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一项关于管理孕期哮喘(MAP)的试验:FeNO水平和后代儿童哮喘的相关性研究

2018/04/04

   摘要
   背景:在澳大利亚纽卡斯尔的单中心双盲,随机对照的妊娠管理哮喘(MAP)试验中,在怀孕的哮喘妇女中比较了使用呼出一氧化氮(FeNO)和哮喘症状的相结合治疗策略(FeNO组)与仅使用临床症状制定治疗策略(临床组)之间疗效的差别(ANZ Clinical Trials Registry,编号12607000561482)。主要结果是FeNO组妊娠期哮喘加重减少了50%。然而,FeNO对其后代哮喘疾病进展的影响尚不清楚。
   目的:我们试图调查FeNO指导的哮喘管理在怀孕期间对后代儿童哮喘发病率的影响。
   方法:179位母亲同意参与这项双盲随访研究,主要目的是确定FeNO指导的哮喘管理对儿童哮喘发病率的影响。
   结果:140名儿童(78%)在4至6岁期间参与了随访。与单纯基于临床症状的方法相比,FeNO的指导显着降低了医生诊断的哮喘(25.9% vs 43.2%; OR 0.46,95%;CI: 0.22-0.96,p = 0.04)。此外,喘息发作(OR 0.27; CI 0.09-0.87,P = 0.03),短效β受体激动剂使用(OR 0.49; CI 0.25-0.97; P = 0.04)和哮喘急诊就诊(OR 0.17,CI 0.04-0.76; p = 0.02)在过去12个月内不太常见于FeNO组母亲所生的孩子。医生诊断的哮喘与基因位点17q21的早发性哮喘的常见高危等位基因相关(rs8069176的p = 0.01; rs8076131的p = 0.03),与呼吸道耐药性(p = 0.02)和高FeNO水平(p= 0.03)也相关。因果分析表明,母亲在MAP试验期间,FeNO引导的哮喘管理可以通过吸入皮质类固醇的“用法”和 “首次改变剂量的时间”对后代儿童哮喘的产生影响(OR 0.83; CI 0.59-0.99和OR 0.90, CI 0.70-1.03)。
   结论:在孕期FeNO引导的哮喘管理可以有效阻止了学龄前儿童的哮喘的发生,这种作用部分是通过MAP试验期间使用和吸入皮质类固醇的剂量改变导致的。
 
(中日友好医院呼吸与危重症医学科 王圆方 摘译 林江涛 审校)
(J Allergy Clin Immunol. 2018 Mar 7. pii: S0091-6749(18)30392-0. doi: 10.1016/j.jaci.2018.02.039. [Epub ahead of print])


 
 
Managing Asthma in Pregnancy (MAP) trial: FeNO levels and childhood asthma
 
Morten M, Collison A, Murphy VE, Barker D, Oldmeadow C, Attia J, Meredith J, Powell H, Robinson PD, Sly PD, Gibson PG, Mattes J.
 
Abstract
Background:The single-centre double-blind, randomised controlled Managing Asthma in Pregnancy (MAP) trial in Newcastle, Australia, compared a treatment algorithm using the fraction of exhaled nitric oxide (FeNO) in combination with asthma symptoms (FeNO group) against a treatment algorithm using clinical symptoms only (clinical group) in pregnant asthmatic women (ANZ Clinical Trials Registry, number 12607000561482). The primary outcome was a 50% reduction in asthma exacerbations during pregnancy in the FeNO group. However, the effect of FeNO-guided management on the development of asthma in the offspring is unknown.
ObjectiveWe sought to investigate the effect of FeNO-guided asthma management during pregnancy on asthma incidence in childhood.
Methods:179 mothers consented to participate in the Growing Into Asthma (GIA) double-blind follow-up study with the primary aim to determine the effect of FeNO-guided asthma management on childhood asthma incidence.
Results:140 children (78%) were followed up at 4 to 6 years of age. FeNO-guided as compared to symptoms only based approach significantly reduced doctor diagnosed asthma (25·9% versus 43·2%; odds ratio [OR] 0.46, 95% confidence interval [CI] 0.22 to 0.96, p=0.04). Furthermore frequent wheeze (OR 0.27; CI 0.09 to 0.87, p=0.03), use of short-acting beta agonists (OR 0.49; CI 0.25 to 0.97; p=0.04), and emergency department visits for asthma (OR 0.17, CI 0.04 to 0.76; p=0.02) in the past 12 months were less common in children born to mothers from the FeNO group. Doctor diagnosed asthma was associated with common risk alleles for early-onset asthma at gene locus 17q21 (p=0·01 for rs8069176; p=0·03 for rs8076131), and higher airways resistance (p=0·02) and FeNO levels (p=0·03). A causal mediation analysis suggested natural indirect effects of FeNO-guided asthma management on childhood asthma through "any use" and "time to first change in dose" of inhaled corticosteroids during the MAP trial (OR 0.83; CI 0.59 to 0.99 and OR 0.90, CI 0.70 to 1.03, respectively).
ConclusionFeNO-guided asthma management during pregnancy prevented doctor diagnosed asthma in the offspring at preschool age, in part mediated through changes in use and dosing of inhaled corticosteroids during the MAP trial.


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