耶鲁大学医学院的研究人员在11月15日的《新英格兰医学杂志》上公布说，他们的研究证实通过对血液样品中一种蛋白质的测量，能够确定处患有最严重形式的哮喘的患者。也就是说，这种蛋白质可能成为一种新的哮喘生物标志物。
这种叫做YKL-40的新生物标志物的确定，使研究人员向着治疗无数一直很难治愈的严重哮喘靠近了一步。这项研究是耶鲁大学与来自威斯康辛大学和法国巴黎大学以及MedImmune公司的研究人员合作完成。
哮喘是一种慢性肺病，在美国影响着3000万人的健康，其中有900万是儿童。这种病的特征是气管慢性炎症和结构性变化，其症状在一些患者中较严重而在其他患者中则比较温和。
研究人员对三个哮喘组和对照组中253名成年患者的YKL-40（类几丁质酶蛋白）蛋白的血清水平。他们发现，与正常人相比，哮喘患者血清中的YKL-40水平明显增加。另外，血液中YKL-40的水平与哮喘的严重程度、肺功能和患者气管壁的厚度有关。
这项研究的结果证实，YKL-40在严重哮喘患者中明显增多。因此，通过进行血液化验来分析哮喘的方法将可能用于哮喘研究和检测治疗哮喘方法的效果。
研究人员表示，今后研究需要确定YKL-40血液化验在哮喘治疗中的作用。而这项新研究则首次确定处能够通过简单的血液化验就能够获得的一个参数。
耶鲁大学医学院 (Yale University School of Medicine)肺病和危重病急救医学部以及内科医药部门主调查员 Geoffrey Chupp 表示，他们希望这些结果会促进未来的研究就YKL-40 水平和疾病活动性如何相关以及该蛋白成为哮喘控制和研究的生物目标的潜在可能获取更多知识。
尽管现阶段还需要更多数据支持这些成果，但是他们相信这些结果能够说明YKL-40的生物特征应该整合到对哮喘病理学的理解中去。
原始出处:
A Chitinase-like Protein in the Lung and Circulation of Patients with Severe Asthma
Geoffrey L. Chupp, M.D., Chun Geun Lee, M.D., Ph.D., Nizar Jarjour, M.D., Yun Michael Shim, M.D., Carole T. Holm, R.N., Susan He, M.D., James D. Dziura, Ph.D., M.P.H., Jennifer Reed, Ph.D., Anthony J. Coyle, Ph.D., Peter Kiener, Ph.D., Mark Cullen, M.D., Martine Grandsaigne, Marie-Christine Dombret, M.D., Michel Aubier, M.D., Marina Pretolani, Ph.D., and Jack A. Elias, M.D.
ABSTRACT
Background The evolutionarily conserved 18-glycosyl-hydrolase family contains true chitinases and chitinase-like proteins that lack enzymatic activity. Acidic mammalian chitinase has recently been associated with animal models of asthma. The related chitinase-like protein, YKL-40 (also called human cartilage glycoprotein 39 [HCgp-39] and chitinase 3–like 1), can be readily measured in the serum. However, its relationship to asthma has not been evaluated.
Methods We quantified serum YKL-40 levels in three cohorts of patients with asthma — one recruited from the patient population at Yale University, one from the University of Paris, and one from the University of Wisconsin — as well as in controls from the surrounding communities. In the Paris cohort, immunohistochemical analysis and morphometric quantitation were used to evaluate the locus of expression of YKL-40 in the lung. The clinical characteristics of the patients with high serum or lung YKL-40 levels were also evaluated.
Results Serum YKL-40 levels were significantly elevated in patients with asthma as compared with controls. In the Paris cohort, lung YKL-40 levels were elevated and were correlated with circulating YKL-40 levels (r=0.55, P<0.001) and with airway remodeling (measured as the thickness of the subepithelial basement membrane) (r=0.51, P=0.003). In all three cohorts, serum YKL-40 levels correlated positively with the severity of asthma and inversely with the forced expiratory volume in 1 second. Patients with elevated levels of YKL-40 had significantly more frequent rescue-inhaler use, greater oral corticosteroid use, and a greater rate of hospitalization than patients with lower levels.
Conclusions YKL-40 is found in increased quantities in the serum and lungs in a subgroup of patients with asthma, in whom expression of chitinase in both compartments correlates with the severity of asthma. The recovery of YKL-40 from these patients indicates either a causative or a sentinel role for this molecule in asthma.
