We found no differences in asthma severity between obese and nonobese asthmatics. Interestingly, obese patients demonstrated more neutrophils in sputum and blood than nonobese patients. The smaller improvement in FEV(1) and sputum eosinophils suggests a worse corticosteroid treatment response in obese asthmatics.

Expression of lipids from the sphingolipid pathway is higher in smokers with COPD compared with smokers without COPD. Considering their potential biologic properties, they may play a role in the pathogenesis of COPD.

The management of bronchiolitis obliterans syndrome (BOS) following hematopoietic cell transplantation (HCT) presents many challenges, both diagnostically and therapeutically. We have developed a computed tomography (CT) voxel-wise methodology termed Parametric Response Mapping (PRM) that quantifies normal parenchyma (PRMNormal), functional small airway disease (PRMfSAD), emphysema (PRMEmph) and parenchymal disease (PRMPD) as relative lung volumes. We now investigate the use of PRM as an imaging biomarker in the diagnosis of BOS. PRM was applied to CT data from four patient cohorts: acute infection (n=11), BOS at onset (n=34), BOS plus infection (n=9), and age-matched, non-transplant controls (n=23). Pulmonary function tests and broncho-alveolar lavage (BAL) were used for group classification. Mean values for PRMfSAD were significantly greater in patients with BOS (38±2%) when compared to those with infection alone (17±4%, p<0.0001) and age-matched controls (8.4±1%, p<0.0001). Patients with BOS had similar PRMfSAD profiles, whether a concurrent infection was present or not. An optimal cut-point for PRMfSAD of 28% of the total lung volume was identified, with values >28% highly indicative of BOS occurrence. PRM may provide a major advance in our ability to identify the small airway obstruction that characterizes BOS, even in the presence of concurrent infection.

BackgroundChronic 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.MethodsHealthy 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.ResultsCOPD 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.ConclusionIn 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0363-2) contains supplementary material, which is available to authorized users.

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BackgroundIt has been suggested that smoking asthmatics benefit less from corticosteroid treatment than never-smoking 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.MethodsWe 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 self-management plan (n=64).ResultsA 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.ConclusionsEx- 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.

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BackgroundCOPD patients have a higher risk of pneumonia when treated with fluticasone propionate (FP) than with placebo, and a lower risk with budesonide (BUD). We hypothesized that BUD and FP differentially affect the mucosal barrier in response to viral infection and/or cigarette smoke.MethodsWe assessed protective effects of equivalent concentrations of BUD and FP on cytokine production and barrier function (electrical resistance) in human bronchial epithelial 16HBE cells and primary bronchial epithelial cells (PBECs) upon exposure to viral mimetic poly-(I:C) and/or cigarette smoke extract (CSE) or epidermal growth factor (EGF).ResultsBUD and FP were equally effective in suppressing poly-(I:C)- and/or CSE-induced IL-8 secretion in 16HBE and PBECs. Poly-(I:C) substantially decreased electrical resistance in 16HBE cells and both BUD and FP fully counteracted this effect. However, FP hardly affected 16HBE barrier dysfunction induced by CSE with/without poly-(I:C), whereas BUD (16 nM) provided full protection, an effect likely mediated by affecting EGFR-downstream target GSK-3β. Similarly, BUD, but not FP, significantly improved CSE-induced barrier dysfunction in PBECs. Finally, BUD, but not FP, exerted a modest but significant protective effect against Streptococcus Pneumoniae-induced barrier dysfunction, and BUD, but not FP, prevented cellular adhesion and/or internalization of these bacteria induced by poly-(I:C) in 16HBE.ConclusionsCollectively, both BUD and FP efficiently control epithelial pro-inflammatory responses and barrier function upon mimicry of viral infection. Of potential clinical relevance, BUD more effectively counteracted CSE-induced barrier dysfunction, reinforcing the epithelial barrier and potentially limiting access of pathogens upon smoking in vivo.