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Risk Factors for Early Remodelling in Severe Asthma in Children (P'tit-ASTHME)

2016年6月15日 更新者:University Hospital, Bordeaux
  • Background: Asthma is a frequent disease characterized by bronchial hyperresponsiveness, inflammation and remodeling. Consistent epidemiological data indicate that outcome of asthma in adults may be determined in early childhood. This may be due to bronchial remodeling, an abnormal repair process that contributes to the development of poorly reversible airway narrowing. It appears very early in the natural history of the disease and involves increased mass of bronchial smooth muscle (BSM). The mechanism of such an increase has been related with an increase in smooth muscle cell proliferation. Recently, we have demonstrated that in severe asthma, BSM increased proliferation is induced by an enhanced mitochondrial biogenesis. Moreover, we have also shown that immature human, non-asthmatic airway smooth muscle cells (ASMC) proliferate to a greater extent than normal adult ASMC, in a similar fashion to adult asthmatic ASMC. Immature ASMC may thus have great potential to stimulate airway remodeling. We thus hypothesized that remodeling is an early process and certain characteristics of ASMC in severe preschool asthma may predispose such children to persistent remodeling with airway obstruction later in life.
  • Purpose: To investigate prognostic factors of airway remodeling in preschool children, with special attention to ASMC proliferation (mitochondrial mass & biogenesis).
  • Methods: In the initial phase of the project, 75 severe asthmatic preschool children (<5 yr) will be prospectively recruited from the "CHU de Bordeaux" and the "CHU de Toulouse" according to the "Haute Autorité de Santé" criteria. Inclusion visit will include written informed consent, asthma control evaluation, clinical examination, lung function testing (exhaled NO, plethysmography), prick tests, chest X Ray and blood sample for total IgE levels. Bronchial specimens from all subjects will be obtained by fiberoptic bronchoscopy at visit 2. Airway remodeling will be evaluated by morphological analysis. After smooth muscle mitochondria will be analyzed by electronic microscopy & immunoblotting. Comparison between the 2 groups will be performed by unpaired t tests for parametric data and x2-tests for non-parametric data. In the second phase of the project, patients will then be followed-up till the age of 7-10 yrs, when another bronchoscopy with biopsies will be performed.

研究概览

地位

完全的

条件

研究类型

介入性

注册 (实际的)

67

阶段

  • 不适用

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习地点

    • Aquitaine
      • Bordeaux、Aquitaine、法国、33000
        • CHU de Bordeaux
    • Languedoc-Roussillon-Midi-Pyrénées
      • Toulouse、Languedoc-Roussillon-Midi-Pyrénées、法国、31026
        • Hôpital des enfants

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

1年 至 5年 (孩子)

接受健康志愿者

有资格学习的性别

全部

描述

Inclusion Criteria:

Asthmatic children

  • Parents (and possibly the child) who gave written informed consent.
  • Affiliated with a social security scheme.
  • Age from 1 to less than 5 years.
  • Severe persistent asthma according to the criteria of the National Health Authority (Annex I) or NEW PROPOSED CRITERIA (adapted ATS (42)):

Major criteria (> 1) Asthma control in mild to moderate level requiring

  1. A continuous or semi continuous (≥ 50% of the year) by oral corticosteroids
  2. A treatment with high doses of inhaled corticosteroids (> 500 micrograms / day of Beclomethasone, or equivalent (> 400 micrograms / day of Budesonide,> 200 micrograms / day of Fluticasone) for at least 6 weeks.

And

minor criteria (> 2)

  1. The need for an additional daily treatment (β2-agonists, long-acting, theophylline, anti-leukotrienes)
  2. Symptoms that require taking daily or almost daily of β2-agonists of short action
  3. persistent obstruction (FEV <80% PEF variability> 20%) (If reliable spirometry, usually> 5 years of age)
  4. One or more seeking care in emergency / year
  5. At least three short courses of oral corticosteroids / year
  6. Rapid Increases caused by the decrease of 25% of the dose of oral corticosteroids or inhaled
  7. ATCD of severe acute asthma who put in life-threatening

Non-asthmatic children

  • Non asthmatic child with indication of endoscopy:

    • Any endoscopy for a disease without acute or chronic inflammation in the biopsy area (≥1 to <5 years (1st part): congenital stridor, double aortic arch, foreign body removal inhaled, ...; ≥ 7 to ≤ 10 years ( 2nd component): inhaled foreign body removal, ...).
    • Parents (and possibly the child) who gave written informed consent.
    • Affiliated with a social security scheme.
  • Children not asthmatic postmortem (retrospective and prospective)

    • Age from 1 to under 5 (1st part) or aged 7 to 10 years (2nd part) on the death
    • Died without pulmonary pathology in the sampled area
  • Non asthmatic child with thoracic surgery:

    • Age from 1 to under 5 (1st part) or aged 7 to 10 years (2nd part).
    • Subject with pulmonary pathology, requiring thoracic surgery lobectomy, non-inflammatory in the sampled area.
    • Parents (and possibly the child) who gave written informed consent.
    • Affiliated with a social security scheme.

Exclusion Criteria:

Asthmatic children:

  • Subject having a severe exacerbation of asthmatic disease requiring hospitalization in the 3 weeks preceding their inclusion.
  • exclusion period on topic compared to another protocol.
  • Subject with significant co-morbidity associated with asthma not of any nature whatsoever
  • bronchial malformations (exclusion criterion ex post).
  • Subject with a dental infection, or nasopharyngeal airway (viral or bacterial) with fever (> 39 ° C) in the 4 weeks preceding the survey.
  • chronic viral infections (hepatitis, HIV).
  • non-specific inclusion criteria to endoscopy:
  • Review of hemostasis abnormal,
  • Subject with a heart condition,
  • Subject is not fasted for over 6 hours.

Children without asthma:

  • Non-asthmatic children with indication of endoscopy:

    • asthma diagnosed by a doctor.
    • exclusion period on topic compared to another protocol.
    • Subject with significant co-morbidity associated with asthma not of any nature whatsoever.
    • bronchial malformations (exclusion criterion ex post).
    • Subject with a dental infection, or nasopharyngeal airway (viral or bacterial) with fever (> 39 ° C) in the 4 weeks preceding the survey.
    • chronic viral infections (hepatitis, HIV).
    • non-specific inclusion criteria to endoscopy:
    • Review of hemostasis abnormal,
    • Subject with a heart condition,
    • Subject is not fasted for over 6 hours.
  • Children postmortem non-asthmatics:

    • asthma diagnosed by a doctor.
    • Subject with a dental infection, or nasopharyngeal airway (viral or bacterial) with fever (> 39 ° C) within 4 weeks before sampling of tissue.
    • chronic viral infections (hepatitis, HIV).
  • Non-asthmatic children with thoracic surgery:

    • asthma diagnosed by a doctor.
    • exclusion period on topic compared to another protocol.
    • Subject with a dental infection, or nasopharyngeal airway (viral or bacterial) with fever (> 39 ° C) within 4 weeks before sampling of tissue.
    • chronic viral infections (hepatitis, HIV).

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:诊断
  • 分配:非随机化
  • 介入模型:并行分配
  • 屏蔽:无(打开标签)

武器和干预

参与者组/臂
干预/治疗
有源比较器:Asthmatic children
假比较器:Non-asthmatic children

研究衡量的是什么?

主要结果指标

结果测量
大体时间
Evaluation of Airway remodeling (distance from the reticular membrane to the smooth muscle).
大体时间:1 day
1 day

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

调查人员

  • 首席研究员:MICHAEL FAYON, Professor、University Hospital, Bordeaux

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2012年3月1日

初级完成 (实际的)

2015年11月1日

研究完成 (实际的)

2015年11月1日

研究注册日期

首次提交

2016年6月15日

首先提交符合 QC 标准的

2016年6月15日

首次发布 (估计)

2016年6月20日

研究记录更新

最后更新发布 (估计)

2016年6月20日

上次提交的符合 QC 标准的更新

2016年6月15日

最后验证

2016年6月1日

更多信息

与本研究相关的术语

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)?

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

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