male smokers were used as test set. FEV(1), FEV(3), FEV(6), FVC, FEV(1)/FVC, FEV(1)/ FEV(6) and FEV(3)/FVC were regressed against age, standing height, weight and body mass index, and the mean and 95% confidence intervals for the lower limit of normal (LLN) values for these parameters were determined.
The percentage of smokers with airflow obstruction in the test population using FEV(1)/FVC < LLN was 15.0%, while using FEV(1)/ FEV(6) < LLN and FEV(3)/FVC < LLN they were respectively 18.5% and 18.1%. Using FEV(1)/FVC < LLN as reference, the sensitivity and specificity of FEV(1)/ FEV(6) < LLN in identifying airflow obstruction were 82.3% and 92.8%, while those for FEV(3)/FVC < LLN were 78.5% and 92.6%; the positive and negative predictive values were 67% and 96.7% for FEV(1)/ FEV(6) < LLN and 65.3% and 96% for FEV(3)/FVC < LLN.
FEV(3)/FVC < LLN and FEV(1)/ FEV(6) < LLN are comparable to FEV(1)/FVC < LLN for detecting airflow obstruction. FEV(3)/FVC < LLN could be useful in screening for airflow obstruction, while FEV(1)/ FEV(6) < LLN is useful in detecting airflow limitation in the elderly or in subjects with severe airflow obstruction.
The International Journal of Tuberculosis and Lung Disease 05/2012; 16(5):681-6. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this review article is to provide an up-to-date summary on the current evidence for or against the use of lung function tests as screening and diagnostic tools for airflow obstruction in chronic obstructive pulmonary disease (COPD), and to consider the relevant issues in context.
COPD is characterized by chronic respiratory symptoms and airflow limitation with only partial reversibility on lung function testing. However, screening on a population basis or of an enriched 'at-risk' subset like chronic smokers is not supported by findings from previous epidemiological studies, screening trials or in currently published clinical management guidelines by professional societies and review bodies. The definition of airflow obstruction and the classification of disease severity of COPD also differ slightly between guidelines and statements from different professional societies.
Given the experience from previous screening trials and controversial classification of airflow obstruction by severity, it is impossible to have accurate screening results for COPD based on lung function tests alone. Clinical respiratory symptoms should be taken into consideration in terms of the diagnosis and management of COPD, as well as in any screening trial or programme that is to be attempted or implemented.
Current opinion in pulmonary medicine 03/2012; 18(2):104-11. · 2.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cigarette smoking is a major risk factor in the development of age-related chronic obstructive pulmonary disease (COPD). The serotonin transporter (SERT) gene polymorphism has been reported to be associated with COPD, and the degree of cigarette smoking has been shown to be a significant mediator in this relationship. The interrelation between circulating serotonin (5-hydroxytyptamine, 5-HT), cigarette smoking and COPD is however largely unknown. The current study aimed at investigating the mediation effects of plasma 5-HT on cigarette smoking-induced COPD and the relation between plasma 5-HT levels and age.
The association between plasma 5-HT, age and COPD was analyzed in a total of 62 COPD patients (ever-smokers) and 117 control subjects (healthy non-smokers and ever-smokers). Plasma 5-HT levels were measured by enzyme-linked immuno assay (EIA).
The elevated plasma 5-HT levels were significantly associated with increased odds for COPD (OR = 1.221, 95% CI = 1.123 to 1.319, p<0.0001). The effect remained significant after being adjusted for age and pack-years smoked (OR = 1.271, 95% CI = 1.134 to 1.408, p = 0.0003). Furthermore, plasma 5-HT was found to mediate the relation between pack-years smoked and COPD. A positive correlation (r = 0.303, p = 0.017) was found between plasma 5-HT levels and age in COPD, but not in the control subjects (r = -0.149, p = 0.108).
Our results suggest that cigarette smoke-induced COPD is partially mediated by the plasma levels of 5-HT, and that these become elevated with increased age in COPD. The elevated plasma 5-HT levels in COPD might contribute to the pathogenesis of this disease.
PLoS ONE 02/2012; 7(2):e31617. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OSA is increasingly recognized as a major health problem in developed countries. Obesity is the most common risk factor in OSA and hence, the prevalence of OSA is undoubtedly rising given the epidemic of obesity. Recent data also suggest that OSA is highly associated with the metabolic syndrome, and it is postulated that OSA contributes to cardiometabolic dysfunction, and subsequently vasculopathy. Current evidence regarding the magnitude of impact on ultimate cardiovascular morbidity or mortality attributable to OSA-induced metabolic dysregulation is scarce. Given the known pathophysiological triggers of intermittent hypoxia and sleep fragmentation in OSA, the potential mechanisms of OSA-obesity-metabolic syndrome interaction involve sympathetic activation, oxidative stress, inflammation and neurohumoral changes. There is accumulating evidence from human and animal/cell models of intermittent hypoxia to map out these mechanistic pathways. In spite of support for an independent role of OSA in the contribution towards metabolic dysfunction, a healthy diet and appropriate lifestyle modifications towards better control of metabolic function are equally important as CPAP treatment in the holistic management of OSA.
[Show abstract][Hide abstract] ABSTRACT: Nocturnal rostral fluid shift has been suggested to be a risk factor for obstructive sleep apnea (OSA) in healthy subjects after lower body positive pressurization. It remains unclear whether this may apply to subjects with nephrotic lower limb edema and, if so, whether disease remission may reverse the accompanying OSA.
Patients who presented with steroid-responsive primary nephrotic syndrome with lower limb edema as the predominant presenting clinical feature were recruited. They underwent one overnight polysomnography (PSG) before treatment and a repeat testing after achieving remission of the nephrotic edema.
Among 23 consecutive nephrotic subjects, 11 (48%) had polysomnographic evidence of sleep apnea [apnea-hypopnea index (AHI)≥5] upon presentation. After steroid-based treatment, there was remission of proteinuria associated with complete disappearance of lower limb edema, significant reduction of body mass index, waist, hip and calf circumferences and total body water mainly in the extracellular compartment. Repeat PSG, performed 8.1±2.6 months later, showed that the overall (N=23) respiratory disturbance index (RDI) and AHI fell from 17.3±5.0 to 8.7±2.5 (P<0.05) and from 16.3±5.1 to 7.8±2.3 (P=0.057), respectively. Among the 11 subjects with sleep apnea detected at baseline, their AHI and RDI fell from 33.4±7.8 to 15.0±3.7 (P<0.05) and from 34.8±7.6 to 16.5±4.0 (P<0.05), respectively. There was also concomitant improvement in sleep efficiency, mean nocturnal oxygen saturation, shorter duration during sleep with oxygen saturation<95 and <90% and reduced desaturation index. There was also subjective improvement in self-reported daytime sleepiness.
Nephrotic lower limb edema is associated with disturbed respiratory breathing and increased propensity to OSA, which was reversed upon remission of the nephrosis. This gathers a unifying concept for the role of nocturnal rostral fluid shift in the pathogenesis of OSA.
[Show abstract][Hide abstract] ABSTRACT: Patients with diabetes mellitus are known to have increased serum levels of advanced glycation end-products (AGEs), and this is also associated with insulin resistance. This study aimed to investigate the relationship between serum AGEs and insulin sensitivity in non-diabetic subjects with obstructive sleep apnoea (OSA).
Adult males with no known comorbidities were recruited from the sleep clinic of a university teaching hospital. They underwent overnight in-laboratory polysomnography. Fasting blood was taken to measure serum AGE and plasma glucose levels. Insulin sensitivity was estimated using the short insulin tolerance test.
In total, 105 subjects with a mean age of 43.5 (standard deviation [SD] 9.2)years, mean body mass index of 27.1 (SD 4.0)kg/m(2), and median apnoea-hypopnoea index (AHI) of 17 (interquartile range 5-46) were analysed. Serum AGE levels were significantly higher in subjects with OSA (AHI ≥5), compared with those without OSA (AHI <5) (3.9 [SD 1.2] vs. 3.2 [SD 0.8]μg/ml, respectively; P=0.037) after adjusting for confounders. AGE levels were positively correlated with AHI (r=0.318, P=0.001), but not with insulin sensitivity. AGE levels decreased in subjects with moderate-to-severe OSA who received continuous positive airway pressure (CPAP) treatment for three months (n=18, P=0.017).
Serum AGE levels correlate with AHI in non-diabetic adult males. This relationship cannot be explained by insulin sensitivity. Supporting the hypothesis of a direct relationship between AHI and AGEs, AGE levels were found to decline with CPAP therapy.
Sleep Medicine 12/2011; 13(1):15-20. · 3.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cigarette smoking is a major risk factor in chronic obstructive pulmonary disease (COPD) with chronic airway inflammation as a key feature. Blockade of serotonin receptor 2A (5-HTR(2A)) with ketanserin has been found to improve lung function in COPD patients. Furthermore, ketanserin has been shown to possess anti-inflammatory properties in vivo. In this study, we investigated the antioxidative and anti-inflammatory properties of ketanserin and its underlying mechanism of action on cigarette smoke-induced interleukin (IL)-8 release in vitro. Primary normal human bronchial epithelial cells and human bronchial epithelial cell line (BEAS-2B) were treated with or without ketanserin prior to exposure to cigarette smoke medium (CSM). Exposure to CSM caused elevation of both mRNA and release of IL-8 with increased phosphorylation of p38 and extracellular signal-regulated kinases 1 and 2 (ERK1/2). Consistently, CSM-induced IL-8 release was blocked by SB203580, U0126, or MEK1 small interfering RNA (siRNA) but not SP600125. On the other hand, CSM caused a dose-dependent decrease in the ratio of reduced glutathione to oxidized glutathione (rGSH/GSSG) together with an increased translocation of Nrf2 to the nucleus demonstrated by Western blot analysis. Knock down of Nrf2 by siRNA completely blocked CSM-induced IL-8 release. Ketanserin suppressed CSM-induced IL-8 release by inhibiting p38, ERK1/2 MAPK, and Nrf2 signaling pathways and partially inhibited CSM-induced reduction of rGSH/GSSG ratio. Our data demonstrated the novel antioxidative and anti-inflammatory role of ketanserin via the Nrf2 signaling pathway in CSM-exposed human bronchial epithelial cells. This may open up new perspectives in the development of novel therapeutic targets in the treatment of cigarette smoke-related COPD.