The effect of inhaled corticosteroids on the development of emphysema in smokers assessed by annual computed tomography.

The objective was to evaluate the effect of inhaled corticosteroids on disease progression in smokers with moderate to severe chronic obstructive pulmonary disease (COPD), as assessed by annual computed tomography (CT) using lung density (LD) measurements. Two hundred and fifty-four current smokers with COPD were randomised to treatment with either an inhaled corticosteroids (ICS), budesonide 400 microg bid, or placebo. COPD was defined as FEV(1) < or = 70% pred, FEV(1)/FVC < or = 60% and no reversibility to beta(2)-agonists and oral corticosteroids. The patients were followed for 2-4 years with biannual spirometry and annual CT and comprehensive lung function tests (LFT). CT images were analysed using Pulmo-CMS software. LD was derived from a pixel-density histogram of the whole lung as the 15th percentile density (PD15) and the relative area of emphysema at a threshold of -910 Hounsfield units (RA-910), and both were volume-adjusted to predicted total lung capacity. At baseline, mean age was 64 years and 64 years; mean number of pack-years was 56 and 56; mean FEV(1) was 1.53 L (51% pred) and 1.53 L (53% pred); mean PD15 was 103 g/L and 104 g/L; and mean RA-910 was 14% and 13%, respectively, for the budesonide and placebo groups. The annual fall in PD15 was -1.12 g/L in the budesonide group and -1.81 g/L in the placebo group (p = 0.09); the annual increase in RA-910 was 0.4% in the budesonide group and 1.1% in the placebo group (p = 0.02). There was no difference in annual decline in FEV(1) between ICS (-54 mL) and placebo (-56 mL) (p = 0.89). Long-term budesonide inhalation shows a non-significant trend towards reducing the progression of emphysema as determined by the CT-derived 15th percentile lung density from annual CT scans in current smokers with moderate to severe COPD.

The extent of emphysema in patients with COPD.

BACKGROUND AND AIMS: The global initiative for COPD (GOLD) adopted the degree of airway obstruction as a measure of the severity of the disease. The objective of this study was to apply CT to assess the extent of emphysema in patients with chronic obstructive pulmonary disease (COPD) and relate this extent to the GOLD stage of airway obstruction. MATERIALS AND METHODS: We included 209 patients with COPD. COPD was defined as FEV(1)/FVC < 0.70 and no reversibility to beta(2)-agonists. All patients were current smokers with a smoking history of >or=20 pack-years. Patients were assessed by lung function measurement and visual and quantitative assessment of CT, from which the relative area of emphysema below -910 Hounsfield units (RA-910) was extracted. RESULTS: Mean RA-910 was 7.4% (n = 5) in patients with GOLD stage I, 17.0% (n = 119) in stage II, 24.2% (n = 79) in stage III and 33.9% (n = 6) in stage IV. Regression analysis showed a change in RA-910 of 7.8% with increasing severity according to GOLD stage (P < 0.001). Combined visual and quantitative assessment of CT showed that 184 patients had radiological evidence of emphysema, whereas 25 patients had no emphysema. CONCLUSION: The extent of emphysema increases with increasing severity of COPD and most patients with COPD have emphysema. Tissue destruction by emphysema is therefore an important determinant of disease severity in COPD.

Identification of patients with chronic obstructive pulmonary disease (COPD) by measurement of plasma biomarkers.

INTRODUCTION: Inflammation is an important constituent of the pathology of chronic obstructive pulmonary disease (COPD), leading to alveolar destruction and airway remodelling. OBJECTIVE: The aim of this study was to assess the difference in plasma biomarkers of inflammation between asymptomatic smokers and patients with COPD. METHODS: We used commercially available enzyme-linked immunosorbent assay kits to measure the plasma levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9), monocyte chemotactic protein-1 (MCP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and tissue inhibitor of metalloproteinase-2 (TIMP-2) on two occasions with a 2-week interval in patients with COPD (n = 20), asymptomatic smokers (n = 10) and healthy lifelong non-smokers (n = 10). The participants were characterised clinically, physiologically and by quantitative computed tomography by measuring the relative area of emphysema below -910 Hounsfield units (RA-910). RESULTS: The results of the biomarker measurements on the two occasions were highly reproducible. Patients with COPD had significantly higher plasma levels of IL-8 (P = 0.004) and significantly lower levels of TIMP-1 (P = 0.02) than smokers and non-smokers. There was no statistically significant difference between the three groups in the level of TNF-alpha, MMP-9, MCP-1 and TIMP-2. The IL-8/TIMP-1 ratio correlated significantly with the degree of airway obstruction measured as forced expiratory volume in 1 second (FEV(1)) % predicted (r = -0.47, P < 0.01); with the diffusion capacity (r = -0.41, P < 0.01); and with the grade of emphysema measured as RA-910 (r = 0.39, P = 0.01). CONCLUSION: These findings suggest that the measurement of plasma biomarkers, such as IL-8/TIMP-1, may aid to discriminate patients with COPD from smokers at lower risk of developing COPD.