SERUM AND BRONCHOALVEOLAR LAVAGE OF N-TERMINAL TYPE-III PROCOLLAGEN PEPTIDES IN IDIOPATHIC PULMONARY FIBROSIS
SERUM AND BRONCHOALVEOLAR LAVAGE OF N-TERMINAL TYPE-III PROCOLLAGEN PEPTIDES IN IDIOPATHIC PULMONARY FIBROSIS
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DOI：
10.1164/ajrccm/146.3.701
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发表时间：
1992-09-01
期刊：
影响因子：
--
通讯作者：
DAVIS, GS
中科院分区：
文献类型：
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作者：
LOW, RB;GIANCOLA, MS;DAVIS, GS
胶原沉积是特发性肺纤维化（IPF）临床病程的主要决定因素。结缔组织代谢标志物的鉴定将显著提高疾病分期和监测这些患者病程的能力。先前的IPF研究表明，血液和支气管肺泡灌洗液中n -末端III型前胶原肽（N-PIIIP）水平升高。我们假设前胶原肽水平升高是胶原沉积增强的标志，这与活动性疾病的间质纤维化特征有关。本研究旨在探讨N-PIIIP恢复与肺功能生理参数的关系。用放射免疫分析法测定了24例IPF患者和29名志愿者血清和支气管肺泡灌洗液（BAL）中的N-PIIIP水平。通过临床病史、体格检查、胸片、肺生理学评估和确证性开肺活检来评估IPF的疾病程度。使用先前描述的临床、放射学和生理学（CRP）评分系统对疾病的严重程度进行分级。BAL中N-PIIIP归一化为白蛋白的水平高于志愿者（1.6倍，p < 0.05）和IPF患者（24倍，p < 0.05）的血清水平，与局部肺生成一致。无论是以浓度表达（健康志愿者0.11 +/- 0.06 ng/ml, IPF 5.0 +/- 14.4，平均+/- SD， p < 0.05）还是以白蛋白表达（健康志愿者2.8 +/- 1.2,IPF 73 +/- 106, p < 0.005）， BAL N-PIIIP在IPF患者中均显著升高。在IPF组，IPF患者运动时肺泡动脉氧梯度与BAL、N-PIIIP/ml （rho = 0.70, p < 0.001）和N-PIIIP/ml白蛋白（rho = 0.76, p < 0.001）呈正相关。CRP评分与血清N-PIIIP浓度相关（rho = 0.48, p < 0.04），血清N-PIIIP归一化为白蛋白（rho = 0.60, p < 0.01）。这些发现表明，测量N-PIIIP水平可能有助于评估疾病活动，并反映进行性IPF特征的持续胶原生成。
Collagen deposition is a prime determinant of clinical course in idiopathic pulmonary fibrosis (IPF). Identification of a marker of connective tissue metabolism would significantly enhance the ability to stage the disease and monitor the course of these patients. Prior studies of IPF have indicated that N-terminal Type III procollagen peptide (N-PIIIP) levels in blood and bronchoalveolar lavage BAL fluid are elevated. We hypothesized that elevated levels of procollagen peptides are a marker of enhanced collagen deposition, which is associated with interstitial fibrosis characterizing active disease. The purpose of the present study was to explore the relationship between N-PIIIP recovery and physiologic parameters of lung function. N-PIIIP levels in sera and bronchoalveolar lavage (BAL) from 24 patients with IPF and 29 volunteers were measured by radioimmunoassay. The extent of disease in IPF was assessed by clinical history, physical examination, chest radiograph, pulmonary physiology evaluation, and confirmatory open-lung biopsy. The severity of disease was graded using a previously described clinical, radiologic, and physiologic (CRP) scoring system. N-PIIIP normalized to albumin was higher in BAL than in serum for both volunteers (1.6-fold; p < 0.05) and IPF patients (24-fold; p < 0.05), consistent with local pulmonary production. BAL N-PIIIP was significantly elevated in IPF patients, whether expressed as concentration (healthy volunteer 0.11 +/- 0.06 ng/ml; IPF, 5.0 +/- 14.4; mean +/- SD; p < 0.05) or normalized to albumin (healthy volunteer, 2.8 +/- 1.2; IPF, 73 +/- 106; p < 0.005). In the IPF group, the alveolar arterial oxygen gradient during exercise in IPF patients correlated positively with BAL and N-PIIIP/ml (rho = 0.70; p < 0.001) and N-PIIIP/ml albumin (rho = 0.76; p < 0.001). The CRP score was correlated with the serum N-PIIIP concentration (rho = 0.48; p < 0.04) and serum N-PIIIP normalized to albumin (rho = 0.60; p < 0.01). These findings suggest that measurements of N-PIIIP levels may be useful in assessing disease activity and reflect the ongoing collagen production that characterizes progressive IPF.