Japanese guidelines for adult asthma 2017

Adult bronchial asthma is characterized by chronic airway inflammation, and presents clinically with variable airway narrowing (wheezes and dyspnea) and cough. Long-standing asthma induces airway remodeling, leading to intractable asthma. The number of patients with asthma has increased; however, the number of patients who die of asthma has decreased (1.2 per 100,000 patients in 2015). The goal of asthma treatment is to enable patients with asthma to attain normal pulmonary function and lead a normal life, without any symptoms. A good relationship between physicians and patients is indispensable for appropriate treatment. Long-term management by therapeutic agents and elimination of the causes and risk factors of asthma are fundamental to its treatment. Four steps in pharmacotherapy differentiate between mild and intensive treatments; each step includes an appropriate daily dose of an inhaled corticosteroid, varying from low to high levels. Long-acting β₂-agonists, leukotriene receptor antagonists, sustained-release theophylline, and long-acting muscarinic antagonist are recommended as add-on drugs, while anti-immunoglobulin E antibody and oral steroids are considered for the most severe and persistent asthma related to allergic reactions. Bronchial thermoplasty has recently been developed for severe, persistent asthma, but its long-term efficacy is not known. Inhaled β₂-agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, and other approaches are used as needed during acute exacerbations, by choosing treatment steps for asthma in accordance with the severity of exacerbations. Allergic rhinitis, eosinophilic chronic rhinosinusitis, eosinophilic otitis, chronic obstructive pulmonary disease, aspirin-induced asthma, and pregnancy are also important issues that need to be considered in asthma therapy.     

Japanese Guideline for Adult Asthma 2014

Adult bronchial asthma (hereinafter, asthma) is characterized by chronic airway inflammation, reversible airway narrowing, and airway hyperresponsiveness. Long-standing asthma induces airway remodeling to cause intractable asthma. The number of patients with asthma has increased, and that of patients who die from asthma has decreased (1.5 per 100,000 patients in 2012). The aim of asthma treatment is to enable patients with asthma to lead a normal life without any symptoms. A good relationship between physicians and patients is indispensable for appropriate treatment. Long-term management with antiasthmatic agents and elimination of the causes and risk factors of asthma are fundamental to its treatment. Four steps in pharmacotherapy differentiate between mild and intensive treatments; each step includes an appropriate daily dose of an inhaled corticosteroid, varying from low to high. Long-acting 02-agonists, leukotriene receptor antagonists, and sustained-release theophylline are recommended as concomitant drugs, while anti-immunoglobulin E antibody therapy has been recently developed for the most severe and persistent asthma involving allergic reactions. Inhaled 02-agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, and others are used as needed in acute exacerbations by choosing treatment steps for asthma exacerbations depending on the severity of attacks. Allergic rhinitis, chronic obstructive pulmonary disease, aspirin-induced asthma, pregnancy, asthma in athletes, and coughvariant asthma are also important issues that need to be considered.     

Executive summary: Japanese guidelines for adult asthma (JGL) 2021

Asthma is characterized by chronic airway inflammation, variable airway narrowing, and sensory nerve irritation, which manifest as wheezing, dyspnea, chest tightness, and cough. Longstanding asthma may result in airway remodeling and become intractable. Despite the increased prevalence of asthma in adults, asthma-associated deaths have decreased in Japan (0.94 per 100,000 people in 2020). The goals of asthma treatment include the control of symptoms and reduction of future risks. A functional partnership between physicians and patients is indispensable for achieving these goals. Long-term management with medications and the elimination of triggers and risk factors are fundamental to asthma treatment. Asthma is managed via four steps of pharmacotherapy (“controllers”), ranging from mild to intensive treatments, depending on disease severity; each step involves daily administration of an inhaled corticosteroid, which varies from low to high dosage. Long-acting β₂ agonists, leukotriene receptor antagonists, sustained-release theophylline, and long-acting muscarinic antagonists are recommended as add-on drugs. Allergen immunotherapy is a new option that is employed as a controller treatment. Further, as of 2021, anti-IgE antibody, anti-IL-5 and anti-IL-5 receptor α-chain antibodies, and anti-IL-4 receptor α-chain antibodies are available for the treatment of severe asthma. Bronchial thermoplasty can be performed for asthma treatment, and its long-term efficacy has been reported. Algorithms for their usage have been revised. Comorbidities, such as allergic rhinitis, chronic rhinosinusitis, chronic obstructive pulmonary disease, and aspirin-exacerbated respiratory disease, should also be considered during the treatment of chronic asthma. Depending on the severity of episodes, inhaled short-acting β₂ agonists, systemic corticosteroids, short-acting muscarinic antagonists, oxygen therapy, and other approaches are used as needed (“relievers”) during exacerbation.     

Japanese Guideline for Adult Asthma

Adult bronchial asthma (hereinafter, asthma) is characterized by chronic airway inflammation, reversible airway narrowing, and airway hyperresponsiveness. Long-standing asthma induces airway remodeling to cause an intractable asthma. The number of patients with asthma has increased, while the number of patients who die from asthma has decreased (1.7 per 100,000 patients in 2009). The aim of asthma treatment is to enable patients with asthma to lead a healthy life without any symptoms. A partnership between physicians and patients is indispensable for appropriate treatment. Long-term management with agents and elimination of causes and risk factors are fundamental to asthma treatment. Four steps in pharmacotherapy differentiate mild to intensive treatments; each step includes an appropriate daily dose of an inhaled corticosteroid (ICS), varying from low to high doses. Long-acting β₂ agonists (LABA), leukotriene receptor antagonists, and theophylline sustained-release preparation are recommended as concomitant drugs, while anti-IgE antibody therapy is a new choice for the most severe and persistent asthma. Inhaled β₂ agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, etc., are used as needed against acute exacerbations. Allergic rhinitis, chronic obstructive pulmonary disease (COPD), aspirin induced asthma, pregnancy, and cough variant asthma are also important factors that need to be considered.     

Effets synergiques et additifs entre les différentes classes d'anti-inflammatoires de l'asthme

Persistent asthma is a chronic airway inflammatory disease that requires treatment with anti-inflammatory drugs. Inhaled corticosteroids are the cornerstone of the treatment of airway inflammation. Clinical studies have shown that asthmatic patients treated with long-acting β₂-agonists and inhaled corticosteroids have more reduced exacerbations than those given higher doses of corticosteroids suggesting synergistic effects on the inflammatory process. The understanding of the molecular modes of action of these two classes of drugs explained part of the enhanced anti-inflammatory activity of the combination therapy. However, the production of cysteinyl-leukotrienes is not well controlled by corticosteroids. Antileukotrienes, by the blockade of the effects of cysteinyl-leukotrienes, exert therefore a complementary antiinflammatory action. In addition, the efficacy of antileukotrienes for the symptomatic treatment of allergic seasonal rhinitis can improve both the quality of life and asthma control in mild to moderate persistent asthmatic patients, with seasonal allergic rhinitis, who are already treated with an antileukotriene as maintenance treatment for their asthma.     

Adverse Effects of β-Agonists

Inhaled β₂-adrenoceptor agonists (β₂-agonists) are the most commonly used asthma medications in many Western countries. Minor adverse effects such as palpitations, tremor, headache and metabolic effects are predictable and dose related. Time series studies suggested an association between the relatively nonselective β-agonist fenoterol and asthma deaths. Three case-control studies confirmed that among patients prescribed fenoterol, the risk of death was significantly elevated even after controlling for the severity of asthma. The Saskatchewan study not only found an increased risk of death among patients dispensed fenoterol, but also suggested this might be a class effect of β₂-agonists. However, in subsequent studies, the long-acting β₂-agonist salmeterol was not associated with increased asthma mortality. In a case-control study blood albuterol (salbutamol) concentrations were found to be 2.5 times higher among patients who died of asthma compared with controls. It is speculated that such toxic concentrations could cause tachyarrhythmias under conditions of hypoxia and hypokalemia.The risk of asthma exacerbations and near-fatal attacks may also be increased among patients dispensed fenoterol, but this association may be largely due to confounding by severity. Although salmeterol does not appear to increase the risk of near-fatal attacks, there is a consistent association with the use of nebulized β₂-agonists. Nebulized and oral β₂-agonists are also associated with an increased risk of cardiovascular death, ischemic heart disease and cardiac failure. Caution should be exercised when first prescribing a β-agonist for patients with cardiovascular disease.A potential mechanism for adverse effects with regular use of β₂-agonists is tachyphylaxis. Tachyphylaxis to the bronchodilator effects of long-acting β₂-agonists can occur, but has been consistently demonstrated only for formoterol (eformoterol) a full agonist, rather than salmeterol, a partial agonist. Tachyphylaxis to protection against induced bronchospasm occurs with both full and partial β₂-agonists, and probably within a matter of days at most. Underlying airway responsiveness to directly acting bronchoconstricting agents is not increased when the bronchodilator effect of the regular β₂-agonist has been allowed to wear off, although there may be an increase in responsiveness to indirectly acting agents. While there has been speculation that underlying airway inflammation in asthma may be made worse by regular use of short-acting β₂-agonists, in contradistinction, a number of studies have shown that long-acting β₂-agonists have positive anti-inflammatory effects.An Australian Cochrane Airways Group systematic review of the randomized, controlled trials of short-acting β-agonists found only minimal and clinically unimportant differences between regular use and use as needed. Regular short-acting treatment was better than placebo. However, a subsequent systematic review has found that regular use of long-acting β-agonists had significant advantages over regular use of short-acting β-agonists. More studies and data are needed on the regular use of β₂-agonists in patients not taking inhaled corticosteroids, and in potentially vulnerable groups, such as the elderly and those with particular genotypes for the β-receptor, who might be more prone to adverse effects.     

Comprehensive Asthma Management: Guidelines for Clinicians

Asthma is a chronic inflammatory disease characterized by reversible airway obstruction and nonspecific airway hyperreactivity. Asthma is managed in steps according to disease symptoms and severity. Treatment goals are to decrease symptoms, improve pulmonary function, and reduce overall morbidity and the associated cost of medical care. Antiasthma drugs are a key component of asthma management that are classified as either long-term-control medications that control symptoms and prevent disease exacerbations, or quick-relief medications that rapidly relieve airway obstruction and acute asthma symptoms. Several new leukotriene (LT) modulators have been developed that promise to improve asthma control, including LT receptor antagonists montelukast and zafirlukast and the 5-lipoxygenase inhibitor zileuton. Each decreases symptoms and the use of rescue medication, and improves pulmonary function in patients with mild intermittent to moderate persistent asthma.     

Eosinophilic airway disorders associated with chronic cough

Chronic cough is a major clinical problem. The causes of chronic cough can be categorized into eosinophilic and noneosinophilic disorders, the former being comprised of asthma, cough variant asthma (CVA), atopic cough (AC) and non-asthmatic eosinophilic bronchitis (NAEB).Cough is one of the major symptoms of asthma. Cough in asthma can be classified into three categories; 1) CVA: asthma presenting solely with coughing, 2) cough-predominant asthma: asthma predominantly presenting with coughing but also with dyspnea and/or wheezing, and 3) cough remaining after treatment with inhaled corticosteroid (ICS) and β2-agonists in patients with classical asthma, despite control of other symptoms. There may be two subtypes in the last category; one is cough responsive to anti-mediator drugs such as leukotriene receptor antagonists and histamine H1 receptor antagonists, and the other is cough due to co-morbid conditions such as gastroesophageal reflux.CVA is one of the commonest causes of chronic isolated cough. It shares a number of pathophysiological features with classical asthma with wheezing such as atopy, airway hyperresponsiveness (AHR), eosinophilic airway inflammation and various features of airway remodeling. One third of adult patients may develop wheezing and progress to classical asthma. As established in classical asthma, ICS is considered the first-line treatment, which improves cough and may also reduce the risk of progression to classical asthma.AC proposed by Fujimura et al. presents with bronchodilator-resistant dry cough associated with an atopic constitution. It involves eosinophilic tracheobronchitis and cough hypersensitivity and responds to ICS treatment, while lacking in AHR and variable airflow obstruction. These features are shared by non-asthmatic eosinophilic bronchitis (NAEB). However, atopic cough does not involve bronchoalveolar eosinophilia, has no evidence of airway remodeling, and rarely progresses to classical asthma, unlike CVA and NAEB. Histamine H1 antagonists are effective in atopic cough, but their efficacy in NAEB is unknown. AHR of NAEB may improve with ICS within the normal range. Taken together, NAEB significantly overlaps with atopic cough, but might also include milder cases of CVA with very modest AHR. The similarity and difference of these related entities presenting with chronic cough and characterized by airway eosinophilia will be discussed.     

An Uncommon Cause of Uncontrolled Asthma: Case Report

Bronchial asthma is one of the most common chronic conditions seen by any health care professional. Multiple stimuli may lead to acute airway hyperresponsiveness and an exacerbation of the disease, gastroesophageal reflux disease being one of them. We report the case of an elderly patient with chronic gastroesophageal reflux disease who secondarily developed a tracheoesophageal fistula, resulting in recurrent exacerbations of previously well-controlled asthma. After endoscopic correction of the fistula, the patient's respiratory disease improved dramatically, with essentially no exacerbations requiring urgent care or hospitalization.     

Exhaled Nitric Oxide and Bronchial Wall Thickening in Asthmatics During and After Acute Exacerbation: Evidence of Bronchial Wall Remodeling

To assess whether bronchial wall thickening during asthma exacerbations is due to active inflammation in severe asthmatics, we measured bronchial wall thickness and exhaled nitric oxide (FeNO) following treatment. Nine asthmatics were compared with seven controls with high-resolution computed tomography, spirometry, and FeNO measurements. The asthmatic bronchial wall area percent and FeNO was greater than controls. Following treatment, the FEV₁ markedly improved, FeNO decreased modestly, and bronchial wall area percent did not change significantly. Bronchial wall thickening persisted after treatment of acute asthma exacerbation despite improvement in spirometry and decline in FeNO, possibly due to chronic airway remodeling.     

低剂量吸入糖皮质激素治疗轻度支气管哮喘回顾性分析

目前指南不再推荐β_2受体激动剂单独用于轻度持续性支气管哮喘(简称哮喘)的规律治疗,而最近临床研究支持吸入糖皮质激素(inhaled corticosteroids,ICS)对轻度持续性哮喘具有明显的益处.本文从轻度哮喘患者的气道炎症特点,ICS的使用策略及其联合用药方面,对近年有关ICS治疗轻度哮喘这一问题进行回顾性分析,为轻度哮喘的治疗提供参考意见.     

Tolerability Profiles of Leukotriene Receptor Antagonists and Long-Acting β2-Adrenoceptor Agonists in Combination with Inhaled Corticosteroids for Treatment of Asthma: A Review

Inhaled corticosteroids, long-acting β₂-adrenoceptor agonists, and leukotriene receptor antagonists are widely used for treatment of asthma. Inhaled corticosteroids are recommended as first-line therapy, whereas long-acting β₂-adrenoceptor agonists and leukotriene receptor antagonists are indicated as add-on therapy in patients not adequately controlled with corticosteroids alone. A number of studies have investigated the efficacy of combinations of these drugs in asthma, but several issues concerning the safety of these treatments are highly debated. This review provides a critical appraisal of the tolerability profiles of long-acting β₂-agonists and leukotriene receptor antagonists used in combination with inhaled corticosteroids for the treatment of asthma.     

Case study: A Combination of Mepolizumab and Omaluzimab injections for severe asthma

A Combination of Mepolizumab and Omaluzimab injections for severe asthma. Introduction. Patients with severe persistent asthma account for a large proportion of asthma morbidity and health care expenditures. In this case report we describe the use of a combination of omalizumab and mepolizumab in severe asthma with elevated IgE levels and eosinophilic phenotype. Case Study: We are treating a 55 year old woman with severe persistent eosinophilic asthma and elevated IgE levels. Her regimen included salmeterol/fluticasone propionate inhaler 500/50 one puff twice a day, budesonide nebulizer twice a day, tiotropium respimat inhaler two puffs daily, montelukast 10 mg daily, Albuterol as needed, Azithromycin 250 mg three times a week, and also omalizumab injections. She was having recurrent asthma exacerbations requiring the use of oral corticosteroids. Due to frequent exacerbations, we referred her for Bronchial Thermoplasty. This procedure was denied by insurance and therefore the patient was started on 20 mg PO prednisone daily. Mepolizumab was added approximately 4 months after starting chronic PO prednisone. We were able to taper down the steroids and she is currently on 4 mg daily. Results: Since we added the mepolizumab injections along with the omalizumab injections, we have been able to decrease the prednisone steadily and currently the patient is on 4 mg daily. The plan is to taper off the corticosteroids slowly as the clinical status allows. Conclusion: Combination of omalizumab and mepolizumab could become the gold standard for severe asthma patients that have elevated IgE levels and an eosinophilic phenotype. Case Report: A Combination of Mepolizumab and Omaluzimab injections for severe asthma.     

Managing patients with chronic severe asthma: Rise to the challenge

Most asthmatic patients with moderate to severe disease can be satisfactorily managed with a combination of inhaled corticosteroids and β₂-agonists. However, there are perhaps 10% of the asthmatic population with persistent symptoms, impaired quality of life and excessive health-care utilization, despite this management regime. These patients often require frequent and even occasionally regular oral corticosteroid use. Chronic, severe asthma is a heterogenous disease with distinct sub-phenotypes. A systematic diagnostic work-up may help to identify these distinct sub-phenotypes and this may help guide treatment and may even provide information about prognosis.Optimal treatment of chronic severe asthma should achieve the best possible asthma control and quality of life with the least dose of systemic corticosteroids. The choice and formulation of therapeutic agent is dictated by the severity of disease and includes conventional, immunosuppressive/immunomodulating and biologic therapies. Unfortunately, current asthma management guidelines offer little contribution to the care of the challenging patient with chronic severe asthma. This review article aims at summarizing the evidence regarding various therapeutic modalities for chronic severe asthma and also aims to provide a practical approach to diagnosis and management for the benefit of those who have a specific interest in this problematic condition.     

Acute Asthma in Children and Adolescents

Children and adolescents experiencing acute exacerbations of asthma benefit from the use of β₂-adrenoceptor agonists (β₂-agonists) and systemic corticosteroids. However, there have been conflicting reports regarding the efficacy of inhaled anticholinergic agents.This article summarizes the evidence provided by randomized controlled trials studying the efficacy of adding inhaled anticholinergic agents to β₂-agonists in nonhospitalized children and adolescents with acute exacerbations of asthma. This systematic review of randomized controlled trials suggests that the addition of inhaled anticholinergic agents to β₂-agonists is beneficial in children and adolescents, particularly those with severe exacerbations of asthma. When given in repeated doses, the addition of inhaled anticholinergic agents to β₂-agonists improves lung function and reduces the risk of hospital admission by 25%. Several treatment regimens, namely ipratropium bromide (250 or 500μg per dose) every 20–60 minutes for two to three doses have been tested with similar beneficial effects. The addition of a single dose of an inhaled anticholinergic agent to β₂-agonists improves lung function but does not prevent hospital admission. The review did not identify any beneficial effects of anticholinergic agents in children with nonsevere asthma. Use of anticholinergic agents was not associated with increase in the incidence of nausea, vomiting or tremor.In conclusion, the addition of repeated doses of an inhaled anticholinergic agent to inhaled β₂-agonist is indicated in the emergency room management of children and adolescents with acute asthma, particularly those with severe exacerbations.     

Treating Moderate-to-Severe Allergic Asthma with a Recombinant Humanized Anti-IgE Monoclonal Antibody (Omalizumab)

Bronchial asthma is a chronic inflammatory disease of the airways which is recognized as a highly prevalent health problem in both the developed and the developing world, with significant human and economic consequences.Allergy is acknowledged as a major risk factor for asthma. The pathogenetic aspects of allergic asthma are characterized by airway inflammation with infiltration of mast cells, basophils, eosinophils, monocytes and T helper type 2 lymphocytes, along with the isotype switching of B cells to generate immunoglobulins of the immunoglobulin E (IgE) class. Increased asthma severity is not only associated with recurrent hospitalization and increased mortality but also with higher social costs.Inhaled corticosteroids are the standard anti-inflammatory medication and are effective for most asthma patients, but there is a substantial number of asthmatics who remain symptomatic even after receiving treatment with inhaled corticosteroids and long-acting beta(2)-adrenoceptor agonists (beta(2)-agonists), and sometimes are in need of systemic corticosteroids to control the disease. These patients account for about 50% of the healthcare costs of asthma.New treatment options more specifically targeting the pathophysiologic events causing development of asthma are therefore required in these patients.A novel therapeutic approach to asthma and other allergic respiratory diseases involves interference with the action of IgE and prevention of subsequent IgE-mediated responses.Omalizumab is a humanized recombinant monoclonal anti-IgE antibody developed for the treatment of allergic diseases, with clear efficacy in adolescent and adult patients with moderate-to-severe allergic asthma. This non-anaphylactogenic anti-IgE antibody inhibits IgE functions by blocking free serum IgE and inhibiting their binding to cellular receptors. Omalizumab therapy is well tolerated and significantly improves symptoms and disease control, and reduces asthma exacerbations and the need to use high dosages of inhaled corticosteroids. Moreover, omalizumab improves quality of life of patients with severe persistent allergic asthma that is inadequately controlled by currently available asthma medications. In conclusion, omalizumab may fulfill an important need in patients with moderate-to-severe asthma inadequately controlled with inhaled corticosteroids +beta(2)-agonists.     

Bronchial thermoplasty failure in severe persistent asthma: a case report

Abstract

Introduction: Bronchial thermoplasty (BT) is an emerging therapy for patients with severe persistent asthma who remain poorly controlled despite standard maximal medical therapy. Thermoplasty elicits asthma control over time by applying thermal radiofrequency energy to airways to ablate underlying smooth muscle. While this therapy is suggested to eliminate such smooth muscle permanently, no human studies have examined the possibility of treatment failure. Case report: We present a 62-year-old female with severe, refractory asthma symptoms who underwent BT without apparent complications. However, severe symptoms including multiple clinical exacerbations persisted despite BT treatment. Repeat endobronchial biopsy done six months after BT treatment demonstrated persistent smooth muscle hyperplasia in multiple airways that previously had been treated. The patient continued to have uncontrolled, refractory asthma despite multiple therapies. Conclusion: This case is the first to describe a failure of BT to reduce or eliminate airway smooth muscle in a patient with severe persistent asthma. It suggests the potential for treatment failure in the management of these patients after BT and highlights the need for further study of potential BT-refractory patients.     

Similarities and differences in asthma and chronic obstructive pulmonary disease exacerbations

There is no generally accepted definition of an exacerbation either for asthma or for chronic obstructive pulmonary disease. There is little consistency among the symptomatic or functional criteria used in different studies. The most consistent criterion is the introduction of systemic corticosteroids for the acute worsening of the disease. The time course of an exacerbation does not seem to differ very much between asthma and chronic obstructive pulmonary disease (COPD). The decrease in peak flow rate is more pronounced in asthma than in COPD. The frequency of exacerbations is linked to disease severity both in asthma and COPD. Common causes are viral infections and increased environmental air pollution, whereas allergen exposure and bacterial infections are more specific for asthma and COPD exacerbations, respectively. Few data are available about the airway pathology of asthma or COPD exacerbations. Eosinophilia and/or neutrophilia have been associated with exacerbations in both diseases. Avoidance of the causal factors decreases exacerbation rate in both diseases. Pharmacologic prevention of exacerbations in asthma has been shown for inhaled corticosteroids, combination therapy with long-acting inhaled beta(2)-agonists and inhaled corticosteroids, and monoclonal anti-IgE. Inhaled corticosteroids, long-acting inhaled beta(2)-agonists, combination therapy with both, and the long-acting inhaled anticholinergic tiotropium decrease the exacerbation rate in COPD.     

Asthma bronchiale

Bronchial asthma, with a prevalence in Germany of 5% among adults and 10% among children, remains a frequent disease. Newer cell biological data show a separate regulation of the allergy (interleukin 4, IL-4, pathway) and of the eosinophilic inflammation in asthma (IL-5 pathway). Both conditions require a therapeutic approach. To prevent irreversible bronchial remodeling, early diagnosis and targeted therapy are decisive. Bronchial asthma is regarded as evident when the paroxysmal character of the disease is confirmed and an—at least intermittent—obstructive ventilation disorder is apparent which responds well to short-acting β₂-adrenergic agents. Current asthma treatment has been assured in many studies (evidence level A) and is based on therapy in stages which classifies therapeutic measures depending on four grades of severity. Accordingly, most patients are largely without complaints, and nocturnal attacks are now rare. New medications are intended to overcome any remaining therapeutic weak points. Antileukotrienes and anti-IgE antibodies can contribute to reducing the necessary corticosteroids. Pharmaceutical agents that intervene in the IL-4 or IL-5 regulation or prevent remodeling are being developed.     

Residual exhaled nitric oxide elevation in asthmatics is associated with eosinophilic chronic rhinosinusitis

Objective: Eosinophilic chronic rhinosinusitis (ECRS) is as a subgroup of chronic rhinosinusitis (CRS) with nasal polyps. ECRS is a refractory disease closely related to bronchial asthma. Fractionated exhaled nitric oxide (FeNO) levels were reportedly elevated in some asthmatics with CRS after adequate treatment, suggesting that residual eosinophilic airway inflammation or ECRS might affect FeNO levels. Methods: To investigate the association between asthma with ECRS and FeNO levels, we examined FeNO levels in 133 asthmatics (99 with ECRS and 34 without ECRS) and 13 patients with ECRS without asthma. The severity of asthma was defined by the Global Initiative for Asthma guidelines and that of sinusitis was evaluated by the sinus CT score based on the Lund–Mackay scale. Results and conclusions: FeNO levels were elevated even in well-controlled asthmatics with ECRS, whereas asthmatics without ECRS and ECRS patients without asthma did not have high FeNO levels (>50?ppb). Although FeNO levels were not correlated with asthma severity, they were positively correlated with the sinus CT score. In asthmatics with ECRS, patients with higher FeNO levels had more severe ECRS and asthma. There is a possibility of having comorbid ECRS, particularly in asthmatics with high FeNO levels even after adequate treatment, including ICS, suggesting that asthma and ECRS may be closely associated as one airway disease with eosinophilic inflammation. Continual awareness of the coexistent ECRS is ideally recommended for asthmatics with high FeNO levels.