Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen, Gentofte, Copenhagen, Denmark.
J Allergy Clin Immunol. 2011 May;127(5):1155-64.e2. doi: 10.1016/j.jaci.2011.02.007. Epub 2011 Mar 24.
Asthmatic symptoms in young children reflect a heterogeneous group of diseases. Symptoms remain the primary end-point in both research and clinical management, but there is a need for standardized symptom assessment.
We sought to explore endotyping of early childhood asthma by prospective daily diary recordings of globally assessed symptoms during the first 6 years of life.
Globally assessed troublesome lung symptoms were recorded in daily diaries during the first 6 years of life in the Copenhagen Prospective Studies on Asthma in Childhood birth cohort born of mothers with asthma. Symptom recordings adjusted for missing values were used to categorize children based on the temporal symptom pattern. We propose an alternative approach of quantitating symptom frequency and longitudinal assessment of age-at-onset to segment children. These different methods were compared by estimating the risk from the well-established genetic risk variants of ORMDL3.
Six years of daily diary recordings were available in 307 children (75% of the birth cohort). We confirmed the archetypal temporal categories of transient early, persistent, and late-onset troublesome lung symptoms based on 3-year periods, finding no benefit from a finer temporal categorization of 2- or 1-year periods. Restricting categorization to symptoms during the summer improved specificity at the expense of sensitivity. Our alternative approach quantitating symptom frequency and age-at-onset exhibited a more powerful association with ORMDL3, whereas the study power was lost by restricting to doctor-verified wheeze.
We propose a novel method for endotyping of early childhood asthma based on the frequency and age-of-onset of globally assessed troublesome lung symptoms analyzed longitudinally. This method showed the closest association with genetic variants, hence underlying molecular mechanisms and endotypes.
幼儿的哮喘症状反映了一组异质性疾病。症状仍然是研究和临床管理的主要终点，但需要标准化的症状评估。
我们旨在通过前瞻性记录儿童生命的前 6 年中每日的全球评估症状，探索婴幼儿哮喘的表型分类。
在患有哮喘的母亲所生的哥本哈根儿童哮喘前瞻性研究出生队列中，在生命的前 6 年中，每日记录全球评估的麻烦性肺部症状。使用调整缺失值的症状记录，根据时间症状模式对儿童进行分类。我们提出了一种替代方法，通过定量症状频率和纵向评估发病年龄来分割儿童。通过估计 ORMDL3 中已建立的遗传风险变异的风险来比较这些不同的方法。
307 名儿童（出生队列的 75%）提供了 6 年的每日日记记录。我们根据 3 年时间段确认了基于暂时性早期、持续性和晚期发作的麻烦性肺部症状的典型时间类别，发现更精细的 2 年或 1 年时间段的时间分类没有好处。将分类限制在夏季症状可提高特异性，但敏感性降低。我们替代方法定量症状频率和发病年龄与 ORMDL3 表现出更密切的关联，而通过限制医生确诊的喘息来进行分类则丧失了研究的效力。
我们提出了一种基于全球评估的麻烦性肺部症状的频率和发病年龄的婴幼儿哮喘表型分类的新方法。该方法与遗传变异具有最密切的关联，因此可以深入了解潜在的分子机制和表型。
