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

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.

[1]  G. O'Connor,et al.  Urinary desmosine excretion in smokers with and without rapid decline of lung function: the Normative Aging Study. , 1996, American journal of respiratory and critical care medicine.

[2]  T. Betsuyaku,et al.  Elastin-derived peptides and neutrophil elastase in bronchoalveolar lavage fluid. , 1996, American journal of respiratory and critical care medicine.

[3]  L. Fabbri,et al.  Airways obstruction, chronic expectoration, and rapid decline of FEV1 in smokers are associated with increased levels of sputum neutrophils. , 1996, Thorax.

[4]  T. Betsuyaku,et al.  Pulmonary function is diminished in older asymptomatic smokers and ex-smokers with low attenuation areas on high-resolution computed tomography. , 1996, Respiration; international review of thoracic diseases.

[5]  P De Vuyst,et al.  Comparison of computed density and microscopic morphometry in pulmonary emphysema. , 1996, American journal of respiratory and critical care medicine.

[6]  T. Betsuyaku,et al.  Excessive neutrophil elastase in bronchoalveolar lavage fluid in subclinical emphysema. , 1995, American journal of respiratory and critical care medicine.

[7]  M. Cosio,et al.  Alveolar inflammation and its relation to emphysema in smokers. , 1995, American journal of respiratory and critical care medicine.

[8]  J C Yernault,et al.  Optimal assessment and management of chronic obstructive pulmonary disease (COPD). The European Respiratory Society Task Force. , 1995, The European respiratory journal.

[9]  W. Bailey,et al.  Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. The Lung Health Study. , 1995, JAMA.

[10]  R. Stockley.  The role of proteinases in the pathogenesis of chronic bronchitis. , 1994, American journal of respiratory and critical care medicine.

[11]  W. Bailey,et al.  Effects of Smoking Intervention and the Use of an Inhaled Anticholinergic Bronchodilator on the Rate of Decline of FEV1 , 1994 .

[12]  D. Lamb,et al.  Neutrophil sequestration in lungs removed at surgery. The effect of microscopic emphysema. , 1994, American journal of respiratory and critical care medicine.

[13]  P. Venge,et al.  Airway inflammation in smokers with nonobstructive and obstructive chronic bronchitis. , 1993, The American review of respiratory disease.

[14]  C. Marquette,et al.  Inactivation of α1-Proteinase Inhibitor by Alveolar Inflammatory Cells from Smoking Patients with or without Emphysema , 1993 .

[15]  G. Snider,et al.  Emphysema: the first two centuries--and beyond. A historical overview, with suggestions for future research: Part 1. , 1992, The American review of respiratory disease.

[16]  E. Perez-stable,et al.  Misclassification of smoking status by self-reported cigarette consumption. , 1992, The American review of respiratory disease.

[17]  M. Jaakkola,et al.  Effect of cigarette smoking on evolution of ventilatory lung function in young adults: an eight year longitudinal study. , 1991, Thorax.

[18]  G. Snider,et al.  Putative Role of Neutrophil Elastase in the Pathogenesis of Emphysema a , 1991, Annals of the New York Academy of Sciences.

[19]  S. Rennard,et al.  Fractional processing of sequential bronchoalveolar lavage to separate bronchial and alveolar samples. , 1990, The American review of respiratory disease.

[20]  J. Bloom,et al.  Subclinical effects of cigarette smoking. A five-year follow-up of physiologic comparisons of healthy middle-aged smokers and nonsmokers. , 1989, Chest.

[21]  H. Tunstall-Pedoe,et al.  Comparison of tests used to distinguish smokers from nonsmokers. , 1987, American journal of public health.

[22]  M. Lebowitz,et al.  Longitudinal changes in forced expiratory volume in one second in adults. Effects of smoking and smoking cessation. , 1987, The American review of respiratory disease.

[23]  M. Lebowitz,et al.  Longitudinal changes in forced expiratory volume in one second in adults. Methodologic considerations and findings in healthy nonsmokers. , 1986, The American review of respiratory disease.

[24]  V L Roggli,et al.  Centrilobular emphysema: CT-pathologic correlation. , 1986, Radiology.

[25]  P. Paré,et al.  The diagnosis of emphysema. A computed tomographic-pathologic correlation. , 1986, The American review of respiratory disease.

[26]  S. Neumann,et al.  Enzyme-linked immunoassay for human granulocyte elastase in complex with alpha 1-proteinase inhibitor. , 1984, Advances in experimental medicine and biology.

[27]  G. Laszlo,et al.  Computed tomography in pulmonary emphysema. , 1982, Clinical radiology.

[28]  ATS statement--Snowbird workshop on standardization of spirometry. , 1979, The American review of respiratory disease.

[29]  M. Lebowitz,et al.  Quantitative relationships between cigarette smoking and ventilatory function. , 1977, The American review of respiratory disease.

[30]  C. Dollery,et al.  Absorption and metabolism of nicotine from cigarettes. , 1975, British medical journal.