A comparative study of electronic cigarette vapor extracts on airway-related cell lines in vitro

The use of electronic cigarettes (ECs) is rapidly increasing worldwide; however, scientific evidence regarding EC cytotoxicity is limited. The aim of this study was to evaluate the acute cytotoxicity of EC vapor extract (ECE) on airway-related cells in vitro. Cigarette smoke extract (CSE), vapor extract of fifteen brands/flavors of ECs and the extract from the E-vehicle (propylene glycol and glycerin) was collected. Extracts, in concentrations of 100–12.5%, were added to human bronchial epithelial (BEAS-2B, IB3-1 and C38), fibroblast (Wi-38) and macrophage (J774 and THP-1) cell lines. Viability was assessed after 24?h using a standard XTT assay. Viability of <70% of control (no extract) was considered cytotoxic according to UNI EN ISO 10993-5 standards. CSE displayed a concentration-dependent influence on cell viability across all four cell lines with 100% producing the most toxic effect, therefore validating the model and indicating higher cytotoxicity than in ECEs. ECEs did reduce viability although this was not correlated with nicotine content or the E-vehicle. However, several flavors proved cytotoxic, with variation between different brands and cell lines. These data indicate that not all ECs are the same and that use of a particular flavor or brand may have differing effects. The cell line used is also an important factor. More research is crucial to ascertain the health effects of different ECs before they can be accepted as a safe alternative to tobacco cigarettes.     

Finding better therapeutic targets for patients with asthma: adenosine receptors?

Recent observations suggest a potential pathophysiological function for adenosine signalling in chronic inflammation of the airways, and development of new selective agonists or antagonists for adenosine receptor subtypes has recently lead to a number of clinical trials of such agents in asthma. The review by Wilson in this issue of the BJP provides a critical perspective on adenosine receptors as rational targets for drug development for anti-asthma drugs with a focus on their efficacy and safety. Important conclusions can be drawn about the function of adenosine receptors in human asthma and approaches to these important targets with novel therapeutic agents.     

Anaerobes in cystic fibrosis patients’ airways

Anaerobes are known to constitute an important part of the airway microbiota in both healthy subjects and cystic fibrosis (CF) patients. Studies on the potential role of anaerobic bacteria in CF and thus their involvement in CF pathophysiology have reported contradictory results, and the question is still not elucidated. The aim of this study was to summarize anaerobe diversity in the airway microbiota and its potential role in CF, to provide an overview of the state of knowledge on anaerobe antibiotic resistances (resistome), and to investigate the detectable metabolites produced by anaerobes in CF airways (metabolome). This review emphasizes key metabolites produced by strict anaerobic bacteria (sphingolipids, fermentation-induced metabolites and metabolites involved in quorum-sensing), which may be essential for the better understanding of lung disease pathophysiology in CF.     

335例纵隔肿瘤病人麻醉分析

 目的　温故知新为纵隔肿瘤病人的麻醉提供经验和参考。方法　回顾335例纵隔肿瘤病人的麻醉过程,总结特殊纵隔肿瘤的麻醉经验。结果　多数病例麻醉过程顺利,25例出现呼吸循环危象,8例术后不能拔除气管内插管。但无一例死亡。结论　小的纵隔肿瘤麻醉处理无特殊。巨大纵隔肿瘤及纵隔肿瘤压迫气管致呼吸道梗阻患者,麻醉插管应慎重,胸腺瘤伴重症肌无力的麻醉中,中短效非去极化肌松药可以应用,但应小量分次给药。     

REVIEW ARTICLE: Sleep apnea in infants

Infancy is a developmental period characterized by instability of the control of breathing. Apneas of short duration are common, mostly central, and more frequent during rapid-eye-movement (REM) sleep. Obstructive apneas are rare in healthy control infants. Triggering factors such as respiratory syncitial virus infection can increase the frequency and the duration of apneas. Upper airway problems related to bone malformations, soft tissue infiltration, and neurologic lesions are responsible for obstructive apneas, but also for episodes of partial airway obstruction or upper airway resistance syndrome. In certain infants, an apparent-life-threatening event has been related to upper airway anomalies. Congenital central hypoventilation syndrome, a rare respiratory control disorder, may be presented by apneas. Polysomnography is the gold standard for the diagnosis of sleep-disordered-breathing in infants. Early diagnosis of abnormal breathing during sleep is of critical importance for the neurocognitive development in infants.     

Resveratrol rescues cAMP-dependent anionic transport in the cystic fibrosis pancreatic cell line CFPAC1

BACKGROUND AND PURPOSE

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-dependent chloride channel in the plasma membrane of epithelia whose mutation is the cause of the genetic disease cystic fibrosis (CF). The most frequent CFTR mutation is deletion of Phe⁵⁰⁸ and this mutant protein (delF508CFTR) does not readily translocate to the plasma membrane and is rapidly degraded within the cell. We hypothesized that treating epithelial cells with resveratrol, a natural polyphenolic, phyto-ooestrogenic compound from grapes, could modulate both the expression and localization of CFTR.

EXPERIMENTAL APPROACH

Cells endogenously expressing CFTR (MDCK1 and CAPAN1 cells) or delF508CFTR (CFPAC1 and airway epithelial cells, deriving from human bronchial biopsies) were treated with resveratrol for 2 or 18 h. The effect of this treatment on CFTR and delF508CFTR expression and localization was evaluated using RT-PCR, Western blot and immunocytochemistry. Halide efflux was measured with a fluorescent dye and with halide-sensitive electrodes. Production of interleukin-8 by these cells was assayed by ELISA.

KEY RESULTS

Resveratrol treatment increased CFTR expression or maturation in immunoblotting experiments in MDCK1 cells or in CFPAC1 cells. Indirect immunofluorescence experiments showed a shift of delF508CFTR localization towards the (peri)-membrane area in CFPAC1 cells and in human airway epithelial cells. A cAMP-dependent increase in membrane permeability to halide was detected in resveratrol-treated CFPAC1 cells, and was inhibited by a selective inhibitor of CFTR.

CONCLUSION AND IMPLICATIONS

These results show that resveratrol modulated CFTR expression and localization and could rescue cAMP-dependent chloride transport in delF508CFTR cells.     

Upper airway collapsibility evaluated by a negative expiratory pressure test in severe obstructive sleep apnea

OBJECTIVES:

To investigate the usefulness of measuring upper airway collapsibility with a negative expiratory pressure application as a screening test for severe obstructive sleep apnea (OSA).

INTRODUCTION:

OSA is a risk factor for cardiovascular disease, and it may have serious consequences. Its recognition may have important implications during the perioperative period. Increased upper airway collapsibility is one of the main determinants of OSA, and its evaluation could be useful for identifying this condition.

METHODS:

Severe OSA and normal subjects (24 in each group) were matched by body mass index and referred to our sleep laboratory. The subjects were enrolled in an overnight sleep study, and a diurnal negative expiratory pressure test was performed. Flow drop (ΔV̇) and expiratory volume were measured in the first 0.2 s (V_0.2) of the negative expiratory pressure test.

RESULTS:

ΔV̇ and V_0.2 (%) values were statistically different between normal and OSA subjects. OSA patients showed a greater decrease in flow than normal subjects. In addition, severely OSA patients exhaled during the first 0.2 s of the negative expiratory pressure application was an average of only 11.2% of the inspired volume compared to 34.2% for the normal subjects. Analysis of the receiver operating characteristics showed that V_0.2 (%) and ΔV̇ could accurately identify severe OSA in subjects with sensitivities of 95.8% and 91.7%, respectively, and specificities of 95.8% and 91.7%, respectively.

CONCLUSIONS:

V_0.2 (%) and ΔV̇ are highly accurate parameters for detecting severe OSA. The pharyngeal collapsibility measurement, which uses negative expiratory pressure during wakefulness, is predictive of collapsibility during sleep.     

The sleep apnea cardiovascular endpoints (SAVE) trial: Rationale and start-up phase

THE SLEEP APNEA CARDIOVASCULAR ENDPOINTS (SAVE) STUDY (CLINICAL TRIALS REGISTRATION NUMBER: NCT00738170) is an academic initiated and conducted, multinational, open, blinded endpoint, randomised controlled trial designed to determine whether treatment of obstructive sleep apnea (OSA) with continuous positive airways pressure (CPAP) can reduce the incidence of serious cardiovascular events in patients with established cardiovascular disease. The answer to this question is of major importance to populations undergoing ageing and lifestyle changes all over the world. The SAVE study brings together respiratory, sleep and cardiovascular clinician-scientists in a unique interdisciplinary collaborative effort with industry sponsors to conduct the largest and most ambitious clinical trial yet conducted in the field of sleep apnea, with a global recruitment target of 5000 patients. Following its launch in Australia and China in late 2008, SAVE has now entered a phase of international expansion with new recruitment networks being established in New Zealand, India and Latin America. This article describes the rationale for the SAVE study, the considerations behind its design, and progress thus far in establishing the recruitment network. The report emphasises the important role that Chinese sleep and cardiovascular investigators have played in the start-up phase of this landmark international project.