Neutrophil-associated activation markers in healthy smokers relates to a fall in DLCOand to emphysematous changes on high resolution CT

Abstract

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.

Rapid Proteome Analysis of Bronchoalveolar Lavage Samples of Lifelong Smokers and Never-Smokers by Micro-Scale Liquid Chromatography and Mass Spectrometry

“…Men 60 years of age were recruited from the randomized population study "Men born in Gö teborg in 1933" (19,20 ). A subset of the study population of 879 participants volunteered to undergo fiberoptic bronchoscopy at the age of 60.…”

“…sampling BAL sampling was carried out under standard conditions (20 ) with the informed consent of the individuals, and the studies were approved by the ethics committees of the Sahlgrenska Hospital (Gbg M 117-01) and Lund University Hospital in Sweden (LU 689-01). After sampling, the BAL fluid was immediately transported on ice to the laboratory for processing and storage at Ϫ80°C (20 ).…”

“…After sampling, the BAL fluid was immediately transported on ice to the laboratory for processing and storage at Ϫ80°C (20 ). The protein concentrations in the recovered BAL fluids were determined by the Coomassie Plus protein assay with bovine serum albumin as the calibrator (21 ).…”

Persistent Airway Inflammation and Emphysema Progression on CT Scan in Ex-Smokers Observed for 4 Years

“…We are aware of a limited number of cross-sectional studies of biomarkers in BAL or sputum in subjects with COPD-E phenotyped by CT scan, including studies from our group 16,17 and others, [24][25][26] but none of these studies has evaluated changes in biomarkers of infl ammation over time in relation to changes in the extent of COPD-E on chest CT scan in subjects with COPD-E who have quit smoking. A longitudinal study by Parr et al 27 of may have emphysematous lesions on CT scan 28 and, thus, be misclassifi ed if only pulmonary function studies and not CT scans are performed. Chest CT scans are providing an important method of documenting the extent of emphysema and have demonstrated that the area of the lung with chest CT scan attenuation values below 2 910 HU and 2 950 HU correlates signifi cantly with macroscopic 29 and microscopic 30 pathologic features of emphysema.…”

Protein Expression Patterns Associated with Progression of Chronic Obstructive Pulmonary Disease in Bronchoalveolar Lavage of Smokers

“…Participants provided informed consent. BAL sampling was carried out under typical conditions (10 ), and the BAL fluid was immediately transported on ice to the laboratory for processing and storage at Ϫ80°C (10 ). The protein concentrations in the recovered BAL were measured by use of Coomassie plus protein assay reagent (Pierce) with bovine serum albumin as a reference (14 ).…”