NCT02806466已完成不适用
Risk Factors for Early Remodelling in Severe Asthma in Children
University Hospital, Bordeaux4 个研究点 分布在 1 个国家目标入组 67 人开始时间: 2012年3月1日最近更新:
适应症
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 67
- 试验地点
- 4
- 主要终点
- Evaluation of Airway remodeling (distance from the reticular membrane to the smooth muscle).
研究概览
简要总结
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 5 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •A continuous or semi continuous (≥ 50% of the year) by oral corticosteroids
- •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.
- •minor criteria (> 2)
- •The need for an additional daily treatment (β2-agonists, long-acting, theophylline, anti-leukotrienes)
- •Symptoms that require taking daily or almost daily of β2-agonists of short action
- •persistent obstruction (FEV <80% PEF variability> 20%) (If reliable spirometry, usually> 5 years of age)
- •One or more seeking care in emergency / year
- •At least three short courses of oral corticosteroids / year
- •Rapid Increases caused by the decrease of 25% of the dose of oral corticosteroids or inhaled
- •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.
排除标准
- •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).
结局指标
主要结局
Evaluation of Airway remodeling (distance from the reticular membrane to the smooth muscle).
时间窗: 1 day
次要结局
未报告次要终点
研究者
研究点 (4)
Loading locations...
相似试验
已完成
不适用
General Risk Factors and Inflammatory Determinants in Older Patients With AsthmaLate-Onset AsthmaChildhood AsthmaAsthmaNCT03278561Gerdien Tramper90
招募中
不适用
A Cohort Study of Risk Factors and Prognosis for Frequent Acute Asthma Exacerbations PhenotypeAsthma ExacerbationsNCT06621056Peking University Third Hospital300
已完成
不适用
The risk factors and clinical course of asthma-related COPDAsthma,COPD,exacerbation,clinical,AsthmaTCTR20150420001Faculty of Medicne, ChiangMai university120
尚未招募
不适用
Retrospective Cohort Study on Asthma With Frequent Acute Attacks PhenotypeAsthmaNCT06026462Qianfoshan Hospital540
终止
不适用
Predictive Factors for Exacerbation Outcome in Severe Refractory AsthmaticsChronic Inflammatory DiseasesAsthmaNCT00721097Nantes University Hospital40