Clinical efficacy of tiotropium in children with asthma

Hou, Juan; Chen, Ying; Long, Zhen; Zhou, Xiaoqin; Shu, Junhua

doi:10.12669/pjms.322.8836

Cited by 10 publications

(13 citation statements)

References 19 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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“…+ 2 controller or high dose ICS (≥400 μg) plus one controller12 weeksPeak FEV 1 (0–3 h)1) Trough FEV 1 2) Peak FVC (0–3 h)3) ACQ–IA score and responder rate4) trough FVC5) FEV 1 AUC (0–3h) 6) rescue medication use7) time to first exacerbation8) time to first severe exacerbation9) ACQ-6 and ACQ-710) FEF 25–75 11) weekly evening PEF12) TolerabilityPrimary and key secondary outcomes were significantly improved only for tiotropium 5 μg. Peak FVC (0–3 h) and trough FVC did not reach significance for any tiotropium dose. Huang J et al [134]2016Moderate persistent asthma6–1480125 μg fluticasone propionate aerosol TD + placebo OD vs 125 μg fluticasone propionate aerosol TD + tiotropium 18 μg dry-powder OD12 weeks(not clearly stated)1) FEV1, FVC and PEF at week 12.2) Asthma exacerbation3) Rescue medication use4) Night time symptoms5) TolerabilityTiotropium 18 as add-on to maintenance therapy significantly improved lung function compared to maintenance therapy alone. Hamelmann E et al [131]2016FEV 1 60–90%predACQ-7 > 1.5 and chronic treatment with ICS (200–800 μg for 12–14 years; 400–800 μg for 15–17 years) +/−LABA +/− LTRA12–17376Add on tiotropium 5 μg, 2.5 μg or placebo to maintenance therapy, with ICS +/− LTRA (LABA not permitted) + open label SABA as rescue medication48 weeksPeak FEV 1 (0–3 h)1) Trough FEV 1 2) Peak FVC (0–3 h)3) FVC AUC (0–3h) 4) Trough FVC5) FEV 1 AUC (0–3h) 6) time to first exacerbation7) time to first severe exacerbation8) ACQ-7 and ACQ-69) AQLQ (S) score and responder rate10) TolerabilityAll functional outcomes were significantly improved compared to placebo for all tiotropium doses. Greatest overall benefit was found for tiotropium 5 μg.…”

Section: Introductionmentioning

confidence: 97%

“…After 12 weeks of treatment, the tiotropium/fluticasone group experienced significant improvements in FEV 1 , FVC and PEF and a reduced usage of SABA on demand therapy and night-time symptoms compared with fluticasone alone [134]. …”

Section: Introductionmentioning

confidence: 99%

The evidence on tiotropium bromide in asthma: from the rationale to the bedside

Radovanovic

Santus

Blasi

et al. 2017

Multidiscip Respir Med

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Severe and poorly controlled asthma still accounts for a great portion of the patients affected. Disease control and future risk management have been identified by international guidelines as the main goals in patients with asthma. The need for new treatment approaches has led to reconsider anticholinergic drugs as an option for asthma treatment. Tiotropium is the first anticholinergic drug that has been approved for children and adults with poorly controlled asthma and is currently considered as an option for steps 4 and 5 of the Global Initiative for Asthma. In large randomized clinical trials enrolling patients with moderate to severe asthma, add-on therapy with tiotropium has demonstrated to be efficacious in improving lung function, decreasing risk of exacerbation and slowing the worsening of disease; accordingly, tiotropium demonstrated to be non inferior compared to long acting beta-agonists in the maintenance treatment along with medium to high inhaled corticosteroids. In view of the numerous ancillary effects acting on inflammation, airway remodeling, mucus production and cough reflex, along with the good safety profile and the broad spectrum of efficacy demonstrated in different disease phenotypes, tiotropium can represent a beneficial alternative in the therapeutic management of poorly controlled asthma. The present extensive narrative review presents the pharmacological and pathophysiological basis that guided the rationale for the introduction of tiotropium in asthma treatment algorithm, with a particular focus on its conventional and unconventional effects; finally, data on tiotropium efficacy and safety. from recent randomized clinical trials performed in all age categories will be extensively discussed.

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“…SNOT-22 and LKES tests were used for assessing the efficacy of salbutamol, montelukast and rhLPHN3 Ab treatments in children with pediatric asthma at the baseline and post-treatment at week 16. Clinical pediatric asthma scores were evaluated as descripted in previous studies (22,23).…”

Section: Dna Binding Activitymentioning

confidence: 99%

Clinical efficacy of recombinant human latrophilin 3 antibody in the treatment of pediatric asthma

Liu¹,

Zhang²,

Liu³

2017

Exp Ther Med

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Abstract. Pediatric asthma is a chronic pulmonary inflammatory disease featuring hypersecretion of mucus and inflammation in the airway, resulting in dysfunction of the airway smooth muscle. Previous evidence demonstrated that latrophilins, a novel family of receptors, present a beneficial effect on airway smooth muscle cells. In the present study, the therapeutic effects of recombinant human latrophilin 3 (rhLPHN3) antibody (Ab) in patients with pediatric asthma were investigated, and the molecular mechanism underlying the function of LPHN3 in the treatment of asthma in clinical practice was examined. A total of 342 pediatric asthma cases were recruited and randomly divided into three groups, receiving treatment with rhLPHN3 Ab (n=134), salbutamol (n=108) or montelukast (n=100) by nasal aerosolization. Each group received the respective clinically tested dose for 16 weeks. Inflammatory factors interleukin (IL)-10, IL-17, IL-4, matrix metallopeptidase-9 (MMP-9), interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) levels in peripheral blood mononuclear cells were analyzed prior to and post treatment. The clinical outcomes revealed that pathological alterations were significantly improved following treatment with rhLPHN3 Ab for patients with pediatric asthma when compared with those receiving salbutamol and montelukast. It was also observed that rhLPHN3 Ab downregulated the plasma concentration levels of IL-10, IL-17, IL-4 and MMP-9, and upregulated IFN-γ and TGF-β levels in the three groups. In addition, clinical data demonstrated that rhLPHN3 Ab significantly promoted E-selectin and mucin 5AC expression, as well as improved the activation of nuclear factor (NF)-κB p65 DNA binding activity and the phosphorylation levels of protein kinase A. Furthermore, rhLPHN3 Ab markedly improved adhesion and proliferation of airway smooth muscle cells, which led to promotion of the contraction of these cells.In conclusion, these clinical data suggest that rhLPHN3 Ab serves an important role in the inhibition of inflammatory mediators through downregulation of NF-κB signaling pathway, which contributes to airway remodeling and bronchodilation in patients with pediatric asthma.

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Clinical efficacy of tiotropium in children with asthma

Cited by 10 publications

References 19 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

The evidence on tiotropium bromide in asthma: from the rationale to the bedside

Clinical efficacy of recombinant human latrophilin 3 antibody in the treatment of pediatric asthma

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