Bronchoalveolar Lavage Desmosine in Bleomycin-Induced Lung Injury in Marmosets and Patients with Adult Respiratory Distress Syndrome

Abstract

Measurement of urinary desmosine in experimental models of emphysema has been used to demonstrate elastin catabolism. In order to evaluate the hypothesis that accelerated elastin degradation also occurs in association with acute lung injury characterized by fibrotic repair, we prepared acid hydrolysates of lung lavage (LL) and used a radioimmunoassay for desmosine to measure concentrations of this elastic-specific crosslink in LL. Lavage desmosine (pmol/100 μl LL) was measured following bleomycin-induced lung injury in marmosets and was shown to be elevated at 1 week (median 6.0, range 5.1—7.8), 2 weeks (8.4, 6.2—8.7), and 4 weeks (7.6, 4.8—7.8) compared to control levels (1.8, 1.4—3.7). Elevations of lavage desmosine after bleomycin were temporarily associated with remodeling of the lung as indicated by increased total lung collagen, reduced diffusing capacity and lung compliance, and histologic evidence of pulmonary fibrosis. Bronchoalveolar lavage (BAL) desmosine was measured in patients with the Adult Respiratory Distress Syndrome (ARDS) and compared with patients at risk, patients with other interstitial lung diseases, and normal healthy controls. BAL desmosine (pmol/100 μl) was not significantly different in patients with ARDS (3.2, 2.1—3.0), patients at risk for ARDS (2.8, 2.5—4.4), and those with interstitial lung disease (3.0, 1.7—5.3) compared to normal controls (2.9, 1.9—4.7). There were poor correlations of BAL desmosine with physiologic indices of severity of disease in patients with ARDS and those at risk. Accelerated elastolysis occurred in the lower respiratory tract during the evaluation of bleomycin-induced pulmonary fibrosis in marmosets but was undetectable in BAL of patients studied within the first 3 days of ARDS.