Urinary desmosine excretion in smokers with and without rapid decline of lung function - The Normative Aging Study

被引:92
作者
Gottlieb, DJ
Stone, PJ
Sparrow, D
Gale, ME
Weiss, ST
Snider, GL
OConnor, GT
机构
[1] BOSTON UNIV, SCH MED, CTR PULM, BOSTON, MA 02118 USA
[2] BOSTON UNIV, SCH MED, DEPT BIOCHEM, BOSTON, MA 02118 USA
[3] HARVARD UNIV, SCH MED, BRIGHAM & WOMENS HOSP, CHANNING LAB, BOSTON, MA USA
[4] VET ADM OUTPATIENT CLIN, NORMAT AGING STUDY, BOSTON, MA USA
[5] VET ADM MED CTR, DEPT RADIOL, BOSTON, MA USA
关键词
D O I
10.1164/ajrccm.154.5.8912738
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
It is hypothesized that smoking-related chronic obstructive pulmonary disease (COPD) results in part from excess lung elastin degradation. Taking advantage of spirometry performed over a 12-yr period at the Normative Aging Study, we conducted a nested case-control study of elastin and collagen degradation rates in current smokers with (n = 10) and without (n = 8) rapid decline of lung function, using a biochemical assay for urinary desmosine (DES), a specific marker for mature elastin degradation, and hydroxylysylpyridinoline (HP), a specific marker for mature fibrillar collagen degradation. Mean urinary excretion of DES in rapid decliners was 36% greater than in slow decliners (9.8 +/- 0.7 [mean +/- SE] versus 7.2 +/- 0.4 mu g/g creatinine, p < 0.01); after adjustment for age and lean body mass (LBM), DES excretion in rapid decliners was 30% greater than in slow decliners (9.6 +/- 0.6 versus 7.4 +/- 0.7 mu g/g creatinine, p = 0.06). Among rapid decliners, there was no difference in DES excretion between those with and those without computed tomogaphic evidence of emphysema. There was no significant difference between rapid and slow decliners in mean urinary excretion of HP (24.7 +/- 1.4 versus 21.6 +/- 1.8 nmol/mmol creatinine, p = 0.18). Among all subjects, rate of decline of FEV(1) was significantly correlated with DES excretion (r = 0.61, p < 0.01). In a linear regression model adjusting for age and LBM, an increase in DES excretion of 1 mu g/g creatinine was associated with an excess decline of FEV(1) of 10.6 ml/yr (p = 0.04). This study provides further evidence in support of the elastase-antielastase hypothesis of the pathogenesis of COPD, and it suggests a role for elastin degradation in both emphysema and small airways disease. Moreover, it suggests that urinary DES excretion may be a useful biochemical marker for the study of interventions designed to prevent the development or progression of COPD.
引用
收藏
页码:1290 / 1295
页数:6
相关论文
共 33 条
[21]   PATHOLOGIC-CHANGES IN PERIPHERAL AIRWAYS OF YOUNG CIGARETTE SMOKERS [J].
NIEWOEHNER, DE ;
KLEINERMAN, J ;
RICE, DB .
NEW ENGLAND JOURNAL OF MEDICINE, 1974, 291 (15) :755-758
[22]  
PELHAM F, 1985, AM REV RESPIR DIS, V132, P821
[23]   PULMONARY-FUNCTION ABNORMALITIES IN PATIENTS WITH CT-DETERMINED EMPHYSEMA [J].
SAKAI, F ;
GAMSU, G ;
IM, JG ;
RAY, CS .
JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY, 1987, 11 (06) :963-968
[24]   COMPARISON OF ELASTIN PEPTIDE CONCENTRATIONS IN BODY-FLUIDS FROM HEALTHY-VOLUNTEERS, SMOKERS, AND PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY-DISEASE [J].
SCHRIVER, EE ;
DAVIDSON, JM ;
SUTCLIFFE, MC ;
SWINDELL, BB ;
BERNARD, GR .
AMERICAN REVIEW OF RESPIRATORY DISEASE, 1992, 145 (04) :762-766
[25]   MARKED LONGEVITY OF HUMAN LUNG PARENCHYMAL ELASTIC FIBERS DEDUCED FROM PREVALENCE OF D-ASPARTATE AND NUCLEAR-WEAPONS RELATED RADIOCARBON [J].
SHAPIRO, SD ;
ENDICOTT, SK ;
PROVINCE, MA ;
PIERCE, JA ;
CAMPBELL, EJ .
JOURNAL OF CLINICAL INVESTIGATION, 1991, 87 (05) :1828-1834
[26]   EMPHYSEMA - THE 1ST 2 CENTURIES AND BEYOND - A HISTORICAL OVERVIEW, WITH SUGGESTIONS FOR FUTURE-RESEARCH .1. [J].
SNIDER, GL .
AMERICAN REVIEW OF RESPIRATORY DISEASE, 1992, 146 (05) :1334-1344
[27]   PUTATIVE ROLE OF NEUTROPHIL ELASTASE IN THE PATHOGENESIS OF EMPHYSEMA [J].
SNIDER, GL ;
CICCOLELLA, DE ;
MORRIS, SM ;
STONE, PJ ;
LUCEY, EC .
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1991, 624 :45-59
[28]   FRACTIONATION OF URINE TO ALLOW DESMOSINE ANALYSIS BY RADIOIMMUNOASSAY [J].
STARCHER, B ;
SCOTT, M .
ANNALS OF CLINICAL BIOCHEMISTRY, 1992, 29 :72-78
[29]   EFFECT OF DIET ON URINARY-EXCRETION OF DESMOSINE AND HYDROXYLYSYL PYRIDINOLINE [J].
STONE, PJ ;
LUCEY, EC ;
SNIDER, GL ;
FRANZBLAU, C .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1994, 149 (01) :174-177
[30]   MEASUREMENT OF URINARY DESMOSINE BY ISOTOPE-DILUTION AND HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY - CORRELATION BETWEEN ELASTASE-INDUCED AIR-SPACE ENLARGEMENT IN THE HAMSTER AND ELEVATION OF URINARY DESMOSINE [J].
STONE, PJ ;
BRYANRHADFI, J ;
LUCEY, EC ;
CICCOLELLA, DE ;
CROMBIE, G ;
FARIS, B ;
SNIDER, GL ;
FRANZBLAU, C .
AMERICAN REVIEW OF RESPIRATORY DISEASE, 1991, 144 (02) :284-290