New Insights Into the Pathogenesis of Cystic Fibrosis

The cystic fibrosis transmembrane regulator (CFTR) should no longer be viewed primarily as a 'chloride channel' but recognized as a channel that also controls the efflux of other physiologically important anions, such as glutathione (GSH) and bicarbonate. More effective approaches to cystic fibrosis treatment may result from this reconceptualization of the CFTR by researchers and clinicians. For example, oxidant damage in cystic fibrosis has been assumed to be a significant part of the pathophysiology of the disease. Generally speaking, antioxidant status in cystic fibrosis is compromised. However, until recently this was seen as secondary to the excessive chemoattraction of neutrophils in this disease caused by mutation of the CFTR protein, leading to a high oxidant burden. New findings suggest that the cystic fibrosis mutations in fact cause a primary dysfunction in the system of one of the body's most important antioxidant and immune-signaling substances: the reduced GSH system. Cystic fibrosis mutations significantly decrease GSH efflux from cells without redundant channels to the CFTR; this leads to deficiency of GSH in the epithelial lining fluid of the lung, as well as in other compartments, including immune system cells and the gastrointestinal tract. This deficiency is exaggerated over time as the higher-than-normal oxidant burden of cystic fibrosis leads to successively larger decrements in GSH without the normal opportunity to fully recover physiologic levels. This GSH system dysfunction may be the trigger for initial depletion of other antioxidants and may also play a role in initiating the over-inflammation characteristic of cystic fibrosis. Proper GSH system functioning also affects immune system competence and mucus viscosity, both of relevance to cystic fibrosis pathophysiology. In a way, cystic fibrosis may be thought of as the first identified disease with GSH system dysfunction.This overview provides a review of the most pertinent recent research findings in this area. Exogenous augmentation of GSH in the lung epithelial lining fluid is possible, and therapeutic approaches include administration of aerosolized buffered GSH, intravenous GSH, and oral GSH. However, it is important to remember that the pathophysiology of cystic fibrosis is multifactorial, and rectification of GSH system dysfunction in patients with cystic fibrosis will not eliminate all harmful effects of the disease. The promising results of two clinical trials of aerosolized buffered GSH in cystic fibrosis patients have been published or accepted for publication at the time of this writing. GSH depletion in lung epithelial lining fluid has also been noted in other respiratory diseases such as COPD, idiopathic pulmonary fibrosis, and adult respiratory distress syndrome, and therapies to augment GSH may also be contemplated in these diseases.     

Relationship Between Asthma Severity and Obesity

The prevalence of both obesity and asthma has risen in recent years. We sought to investigate whether obesity may be related to asthma. We undertook a retrospective medical record review of patient records at an inner‐city academic asthma center. Obesity was defined as a body mass index (BMI) greater than 30. Asthma severity was defined by using the National Heart Lung and Blood Institute 1997 guidelines. Adults with a history of cigarette smoking or other lung disease were excluded. A total of 143 individuals aged 18–88 with a mean age of 43.9 met the entry criteria. There were 113 females and 30 males. Seventy‐two percent of the sample was obese. The Spearman correlation coefficient showed a linear relationship between asthma severity and BMI (r = 0.40, p < 0.0001). Females with asthma were significantly more overweight than males, mean BMI 35.9 vs. 32.14, respectively (p = 0.01). The prevalence of obesity in the 13 patients on long‐term oral corticosteroids was 100%. Prevalence of obesity increases with increasing asthma severity in adults. The association of asthma severity with obesity suggests that obesity may be a potentially modifiable risk factor for asthma or asthma‐like symptoms.     

Current Thinking on the Relationship Between Rhinosinusitis and Asthma

An observation made initially on clinical grounds and epidemiologic evidence, i.e., that rhinosinusitis and asthma are closely linked diseases is now supported by a growing body of scientific evidence. Most recent evidence supports the characterization of rhinosinusitis and asthma as two compartmental expressions of a common mucosal susceptibility to exogenous stimuli. In addition, there is evidence that the compartmental processes can affect and amplify each other via a systemic intermediary. The bone marrow is involved in this process, and IL-5 may be a key cytokine for orchestrating the systemic interaction. These facts argue that rhinosinusitis and asthma are not simply localized disease processes but part of a systemic inflammatory disease affecting the respiratory tract. They also provide a compelling rationale for combined treatment strategies with consideration of the treatment of rhinosinusitis as a means of improving asthma control and monitoring for signs of bronchial involvement in those with rhinosinusitis.     

小儿哮喘病与BMI的相关性研究

目的 研究儿童肥胖与哮喘的相关性。方法观察200例儿童,其中哮喘患儿100例,对照组100例,计算BMI值,BMI-[体重（kg）／[身高（m）]^2。当BMI≥同年龄、同性别的第95百分位数或BMI〉30诊断肥胖。结果22％哮喘患儿肥胖,而对照组为8％,两组相比较,差别有显著性。两组儿童在年龄分布和性别构成上差异均没有显著性。结论哮喘是儿童肥胖发病的危险因素。     

Relationship Satisfaction Moderates the Association Between Catastrophic Cognitions and Asthma Symptoms

The tendency to have catastrophic beliefs and interpretations when anxious has been associated with less optimal disease management among persons with asthma. The goal of the present study was to examine the mediating effect of relationship satisfaction on the association between catastrophic cognitions and asthma symptom reporting in a sample of couples in which one partner has asthma. The participants were 50 patients with mild-to-moderate asthma and their partners. The results indicated that catastrophic cognitions were significantly associated with greater asthma symptoms related to rapid breathing, irritability, and panic/fear, after controlling for asthma severity. Among participants with high relationship satisfaction, catastrophic cognitions were significantly associated with panic/fear, irritability, anger, and loneliness. Among participants with low relationship satisfaction, catastrophic cognitions were significantly associated with dyspnea, congestion, and rapid breathing. These results are discussed in terms of potentially reflecting patients’ perceptions of the fit between their coping needs and the support available in their intimate relationships.     

Relationship Between Lung Function and Asthma Symptoms in Patients with Difficult to Control Asthma

Several studies have demonstrated a poor relationship between measures of asthma control and lung function in patients with asthma. We sought to examine this relationship in a cohort of difficult to control asthmatics attending a hospital outpatient clinic. FEV₁% and asthma control scores (ACSs) were measured at the first clinic visit and at a follow-up visit. A total of 59 patients took part in the study. At the initial visit, FEV₁% correlated with limitation of activity (p = 0.002), shortness of breath (p = 0.02), wheezing (p = 0.029), and ACS (p = 0.014). However, at follow-up, there was no correlation between FEV₁% and any measured index of asthma control. When patients with severe fixed airflow obstruction were excluded from the analysis (n = 16), FEV₁% at follow-up became significantly correlated with night waking (p = 0.02), wheezing (p = 0.05), and ACS (p = 0.036). The improvement in asthma control score at follow-up was significantly and strongly associated (r = 0.51 for total asthma control, p < 0.001) with the improvement in lung function in patients without severe fixed airflow obstruction. Lung function was not associated with any measure of asthma control in patients with severe fixed airflow obstruction. FEV₁% correlates well with asthma symptoms in difficult asthma patients with poor control but not when control improves. This loss of relationship is due to subjects with severe fixed airflow obstruction where good subjective control does not exclude the presence of significant obstruction. How severe fixed airflow obstruction should be prevented, delayed, or managed in asthma requires further research.     

Novel Insights Into E3 Ubiquitin Ligase in Cancer Chemoresistance

Drug resistance can obstruct successful cancer chemotherapy. The ubiquitin-proteasome pathway has emerged as a crucial player that controls steady-state protein levels regulating multiple biological processes, such as cell cycle, cellular proliferation, apoptosis, and DNA damage response, which are involved in oncogenesis, cancer development, prognosis, and drug resistance. E3 ligases perform the final step in the ubiquitination cascade, and determine which protein becomes ubiquitylated by specifically binding the substrate protein. They are promising drug targets thanks to their ability to regulate protein stability and functions. Although patient survival has increased in recent years with the availability of novel agents, chemoresistance remains a major problem in cancer management. E3 ligases attract increasing attention with advances in chemoresistance knowledge. To explore the role of E3 ligase in cancer chemotherapy resistance and the underlying mechanism, we summarize the growing number of E3 ligases and their substrate proteins, which have emerged as crucial players in cancer chemoresistance and targeted therapies.     

The Relationship Between Asthma-Specific Quality of Life and Asthma Control

Few studies have quantitatively addressed the relationship between asthma-specific quality of life and asthma control as assessed by validated tools. Questionnaires were completed at home by a random sample of 542 adult asthmatic patients. The correlations of the two asthma control tools (Asthma Control Test? and Asthma Therapy Assessment Questionnaire?) with the quality of life tool (mini-Asthma Quality of Life Questionnaire) were strongest with the symptoms and activity domains (r = 0.63–0.77); lower with the emotions domain (r = 0.57–0.64); and lowest with the environment domain (r = 0.38–0.43). Asthma control tools reflect the symptoms and activity themes of asthma quality of life well, but reflect the environmental domain less well.     

The Relationship Between Asthma-Specific Quality of Life and Asthma Control

Few studies have quantitatively addressed the relationship between asthma-specific quality of life and asthma control as assessed by validated tools. Questionnaires were completed at home by a random sample of 542 adult asthmatic patients. The correlations of the two asthma control tools (Asthma Control Test™ and Asthma Therapy Assessment Questionnaire™) with the quality of life tool (mini-Asthma Quality of Life Questionnaire) were strongest with the symptoms and activity domains (r = 0.63-0.77); lower with the emotions domain (r = 0.57-0.64); and lowest with the environment domain (r = 0.38-0.43). Asthma control tools reflect the symptoms and activity themes of asthma quality of life well, but reflect the environmental domain less well.     

New Insights Into Mechanisms of Acute Kidney Injury in Heart Disease

Acute kidney injury is a frequent occurrence in patients with heart disease, and is associated with higher risk of adverse outcomes, including mortality. In the setting of decompensated heart failure, acute kidney injury can occur from hemodynamic and neurohormonal activation, venous congestion, and nephrotoxic medications. Certain medications, such as loop diuretics, renin angiotensin system blockers, and mineralocorticoid antagonists can seemingly cause acute kidney injury. However, this increase in creatinine level is not always associated with adverse outcomes and should be carefully differentiated so as to allow deliberate continuation of these cardio- and nephroprotective agents. In other settings such as cardiac surgery, acute kidney injury can occur from factors related to the cardiopulmonary bypass, renal hypoperfusion, or other perioperative factors. Last, patients with heart disease commonly undergo imaging procedures that require contrast administration. Contrast can indeed cause acute kidney injury, but these interventional procedures also can result in kidney injury from atheroembolic phenomena. This is well documented by the recent data reporting a higher risk of acute kidney injury from femoral compared with radial access. The advent of biomarkers of kidney injury present an opportunity for early detection, accurate differential diagnosis, as well as potentially designing innovative biomarker-enriched adaptive clinical trials.     

居室空气污染与儿童哮喘关系的调查

目的 了解居室内空气污染对儿童哮喘的影响.方法 采用病例-对照流行病学研究设计、通过问卷收集50例儿童哮喘患者及50例非哮喘儿童对照相关信息.结果 单因素分析结果显示,达到显著性水平的危险因素包括:被动吸烟(OR=3.55)、室内装修(OR=1.89)、家族过敏史(OR=3.43)以及个体过敏史(OR=4.93).条件logisfic多元回归分析中,被动吸烟、室内装修、家族过敏史和个体过敏史进入了最终模型,OR值分别为3.37,1.74,3.50.4.59.结论 儿童哮喘的高发除了遗传因素以外,最主要的是室内小环境污染(呼吸带水平)对儿童呼吸系统健康的影响尤为严重.因此避免室内过度装修,被动吸烟,可以降低室内污染程度,最终达到保护儿童健康的目的 .