Eosinophilic bronchitis: an imortant cause of prolonged cough

The recent development of noninvasive techniques to measure airway inflammation has led to the recognition of eosinophilic bronchitis, a condition characterized by a sputum eosinophilia identical to that seen in asthma, but without any of the functional abnormalities associated with asthma. The condition is interesting for a number of reasons. Firstly, eosinophilic bronchitis is a common cause of chronic cough, which is important to recognize as it responds well to corticosteroids. However, recognition is not straightforward because it requires assessment of airway inflammation. Secondly, the natural history of eosinophilic bronchitis is uncertain. Some patients with chronic obstructive pulmonary disease without a history of previous asthma have sputum eosinophilia, thus one possibility is that eosinophilic bronchitis may develop into fixed airflow obstruction. Finally, the difference in the association of eosinophilic airway inflammation to airway dysfunction between eosinophilic bronchitis and asthma is of interest as it is possible that it reflects important differences in the nature or site of the airway inflammation. Further study of this interesting condition may shed light on the relationship between airway inflammation and airway responsiveness, leading to a greater understanding of both eosinophilic bronchitis and asthma.     

Eosinophilic bronchitis: an important cause of prolonged cough

The recent development of noninvasive techniques to measure airway inflammation has led to the recognition of eosinophilic bronchitis, a condition characterized by a sputum eosinophilia identical to that seen in asthma, but without any of the functional abnormalities associated with asthma. The condition is interesting for a number of reasons. Firstly, eosinophilic bronchitis is a common cause of chronic cough, which is important to recognize as it responds well to corticosteroids. However, recognition is not straightforward because it requires assessment of airway inflammation. Secondly, the natural history of eosinophilic bronchitis is uncertain. Some patients with chronic obstructive pulmonary disease without a history of previous asthma have sputum eosinophilia, thus one possibility is that eosinophilic bronchitis may develop into fixed airflow obstruction. Finally, the difference in the association of eosinophilic airway inflammation to airway dysfunction between eosinophilic bronchitis and asthma is of interest as it is possible that it reflects important differences in the nature or site of the airway inflammation. Further study of this interesting condition may shed light on the relationship between airway inflammation and airway responsiveness, leading to a greater understanding of both eosinophilic bronchitis and asthma.     

Evaluation of functional,autonomic and inflammatory outcomes in children with asthma

Asthma is common in childhood. This respiratory disease is characterized by persistent inflammation of the airways even when the child is not in thethroes of an attack. Chronic inflammation is caused by an imbalance between pro-inflammatory and antiinflammatory mechanisms as well as autonomic dysfunction, which plays an important role in the pathogenesis and control of this condition. The impact of these physiopathological aspects leads to inactivity and a sedentary lifestyle, which exerts an influence on functional capacity and control of the disease. The main objective of non-pharmacological therapy is the clinical control of asthma and the minimization of airway obstruction and hyperinflation during an attack. These factors can be controlled with noninvasive ventilation. The aim or the present review was to describe important neural, inflammatory and functional mechanisms that affect children with asthma.     

The inflammatory response in asthma.

Asthma is remarkably underdiagnosed and undertreated. While the clinical hallmark of asthma is reversible airflow obstruction, airway inflammation is the major pathologic feature. Studies have linked airway hyperresponsiveness, the basic physiologic defect in asthma, with airway inflammation, even in patients who have mild asthma. Management is directed toward treating the underlying disease process with anti-inflammatory therapy and alleviating breakthrough symptoms with bronchodilators.     

Clinical applications of exhaled nitric oxide for the diagnosis and management of asthma: a consensus report

BACKGROUND: Patients with asthma routinely exhibit elevated levels of fractionated exhaled nitric oxide (FE(NO)), and this observation has led to studies investigating FE(NO) as a potential marker of airway inflammation. FE(NO) has been shown to enhance the diagnosis of asthma, detect deterioration in control of patients with asthma, and monitor response to anti-inflammatory therapy. OBJECTIVES: The aim of this work was to determine if FE(NO) measurement provides a noninvasive, well-tolerated, and standardized technique to monitor airway inflammation, and if it has the potential to complement standard asthma monitoring tools (eg, symptom diaries, control questionnaires, and pulmonary function testing) and to improve asthma control and patient outcomes. METHODS: Thirteen experts in the diagnosis and treatment of asthma met to discuss the use of FE(NO) in the diagnosis and management of patients with asthma. Participants were selected by Aerocrine, a medical, technical company with headquarters in Stockholm, Sweden, in consultation with their medical education partner Cadent Medical Communications located in Irving, Texas, to represent a diversity of specialists, including both clinicians and investigators, in the fields of allergy, immunology, and pulmonology. All participants were nominally compensated for their time to attend this closed scientific roundtable discussion. The meeting was supported by an educational grant from Aerocrine. This report represents the overall consensus reached by the participants on the clinical applicability of this technique. RESULTS: Our understanding of asthma has expanded so that investigators are now focusing on inflammation in addition to airway obstruction and hyper-reactivity. Whereas patient history, symptoms, and pulmonary function testing can assist in diagnosing asthma, they are not direct measures of the extent of airway inflammation. Elevated FE(NO) levels have been shown to reflect airway inflammation and to occur together with other conventional markers used to detect inflammation. Studies have confirmed increased levels of FE(NO) in both adults and children with asthma. In most studies, FE(NO) was found to be elevated 2- to 3-fold compared with normal controls. There are many determinants of FE(NO) levels, however, and factors other than inflammation must be considered when FE(NO) measurement is used to diagnose and monitor asthma. FE(NO) measurement alone is not sufficient for diagnosing or monitoring asthma, but it can be a valuable addition to current clinical tools. CONCLUSIONS: FE(NO) measurement is a noninvasive and reproducible test that is a surrogate measure of airway inflammation in patients with asthma. The test has demonstrated utility in diagnosing and managing asthma and in predicting response to therapy and, therefore, may be an important tool to incorporate into clinical care.     

Asthma,asthma medication and autonomic nervous system dysfunction

Asthma is associated with autonomic nervous imbalance: an increased bronchial sensitivity to cholinergic constrictors and possibly a decreased sensitivity to β₂‐adrenergic dilators have been reported in this disease. Also, non‐adrenergic and non‐cholinergic (NANC) mediators have a small regulatory effect on airway function. These mediators contribute to the pathogenesis of asthma not only by regulating smooth muscle tone in the airways but also by affecting pulmonary blood flow, endothelial permeability and airway secretions. In many studies increased parasympathetic responsiveness has been associated with clinical asthma or the worsening of asthma in adults. However, most of the studies in children have not found association between autonomic dysfunction and asthma. Therefore, the autonomic dysfunction in asthma may be related to more advanced disease or long‐term asthma medication in adults. This article briefly reviews the relationships between airway inflammation, β₂‐agonist, anticholinergic and glucocorticoid medication as well as autonomic nervous function in asthma.     

Biologic markers of airway inflammation in asthma

Asthma is a serious chronic disease of the airways that affects approximately 14% of the population in the United States. The fundamental pathophysiologic component of asthma is airway narrowing, which causes airflow obstruction. Both inflammation and bronchoconstriction contribute to airway narrowing. The pathogenesis of airway inflammation in asthma and the natural history of the disease are the subject of intense research and study in many countries of the world. The mechanisms of airway inflammation are only partially understood but are the basis for the devastating symptoms that affect the quality of life of millions of people. Treatment of asthma is directed at decreasing airway inflammation to gain long-term control of the disease.     

Asthma: 2015 and beyond

Asthma is a multifactorial, chronic inflammatory disease of the airways. The knowledge that asthma is an inflammatory disorder has become a core fundamental in the definition of asthma. Asthma's chief features include a variable degree of air-flow obstruction and bronchial hyper-responsiveness, in addition to the underlying chronic airways inflammation. This underlying chronic airway inflammation substantially contributes to airway hyper-responsiveness, air-flow limitation, respiratory symptoms, and disease chronicity. However, this underlying chronic airway inflammation has implications for the diagnosis, management, and potential prevention of the disease. This review for the respiratory therapy community summarizes these developments as well as providing an update on asthma epidemiology, natural history, cause, and pathogenesis. This paper also provides an overview on appropriate diagnostic and monitoring strategies for asthma, pharmacology, and newer therapies for the future as well as relevant management of acute and ambulatory asthma, and a brief review of educational approaches.     

Lebrikizumab in the treatment of asthma

ABSTRACT

Introduction: Severe asthma continues to be a major clinical problem despite the availability of effective asthma medications such as inhaled corticosteroids. Several targeted biologic therapies are emerging to treat patients with severe asthma.

Areas covered: This review provides an update of information on lebrikizumab, a novel monoclonal antibody that targets IL-13 and is currently in advanced stages of development. It describes the role of IL-13, a key effector cytokine in Type 2 (T2) airway inflammation in asthma and discusses the results of recent phase 2 trials investigating lebrikizumab’s efficacy and safety in patients with severe asthma. Furthermore, it provides insight into the current ongoing trials with lebrikizumab and outlines future research needs.

Expert opinion: Several emerging therapeutic targets have been identified for patients with severe asthma. By specifically targeting IL-13, lebrikizumab has the potential to block several downstream signals that play a role in disease progression including airway inflammation, mucus hypersecretion and airway remodeling. The effects of lebrikizumab have been more marked in individuals with high serum periostin levels which reflect underlying IL-13 activity and T2 airway inflammation. Ongoing trials with lebrikizumab aim to further examine its long-term safety and efficacy in a larger population and explore its effects on airway inflammation and function.     

Understanding airway wall remodeling in asthma: a basis for improvements in therapy?

Current strategies for the management of asthma focus on suppressing airway inflammation. Other characteristic features of human asthma, such as airway hyperreactivity and the structural changes collectively referred to as airway remodeling, are largely ignored in existing guidelines for monitoring the effectiveness of treatment. Evidence is accumulating that pharmacologic therapy targeting airway wall remodeling may be valuable in treating asthma. However, development of appropriate therapeutic agents will require a better understanding of the pathogenesis of remodeling, which appears to be regulated by a variety of cytokines and growth factors produced by inflammatory, epithelial, and stromal cells. Furthermore, testing the effectiveness of novel agents that specifically target the process of remodeling will require appropriate experimental models, but most currently available animal models of asthma have major limitations. A recently described murine model of chronic human asthma offers considerable potential for dissection of the mechanisms of airway wall remodeling, as well as for investigation of the therapeutic potential of drugs that can modulate chronic inflammation and remodeling.     

靶向Th17细胞免疫治疗中重度哮喘的作用

支气管哮喘（简称哮喘）是多种炎症细胞和炎性介质参与的慢性气道炎症性疾病。Thl/Th2免疫反应失衡是哮喘主要的发病机制,而嗜酸粒细胞性气道炎症和气道高反应性为哮喘的显著临床特征。Th17细胞通过活化和募集中性粒细胞,促进气道炎症发生发展,尤其与中重度哮喘密切相关。Th17细胞为中重度哮喘提供了潜在的治疗靶点。深入研究Th17细胞分化调控机制,有望为治疗中性粒细胞性哮喘带来新的愿景。     

Asthma diagnosis and management

Asthma is a chronic inflammatory airway disease that is commonly seen in the emergency department (ED). This article provides an evidence-based review of diagnosis and management of asthma. Early recognition of asthma exacerbations and initiation of treatment are essential. Treatment is dictated by the severity of the exacerbation. Treatment involves bronchodilators and corticosteroids. Other treatment modalities including magnesium, heliox, and noninvasive ventilator support are discussed. Safe disposition from the ED can be considered after stabilization of the exacerbation, response to treatment and attaining peak flow measures.     

Fas-positive T cells regulate the resolution of airway inflammation in a murine model of asthma

Persistent airway inflammation, mucus production, and airway hyperreactivity are the major contributors to the frequency and severity of asthma. Why lung inflammation persists in asthmatics remains unclear. It has been proposed that Fas-mediated apoptosis of inflammatory cells is a fundamental mechanism involved in the resolution of eosinophilic airway inflammation. Because infiltrating eosinophils are highly sensitive to Fas-mediated apoptosis, it has been presumed that direct ligation of Fas on eosinophils is involved. Here, we utilize adoptive transfers of T cells to demonstrate that the delayed resolution of eosinophilia in Fas-deficient mice is a downstream effect of Fas deficiency on T cells, not eosinophils. Interestingly, the mice that received Fas-deficient T cells, but not the controls, developed a persistent phase of inflammation that failed to resolve even 6 wk after the last challenge. This persistent phase correlated with decreased interferon (IFN)gamma production by Fas-deficient T cells and could be reproduced with adoptive transfer of IFNgamma-deficient T cells. These data demonstrate that Fas deficiency on T cells is sufficient for the development of long-term allergic airway disease in mice and implies that deregulation of death receptors such as Fas on human T cells could be an important factor in the development and/or chronic nature of asthma.     

哮喘患者吸入激素用药依从性研究进展

支气管哮喘(哮喘)是一种气道慢性炎症疾病,激素是最有效的控制气道炎症的药物,但目前哮喘患者吸入激素用药依从性偏低.本文从用药依从性定义、激素用药依从性现状、评价方法、影响因素及干预措施等方面对哮喘患者吸入激素用药依从性的研究进展作一综述.

Abstract：

Bronchial asthma (asthma) is a kind of chronic airway inflammatory disease. Corticosteroid is the most effective drugs used to control airway inflammation.However, the medication compliance of the patient who inhale corticosteroid is still very low at present.This article mainly summarized the process on the medication compliance of the inhaled corticosteroid from the following aspects: the definition, the present situation , the evaluation methods, the affecting factors and the interventions.     

Approaches to acute asthma and status asthmaticus in children

Asthma is the most common chronic disease in pediatric patients and is the leading cause of childhood disability. The functional abnormalities of this disease--namely, airway obstruction and hyperresponsiveness--are consequences primarily of airway inflammation. Outpatient therapy for acute asthma, as well as therapy for status asthmaticus (episodes of asthma unresponsive to usually effective outpatient therapy and necessitating hospitalization), primarily addresses treatment of airway inflammation. The goal of office and emergency room management of acute asthma is reversal of airway obstruction by the administration of inhaled beta-adrenergic medications. The therapy for status asthmaticus consists of intravenously administered aminophylline, corticosteroids, nebulized beta-adrenergic agents, and oxygen. Respiratory failure, the inability to maintain adequate elimination of CO2, may be effectively treated by adding continuous nebulization of albuterol. Mechanical ventilation will still be necessary in the rare patient who does not respond to pharmacologic therapy. Acute exacerbations of asthma, as well as status asthmaticus, can best be prevented by establishing effective maintenance programs individualized for each patient.     

Noninvasive Markers of Airway Inflammation in Asthma

Background: Although airway inflammation plays a major role in the pathophysiology of asthma, quantitative markers of airway nflammation are limited in clinical practice. Objective: To determine if the levels of noninvasive markers of eosinophil‐catalyzed oxidation, lipid peroxidation, and nitric oxide (NO) production are associated with asthma. Methods: Participants were enrolled from academic medical centers participating in the Severe Asthma Research Program. Clinical characteristics, laboratory data, pulmonary function tests, and the levels of the following noninvasive markers were obtained: urinary bromotyrosine (BrTyr), a marker of eosinophil‐catalyzed oxidation, urinary F₂‐isoprostanes (F₂‐lsoPs), markers of lipid peroxidation, and exhaled NO, a marker of airway inflammation. Results: Fifty‐seven asthmatic participants and 38 healthy participants were enrolled. BrTyr, F₂‐lsoPs, and exhaled NO were each significantly increased in asthmatic participants versus controls (p < 0.01). An elevated level (greater than the median) of any marker was associated with a significant 3‐ to 6‐fold greater odds of having asthma. Participants with two or more elevated marker levels showed an 18‐fold greater odds of having asthma. Relationships were also noted with airflow obstruction and bronchodilator response. Conclusion: The findings from this pilot study indicate that urinary levels of BrTyr and F₂‐lsoPs, in addition to exhaled NO levels, are associated with asthma.     

Inflammatory mechanisms and treatment of obstructive airway diseases with neutrophilic bronchitis

Obstructive airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) are major global health issues. Although considered as distinct diseases, airway inflammation is a key underlying pathophysiological process in asthma, COPD and bronchiectasis. Persistent neutrophilic airway inflammation (neutrophilic bronchitis) occurs with innate immune activation and is a feature of each of these airway diseases. Little is known about the mechanisms leading to neutrophilic bronchitis and few treatments are effective in reducing neutrophil accumulation in the airways.There is a similar pattern of inflammatory mediator release and toll like receptor 2 expression in asthma, COPD and bronchiectasis. We propose the existence of an active amplification mechanism, an effector arm of the innate immune system, involving toll like receptor 2, operating in persistent neutrophilic bronchitis.Neutrophil persistence in the airways can occur through a number of mechanisms such as impaired apoptosis, efferocytosis and mucus hypersecretion, all of which are impaired in airways disease. Impairment of neutrophil clearance results in a reduced ability to respond to bacterial infection. Persistent activation of airway neutrophils may result in the persistent activation of the innate immune system resulting in further airway insult.Current therapies are limited for the treatment of neutrophilic bronchitis; possible treatments being investigated include theophylline, statins, antagonists of pro-inflammatory cytokines and macrolide antibiotics. Macrolides have shown great promise in their ability to reduce airway inflammation, and can reduce airway neutrophils, levels of CXCL8 and neutrophil proteases in the airways. Studies also show improvements in quality of life and exacerbation rates in airways diseases.     

A panel of multiple markers associated with chronic systemic inflammation and the risk of atherogenesis is detectable in asthma and chronic obstructive pulmonary disease

Asthma and chronic obstructive pulmonary disease (COPD) are both lung diseases involving chronic inflammation of the airway. The injury is reversible in asthma whereas it is mostly irreversible in COPD. Both patients of asthma and COPD are known at risk for cardiovascular disease (CVD) and type 2 diabetes (T2DM), nephropathy, and cancer. We measured multiple risk markers for atherogenesis in 55 patients with asthma and 62 patients with COPD. We wanted to know whether risk markers for atherogenesis corresponding to sequence of events of chronic inflammation were also detectable in the airway inflammatory diseases. Elevation of almost all markers involving inflammation of the endothelial cells in the coronary artery were detectable in asthma and COPD involving the inflammation of the epithelial cell lining of the airway. Both the level and % elevation of all markers were found mostly higher in COPD, the more severe form of the lung disease. We believe that these markers are useful for predicting risk of developing clinical complications such as CVD.     

An overview of drug therapy for chronic adult asthma.

Asthma involves bronchoconstrictor mechanisms, possible abnormalities of airway smooth muscles and an inflammatory response. Past emphasis on bronchodilator therapy ignored the underlying inflammatory response. Since chronic asthma can eventually lead to irreversible airflow obstruction from uncontrolled inflammation, current drug therapy stresses both inflammation reduction and bronchodilatation. This article discusses the rationale of current pharmacologic management for the adult client with chronic asthma and presents a step-care approach for management of the disease. Inhaled beta-agonists--effective bronchodilators--are the primary drug of choice. Steroids administered via inhalation are the most effective anti-inflammatory agents available. Cromolyn sodium is useful for prophylactic management of asthma. Theophylline, previously the cornerstone of asthma treatment, is now introduced later in the therapeutic plan as an additional bronchodilator. Inhaled anticholinergics may be tried as adjunctive asthma treatment. With careful assessment, intervention and management, health care providers can successfully care for most adult clients with chronic asthma.     

Diseases to differentiate from COPD, with emphasis on bronchial asthma

Differential diagnosis of chronic obstructive pulmonary disease (COPD) from asthma is not a difficult task for many clinicians. Patients with COPD have a history of heavy smoking and show a slowly progressive dyspnea on exertion and there is little variability in symptoms, and they show a poor response to bronchodilators and corticosteroids. Asthma usually begins in early childhood with atopy, shows episodic dyspnea with wheezing, especially during night and early morning. Some patients, however, show adult onset, irreversible airflow limitation, and neutrophilic airway inflammation. The airway remodeling in asthma may be the cause of confusing pathophysiology. Other diseases showing airway hyperresponsiveness, such as allergic bronchopulmonary aspergillosis, Churg-Strauss syndrome, and left heart failure presenting cardiac asthma, may sometimes show similar clinical pictures to COPD. Chronic airway diseases are also possible candidates for differential diagnosis of COPD. Bronchiectasis, sinobronchial syndrome, diffuse panbronchiolitis, obliterative bronchiolitis, and other chronic airway diseases should be considered. Some interstitial lung diseases, such as smoking-related interstitial lung diseases and lymphangioleiomyomatosis, often show obstructive ventilatory impairment, and therefore should be considered in differential diagnosis of COPD.