A phase III randomized controlled trial of tiotropium add-on therapy in children with severe symptomatic asthma

Szefler, Stanley J.; Murphy, Kevin R.; Harper, Thomas B.; Boner, Attilio; Laki, István; Engel, Michael; Azzi, Georges El; Moroni-Zentgraf, Petra; Finnigan, Helen; Hamelmann, Eckard

doi:10.1016/j.jaci.2017.01.014

Cited by 110 publications

(122 citation statements)

References 58 publications

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“…64,65 An additional study in new onset asthma 66 did not meet our inclusion criteria. The limited number of published pediatric data preclude making any firm recommendations for children aged 6-11 years.…”

Section: Efficacy In Adolescent and Pediatric Individualsmentioning

confidence: 99%

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Recognition and management of severe asthma: A Canadian Thoracic Society position statement

FitzGerald

Lemière

Lougheed

et al. 2017

Canadian Journal of Respiratory, Critical Care, and Sleep Medic

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RATIONALE: While severe asthma affects approximately 5% of all individuals with asthma, this small minority of individuals accounts for a large proportion of the asthma-related costs. Greater understanding of the pathophysiology of asthma combined with the emergence of novel biologic therapies for severe asthma supported the need for a thorough review of the diagnosis, investigation, phenotyping, and management of severe asthma. OBJECTIVES: We aimed to propose a practical approach to distinguish uncontrolled asthma due to inadequate asthma management from severe asthma despite optimal asthma management. Moreover, based on emerging scientific evidence, we sought to provide guidance for characterizing individuals with severe asthma and considering a phenotype-specific management. We also aimed to review other novel new potential therapeutic approaches. METHODS: We systematically reviewed the relevant literature focusing on randomized controlled trials and when available, systematic reviews of randomized controlled trials. The proposed key messages, based on scientific evidence and expert opinion, were agreed upon by unanimous consensus. MAIN RESULTS: We defined severe asthma and outlined its significant impact from the societal and patient perspectives. We outlined a practical approach to distinguish severe from uncontrolled but not severe asthma, based on stepwise investigation and management of potential reasons for uncontrolled asthma. After reviewing the current evidence we concluded that: 1) Several biomarkers (e.g. sputum or blood eosinophil count, total IgE, or FeNO) can help identify potential responders to new therapeutic options; 2) Tiotropium may be considered as an add-on therapy for individuals 12 years of age and over with severe asthma uncontrolled despite combination ICS/LABA therapy; 3) The chronic use of macrolides may decrease asthma exacerbations in individuals 18 years of age and over with severe asthma independent of their inflammatory profile; 4) Children aged 6 years and older and adults who are sensitized to at least one relevant perennial allergen and who remain poorly controlled asthmatics despite high dose ICS and a second controller can benefit from the addition of anti-IgE therapy to reduce asthma exacerbations; due to the known risk of side effects associated with high-dose ICS in children, omalizumab should also be considered in children and adolescents who repeatedly exacerbate or have poor control when therapy is stepped down from high-dose to moderate-dose ICS and at least one other controller; 5) Anti-IL5 therapies may be considered for adults 18 years of age and over with severe eosinophilic asthma who experience recurrent asthma exacerbations in spite of high doses of ICS in addition to at least one other controller; and 6) Although bronchial thermoplasty has shown a decrease in asthma exacerbations in one study, its role in the treatment of severe asthma remains uncertain. CONCLUSIONS: After reviewing existing and emerging therapies for severe asthma, we developed ke...

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Section: Efficacy In Adolescent and Pediatric Individualsmentioning

confidence: 99%

“…[61][62][63][68][69][70][71] Published safety data in children is limited to date, but appears similar to adult and adolescent data. [64][65][66] No deaths related to treatment were reported.…”

Section: Safetymentioning

confidence: 99%

Recognition and management of severe asthma: A Canadian Thoracic Society position statement

FitzGerald

Lemière

Lougheed

et al. 2017

Canadian Journal of Respiratory, Critical Care, and Sleep Medic

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“…Three RCTs including around 900 asthmatics were selected for analysis . Figure summarized the study selection process.…”

Section: Resultsmentioning

confidence: 99%

Efficacy and safety of tiotropium in school‐age children with moderate‐to‐severe symptomatic asthma: A systematic review

Rodrigo

Neffen²

2017

Pediatric Allergy Immunology

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“…Several large, high quality randomised controlled trials (one of which enrolled asthma patients with persistent post-bronchodilator airflow limitation 176 ) have consistently shown improvements in FEV 1 in patients with asthma, both in children and in adults, when tiotropium is added to inhaled corticosteroid and inhaled corticosteroid/LABA therapies. [176][177][178][179][180][181][182] Several studies have also shown a reduction in exacerbation risk, 179 183 as well as asthma symptom control. [179][180][181][182] Whether LAMA compounds other than tiotropium have similar positive effects is yet to be tested, but the clinical improvements observed in both COPD and asthma patients suggest that LAMA therapies may be an option for patients with ACOS.…”

Section: Possibilities For Therapeutic Interventionmentioning

confidence: 99%

Asthma-COPD overlap syndrome: pathogenesis, clinical features, and therapeutic targets

Leung

Sin

2017

BMJ

138

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Asthma-COPD overlap syndrome (ACOS) or asthma-COPD overlap captures the subset of patients with airways disease who have features of both asthma and chronic obstructive pulmonary disease (COPD). Although definitions of ACOS vary, it is generally thought to encompass persistent airflow limitation in a patient older than 40 years of age with either a history of asthma or large bronchodilator reversibility. ACOS affects about a quarter of patients with COPD and almost a third of patients who previously had asthma. Compared with their counterparts with asthma or COPD alone, patients with ACOS have significantly worse respiratory symptoms, poorer quality of life, and increased risk of exacerbations and hospital admissions. Whether this condition emerges after gradual shifts in airway remodelling and inflammation in a patient with COPD, as the result of noxious exposures in a patient with asthma, or even as a de novo disease with its own pathology is yet to be determined. Nevertheless, using treatments developed for asthma or COPD that target eosinophilic, neutrophilic, or paucigranulocytic airway inflammation may be a helpful approach to these patients until further clinical trials can be performed.

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A phase III randomized controlled trial of tiotropium add-on therapy in children with severe symptomatic asthma

Abstract: Once-daily tiotropium Respimat 5 μg improved lung function and was well tolerated as add-on therapy to ICS with other maintenance therapies in children with severe symptomatic asthma.

Cited by 110 publications

References 58 publications

Recognition and management of severe asthma: A Canadian Thoracic Society position statement

Recognition and management of severe asthma: A Canadian Thoracic Society position statement

Efficacy and safety of tiotropium in school‐age children with moderate‐to‐severe symptomatic asthma: A systematic review

Asthma-COPD overlap syndrome: pathogenesis, clinical features, and therapeutic targets

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