Clinical Evaluation of Fiducial Marker Pre-Planning for Virtual Bronchoscopic Navigation Implantation in Lung Tumour Patients Treated With CyberKnife.

Purpose: For the treatment of invisible lung tumours with CyberKnife (CK), fiducial markers (FMs) were implanted as an internal surrogate under virtual bronchoscopic navigation (VBN). This research aims to study the benefits of introducing an additional procedure in assigning the optimal FM positions using a pre-procedure planning system and performing virtual simulation before implantation. The objectives were 1) to reduce the duration of the FM implantation procedure, 2) to reduce the radiation exposure in dose area product (DAP) (dGy*cm2) to patients, and 3) to increase the number of FMs implanted around the tumour. Methods and Materials: This study is retrospective, single-centre, and observational in nature. A total of 32 patients were divided into two groups. In Group 1, 18 patients underwent conventional VBN FM implantation. In Group 2, 14 patients underwent additional pre-procedure planning and simulation. The steps of pre-procedure planning include 1) importing CT images into the treatment planning system (Eclipse, Varian Medical Systems, Inc.) and delineating five to six FMs in their ideal virtual positions and 2) copying the FM configuration into VBN planning software (LungPoint Bronchus Medical, Inc.) for verification and simulation. Finally, the verified FMs were deployed through VBN with the guidance of the LungPoint planning software. Results: A total of 162 FMs were implanted among 35 lesions in 32 patients aged from 37 to 92 (median = 66; 16 men and 16 women). Results showed that 1) the average FM insertion time was shortened from 41 min (SD = 2.05) to 23 min (SD = 1.25), p = 0.00; 2) the average absorbed dose of patients in DAP was decreased from 67.4 cGy*cm2 (SD = 14.48) to 25.3 cGy*cm2 (SD = 3.82), p = 0.01 (1-tailed); and 3) the average number of FMs implanted around the tumour was increased from 4.7 (SD = 0.84) to 5.6 (SD = 0.76), p = 0.00 (1-tailed). Conclusion: Pre-procedure planning reduces the FM implantation duration from 41.1 to 22.9 min, reduces the radiation exposure in DAP from 67.4 to 25.3 dGy*cm2, and increases the number of FMs inserted around the tumour from 4.7 to 5.6.

Efficacy and safety of virtual bronchoscopic navigation with fused fluoroscopy and vessel mapping for access of pulmonary lesions.

BACKGROUND AND OBJECTIVE: Virtual bronchoscopic navigation (VBN) with fused fluoroscopy and vessel mapping provides a point of entry (POE) for puncturing airway wall to biopsy lesions. The study was designed to evaluate the safety and efficacy of this technology to diagnose peripheral pulmonary lesions. METHODS: It was a prospective, single-arm, multicentre study. Patients underwent lesions biopsy with the Archimedes® VBN System via a POE using one of the two techniques: (1) bronchoscopic transparenchymal nodule access (BTPNA) and (2) guided transbronchial needle aspiration (TBNA). Biopsy yield, sampling yield and diagnostic yield were mainly determined in lesions biopsy attempted. RESULTS: One hundred and thirty patients underwent anaesthesia and constituted the intention-to-treat population. One hundred and four patients with 114 lesions had biopsy attempted. Mean lesion size was 2.4 ± 1.13 cm. Sufficient tissue samples were obtained from 86 lesions with a biopsy yield of 75.4%. Nevertheless, sufficient samples for diagnosis based on histology ± cytology were obtained from 107 lesions with a sampling yield of 93.9%. Follow-up was conducted for more than 1 year, with a diagnostic yield of 75.4% and 72.8%, respectively, on high and low estimate with consideration of three lesions without follow-up. Two (1.9%) pneumothoraxes and one (1.0%) mild bleeding occurred. CONCLUSION: BTPNA and guided TBNA contribute to safe and effective sampling of peripheral pulmonary lesions. A relatively high biopsy yield was obtained independent of the presence or absence of a bronchus sign (BS), and high sampling yield and diagnostic yield were obtained independent of location, lesion size and presence or absence of a BS.

Proteinuria is associated with sleep apnea in chronic kidney disease.

BACKGROUND: The prevalence and severity of sleep apnea (SA) in the chronic kidney disease (CKD) population is not well characterized. Recent studies have yielded highly variable prevalence rates due to cohort heterogeneity and interstudy inconsistencies in defining SA. This study sought to determine the association of SA with CKD by recruiting a uniform cohort to undertake overnight polysomnography (PSG). METHODS: A total of 141 male Chinese CKD patients, ages 40-60 years, underwent overnight PSG to delineate the prevalence and severity of SA and nocturnal hypoxemia (NH). Body mass index (BMI), neck girth, estimated glomerular filtration rate, urinary protein excretion and Epworth sleepiness scale (ESS) score were collected at baseline to determine associative factors. RESULTS: The prevalence rates of SA and NH were 35.5 and 10.6%, respectively, in this study population [mean (±SD) age 51.44 ± 6.05 years; BMI 26.05 ± 4.22 kg/m(2)]. The adjusted odds ratios (ORs) for SA by BMI and proteinuria were 1.18 [95% confidence interval (CI) 1.02, 1.37; P ≤ 0.05] and 1.57 (95% CI 1.12, 2.46; P ≤ 0.05), respectively. The adjusted ORs for the median cohort oxygen desaturation index (ODI) by BMI and proteinuria were 1.23 (95% CI 1.05, 1.45; P ≤ 0.05) and 1.75 (95% CI 1.12, 2.76; P ≤ 0.05). However, no significant correlation between the prevalence and severity of SA and NH with progressive renal deterioration was observed. Furthermore, no significant mean difference in the apnea-hypopnea index and ODI was observed for an ESS above and below 10. CONCLUSIONS: SA is prevalent in CKD patients and strongly correlated with BMI and proteinuria, but not with renal function. The ESS is an investigative tool that lacks discriminatory power in patients with renal insufficiency. Therefore clinical vigilance for SA is paramount when attending to CKD patients with significant proteinuria.

Ancient origin of mast cells.

The sentinel roles of mammalian mast cells (MCs) in varied infections raised the question of their evolutionary origin. We discovered that the test cells in the sea squirt Ciona intestinalis morphologically and histochemically resembled cutaneous human MCs. Like the latter, C. intestinalis test cells stored histamine and varied heparin·serine protease complexes in their granules. Moreover, they exocytosed these preformed mediators when exposed to compound 48/80. In support of the histamine data, a C. intestinalis-derived cDNA was isolated that resembled that which encodes histidine decarboxylase in human MCs. Like heparin-expressing mammalian MCs, activated test cells produced prostaglandin D2 and contained cDNAs that encode a protein that resembles the synthase needed for its biosynthesis in human MCs. The accumulated morphological, histochemical, biochemical, and molecular biology data suggest that the test cells in C. intestinalis are the counterparts of mammalian MCs that reside in varied connective tissues. The accumulated data point to an ancient origin of MCs that predates the emergence of the chordates >500million years ago, well before the development of adaptive immunity. The remarkable conservation of MCs throughout evolution is consistent with their importance in innate immunity.

Impact of nephrotic edema of the lower limbs on obstructive sleep apnea: gathering a unifying concept for the pathogenetic role of nocturnal rostral fluid shift.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The value of autofluorescence bronchoscopy combined with white light bronchoscopy compared with white light alone in the diagnosis of intraepithelial neoplasia and invasive lung cancer: a meta-analysis.

OBJECTIVE: To compare the accuracy of autofluorescence bronchoscopy (AFB) combined with white light bronchoscopy (WLB) versus WLB alone in the diagnosis of lung cancer. METHODS: The Ovid, PubMed, and Google Scholar databases from January 1990 to October 2010 were searched. Two reviewers independently assessed the quality of the trials and extracted data. The relative risk for sensitivity and specificity on a per-lesion basis of AFB + WLB versus WLB alone to detect intraepithelial neoplasia and invasive cancer were pooled by Review Manager. RESULTS: Twenty-one studies involving 3266 patients were ultimately analyzed. The pool relative sensitivity on a per-lesion basis of AFB + WLB versus WLB alone to detect intraepithelial neoplasia and invasive cancer was 2.04 (95% confidence interval [CI] 1.72-2.42) and 1.15 (95% CI 1.05-1.26), respectively. The pool relative specificity on a per-lesion basis of AFB + WLB versus WLB alone was 0.65 (95% CI 0.59-0.73). CONCLUSIONS: Although the specificity of AFB + WLB is lower than WLB alone, AFB + WLB seems to significantly improve the sensitivity to detect intraepithelial neoplasia. However, this advantage over WLB alone seems much less in detecting invasive lung cancer.

The catalytic architecture of leukotriene C4 synthase with two arginine residues.

Leukotriene (LT) C(4) and its metabolites, LTD(4) and LTE(4), are involved in the pathobiology of bronchial asthma. LTC(4) synthase is the nuclear membrane-embedded enzyme responsible for LTC(4) biosynthesis, catalyzing the conjugation of two substrates that have considerably different water solubility; that amphipathic LTA(4) as a derivative of arachidonic acid and a water-soluble glutathione (GSH). A previous crystal structure revealed important details of GSH binding and implied a GSH activating function for Arg-104. In addition, Arg-31 was also proposed to participate in the catalysis based on the putative LTA(4) binding model. In this study enzymatic assay with mutant enzymes demonstrates that Arg-104 is required for the binding and activation of GSH and that Arg-31 is needed for catalysis probably by activating the epoxide group of LTA(4).

The efficacy of oral appliances in the treatment of severe obstructive sleep apnea.

OBJECTIVES: The purpose of this study is to evaluate the efficacy of oral appliance (OA) treatment for subjects with severe obstructive sleep apnea (OSA) and to determine the dental parameters associated with treatment outcomes. STUDY DESIGN: This study uses a prospective longitudinal design. METHODS: Consecutive Chinese subjects with severe OSA who refused continuous positive airway pressure treatment were recruited. Their dental measurements were taken from lateral cephalometric radiographs. Polysomnograms with OA were repeated at 3 months and 1 year. Blood pressure was taken in the morning after sleep studies. RESULTS: Thirty-four subjects were evaluated at 3 months and 1 year according to the principle of intention-to-treat analysis. OA reduced AHI significantly in subjects with favorable responses, from 49.3 (37.4-67) to 12.5 (6.1-15.7), p < 0.001 at 3 months and from 47.5 (41.1-72.9) to 13.1 (6.0-14.0), p < 0.001 at 1 year. These OSA subjects had an increased overjet at baseline compared to those with unfavorable responses (p ≤ 0.05). Systolic blood pressure was significantly reduced in those hypertensive OSA subjects after 3 months and 1 year of treatment. CONCLUSIONS: OA reduces the severity of sleep apnea, and the effect is maintained at 1 year in subjects with retrognathism. OA appears to reduce systolic blood pressure in hypertensive OSA subjects at 3 months and 1 year.

Characterization of a novel human mast cell line that responds to stem cell factor and expresses functional FcεRI.

BACKGROUND: Studies of human mast cells (MCs) are constrained by the paucity of functional cell lines, the expense of maintaining MCs in culture, and technical complexities. OBJECTIVE: We derived and characterized a human MC line that arose spontaneously from a culture of nontransformed hematopoietic progenitor cells. METHODS: CD34(+) enriched mononuclear cells derived from a donor with aspirin-exacerbated respiratory disease were cultured for 8 weeks with stem cell factor and IL-6 and with IL-3 for the first week only. The cells (termed LUVA cells) survived and proliferated without further addition of any growth factors and have been maintained in culture for approximately 2 years. RESULTS: LUVA cells possess metachromatic cytoplasmic granules that are immunoreactive for tryptase, cathepsin G, and carboxypeptidase A3. They express transcripts encoding FcεRI, c-kit, chymase, tryptase, histidine decarboxylase, carboxypeptidase A3, and the type 1 receptor for cysteinyl leukotrienes. Flow cytometry confirmed uniform expression of FcεRI, c-kit, and FcγRII. FcεRI cross-linkage induced the release of ß-hexosaminidase, prostaglandin D(2), thromboxane A(2), and macrophage inflammatory protein 1ß. Immortalization was not associated with either a known genomic mutation of c-kit in the donor or a somatic mutation of c-kit within the cells, and it was not associated with c-kit autophosphorylation. CONCLUSIONS: LUVA cells are an immortalized human MC line that can be maintained without stem cell factor and display high levels of normally signaling c-kit and FcεRI. These cells will prove valuable for functional human MC studies.

Oxidative stress suppresses cysteinyl leukotriene generation by mouse bone marrow-derived mast cells.

Cysteinyl leukotrienes and oxidative stress have both been implicated in bronchial asthma; however, there is no previous study that focused on the ability of oxidative stress to alter cysteinyl leukotriene generation. In this study, treatment of bone marrow-derived mast cells with prostaglandin D(2) reduced their ability to generate leukotriene (LT) C(4) upon calcium ionophore stimulation but had little effect on LTB(4) generation. This effect could be reproduced by a selective agonist of the DP(2) receptor, 15R-methyl prostaglandin D(2) (15R-D(2)). 15R-D(2) dose-dependently inhibited LTC(4) generation with an IC(50) of 2 µM, and the effect was not altered by a DP(2)/thromboxane antagonist or by a peroxisome proliferator-activated receptor-γ antagonist. 15R-D(2) exerted its suppressive effect via a reduction in intracellular GSH, a mechanism that involved the conjugation of its non-enzymatic breakdown product to GSH. At 10 µM, 15R-D(2) reduced LTC(4) generation to 10%, intracellular GSH to 50%, and LTC(4) synthase (LTC(4)S) activity to 33.5% of untreated cells without altering immunoreactive LTC(4)S protein expression or 5-lipoxygenase activity. The effects of 15R-D(2) on LTC(4)S activity could be partially reversed by reducing reagent. The sulfhydryl-reactive oxidative agent diamide suppressed LTC(4)S activity and induced a reversible formation of covalent dimer LTC(4)S. LTC(4)S bearing a C56S mutation was resistant to the effect of diamide. Covalent dimer LTC(4)S was observed in nasal polyp biopsies, indicating that dimerization and inactivation of LTC(4)S can occur at the site of inflammation. These results suggest a cellular redox regulation of LTC(4)S function through a post-translational mechanism.

Joint tissues amplify inflammation and alter their invasive behavior via leukotriene B4 in experimental inflammatory arthritis.

Mechanisms by which mesenchymal-derived tissue lineages participate in amplifying and perpetuating synovial inflammation in arthritis have been relatively underinvestigated and are therefore poorly understood. Elucidating these processes is likely to provide new insights into the pathogenesis of multiple diseases. Leukotriene B(4) (LTB(4)) is a potent proinflammatory lipid mediator that initiates and amplifies synovial inflammation in the K/BxN model of arthritis. We sought to elucidate mechanisms by which mesenchymal-derived fibroblast-like synoviocytes (FLSs) perpetuate synovial inflammation. We focused on the abilities of FLSs to contribute to LTB(4) synthesis and to respond to LTB(4) within the joint. Using a series of bone marrow chimeras generated from 5-lipoxygenase(-/-) and leukotriene A(4) (LTA(4)) hydrolase(-/-) mice, we demonstrate that FLSs generate sufficient levels of LTB(4) production through transcellular metabolism in K/BxN serum-induced arthritis to drive inflammatory arthritis. FLSs-which comprise the predominant lineage populating the synovial lining-are competent to metabolize exogenous LTA(4) into LTB(4) ex vivo. Stimulation of FLSs with TNF increased their capacity to generate LTB(4) 3-fold without inducing the expression of LTA(4) hydrolase protein. Moreover, LTB(4) (acting via LTB(4) receptor 1) was found to modulate the migratory and invasive activity of FLSs in vitro and also promote joint erosion by pannus tissue in vivo. Our results identify novel roles for FLSs and LTB(4) in joints, placing LTB(4) regulation of FLS biology at the center of a previously unrecognized amplification loop for synovial inflammation and tissue pathology.

Cysteinyl-leukotriene type 1 receptors transduce a critical signal for the up-regulation of eosinophilopoiesis by interleukin-13 and eotaxin in murine bone marrow.

IL-13 and eotaxin play important, inter-related roles in asthma models. In the lungs, CysLT, produced by the 5-LO-LTC4S pathway, mediate some local responses to IL-13 and eotaxin; in bone marrow, CysLT enhance IL-5-dependent eosinophil differentiation. We examined the effects of IL-13 and eotaxin on eosinophil differentiation. Semi-solid or liquid cultures were established from murine bone marrow with GM-CSF or IL-5, respectively, and the effects of IL-13, eotaxin, or CysLT on eosinophil colony formation and on eosinophil differentiation in liquid culture were evaluated, in the absence or presence of: a) the 5-LO inhibitor zileuton, the FLAP inhibitor MK886, or the CysLT1R antagonists, montelukast and MK571; b) mutations that inactivate 5-LO, LTC4S, or CysLT1R; and c) neutralizing mAb against eotaxin and its CCR3 receptor. Both cytokines enhanced GM-CSF-dependent eosinophil colony formation and IL-5-stimulated eosinophil differentiation. Although IL-13 did not induce eotaxin production, its effects were abolished by anti-eotaxin and anti-CCR3 antibodies, suggesting up-regulation by IL-13 of responses to endogenous eotaxin. Anti-CCR3 blocked eotaxin completely. The effects of both cytokines were prevented by zileuton, MK886, montelukast, and MK571, as well as by inactivation of the genes coding for 5-LO, LTC4S, and CysLT1R. In the absence of either cytokine, these treatments or mutations had no effect. These findings provide evidence for: a) a novel role of eotaxin and IL-13 in regulating eosinophilopoiesis; and b) a role for CysLTRs in bone marrow cells in transducing cytokine regulatory signals.

Obstructive sleep apnoea: definitions, epidemiology & natural history.

Obstructive sleep apnoea (OSA) is increasingly being recognized as an important health issue in the last two to three decades. It is characterized by frequent episodes of upper airway collapse during sleep, causing recurrent arousals, intermittent hypoxaemia, sleep fragmentation and poor sleep quality. There is accumulating evidence that OSA is being considered as an independent risk factor for hypertension, glucose intolerance / diabetes mellitus, cardiovascular diseases and stroke, leading to increased cardiometabolic morbidity and mortality. The prevalence rates of OSA have been estimated in the range of 2 to 10 per cent worldwide, and the risk factors for obstructive sleep apnoea include advanced age, male sex, obesity, family history, craniofacial abnormalities, smoking and alcohol consumption. The common clinical presenting symptoms are heavy snoring, witnessed apnoeas and daytime hypersomnolence, which would help to identify the affected individuals. With increasing awareness of this disease entity and associated complications in our society, there have been increased referrals to sleep physicians or expertise for further investigations and diagnostic evaluation. Early recognition and treatment of obstructive sleep apnoea may prevent from adverse health consequences. Some of the epidemiological aspects of obstructive sleep apnoea in adults are reviewed.

Sleep apnea is a novel risk predictor of cardiovascular morbidity and death in patients receiving peritoneal dialysis.

Sleep apnea syndrome is increasingly recognized in peritoneal dialysis patients; however, its prognostic implication in this population is unknown. To study this, we prospectively followed the clinical outcome of 93 peritoneal dialysis patients with baseline polysomnography. Of these, 51 were diagnosed with the syndrome defined by an apnea-hypopnea index (AHI) of at least 15 per hour. During a median follow-up of 41 months, there were 30 deaths, of which 17 were due to cardiovascular causes. Kaplan-Meier analysis for the entire follow-up period indicated that patients with sleep apnea at baseline had significantly higher all-cause and cardiovascular mortality during follow-up than those without. Minimal nocturnal saturation and desaturation indices were predictors of mortality and cardiovascular events at univariate analysis. Multivariable Cox regression analysis identified significant sleep apnea syndrome at baseline as an independent predictor of increased all-cause mortality independent of age, male gender, and diabetic status. Further, an absolute increase in the AHI was associated with an incremental risk of cardiovascular events. Thus, sleep apnea syndrome, detected at the start of peritoneal dialysis, is a novel risk predictor for subsequent mortality and cardiovascular events.

Erlotinib as salvage treatment after failure to first-line gefitinib in non-small cell lung cancer.

PURPOSE: Chemotherapy is the mainstay treatment for advanced non-small cell lung cancer (NSCLC). Gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has been recently shown to be effective as a first-line treatment in Asian patients with advanced NSCLC, especially for those with favourable clinical features such as female, non-smoker and adenocarcinoma. However, resistance to gefitinib ensues invariably and there is little evidence as for the effectiveness of subsequent salvage treatment. The purpose of this study is to evaluate the efficacy of erlotinib, another EGFR-TKI, after failed first-line use of gefitinib. METHOD: Retrospective review of NSCLC patients with favourable clinical features who received gefitinib as first-line treatment and subsequent salvage treatment with erlotinib. RESULTS: A total of 21 patients with NSCLC were included in the study. Among them, 18 (85.7%) patients had disease control with gefitinib and 12 (57.1%) patients with salvage erlotinib. There was an association between the disease control with gefitinib and erlotinib (p = 0.031). The disease control rate of erlotinib was independent of the chemotherapy use between the two EGFR-TKIs. CONCLUSION: For NSCLC patients with favourable clinical features, erlotinib was effective in those who had prior disease control with first-line gefitinib.

Capecitabine as salvage treatment for lymphoepithelioma-like carcinoma of lung.

Lymphoepithelioma-like carcinoma (LELC) of lung has previously demonstrated good clinical response to 5-fluorouracil containing chemotherapy regimen, similar to the observation in undifferentiated nasopharyngeal carcinoma. Capecitabine, which is converted into active 5-fluorouracil within tumor cells, has been found effective in colorectal, breast, and recently nasopharyngeal carcinomas. We report our experience in five patients with advanced or metastatic LELC of lung who were treated with single agent capecitabine as salvage chemotherapy. The finding of disease control in three of five patients, especially with exceptionally durable stable disease (14.8 months) in one patient, suggests the potential clinical activity of capecitabine in LELC of lung. Future studies on capecitabine-containing chemotherapy regimens in LELC of lung are warranted.

Determinants of daytime blood pressure in relation to obstructive sleep apnea in men.

This study investigated the roles of different potential pathophysiological mechanisms in the determination of blood pressure in relation to obstructive sleep apnea. The study was designed as a cross-sectional study. Consecutive healthy male subjects who were to undergo polysomnography were recruited. Demographic and anthropometric data were collected. Blood pressure measurements were taken in the evening before sleep and the next morning on waking. Overnight urinary samples for catecholamines and fasting blood for cortisol, insulin, glucose, and lipids were taken. Ninety-four men were analyzed, with a mean age of 43.7 +/- 9.3 years and mean apnea-hypopnea index (AHI) of 27.5 +/- 26.2 events/h. Sixty-nine patients (73%) had obstructive sleep apnea (AHI >or= 5). Urinary catecholamines were positively correlated with severity of sleep apnea, independent of obesity. Blood pressure measurements correlated with age, obesity, severity of sleep apnea, and urinary catecholamines. Regression analysis showed that sleep indices and urinary catecholamines were independent determinants of morning systolic and diastolic blood pressure, respectively, while total cholesterol and waist circumference were respective additional factors. Urinary catecholamines and waist circumference were determinants of evening blood pressure, with morning cortisol being an additional determinant for diastolic blood pressure. Obstructive sleep apnea and related sympathetic activity contributed significantly to the determination of daytime blood pressure in overweight middle-aged men without overt cardiometabolic diseases, and other contributing factors include abdominal obesity, total cholesterol, and cortisol levels.

Improvement in sleep apnea during nocturnal peritoneal dialysis is associated with reduced airway congestion and better uremic clearance.

BACKGROUND AND OBJECTIVES: Among peritoneal dialysis (PD) patients, nocturnal PD (NPD) is known to improve sleep apnea compared with continuous ambulatory peritoneal dialysis (CAPD), but the contributing factors are unclear. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Thirty-eight incident ESRD patients underwent overnight polysomnography (PSG) during NPD and CAPD. Bioelectrical impedance analysis, magnetic resonance imaging of the upper airway, and urea kinetics (Kt/V) during sleep were measured on both occasions. RESULTS: The prevalence of severe sleep apnea (apnea-hypopnea index, AHI > or = 15/h) was 21.1% during NPD, and 42.1% during CAPD. Mean AHI increased from 9.6 +/- 2.7/h during NPD to 21.5 +/- 4.2/h during CAPD. Both obstructive and central apnea worsened after conversion to CAPD. NPD achieved greater reductions in total body water, hydration fraction, and net ultrafiltration than CAPD during sleep. Overnight peritoneal Kt/V and creatinine clearance were lower after conversion. Both peritoneal Kt/V and peritoneal creatinine clearance correlated with AHI, as did their changes after conversion. Volumetric magnetic resonance imaging revealed reduced pharyngeal volumes and cross-sectional area, and tongue enlargement after conversion. CONCLUSIONS: Improvement in sleep apnea during NPD versus CAPD is associated with better fluid and uremic clearance and reduced upper airway congestion during sleep.

Gastroesophageal reflux disease is associated with poor asthma control, quality of life, and psychological status in Chinese asthma patients.

BACKGROUND: Both asthma and gastroesophageal reflux disease (GERD) are common, often coexist, and have significant impact on a patient's quality of life. Our aim was to determine the prevalence of GERD in asthmatic patients at a major hospital in Hong Kong, and to examine the impact of GERD and its association with asthma control. METHODS: Patients with asthma who attended the respiratory clinic at Queen Mary Hospital, Hong Kong, were recruited. Demographic data were collected, and a validated Chinese GERD questionnaire was used. The Medical Outcomes Study 36-item short form (SF-36) was used to assess quality of life, and the Hospital Anxiety and Depression Scale (HADS) was used to assess psychological status. Asthma control was assessed by the asthma control test. RESULTS: A total of 218 patients were recruited; 40.4% of asthmatic patients (88 patients) had GERD, as defined by the GERD questionnaire. Compared with those patients without GERD, those with GERD had significantly worse asthma control (p = 0.022), worse quality of life in all domains of the SF-36 (all p < 0.01), and more anxiety (6.82 vs 4.90, respectively; p < 0.001) and depression (6.09 vs 4.05, respectively; p < 0.001) as reflected by HADSs. CONCLUSIONS: A significant proportion of asthmatic patients in Hong Kong have GERD, and this is associated with poorer asthmatic control, quality of life, and psychological status.