Decline in FEV1 in Community-Based Older Volunteers with Higher Levels of Neutrophil Elastase in Bronchoalveolar Lavage Fluid

Abstract

Background: Neutrophil elastase (NE) is thought to be one of the key proteinases in the development of chronic obstructive pulmonary disease (COPD). Previously, we have shown that the NE-α1-proteinase inhibitor (NE-α1PI) complex in bronchoalveolar lavage (BAL) fluid was markedly elevated in asymptomatic smokers who had subclinical emphysema on CT scans. We proposed that excessive NE-α1PI complex in BAL fluid was a factor which might differentiate smokers who were developing emphysema from others. Objective: In this study, we addressed the question of whether elevated levels of the NE-α1PI complex in BAL fluid are linked to the accelerated decline in pulmonary functions in those subjects. Methods: We conducted a follow-up study to analyze the decline in FEV₁ for 4.3 years on average for 26 community-based volunteers who had received pulmonary function tests, CT scans and BAL. The levels of the NE-α1PI complex in BAL fluid and in plasma was measured. Results: Neither pulmonary function measurements nor the presence of emphysema on CT scans could predict the decline in FEV₁. The number of inflammatory cells in BAL fluid was also not an indicator of progression. By contrast, subjects with higher levels of the NE-α1PI complex in BAL fluid had a significantly accelerated decline in FEV₁ compared to those with lower levels. Conclusion: These data seem to support the hypothesis that NE in the lung is related to the onset and/or progression of COPD.