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Title: Characterization of COPD with biomarkers of inflammation and quantitative CT
Author: Miller, Joy J.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2011
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Background: The aim of this thesis was to investigate the role of inflammation in the airways and in the systemic compartment in COPD compared to healthy subjects, and to investigate the relationship between inflammation and the clinical and radiological features of COPD. Methods: 182 COPD patients and 96 healthy control subjects were recruited. Post-bronchodilator spirometry, smoking history, body mass index (BMI), exacerbation frequency, St George's Respiratory Questionnaire (SGRQ) scores, MRC dyspnoea and chronic bronchitis scores, oxygen saturations, 6 minute walking distance and BODE index scores were recorded. Highly sensitive C-reactive protein (CRP), total white cell count and neutrophils were measured in blood. Percentage (%) neutrophils, IL-lp, IL-6 and IL-8 were measured in induced sputum. COPD patients had a quantitative CT scan on inspiration and expiration. Lung volume and density (pixel index -910 HU, pixel index -950 HU, and 15th percentile) were determined using in-house software. Results: Systemic inflammation was increased in COPD subjects compared to healthy controls: CRP (p < 0.001), blood neutrophils (p < 0.001). Pulmonary inflammation was also increased in COPD subjects compared to healthy controls: induced sputum % neutrophils (p=0.001), IL-6 (p=0.02) and IL-8 (p=0.01). Induced sputum IL-1J3 was not increased in COPD compared to controls. Blood neutrophils, CRP, sputum IL-6 and IL-8 were higher in COPD patients compared to healthy controls after adjusting for age, gender and smoking status. Induced sputum was not reliably attainable particularly in healthy control subjects (sample available for 65% of COPD subjects and 26% of healthy controls). In COPD subjects, blood neutrophils (p=0.03) and sputum % neutrophils (p=0.004) were independently related to FEVi after adjusting for age, gender, smoking status and inhaled corticosteroid use. Blood neutrophils and CRP correlated significantly with each other (r=0.408, p < 0.001), but were not associated with any of the sputum markers of inflammation. Systemic inflammation was associated with SGRQ total score (neutrophils p=0.02, CRP p < 0.001) and MRC dyspnoea score (neutrophils p=0.005, CRP p=0.003) after adjusting for FEVi and smoking status. Blood neutrophils (p=0.02) were associated with oxygen saturations < 93%. BODE index scores correlated with blood neutrophils, (p=0.005), CRP (p=0.03) and sputum IL-8 (p=0.02). After adjusting for potential confounding factors; exacerbation frequency and BMI were not associated with markers of blood or sputum inflammation. Quantitative CT lung volume and density (pixel index -910, pixel index -950 and 15th percentile) on inspiration and expiration were associated with postbronchodilator FEVi % predicted and FEVi/FVC ratio (p<0.001) but not with any of the markers of pulmonary or systemic inflammation. Expiratory CT parameters correlated better with lung function than inspiratory parameters. Lung volumes were inversely associated with BMI on inspiration (r=-0.225, p=0.015) and expiration (r=-0.296, p=0.001). BMI was associated with 15th percentile on inspiration (r=0.518, p < 0.001) and expiration (r=0.534, p < 0.001) and inversely with pixel index -910 and -950 (p < 0.001). BMI was associated with lung density independent of airflow limitation (p=0.03). Lung volume and density were not associated with age, gender, current smoking status, smoking pack years, SGRQ scores, MRC dyspnoea or chronic bronchitis score, exacerbation frequency, oxygen saturations or BODE index. Conclusion: Markers of inflammation in blood and sputum were increased in COPD compared to healthy controls. Blood and sputum % neutrophils were associated with airflow limitation, but not with lung density. Pulmonary and systemic inflammatory markers had different profiles according to different clinical features of COPD. Inflammatory markers and lung density may be useful in characterizing COPD patients in addition to airflow limitation alone.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available