Japanese guidelines for adult asthma 2020

Bronchial asthma is characterized by chronic airway inflammation, which manifests clinically as variable airway narrowing (wheezes and dyspnea) and cough. Long-standing asthma may induce airway remodeling and become intractable. The prevalence of asthma has increased; however, the number of patients who die from it has decreased (1.3 per 100,000 patients in 2018). The goal of asthma treatment is to control symptoms and prevent future risks. A good partnership between physicians and patients is indispensable for effective treatment. Long-term management with therapeutic agents and the elimination of the triggers and risk factors of asthma are fundamental to its treatment. Asthma is managed by four steps of pharmacotherapy, ranging from mild to intensive treatments, depending on the severity of disease; each step includes an appropriate daily dose of an inhaled corticosteroid, which may vary from low to high. Long-acting β₂-agonists, leukotriene receptor antagonists, sustained-release theophylline, and long-acting muscarinic antagonists are recommended as add-on drugs, while anti-immunoglobulin E antibodies and other biologics, and oral steroids are reserved for very 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 selecting treatment steps for asthma based on the severity of the exacerbations. Allergic rhinitis, eosinophilic chronic rhinosinusitis, eosinophilic otitis, chronic obstructive pulmonary disease, aspirin-exacerbated respiratory disease, and pregnancy are also important conditions 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.     

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.     

妊娠期支气管哮喘治疗进展

临床研究已证明妊娠期重度及控制不佳的支气管哮喘(简称哮喘)与母亲及胎儿严重并发症相关.对于妊娠期哮喘患者,接受药物治疗比存在哮喘症状和哮喘发作更安全.所有程度的持续妊娠哮喘患者都应当应用吸入糖皮质激素作为控制药物,首选布地奈德.白三烯受体拮抗剂可以缓解支气管痉挛、减轻症状、改善肺功能.长效β2受体激动剂对于正在应用吸入糖皮质激素的患者可作为首选的添加药物.吸入短效β2受体激动剂可以作为缓解药物.对于正在接受维持量或接近维持量治疗,无不良反应、临床疗效好的妊娠哮喘患者可以继续进行变应原免疫治疗.     

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.     

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.     

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.     

Asthma exacerbations: pharmacological prevention

Asthma exacerbations are responsible for many emergency medical interventions and account for a significant proportion of the health costs of the disease. Increased airway inflammation is a key feature of exacerbations in asthma and therefore inhaled corticosteroids (ICS) are considered as first-line therapy for long-term asthma control. ICS have been demonstrated to reduce the risk of asthma exacerbations, as well as improving lung function. Oral leukotriene receptor antagonists also reduce the incidence of asthma exacerbations but are less effective than ICS. In patients with inadequately controlled persistent asthma despite low-dose ICS, the addition of a long-acting inhaled beta-agonist (LABA) should be considered. LABA should not be given alone and should always be associated with ICS in asthma. The anti-immunoglobulin E antibody, omalizumab, reduces severe exacerbations and emergency visits in patients with severe allergic asthma. In clinical trials measurement of the inflammatory response in induced sputum could provide information concerning appropriate drug therapy. Asthma-associated comorbidities should be investigated and treated, particularly in severe asthma. Despite a high prevalence of both gastro-oesophageal reflux and allergic rhinitis among patients with asthma, treatment with proton-pump inhibitors or nasal corticosteroids does not reduce the rate of asthma exacerbations.     

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.     

Interleukin-5 Antagonists Usher in a New Generation of Asthma Therapy

Asthma is the most common chronic respiratory disease in the USA. A subset of patients with asthma have refractory symptoms, persistent eosinophilic inflammation, and recurrent exacerbations despite maximal medical therapy. The monoclonal antibodies targeting the IL-5 pathway are a new class of medications designed to target severe eosinophilic asthma. There are two medications clinically available: mepolizumab and reslizumab, both of which target IL-5. A third medication, benralizumab, is currently under development and targets the IL-5 receptor. Clinical data suggest these medications can reduce asthma exacerbations and improve lung function in patients with peripheral eosinophilia and poorly controlled asthma despite maximal medical therapy. The anti-IL-5 medications are among the first targeted molecular therapies for asthma and will usher in an exciting new era in the treatment of severe asthma.     

Effects of regular treatment with combination of salmeterol/fluticasone propionate and salmeterol alone in cough variant asthma

Objective: Cough variant asthma (CVA) is an important cause of chronic cough, and pathophysiological features of the disease appear to be similar to typical asthma. Because CVA is recognized as a precursor of asthma, early intervention with long-term anti-inflammatory agents may be recommended. However, the role of combination therapy with inhaled corticosteroid and β₂-agonist in the treatment of CVA has not been elucidated. To evaluate the effectiveness of the combination therapy, we investigated the clinical impact of regular treatment with salmeterol/fliticasone propionate combination (SFC) and inhaled salmeterol (SAL) alone in patients with CVA. Methods: The study was a randomized, controlled, parallel-group multi-center trial. Forty-three CVA patients were assigned to SFC (50/100?µg once daily) or SAL (50?µg twice daily) for 12 weeks. Then, these medications were stopped for the next 24 weeks. Main outcome measures were cough symptoms, pulmonary function and airway inflammation. Results: Treatment with each of SFC and SAL significantly decreased cough scores and increased FEV₁ and PEF, where the efficacy was more pronounced with SFC than SAL. SFC also decreased sputum eosinophil counts and eosinophil cationic protein contents, whereas SAL had no effect. After discontinuation of the treatment, cough scores increased, pulmonary function and eosinophilic airway inflammation were aggravated and returned to the baseline levels. Conclusions: Maintenance therapy with SFC provides further improvements in cough symptoms, pulmonary function and airway inflammation, and discontinuation of the therapy causes worsening of the disease, indicating that stopping or interrupting anti-inflammatory therapy may not be advisable in patients with CVA.     

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.     

Eosinophils, bronchitis and asthma: pathogenesis of cough and airflow obstruction

Eosinophilic airway inflammation is commonly observed in chronic cough in patients with asthma and non-asthmatic eosinophilic bronchitis. Indeed asthma and non-asthmatic eosinophilic bronchitis are amongst the commonest causes of chronic cough accounting for about 25 and 10% of cases respectively. In most cases the trigger that causes the cough is uncertain; however removal of potential triggers is important to consider in particular with respect to occupational exposure to known sensitizers. In both conditions the cough improves subjectively and objectively following treatment with corticosteroids. This improvement is associated with the presence of an airway eosinophilia, but whether eosinophilic inflammation is the cause of cough or an epiphenomenon is uncertain. The success of anti-IL5 to reduce eosinophilic inflammation and asthma exacerbations contrasts with the lack of efficacy to modify cough in asthma and therefore challenges a causal association. Both asthma and non-asthmatic eosinophilic bronchitis can lead onto airway remodeling and result in persistent airflow obstruction. However, response to corticosteroid therapy in both conditions is generally very good and the limited long term data available suggests that both usually have a benign course. Interestingly, improvement in airway remodeling in response to anti-IL5 observed using CT imaging and analysis of sub-epithelial matrix deposition does suggest that the eosinophil may play a causal role in airway remodeling.     

Formoterol attenuates neutrophilic airway inflammation in asthma

STUDY OBJECTIVES: Airway neutrophil levels are increased in patients with severe asthma and during asthma exacerbations. Long-acting beta2-agonists (LABAs), such as formoterol, reduce the number of asthma exacerbations. While beta2-agonists may affect neutrophil function in vitro, it is uncertain whether they have effects on neutrophilic inflammation in asthmatic patients in vivo. DESIGN: In a double-blind randomized crossover study, we evaluated the effects of 4 weeks of treatment with formoterol (Turbuhaler), 24 microg bid, compared to placebo on sputum neutrophil numbers and interleukin (IL)-8 levels in asthmatic patients. Therapy with budesonide (administered via Turbuhaler), 400 microg bid for 4 weeks, was added at the end as a "gold standard" antiinflammatory effect comparison. PATIENTS: We studied 15 steroid-na?ve nonsmoking patients who ranged from 19 to 51 years of age and had mild persistent asthma. RESULTS: Formoterol therapy significantly reduced sputum IL-8 levels and neutrophil numbers compared to placebo. There was a significant correlation between the reduction in sputum IL-8 levels and the number of neutrophils, indicating that formoterol may attenuate neutrophilic airway inflammation by inhibiting IL-8 production. CONCLUSIONS: Our data suggest that the LABA formoterol reduces neutrophilic airway inflammation in patients with mild asthma and that this might be beneficial in preventing asthma exacerbations.     

Pharmacological modulation of β-adrenoceptor function in patients with coexisting chronic obstructive pulmonary disease and chronic heart failure

Pharmacological modulation of β-adrenoceptor function is one of the critical issues in the treatment of patients with concurrent chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF). A volume of published evidence sustains the role of long-acting β₂-agonists in the treatment of stable COPD, but β-agonists seem to be detrimental when used for long term in CHF. β₂-agonists may exacerbate heart failure and, in any case, they induce adverse cardiac effects in COPD patients with pre-existing cardiovascular disease. The adverse effects of β₂-agonists are likely to be exacerbated in COPD patients with coexistent CHF. β-Blockers are the standard treatment in CHF, but they can worsen FEV₁ and airway hyperresponsiveness and reluctance exists to prescribe these agents to COPD patients, despite the anticipated beneficial cardiovascular effects. Although the literature is reassuring, there are currently no prospective long-term studies on the safety of β-blockers in COPD. Therefore, although β-blockers can be introduced in any medical setting for treating patients with concurrent COPD and CHF, it still seems appropriate to only use those β-blockers that are more selective for the β₁-AR but without ISA at the lowest dose and to titrate them slowly with attention to lung function and symptoms, adding an inhaled antimuscarinic agent when bronchodilation is needed.     

A Comparison of Budesonide/Formoterol Maintenance and Reliever Therapy Versus Conventional Best Practice in Asthma Management in Spain

Objective. To study the effectiveness and safety in a real-life setting of budesonide/formoterol (Symbicort) Maintenance And Reliever Therapy® (Symbicort SMART®), a simplified management approach with one inhaler, compared with conventional best practice (CBP) with multiple inhalers in patients with persistent asthma. Design. Open-label randomized controlled parallel-group trial, 6-month treatment. Participants. A total of 654 adult patients, with persistent asthma receiving treatment with inhaled corticosteroids (ICS), either alone or in conjunction with long-acting β₂-agonist. Main outcome measures. Time to first severe asthma exacerbation and number of severe asthma exacerbations. Results. No difference between groups was seen in time to first severe exacerbation (p = .2974). Exacerbation rates were low in both groups. A total of 22 patients in the Symbicort SMART group experienced a total of 24 severe asthma exacerbations, and 31 patients in the CBP group experienced a total of 34 severe asthma exacerbations (annual rate 0.16 vs. 0.22, p = .2869). The mean daily dose of ICS expressed in beclomethasone dipropionate equivalent was significantly lower in the Symbicort SMART group (including as-needed use) versus the CBP group (799 μg vs.1184 μg; p < .001). Mean scores in Asthma Control Questionnaire, five-question version, improved significantly in the SMART group compared with the CBP group (p = .0292). Symbicort SMART and CBP were equally well tolerated. The mean drug cost per patient per 6 months was lower for the patients in the SMART group compared with patients receiving CBP (€295.32 vs. €387.98, p < .0001). Conclusions. A simplified regimen using budesonide/formoterol maintenance and reliever therapy (Symbicort SMART) was at least as effective at improving clinical control compared with CBP with a significantly lower ICS dose and lower drug costs.     

Treating asthma: is there a place for leukotriene receptor antagonists?

Asthma is a chronic disorder, characterized by airway hyperresponsiveness (AHR), airway inflammation and airway remodelling. Evidence has been provided for a relationship between pathophysiology, airway inflammation and remodelling. Moreover, these asthma features have been shown to respond to anti-inflammatory therapy. According to current guidelines, monitoring of asthma is predominantly based on symptoms and lung function data. However, these parameters appeared as poor indices for asthma control. Alternatively, asthma control relates well to exacerbations and (anamnestic) surrogate biomarkers of airway inflammation. Hence, appropriate treatment of asthma should primarily target the airway inflammation. According to current guidelines for asthma management, anti-inflammatory therapy with inhaled corticosteroids (ICS) is the cornerstone in the treatment of persistent asthma. To further optimize asthma control, add-on therapy with long-acting beta2-agonists (LABA) or leukotriene receptor antagonists (LTRA) should be combined with low to high doses of ICS. While the first combination focuses on optimal control of symptoms and lung function, the second provides a more complete suppression of the airway inflammation. In this paper we discuss treatment of asthma according to current guidelines versus new insights, addressing practical issues.     

Principal findings of systematic reviews for chronic treatment in childhood asthma

Objective: To summarize the principal findings pertaining to most effective long-term pharmacologic treatment of childhood asthma. Methods: Systematic reviews of randomized clinical trials (SRCTs) on pharmacologic chronic treatment in children (1–18 years) with persistent asthma were retrieved through MEDLINE, EMBASE, CINAHL, SCOPUS, and CDSR (up to January2014). Results: One hundred eighty-three SRCTs were searched from databases. Among those, 39 SRCTs were included: two were related to step 1, 24 to step 2, nine to steps 3 and 4, and four to step 5 (according with NAEPP and GINA guidelines). The methodological quality of these SRCTs was determined by using the AMSTAR tool. Results: For step 1: addition of ipatropium bromide to short-acting beta2-agonists does not show any benefit. For step 2: in preschoolers, inhaled corticosteroids (ICSs) reduce severe exacerbations and improve other clinical and lung function parameters. In children, ICSs are superior to leukotriene receptor antagonist (LTRA), cromones, or xantines in reducing severe exacerbations, improving lung function and other clinical outcomes. Fluticasone propionate (FP) is better than beclomethasone dipropionate (BDP) or budesonide only for lung function; but similar to hydrofluoroalkane-BDP or to ciclosenide. Compared to low ICSs doses, moderate doses result in only better lung function, but this is not true for FP. For steps 3 and 4: adding LTRA to ICS confers a small benefit; adding LABA improves lung function but does not reduce exacerbations more than double or higher ICS doses. For step 5: adding omalizumab decreases exacerbations. Conclusions: SRCTs are useful for guiding decisions in chronic childhood asthma treatment.     

Inhaled long-acting muscarinic antagonists in asthma – A narrative review

Long-acting muscarinic antagonists (LAMAs) have a recognised role in the management of chronic obstructive pulmonary disease. In asthma, muscarinic antagonists (both short- and long-acting) were historically considered less effective than β₂-agonists; only relatively recently have studies been conducted to evaluate the efficacy of LAMAs, as add-on to either inhaled corticosteroid (ICS) monotherapy or ICS/long-acting β₂-agonist (LABA) combinations. These studies led to the approval of the first LAMA, tiotropium, as an add-on therapy in patients with poorly controlled asthma. Subsequently, a number of single-inhaler ICS/LABA/LAMA triple therapies have been approved or are in clinical development for the management of asthma. There is now substantial evidence of the efficacy and safety of LAMAs in asthma that is uncontrolled despite treatment with an ICS/LABA combination. This regimen is recommended by GINA as an optimisation step for patients with severe asthma before any biologic or systemic corticosteroid treatment is initiated.This narrative review summarises the potential mechanisms of action of LAMAs in asthma, together with the initial clinical evidence supporting this use. We also discuss the studies that led to the approval of tiotropium for asthma and the data evaluating the efficacy and safety of the various triple therapies, before considering other potential uses for triple therapy.