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Background: Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease characterized by fibrosis and progressive loss of lung function. The pathophysiological pathways involved in IPF are not well understood. Abnormal lipid metabolism has been described in various other chronic lung diseases including asthma and chronic obstructive pulmonary disease (COPD). However, its potential role in IPF pathogenesis remains unclear.Methods: In this study, we used ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) to characterize lipid changes in plasma derived from IPF patients with stable and progressive disease. We further applied a data-independent acquisition (DIA) technique called SONAR, to improve the specificity of lipid identification.Results: Statistical modelling showed variable discrimination between the stable and progressive subjects, revealing differences in the detection of triglycerides (TG) and phosphatidylcholines (PC) between progressors and stable IPF groups, which was further confirmed by mass spectrometry imaging (MSI) in IPF tissue.Conclusion: This is the first study to characterise lipid metabolism between stable and progressive IPF, with results suggesting disparities in the circulating lipidome with disease progression. [ABSTRACT FROM AUTHOR]

Background: Adoption and maintenance of healthy behaviours is pivotal to chronic disease self-management as this influences disease progression and impact. This qualitative study investigated health behaviour changes adopted by participants with moderate or severe chronic obstructive pulmonary disease (COPD) recruited to a randomised controlled study of telephone-delivered health-mentoring. Methods: Community nurses trained as health-mentors used a patient-centred approach with COPD patients recruited in general practice to facilitate behaviour change, using a framework of health behaviours; 'SNAPPS' Smoking, Nutrition, Alcohol, Physical activity, Psychosocial well-being, and Symptom management, through regular phone calls over 12 months. Semi-structured interviews in a purposive sample sought feedback on mentoring and behaviour changes adopted. Interviews were analysed using iterative thematic and interpretative content approaches by two investigators. Results: Of 90 participants allocated to health-mentoring, 65 (72%) were invited for interview at 12-month follow up. The 44 interviewees, 75% with moderate COPD, had a median of 13 mentor contacts over 12 months, range 5-20. Interviewed participants (n = 44, 55% male, 43% current smokers, 75% moderate COPD) were representative of the total group with a mean age 65 years while 82% had at least one additional co-morbid chronic condition. Telephone delivery was highly acceptable and enabled good rapport. Participants rated 'being listened to by a caring health professional' as very valuable. Three participant groups were identified by attitude to health behaviour change: 14 (32%) actively making changes; 18 (41%) open to and making some changes and 12 (27%) more resistant to change. COPD severity or current smoking status was not related to group category. Mentoring increased awareness of COPD effects, helping develop and personalise behaviour change strategies, even by those not actively making changes. Physical activity was targeted by 43 (98%) participants and smoking by 14 (74%) current smokers with 21% reporting quitting. Motivation to maintain changes was increased by mentor support. Conclusions: Telephone delivery of health-mentoring is feasible and acceptable to people with COPD in primary care. Health behaviours targeted by this population, mostly with moderate disease, were mainly physical activity and smoking reduction or cessation. Health-mentoring increased motivation and assisted people to develop strategies for making and sustaining beneficial change. Trial registration: ACTR12608000112368 [ABSTRACT FROM AUTHOR]

Background: The reticular basement membrane (Rbm) in smokers and especially smokers with COPD is fragmented with "clefts" containing cells staining for the collagenase matrix-metalloproteinase-9 (MMP-9) and fibroblast protein, S100A4. These cells are also present in the basal epithelium. Such changes are likely hallmarks of epithelial mesenchymal transition (EMT). We aimed to confirm the epithelial origin of these Rbm cells, and to exclude potential confounding by infiltrating inflammatory cells.Methods: Endobronchial biopsy sections from 17 COPD current smokers, with documented Rbm splitting and cellularity were stained for neutrophil elastase (neutrophil marker), CD68 (macrophage/mature fibroblasts), CD4+/CD8+ T lymphocytes, CD19 (B-cells), CD11c (dendritic cells/inflammatory cells), and S100 (Langerhans cells). The number of cells in the Rbm and epithelium staining for these "inflammatory" cell markers were then compared to numbers staining for S100A4, "a documented EMT epitope". Slides were double stained for S100A4 and cytokeratin(s).Results: In the basal epithelium significantly more cells stained for S100A4 compared to infiltrating macrophages, fibroblasts or immune cells: median, 26 (21.3 - 37.3) versus 0 (0 - 9.6) per mm, p < 0.003. Markedly more S100A4 staining cells were also observed in the Rbm compared to infiltrating macrophages, neutrophils, fibroblasts or immune cells or any sub-type: 58 (37.3 - 92.6) versus 0 (0 - 4.8) cells/mm Rbm, p < 0.003. Cells in the basal epithelium 26 (21.3 - 37.3) per mm) and Rbm (5.9 (2.3 - 13.8) per mm) frequently double stained for both cytokeratin and S100A4.Conclusions: These data provide additional support for active EMT in COPD airways. [ABSTRACT FROM AUTHOR]

Background: Little is known about airway remodelling in bronchial biopsies (BB) in smokers and chronic obstructive pulmonary disease (COPD). We conducted an initial pilot study comparing BB from COPD patients with nonsmoking controls. This pilot study suggested the presence of reticular basement membrane (Rbm) fragmentation and altered vessel distribution in COPD. Methods: To determine whether Rbm fragmentation and altered vessel distribution in BB were specific for COPD we designed a cross-sectional study and stained BB from 19 current smokers and 14 ex-smokers with mild to moderate COPD and compared these to 15 current smokers with normal lung function and 17 healthy and nonsmoking subjects. Results: Thickness of the Rbm was not significantly different between groups; although in COPD this parameter was quite variable. The Rbm showed fragmentation and splitting in both current smoking groups and ex-smoker COPD compared with healthy nonsmokers (p < 0.02); smoking and COPD seemed to have additive effects. Rbm fragmentation correlated with smoking history in COPD but not with age. There were more vessels in the Rbm and fewer vessels in the lamina propria in current smokers compared to healthy nonsmokers (p < 0.05). The number of vessels staining for vascular endothelial growth factor (VEGF) in the Rbm was higher in both current smoker groups and ex-smoker COPD compared to healthy nonsmokers (p < 0.004). In current smoker COPD VEGF vessel staining correlated with FEV1% predicted (r = 0.61, p < 0.02). Conclusions: Airway remodelling in smokers and mild to moderate COPD is associated with fragmentation of the Rbm and altered distribution of vessels in the airway wall. Rbm fragmentation was also present to as great an extent in ex-smokers with COPD. These characteristics may have potential physiological consequences. [ABSTRACT FROM AUTHOR]