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Background: Nasal gene expression profiling is a promising method to characterize COPD non-invasively. We aimed to identify a nasal gene expression profile to distinguish COPD patients from healthy controls. We investigated whether this COPD-associated gene expression profile in nasal epithelium is comparable with the profile observed in bronchial epithelium.Methods: Genome wide gene expression analysis was performed on nasal epithelial brushes of 31 severe COPD patients and 22 controls, all current smokers, using Affymetrix Human Gene 1.0 ST Arrays. We repeated the gene expression analysis on bronchial epithelial brushes in 2 independent cohorts of mild-to-moderate COPD patients and controls.Results: In nasal epithelium, 135 genes were significantly differentially expressed between severe COPD patients and controls, 21 being up- and 114 downregulated in COPD (false discovery rate < 0.01). Gene Set Enrichment Analysis (GSEA) showed significant concordant enrichment of COPD-associated nasal and bronchial gene expression in both independent cohorts (FDRGSEA < 0.001).Conclusion: We identified a nasal gene expression profile that differentiates severe COPD patients from controls. Of interest, part of the nasal gene expression changes in COPD mimics differentially expressed genes in the bronchus. These findings indicate that nasal gene expression profiling is potentially useful as a non-invasive biomarker in COPD.Trial Registration: ClinicalTrials.gov registration number NCT01351792 (registration date May 10, 2011), ClinicalTrials.gov registration number NCT00848406 (registration date February 19, 2009), ClinicalTrials.gov registration number NCT00807469 (registration date December 11, 2008). [ABSTRACT FROM AUTHOR]

Background: To investigate if age, gender and smoking are associated with airway wall thickness (AWT) measured by high resolution computed tomography (HRCT) and if higher AWT is associated with lower levels of pulmonary function in healthy current- and never-smokers with a wide age range.Methods: HRCT scans were performed in 99 subjects (48 never- and 51 current-smokers, median age 39 years [IQR 22 - 54], 57% males). The AWT at an internal perimeter of 10 mm (AWT Pi10) was calculated as an overall measurement of AWT, based on all measurements throughout the lungs. Extensive pulmonary function testing was performed in all subjects.Results: Higher age was associated with a lower AWT Pi10 (b = -0.003, p < 0.001). Current-smokers had a higher AWT Pi10 than never-smokers (mean 0.49 mm versus 0.44 mm, p = 0.022). In multivariate analysis, age and current-smoking were independently associated with AWT Pi10 (age b = -0.002, p < 0.001, current-smoking b = 0.041, p = 0.021), whereas gender was not (b = 0.011, p = 0.552). Higher AWT Pi10 was associated with a lower FEV1, FEV1/FVC, FEF25-75 and higher R5, R20 and X5.Conclusions: AWT decreases with higher age, possibly reflecting structural changes of the airways. Additionally, current-smokers have a higher AWT, possibly due to remodeling or inflammation. Finally, higher AWT is associated with a lower level of pulmonary function, even in this population of healthy subjects.Trial Registration: This Study was registered at www.clinicaltrials.gov with number NCT00848406 on 19 February 2009. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by chronic airway inflammation and emphysema, and is caused by exposure to noxious particles or gases, e.g. cigarette smoke. Smoking and oxidative stress lead to accelerated formation and accumulation of advanced glycation end products (AGEs), causing local tissue damage either directly or by binding the receptor for AGEs (RAGE). This study assessed the association of AGEs or RAGE in plasma, sputum, bronchial biopsies and skin with COPD and lung function, and their variance between these body compartments.Methods: Healthy smoking and never-smoking controls (n = 191) and COPD patients (n = 97, GOLD stage I-IV) were included. Autofluorescence (SAF) was measured in the skin, AGEs (pentosidine, CML and CEL) and sRAGE in blood and sputum by ELISA, and in bronchial biopsies by immunohistochemistry. eQTL analysis was performed in bronchial biopsies.Results: COPD patients showed higher SAF values and lower plasma sRAGE levels compared to controls and these values associated with decreased lung function (p <0.001; adjusting for relevant covariates). Lower plasma sRAGE levels significantly and independently predicted higher SAF values (p < 0.001). One SNP (rs2071278) was identified within a region of 50 kB flanking the AGER gene, which was associated with the gene and protein expression levels of AGER and another SNP (rs2071278) which was associated with the accumulation of AGEs in the skin.Conclusion: In COPD, AGEs accumulate differentially in body compartments, i.e. they accumulate in the skin, but not in plasma, sputum and bronchial biopsies. The association between lower sRAGE and higher SAF levels supports the hypothesis that the protective mechanism of sRAGE as a decoy-receptor is impaired in COPD. [ABSTRACT FROM AUTHOR]

Background: It has been suggested that smoking asthmatics benefit less from corticosteroid treatment than neversmoking asthmatics. We investigated differences in blood and sputum inflammatory profiles between ex-, current-, and never-smokers and assessed their ICS treatment response after 2-week and 1-year treatment. Methods: We analyzed FEV1, PC20 methacholine and PC20 AMP, (differential) cell counts in sputum and blood in ex-, current- and never-smokers at baseline (n=114), after 2-week treatment with fluticasone 500 or 2000 μg/day (n=76) and after 1-year treatment with fluticasone 500 μg/day or a variable dose of fluticasone based on a selfmanagement plan (n=64). Results: A total of 114 patients were included (29 ex-, 30 current- and 55 never-smokers. At baseline, ex- and current-smokers had less eosinophils in sputum and blood than never-smokers. Blood neutrophil counts were higher in current- than in never-smokers. A higher number of cigarettes smoked daily was associated with lower blood and sputum eosinophils. After 2-week ICS treatment, FEV1 %predicted improved less in current-smokers than never-smokers (2.4% versus 8.1%, p=0.010) and ex-smokers tended to improve less than never-smokers (4.1%, p=0.067). In contrast, no differences in ICS treatment response in lung function or inflammatory cells were found between the three groups after 1 year. Conclusions: Ex- and current-smokers have less eosinophils and more neutrophils in their sputum and blood than never-smokers. Although ex- and current-smokers have a reduced short-term corticosteroid treatment response, we did not find a difference in their long-term treatment response. [ABSTRACT FROM AUTHOR]