Background: The predominant emphysema phenotype is associated with more severe airflow limitation in patients with chronic obstructive pulmonary disease (COPD). A study was undertaken to investigate whether COPD patients, with or without emphysema quantitatively confirmed by high resolution computed tomography (HRCT), have different COPD severity as assessed by the BODE index (body mass index, airflow obstruction, dyspnoea, exercise performance) and inspiratory capacity to total lung capacity ratio (IC/TLC), and by different biological markers of lung parenchymal destruction. Methods: Twenty six outpatients with COPD and eight healthy non-smokers were examined. Each subject underwent HRCT scanning, pulmonary function tests, cell counts, and measurements of neutrophil elastase, matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 in induced sputum, as well as measurement of desmosine, a marker of elastin degradation in urine, plasma and sputum. Results: Patients with HRCT confirmed emphysema had a higher BODE index and lower IC/TLC ratio than subjects without HRCT confirmed emphysema and controls. Forced expiratory volume in 1 second (FEV 1 ), FEV 1 /forced vital capacity ratio, and carbon monoxide transfer coefficient were lower, whereas the number of eosinophils, MMP-9, and the MMP-9/TIMP-1 ratio in sputum were higher in patients with emphysema. In COPD patients the number of sputum eosinophils was the biological variable that correlated positively with the HRCT score of emphysema (p = 0.04). Conclusions: These results suggest that COPD associated with HRCT confirmed emphysema is characterised by more severe lung function impairment, more intense airway inflammation and, possibly, more serious systemic dysfunction than COPD not associated with HRCT confirmed emphysema.

EvA (Emphysema versus Airway disease) is a multicentre project to study mechanisms and identify biomarkers of emphysema and airway disease in chronic obstructive pulmonary disease (COPD). The objective of this study was to delineate objectively imaging-based emphysema-dominant and airway disease-dominant phenotypes using quantitative computed tomography (QCT) indices, standardised with a novel phantom-based approach.441 subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1–3) were assessed in terms of clinical and physiological measurements, laboratory testing and standardised QCT indices of emphysema and airway wall geometry.QCT indices were influenced by scanner non-conformity, but standardisation significantly reduced variability (p<0.001) and led to more robust phenotypes. Four imaging-derived phenotypes were identified, reflecting “emphysema-dominant”, “airway disease-dominant”, “mixed” disease and “mild” disease. The emphysema-dominant group had significantly higher lung volumes, lower gas transfer coefficient, lower oxygen (PO2) and carbon dioxide (PCO2) tensions, higher haemoglobin and higher blood leukocyte numbers than the airway disease-dominant group.The utility of QCT for phenotyping in the setting of an international multicentre study is improved by standardisation. QCT indices of emphysema and airway disease can delineate within a population of patients with COPD, phenotypic groups that have typical clinical features known to be associated with emphysema-dominant and airway-dominant disease.

CT is the gold standard in identifying crowned dens syndrome, as it is able to depict the shape and site of calcification and any bone erosions. Radiography of other joints (wrist, knee, pubic symphysis) may help to ascertain whether the disease is due to calcium pyrophosphate dihydrate or hydroxyapatite crystals, and is therefore recommended for routine patient management. Magnetic resonance imaging (MRI) is indicated for the study of neurological complications.

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Background:The predominant emphysema phenotype is associated with more severe airflow limitation in patients with chronic obstructive pulmonary disease (COPD). We investigated whether COPD patients with or without quantitatively HRCT scan-documented emphysema have different COPD severity, as assessed by BODE (body mass index, airflow obstruction, dyspnea, exercise performance) Index and inspiratory capacity-to-total lung capacity ratio (IC/TLC), and by different biological markers of lung parenchymal destruction. Methods: We examined 26 outpatients with COPD and 8 healthy nonsmokers. Each subject underwent HRCT scan, pulmonary function tests, cell counts and measurements of neutrophil elastase, matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 in induced sputum, as well as measurement of desmosine, a marker of elastin degradation in urine, plasma and sputum. Results: As compared with subjects without HRCT documented emphysema and controls, patients with HRCT scan-documented emphysema had higher BODE Index and lower IC/TLC. Forced expiratory volume in one second (FEV 1 ), FEV 1 /forced vital capacity ratio, and carbon monoxide transfer coefficient were lower, whereas the number of eosinophils, MMP-9 and the MMP-9/TIMP-1 ratio in sputum were higher in patients with emphysema. In COPD patients, the number of sputum eosinophils was the biological variable that correlated positively with the HRCT score of emphysema (p = 0.04). Conclusions:These results suggest that COPD associated with HRCT scan documented emphysema is characterized by more severe lung function impairment, more intense airway inflammation, and, possibly, more serious systemic dysfunctioning, as compared with COPD not associated with HRCT scan-documented emphysema.Word counts: 242 Key words: chronic obstructive pulmonary disease, emphysema, biological markers, outcomes. INTRODUCTIONChronic obstructive pulmonary disease (COPD) is characterized by the progressive development of airflow limitation that is not fully reversible.[1] Chronic airflow limitation may be caused by increased resistance of the small conducting airways and increased compliance of the lung due to emphysema.[1] We have previously shown that COPD patients with HRCT-documented emphysema have more severe airflow limitation.[2] Now we hypothesize that COPD patients with emphysema, as quantitatively assessed by HRCT, may be associated with more severe disease and may be characterized by biological markers of lung parenchymal destruction, measurable by noninvasive methods. The BODE (body mass index, airflow obstruction, dyspnea, exercise performance) Index and the inspiratory capacity-to-total lung capacity ratio (IC/TLC) have been recently demonstrated to grade properly the severity of COPD, as a systemic and respiratory disease, and to predict the outcome in these patients. [3][4] The higher the BODE Index and the lower the IC/TLC ratio, the higher is the risk of death from any cause and respiratory causes in subjects with COPD. There have been...