Stein R T, Holberg C J, Morgan W J, Wright A L, Lombardi E, Taussig L, Martinez F D
Respiratory Sciences Center, University of Arizona, Tucson 85724, USA.
Thorax. 1997 Nov;52(11):946-52. doi: 10.1136/thx.52.11.946.
There is increasing evidence that wheezing during childhood may be a heterogeneous condition, and that different forms of wheezing may be associated with different risk factors and prognosis. The aim of this study was to determine if measures of airway lability and of atopy could identify distinct wheezing phenotypes during childhood.
In a cohort of children followed from birth peak flow variability (n = 600) was evaluated and methacholine challenge responsiveness (n = 397) was measured at age 11 in relation to wheezing before the age of three, and at age six and 11 years total serum IgE and skin test reactivity to allergens were determined.
Neither positive peak flow variability nor methacholine hyperresponsiveness measured at age 11 were associated with wheezing occurring only during the first three years of life. Both methacholine hyperresponsiveness and positive peak flow variability were associated with wheezing at both ages six and 11 (OR 5.1 (95% CI 2.4 to 10.6) and 2.3 (1.2 to 4.5), respectively). In addition, positive peak flow variability was associated with wheezing up to the age of six but not at age 11 in non-atopic children (OR 2.9 (95% CI 1.0 to 8.8)). Methacholine hyperresponsiveness measured at age 11 was more frequently observed in boys (OR 2.1 (95% CI 1.2 to 3.5)) and was strongly associated with serum IgE levels measured at ages six and 11 (p < 0.001) and with positive skin test reactivity (OR 4.5 (95% CI 2.0 to 10.1)). Peak flow variability was unrelated to sex or markers of atopy (IgE and skin test reactivity).
Methacholine responsiveness and peak flow variability assessed at age 11, together with markers of atopy (IgE and skin test reactivity to allergens) identify three different wheezing phenotypes in childhood: "transient early wheezing" limited to the first three years of life and unrelated to increased airway lability; "non-atopic wheezing" of the toddler and early school years associated with positive peak flow variability but not with methacholine hyperresponsiveness; and "IgE-associated wheeze/asthma" associated with persistent wheezing at any age and with methacholine hyperresponsiveness, peak flow variability, and markers of atopy.
越来越多的证据表明，儿童期喘息可能是一种异质性疾病，不同形式的喘息可能与不同的危险因素和预后相关。本研究的目的是确定气道易激性指标和特应性指标是否能识别儿童期不同的喘息表型。
在一个从出生开始随访的儿童队列中，评估了600名儿童的呼气峰值流速变异性，并在11岁时测量了397名儿童对乙酰甲胆碱激发试验的反应性，同时记录三岁前、六岁和11岁时的喘息情况，并测定了总血清IgE水平以及对过敏原的皮肤试验反应性。
11岁时测得的呼气峰值流速变异性阳性或乙酰甲胆碱高反应性均与仅在生命的前三年出现的喘息无关。乙酰甲胆碱高反应性和呼气峰值流速变异性阳性均与六岁和11岁时的喘息相关（比值比分别为5.1（95%可信区间2.4至10.6）和2.3（1.2至4.5））。此外，在非特应性儿童中，呼气峰值流速变异性阳性与六岁前的喘息相关，但与11岁时的喘息无关（比值比2.9（95%可信区间1.0至8.8））。11岁时测得的乙酰甲胆碱高反应性在男孩中更常见（比值比2.1（95%可信区间1.2至3.5）），并且与六岁和11岁时测得的血清IgE水平密切相关（p<0.001），也与皮肤试验反应阳性相关（比值比4.5（95%可信区间2.0至10.1））。呼气峰值流速变异性与性别或特应性标志物（IgE和皮肤试验反应性）无关。
11岁时评估的乙酰甲胆碱反应性、呼气峰值流速变异性以及特应性标志物（IgE和对过敏原的皮肤试验反应性）可识别儿童期三种不同的喘息表型：“短暂早期喘息”，局限于生命的前三年，与气道易激性增加无关；“非特应性喘息”，发生在幼儿期和小学早期，与呼气峰值流速变异性阳性相关，但与乙酰甲胆碱高反应性无关；以及“IgE相关喘息/哮喘”，与任何年龄的持续性喘息、乙酰甲胆碱高反应性、呼气峰值流速变异性和特应性标志物相关。
