Neutrophil-associated activation markers in healthy smokers relates to a fall in DL(CO) and to emphysematous changes on high resolution CT

Respir Med. 2001 May;95(5):363-73. doi: 10.1053/rmed.2001.1050.


Smoking is a risk factor for developing chronic obstructive pulmonary disease (COPD), but there are no good indicators for early identification of subjects who will develop symptomatic COPD. The aim of this study was to investigate inflammatory mechanisms related to changes in lung function and emphysematous changes on high resolution computed tomography (HRCT) in 'healthy' smokers. Subjects were 60-year-old men from a population study. Bronchoscopy was performed in 30 smokers and 18 who had never smoked. Blood tests, lung function measurements and HRCT were carried out in 58 and 34 subjects, respectively. In comparison with never-smokers, smokers had higher levels of myeloperoxidase (MPO), human neutrophil lipocalin (HNL), eosinophil cationic protein (ECP) and lysozyme in blood, higher levels of MPO, interleukin-8 (IL-8) and HNL in bronchial lavage (BL), and of IL-8, HNL and interleukin-lbeta (IL-1beta) in bronchoalveolar lavage (BAL). Smokers also had lower levels of Clara cell protein 16 (CC-16) in blood. HNL in BL and BAL showed strong correlations to other inflammatory markers (MPO, IL-8, IL-1beta). The variations in MPO in BL were explained by variations in HNL (R2 =0.69), while these variations in BAL were explained by variations in HNL and IL-1beta (R2 = 0.76). DL(CO) was the lung function variable most closely related to MPO and IL-8 in BL and BAL and to IL-1beta in BAL. In a multiple regression analysis, MPO, IL-1beta, IL-8 and CC-16 in BL and MPO in BAL contributed to the explanation of variations in DL(CO) to 41% and 22%. respectively, independent of smoking habits. In smokers with emphysematous lesions on HRCT, HNL in BAL correlated to emphysema score (r(s) = 0.71). We conclude that 'healthy' smoking men with a near normal FEV1 show signs of inflammation in the lower airways that are related to a decrease in DL(CO) and to emphysematous lesions on HRCT. This inflammation seems to be the result of both monocyte/macrophage and neutrophil activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins*
  • Biomarkers / analysis
  • Blood Proteins / analysis
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoscopy
  • Carrier Proteins / analysis
  • Eosinophil Granule Proteins
  • Humans
  • Interleukin-1 / analysis
  • Interleukin-8 / analysis
  • Lipocalin-2
  • Lipocalins
  • Male
  • Middle Aged
  • Muramidase / analysis
  • Neutrophil Activation / physiology*
  • Oncogene Proteins*
  • Peroxidase / analysis
  • Proto-Oncogene Proteins
  • Pulmonary Emphysema / diagnostic imaging*
  • Pulmonary Emphysema / etiology
  • Pulmonary Emphysema / physiopathology
  • Regression Analysis
  • Respiratory Function Tests
  • Ribonucleases*
  • Smoking / adverse effects
  • Smoking / physiopathology*
  • Tomography, X-Ray Computed / methods


  • Acute-Phase Proteins
  • Biomarkers
  • Blood Proteins
  • Carrier Proteins
  • Eosinophil Granule Proteins
  • Interleukin-1
  • Interleukin-8
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Oncogene Proteins
  • Proto-Oncogene Proteins
  • Peroxidase
  • Ribonucleases
  • Muramidase