肥胖人群并发支气管哮喘的可能机制——氧化应激

流行病学显示肥胖会增加支气管哮喘患病率和发病率,尽管对二者间联系研究已超过十余年,这种关联确切机制仍不清楚。肥胖人群氧化应激增加,氧化标记物在支气管哮喘患者亦有升高。氧化应激可能是肥胖人群并发支气管哮喘的机制。瘦素与脂连素比值增加,氧化应激增强。脂肪组织含量高,炎症介质增加,氧化应激增强。支气管哮喘患者氧化应激增强,氧化与抗氧化失衡。肥胖与支气管哮喘基因重合序列中存在炎症介质相关基因,同时患有肥胖与支气管哮喘的个体无论在肺脏局部还是全身循环中都可找到炎症反应及氧化应激证据,氧化应激极可能为肥胖与支气管哮喘反应链上关键环节。     

肥胖人群并发支气管哮喘的可能机制——氧化应激

流行病学显示肥胖会增加支气管哮喘患病率和发病率,尽管对二者间联系研究已超过十余年,这种关联确切机制仍不清楚.肥胖人群氧化应激增加,氧化标记物在支气管哮喘患者亦有升高.氧化应激可能是肥胖人群并发支气管哮喘的机制.瘦素与脂连索比值增加,氧化应激增强.脂肪组织含量高,炎症介质增加,氧化应激增强.支气管哮喘患者氧化应激增强,氧化与抗氧化失衡.肥胖与支气管哮喘基因重合序列中存在炎症介质相关基因,同时患有肥胖与支气管哮喘的个体无论在肺脏局部还是全身循环中都可找到炎症反应及氧化应激证据.氧化应激及可能为肥胖与支气管哮喘反应链上关键环节.     

巨噬细胞极化与肥胖型哮喘

肥胖和支气管哮喘(简称哮喘)之间的相关性日益受到关注,大量研究证明两者之间存在关联,但是其机制尚不明确.肥胖导致机体产生的慢性低度炎症,可能是解释肥胖和哮喘关联性的因素之一.研究证明,脂肪组织中浸润的免疫细胞和炎症细胞,释放细胞因子,诱发炎症反应,损害肺、肝、心脏等其他终末器官,并引发慢性疾病如哮喘、脂肪肝、冠心病等.其中,巨噬细胞是比较重要的免疫细胞.通过巨噬细胞介导的炎症反应解释肥胖与哮喘之间的关系不容忽视.本文就巨噬细胞及其亚型特点作一综述,并阐述其与肥胖和哮喘的关联.     

不同糖皮质激素治疗对肥胖哮喘小鼠全身和气道的影响

目的对比布地奈德雾化治疗和地塞米松口服治疗对肥胖哮喘小鼠的疗效和炎症改变。方法将75只C57/6J小鼠随机分为5组,正常组(A组)、哮喘组(B组)、肥胖哮喘组(C组)、布地奈德雾化治疗组(D组)、地塞米松口服治疗组(E组),建立饮食诱导的慢性肥胖哮喘模型。末次激发后24 h,取肺泡灌洗液(BALF)进行细胞计数及分类,ELLISA法测定血清中IL-17浓度,肺组织病理切片观察各组小鼠炎症评分,测定气管壁总面积(WAt)、气道平滑肌面积(WAm)和管腔基底膜周长(Pbm)。结果除A组外,其余四组小鼠均出现不同程度的哮喘发作,实验结束前B组无小鼠死亡,C组有2只小鼠死亡,D组有1只小鼠死亡,而E组有5只小鼠死亡。C组BALF中白细胞总数,中性粒细胞数、嗜酸性粒细胞数、血清IL-17浓度以及病理切片炎症评分、气管壁总厚度(WAt/Pbm)、气道平滑肌厚度(WAm/Pbm)明显高于A、B两组。两治疗组的BALF中白细胞总数、嗜酸性粒细胞数,以及病理切片炎症评分均较C组下降,但气管壁总厚度(WAt/Pbm)、气道平滑肌厚度(WAm/Pbm)改善不明显(P0.05)。E组血清IL-17浓度较C组下降(P0.05),但D组和C组无显著性差异(P0.05)。结论雾化布地奈德能够改善肥胖哮喘小鼠的气道炎症,但不能改善气道重建和全身炎症。地塞米松口服治疗虽有助于改善肥胖哮喘的全身炎症反应,但气道重建无益,且带来更高的病死率。     

肥胖型支气管哮喘与脂质代谢相关作用机制及研究进展

支气管哮喘(哮喘)是一种常见的慢性异质性气道炎症疾病, 气道高反应性和可逆性气道阻塞及气道重塑是其主要病理特征。肥胖作为体内脂肪过多沉积引起的代谢疾病, 已成为不可忽视的全球公共卫生问题。随着肥胖人口的不断增加, 肥胖型哮喘的患病率也呈逐年上升趋势。2014年全球哮喘防治倡议指南已将肥胖型哮喘作为一种新的哮喘表型。肥胖是一种典型的脂质代谢相关疾病, 近年研究发现哮喘的发生发展与脂质代谢有一定的关联。本文将讨论脂质代谢在肥胖相关哮喘发生发展中的作用。     

非2型哮喘的发病机制及治疗研究进展

支气管哮喘(哮喘)是一种高度异质性疾病,以慢性气道炎症为特征。哮喘包含2种内型,2型哮喘和非2型哮喘。约半数患者为非2型哮喘,对糖皮质激素反应差,现有治疗方法难以控制,这是现代医学面临的新挑战。非2型哮喘的发病机制包括中性粒细胞炎症、1型免疫应答、3型免疫应答、全身性炎症反应、代谢异常和非炎症机制。用于治疗的方法有非药...     

肥胖与支气管哮喘研究进展

肥胖与支气管哮喘(简称哮喘)关系的研究日益受到关注,大量研究证实两者具有关联性,但其关联机制尚不明确.另外,有关肥胖对哮喘患者影响的研究尚未得到一致的结论.深入探讨肥胖与哮喘的相关性,将为哮喘的防治提供新的方向.     

肥胖与哮喘的研究进展

哮喘是一种慢性疾病,目前已从遗传基因、脂肪因子、炎性损伤、肥胖相关并发疾病等方面提出了各种假说以解释肥胖与哮喘的关系,但机制尚不明确。肥胖与哮喘仍是研究人员感兴趣的话题,本文综述了肥胖与哮喘之间的最新研究进展,以期为临床提供参考。     

阻塞性睡眠呼吸暂停低通气综合征与哮喘

最近研究表明阻塞性睡眠呼吸暂停低通气综合征(OSAHS)是支气管哮喘急性加重的独立危险因素。OSAHS常涉及睡眠时上气道吸气气流受限及气道塌陷,常与日间症状如嗜睡、抑郁、精力难以集中等相关。支气管哮喘常表现为气道慢性炎症、气道高反应、可逆性气道气流受限等。现已有大量学者对其相关性作出研究,但未达成统一共识。目前认为神经反射因素、胃食管反流、气道及全身炎症反应、睡眠结构紊乱、肥胖、心血管疾病、激素治疗及鼻部疾病等可能是OSAHS与哮喘相互影响及作用的机制。本文就OSAHS与哮喘的相关性及其机制作一综述。     

哮喘患者痰中炎性标志物检测的意义

哮喘患者痰中炎性标志物检测的意义孙滨邓火金哮喘是多种炎症细胞、介质和细胞因子共同作用导致的气道炎症，即使是轻症哮喘，气道亦有炎症表现。因此，如何客观地评价气道炎症的程度成为判断哮喘病情和指导治疗的基础。但由于哮喘炎症在病因、发病机制和病理特征方面均有...     

Relationship between obesity and asthma

The prevalences of both obesity and asthma have clearly increased in recent decades, giving rise to speculation that they may be related. Studies have found that obesity precedes and predicts the onset of asthma (time effect), that increased obesity leads to more severe asthma (dose-response effect), that weight reduction (by diet or gastric bypass) improves asthmatic symptoms, and that obesity co-occurs with intermediate asthma phenotypes (obese young girls undergoing early menarche). In the light of that evidence, we can finally suggest a causal relationship between obesity and asthma. Various biological mechanisms (immunologic and inflammatory, hormonal, genetic, nutritional, mechanical, and others related to physical activity) have been put forth to explain the relationship. However, this relation is complex, involving not only the interaction of genetic and environmental factors in triggering both diseases but also the likely participation of several mechanisms at once.     

Obesity and asthma: implications for treatment

PURPOSE OF REVIEW: Epidemiological data as well as data from mouse models of asthma indicate a relationship between obesity and asthma. The purpose of this review is to evaluate recent data addressing this relationship and its biological basis, and to evaluate the implications of these data for treatment. RECENT FINDINGS: Obesity increases the prevalence, incidence, and possibly severity of asthma, while weight loss in the obese improves asthma outcomes. Obesity also influences asthma control and the response to standard asthma therapeutics. Moreover, obese mice exhibit innate airway hyperresponsiveness and increased responses to common asthma triggers. The biological basis for the relationship between obesity and asthma may be the result of common etiologies, comorbidities, effects of obesity on lung volume, or adipokines such as tumor necrosis factor alpha, leptin, and adiponectin. SUMMARY: Understanding the mechanistic basis for the relationship between obesity and asthma may lead to new therapeutic strategies for treatment of this susceptible population.     

Obesity and asthma: evidence for and against a causal relation.

The evidence for an association between asthma and obesity in adults, and in children and adolescents, is reviewed. Few studies in adults measured height and weight, whereas the majority in children did. Evidence for the association is strong, but that for a gender interaction is weak. There is sufficient evidence to rule out asthma preceding obesity as an explanation, and that increased perception of symptoms in the obese, or a purely mechanical effect, is responsible. However, direct causality is unlikely, because in children the association is of recent origin, and trends in obesity do not explain the rising prevalence of asthma. Atopy was not associated with obesity in a large adult study. Potential explanations that require further investigation are that gastroesophageal reflux as a result of obesity causes asthma, that physical inactivity may promote both obesity and asthma, and that the diets of obese subjects may potentiate asthma.     

Optimizing respiratory function assessments to elucidate the impact of obesity on respiratory health

There is an increasing prevalence of obesity worldwide and its impact on respiratory health is of significant concern. Obesity affects the respiratory system by several mechanisms, including by direct mechanical changes due to fat deposition in the chest wall, abdomen and upper airway, as well as via systemic inflammation. The increased mechanical load in obese individuals leads to reduced chest wall and lung compliance and increased work of breathing. While there is generally minimal effect on spirometric values, as body mass index increases, the expiratory reserve volume, and hence functional residual capacity, reduces, often approaching residual volume in more severe obesity. The majority of evidence however suggests that obese individuals free from lung disease have relatively normal gas exchange. The link between asthma and obesity, while initially unclear, is now recognized as being a distinct asthma phenotype. While studies investigating objective markers of asthma have shown that there is no association between obesity and airway hyper‐responsiveness, a recent working group identified obesity as a major risk factor for the development of asthma in all demographic groups. Although the temptation may be to attribute obesity as the cause of dyspnoea in symptomatic obese patients, accurate respiratory assessment of these individuals is necessary. Lung function tests can confirm that any altered physiology are the known respiratory consequences of obesity. However, given that obesity causes minimal changes in lung function, significant abnormalities warrant further investigation. An important consideration is the knowledge that many of the respiratory physiology consequences of obesity are reversible by weight loss.     

Effects of obesity and weight loss on airway physiology and inflammation in asthma

Obesity is a major risk factor for asthma, but the mechanisms for the development of asthma in the setting of obesity are not known. The purpose of this article is to review the effects of obesity on airway inflammation in patients with asthma, and to discuss the effects of obesity on airway reactivity in patients with asthma.Obesity is particularly a risk factor for non-atopic asthma. Airway eosinophilic inflammation is not increased in obesity, in fact the preponderance of the evidence suggests that airway eosinophilia is decreased in obesity. There is some preliminary data suggesting that airway neutrophilia may be increased in obesity, and that this may be particularly related to dietary fats. Obesity also alters adaptive immunity, and may suppress lymphocyte function typically associated with asthmatic airway inflammation.Population based studies are somewhat inconsistent on the relationship between airway reactivity and asthma, however, recent studies in bariatric surgery show that weight loss surgery in severely obese patients decreases airway reactivity. One study suggested that this was particularly the case for those with low IgE (a marker of a low T_H2 asthma phenotype), suggesting there may be some heterogeneity in asthma in obesity.There are likely to be two phenotypes of asthma in the obese: one group with early onset disease and asthma complicated by obesity, and a 2nd group with late onset disease with asthma consequent to obesity. Obesity leads to profound changes in airway function, and adaptive and innate immune responses which alter the nature of pre-existing allergic airway disease, and also cause new onset asthmatic disease.     

Associations between central obesity and asthma in children and adolescents: a case–control study

Introduction: Evidence supports a significant yet weak association between high-body weight and asthma in children. However, most studies investigating the obesity–asthma link use Body Mass Index (BMI) to evaluate body fatness. The relationship between body fat distribution and asthma remains largely unknown, especially in children. This pediatric case–control investigation examined associations between central obesity/high-body weight and asthma diagnosis. Methods: Five-hundred and fourteen children (217 physician diagnosed asthma cases and 297 healthy controls) of 5–11 years were recruited. Height, weight and waist circumference were measured. Asthma symptoms, past medical history, personal lifestyle, socioeconomic status, diet and physical activity history were also collected. Results: A higher proportion of children with asthma were centrally obese [(≥90th waist percentile) 15.2 vs. 9.4%, p<0.0001; (≥90th waist-to-height ratio percentile) 39.6 vs. 24.2%, p<0.0001)]. Regression analyses revealed that centrally obese children were more likely to have asthma (high-waist circumference (OR?=?1.99, 95% CI: 1.07-3.68) and high-waist circumference to height ratio (OR?=?2.24, 95% CI: 1.47-3.40), following adjustment for various confounders. Overweight/obese participants (BMI defined) were more likely to be asthmatic [odds ratio (OR)?=?1.52, 95% confidence interval (CI): 1.03-2.70)] when compared to controls. Conclusions: Presence of central obesity and high-body weight (at least overweight) as assessed by waist circumference, waist-to-height ratio, and BMI are associated with asthma diagnosis. More studies are needed, especially in children and adolescents, to confirm these findings and better understand how body fat distribution impacts the obesity–asthma relationship.     

Eotaxin and obesity

CONTEXT: Asthma and obesity incidence is increasing worldwide, and asthma is often more severe in the obese. Eotaxin, a CC chemokine, is important in extrinsic asthma, an inflammatory disorder. OBJECTIVE: Our objective was to examine the relation between eotaxin and obesity. DESIGN: We conducted a comparison study of eotaxin in mice fed high-fat vs. standard chow diet for 26 wk, in obese vs. lean humans, in obese humans before and after 4-6 wk of weight loss, and in sc vs. visceral adipose tissue from patients undergoing bariatric surgery. SETTING: Our clinical study occurred in an outpatient weight loss program. PATIENTS: Patients were obese adults with metabolic syndrome (n = 40) and nine morbidly obese bariatric surgery patients. INTERVENTION: Intervention was a very-low-calorie diet. MAIN OUTCOME MEASURES: We assessed circulating eotaxin and eotaxin mRNA levels in adipose tissue. RESULTS: Serum eotaxin levels were significantly higher in obese mice, and adipose mRNA levels correlated positively with serum eotaxin levels. Adipose tissue explants from obese mice showed increased secretion of eotaxin compared with explants from lean mice. In obese patients, plasma eotaxin levels were significantly higher than in lean controls and significantly reduced after weight loss, and eotaxin mRNA levels were 4.7-fold higher in visceral than sc adipose tissue. CONCLUSIONS: Circulating eotaxin and eotaxin mRNA levels in visceral adipose tissue were increased in obesity in mice and humans. Adipose tissue explants secrete eotaxin, and the stromal/vascular component of adipose tissue seems to be the predominant source of eotaxin. Diet-induced weight loss in humans led to reduction in plasma eotaxin levels, demonstrating that clinical interventions that target obesity can modulate systemic eotaxin levels.     

Pediatric obesity‐related asthma: A prototype of pediatric severe non‐T2 asthma

Childhood obesity contributes to many diseases, including asthma. There is literature to suggest that asthma developing as a consequence of obesity has a nonallergic or non‐T2 phenotype. In this review, obesity‐related asthma is utilized as a prototype of non‐T2 asthma in children to discuss several nonallergic mechanisms that underlie childhood asthma. Obesity‐related asthma is associated with systemic T helper (Th)1 polarization occurring with monocyte activation. These immune responses are mediated by insulin resistance and dyslipidemia, metabolic abnormalities associated with obesity, that are themselves associated with pulmonary function deficits in obese asthmatics. As in other multifactorial diseases, there is both a genetic and an environmental contribution to pediatric obesity‐related asthma. In addition to genetic susceptibility, differential DNA methylation is associated with non‐T2 immune responses in pediatric obesity‐related asthma. Initial investigations into the biology of non‐T2 immune responses have identified the upregulation of genes in the CDC42 pathway. CDC42 is a RhoGTPase that plays a key role in Th cell physiology, including preferential naïve Th cell differentiation to Th1 cells, and cytokine production and exocytosis. Although these novel pathways are promising findings to direct targeted therapy development for obesity‐related asthma to address the disease burden, there is evidence to suggest that dietary interventions, including diet modification, rather than caloric restriction alone, decrease disease burden. Adoption of a diet rich in micronutrients, including carotenoids and 25‐OH cholecalciferol, a vitamin D metabolite, may be beneficial since these are positively correlated with pulmonary function indices, while being protective against metabolic abnormalities associated with the obese asthma phenotype.     

Prevalence and incidence of asthma related to waist circumference and BMI in a Swedish community sample

Both asthma and obesity have become more common in affluent societies during the recent decades and several studies have shown a correlation between the presence of asthma and obesity. In order to further study this association we have investigated a population from a community in southern Sweden, where almost all inhabitants had their body indices measured as part of a study on diabetes at a primary care centre. An asthma unit working with a structured care programme for asthma was available. This organisation enabled us to study whether body mass index and waist circumference was associated with having or developing asthma. There was a significant association between both overweight, increased waist circumference and asthma, P < 0.01. The risk for developing asthma was associated with increased body weight and abdominal circumference, P < 0.05. The increase in asthma morbidity in the overweight subjects was found almost exclusively in the non-atopic asthma patients. This study confirms earlier findings of an increased prevalence of asthma in obese and overweight patients. Increased obesity and especially abdominal obesity is thus a risk factor for asthma, which probably contributes to the high prevalence of asthma in affluent societies.     

The gut microbiota and its relationship to diet and obesity: new insights

Obesity develops from a prolonged imbalance of energy intake and energy expenditure. However, the relatively recent discovery that the composition and function of the gut microbiota impacts on obesity has lead to an explosion of interest in what is now a distinct research field. Here, research relating to the links between the gut microbiota, diet and obesity will be reviewed under five major headings: (1) the gut microbiota of lean and obese animals, (2) the composition of the gut microbiota of lean and obese humans, (3) the impact of diet on the gut microbiota, (4) manipulating the gut microbiota and (5) the mechanisms by which the gut microbiota can impact on weight gain.