leptin and Asthma

Obesity-related asthma is associated with a high disease burden and a poor response to existent asthma therapies, suggesting that it is a distinct asthma phenotype. The proposed mechanisms that contribute to obesity-related asthma include the effects of the mechanical load of obesity, adipokine perturbations, and immune dysregulation. Each of these influences airway smooth muscle function. Mechanical fat load alters airway smooth muscle stretch affecting airway wall geometry, airway smooth muscle contractility, and agonist delivery; weight loss strategies, including medically induced weight loss, counter these effects. Among the metabolic disturbances, insulin resistance and free fatty acid receptor activation influence distinct signaling pathways in the airway smooth muscle downstream of both the M2 muscarinic receptor and the β

Topics: Asthma; Humans; Insulin Resistance; Leptin; Pediatric Obesity; Weight Loss

Respiratory viruses are associated with significant global morbidity and mortality, as well as socioeconomic factors. Certain conditions and patient groups are more susceptible to develop severe viral respiratory tract infections (RTIs).. To summarise the data on deregulated immune pathways that have been associated with increased susceptibility to severe viral RTIs in certain populations. We also describe the commonalities of the defective immune pathways across these susceptible populations that may represent possible targets for future therapeutic or preventative approaches.. We conducted free searches in Medline, Scopus, and Google Scholar for studies focusing on potential mechanisms of immune dysfunction that may be associated with severe viral RTIs in susceptible populations with conditions including pregnancy, obesity, diabetes mellitus, hypertension, cardiovascular disease, asthma, chronic obstructive pulmonary disease (COPD), chronic kidney disease, and extremes of age. We considered preclinical/animal data, original human studies, and reviews.. Innate and adaptive immune responses become quantitatively and qualitatively compromised in aging, obesity, and diabetes mellitus, with the most pronounced changes affecting T cells. Moreover, immune dysregulation by the so-called inflamm-aging results in chronic low-grade inflammation in such conditions. Increased leptin levels affect the immune system particularly in obesity, while leptin dysregulation plays a role in asthma and COPD pathogenesis. Deficient production of interferon (IFN) type I and III in response to rhinovirus contributes to asthma exacerbations. Similar attenuation of IFN production in response to influenza and rhinovirus has been documented in pregnancy. Dampened type I IFN responses have also been found in diet-induced obese mice and in obese individuals.. Immunosenescence and chronic low-grade inflammation accompanying aging and a variety of chronic conditions, such as diabetes, obesity, asthma, COPD, chronic renal disease, and hypertension, contribute to the poor outcomes observed following viral respiratory infections. Commonly affected pathways may represent potential future therapeutic targets.

Topics: Animals; Asthma; Disease Susceptibility; Enterovirus Infections; Humans; Hypertension; Immunity; Inflammation; Interferons; Leptin; Mice; Obesity; Pneumonia; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Rhinovirus

Stunting, which results from chronic malnutrition, is common in children from low- and middle-income countries. Several studies have reported an association between obesity and asthma. However, only a handful of studies have identified stunting as a significant risk factor for wheezing, a symptom of asthma, although the underlying mechanism remains unclear. This article aimed to review possible mechanisms underlying asthma in stunted children. Overall, changes in diet or nutritional status and deficiencies in certain nutrients, such as vitamin D, can increase the risk of developing asthma. Vitamin D deficiency can cause linear growth disorders such as stunting in children, with lower levels of 25(OH)D found in underweight and stunted children. Stunted children show a decreased lean body mass, which affects lung growth and function. Low leptin levels during undernutrition cause a Th1-Th2 imbalance toward Th2, resulting in increased interleukin (IL)-4 cytokine production and total immunoglobulin E (IgE). Studies in stunted underweight children have also found an increase in the proportion of the total number of B cells with low-affinity IgE receptors (CD23+). CD23+ plays an important role in allergen presentation that is facilitated by IgE to T cells and strongly activates allergen-specific T cells and the secretion of Th2-driving cytokines. Stunted children present with low vitamin D and leptin levels, impaired lung growth, decreased lung function, and increased IL-4 and CD23+ levels. All of these factors may be considered consequential in asthma in stunted children.

Topics: Allergens; Asthma; Child; Cytokines; Growth Disorders; Humans; Immunoglobulin E; Interleukin-4; Leptin; Receptors, IgE; Risk Factors; Thinness; Vitamin D; Vitamins

Leptin is an adipokine directly correlated with the proinflammatory obese-associated phenotype. Leptin has been demonstrated to inhibit adipogenesis, promote fat demarcation, promote a chronic inflammatory state, increase insulin sensitivity, and promote angiogenesis. Leptin, a regulator of the immune response, is implicated in the pathology of asthma. Studies involved in the key cell reaction and animal models of asthma have provided vital insights into the proinflammatory role of leptin in asthma. Many studies described the immune cell and related cellular pathways activated by leptin, which are beneficial in asthma development and increasing exacerbations. Subsequent studies relating to animal models support the role of leptin in increasing inflammatory cell infiltration, airway hyperresponsiveness, and inflammatory responses. However, the conclusive effects of leptin in asthma are not well elaborated. In the present study, we explored the general functions and the clinical cohort study supporting the association between leptin and asthma. The main objective of our review is to address the knowns and unknowns of leptin on asthma. In this perspective, the arguments about the different faces of leptin in asthma are provided to picture the potential directions, thus yielding a better understanding of asthma development.

Topics: Adipokines; Animals; Asthma; Cohort Studies; Leptin; Obesity

Asthma and obesity are considered as highly prevalent diseases with a great impact on public health. Obesity has been demonstrated to be an aggravating factor in the pathogenesis of asthma. Adipose tissue secretes proinflammatory cytokines and mediators, including leptin, which may promote the development and severity of asthma in obese patients. This study is a systematic review and a meta-analysis based on the relationship between leptin and asthma during obesity. MEDLINE, Cochrane, EMBASE and CINAHL databases were used. Data heterogeneity was analyzed using Cochran’s Q and treatment effect with the DerSimonian and Laird method. Random effect analyses were carried out to test data sensitivity. Asymmetry was estimated using Begg’s and Egger’s tests. All studies showed significant differences in leptin levels. The effect of the measures (p < 0.001), data sensitivity (p < 0.05) and data asymmetry were statistically significant, as well as tBegg’s test (p = 0.010) and Egge’s test (p < 0.001). Despite the existing limiting factors, the results of this study support the relevant role of leptin in the pathophysiology of asthma in obese subjects. Nevertheless, further studies are needed to obtain better insight in the relationship between leptin and asthma in obesity.

Topics: Adipose Tissue; Asthma; Cytokines; Humans; Leptin; Obesity

Adiponectin is an adipokine associated with the healthy obese phenotype. Adiponectin increases insulin sensitivity and has cardio and vascular protection actions. Studies related to adiponectin, a modulator of the innate and acquired immunity response, have suggested a role of this molecule in asthma. Studies based on various asthma animal models and on the key cells involved in the allergic response have provided important insights about this relation. Some of them indicated protection and others reversed the balance towards negative effects. Many of them described the cellular pathways activated by adiponectin, which are potentially beneficial for asthma prevention or for reduction in the risk of exacerbations. However, conclusive proofs about their efficiency still need to be provided. In this article, we will, briefly, present the general actions of adiponectin and the epidemiological studies supporting the relation with asthma. The main focus of the current review is on the mechanisms of adiponectin and the impact on the pathobiology of asthma. From this perspective, we will provide arguments for and against the positive influence of this molecule in asthma, also indicating the controversies and sketching out the potential directions of research to complete the picture.

Topics: Adipokines; Adiponectin; Asthma; Humans; Insulin Resistance; Leptin; Obesity

There is some evidence which shows that higher levels of serum leptin and lower levels of serum adiponectin are associated with the diagnosis of asthma. This meta-analysis evaluated the association of serum leptin and adiponectin levels with the diagnosis of asthma. We searched the MEDLINE, Cochrane, EMBASE and CINAHL Plus databases up to July 2015. Eligible studies were randomized controlled trials, prospective studies, retrospective studies, case-control studies and cohort studies. 13 studies with 3642 patients were included in the study. The meta-analysis found that in the overall study population, the diagnosis of asthma was associated with higher levels of leptin (pooled standardized difference in means=0.867, 95% CI 0.416 to 1.318, p<0.001) and lower levels of adiponectin (pooled standardized difference in means=-0.371, 95% CI -0.728 to -0.014, p=0.042) in patients with asthma compared with controls. Subgroup analysis found that higher leptin levels were associated with asthma both in adults (standardized difference in means=1.374, 95% CI 0.621 to 2.126, p<0.001) and children (standardized difference in means=0.302, 95% CI 0.010 to 0.594, p=0.042). However, borderline association of adiponectin with asthma was seen in adults (p=0.05), but not in children (p=0.509). Sensitivity analysis indicated that the findings for leptin were robust. Our findings are consistent with higher levels of serum leptin being associated with asthma regardless of age, and low adiponectin levels being associated with asthma in adults only.

Topics: Adiponectin; Adolescent; Adult; Age Distribution; Aged; Asthma; Child; Child, Preschool; Female; Humans; Leptin; Male; Middle Aged; Publication Bias

This review article introduces the research advances in the pathophysiological mechanism of obesity in inducing pediatric bronchial asthma, including the role of leptin in obesity and asthma, the association of plasminogen activator inhibitor-1 with obesity and asthma, the association of adiponectin and interleukins with obesity and asthma, and the influence of neurotransmitter on asthma. In particular, this article introduces the latest research on the inhibition of allergic asthma through targeting at the nociceptor of dorsal root ganglion and blocking the signaling pathway of the nociceptor.

Topics: Asthma; Humans; Leptin; Nerve Growth Factor; Neurotransmitter Agents; Obesity; Plasminogen Activator Inhibitor 1

Obesity is a risk factor for asthma, and obese asthmatics have lower disease control and increased symptom severity. Several putative links have been proposed, including genetics, mechanical restriction of the chest and the intake of corticosteroids. The most consistent evidence, however, comes from studies of cytokines produced by the adipose tissue called adipokines. Adipokine imbalance is associated with both proinflammatory status and asthma. Although reverse causation has been proposed, it is now acknowledged that obesity precedes asthma symptoms. Nevertheless, prenatal origins of both conditions complicate the search for causality. There is a confirmed role of neuro-immune cross-talk mediating obesity-induced asthma, with leptin playing a key role in these processes. Obesity-induced asthma is now considered a distinct asthma phenotype. In fact, it is one of the most important determinants of asthma phenotypes. Two main subphenotypes have been distinguished. The first phenotype, which affects adult women, is characterised by later onset and is more likely to be non-atopic. The childhood obesity-induced asthma phenotype is characterised by primary and predominantly atopic asthma. In obesity-induced asthma, the immune responses are shifted towards T helper (Th) 1 polarisation rather than the typical atopic Th2 immunological profile. Moreover, obese asthmatics might respond differently to environmental triggers. The high cost of treatment of obesity-related asthma, and the burden it causes for the patients and their families call for urgent intervention. Phenotype-specific approaches seem to be crucial for the success of prevention and treatment.

Topics: Adipokines; Adult; Asthma; Female; Humans; Hypersensitivity, Immediate; Leptin; Male; Obesity; Pediatric Obesity

Obesity is a major risk factor for asthma. Likewise, obesity is known to increase disease severity in asthmatic subjects and also to impair the efficacy of first-line treatment medications for asthma, worsening asthma control in obese patients. This concept is in agreement with the current understanding that some asthma phenotypes are not accompanied by detectable inflammation, and may not be ameliorated by classical anti-inflammatory therapy. There are growing evidences suggesting that the obesity-related asthma phenotype does not necessarily involve the classical T(H)2-dependent inflammatory process. Hormones involved in glucose homeostasis and in the pathogeneses of obesity likely directly or indirectly link obesity and asthma through inflammatory and non-inflammatory pathways. Furthermore, the endocrine regulation of the airway-related pre-ganglionic nerves likely contributes to airway hyperreactivity (AHR) in obese states. In this review, we focused our efforts on understanding the mechanism underlying obesity-related asthma by exploring the T(H)2-independent mechanisms leading to this disease.

Topics: Adiponectin; Adipose Tissue; Adiposity; Airway Resistance; Animals; Asthma; Humans; Leptin; Models, Biological; Obesity; Th2 Cells

Asthma is a prevalent respiratory disorder triggered by a variety of inhaled environmental factors, such as allergens, viruses, and pollutants. Asthma is characterized by an elevated activation of the smooth muscle surrounding the airways, as well as a propensity of the airways to narrow excessively in response to a spasmogen (i.e. contractile agonist), a feature called airway hyperresponsiveness. The level of airway smooth muscle (ASM) activation is putatively controlled by mediators released in its vicinity. In asthma, many mediators that affect ASM contractility originate from inflammatory cells that are mobilized into the airways, such as eosinophils. However, mounting evidence indicates that mediators released by remote organs can also influence the level of activation of ASM, as well as its level of responsiveness to spasmogens and relaxant agonists. These remote mediators are transported through circulating blood to act either directly on ASM or indirectly via the nervous system by tuning the level of cholinergic activation of ASM. Indeed, mediators generated from diverse organs, including the adrenals, pancreas, adipose tissue, gonads, heart, intestines, and stomach, affect the contractility of ASM. Together, these results suggest that, apart from a paracrine mode of regulation, ASM is subjected to an endocrine mode of regulation. The results also imply that defects in organs other than the lungs can contribute to asthma symptoms and severity. In this review, I suggest that the endocrine mode of regulation of ASM contractility is overlooked.

Topics: Adaptation, Physiological; Adiponectin; Androgens; Animals; Asthma; Bronchodilator Agents; Dehydroepiandrosterone; Epinephrine; Estrogens; Female; Fibrin; Gastrin-Releasing Peptide; Gastrointestinal Hormones; Glucocorticoids; Humans; Insulin; Leptin; Lung; Male; Muscle Contraction; Muscle, Smooth; Natriuretic Peptides; Progesterone; Respiratory Physiological Phenomena; Respiratory System; Theophylline; Thyroid Hormones; Urokinase-Type Plasminogen Activator

Leptin is an adipocyte-derived hormone, recognized as a critical mediator of the balance between food intake and energy expenditure by signalling through its functional receptor (Ob-Rb) in the hypothalamus. Structurally, leptin belongs to the long-chain helical cytokine family, and is now known to have pleiotropic functions in both innate and adaptive immunity. The presence of the functional leptin receptor in the lung together with evidence of increased airspace leptin levels arising during pulmonary inflammation, suggests an important role for leptin in lung development, respiratory immune responses and eventually pathogenesis of inflammatory respiratory diseases. The purpose of this article is to review our current understanding of leptin and its functional role on the different resident cell types of the lung in health as well as in the context of three major respiratory conditions being chronic obstructive pulmonary disease (COPD), asthma, and pneumonia.

Topics: Adaptive Immunity; Animals; Asthma; Humans; Immunity, Innate; Inflammation; Leptin; Lung; Pneumonia; Pulmonary Disease, Chronic Obstructive

Leptin is a product of the obese (ob) gene and acts through its receptor Ob-R. Leptin is primarily known for its role as a hypothalamic modulator of food, especially in intake, energy balance, fat stores and body weight. Recent studies have shown that leptin may be involved in the development of respiratory diseases such as pulmonary artery hypertension, chronic obstructive pulmonary disease, lung neoplasms and asthma. Therefore, further studies are needed to elucidate the mechanisms accounting for the association between leptin and respiratory diseases, which may lead to the development of novel approaches to the prevention and treatment of these diseases. Here we give an overview of the distribution and physiological function of leptin and ob-R, and summarize the recent progress in the relationship between leptin and respiratory diseases.

Topics: Animals; Asthma; Humans; Leptin; Lung Neoplasms; Pulmonary Disease, Chronic Obstructive; Receptors, Leptin; Respiratory Tract Diseases

Asthma and obesity have been increasing in prevalence internationally among children. Evidence points to an association between these chronic morbidities, suggesting the development of an 'obese asthma' phenotype in childhood. This review summarises the evidence that the proinflammatory environment created by excess adiposity may provide a mechanism leading to obese asthma in children and adolescents. Weight loss studies conducted in children without asthma have demonstrated a reduction in systemic inflammation. However, the impact of weight loss in the obese paediatric population with asthma has not been investigated. The paucity of information highlights the need for high quality randomised controlled trials of weight loss in this population that include assessment of systemic and airway inflammation, and clinical asthma outcomes. This will lead to refinements in management approaches for these patients.

Topics: Adiponectin; Adolescent; Asthma; C-Reactive Protein; Child; Comorbidity; Humans; Inflammation; Leptin; Obesity; Phenotype; Tumor Necrosis Factor-alpha; Weight Loss

Both allergic disorders and obesity keep increasing in industrialized countries. Even though a strong association between obesity and allergy- related diseases has been reported in several studies, no published data show a scientific and firm link in-between the two conditions. In general, obesity and weight gain have been associated with an increased risk of asthma and allergic rhinitis. Asthma, allergic rhinitis and obesity have a common inflammatory pattern that could therefore justify their association. In fact, the chronic inflammation that characterizes the increase in white adipose tissue typically pushes the immune system toward a Th2 pattern. Such a polarization might, consequentially, worsen a pre-existing allergic disease or even stimulate the evolution from a sensitization to a respiratory form of allergy. Several studies have been published on the role of different adipokines on allergic diseases. We focus our review on the role of adipokines on asthma and allergic rhinitis.

Topics: Adipokines; Adiponectin; Asthma; Child; Humans; Hypersensitivity; Leptin; Rhinitis, Allergic, Seasonal

The worldwide pandemic of obesity is creating unique challenges for the diagnosis and treatment of asthma. A wealth of epidemiologic literature has established that whereas asthma can lead to obesity, obesity is a risk factor for asthma, but mechanisms are unclear. This review assesses the current understanding of the relationship between obesity and asthma.. Recent studies are developing a more sophisticated understanding of the possible inflammatory, immunologic, genetic, and mechanical mechanisms underlying the association between obesity and asthma. Obese asthma may be a unique phenotype of asthma, with a more difficult clinical course and altered response to asthma controller therapy. Adipokines such as leptin and adiponectin are thought to be important, but there is new interest in other inflammatory mechanisms related to visceral obesity, insulin resistance, and the metabolic syndrome.. There are still far more questions than answers as to how obesity might cause or worsen asthma. It is clear that weight gain and obesity are particularly troublesome in asthmatics, and clinicians should target these individuals for aggressive intervention. Randomized controlled trials are needed to determine the best treatment approaches for obese asthma, and prospective studies in which both obesity and asthma are well characterized are needed to better understand the underlying mechanisms.

Topics: Adipokines; Asthma; Humans; Insulin Resistance; Leptin; Obesity; Protein Kinase C-alpha

Epidemiological data indicate that obesity is a risk factor for asthma, but the mechanistic basis for this relationship is not established. Here we review data from human subjects and animal models investigating the relationship between obesity and airway hyperresponsiveness, a characteristic feature of asthma. We discuss obesity as a state of chronic systemic inflammation resulting from interactions between adipocytes and adipose tissue macrophages that are recruited to obese adipose tissue. Finally, we focus on the possibility that aspects of this inflammation, particularly obesity-related changes in TNF-alpha, leptin, and adiponectin, may contribute to airway hyperresponsiveness in obesity. Determining how obesity promotes asthma may uncover novel therapeutic strategies that are effective in the obese asthmatic subject.

Topics: Adiponectin; Adipose Tissue; Adult; Animals; Asthma; Bronchial Hyperreactivity; Child; Female; Humans; Inflammation; Inflammation Mediators; Leptin; Male; Obesity; Risk Factors; Tumor Necrosis Factor-alpha

Recent data suggest that obstructive sleep apnea syndrome (OSAS) is an independent risk factor for asthma exacerbations. Neuromechanical reflex bronchoconstriction, gastroesophageal reflux, inflammation (local and systemic), and the indirect effect on dyspnea of OSAS-induced cardiac dysfunction have been suggested as mechanisms that lead to worsening asthma control in patients with concomitant OSAS. Vascular endothelial growth factor-induced airway angiogenesis, leptin-related airway changes, and OSAS-induced weight gain also may play a common mechanistic role linking both disorders. Several studies have confirmed that asthmatic patients are more prone to develop OSAS symptoms than are members of the general population. The common asthmatic features that promote OSAS symptoms are nasal obstruction, a decrease in pharyngeal cross sectional area, and an increase in upper airway collapsibility. Clarifying the nature of the relationship between OSAS and asthma is a critical area with important therapeutic implications.

Topics: Animals; Asthma; Bronchi; Bronchoconstriction; Comorbidity; Dyspnea; Gastroesophageal Reflux; Glottis; Heart Failure; Humans; Inflammation; Laryngeal Nerves; Leptin; Neovascularization, Pathologic; Reflex, Abnormal; Risk Factors; Sleep Apnea, Obstructive; Vagus Nerve; Vascular Endothelial Growth Factor A; Weight Gain

According to the definition (body mass index>97 degrees percentile), overweight and obesity concern 15% of French children. The parallel trends in the increase in asthma and obesity may indicate a potential link between these two conditions. The purpose of this study was to review the epidemiological data indicating a relationship between asthma and obesity, to evaluate the consequences of obesity on asthma and to assess the mechanisms of this association. We conclude with the implications for treatment strategies.

Topics: Adipokines; Adolescent; Adrenal Cortex Hormones; Airway Resistance; Anti-Asthmatic Agents; Asthma; Body Mass Index; Child; Child, Preschool; Comorbidity; Cross-Sectional Studies; Exercise; Humans; Leptin; Longitudinal Studies; Lung Volume Measurements; Obesity; Overweight; Respiratory Hypersensitivity; Risk Factors; Treatment Outcome; Weight Loss

To review the concept of a possible link between asthma and obstructive sleep apnea syndrome (OSAS) and the impact on asthma symptoms of treatment of OSAS with continuous positive airway pressure (CPAP) in patients with both conditions.. The Ovid, MEDLINE, and PubMed databases from 1950 to the present were searched for relevant articles regarding a possible relationship between asthma and OSAS and the effectiveness of CPAP in treating OSAS.. Articles describing pathophysiologic conditions occurring in OSAS that may be linked to asthma pathogenesis were used for this review.. The data suggest that OSAS is an independent risk factor for asthma exacerbations. CPAP has been shown in prospective clinical studies to have a positive impact on asthma outcome in patients with concomitant OSAS. Ameliorative mechanisms of treatment with CPAP include mechanical and neuromechanical effects, gastroesophageal acid reflux suppression, local and systemic anti-inflammatory effects (including suppression of increased serum levels of inflammatory cytokines, chemokines, and vascular endothelial growth factor), cardiac function improvements, leptin level suppression, weight reduction, and sleep restoration.. Asthma and OSAS are increasingly troublesome public health issues. Mounting evidence implicates OSAS as a risk factor for asthma exacerbations, thereby linking these 2 major epidemics. We describe potential mechanisms whereby CPAP, the first line of therapy for OSAS, might modify airway smooth muscle function and asthma control in patients with both disorders. Despite the ever-increasing population of patients with both disorders, large, prospective, randomized controlled studies are necessary to more fully evaluate CPAP and asthma outcomes.

Topics: Asthma; Continuous Positive Airway Pressure; Gastroesophageal Reflux; Heart; Humans; Inflammation; Leptin; Obesity; Respiratory Mechanics; Risk Factors; Sleep; Sleep Apnea, Obstructive

The prevalence of obesity has considerably increased during the past thirty years. Possible consequences of obesity on respiratory physiology include a restrictive disorder, changes in ventilatory mechanics and an alteration of respiratory drive. Apart from the well established relation between obesity and obstructive sleep apnea-hypopnea syndrome, obesity is associated with two other respiratory disorders. On one hand, epidemiological and animal data suggest a causal relationship between obesity and asthma. On the other hand, morbid obesity is associated, through an alteration of the respiratory drive involving leptin, with a diurnal and nocturnal alveolar hypoventilation defining the obesity-hypoventilation syndrome. These data emphasize the necessity for the medical practitioner to investigate any respiratory symptomatology in obese patients.

Topics: Animals; Asthma; Body Mass Index; Humans; Leptin; Obesity; Obesity Hypoventilation Syndrome; Prevalence; Respiratory Tract Diseases; Sleep Apnea, Obstructive; Switzerland

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.

Topics: Adolescent; Adult; Airway Resistance; Asthma; Child; Chromosome Mapping; Cytokines; Diet; Disease Susceptibility; Female; Hormones; Humans; Inflammation; Leptin; Male; Menarche; Motor Activity; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Respiratory Mechanics; Sex Factors; Weight Loss

Epidemiological data indicate that obesity is a risk factor for incident asthma, and that obesity is also associated with increased asthma severity. Importantly, obesity antedates asthma. The observations that weight loss improves asthma and that obese mice have innate airway hyperresponsiveness and increased responses to asthma triggers also support a relationship between obesity and asthma. The basis for this relationship is unknown, but might be the result of common etiologies, comorbidities, effects of obesity on lung volume or adipokines. Understanding the mechanistic basis for the relationship between obesity and asthma could lead to new therapeutic strategies for treatment of this susceptible population.

Topics: Adiponectin; Adipose Tissue; Animals; Asthma; Body Weight; Comorbidity; Humans; Leptin; Mice; Mice, Obese; Obesity; Respiratory Function Tests; Risk Factors; Tumor Necrosis Factor-alpha

Asthma and obesity are prevalent disorders, each with a significant public health impact, and a large and growing body of literature suggests an association between the two. The systemic inflammatory milieu in obesity leads to metabolic and cardiovascular complications, but whether this environment alters asthma risk or phenotype is not yet known. Animal experiments have evaluated the effects of leptin and obesity on airway inflammation in response to both allergic and nonallergic exposures and suggest that airway inflammatory response is enhanced by both endogenous and exogenous leptin. Cross-sectional and prospective cohort studies of humans have shown a modest overall increase in asthma incidence and prevalence in the obese, although body mass index does not appear be a significant modifier of asthma severity. Studying the obesity-asthma relationship in large cohorts, in which self-reports are frequently used to ascertain the diagnosis of asthma, has been complicated by alterations in pulmonary physiology caused by obesity, which may lead to dyspnea or other respiratory symptoms but do not fulfill accepted physiologic criteria for asthma. Recent investigations toward elucidating a shared genetic basis for these two disorders have identified polymorphisms in specific regions of chromosomes 5q, 6p, 11q13, and 12q, each of which contains one or more genes encoding receptors relevant to asthma, inflammation, and metabolic disorders, including the beta(2)-adrenergic receptor gene ADRB2 and the glucocorticoid receptor gene NR3C1. Further research is warranted to synthesize these disparate observations into a cohesive understanding of the relationship between obesity and asthma.

Topics: Adipocytes; Animals; Asthma; Body Mass Index; Comorbidity; Compliance; Cytokines; Gonadal Steroid Hormones; Humans; Inflammation; Leptin; Obesity; Polymorphism, Genetic; Respiratory Hypersensitivity; Sex Factors

Both asthma and obesity are large and growing public health issues. Mounting evidence now implicates obesity as a major risk factor for asthma, thus linking these 2 major epidemics. Moreover, both in human subjects and in mice, obesity appears to predispose toward airway hyperresponsiveness. This review describes potential mechanisms whereby obesity might modify airway smooth muscle function to explain these observations. These mechanisms include both static and dynamic mechanical factors attributable to decreases in functional residual capacity and decreases in tidal volume that are observed in the obese. They include also obesity-related changes in lung development, chronic systemic inflammation (including increased serum levels of inflammatory cytokines and chemokines), and adipocyte-derived factors, including leptin, adiponectin, and plasminogen activator inhibitor.

Topics: Adiponectin; Animals; Asthma; Cytokines; Functional Residual Capacity; Humans; Inflammation; Intercellular Signaling Peptides and Proteins; Leptin; Muscle, Smooth; Obesity; Plasminogen Activators; Respiratory System

Oral corticosteroids (OCS) are an efficacious treatment for asthma exacerbations, yet risk of adverse effects may decrease patient adherence to therapy. In particular, changes in appetite and dietary intake, which lead to weight gain and changes in body composition, are considered undesirable.. To determine whether 10-day OCS therapy in adults with asthma causes changes in leptin, appetite, dietary intake, body weight and body composition.. Double-blinded, placebo-controlled randomized cross-over trial of 10 days prednisolone (50 mg) in adults with stable asthma (n = 55) (ACTRN12611000562976). Pre- and post-assessment included spirometry, body weight, body composition measured by dual-energy X-ray absorptiometry and bioelectrical impedance analysis, appetite measured using a validated visual analogue scale (VAS) and dietary intake assessed using 4-day food records. Leptin was measured as a biomarker of appetite and eosinophils as an adherence biomarker. Outcomes were analysed by generalized linear mixed models.. Subject adherence was confirmed by a significant decrease in blood eosinophils (× 10(9) /L) following prednisolone compared to placebo [Coef. -0.29, 95% CI: (-0.39, -0.19) P < 0.001]. There was no difference in serum leptin (ng/mL) [Coef. 0.13, 95% CI: (-3.47, 3.72) P = 0.945] or appetite measured by VAS (mm) [Coef. -4.93, 95% CI: (-13.64, 3.79) P = 0.267] following prednisolone vs. placebo. There was no difference in dietary intake (kJ/day) [Coef. 255, 95% CI: (-380, 891) P = 0.431], body weight (kg) [Coef. -0.38, 95% CI: (-0.81, 0.05) P = 0.083] or body fat (%) [Coef. -0.31, 95% CI: (-0.81, 0.20) P = 0.230]. Symptoms including sleep and gastrointestinal disturbance were reported significantly more often during prednisolone vs. placebo.. Short-term OCS in stable asthma did not induce significant changes in appetite, dietary intake, body weight or composition, although other adverse effects may require medical management. This evidence may assist in increasing medication adherence of asthmatics prescribed OCS for exacerbations.

Topics: Administration, Oral; Adrenal Cortex Hormones; Adult; Aged; Appetite; Asthma; Australia; Body Composition; Body Weight; Body Weights and Measures; Cross-Over Studies; Eosinophils; Female; Humans; Leptin; Leukocyte Count; Male; Middle Aged; Surveys and Questionnaires; Young Adult

Cross-sectional and longitudinal reports show that obese adults have more asthma than non-obese adults. A proposed mechanism is via effects of adipokines (leptin and adiponectin) on the immune system.. We wished to measure the associations of asthma and other atopic diseases with serum adipokine levels and to find whether the associations with asthma were strong enough to rule out the possibility that they are secondary to the association of fatness measures with asthma.. The Global Asthma and Allergy Network of Excellence (GA(2) LEN) clinical follow-up survey is a clinical survey, embedded in a larger multi-centre cross-sectional postal survey, involving, with a case/control design, enrichment of the sample with subjects with asthma and chronic rhinosinusitis (CRS). We recorded serum leptin or adiponectin in 845 men and 1110 women in 15 centres and also anthropometric measures of fatness including body mass index and waist/hip ratio, current asthma, and specific skin prick and IgE sensitisation. We used inverse sampling-probability-weighted rank and regression statistics to measure population associations of disease outcomes with adipokines in males and females, adjusting for confounders (area, age, smoking history, and number of elder siblings) and also mutually adjusting associations with adipokines and fatness measures.. One thousand nine hundred and fifty-five subjects aged 16-77 years had information on leptin or adiponectin levels. Leptin and leptin/adiponectin ratio were positively associated with the level of asthma, especially in females (Somers' D of leptin by asthma score, 0.20; 95% CI, 0.08-0.30; P = 0.00079). These associations were attenuated after adjusting for confounders and became non-significant after additionally adjusting for fatness measures and multiple comparisons.. Asthma levels are positively associated with serum leptin. However, we cannot rule out the possibility that this association is secondary to associations of both with fatness measures.

Topics: Adiponectin; Adolescent; Adult; Aged; Asthma; Cross-Sectional Studies; Female; Follow-Up Studies; Humans; Leptin; Male; Middle Aged; Obesity; Rhinitis, Allergic, Perennial; Sex Factors; Skin Tests

To assess the effects of weight loss on adipokines, asthma-related symptoms, exercise-induced bronchospasm (EIB) and lung function, and to evaluate the role of leptin and adiponectin levels on lung function after treatment in obese adolescents.. 84 postpubertal obese adolescents were enrolled and distributed in quartiles according to weight loss (low (<2.5 kg), low to moderate (>2.5 and <8 kg), moderate (<8 and <14 kg) and massive (<14 kg)). Body composition was measured by plethysmography, and visceral and subcutaneous fat were detected by ultrasound. Serum levels of adiponectin and leptin were analyzed. Lung function, asthma and EIB were evaluated according to the American Thoracic Society criteria. Patients were submitted to 1 year of interdisciplinary intervention consisting of physiotherapy, medical, nutritional, exercise, and psychological therapy.. After treatment the moderate and massive weight loss promoted an increase in adiponectin and adiponectin/leptin (A/L) ratio as well as a decrease in leptin levels and a reduction in EIB frequency and asthma-related symptoms. Furthermore, the reduction in leptin levels was a predictor factor to improvement in lung function.. Interdisciplinary therapy was able to decrease EIB and asthma-related symptoms and to improve pro/anti-inflammatory adipokines. Additionally, the leptin concentration was a predictor factor to explain changes in lung function.

Topics: Adiponectin; Adolescent; Asthma; Asthma, Exercise-Induced; Diet; Exercise; Female; Humans; Leptin; Lung; Male; Obesity; Physical Therapy Modalities; Psychotherapy; Weight Loss; Weight Reduction Programs

The relationship between obesity and asthma remains inadequately defined. Studies about how obesity affects asthma control and lung function show conflicting results. Additional focus on the effect of age as a modifier may make clearer the interaction between obesity and asthma phenotype. We sought to use a diverse and well-phenotyped cohort of asthmatic patients to determine how age impacts the relationship between obesity and spirometry, peak flow variability, airflow perception, and asthma control.. The characteristics of 490 patients with mild persistent asthma taken from 2,794 study visits from a prospective trial studying strategies of step-down therapy were included in this post hoc analysis. A longitudinal mixed-effect model was used to determine if age affects the relationship between obesity and asthma characteristics, including spirometry, asthma control, airway pH, and perception of airflow changes.. The effect of obesity on asthma outcomes changes with age and gender. Obese 6- to 11-year-old children had the largest reduction in lung function but reported relatively fewer asthma symptoms than did similar nonobese asthmatics. Obese 12- to 17-year-olds showed a trend toward greater airflow obstruction and asthma symptoms compared with nonobese asthmatics. Adults in general displayed few obesity-related alterations in asthma phenotype. Female gender among 12- to 17- and 18- to 44-year-olds was associated with greater obesity-related asthma impairment.. Age is a significant effect modifier on the relationship between obesity and asthma phenotype. With increasing age, the influence of obesity on the asthma phenotype is generally reduced. The asthma phenotype may be most impacted by obesity among children and women.. ClinicalTrials.gov; No.: NCT00156819; URL: www.clinicaltrials.gov.

Topics: Adolescent; Adult; Age Factors; Aged; Aging; Anti-Asthmatic Agents; Asthma; Body Mass Index; Child; Female; Forced Expiratory Volume; Humans; Leptin; Male; Middle Aged; Obesity; Phenotype; Predictive Value of Tests; Prognosis; Reference Values; Respiratory Function Tests; Risk Assessment; Severity of Illness Index; Sex Factors; Total Lung Capacity; Treatment Outcome; Young Adult

Adipokines are involved in the regulation of many inflammatory processes and are present at very high concentrations in cord blood of term infants.. We analysed data of a large prospective birth cohort study to examine whether adiponectin and leptin concentration in cord blood are determinants of wheezing disorders in children within the first 2 years of life.. Seven hundred and forty mothers and their newborns were included in this analysis. Adiponectin and leptin concentrations were measured in cord blood. The cumulative incidence of physician-reported asthma or obstructive bronchitis was recorded during a 2-year follow-up.. During the first 2 years of life, asthma or obstructive bronchitis was reported by the caring paediatricians for 157 (19.6%) of the children. We found a strong interaction of cord blood adiponectin and history of atopic disease in the mother with respect to the risk of physician-reported asthma or obstructive bronchitis (P=0.006). Compared with children with cord blood levels in the middle quintile (reference category), the odds ratios for physician-reported asthma or obstructive bronchitis in the bottom quintile and top quintile were 0.14 [95% confidence interval (CI) 0.02-0.90] and 2.12 (95% CI 0.67-6.66), respectively (P for trend=0.0003), among children of mothers with a history of atopy. This association was independent of other established risk factors. Leptin levels in cord blood were not associated with risk of asthma or obstructive bronchitis.. In children of mothers with a history of atopy, concentrations of adiponectin in cord blood could play an important role in determining risk of wheezing disorders in early childhood.

Topics: Adiponectin; Adult; Asthma; Bronchitis; Child, Preschool; Female; Fetal Blood; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Leptin; Male; Predictive Value of Tests; Prospective Studies; Respiratory Sounds; Risk Factors

Serum leptin levels exhibit a marked diurnal variation in children. The aim of the present study was to investigate whether the timing of administration of exogenous glucocorticoids, which have been found to increase serum leptin, affects the diurnal rhythm. Four girls and four boys aged 10.6 to 15.8 (mean 13.2) years with asthma were studied. The design was an open 2-period cross-over trial with a 1-day run in, two 4-day periods of prednisolone 5 mg in the morning or in the evening, with a 3-week washout in between treatment periods. During run in and on the last day of the prednisolone periods a fasting blood sample was drawn at 08.00 h, and thereafter samples were obtained every 2 h throughout the day until 08.00 h the next morning. Serum leptin was measured by a specific radioimmunoassay. During all periods, leptin levels were low during the day with a nadir at 10.00 h (run-in [mean +/- SEM]: 3.9+/-1.28; morning prednisolone: 5.2+/-1.58; evening prednisolone: 5.7+/-2.02 microg/l). Increases in leptin levels were detected from 20.00 h with zeniths at 24.00 h (run in: 7.2+/-1.86; evening prednisolone: 9.2+/-2.36 microg/l) and 02.00 h (morning prednisolone: 9.4+/-1.78 microg/l) (F = 115.5; p <0.01). As compared to run in, leptin levels were increased at all time points during prednisolone treatment in the morning (F = 16.0, p = 0.01) and in the evening (F = 12.6, p = 0.01). No statistically significant differences were found in leptin levels during prednisolone in the morning or in the evening (F = 0.44, p = 0.53). Therefore, the timing of administration of exogenous glucocorticoids does not affect diurnal leptin rhythms in children.

Topics: Adolescent; Anti-Inflammatory Agents; Asthma; Child; Circadian Rhythm; Cross-Over Studies; Female; Humans; Leptin; Male; Prednisolone; Puberty

Leptin, a 167-amino-acid peptide, is a recently discovered hormone which is believed to play a major role in the regulation of body weight. Systemic administration of exogenous glucocorticoids has been found to increase circulating leptin levels. In this study, we aimed to assess serum leptin in children with asthma treated with inhaled budesonide 800 micrograms day-1. Ten boys and three girls with asthma, all adolescents aged from 12.9 to 16.6 years, were studied in a randomized double-blind two-period cross-over trial with 4-week treatment periods and a 1-week wash out. Placebo was given during one period and 800 micrograms budesonide during the other via a 750 ml volume spacer (Nebuhaler, Astra Draco, Lund, Sweden). On the last day of the placebo and budesonide periods blood samples were taken and serum leptin was measured by a specific radioimmunoassay. The difference in mean (SEM) leptin concentration between the budesonide and placebo period was 0.2 (0.4) microgram l-1 (P = 0.71; t = -0.4; df = 12, 95% confidence interval -0.9-0.7 microgram l-1). Inhaled budesonide 800 micrograms per day from a Nebuhaler does not influence circulating leptin levels, suggesting that regulation of body weight is unaffected.

Topics: Administration, Topical; Adolescent; Anti-Inflammatory Agents; Appetite; Asthma; Biomarkers; Body Weight; Budesonide; Child; Cross-Over Studies; Double-Blind Method; Female; Glucocorticoids; Humans; Leptin; Male; Proteins

Asthma and obesity are both inflammatory complications of pregnancy and when combined contribute to an increased risk of uncontrolled asthma during pregnancy and poor perinatal outcomes. Our previous work has identified the presence of maternal asthma is associated with a proinflammatory milieu in the placenta and reduced fetal growth. The current study was designed to determine the relationships between immunomodulatory metabolic pathways and inflammation and establish whether these pathways are associated with uncontrolled asthma in obese pregnant women.. Fifty-three obese (BMI >30) pregnant women were recruited prospectively. Participants were classified as having no asthma, controlled asthma, and uncontrolled asthma based on a doctor diagnosis and assessment using the Asthma Control Questionnaire (ACQ). Circulating plasma concentrations of metabolic hormones leptin, adiponectin, insulin, glucose, and extracellular vesicle (EVs) associated cytokines were measured at 18- and 36-weeks gestation.. Concentrations of metabolic and inflammatory markers among obese participants with or without asthma were not significantly different throughout gestation. However total adiponectin concentrations increased as gestation progressed in obese, non-asthmatic women but did not increase in women with asthma. Plasma adiponectin and leptin levels in women with uncontrolled asthma were positively correlated with EV inflammatory markers including GM-CSF, IL-6, TNFα and IFNγ protein.. This study demonstrated that most metabolic markers remain unchanged with the presence and severity of asthma in obese pregnant women. However, differences in the associations between metabolic and inflammatory pathways were observed in women with asthma and may be one of the mechanisms contributing to uncontrolled asthma in obese pregnant women.

Topics: Adiponectin; Asthma; Female; Humans; Leptin; Obesity; Pregnancy; Pregnancy Complications

More than 50% of people with asthma in the United States are obese, and obesity often worsens symptoms of allergic asthma and impairs response to treatment. Based on previously established roles of the epithelial NADPH oxidase DUOX1 in allergic airway inflammation, we addressed the potential involvement of DUOX1 in altered allergic inflammation in the context of obesity. Intranasal house dust mite (HDM) allergen challenge of subjects with allergic asthma induced rapid secretion of IL-33, then IL-13, into the nasal lumen, responses that were significantly enhanced in obese asthmatic subjects (BMI >30). Induction of diet-induced obesity (DIO) in mice by high-fat diet (HFD) feeding similarly enhanced acute airway responses to intranasal HDM challenge, particularly with respect to secretion of IL-33 and type 2/type 3 cytokines, and this was associated with enhanced epithelial DUOX1 expression and was avoided in DUOX1-deficient mice. DIO also enhanced DUOX1-dependent features of chronic HDM-induced allergic inflammation. Although DUOX1 did not affect overall weight gain by HFD feeding, it contributed to glucose intolerance, suggesting a role in glucose metabolism. However, glucose intolerance induced by short-term HFD feeding, in the absence of adiposity, was not sufficient to alter HDM-induced acute airway responses. DIO was associated with enhanced presence of the adipokine leptin in the airways, and leptin enhanced DUOX1-dependent IL-13 and mucin production in airway epithelial cells. In conclusion, augmented inflammatory airway responses to HDM in obesity are associated with increases in airway epithelial DUOX1, and by increased airway epithelial leptin signaling.

Topics: Allergens; Animals; Asthma; Diet; Disease Models, Animal; Dual Oxidases; Glucose Intolerance; Inflammation; Interleukin-13; Interleukin-33; Leptin; Mice; Obesity; Pyroglyphidae

Children hospitalized for bronchiolitis have increased risk of asthma and low lung function persisting into adulthood, but the underlying mechanisms are poorly understood. Body mass index (BMI) and adipokines are associated with respiratory morbidity. We aimed to investigate if associations between BMI and adipokines and the outcomes asthma, atopy, and lung function differed between young adults previously hospitalized for bronchiolitis and control subjects.. This sub study of a historical cohort enrolled 185 young adults previously hospitalized for bronchiolitis and 146 matched control subjects. Exposures (BMI and the adipokines: adiponectin, leptin, resistin, and ghrelin) and outcomes (asthma, atopy, and lung function) were measured cross-sectionally at 17-20 years of age. Associations were tested in regression models, and differences between the post-bronchiolitis- and control group were tested by including interaction terms.. BMI was associated with asthma and lung function, but we did not find that the associations differed between the post-bronchiolitis- and control group. We also found some associations between adipokines and outcomes, but only associations between adiponectin and forced vital capacity (FVC) and between resistin and current asthma differed between the groups (p-value interaction term 0.027 and 0.040 respectively). Adiponectin tended to be positively associated with FVC in the post-bronchiolitis group, with an opposite tendency in the control group. Resistin was positively associated with current asthma only in the control group.. The increased prevalence of asthma and impaired lung function observed in young adults previously hospitalized for bronchiolitis do not seem to be related to growth and fat metabolism.

Topics: Adipokines; Adiponectin; Asthma; Body Mass Index; Bronchiolitis; Humans; Leptin; Lung; Resistin; Respiratory Function Tests; Young Adult

Topics: Asian; Asthma; Black People; Female; Humans; Leptin; Male; Prognosis; White People

Asthma is a chronic inflammatory disorder of the airways with diverse overlapping pathologies and phenotypes contributing to a significant heterogeneity in clinical manifestations. Obesity may modify asthma risk, phenotype, and prognosis. A suggested mechanism linking obesity and asthma is through systemic inflammation. Adipokines secreted by adipose tissue were suggested to provide a link between obesity and asthma.. To have an understanding for the contribution of adiponectin, resistin and MCP-1 to development of distinct asthma phenotype in overweight/obese children through assessment of their serum level and correlation to pulmonary function tests.. The study included 29 normal weight asthmatics, 23 overweight/obese asthmatic children and 30 controls. All cases were subjected to detailed history taking, thorough examination and pulmonary function tests. Serum adiponectin, resistin, MCP-1 and IgE were assessed to all recruited subjects.. This work could suggest that adiponectin may play a role in overweight/obese asthma phenotype where it is possible to have a dual action (pro & anti- inflammatory). It seems that resistin had no role in asthma pathogenesis.

Topics: Adiponectin; Asthma; Body Mass Index; Child; Humans; Leptin; Monocytes; Overweight; Pediatric Obesity; Phenotype; Resistin

Obesity-related asthma is a kind of nonallergic asthma with excessive neutrophil infiltration in the airways. However, the underlying mechanisms have been poorly elucidated. Among the adipokines related to obesity, leptin is related to the inflammatory response. However, little is understood about how leptin acts on the leptin receptor (obR) in neutrophilic airway inflammation in obesity-associated asthma. We explored the inflammatory effects of leptin/obR signaling in an obesity-related neutrophilic airway inflammation mouse model.. We established a neutrophilic airway inflammation mouse model using lipopolysaccharide (LPS)/ovalbumin (OVA) sensitization and OVA challenge (LPS + OVA/OVA) in lean, obese, or db/db (obR deficiency) female mice. Histopathological, bronchoalveolar lavage fluid (BALF) inflammatory cell, and lung inflammatory cytokine analyses were used to analyze airway inflammation severity. Western blotting, flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay (ELISA) were used to evaluate the underlying mechanisms. In vitro bone marrow-derived macrophage (BMDM) and bone marrow-derived neutrophil experiments were performed.. We found that the serum leptin level was higher in obese than in lean female mice. Compared to LPS/OVA + OVA-treated lean female mice, LPS/OVA + OVA-treated obese female mice had higher peribronchial inflammation levels, neutrophil counts, Th1/Th17-related inflammatory cytokine levels, M1 macrophage polarization levels, and long isoform obR activation, which could be decreased by the obR blockade (Allo-Aca) or obR deficiency, suggesting a critical role of leptin/obR signaling in the pathogenesis of obesity-related neutrophilic airway inflammation in female mice. In in vitro experiments, leptin synergized with LPS/IFN-γ to promote the phosphorylation of the long isoform obR and JNK/STAT3/AKT signaling pathway members to increase M1 macrophage polarization, which was reversed by Allo-Aca. Moreover, leptin/obR-mediated M1 macrophage activity significantly elevated CXCL2 production and neutrophil recruitment by regulating the JNK/STAT3/AKT pathways. In clinical studies, obese patients with asthma had higher serum leptin levels and M1 macrophage polarization levels in induced sputum than non-obese patients with asthma. Serum leptin levels were positively correlated with M1 macrophage polarization levels in patients with asthma.. Our results demonstrate leptin/obR signaling plays an important role in the pathogenesis of obesity-related neutrophilic airway inflammation in females by promoting M1 macrophage polarization.

Topics: Animals; Asthma; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Female; Inflammation; Leptin; Lipopolysaccharides; Lung; Macrophages; Mice; Mice, Inbred BALB C; Obesity; Ovalbumin; Proto-Oncogene Proteins c-akt; Receptors, Leptin; Signal Transduction

Obesity complicates the clinical manifestations of asthma in children. However, few studies have examined longitudinal outcomes or markers of systemic inflammation in obese asthmatic children.. We hypothesized that obese children with asthma would have: (1) poorer clinical outcomes over 12 months, (2) decreased responsiveness to systemic corticosteroid administration, (3) greater markers of systemic inflammation, and (4) unique amino acid metabolites associated with oxidative stress.. Children 6 to 17 years of age (lean, N = 257; overweight, N = 99; obese, N = 138) completed a baseline visit and follow-up visit at 12 months. Outcome measures included asthma control, quality of life, lung function, and exacerbations. A subset received intramuscular triamcinolone and were re-evaluated at 7(+7) days. Leptin, adiponectin, C-reactive protein, total cholesterol, interleukin (IL)-1β, IL-6, IL-17, interferon gamma, tumor necrosis factor alpha, monocyte-chemoattractant protein-1, and amino acid metabolites were also quantified in plasma as potential biomarkers of outcomes in obese children.. Obesity was associated with more symptoms, poorer quality life, and more exacerbations that persisted over 1 year despite greater medication requirements. Obese children also had minimal clinical improvement in asthma control and lung function after intramuscular triamcinolone. Leptin, C-reactive protein, and amino acid metabolites associated with glutathione synthesis and oxidative stress differed in obese children. Within the obese group, lower concentrations of arginine-related metabolites also distinguished uncontrolled from controlled asthma at 12 months.. Obesity is associated with poorer asthma outcomes and unique systemic inflammatory features that may not be adequately modified with conventional asthma therapies. Novel approaches may be needed given increased symptoms and unique inflammation and oxidative stress in obese children with asthma.

Topics: Amino Acids; Asthma; Biomarkers; C-Reactive Protein; Child; Humans; Inflammation; Leptin; Pediatric Obesity; Quality of Life; Triamcinolone

Asthma patients with comorbid obesity exhibit increased disease severity, in part, due to airway remodeling, which is also observed in mouse models of asthma and obesity. A mediator of remodeling that is increased in obesity is leptin. We hypothesized that in a mouse model of allergic airways disease, mice receiving exogenous leptin would display increased airway inflammation and fibrosis.. Five-week-old male and female C57BL/6J mice were challenged with intranasal house dust mite (HDM) allergen or saline 5 days per week for 6 weeks (n = 6-9 per sex, per group). Following each HDM exposure, mice received subcutaneous recombinant human leptin or saline. At 48 h after the final HDM challenge, lung mechanics were evaluated and the mice were sacrificed. Bronchoalveolar lavage was performed and differential cell counts were determined. Lung tissue was stained with Masson's trichrome, periodic acid-Schiff, and hematoxylin and eosin stains. Mouse lung fibroblasts were cultured, and whole lung mRNA was isolated.. Leptin did not affect mouse body weight, but HDM+leptin increased baseline blood glucose. In mixed-sex groups, leptin increased mouse lung fibroblast invasiveness and increased lung Col1a1 mRNA expression. Total lung resistance and tissue damping were increased with HDM+leptin treatment, but not leptin or HDM alone. Female mice exhibited enhanced airway responsiveness to methacholine with HDM+leptin treatment, while leptin alone decreased total respiratory system resistance in male mice.. In HDM-induced allergic airways disease, administration of exogenous leptin to mice enhanced lung resistance and increased markers of fibrosis, with differing effects between males and females.

Topics: Allergens; Animals; Asthma; Biomarkers; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Female; Fibrosis; Humans; Hypersensitivity; Leptin; Lung; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Obesity; Pulmonary Disease, Chronic Obstructive; Pulmonary Fibrosis; Pyroglyphidae; RNA, Messenger

(1) Background: The relationship between obesity and asthma is still uncertain. This study aimed to investigate the effect of overweight/obesity on the pulmonary function of patients with new-onset pediatric asthma and explore the possible causative factors related to concomitant obesity and asthma. (2) Methods: Patients aged 5 to 17 years old with newly diagnosed mild to moderate asthma were recruited from June 2018 to May 2019, from a respiratory clinic in Shanghai, China. Participants were categorized into three groups: normal weight, overweight, and obese asthma. A family history of atopy and patients' personal allergic diseases were recorded. Pulmonary function, fractional exhaled nitric oxide (FeNO), eosinophils, serum-specific immunoglobulins E (sIgE), serum total IgE (tIgE), and serum inflammatory biomarkers (adiponectin, leptin, Type 1 helper T, and Type 2 helper T cytokines) were tested in all participants. (3) Results: A total of 407 asthma patients (197 normal weight, 92 overweight, and 118 obese) were enrolled. There was a reduction in forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC), FEV1/FVC%, and FEF25-75% in the overweight/obese groups. No difference was found between the study groups in the main allergy characteristics. Leptin levels were higher while adiponectin was lower in asthmatics with obesity. Higher levels of IL-16 were found in overweight/obese asthmatic individuals than in normal-weight individuals. (4) Conclusions: Obesity may have an effect on impaired pulmonary function. While atopic inflammation plays an important role in the onset of asthma, nonatopic inflammation (including leptin and adiponectin) increases the severity of asthma in overweight/obese patients. The significance of different levels of IL-16 between groups needs to be further studied.

Topics: Adiponectin; Adiposity; Adolescent; Asthma; Biomarkers; Child; Child, Preschool; China; Forced Expiratory Volume; Humans; Hypersensitivity, Immediate; Inflammation; Interleukin-16; Leptin; Obesity; Overweight

Adult-onset asthma (AOA) is usually more severe compared to childhood onset asthma (CoA). Given the increasing evidence that AoA is associated with obesity, we investigated the relationship of other related metabolic comorbid conditions with AoA compared to CoA.. This cross-sectional study compared the metabolic syndrome and lipid derived inflammatory markers in patients with AoA, CoA and age- and sex-matched control subjects without asthma. Participants were asthma patients visiting the outpatient clinic of two teaching hospitals in Rotterdam, The Netherlands. All participants underwent lung function tests, blood tests and physical activity tracking. AoA was defined as asthma age of onset after the age of 18 years. Metabolic syndrome was defined according to the international joint interim statement criteria.. AoA was associated with the metabolic syndrome and its related pro-inflammatory endocrine and cytokine status. This may suggest adipose tissue derived inflammatory markers play a role in the pathophysiology of AoA.

Topics: Adiponectin; Adolescent; Adult; Age of Onset; Asthma; Biomarkers; Body Mass Index; Child; Cross-Sectional Studies; Humans; Interleukin-6; Leptin; Male; Metabolic Syndrome; Middle Aged; Respiratory Function Tests

The aim of this study was to assess the diaphragm kinetics, respiratory function, and serum dosage of leptin and inflammatory cytokines (IL-6 and TNF-α) in three clinical groups: obese, asthmatic, and healthy.. This is a clinical exploratory study performed on 73 youths (12-24 years of age, 42.5% male) allocated into three groups: obesity (OG, n=33), body mass index (BMIz-score) ≥ +2, asthmatic (AG, n=26) controlled mild asthmatics, classified by GINA, and Healthy Control Group (CG, n=14). The participants were subjected to diaphragmatic ultrasound, spirometry, maximal respiratory pressure, serum leptin levels, and IL-6 and TNF-α whole blood cell culture levels.. Diaphragm thickness was higher in OG in comparison to AG and CG (2.0±0.4 vs 1.7±0.5 and 1.6±0.2, both with p<0.05). Maximal voluntary ventilation (MVV) was significantly lower in OG and AG in relation to the CG (82.8±21.4 and 72.5±21.2 vs 102.8±27.3, both with p<0.05). OG has the highest leptin rate among the groups (with the other two groups had p<0.05). All groups had similar TNF-α and IL-6 levels.. The muscular hypertrophy found in the diaphragm of the obese individuals can be justified by the increase in respiratory work imposed by the chronic condition of the disease. Such increase in thickness did not occur in controlled mild asthmatics. The IL-6 and TNF-α markers detected no evidence of muscle inflammation, even though leptin was expected to be altered in obese individuals. Both obese and asthmatic patients had lower pulmonary resistance than the healthy ones.. O objetivo deste estudo foi avaliar a cinética diafragmática, a função respiratória e a dosagem sérica de leptina e citocinas inflamatórias (IL-6 e TNF-α) em três grupos clínicos: obeso, asmático e saudável.. Estudo clínico-exploratório realizado com 73 jovens (12-24 anos, sendo 42,5% do sexo masculino) alocados em três grupos: obesidade (GO, n = 33), índice de massa corporal (IMC z-score) ≥ + 2 e asmáticos leves controlados (GA, n = 26), classificados pela GINA, e grupo controle saudável (GC, n = 14). Os participantes foram submetidos à ultrassonografia diafragmática, espirometria, pressão respiratória máxima, níveis séricos de leptina e níveis de IL-6 e TNF-α em hemocultura total.. A espessura do diafragma foi maior no GO em comparação ao GA e GC (2,0 ± 0,4 vs 1,7 ± 0,5 e 1,6 ± 0,2, respectivamente, com p < 0,05). A ventilação voluntária máxima (VVM) foi significativamente menor no GO e GA em relação ao GC (82,8 ± 21,4 e 72,5 ± 21,2 vs 102,8 ± 27,3, respectivamente, com p < 0,05). O GO tem a maior taxa de leptina entre todos os grupos (com os outros dois grupos, p < 0,05). Os três grupos tinham níveis semelhantes de TNF-α e IL-6.. A hipertrofia muscular encontrada no diafragma de indivíduos obesos pode ser justificada pelo aumento do trabalho respiratório imposto pela condição crônica da doença. Esse aumento de espessura não ocorreu em asmáticos leves controlados. Os marcadores IL-6 e TNF-α não detectaram evidências de inflamação muscular, embora fosse esperado que a leptina estivesse alterada em indivíduos obesos. Pacientes obesos e asmáticos apresentaram menor resistência pulmonar do que os saudáveis.

Topics: Adolescent; Asthma; Diaphragm; Female; Humans; Kinetics; Leptin; Male; Obesity; Tumor Necrosis Factor-alpha; Young Adult

Leptin, as a major adipokine, positively correlates with the body's fat, while atopy is an important feature in the development of childhood asthma. We aimed to evaluate the relationship between leptin, parameters of obesity, and atopy in children with asthma. The study included 112 children (73 boys, 39 girls, mean age 11.1±2.4). 41 were overweight, 38 had asthma and a normal body mass index (BMI), and 33 were overweight asthmatics. Serum leptin levels, BMI, waist circumference (WC), and waist to hips ratio (WHR) were measured. Skin prick test (SPT)/CAP, total serum IgE, fractional exhaled nitric oxide (FeNO), and pulmonary function tests were performed. In asthmatic children, serum leptin median level was 9.2±16.2 ng/ml, in overweight children was 30.6±21.6 ng/ml, and in overweight asthmatics was 31.1±20.3 ng/ml with a significant difference between the groups (p=0.0374), yet with a significantly lower median level in the group of children with asthma compared to the overweight children: with asthma (p=0.00001) and without asthma (p=0.00001). In the three groups of patients, BMI and WC displayed a significant positive correlation with leptin (for BMI r=0.652 vs. r=0.530 vs. r=0.563, respectively and for WC r=0.508 vs. r=0.426 vs. r=0.527, respectively). No significant correlations of leptin within atopy parameters (Eo, IgE, SPT/CAP, FeNO) in all three analyzed groups (p>0.05) was detected.

Topics: Adolescent; Asthma; Body Mass Index; Child; Female; Humans; Leptin; Male; Obesity; Waist Circumference

Asthma and atopy are considered condition associated with obesity, being affected by genetic and environmental factors. The LEP and ADIPOQ genes, responsible for the expression and secretion of leptin and adiponectin, respectively, and polymorphisms in such genes have been linked to both diseases, independently, and also with the obesity-associated asthma phenotype in populations with high European ancestry and high-income countries. However, in mixed populations, there are few studies evaluating the impact of these variants in genes associated with the phenotype of asthma and obesity. Thus, the aim of this study was to investigate variants in LEP and ADIPOQ associated with asthma and atopy, and whether overweight modifies that effect.. The study involved 203 asthmatics children and 813 control subjects (between 5 and 11 years old), with or without overweight, from the SCAALA (Asthma and Allergy Social Changes in Latin America) program. Among them, 831 had data for allergy markers, being 258 atopic and 573 non-atopic. Genotyping was performed using a commercial panel Omnium Illumina 2.5. Logistic regression was performed to identify associations expected by using PLINK 1.09 and three genetic models: additive, dominant and recessive adjusted for sex, age, helminth infection, BMI and Principal Components (PC) 1 and 2, for ancestry, in order to control the confounding factor by population structure.. For asthma, G allele of rs822396, in ADIPOQ, was positively associated in additive model (OR 1.4, 95% CI 1.08-1.83) and T allele of rs1063537 in dominant model (OR 1.52, 95% CI 1.01-2.30). In LEP, rs11763517 (C allele) and rs11760956 (A allele) were both negatively associated with asthma in the additive model (OR 0.70, 95% CI 0.54-0.91; OR 0.66, 95% CI 0.50-0.89) respectively, and the A allele of rs2167270 in dominant model (OR 0.71, 95% CI 0.51-0.98). The G allele of rs12706832 showed a positive association with asthma in the recessive model (OR 1.66, 95% CI 1.06-2.61). When the population was stratified by the BMI / Age Z-Score, the protection observed for asthma between the variants rs11760956, rs11763517 and rs2167270 was lost overweight individuals; The protection observed for atopy was lost in all variants (rs16861205, rs2167270 and rs17151919) in the overweight group.. These results suggest that SNPs on the LEP and ADIPOQ genes may have an impact on atopy and asthma. Furthermore, we also show that the asthma and atopy protection attributed to variants on LEP and ADIPOQ genes is lost in individuals exposed to overweight.

Topics: Adiponectin; Asthma; Child; Child, Preschool; Cohort Studies; Female; Genotype; Humans; Hypersensitivity, Immediate; Leptin; Male; Overweight; Polymorphism, Single Nucleotide; Prospective Studies

Obesity-associated asthma is a phenotype of severe asthma. Late-onset, non-eosinophilic and female-dominant phenotype is highly symptomatic and difficult to treat. Leptin, an adipokine, exerts an immunomodulatory effect. IL-33 associated with innate immunity induces type 2 inflammation and is present in adipose tissue. The purpose of this study was to elucidate the pathogenesis of obesity-associated asthma by focusing on the interaction between leptin and IL-33.. In leptin-deficient obese (ob/ob) and wild-type mice, IL-33 was instilled intranasally on three consecutive days. In part of the mice, leptin was injected intraperitoneally prior to IL-33 treatment. The mice were challenged with methacholine, and airway hyperresponsiveness (AHR) was assessed by resistance (Rrs) and elastance (Ers) of the respiratory system using the forced oscillation technique. Cell differentiation, IL-5, IL-13, eotaxin, keratinocyte-derived chemokine (KC) in bronchoalveolar lavage fluid (BALF) and histology of the lung were analyzed. For the in vitro study, NCI-H292 cells were stimulated with IL-33 in the presence or absence of leptin. Mucin-5AC (MUC5AC) levels were measured using an enzyme-linked immunosorbent assay.. Ob/ob mice showed greater Rrs and Ers than wild-type mice. IL-33 with leptin, but not IL-33 alone, enhanced Ers rather than Rrs challenged with methacholine in ob/ob mice, whereas it enhanced Rrs alone in wild-type mice. IL-33-induced eosinophil numbers, cytokine levels in BALF, eosinophilic infiltration around the bronchi, and goblet cell metaplasia were less in ob/ob mice than in wild-type mice. However, leptin pretreatment attenuated these changes in ob/ob mice. MUC5AC levels were increased by co-stimulation with IL-33 and leptin in vitro.. Ob/ob mice show innate AHR. IL-33 with leptin, but not IL-33 alone, induces airway inflammation and goblet cell metaplasia and enhances AHR involving peripheral airway closure. This is presumably accelerated by mucus in ob/ob mice. These results may explain some aspects of the pathogenesis of obesity-associated asthma.

Topics: Animals; Asthma; Bronchi; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Female; Goblet Cells; Inflammation; Interleukin-33; Leptin; Metaplasia; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity

A relationship between adiposity and asthma has been described in some cohort studies, but little is known about trajectories of adiposity throughout early childhood among children at high risk for developing asthma in urban United States cities. Moreover, early life trajectories of adipokines that have metabolic and immunologic properties have not been comprehensively investigated.. Our objective was to characterize trajectories of adiposity in a longitudinal birth cohort of predominately Black and Latinx children (n = 418) using several different repeated measures including body mass index (BMI) z score, bioimpedance analysis, leptin, and adiponectin in the first 10 years of life.. In a longitudinal birth cohort of predominately Black and Latinx children, we used repeated annual measures of BMI, bioimpedance analysis (ie, percentage of body fat), leptin, and adiponectin to create trajectories across the first 10 years of life. Across those trajectories, we compared asthma diagnosis and multiple lung function outcomes, including spirometry, impulse oscillometry, and methacholine response.. Three trajectories were observed for BMI z score, bioimpedance analysis, and leptin and 2 for adiponectin. There was no association between trajectories of BMI, percentage of body fat, leptin, or adipokine and asthma diagnosis or lung function (P > .05).. Trajectories of adiposity were not associated with asthma or lung function in children at high risk for developing asthma. Risk factors related to geography as well as social and demographic factors unique to specific populations could explain the lack of association and should be considered in obesity and asthma studies.

Topics: Adiponectin; Adiposity; Asthma; Birth Cohort; Body Mass Index; Child; Female; Humans; Leptin; Male; Minority Groups; Obesity; Pregnancy; Respiratory Function Tests; Risk; United States; Urban Population

The hormone leptin has been suggested to play a role in the respiratory and immune systems. Evidence on sex-specific concentrations of leptin in human milk and sex-specific associations with the development of asthma and wheeze has been put forward but is still scarce.. To investigate whether male and female infants receive different levels of leptin through human milk and whether leptin is implicated in the development of asthma and wheeze in a sex-dependent manner using data from the two Ulm Birth Cohort studies.. Leptin data were available from human milk samples collected at 6 weeks (Ulm Birth Cohort Study [UBCS, n = 678; Ulm SPATZ Health Study, n = 587]), and, in SPATZ only, at 6 months (n = 377) and 12 months (n = 66) of lactation. Sex-specific associations with doctor-diagnosed asthma and wheeze phenotypes were assessed in crude and adjusted models using logistic regression. Adjustments were made for maternal allergy, exclusive breastfeeding, infant age at the time of milk sampling, and child BMI z-score.. At 6 weeks, leptin levels (median [min, max], in ng/L) were higher in the milk for girls (197 [0.100, 4120]) than in milk for boys (159 [1.02, 3280], p = .045) in UBCS. No significant sex differences were observed in SPATZ (p = .152). There were no significant associations of leptin with asthma or wheeze in both studies, even in a sex-dependent manner (p > .05).. It remains unclear whether male and female infants receive different levels of leptin through human milk. However, leptin in human milk may not be associated with history and development of asthma and wheeze in a sex-specific manner.

Topics: Asthma; Birth Cohort; Cohort Studies; Female; Humans; Infant; Leptin; Male; Milk, Human; Phenotype; Respiratory Sounds; Sex Characteristics

Previous studies showed a close relationship between obesity and asthma. In this study, we investigated the expression of endoplasmic reticulum (ER) stress genes in the lung tissue of obese ovalbumin (OVA)-sensitized male and female rats.. The rats were divided into eight groups (n = 5 per group) as follows: female and male rats fed with normal diet (FND and MND, respectively), female and male OVA-sensitized rats fed with normal diet (F-OND and M-OND, respectively), female and male rats fed with high-fat diet (F-HFD and M-HFD, respectively), female and male OVA-sensitized rats fed with high-fat diet (F-OHFD and M-OHFD, respectively). All rats were fed with a high-fat diet or standard pelts for 8 weeks, and for another 4 weeks, they were sensitized by OVA or saline. At the end of the study, lung tissue NF-kB protein level was assessed, and ER stress markers genes expression was determined by Real Time-PCR.. OVA-sensitization and diet-induced obesity caused the curve of methacholine concentration-response to shift to the left. In addition, the results indicated that the EC50 (the effective concentration of methacholine generating 50% of peak response) in F-OHFD rats was statistically lower than that of the M-OHFD group (p < 0.05). Moreover, the results showed that diet-induced obesity increased the expression of ATF4, ATF6, GRP78, XBP-1, and CHOP as well as the protein level of NF-kB in this experimental model of asthma, markedly in the F-OHFD group.. The results suggest that ER stress may be involved in the pathogenesis of asthma observed in obese OVA-sensitized rats, especially in the female animals.

Topics: Animals; Asthma; Diet, High-Fat; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Female; Gene Expression Regulation; HSP70 Heat-Shock Proteins; Leptin; Lung; Male; Membrane Proteins; Methacholine Chloride; NF-kappa B; Obesity; Ovalbumin; Rats; Rats, Wistar; Signal Transduction; Time Factors

The purpose of this study was to explore the potential contracting effect of leptin on isolated guinea pig tracheal smooth muscle (TSM), the possible mechanism, and the impact of epithelium denudation or allergen sensitization, respectively. An in vitro experiment investigated the effect of leptin at a concentration of 250-1000 nmol/L on isolated guinea pig TSM with an intact or denuded epithelium. Ovalbumin and IgE were used to test the impact of active and passive sensitization. The isolated TSM strips were incubated in Krebs solution and aerated with carbogen (95% O

Topics: Animals; Asthma; Disease Models, Animal; Guinea Pigs; Humans; Leptin; Male; Muscle Contraction; Muscle, Smooth; Ovalbumin; Receptors, Leptin; Trachea

Topics: Asthma; Child, Preschool; Female; Fetal Blood; Humans; Leptin; Mothers; Obesity

Exacerbations are critical events in the course of asthma and chronic obstructive pulmonary disease (COPD). These events are potentially life-threatening, and the studies have shown that they have tremendous implications on long-term disease control and the overall prognosis of the patients. The aim of this study was to examine adipokines, cytokines and C-reactive protein (CRP) as potential biomarkers in asthma and COPD.. Prospective cohort study of COPD and asthma patients treated for acute exacerbations. Thirty-nine COPD patients and 15 asthmatic patients were included in the study. Leptin, adiponectin, resistin, interleukin (Il)-6, 8, 18, tumor necrosis factor-a (TNF-a), and CRP were measured at three time points: on admission, at resolution and at the stable phase. Pre- and post-bronchodilation spirometry was additionally performed at resolution and at the stable phase.. In COPD patients, leptin, leptin/adiponectin (L/A) ratio and resistin were elevated on admission compared to the stable phase. In asthmatic patients, leptin levels were raised on admission compared to the stable phase, and adiponectin was elevated at resolution compared to admission. In both diseases, CRP was significantly increased on admission compared to both resolution and stable disease. Finally, TNF-a could distinguish between asthma and COPD stable phase.. Leptin and CRP levels may be useful biomarkers in monitoring COPD and asthma response to treatment during an exacerbation episode. Hypoadiponectinemia was detected in asthma and COPD during all stages of the diseases. TNF-a could distinguish between asthma and COPD stable phase.

Topics: Adiponectin; Asthma; Biomarkers; C-Reactive Protein; Case-Control Studies; Female; Humans; Interleukin-6; Leptin; Male; Middle Aged; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Tumor Necrosis Factor-alpha

Obesity is a likely risk factor for asthma. However, underlying mechanisms by which obesity affects asthma activity remain poorly understood. This study aimed to investigate the role of leptin, an adipocyte-derived proinflammatory protein, as a mediator in the association between body adiposity (assessed using BMI, waist circumference, and body fat percentage) and persistent asthma.. A causal approach to mediation analysis was used to disentangle total and direct effects and the indirect effect mediated by leptin, using data from the French prospective French Epidemiological Study on the Genetics and Environment of Asthma (EGEA) (baseline: 2003-2007; follow-up: 2011-2013; mean follow-up time: 7 years). A total of 331 participants with current asthma at baseline were included.. Per 1-SD increment in BMI, waist circumference, and body fat percentage, the adjusted odds ratios of the total effect were 1.59 (95% CI: 0.95-2.97), 2.06 (1.06-4.00), and 3.25 (1.01-9.41), respectively; the odds ratios of the indirect effect mediated by leptin were 1.68 (1.09-2.46), 1.55 (0.99-2.57), and 1.99 (0.94-4.83), respectively.. Leptin partly (> 60%) mediated the association between high body adiposity and persistent asthma over time. Using a newly developed analytic approach, this longitudinal study brought new insight into one mechanism by which obesity may affect asthma activity.

Topics: Adiposity; Adult; Asthma; Female; Humans; Leptin; Longitudinal Studies; Male; Risk Factors

This study aims to investigate the correlations of asthma in children with body mass index (BMI), adiponectin, and leptin.. A total of 122 children with asthma in our hospital from January 2017 to February 2018 were randomly selected and divided into control group (normal) and observation group (BMI > 28 kg/m. Body mass index, leptin level, forced vital capacity (FVC), FVC%, and forced expiratory volume in 1s (FEV1)/FVC in observation group were significantly higher than those in control group (P < 0.05), while the adiponectin level, forced expiratory capacity in 1s (FEC1), and FEV1% in observation group were significantly lower than those in control group (P < 0.05). The amount of severe patients in observation group was much larger than that in control group. The severity of disease was positively correlated with BMI and leptin and negatively correlated with adiponectin. BMI, adiponectin, and leptin were identified as risk factors for asthma in children.. Adiponectin, leptin, and BMI are involved in the pathogenesis of asthma in children, suggesting they might be therapeutic targets for clinical treatment.

Topics: Adiponectin; Adolescent; Asthma; Body Mass Index; Case-Control Studies; Child; Female; Forced Expiratory Volume; Humans; Leptin; Logistic Models; Male; Respiratory Function Tests; Vital Capacity

Topics: Adult; Asthma; Calcitriol; CD4-Positive T-Lymphocytes; Cytokines; Female; Humans; Hypersensitivity; Immunoglobulin E; In Vitro Techniques; Interleukin-10; Interleukin-17; Interleukin-5; Interleukin-6; Leptin; Male; Middle Aged; Obesity; Severity of Illness Index; Th1 Cells; Th17 Cells; Vitamin D; Vitamins; Young Adult

Obesity negatively impacts asthma control, but the inflammatory mechanisms are poorly understood.. To explore which systemic inflammatory mediators mediate the effects of obesity on asthma control.. The subjects with stable asthma (n = 108) underwent assessment of clinical characteristics, which included using The Asthma Control Questionnaire (ACQ)-6. Obesity was defined as a body mass index (BMI) of ≥30 kg/m2, overweight was defined as BMI between 25 to 29.9 kg/m2, and lean weight was defined as BMI < 25 kg/m2. Body composition, including fat mass (FM), visceral fat area (VFA), and percentage body fat (PBF) was analyzed by bioimpedance. Serum interleukin (IL) 4, IL-5, IL-8, IL-13, IL-17, chemokine (C-C motif) ligand (CCL) 17, CCL22, leptin, adiponectin, C-reactive protein (CRP), and interferon (IFN) gamma were measured by using ELISA. Linear regression models were fitted according to the Baron and Kenny procedures for mediation analysis.. FM (12.73 ± 3.95 versus 18.59 ± 2.95 versus 27.82 ± 5.17 kg; p < 0.0001), VFA (65.99 ± 23.17 versus 93.96 ± 10.28 versus 123.10 ± 18.34 cm2; p < 0.0001), PBF (23.86 ± 7.46 versus 30.74 ± 5.08 versus 36.21 ± 6.28 %; p = 0.0003) and ACQ-6 values (0.83 [0, 1.17]) versus 1.15 [0.50, 1.75] versus 1.33 [0.83, 1.83] score; p = 0.002) were different among lean (n = 52), overweight (n = 37), and obese (n = 19) subjects. Serum levels of leptin, IL-5, IL-13, IL-17, CCL17, CRP, and IFN-gamma in the obese group were significantly elevated compared with the subjects who were lean or overweight (all p < 0.05). The mediation analyses found that the effect of obesity, assessed by BMI, on ACQ-6 was significantly mediated through IL-13 and CCL17. Furthermore, IL-13 and CCL17 mediated the effects of body composition (FM, VFA and PBF) on ACQ-6. The effects of obesity assessed by body composition, but not by using BMI, on ACQ-6 were mediated by leptin.. Our mediation analysis confirmed that systemic inflammation biomarkers, such as leptin, CCL17, IL-4, and IL-13, mediated the effects of obesity on asthma control. This warrants prospective exploration in this distinct asthma phenotype in the future.

Topics: Asthma; Biomarkers; Body Composition; Body Mass Index; Chemokine CCL17; Humans; Inflammation; Interleukin-13; Interleukin-4; Leptin; Obesity

The co-occurrence of obesity aggravates asthma symptoms. Diet-induced obesity increases helper T cell (TH) 17 cell differentiation in adipose tissue and the spleen. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pravastatin can potentially be used to treat asthma in obese patients by inhibiting interleukin 17 (IL-17) expression. This study investigated the combined effects of pravastatin and anti-IL-17 antibody treatment on allergic inflammation in a mouse model of obesity-related asthma.. High-fat diet (HFD)-induced obesity was induced in C57BL/6 mice with or without ovalbumin (OVA) sensitization and challenge. Mice were administered the anti-IL-17 antibody, pravastatin, or both, and pathophysiological and immunological responses were analyzed.. HFD exacerbated allergic airway inflammation in the bronchoalveolar lavage fluid of HFD-OVA mice as compared to OVA mice. Blockading of the IL-17 in the HFD-OVA mice decreased airway hyper-responsiveness (AHR) and airway inflammation compared to the HFD-OVA mice. Moreover, the administration of the anti-IL-17 antibody decreased the leptin/adiponectin ratio in the HFD-OVA but not the OVA mice. Co-administration of pravastatin and anti-IL-17 inhibited airway inflammation and AHR, decreased goblet cell numbers, and increased adipokine levels in obese asthmatic mice.. These results suggest that the IL-17-leptin/adiponectin axis plays a key role in airway inflammation in obesity-related asthma. Our findings suggest a potential new treatment for IL-17 as a target that may benefit obesity-related asthma patients who respond poorly to typical asthma medications.

Topics: Adiponectin; Adipose Tissue; Animals; Anti-Asthmatic Agents; Antibodies; Asthma; Bronchoconstriction; Diet, High-Fat; Disease Models, Animal; Female; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Interleukin-17; Leptin; Lung; Mice, Inbred C57BL; Obesity; Pravastatin; Th17 Cells; Th2 Cells

Allergic asthma and obesity are major public health problems in the world. Recent Meta-analysis studies implicated a positive relationship between serum leptin, which is elevated in obese individuals, and the risk of asthma. However, it is not well understood how obesity-associated elevation of leptin increases the risk of asthma. In the current study, we have found that leptin induces the unfolded protein response factor XBP1s in an mTOR- and MAPK-dependent manner in pro-allergic TH2 cells; in vivo, mice fed with high fat diet had increased serum leptin as observed in human obese population and exacerbated asthmatic symptoms, associated with increased XBP1s expression in splenic CD4

Topics: Animals; Asthma; Cells, Cultured; Diet, High-Fat; Disease Models, Animal; Inflammation; Leptin; Mice, Inbred C57BL; Th2 Cells; Unfolded Protein Response; X-Box Binding Protein 1

Leptin may induce inflammation in asthma by activation of Th2 cells. It has also been demonstrated that leptin expression increases upon inflammation and that asthmatic patients show increased serum leptin levels. We hypothesized that the polymorphism in leptin (LEP) and leptin receptor (LEPR) genes is associated with childhood asthma and may affect their serum level. To our knowledge, there are no reports analyzing LEP and LEPR polymorphisms in association with their serum levels in childhood asthma.. We analyzed 35 subjects: 25 asthmatic pediatric patients and 10 healthy children aged from 6 to 18. The diagnosis of allergic asthma was based on clinical manifestation, lung function, positive skin prick tests and increased immunoglobulin E levels. The polymorphisms were genotyped with use of polymerase chain reaction-restriction fragment length polymorphism method. Serum levels of leptin and leptin receptor were determined using BioVendor enzyme-linked immunosorbent assay kits. Statistical analysis was done with Statistica v.12.. We observed that leptin levels were increased in asthmatic subjects as compared to healthy controls and were significantly higher during exacerbation than in the asymptomatic period (P = 0.025). We observed that LEP polymorphism (rs13228377) was associated with higher serum leptin levels in asthma and these two variables had high predictive value for asthma risk (P = 0.007, odds ratio 17.5, predictive accuracy 83.9%). LEPR polymorphisms did not show association with its serum level and asthma risk.. LEP polymorphism may increase asthma risk via influence on its serum level.

Topics: Adolescent; Asthma; Case-Control Studies; Child; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Male; Polymerase Chain Reaction; Polymorphism, Genetic; Predictive Value of Tests; Receptors, Leptin

Mucus hypersecretion and plugging of lower respiratory tract airways due to mucus plugs have long been recognized as the leading cause of the morbidity and mortality in asthma. MUC5AC protein is a major component of airway mucus. Here, we showed that interleukin (IL)-13 induced MUC5AC production and secretion, and leptin expression in the human bronchial epithelial cell line-16 (HBE16) cells in a concentration-dependent manner. Leptin knockdown suppressed MUC5AC production and secretion induced by IL-13. We further investigated the molecular mechanism by which leptin functioned, and found that leptin regulated IL-13-induced MUC5AC production and secretion via the JAK2-STAT3 pathway. Subsequently, Munc18b, a limiting component of the exocytic machinery of airway epithelial and mast cells, was found that when knockdown, MUC5AC secretion was significantly inhibited. SABiosciences ChIP search tool identified three STAT3 binding sites with Munc18b promoter. Chromatin immunoprecipitation analysis further confirmed that Stat3 upregulated Munc18b expression by directly binding to its promoter. These data suggested that leptin promotes MUC5AC secretion via JAK2-STAT3-MUNC18b regulatory network. Taken together, our data highlight a positive feedback role and molecular mechanism for leptin in the control of MUC5AC production and secretion from airway epithelial cells stimulated by IL-13, which encourage further exploration of the therapeutic potentials of manipulating leptin in the treatment of mucus hypersecretion in chronic inflammation lung diseases.

Topics: Asthma; Bronchi; Cell Line; Humans; Interleukin-13; Janus Kinase 2; Leptin; Mucin 5AC; Mucus; Respiratory Mucosa; Signal Transduction; STAT3 Transcription Factor

Recent studies have highlighted the possible involvement of leptin in inflammation. The leptin receptor is also expressed by alveolar macrophages, T lymphocytes and bronchial epitelial cells, suggesting a possible role in the cascade of airway inflammation.. The aim of the study was to evaluate the levels of leptin in exhaled breath condensate (EBC) from asthmatic, normal- and overweight children, in relationship with airway inflammation.. 15 asthmatic non-obese children, 15 healthy non-asthmatic non-obese children, 11 obese children with asthma (OA) and 20 obese children without asthma (ONA) were enrolled. Body impedance of body weight, EBC collection, FeNO, spirometry and a blood sampling for serum leptin were assessed.. Leptin EBC levels were significantly higher (3.9 ng ml. This study shows that leptin is measurable in EBC in children and that EBC-leptin levels are significantly higher in the obese subjects and in asthmatic ones compared with healthy subjects. Leptin may therefore represent a non-invasive marker of non-specific airway inflammation in children.

Topics: Adiposity; Adolescent; Asthma; Biomarkers; Body Mass Index; Breath Tests; Child; Exhalation; Female; Humans; Leptin; Male; Nitric Oxide; Obesity; Pilot Projects; Respiratory Function Tests; Spirometry; Waist Circumference

Obesity can cause or worsen asthma. Compared with common asthma, obese asthma is difficult to control. Statins are effective serum cholesterol-lowering agents in clinical practice, and they also have anti-inflammatory properties, which in theory are potentially beneficial in asthma. Many studies have shown that simvastatin has good therapeutic effect in animal models of asthma. However, the therapeutic effect and action mechanism of simvastatin for obese asthma remain unclear. Leptin, a satiety hormone, is in positive correlation with total body fat mass and may also play a significant role in the pathogenesis of asthma. In this study, we use the method of high-fat diet and ovalbumin (OVA) sensitization and challenge to establish the mouse model of obesity and asthma, and find that obese asthmatic mice has higher levels of glucose, lipid and leptin in serum, and neutrophil percentage in bronchoalveolar lavage fluid (BALF), and more severe airway inflammation and structural changes in lung tissues than non-obese asthmatic mice, and respond poorly to dexamethasone treatment, which indicates that obese asthma might belong to steroid-resistant (SR) asthma. Simvastatin treatment reduces the levels of glucose, lipid, leptin and neutrophil percentage, and improves airway inflammation and remodeling, which can be as a potential therapeutic target used in the treatment of obese asthma in humans. Correlation analysis shows that there is positive correlation between neutrophil percentage and serum leptin/cholesterol level, which indicates that the therapeutic efficacy of simvastatin on obese asthma might be associated with improving dyslipidemia and decreasing leptin level.

Topics: Animals; Asthma; Blood Glucose; Body Weight; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Dyslipidemias; Female; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Leptin; Leukocyte Count; Lipids; Lung; Mice; Mice, Inbred C57BL; Obesity; Simvastatin

To study the peripheral blood level of leptin and adiponectin and their possible effect on the functional status of the respiratory system in young asthmatic patients in relation to body mass index (BMI) for the optimization of asthma therapy.. Examinations were made in 133 people, including a study group of 93 patients with asthma who were divided into 2 groups according to BMI: 1) those with a BMI of less 25 kg/m2 and 2) those with a BMI of 30 kg/m2 or more, as well as a control group of 40 apparently healthy patients. The investigators studied external respiratory function (ERF), the peripheral blood levels of leptin and adiponectin, the biochemical composition of plasma, by determining total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides.. Lipid metabolic disorders as dyslipidemia and hypercholesterolemia, increased severity of disease, and decreased ERF were recorded in the concomitance of obesity and asthma. The peripheral blood level of leptin in young asthmatic patients with obesity was found to be associated with higher BMI.. A more severe course of disease presenting with decreased ERF, impaired lipid metabolism, and elevated peripheral blood leptin levels were noted in the concomitance of asthma and obesity at a young age.. Цель исследования. Изучить уровень лептина и адипонектина в периферической крови и их возможное влияние на функциональное состояние респираторной системы у больных бронхиальной астмой (БА) молодого возраста в зависимости от индекса массы тела (ИМТ) для оптимизации противоастматической терапии. Материалы и методы. Обследованы 133 человека: 93 больных БА, которых разделили на 2 группы с учетом ИМТ, и 40 практически здоровых добровольцев, составивших группу контроля. В 1-ю группу включили больных БА с ИМТ менее 25 кг/м2, во 2-ю группу - больные БА с ИМТ 30 кг/м2 и более. Изучали функцию внешнего дыхания (ФВД), уровни лептина и адипонектина в периферической крови, биохимический состав плазмы крови с определением общего холестерина (ХС), ХС липопротеидов высокой плотности, ХС липопротеидов низкой плотности, триглицеридов. Результаты. При сочетании ожирения и БА зарегистрированы нарушение липидного обмена по типу дислипидемии и гиперхолестеринемии, увеличение тяжести заболевания, снижения показателей ФВД. Установлено, что уровень лептина в периферической крови у больных БА молодого возраста с ожирением ассоциирован с повышением ИМТ. Заключение. При сочетании БА и ожирения в молодом возрасте отмечается более тяжелое течение заболевания, проявляющееся снижением показателей ФВД, нарушением липидного обмена и повышением уровня лептина в периферической крови.

Topics: Adiponectin; Adult; Asthma; Body Mass Index; Comorbidity; Dyslipidemias; Female; Humans; Hypercholesterolemia; Leptin; Male; Obesity; Young Adult

Childhood obesity is a risk factor for asthma, but the molecular mechanisms linking both remain elusive. Since obesity leads to chronic low-grade inflammation and affects metabolic signaling we hypothesized that postnatal hyperalimentation (pHA) induced by maternal high-fat-diet during lactation leads to early-onset obesity and dysregulates pulmonary adipocytokine/insulin signaling, resulting in metabolic programming of asthma-like disease in adult mice. Offspring with pHA showed at postnatal day 21 (P21): (1) early-onset obesity, greater fat-mass, increased expression of IL-1β, IL-23, and Tnf-α, greater serum leptin and reduced glucose tolerance than Control (Ctrl); (2) less STAT3/AMPKα-activation, greater SOCS3 expression and reduced AKT/GSK3β-activation in the lung, indicative of leptin resistance and insulin signaling, respectively; (3) increased lung mRNA of IL-6, IL-13, IL-17A and Tnf-α. At P70 body weight, fat-mass, and cytokine mRNA expression were similar in the pHA and Ctrl, but serum leptin and IL-6 were greater, and insulin signaling and glucose tolerance impaired. Peribronchial elastic fiber content, bronchial smooth muscle layer, and deposition of connective tissue were not different after pHA. Despite unaltered bronchial structure mice after pHA exhibited significantly increased airway reactivity. Our study does not only demonstrate that early-onset obesity transiently activates pulmonary adipocytokine/insulin signaling and induces airway hyperreactivity in mice, but also provides new insights into metabolic programming of childhood obesity-related asthma.

Topics: Adipokines; AMP-Activated Protein Kinases; Animals; Asthma; Collagen Type I; Diet, High-Fat; Female; Inflammation; Insulin; Interleukins; Lactation; Leptin; Lung; Male; Mice, Inbred C57BL; Obesity; Signal Transduction; STAT3 Transcription Factor; Suppressor of Cytokine Signaling 3 Protein

Allergic asthma and obesity are the leading health problems in the world. Many studies have shown that obesity is a risk factor of development of asthma. However, the underlying mechanism has not been well established. In this study, we demonstrate that leptin, an adipokine elevated in obese individuals, promoted proliferation and survival of pro-allergic type 2 helper T cells and group 2 innate lymphoid cells and production of type 2 cytokines, which together contribute to allergic responses. Leptin activates mTORC1, MAPK, and STAT3 pathways in TH2 cells. The effects of leptin on TH2 cell proliferation, survival, and cytokine production are dependent on the mTORC1 and MAPK pathways as revealed by specific inhibitors. In vivo, leptin-deficiency led to attenuated experimental allergic airway inflammation. Our results thus support that obesity-associated elevation of leptin contributes to the increased susceptibility of asthma via modulation of pro-allergic lymphocyte responses.

Topics: Animals; Asthma; Cell Proliferation; Cytokines; Extracellular Signal-Regulated MAP Kinases; Leptin; MAP Kinase Signaling System; Mechanistic Target of Rapamycin Complex 1; Mice; Mice, Knockout; Multiprotein Complexes; Obesity; STAT3 Transcription Factor; Th2 Cells; TOR Serine-Threonine Kinases

The study aimed to compare the effect of obesity with and without metabolic syndrome on asthma severity, quality of life, sleep quality, sleep disordered breathing and inflammatory markers as compared to non-obese asthma patients.. 60 asthma patients recruited for the study were divided equally into non-obese (NOA), obese without metabolic syndrome (OANMS) and obese with metabolic syndrome (OAMS) groups. Study cohorts were assessed for severity of asthma, quality of life and quality of sleep using questionnaires and inflammatory markers (FENO, hs-CRP, IL-5, IL-6 and leptin). Institutional ethical committee approved the study.. The results suggests OAMS patients may be a subtype of asthmatics having significantly severe asthma (p < 0.05), poor quality of life (p < 0.05), high risk of OSA (p< 0.05), decreased lung volumes (FRC) (p< 0.05), higher levels of inflammatory markers (leptin and IL-6) (p < 0.05), and high incidence of sleep disordered breathing (p < 0.05) in comparison to NOA and OANMS patients.. The present study has shown that obese asthmatics especially with metabolic syndrome represent a subtype of asthmatic population. Hence, the treatment of metabolic syndrome may be necessary in addition to asthma to achieve optimal control.

Topics: Adolescent; Adult; Asthma; Biomarkers; C-Reactive Protein; Cohort Studies; Cytokines; Female; Humans; Immunoglobulin E; India; Leptin; Male; Metabolic Syndrome; Middle Aged; Nitric Oxide; Obesity; Quality of Life; Severity of Illness Index; Sleep Apnea Syndromes; Surveys and Questionnaires; Young Adult

Airway inflammation is involved in the pathogenesis of bronchopulmonary dysplasia (BPD). The aim of the study was to evaluate the inflammatory activity in plasma and exhaled air in very low birth weight (VLBW) BPD survivors at school age.. Twenty-one 6-14-year-old former VLBW (birth weight ≤1,500 g) children with severe radiographic BPD (radBPD), 19 without radBPD (nonBPD group) and 19 non-asthmatic term controls underwent measurement of eosinophil cationic protein, IL-6, IL-8, adiponectin, adipsin, leptin, and resistin in plasma, leukotriene B4 and 8-isoprostane in exhaled breath condensate, and NO in exhaled breath. Background data were obtained from patient records, clinical examination and parental questionnaire. Both univariate and multivariate models were applied in the statistical analysis.. There were no significant differences between the groups in any of the inflammatory markers measured. Five (25%) radBPD and 2 (11%) nonBPD children reported asthma (P = 0.058). In logistic regression analysis, exposure to chorioamnionitis was associated with low IL-8 (OR 29.0, 95% CI 3.27-258) and postnatal corticosteroid therapy with high adiponectin (OR 32.0, 95% CI 1.29-793). High body mass index standard deviation score (BMI-SDS) was associated with high plasma adipsin (OR 2.47, 95% CI 1.07-5.75) and leptin (OR 5.76, 95%CI 1.83-18.2) levels.. The inflammatory activity seems to decrease by school age in VLBW BPD survivors. Chorioamnionitis and postnatal corticosteroid treatment may modulate the inflammatory responsiveness in VLBW subjects even up to school age. The respiratory outcome in VLBW infants might be improved by preventing excessive weight gain.

Topics: Adiponectin; Adolescent; Asthma; Biomarkers; Body Mass Index; Bronchopulmonary Dysplasia; Child; Chorioamnionitis; Complement Factor D; Female; Finland; Glucocorticoids; Humans; Infant, Newborn; Infant, Very Low Birth Weight; Interleukin-6; Interleukin-8; Leptin; Logistic Models; Pregnancy; Survivors

To determine the changes in the expression of leptin and its receptor in the lungs of mice with varying degrees of asthma before and after budesonide treatment.. Forty Balb/c mice were randomly assigned into 4 groups with 10 animals in each. One group received no treatment (control group) and the other groups were challenged with either nebulized ovalbumin (OVA) for three days (3-day group) or seven days (7-day group), or with nebulized ovalbumin followed by budesonide administration (treatment group). Changes in airway inflammation were observed using hematoxylin-eosin staining. The protein and mRNA levels of leptin and its receptor in lung tissues were determined using immunohistochemistry/Western blot and real-time PCR, respectively.. The two asthmatic groups showed more significant pathological changes in the airway than the control and the treatment groups. Mice that were challenged by OVA for seven days showed more marked pathological changes in the airway compared with mice challenged by OVA for three days. The protein and mRNA levels of leptin in the lung tissues of the 3-day group were significantly higher than those of the control group (P<0.01), but significantly lower than those of the 7-day group (P<0.01). The protein levels of leptin receptor in the lung tissues of the 3-day group were significantly lower than those of the control group (P<0.01). The treatment group showed increased protein levels of leptin receptor compared with the 7-day group (P<0.01). No significant difference was noted between the four groups with respect to the mRNA levels of leptin receptor in the lung tissues.. Leptin is highly expressed whereas its receptor is lowly expressed in the lung tissues of asthmatic mice. Budesonide can increase the expression of leptin receptor, but has no significant impact on the expression of leptin.

Topics: Animals; Asthma; Blotting, Western; Budesonide; Immunohistochemistry; Leptin; Lung; Male; Mice; Mice, Inbred BALB C; Receptors, Leptin; RNA, Messenger

Infection of human bronchial epithelial cells (hBECs) with respiratory syncytial virus (RSV) has been shown to induce a Th lymphocyte subset drift, e.g. enhanced differentiation of Th2 and Th17 subsets, which is a classic characteristic of asthma. However, the molecules responsible for the drift in Th subsets remain unknown. This study aims to determine the expression of leptin in RSV-infected hBECs, and its role in Th2 and Th17 cell differentiation and extracellular regulated kinase (ERK) 1/2 phosphorylation.. Cultured hBECs were infected with RSV. mRNA expression of the LEP gene in cells was measured by real-time PCR while LEP protein secretion in culture medium was measured by ELISA. Th differentiation was investigated in cultured human peripheral blood mononuclear cells following stimulation with recombinant human leptin. Th2 and Th17 subsets were examined by flow cytometry. Phosphorylation of the ERK1/2 protein in lymphocytes was detected by Western blot and immunofluorescence.. LEP mRNA expression was significantly upregulated in RSV-infected hBECs while the leptin protein level in the supernatants of RSV-infected hBECs was significantly increased. Stimulation of lymphocytes with leptin increased the differentiation of the Th17 subset and ERK1/2 phosphorylation, but suppressed Th2 subset differentiation.. Leptin was oversecreted by RSV-infected hBECs, which promoted Th17 subset differentiation but suppressed Th2 subset differentiation possibly via regulating ERK1/2 phosphorylation.

Topics: Asthma; Cell Differentiation; Cell Line; Epithelial Cells; Extracellular Signal-Regulated MAP Kinases; Humans; Leptin; Phosphorylation; Respiratory Mucosa; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; RNA, Messenger; Th17 Cells; Th2 Cells

Topics: Animals; Asthma; Humans; Leptin; Pneumonia; Pulmonary Disease, Chronic Obstructive

Community-based studies of obesity, asthma, biomarkers of oxidative stress, and adipokines among low-income, urban, minority populations are lacking. Oxidative stress, perhaps modulated by adipokines, may increase airway inflammation in obese individuals.. To characterize associations between obesity and asthma in a low-income, urban, minority community and evaluate adipokines, biomarkers of inflammation, and oxidant-antioxidant balance in association with asthma and obesity.. A door-to-door evaluation of asthma and obesity prevalence was performed in a low-income housing development. Nonsmoking adults and children underwent additional evaluation, including allergy skin testing, and measures of serum adipokines, and indicators of oxidative stress in blood and exhaled breath.. The prevalences of current asthma and a body mass index in the 85th percentile or higher were 15.8% and 35.3%, respectively, among 350 nonsmokers older than 4 years. Asthma and obesity were not associated with one another (odds ratio, 1.0; 95% confidence interval, 0.55-1.84). Among 116 nonsmoking participants who underwent biomarker evaluation, obesity was not associated with exhaled nitric oxide. In multivariate logistic models that adjusted for age category, sex, and a body mass index in 85th percentile or higher, leptin concentrations in the highest quartile were associated with asthma (odds ratio, 8.34; 95% confidence interval, 1.29-50.2) but not with atopy. Adiponectin was associated with total antioxidant capacity in exhaled breath.. Asthma and obesity, although both common in a low-income, minority community, were not associated with one another. Nevertheless, adipokines were associated with asthma status and with markers of oxidative stress in the lungs, providing some support for an adipokine-inflammatory mechanistic link between the two conditions.

Topics: Adiponectin; Adult; Asthma; Biomarkers; Child, Preschool; Data Collection; Female; Humans; Leptin; Male; Minority Groups; Obesity; Oxidative Stress; Poverty; Urban Population

The increasing prevalence of both asthma and obesity are major health problems. Recent studies established a possible link between obesity and asthma; however, the underlying mechanism is not clear. The aim of the study was to analyze the prevalence of metabolic syndrome in postmenopausal subjects with asthma and search the interactions between adipokines, metabolic syndrome, and asthma. A total of 45 female patients (57.5 ± 13.9 years) with asthma and 30 healthy subjects (59.6 ± 12.8 years) in postmenopausal status were enrolled in this study. For the diagnosis of metabolic syndrome, modified World Health Organization diagnostic criteria were used. Blood levels of glucose, lipid profile, HbA1c, insulin, CRP, leptin, adiponectin, tumor necrosis factor-alpha, interleukin (IL)-6, IL-8 and plasminogen activator inhibitor-1 (PAI-1) were measured. The mean body mass index was 29.6 ± 5.4 for asthma patients and 28.2 ± 5.3 for the control group. The incidence of metabolic syndrome was found as 26 % for both groups. Insulin resistance as calculated by homeostasis model assessment (HOMA-IR) and fasting insulin levels were significantly higher in asthma patients (p < 0.001 for both parameters). Leptin levels were significantly higher (p = 0.001) and adiponectin levels were lower (p = 0.029) in asthma patients compared to controls. We concluded that although incidence of obesity and metabolic syndrome was not higher in postmenopausal asthma patients than controls, there was an impairment of glucose metabolism and altered adipokine levels in asthma patients.

Topics: Adiponectin; Asthma; Blood Glucose; Body Mass Index; Female; Humans; Insulin Resistance; Leptin; Lipids; Metabolic Syndrome; Middle Aged; Obesity; Postmenopause

In the USA, Puerto Rican children have a higher prevalence of asthma than other Latino ethnicities, and acculturation is one of hypothesized reasons for this difference. We examined associations between sociocultural characteristics and serum leptin, high-sensitivity C-reactive protein (hsCRP), and body mass index (BMI), and further, among hsCRP, leptin levels, BMI percentiles, and allergic sensitization in 2-year-old children.. IgE antibodies, leptin, and hsCRP concentrations were measured in serum from Puerto Rican toddlers (n = 143) born in New York City with a maternal history of allergy and/or asthma. Demographic and home characteristics questionnaires were administered to the mother, postpartum and two years later. Children's weight and height were measured to determine BMI percentiles.. More girls (60%) had leptin levels above the median compared with boys (37%) (p = 0.0063). Leptin was positively correlated with BMI (r = 0.25; p = 0.0042). Children in daycare were more likely to be obese (40% vs. 24% p < 0.06). Maternal birthplace was significantly associated with children's leptin but not with hsCRP. Leptin levels were lower for children whose mothers were born on the US mainland (GM = 2.5 ng/ml, 95% CI [2.2-2.7]) compared with those whose mothers were born in Puerto Rico or another country (GM = 3.2 ng/ml, 95% CI [2.2-3.9], t-test p = 0.01). Mothers born in another country were more likely than those born in the US mainland or Puerto Rico to have obese children (60% vs. 26% p < 0.02). Leptin, hsCRP, and BMI percentile were not associated with sensitization to any of the measured inhalant allergens or total IgE.. Even at a very young age, some acculturation factors were associated with biomarkers and anthropometric measures of obesity among this Puerto Rican pediatric population. To our knowledge, this is the first study demonstrating the association of mother's birth place with child BMI and leptin as early as 24 months.

Topics: Asthma; Biomarkers; Body Mass Index; C-Reactive Protein; Child, Preschool; Female; Humans; Immunoglobulin E; Leptin; Male; New York City; Obesity; Puerto Rico; Risk Factors; Sex Factors; Socioeconomic Factors

A clear relationship between asthma and obesity has been reported, but the mechanisms remain unclear. The aim of this study was to evaluate the influence of obesity on eosinophil activity (chemotaxis and adhesion) in asthmatic children and adolescents compared with cells from healthy volunteers.. Asthmatic obese (AO), asthmatic non-obese (ANO), non-asthmatic obese (NAO) and non-asthmatic non-obese (NANO) individuals were included in the present study. The chemotaxis of eosinophils after stimulation with eotaxin (300 ng/ml), platelet-activating factor (10 μM; PAF) and RANTES (100 ng/ml) was performed using a microchemotaxis chamber. The eosinophil peroxidase activity was measured to determine the adhesion activity of eosinophils cultivated on fibronectin-coated plates. The serum leptin, adiponectin, TNF-α and IgE levels were quantified using ELISA assays.. The serum IgE levels and eosinophil counts were significantly higher in asthmatic (obese and non-obese) individuals compared with non-asthmatic individuals (obese and non-obese). Spontaneous eosinophil chemotaxis was greater in the AO group compared with either the ANO or NANO groups. The activation of eosinophils using eotaxin and PAF increased eosinophil chemotaxis in the AO group. RANTES treatment increased eosinophil chemotaxis in the NAO group compared with the NANO or ANO groups. The activation of eosinophils using eotaxin significantly increased eosinophil adhesion in the AO group compared with other groups. The serum leptin and TNF-α levels were higher in obese subjects (asthmatic and non-asthmatic), whereas the levels of adiponectin did not significantly differ among these groups.. This study is the first to show increased eosinophilic activity (chemotaxis and adhesion) associated with high serum leptin and TNF-α levels in atopic asthmatic obese children and adolescents compared with non-obese healthy volunteers.

Topics: Adolescent; Asthma; Case-Control Studies; Cell Adhesion; Chemokine CCL11; Chemokine CCL5; Chemotaxis; Child; Cross-Sectional Studies; Eosinophils; Female; Humans; Immunoglobulin E; Leptin; Male; Obesity; Peroxidase; Platelet Activating Factor; Tumor Necrosis Factor-alpha

Adiponectin is divided into high-molecular-weight (HMW), middle-molecular-weight (MMW) and low-molecular-weight (LMW) types. While HMW adiponectin has been studied by many researchers, the roles of MMW and LMW adiponectin have not yet been sufficiently elucidated. In addition, there are conflicting findings regarding the role of adiponectin in chronic inflammatory diseases, especially asthma. Therefore, we compared patients who suffered episodes of asthma in the past (=asthmatics) with those who did not (=non-asthmatics) in order to investigate the relationship between asthma and HMW, MMW and LMW adiponectin. The subjects in this study included 76 university students. None of the subjects were smokers, on regular medications or seeing a doctor regularly at the time. Fourteen subjects reported past histories of asthma. We also measured and compared the levels of leptin and ghrelin to that of adiponectin, as these hormones are connected with inflammatory conditions. Although the physical data of the asthmatics were similar to those of the non-asthmatics, the levels of ghrelin and all fractions of adiponectin tended to be lower in the asthmatics than in the non-asthmatics. While the levels of MMW and LMW adiponectin in the asthmatics were found to be significantly low, the levels of ghrelin and HMW adiponectin were not clear. According to a multivariate regression analysis of the MMW and LMW adiponectin levels, asthma was found to be more significantly associated with the LMW adiponectin level than age, waist circumference or HDL-C. The results suggest that LMW adiponectin may be associated with episodes of asthma in males.

Topics: Adiponectin; Adolescent; Adult; Asthma; Female; Ghrelin; Humans; Inflammation; Leptin; Male

Epidemiological data indicate an increasing incidence of asthma in the obese individuals recent decades, while very little is known about the possible association between them. Here, we compared the roles of adipocyte-derived factors, including leptin, adiponectin and resistin on proliferation, wound repair and apoptosis in human bronchial epithelial cells (HBECs) which play an important role in the pathogenesis of asthma. The results showed that exogenous globular adiponectin (gAd) promoted proliferation, cell-cycle and wound repair of HBECs. This effect may be relevant to Ca(2+)/calmodulin signal pathway. Besides, gAd inhibited apoptosis induced by ozone and release of lactate dehydrogenase (LDH) of HBECs via regulated adipoR1 and reactive oxygen species. No effects of leptin or resistin on proliferation, wound repair and apoptosis of HBECs were detectable. These data indicate that airway epithelium is the direct target of gAd which plays an important role in protecting HBECs from mechanical or oxidant injuries and may have therapeutic implications in the treatment of asthma.

Topics: Adiponectin; Apoptosis; Asthma; Bronchi; Calcium; Calcium Signaling; Cell Proliferation; Epithelial Cells; Humans; Leptin; Obesity; Reactive Oxygen Species; Resistin; Wound Healing

The mechanisms underlying the relationship between obesity and asthma have not been fully established. Data in the literature suggest that adipose tissue-derived hormones may be implicated. However, no definite conclusions regarding the role of leptin and adiponectin with asthma are available. No studies have examined the role of ghrelin in asthma.. We assessed the circulating concentrations of leptin, adiponectin, and ghrelin in 32 postmenopausal stable asthma patients, 37 female asthmatics during exacerbations and 8 weeks later, and 22 controls. We examined the relationship between the three peptides and indexes of pulmonary function, airway inflammation, and atopy.. Stable asthma patients exhibited higher leptin and lower ghrelin concentrations compared with controls. Patients with severe asthma had higher leptin and lower adiponectin levels versus patients with mild to moderate asthma. Both leptin concentrations and leptin/adiponectin ratio served as markers for discriminating asthma patients from controls on the one hand, and severe from mild to moderate asthmatics on the other. Leptin levels were inversely correlated with both FEV(1)/FVC and FEF(25-75) in patients with mild to moderate asthma. Atopic asthma patients had higher leptin concentrations than nonatopic asthma patients. There was a positive correlation between serum leptin and total IgE levels in atopic asthmatics. Finally, serum leptin levels and leptin/adiponectin ratio were significantly increased during asthma exacerbations, while adiponectin and ghrelin levels were significantly decreased.. Our findings suggest that leptin, adiponectin, and ghrelin may play a significant role in the pathogenesis of asthma during both stable state and asthma exacerbation, independent of obesity.

Topics: Adiponectin; Area Under Curve; Asthma; Female; Forced Expiratory Volume; Ghrelin; Humans; Inflammation; Leptin; Middle Aged; Obesity; Postmenopause; ROC Curve

Impaired lung function caused by decreased airway diameter (bronchoconstriction) is frequently observed whether body weight is abnormally high or low. That these opposite conditions affect the airways similarly suggests that the regulation of airway diameter and body weight are intertwined. We show here that, independently of its regulation of appetite, melanocortin pathway, or sympathetic tone, leptin is necessary and sufficient to increase airway diameter by signaling through its cognate receptor in cholinergic neurons. The latter decreases parasympathetic signaling through the M(3) muscarinic receptor in airway smooth muscle cells, thereby increasing airway diameter without affecting local inflammation. Accordingly, decreasing parasympathetic tone genetically or pharmacologically corrects bronchoconstriction and normalizes lung function in obese mice regardless of bronchial inflammation. This study reveals an adipocyte-dependent regulation of bronchial diameter whose disruption contributes to the impaired lung function caused by abnormal body weight. These findings may be of use in the management of obesity-associated asthma.

Topics: Animals; Asthma; Body Weight; Bronchi; Bronchoconstriction; Cholinergic Antagonists; Cholinergic Neurons; Diet, High-Fat; Inflammation; Leptin; Mice; Mice, Inbred C57BL; Mice, Obese; Myocytes, Smooth Muscle; Obesity; Parasympathetic Nervous System; Receptor, Muscarinic M3; Signal Transduction

Obese asthma presents via altered airway and systemic inflammation in adults. This has not been comprehensively described in children. The aim of the present study was to compare airway and systemic inflammation in obese and nonobese asthmatic children and controls. In a cross-sectional study, children aged 8-17 years were assigned to one of four groups: obese asthma (OA, n=74); nonobese asthma (NOA, n=249); obese control (OC, n=9); nonobese control (NOC, n=29). Lung function, and both sputum and systemic inflammatory biomarkers were measured. Non-eosinophilic asthma was more prevalent among OA females (60.0%) versus OA males (30.8%). However, there were no differences in the percentage of eosinophils or neutrophils between OA and NOA. Leptin was higher in OC, but not OA, versus NOA and NOC, while adiponectin was reduced in OA versus NOC only. Expiratory reserve volume was reduced in OA, versus NOC. Residual volume (RV) and RV/total lung capacity were reduced in OC versus OA, and OC versus OA and NOA, respectively. Obesity was associated with significant lung restriction in children with and without asthma. Obesity was not associated with significantly altered airway or systemic inflammation in asthmatic children. However, the higher prevalence of non-eosinophilic asthma in female obese asthmatics, compared to males, warrants further investigation.

Topics: Adiponectin; Adolescent; Asthma; Biomarkers; Child; Cohort Studies; Cross-Sectional Studies; Female; Humans; Inflammation; Leptin; Male; Nitric Oxide; Obesity; Quality of Life; Sex Factors; Sputum; Surveys and Questionnaires

Previous studies have shown that delayed neutrophil apoptosis is associated with chronic airway diseases. Leptin is an adipocyte-derived hormone that acts as a regulator of energy homeostasis and food intake. Emerging evidence suggests that leptin can regulate immune responses including the release of proinflammatory cytokines and protection of inflammatory cells from apoptosis. Serum leptin is increased during allergic reactions in the airways. However, the expression and function of leptin receptor in neutrophils isolated from children is not known.. Flow cytometry was used to detect leptin receptor expression in neutrophils isolated from allergic asthmatic (n = 14), allergic non asthmatic (n = 21), non allergic asthmatic (n = 7) and healthy children (n = 23); confocal laser scanning microscopy combined with immunofluorescence was performed to detect intracellular pool of leptin receptor; Annexin-V/PI staining and caspase 3 activity was used to determine neutrophil survival. Pharmacological inhibitors were utilized to understand the role of MAPK and NF-κB pathway in leptin-induced neutrophil survival.. A heterogeneous leptin receptor expression was observed on neutrophils isolated from children. Neutrophils isolated from healthy children expressed more leptin receptor than those from allergic asthmatic (P<0.05) but not allergic non-asthmatic (P>0.05) or non-allergic asthmatic children (n = 7, P>0.05). Neutrophils isolated from children express an intracellular pool of leptin receptor that was mobilized to the cell surface upon GM-CSF stimulation. Finally, leptin exhibited anti-apoptotic properties on neutrophils via NF-κB and MEK1/2 MAPK pathway. Collectively, our data suggest that leptin may enhance airway inflammation by promoting neutrophil survival.

Topics: Annexin A5; Apoptosis; Asthma; Caspase 3; Child; Flow Cytometry; Fluorescent Antibody Technique; Humans; Leptin; Microscopy, Confocal; Neutrophils; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Receptors, Leptin; Signal Transduction

The simultaneous rise in the prevalence of asthma and obesity in the world, have demonstrated the importance of the development of treatment strategies. The purpose of this study was to evaluate the short- and long-term results of interdisciplinary therapy on inflammatory biomarkers and lung function in asthmatics obese adolescents.. Seventy-six post-pubertal obese adolescents were recruited, including 50 non-asthmatics [body mass index (BMI), 36 ± 5 kg/m(2) ) and 26 asthmatics (BMI, 39 ± 4 kg/m(2) ). Body composition was measured by plethysmography, and visceral fat was analyzed by ultrasound. Serum levels of adiponectin, leptin, and C-reactive protein (CRP) were analyzed. Asthma and lung function were evaluated according to the American Thoracic Society criteria. Patients were submitted to 1-year weight loss interdisciplinary intervention consisting of medical, nutritional, exercise, and psychological therapy.. After interdisciplinary intervention, the lung function and pro/anti-inflammatory adipokines improved significantly in both groups. Most importantly, there was an increase in adiponectin [4 (1.86-12.9) to 5.1 (2.48-16)], a reduction in CRP [2,073 (385-9,174) to 1,538 (205-7,083)] and leptin concentrations [59 (29-69) to 33 (9-49)] in the asthmatics patients. Furthermore, it was observed a reduction in asthma severity after treatment. In addition, Δ adiponectin was an independent factor to improve lung function after therapy in both groups.. Interdisciplinary therapy resulted in beneficial changes in inflammatory biomarkers profile and lung function in asthmatic and non-asthmatic obese adolescents. Additionally, for the first time we showed that change in adiponectin level was an independent predictor to improve lung function in Brazilian obese adolescents.

Topics: Adipokines; Adiponectin; Adolescent; Asthma; Biomarkers; Body Mass Index; C-Reactive Protein; Combined Modality Therapy; Diet Therapy; Exercise; Female; Humans; Leptin; Lung; Male; Obesity; Psychotherapy, Group; Spirometry; Weight Loss; Young Adult

Obesity is associated with increased prevalence and severity of asthma. Adipose tissue macrophages can contribute to the systemic proinflammatory state associated with obesity. However, it remains unknown whether alveolar macrophages have a unique phenotype in overweight/obese patients with asthma.. We hypothesized that leptin levels would be increased in the bronchoalveolar lavage fluid from overweight/obese subjects and, furthermore, that leptin would alter the response of alveolar macrophages to bacterial LPS.. Forty-two subjects with asthma and 46 healthy control subjects underwent research bronchoscopy. Bronchoalveolar lavage fluid from 66 was analyzed for the level of cellular inflammation, cytokines, and soluble leptin. Cultured primary macrophages from 22 subjects were exposed to LPS, leptin, or leptin plus LPS. Cytokines were measured in the supernatants.. Leptin levels were increased in overweight/obese subjects, regardless of asthma status (P = 0.013), but were significantly higher in overweight/obese subjects with asthma. Observed levels of tumor necrosis factor-α were highest in overweight/obese subjects with asthma. Ex vivo studies of primary alveolar macrophages indicated that the response to LPS was most robust in alveolar macrophages from overweight/obese subjects with asthma and that preexposure to high-dose leptin enhanced the proinflammatory response. Leptin alone was sufficient to induce production of proinflammatory cytokines from macrophages derived from overweight/obese subjects with asthma.. Ex vivo studies indicate that alveolar macrophages derived from overweight/obese subjects with asthma are uniquely sensitive to leptin. This macrophage phenotype, in the context of higher levels of soluble leptin, may contribute to the pathogenesis of airway disease associated with obesity.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Asthma; Biomarkers; Bronchoalveolar Lavage Fluid; Bronchoscopy; Case-Control Studies; Cells, Cultured; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Linear Models; Lipopolysaccharides; Macrophages, Alveolar; Male; Middle Aged; Obesity; Overweight; Phenotype; Young Adult

Obesity and asthma are characterized by the presence of inflammation. Leptin and adiponectin are circulating hormones produced by adipose tissue that regulate several metabolic and inflammatory functions. We aimed to determine whether obesity influences asthmatic inflammation as well as the contribution of leptin or/and adiponectin to a possible linkage between asthmatic and obesity-related inflammation.. One hundred patients with asthma and 60 healthy controls were studied. Subjects who had a comorbid illness that could interfere with the proposed tests were excluded. All subjects were divided into three groups (normal range, pre-obese, obese) according to the criteria of the current WHO international classification for body mass index (BMI). Possible associations between variables expressing airway inflammation, bronchial hyper-responsiveness, systemic inflammation and obesity, as assessed by BMI, were evaluated. Leptin and adiponectin were also measured and were associated with asthma airway and systemic inflammatory variables to elucidate possible associations.. Obese patients had significant higher values of LTE(4) /creatinine in urine compared with pre-obese and normal range ones. In a linear regression model, the only significant associations were those between BMI and LTE(4) /creatinine in urine. Using the same model, log leptin and log adiponectin presented positive and negative associations, respectively with LTE(4) /creatinine in urine. No other significant associations were observed in both patients and healthy subjects.. In a selected cohort of asthmatic patients, obesity is significantly associated with increased urinary leukotriene levels. Alterations of leptin/adiponectin balance may be related to the presence of leukotriene inflammation in obese asthmatic patients.

Topics: Adiponectin; Adolescent; Adult; Aged; Aged, 80 and over; Asthma; Body Mass Index; Case-Control Studies; Female; Humans; Inflammation; Leptin; Leukotrienes; Male; Middle Aged; Obesity; Young Adult

To investigate the association between the clinical severity of childhood asthma and serum leptin levels, to define whether the severity of asthma correlates with body mass index (BMI) or serum leptin levels and to examine the sensitivity of leptin levels in predicting asthma severity.. This study was conducted in 65 patients, aged 2 to 14 yrs with newly diagnosed asthma without any chronic co-morbidity. The subjects were distributed into three groups according to the severity of asthma.. Intra-group serum leptin levels before and after treatment did not show significant difference (p>0.05). Inter-group pre-treatment leptin levels were different significantly (p<0.01) and the difference originated from Group I and III as well as Group II and III. No correlation existed between leptin levels and BMI (p>0.05).. Leptin levels correlated with the clinical severity of asthma and this was suggested to be associated with the severity of inflammation in asthma. More studies are required to evaluate leptin levels in predicting asthma severity.

Topics: Adolescent; Asthma; Biomarkers; Body Mass Index; Child; Child, Preschool; Female; Humans; Leptin; Male; Sensitivity and Specificity; Severity of Illness Index

To understand the role of leptin and adiponectin in obese asthmatics.. We compared serum leptin, adiponectin and sputum leptin levels in 44 non-obese and 44 obese subjects.. We found higher serum leptin (P < 0.0001) and lower adiponectin (P = 0.0002) levels in obese asthmatics. Sputum leptin was correlated with body mass index (BMI; r = 0.34, P = 0.03) and serum leptin (r = 0.43, P = 0.005); however, this last correlation was not significant after adjusting for BMI (r = 0.26, P = 0.11).. Airway inflammation in obese asthmatics may present a different pattern involving leptin. Sputum leptin levels may partially originate from systemic circulation, with other contributing mechanisms.

Topics: Adiponectin; Adult; Asthma; Biomarkers; Female; Humans; Leptin; Male; Middle Aged; Obesity; Sputum

Obesity-mediated changes in plasma adipokines have been associated with increased systemic inflammation and oxidative stress. However, it is unknown whether obesity induces similar changes in airway levels of these adipokines and whether these changes are associated with increased airway biomarkers of inflammation and oxidative stress.. Lean and obese asthmatics and controls underwent bronchoscopy with bronchoalveolar lavage (BAL), spirometry, and provided fasting plasma leptin and adiponectin. Biomarkers of oxidation and inflammation in the BAL included exhaled nitric oxide (NO), 8-isoprostanes, pH, and nitrogen oxide products (NOx).. Out of a total of 48 subjects, 44% had asthma and 56% were healthy controls. Among subjects with asthma, 66% were obese, 10% overweight, and 24% lean; in the controls these proportions were 63%, 11%, and 26%, respectively. After adjusting for age, sex, smoking history, ethnicity, and prebronchodilator forced exhalation in 1 second (FEV(1)), obesity was associated with higher BAL and plasma leptin levels in asthmatics and controls. Increasing BMI was associated with increased BAL leptin and was marginally and inversely associated with BAL adiponectin. Significant associations between BAL and plasma levels were only observed for leptin. No significant associations were observed between BAL and plasma adipokines with the airway biomarkers of oxidation and inflammation.. Increasing BMI is associated with changes in the concentrations of airway adipokines in asthmatics and healthy controls; however, these associations are not related with biomarkers of airway oxidation or inflammation.

Topics: Adiponectin; Adolescent; Adult; Asthma; Biomarkers; Body Mass Index; Bronchoalveolar Lavage Fluid; Case-Control Studies; Female; Humans; Inflammation; Leptin; Lung; Male; Middle Aged; Obesity; Oxidative Stress; Thinness; Young Adult

It has been shown that the prevalence of asthma in obese people has increased in recent years. The aim of this study was to evaluate factors involved in the relationship between asthma and obesity in women,. We evaluated serum leptin levels, fractional exhaled nitric oxide (FE(N0), asthma control (using theAsthma Control Test [ACT]), and presence of atopy in 41 obese women with asthma and 40 non-obese women with asthma. We also compared the relationship between body mass index (BMI) and these parameters between the 2 groups.. Serum leptin levels were significantly higher in obese asthmatics than in nonobese asthmatics (P < .05). In the obese group, leptin levels were positively correlated with FE(O) levels (r = 0.439, P = .004). Uncontrolled asthma (ACT score <20) was detected in 61% of women in the obese group compared to just 38% of those in the nonobese group (P = -.035). In atopic patients, total immunoglobulin E levels were positively correlated with leptin levels (r = 0.329, P = .038). When the 81 women were classified according to asthma control, high BMI was found to be the only significant factor that contributed to poor asthma control.. We have shown that serum leptin levels might have a role in poor asthma control in obese patients, and can conclude that obesity is an important factor in uncontrolled asthma.

Topics: Adult; Aged; Anti-Asthmatic Agents; Asthma; Body Mass Index; Breath Tests; Cross-Sectional Studies; Female; Humans; Hypersensitivity, Immediate; Leptin; Middle Aged; Nasal Polyps; Nitric Oxide; Obesity; Prevalence; Sinusitis; Skin Tests; Spirometry; Treatment Outcome; Turkey

Obesity is a risk factor for asthma. Studies in mice suggest that the adipokines leptin and adiponectin affect asthmatic responses. The purpose of this study was to determine if adipokines associated with obesity are (1) altered in obese women with asthma compared to controls and (2) associated with increased cytokines and chemokines involved in allergic inflammation.. We performed a cross-sectional study of asthmatic and non-asthmatic obese premenopausal women. Participants answered questionnaires and performed lung function tests. Serum and peripheral blood mononuclear cells (PBMCs) were collected for analysis of cytokines and adipokines.. A total of 22 asthmatic (mean body mass index 40.0 ± 5.1 kg/m(2)) and 20 non-asthmatic women (mean body mass index 41.3 ± 5.6 kg/m(2)) participated. We found no difference in serum adipokine concentrations between asthmatics and non-asthmatics. Serum adiponectin correlated positively with PBMC eotaxin (r(s) = 0.55, p = .0003) and RANTES (regulated upon activation, normal T-cell expressed, and secreted) (r(s) = 0.36, p = .03), whereas serum leptin correlated negatively with PBMC eotaxin (r(s) = -0.34, p = .04). There was a negative correlation between serum adiponectin and PBMC interferon-γ (r(s) = -0.41, p = .01).. Perturbations of adipokines that occur in obesity were correlated with decreased cytokine production typically associated with allergic responses in PBMC of obese premenopausal women. This study suggests that although obese asthmatics may have elements of Th2-mediated inflammation, adipokine derangements in obesity are associated with Th1 rather than Th2 bias. Obesity has complex effects on allergic inflammation and is likely to be important modifier of the pathogenesis of airway disease in asthma.

Topics: Adiponectin; Adolescent; Adult; Asthma; Cross-Sectional Studies; Female; Humans; Leptin; Leukocytes, Mononuclear; Lung; Middle Aged; Obesity; Respiratory Function Tests; Statistics, Nonparametric; Th1 Cells; Th2 Cells; Young Adult

Intrinsic asthma, etiology unknown, occurs later in life, mostly in females. It is associated with nasal polyps and massive eosinopillic infiltration of the respiratory mucous membrane, aspirin intolerance and steroid dependence. The aim of the study was to determine the cytokine and chemokine profile in sera of intrinsic asthmatics and control subjects.. Blood was taken from 10 intrinsic asthmatic female and 12 control female subjects. Expression profile of 42 different cytokines and chemokines were measured using a microarray composed of antibodies against the cytokines and chemokines. Complete blood count and C-reactive protein were measured, to assess the state of inflammation in both groups.. We have identified Macrophage Colony Stimulating Factor, a proinflammatory cytokine and Monocyte Chemoattractant Protein 2, a CC chemokine as having significantly higher expression levels in intrinsic asthmatic subjects compared to controls (341.71±31.28 SEM Signal intensity) versus (247.97±28.09 SEM Signal intensity), p=0.036 and (397.07±38.19 SEM Signal intensity) versus (311.33±28.76 SEM Signal intensity), p=0.036, respectively. There were no significant differences in the other cytokines and chemokines measured nor were there any differences in the inflammatory measurements between the two groups except for eosinophil counts, the hall mark of intrinsic asthma.. Macrophage Colony Stimulating Factor and Monocyte Chemoattractant Protein are elevated in sera of intrinsic asthmatics compared to normal controls. These cytokines may have a critical role in the inflammatory pathology of intrinsic asthma.

Topics: Adult; Asthma; Blood Cell Count; C-Reactive Protein; Case-Control Studies; Chemokine CCL8; Female; Humans; Inflammation Mediators; Intercellular Signaling Peptides and Proteins; Leptin; Lymphokines; Macrophage Colony-Stimulating Factor; Oncostatin M; Thrombopoietin; Young Adult

Topics: Adolescent; Asthma; Breath Tests; Child; Exhalation; Female; Humans; Leptin; Male; Overweight; Pilot Projects

Topics: Adiponectin; Adult; Asthma; Cohort Studies; Fasting; Female; Humans; Leptin; Male; New Zealand; Obesity; Sample Size; Sex Characteristics; United States

Increased BMI is a risk factor for asthma in children and may be related to adipokines. Adipokines affect insulin-stimulated glucose uptake in vitro but, to date there is little evidence for such a role in vivo. We explored relationships between obesity and allergic asthma in children.. Twenty-one allergic asthmatics (AA) and 10 non-allergic healthy controls, aged 6-17.9 years were studied. AA group included children with a positive mannitol challenge test, >25 ppb of exhaled nitric oxide and a positive skin prick test. BMI z-scores were calculated. Blood levels of insulin, glucose, leptin, resistin, tumour necrosis factor-alpha, IL-4, IL-5 and IL-6 were measured. Insulin resistance (IR) was estimated using the homeostasis model assessment (HOMA).. There was no significant difference in BMI z-scores between AA and healthy controls (mean: 0.01 vs -0.10). However, significant differences were found in the blood levels of IL-6 (P = 0.05), IL-4 (P = 0.04), IL-5 (P = 0.01) and leptin (P = 0.02). IR was only found in the AA group (42.85%). Homeostasis model assessment insulin resistance (HOMA-IR) was significantly related to IL-6 (r = 0.44, P = 0.05) and tumour necrosis factor-alpha (r = -0.45, P = 0.05).. IR was observed in AA. Our findings are suggestive of a complex interaction between the inflammatory state and adiposity, allergy and asthma.

Topics: Adolescent; Asthma; Australia; Blood Glucose; Body Mass Index; Child; Female; Humans; Insulin; Insulin Resistance; Interleukins; Leptin; Male; Mannitol; Nitric Oxide; Obesity; Resistin; Risk Factors; Skin Tests; Tumor Necrosis Factor-alpha

Arachidonic acid (AA) is considered essential in fetal development and some of its metabolites are thought to be important mediators of the immune responses. Therefore, we studied whether prenatal exposure to AA is associated with some immune-related clinical conditions and plasma markers in childhood. In 280 children aged 7 years, atopy, lung function and plasma inflammation markers were measured and their relationships with early AA exposure were studied by linear and logistic regression analyses. AA exposure was deduced from AA concentrations in plasma phospholipids of the mothers collected at several time points during pregnancy and at delivery, and in umbilical cord plasma and arterial and venous wall phospholipids. In unadjusted regression analyses, significant positive associations were observed between maternal AA concentrations at 16 and 32 weeks of pregnancy (proxies for fetal AA exposure) and peak expiratory flow decline after maximal physical exercise and plasma fibrinogen concentrations of their children, respectively. However, after correction for relevant covariables, only trends remained. A significant negative relationship was observed between AA concentrations in cord plasma (reflecting prenatal AA exposure) and the average daily amplitude of peak expiratory flow at rest, which lost significance after appropriate adjustment. Because of these few, weak and inconsistent relationships, a major impact of early-life exposure to AA on atopy, lung function and selected plasma inflammation markers of children at 7 years of age seems unlikely.

Topics: Arachidonic Acid; Asthma; Biomarkers; C-Reactive Protein; Child; Child Development; Female; Fetal Blood; Fibrinogen; Follow-Up Studies; Humans; Hypersensitivity; Infant, Newborn; Leptin; Linear Models; Peak Expiratory Flow Rate; Pregnancy; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Prenatal Exposure Delayed Effects; Prospective Studies; Respiratory Function Tests; von Willebrand Factor

Mounting evidence implicates obesity as a major risk factor for asthma. Leptin and adiponectin produced by fat tissues play a critical role in the regulation of body weight and allergic inflammation.. The aim of this study was to evaluate the effects of leptin and adiponectin on development of asthma.. We measured the leptin and adiponectin in serum from patients with asthma (n = 60) and normal control subjects (n = 30) by enzyme-linked immunosorbent assay.. Logarithmic leptin and adiponectin concentration was not different between asthmatics and control subjects. Although the logarithmic adiponectin level was not different by gender in asthmatics, the logarithmic leptin concentration was significantly higher in females than in male asthmatics (2.41 +/- 0.05 ng/mL vs. 2.01 +/- 0.05 ng/mL, p = 0.001). The leptin/adiponectin ratio was also significantly higher in females than in male asthmatics. The leptin/adiponectin ratio was correlated with body mass index (r = 0.210, p = 0.05) in asthmatics.. Our results suggest that serum leptin and adiponectin may be associated with gender and obesity regardless of development of asthma.

Topics: Adiponectin; Adolescent; Adult; Aged; Asthma; Body Mass Index; Bronchial Provocation Tests; Eosinophils; Female; Forced Expiratory Volume; Humans; Immunoglobulin E; Leptin; Male; Middle Aged; Obesity; Sex Factors; Vital Capacity; Young Adult

Increased serum leptin levels have been observed in asthmatic patients. Leptin, via proliferation and activation of Th2 cells, may induce inflammation in asthma. It has also been demonstrated that leptin mRNA expression and protein levels increase in response to inflammatory stimuli. We hypothesized that polymorphisms in the leptin receptor, leptin and ghrelin genes, may affect their expression and, therefore, be responsible for altered response to increased leptin levels observed in asthma. To our knowledge, there were no studies on a potential role of LEPR, LEP, and GHRL polymorphisms in asthma.. We analyzed 129 pediatric patients with asthma and 114 healthy children from the control group ranging from 6 to 18 years of age. The diagnosis of allergic asthma was based on clinical symptoms, the lung function test, and the positive skin prick test and/or increased immunoglobulin E (IgE) levels. Polymorphisms were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Statistical analyses were performed with Statistica v.7.1 software (Statistica, StatSoft, Poland; available free at http://www.broad.mit.edu/mpg/haploview/index.php). Linkage disequilibrium analysis was performed with Haploview v.4.0.. We observed a statistically significant association of the 3'UTR A/G and the -2549A/G polymorphisms of the leptin gene with asthma. No association with asthma was observed for the K109R and the Q223R polymorphisms of the LEPR gene and the Met72Leu polymorphism of the ghrelin gene. In the analysis of body mass index (BMI) stratified by genotype, we found an association of the -2549A/G LEP, but not of LEPR and GHRL polymorphisms, with higher BMI values in asthmatic patients. We found suggestive evidence for linkage between the two polymorphisms of the LEPR gene (D' = 0.84 CI: 0.71-0.92; r(2) = 0.29) in linkage disequilibrium analysis: The GG haplotype was more frequent in the control healthy group (p = 0.057). No linkage disequilibrium was detected between LEP polymorphisms.. Polymorphisms of the leptin gene may be associated with asthma and higher BMI in asthmatic patients. Polymorphisms of the LEPR and GHRL seem unlikely to be associated with asthma or BMI in our sample. The results of haplotype analysis for the LEPR gene may suggest a protective role of the GG haplotype against asthma; however, studies on larger groups are necessary to confirm the observed trend towards association.

Topics: Adolescent; Asthma; Body Mass Index; Child; Energy Metabolism; Female; Gene Frequency; Genotype; Ghrelin; Haplotypes; Humans; Leptin; Linkage Disequilibrium; Male; Poland; Polymorphism, Single Nucleotide; Receptors, Leptin

The prevalence of asthma and obesity is increasing concomitantly, but many aspects of this link are unclear. Our objective was to examine whether obesity is associated with asthma in three time points of life, and whether immunomodulatory adipokines, leptin and adiponectin are linked to overweight-associated asthma.. We studied the association between obesity and asthma at ages 3-18 years [mean (SD), 10 years (5), n = 3582, year 1980], 9-24 years [16 years (5), n = 2764, 1986] and 24-39 years [32 years (5), n = 2620, 2001] in a prospective cohort study and further tested for associations with serum leptin and adiponectin concentrations. Data on allergy status, smoking and other laboratory values (serum insulin, plasma C-reactive protein and serum lipid values) were also analyzed.. Allergy and parental asthma were significantly associated with asthma at all ages. At ages 24-39 years, but not earlier, body mass index (BMI) (odds ratio, OR 1.05; P = 0.019) and female gender (OR 1.56; P = 0.031) were independently associated with asthma. Increase in BMI was also associated with incident asthma during adulthood (OR 1.08; P = 0.030). Levels of leptin, adiponectin or any other obesity-related biomarker were not independently associated with asthma.. Asthma is linked with obesity in adults, but our results do not support a significant role for leptin, adiponectin or any other obesity-related biomarker studied in this association. Other factors should be sought for better understanding the connection between obesity and asthma.

Topics: Adipokines; Adiponectin; Adolescent; Adult; Asthma; Body Mass Index; C-Reactive Protein; Child; Child, Preschool; Cohort Studies; Female; Finland; Humans; Leptin; Male; Obesity; Prospective Studies; Risk Factors; Sex Factors; Young Adult

The increase of asthma has paralleled the rising obesity during the past decades. Obesity is characterized by the increase of leptin in the circulation. Leptin is an obesity gene product, and it can stimulate the production of pro-inflammatory mediators, such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and interferon (IFN)-gamma. There is a link between leptin and asthma, especially in children. It remains unclear however, if leptin is in the pathway of obesity-asthma relationship and if it plays a distinctive role in asthma in obese vs. non-obese subjects. Since leptin is in a positive feedback loop with the pro-inflammatory cytokines such as TNF-alpha, there is a possibility that leptin is involved as a regulatory rather than an etiologic mechanism of asthma development. Weight loss is associated with decreased circulating leptin concentration in children. Weight control program may need to be considered in the treatment of asthma in obese children.

Topics: Asthma; Humans; Interferon-gamma; Interleukin-6; Leptin; Obesity; Tumor Necrosis Factor-alpha

The adipokine leptin is a potential new mediator for bronchial epithelial homeostasis. Asthma is a chronic inflammatory disease characterized by airway remodeling that might affect disease chronicity and severity. TGF-beta is a tissue growth factor the dysregulation of which is associated with airway remodeling.. We sought to determine whether a bronchial epithelial dysfunction of the leptin/leptin receptor pathway contributes to asthma pathogenesis and severity.. We investigated in vitro the presence of leptin/leptin receptor on human bronchial epithelial cells. Then we studied the effect of TGF-beta and fluticasone propionate on leptin receptor expression. Finally, the role of leptin on TGF-beta release and cell proliferation was analyzed. Ex vivo we investigated the presence of leptin/leptin receptor in the epithelium of bronchial biopsy specimens from subjects with asthma of various severities and from healthy volunteers, and some features of airway remodeling, such as reticular basement membrane (RBM) thickness and TGF-beta expression in the epithelium, were assessed.. In vitro bronchial epithelial cells express leptin/leptin receptor. TGF-beta decreased and fluticasone propionate increased leptin receptor expression, and leptin decreased the spontaneous release of TGF-beta and increased cell proliferation. Ex vivo the bronchial epithelium of subjects with mild, uncontrolled, untreated asthma showed a decrease expression of leptin and its receptor and an increased RBM thickness and TGF-beta expression when compared with values seen in healthy volunteers. Furthermore, severe asthma was associated with a reduced expression of leptin and its receptor and an increased RBM thickness with unaltered TGF-beta expression.. Decreased expression of leptin/leptin receptor characterizes severe asthma and is associated with airway remodeling features.

Topics: Adult; Androstadienes; Asthma; Bronchi; Cell Line; Cell Proliferation; Chromones; Enzyme Inhibitors; Female; Fluticasone; Humans; Imidazoles; Leptin; Male; Middle Aged; Morpholines; Pyridines; Receptors, Leptin; Recombinant Proteins; Respiratory Mucosa; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha

To investigate the effects of leptin on airway inflammation and the expression of Th1/Th2 cytokines.. The obesity and acute asthma models were established in 40 female SD rats, which were randomly divided into a normal weight control group (group A), a normal weight asthmatic group (group B), a normal weight intervention group (group C), an obese control group (group D) and an obese asthmatic group (group E). The airway resistance and airway responsiveness were calculated by transpulmonary pressure and gas flow rate. The numbers of leukocytes, eosinophils (EOS) and neutrophils (N) in bronchoalveolar lavage fluid (BALF) were counted. The concentrations of interleukin-4 (IL-4), interferon-gamma (IFN-gamma) and leptin in serum and BALF were determined by ELISA. The protein and mRNA expression of leptin was measured by Western blot and RT-PCR respectively.. The airway resistance in group C and E [(0.890 +/- 0.106) cm H2Oxml(-1)xs(-1), (1.024 +/- 0.096) cm H2Oxml(-1)xs(-1), (1.129 +/- 0.107) cm H2Oxml(-1)xs(-1), (0.946 +/- 0.104) cm H2Oxml(-1)xs(-1), (1.124 +/- 0.095) cm H2Oxml(-1)xs(-1), (1.135 +/- 0.105) cm H2Oxml(-1)xs(-1), respectively.] was increased significantly compared to group B [(0.638 +/- 0.128) cm H2Oxml(-1)xs(-1), (0.745 +/- 0.073) cm H2Oxml(-1)xs(-1), (0.773 +/- 0.090) cm H2Oxml(-1)xs(-1)] (q = 7.128, 8.712, 8.318, 11.300, 11.258, 11.447, all P < 0.05). The numbers of leukocyte and neutrophils in group C and E [(91 +/- 9) x 10(4)/ml, (108 +/- 21) x 10(4)/ml, (12.4 +/- 4.0) x 10(4)/ml, (14.2 +/- 5.9) x 10(4)/ml, respectively.] were increased significantly compared to group B [(79 +/- 7) x 10(4)/ml, (2.4 +/- 1.1) x 10(4)/ml] (q = 2.923, 7.063, 8.629, 10.182, all P < 0.05). The concentrations of IFN-gamma were [(42.3 +/- 3.5) ng/L, (45.1 +/- 4.8) ng/L, (19.2 +/- 1.8) ng/L, (20.3 +/- 1.5) ng/L] in group C and E respectively, which were significantly higher than those of group B [(16.5 +/- 1.4) ng/L, (9.3 +/- 1.0) ng/L] (q = 21.607, 23.952, 16.919, 18.799, all P < 0.05). The protein and mRNA expression of leptin in lung tissue in group C and E [(0.40 +/- 0.07) ng/L, (0.44 +/- 0.05) ng/L, (0.34 +/- 0.06) ng/L, (0.38 +/- 0.04) ng/L, respectively.] were remarkably higher than those of group B [(0.31 +/- 0.03) ng/L, (0.21 +/- 0.04) ng/L] (q = 4.648, 6.713, 8.222, 10.752, all P < 0.05).. Leptin could aggravate airway inflammation featured by infiltration of neutrophils and enhancement of Th1 type inflammation.

Topics: Animals; Asthma; Female; Interferon-gamma; Interleukin-4; Leptin; Neutrophils; Rats; Rats, Sprague-Dawley

The aim of this study was to measure plasma leptin level in patients with bronchial asthma (BA) and compare it with clinical features of the disease. It included 21 healthy subjects, 9 patients with extrapulmonary allergy, and 18 with partially controllable BA. Plasma leptin was measured by ELISA. Patients with BA showed a much higher leptin level and its significant difference depending on body mass index. Correlation analysis revealed significant correlation between leptin level and degree of eosinophilia in peripheral blood and phlegm, epidermal and iatrogenic sensitization, per os glucocorticoid therapy, concomitant pathology, such as type 2 diabetes, thyroid diseases, cardiological problems (CHD, hypertensive disease), and their complications (acute myocardial infarction, stroke). The reported phenomenon of elevated plasma leptin level in BA patients and its correlation with a number of clinical features open up a possibility for further investigation into the role of obesity in BA pathogenesis and its progress, for the search of new ways to manage the disease.

Topics: Asthma; Enzyme-Linked Immunosorbent Assay; Humans; Leptin

Obesity is thought to increase the risk of asthma, especially in women. It has been proposed that this association could be due to the immune-modulating effect of adipokines secreted by adipose tissue.. To investigate whether aspects of the asthma phenotype are associated with higher levels of the proinflammatory adipokine leptin and lower levels of the anti-inflammatory adipokine adiponectin in a cross-sectional analysis of a group of young adults.. Associations between leptin and adiponectin and a diagnosis of asthma, symptoms of wheeze, bronchodilator response, airflow obstruction, and exhaled nitric oxide were evaluated by logistic or linear regression in a population-based birth cohort of approximately 1,000 men and women aged 32 years. Further analyses adjusted for smoking and body fat.. There were no significant associations between leptin and any of the markers of the asthma phenotype in either men or women. In men, higher levels of adiponectin were associated with lower levels of exhaled nitric oxide but an increased risk of bronchodilator responsiveness. The inverse association with exhaled nitric oxide remained significant after adjustment for body fat, but the association with bronchodilator responsiveness did not. Adiponectin levels were not associated with any markers of asthma in women.. The inverse association between adiponectin and exhaled nitric oxide in men warrants further investigation. However, the findings indicate that levels of leptin and adiponectin are unlikely to mediate the previously observed association between obesity and asthma.

Topics: Adiponectin; Adult; Asthma; Breath Tests; Bronchial Provocation Tests; Cohort Studies; Female; Forced Expiratory Volume; Humans; Leptin; Male; New Zealand; Nitric Oxide; Obesity; Respiratory Sounds; Sex Characteristics; Smoking; Vital Capacity

To determine the role of serum leptin in infants with wheezing after respiratory syncytial virus infected.. 43 infants infected with RSV were given blood samples to detect leptin concentration with radioimmunoassays (RIA) within 24 hours after admission into hospital, discharged and 12 weeks later. Then, they were followed up for 2 years. 10 healthy children of the same age served as controls.. 41.9% infants developed asthma after infected with RSV. Compared to control group, the serum level of leptin in the asthma group and non-asthma group were significantly higher before treatment (t = 3.41 and 2.64 respectively, P < 0.05). When they were discharged, the serum level of leptin in the asthma group was significantly higher than that in non-asthma group and control group (t = 5.74 and 6.23, respectively, P < 0.05). 12 weeks later, the serum level of leptin in the asthma group was still significantly higher than that in non-asthma group and control group (t = 6.32 and 6.11, respectively, P < 0.05), but there were no difference between non-asthma group and control group (t = 0.81, P > 0.05).. The serum level of leptin in infants with asthma after RSV infected was higher than that in healthy and non-asthma children. Persistent higher level of leptin may play an important role in infants with asthma after RSV infected.

Topics: Asthma; Case-Control Studies; Child, Preschool; Female; Follow-Up Studies; Humans; Infant; Leptin; Male; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses

Topics: Adolescent; Asthma; Biomarkers; Child; Comorbidity; Female; Humans; Inflammation Mediators; Leptin; Leukocytes; Male; Obesity; Peroxidase; Prognosis; Retrospective Studies

There is growing evidence for an association between obesity and asthma, but little is known about the underlying mechanisms. We hypothesized that high plasma leptin and low plasma adiponectin concentrations might be related to asthma and allergies in children. Plasma leptin and adiponectin concentrations were measured in a cross-sectional study involving 462 children aged 10 years. Information on disease symptoms and diagnosis was collected by parental questioning. Multivariate linear and logistic regression models were used to assess the association between biomarkers and disease. High leptin levels were associated with increased lifetime prevalence of asthma [odds ratio (OR): 3.76; 95% confidence interval (CI): 1.42-9.92]. The relationship was particularly strong for non-atopic asthma (OR: 5.51; 95% CI: 1.99-17.51). No associations were observed between plasma leptin levels and hay fever, and rhinoconjunctivitis. Low adiponectin levels were associated with increased prevalence of both symptoms of atopic dermatitis (OR: 3.23; 95% CI: 1.28-7.76) and ever-diagnosed eczema (OR: 2.35; 95% CI: 1.13-4.89). In girls and non-atopic children, stronger associations for both leptin and adiponectin levels with asthma than in boys and atopic children were observed. These results suggest that adipokines may contribute to increased asthma and allergy risk in obese subjects. Stronger associations among girls with non-atopic asthma may indicate diverse pathological mechanisms.

Topics: Adiponectin; Asthma; Child; Conjunctivitis; Cross-Sectional Studies; Eczema; Female; Germany; Humans; Leptin; Logistic Models; Male; Obesity; Sex Factors; Surveys and Questionnaires

Topics: Asthma; Humans; Leptin; Obesity; T-Lymphocytes, Regulatory

Obesity is considered a risk factor for asthma. However, the mechanism that connects the two is not well understood. In this study we investigated the relationship between inflammatory cytokines and acute phase reactants in obesity, and asthma.. Asthmatic and control subjects were divided into 2 sub-groups: obese and non-obese. Anthropomorphic parameters, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), leptin, tumour necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were compared between obese, asthmatics and control subjects of normal weight. Respiratory function tests and allergy skin tests were also performed in the patients with asthma.. ESR, CRP, TNF-alpha, IL-6, and leptin levels in obese asthma patients were higher than in the healthy controls (P < 0.01). TNF-alpha, IL-6, and leptin levels were higher in obese asthma patients than in non-obese asthma patients (P < 0.01). Inflammatory markers were related to parameters of obesity. No association was found between allergy test results and obesity (P > 0.05).. We identified a relationship between acute phase reactants and inflammatory cytokines, and the criteria for obesity in obese asthma patients. Inflammation markers were at their highest levels in obese asthma patients. Leptin levels were considerably higher in obese patients than in normal weight controls. Like obesity, leptin is suggested to play a role in the pathogenesis of asthma.

Topics: Adult; Analysis of Variance; Asthma; Body Mass Index; C-Reactive Protein; Cytokines; Female; Fibrinogen; Humans; Interleukin-6; Leptin; Middle Aged; Obesity; Tumor Necrosis Factor-alpha; Waist Circumference; Waist-Hip Ratio; Young Adult

Obesity has been associated with an increased prevalence of asthma and poorer control of this disease. However, the mechanisms by which obesity can influence airway function and make asthma more difficult to control remain uncertain. The physiological changes associated with obesity can contribute to respiratory symptoms and these should be differentiated from those caused by asthma. Obesity can possibly influence the development of asthma through genetic, developmental, hormonal, neurogenic or mechanical influences. Breathing at low lung volumes and changes in the pattern of breathing in obese subjects may alter airway smooth muscle plasticity and airway function. The release by adipocytes of various cytokines and mediators such as Interleukin-6, TNF-alpha, eotaxin, and leptin, and the reduction of anti-inflammatory adipokines in obese subjects may possibly contribute to the development or increased clinical expression of asthma in promoting airway inflammation. Reduced asthma control and impaired response to asthma therapy have been reported in obese patients. Obesity-related co-morbidities such as Sleep Apnea and Gastro-esophageal reflux may also contribute to this poor control. Weight loss improves asthma control and reduces medication needs. Research is needed to better define the optimal management of obese asthmatic patients.

Topics: Asthma; Body Mass Index; Canada; Cytokines; Humans; Leptin; Obesity; Prevalence; Risk Factors; Treatment Outcome; Weight Loss

Although the prevalences of asthma and obesity are increasing substantially in recent decades, very little is known about the possible association between them. We evaluated the roles of leptin, adiponectin, and resistin, which are adipokines produced by adipose tissue, on childhood asthma, and their association with pulmonary function and bronchial hyperresponsiveness. We studied 149 atopic asthmatic children, 37 non-atopic asthmatic children, and 54 healthy children. Body mass index was calculated using height and weight, which were measured on the same day that pulmonary function tests and methacholine challenge tests were performed. Skin prick tests were performed, and total eosinophil count, total serum immunoglobulin E (IgE), serum eosinophil cationic protein, leptin, adiponectin, and resistin were measured in all subjects. Atopic asthmatics had lower resistin levels compared with non-atopic asthma and control groups, but leptin and adiponectin did not show any difference among these three groups. Resistin demonstrated positive correlation with methacholine PC(20) and negative correlations with eosinophil count and serum total IgE. Leptin and adiponectin showed associations with forced expiratory volume in 1 s or forced expiratory flow between 25-75%. Multiple regression analysis revealed that resistin was a significant predictive factor for asthma. There was no direct association between asthma and leptin or adiponectin. Our findings suggest that resistin may play a negative predictive role in asthma. Adiponectin and leptin showed close associations with pulmonary function and may have disease-modifying effects in children with asthma.

Topics: Adiponectin; Asthma; Body Mass Index; Child; Eosinophil Cationic Protein; Eosinophils; Female; Humans; Immunoglobulin E; Leptin; Male; Resistin; Skin Tests

Recently, it has been shown that increasing body mass index (BMI) in asthma is associated with reduced exhaled NO. Our objective in this study was to determine if the BMI-related changes in exhaled NO differ across asthmatics and controls, and to determine if these changes are related to increased airway oxidative stress and systemic levels of leptin and adiponectin.. Observational study of the association of BMI, leptin, and adiponectin with exhaled nitric oxide (NO) and exhaled 8-isoprostanes in 67 non-smoking patients with moderate to severe persistent asthma during baseline conditions and 47 controls. Measurements included plasma levels of leptin, adiponectin, exhaled breath condensates for 8-isoprostanes, exhaled NO, pulmonary function tests, and questionnaires regarding asthma severity and control.. In asthmatics, BMI and the ratio of leptin to adiponectin were respectively associated with reduced levels of exhaled NO (beta = -0.04 [95% C.I. -0.07, -0.1], p < 0.003) and (beta = -0.0018 [95% C.I. -0.003, -0.00034], p = 0.01) after adjusting for confounders. Also, BMI was associated with increased levels of exhaled 8-isoprostanes (beta = 0.30 [95% C.I. 0.003, 0.6], p = 0.03) after adjusting for confounders. In contrast, we did not observe these associations in the control group of healthy non-asthmatics with a similar weight distribution.. In adults with stable moderate to severe persistent asthma, but not in controls, BMI and the plasma ratio of leptin/adiponectin is associated with reduced exhaled NO. Also, BMI is associated with increased exhaled 8-isoprostanes. These results suggest that BMI in asthmatics may increase airway oxidative stress and could explain the BMI-related reductions in exhaled NO.

Topics: Adiponectin; Adult; Aged; Asthma; Body Mass Index; Exhalation; Female; Humans; Isoprostanes; Leptin; Male; Middle Aged; Nitric Oxide; Severity of Illness Index

Topics: Asthma; Child; Female; Ghrelin; Humans; Hypersensitivity; Immunoglobulin E; Leptin; Male; Obesity; Peptide Hormones

Leptin, a pro-inflammatory cytokine produced by adipose tissue, has previously been shown to be associated with asthma in children. We hypothesised that high serum leptin concentrations would also be associated with asthma in adults.. The Third National Health and Nutrition Examination Survey is a cross sectional study that included fasting serum leptin concentrations and self-report of doctor diagnosed asthma. Data were analysed using multivariable logistic regression analysis.. Of 5876 participants, those with current asthma had a higher mean unadjusted leptin concentration than those who had never had asthma (geometric mean (SE) 9.2 (0.6) microg/l v 7.6 (0.2) microg/l; p = 0.02). After adjustment for triceps skinfold thickness and other covariates, the association between leptin and asthma appeared stronger in women than in men, and in premenopausal women than in postmenopausal women. Body mass index (BMI) was also associated with current asthma in women, but this association was not significantly affected by adjustment for leptin concentrations.. The results of this large population based study support the hypothesis that leptin is associated with asthma in women. In addition, while BMI also is related to asthma in women, this study does not support the suggestion that leptin contributes significantly to this association.

Topics: Adult; Asthma; Biomarkers; Body Mass Index; Cross-Sectional Studies; Female; Humans; Leptin; Male; Middle Aged; Regression Analysis

Topics: Asthma; Body Mass Index; Case-Control Studies; Exhalation; Female; Humans; Inflammation Mediators; Leptin; Male; Nitric Oxide; Obesity

Although there is evidence of a positive association between asthma and obesity in adults and children, very little is known about the role of leptin in asthmatic children.. The aims of this study were to evaluate the relation between leptin and parameters of atopy and asthma in children.. Body mass index (BMI) and serum leptin levels were measured in 102 (37 female, 65 male; mean age, 5.9 +/- 3.4 years) asthmatic and 33 (14 female, 19 male; mean age, 6.1 +/- 3.4 years) healthy children. Skin prick tests, total serum IgE, and pulmonary function tests were performed and were completed.. A significant difference was observed in serum leptin levels between asthmatic and healthy children. Median (interquartile range) levels were 3.53 (2.06-7.24) ng/mL and 2.26 (1.26-4.71) ng/mL, respectively (P=.008). Subgroup analysis revealed that this difference in leptin levels was confined entirely to boys: 3.09 (1.99-7.51) ng/mL in boys with asthma versus 1.52 (1.06-3.17) ng/mL in boys without asthma (P=.003). By logistic regression analysis, we found that leptin was a predictive factor for having asthma (odds ratio, 1.98; CI, 1.10-3.55; P=.021), whereas sex, age, or BMI were not. In a stepwise multiple regression analysis including sex (P=.001), age (P=.016), BMI (P <.001), and asthma (P=.022), all of these variables were found to affect log leptin levels (R2=0.404). There was no significant sex difference in serum leptin levels among asthmatic children, whereas healthy boys had significantly lower leptin levels than healthy girls (P=.019). Atopic asthmatic subjects had significantly higher leptin levels than nonatopic asthmatic subjects (P=.038) with similar BMI. A significant, but weak, correlation was observed between leptin levels and IgE in the overall group of asthmatic children (r=0.231; P=.019). Again, this correlation was confined entirely to boys (r=0.319; P=.010). There was no relation between leptin levels and skin prick tests, pulmonary function tests, passive smoking, birth weight, and duration of breast-feeding.. Our findings suggest that leptin may play a role in atopic asthma. High serum leptin levels in asthmatic boys may partly explain the higher prevalence of childhood asthma in male sex.

Topics: Asthma; Body Mass Index; Child; Child, Preschool; Female; Forced Expiratory Volume; Humans; Immunoglobulin E; Interleukin-6; Leptin; Male; Sex Factors; Tumor Necrosis Factor-alpha

Recent observations suggest the presence of an interaction between leptin and the inflammatory system; however, there is no adequate knowledge about the role of leptin in atopic states such as asthma.. To evaluate the potential role of leptin in relation to bronchial asthma and inhaled corticosteroid therapy.. Twenty-three children with mild-to-moderate, newly diagnosed asthma enrolled in this 2-period trial. The control group consisted of 20 age- and sex-matched children. Serum leptin levels were measured in patients at initiation and after 4 weeks of budesonide treatment and were compared with control group measurements.. Asthmatic children had higher mean +/- SD serum leptin levels at admission (19.3 +/- 5.1 ng/mL) than after budesonide treatment (10.6 +/- 1.6 ng/mL) and vs control group measurements (9.8 +/- 1.6 ng/mL) (P < .001). There was a significant correlation between serum leptin levels before and after budesonide treatment (r = 0.68; P = .007). Mean +/- SD body mass indices in patients and controls were 16.7 +/- 2.1 and 16.9 +/- 2.6 kg/m2, respectively. Serum leptin levels did not correlate with body mass indices before budesonide treatment in the study group (r = -0.13; P = .65) but correlated well after budesonide treatment (r = 0.58; P = .009) and in the control group (r = 0.65; P = .008).. The role of leptin elevation in children with asthma might be a regulatory mechanism rather than being etiologic, but a question may be raised whether it is possible that leptin may contribute to poor patient outcomes. Further research, both basic and clinical, is essential to explain the exact mechanism.

Topics: Anti-Asthmatic Agents; Asthma; Body Mass Index; Budesonide; Child; Child, Preschool; Female; Humans; Leptin; Male; Treatment Outcome

Obesity is suggested as a risk factor for asthma, but the mechanisms are unclear. The relationship between obesity and asthma has not been considered in children born with very low-birth weight (VLBW). We hypothesized that overweight was a contributing factor for asthma in VLBW children, and that leptin and leptin-associated cytokines might play roles in overweight-related asthma. Seventy-four VLBW and 64 normal birth weight (NBW) children participated in a 12-yr follow up study assessing asthma and allergy. Twenty-seven (12 VLBW) of the 138 children were overweight according to the proposed international definition. The diagnosis of current asthma was made by a pediatrician. Serum levels of leptin and interferon (IFN)-gamma were analyzed by enzyme-linked immunosorbent assay (ELISA). Leptin levels were considerably higher in the overweight than in the non-overweight children (median value: 18.1 vs. 2.8 ng/ml, p < 0.001). In the overweight children, current asthmatics had twice as high levels of leptin as children without current asthma (median value: 30.8 vs. 14.3 ng/ml, p = 0.14), but this was not the case in the non-overweight children. IFN-gamma was more often detected in the overweight than in the non-overweight children (61% vs. 12%, p < 0.001), and there was a positive correlation between the levels of leptin and the levels of IFN-gamma (Rho = 0.40, p < 0.001). In the VLBW group, the overweight children had a significantly increased risk for current asthma compared with the non-overweight children after adjustment for the neonatal risk factors [adjusted odds ratio (OR) 5.8, 95% confidence interval (CI): 1.2-27]. Thus, overweight was associated with asthma in the VLBW children. Our hypothesis remained that leptin might be involved in the pathogenesis of asthma in the overweight children, and IFN-gamma might be a pathway in the process of leptin-induced inflammation.

Topics: Asthma; Child; Comorbidity; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Infant, Newborn; Infant, Very Low Birth Weight; Leptin; Male; Obesity; Odds Ratio; Sex Factors; Skin Tests; Spirometry; Statistics, Nonparametric; Sweden

Leptin (LEP) and neuropeptide Y (NPY) are involved in the maintenance of energy balance and create regulatory loops on central and peripheral stage between neuropeptides and hormones, additionally regulated by other physiological stimuli. According to data confirming tendency to overweight and obesity in asthmatic children we have examined the influence of mild asthma on neurohormonal balance. 43 children, aged 7-17 years, including 27 steroid naive mild asthmatic children aged (mean+/-SD) 12.3+/-2.6 years and 16 age matched healthy children participated in the study. Serum LEP and NPY levels were measured radioimmunologically (RIA). Serum leptin level in asthmatic children was 2.84+/-2.1 ng/ml and did not differ to that of healthy children -3.49+/-1.65 ng/ml, both in boys (p=0.85) and girls (0.49). Similarly, we did not observe any differences between NPY levels in asthmatic (113.5+/-31.1 micromol/ml) and healthy (98.5+/-21.9 micromol/ml (p=0.17)), irrespective to sex. Significant correlations between leptin levels and body mass index (BMI) in asthmatics (r=0.62, p=0.01) and healthy children (r=0.56, p=0.02) were observed. We conclude, that mild asthma in children seems not to affect neurohormonal regulation of energy balance.

Topics: Adolescent; Asthma; Body Mass Index; Case-Control Studies; Child; Female; Humans; Leptin; Male; Neuropeptide Y; Radioimmunoassay

To estimate leptin production in long-term steroid therapy, insulin resistance and obesity.. Leptin concentrations were measured with enzyme immunoassay in 101 patients with bronchial asthma and diabetes mellitus and 31 healthy controls with overweight. The mean age was 54.4 +/- 14.1 years in males and 56.8 +/- 12.1 years in females. The body mass index ranged from 18 to 47 kg/m2, while leptin varied from 0.1 to 105.8 ng/ml.. Leptin was highest in patients with bronchial asthma and steroids-induced diabetes mellitus, lower in patients with diabetes mellitus type 2 and obese controls while it was lowest in patients with atopic bronchial asthma.. Steroids and insulin resistance participate in the regulation of leptin production. Steroids induce hyperleptinemia in vivo more intensively than insulin.

Topics: Adult; Aged; Asthma; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Humans; Insulin Resistance; Leptin; Male; Middle Aged

Some epidemiologic surveys have demonstrated that asthma is more prevalent in obese children and adults. However, the mechanism of association between obesity and asthma has not been fully clarified. This report investigates a murine model for antigen-induced asthma and diet-induced obesity from an immunologic perspective. For the induction of obesity, C57BL/6J mice were fed a high-fat diet supplemented with lard or soybean oil. Mice were then sensitized and challenged with ovalbumin (OVA) to induce allergic lung inflammation. OVA-specific serum immunoglobulin levels were lower in obese mice compared with non-obese control mice. The decline of OVA-specific IgE in the soybean oil group was found to be especially pronounced. However, obese mice with OVA-induced asthma showed a higher sensitivity of antigen-induced T-cell responses, and increased gamma interferon (IFN-gamma) production of splenocytes with phytohemagglutinin (PHA) stimulation. Furthermore, mast cell numbers in the tracheal mucosa were increased in obese mice upon sensitization by OVA. These results suggest that obesity-induced changes in T-cell function may be partly involved in the pathophysiology of asthma in human obesity, rather than Ig E-mediated allergic responses.

Topics: Adipose Tissue; Animals; Asthma; Body Weight; Cell Division; Diet; Dietary Fats; Energy Metabolism; Immunoglobulins; Interferon-gamma; Interleukin-2; Leptin; Mice; Mice, Inbred C57BL; Mitogens; Obesity; Ovalbumin; Respiratory Hypersensitivity; Spleen