①背景:目前缺乏预测儿童哮喘发病的生物标志物，最好是非侵入性的②目的:对早期2型炎症的生物标志物与哮喘发病的关系知之甚少。我们评估了空气变应原致敏、外周血嗜酸性粒细胞和血清骨膜蛋白作为儿童哮喘的潜在生物标志物。③方法:对参与哮喘儿童起源研究的儿童从出生起进行前瞻性随访。收集2岁、4岁、6岁和11岁的血液样本，测量244名儿童的血清特异性IgE水平、血嗜酸性细胞计数和骨膜球蛋白水平。评估这些生物标志物、年龄和哮喘之间的关系。④结果:儿童血清骨膜蛋白水平大约比以前观察到的成人水平高2- 3倍。最高水平为2岁(145 ng/mL)， 4 - 11岁(128 - 130 ng/mL)无明显变化。2岁时，骨膜蛋白水平为150 ng/mL或更高，预测6岁时哮喘(优势比[or]， 2.3;95%可信区间,1.3 - -4.4)。嗜酸性粒细胞数为300个/mL或更多，2岁时空气变应原致敏均与6岁时哮喘风险增加有关(or, 3.1;95% CI, 1.7-6.0; OR, 3.3;95%可信区间,1.7 - -6.3)。具有任何2种生物标记物的儿童到学龄时患哮喘的风险显著增加(>_2种生物标记物vs .无:OR, 6.6;95%可信区间,2.7 - -16.0)。⑤结论:儿童血清骨膜蛋白水平明显高于成人，可能与骨更新有关，骨更新影响了其在儿童中的临床应用。生命早期空气变应原致敏和血嗜酸性粒细胞升高是哮喘发展的可靠预测因子。有证据表明，儿童早期激活多种途径的2型炎症是哮喘发展的最大风险。(J Allergy Clin Immunol 2016;nnn:nnn-nnn.)
Relationships among aeroallergen sensitization, peripheral blood eosinophils, and periostin in pediatric asthma development
Background: Biomarkers, preferably noninvasive, that predict asthma inception in children are lacking.
Objective: Little is known about biomarkers of type 2 inflammation in early life in relation to asthma inception. We evaluated aeroallergen sensitization, peripheral blood eosinophils, and serum periostin as potential biomarkers of asthma in children.
Methods: Children enrolled in the Childhood Origins of Asthma study were followed prospectively from birth. Blood samples were collected at ages 2, 4, 6, and 11 years, and serum- specific IgE levels, blood eosionophil counts, and periostin levels were measured in 244 children. Relationships among these biomarkers, age, and asthma were assessed.
Results: Serum periostin levels were approximately 2- to 3-fold higher in children than previously observed adult levels. Levels were highest at 2 years (145 ng/mL), and did not change significantly between 4 and 11 years (128 and 130 ng/mL). Age2 year periostin level of 150 ng/mL or more predicted asthma at age 6 years (odds ratio [OR], 2.3; 95% CI, 1.3-4.4). Eosinophil count of 300 cells/mL or more and aeroallergen sensitization at age 2 years were each associated with increased risk of asthma at age 6 years (OR, 3.1; 95% CI, 1.7-6.0 and OR, 3.3; 95% CI,1.7-6.3). Children with any 2 of the biomarkers had a significantly increased risk of developing asthma by school age (>_2 biomarkers vs none: OR, 6.6; 95% CI, 2.7-16.0).
Conclusions: Serum periostin levels are significantly higher in children than in adults, likely due to bone turnover, which impairs clinical utility in children. Early life aeroallergen sensitization and elevated blood eosinophils are robust predictors of asthma development. Children with evidence of activation of multiple pathways of type 2 inflammation in early life are at greatest risk for asthma development. (J Allergy Clin Immunol 2016;nnn:nnn-nnn.)
Halie M. Anderson, MD,a Robert F. Lemanske, Jr, MD,a Joseph R. Arron, MD, PhD,b Cecile T. J. Holweg, PhD,b Victoria Rajamanickam, MS,c Ronald E. Gangnon, PhD,c James E. Gern, MD,a and Daniel J. Jackson