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Introduction A subset of COPD patients develops advanced disease with severe airflow obstruction, hyperinflation and extensive emphysema. We propose that the pathogenesis in these patients differs from mild–moderate COPD and is reflected by bronchial gene expression. The aim of the present study was to identify a unique bronchial epithelial gene signature for severe COPD patients. Methods We obtained RNA sequencing data from bronchial brushes from 123 ex-smokers with severe COPD, 23 with mild–moderate COPD and 23 non-COPD controls. We identified genes specific to severe COPD by comparing severe COPD to non-COPD controls, followed by removing genes that were also differentially expressed between mild–moderate COPD and non-COPD controls. Next, we performed a pathway analysis on these genes and evaluated whether this signature is retained in matched nasal brushings. Results We identified 219 genes uniquely differentially expressed in severe COPD. Interaction network analysis identified VEGFA and FN1 as the key genes with the most interactions. Genes were involved in extracellular matrix regulation, collagen binding and the immune response. Of interest were 10 genes (VEGFA, DCN, SPARC, COL6A2, MGP, CYR61, ANXA6, LGALS1, C1QA and C1QB) directly connected to fibronectin 1 (FN1). Most of these genes were lower expressed in severe COPD and showed the same effect in nasal brushings. Conclusions We found a unique severe COPD bronchial gene signature with key roles for VEGFA and FN1, which was retained in the upper airways. This supports the hypothesis that severe COPD, at least partly, comprises a different pathology and supports the potential for biomarker development based on nasal brushes in COPD.

Refractory breathlessness is a devastating symptom in chronic obstructive pulmonary disease (COPD). Symptom-focused breathlessness services, involving palliative care teams, offer individualized support but are not yet widely available for people with nonmalignant disease among which COPD. Our primary aim was to demonstrate the feasibility of setting up a breathlessness service specifically for COPD patients within a respiratory outpatient clinic. Our secondary aims were to assess how many sessions patients need to complete the intervention; to obtain an indication of effect size (on the Chronic Respiratory Questionnaire (CRQ), subset mastery domain); and to evaluate patient and professional satisfaction. We conducted a non-randomized single-center feasibility study. Participants had COPD and refractory breathlessness. During at least one session with a respiratory nurse and a pulmonologist, and one session with a physiotherapist, patients learned non-pharmacological interventions to manage breathlessness. Of 34 screened patients, 19 were included. All completed the intervention. A median of two clinical visits and two telephone calls were needed to complete the intervention. The mean improvement of 1.55 in CRQ, mastery domain, significantly exceeded the clinically important difference of 0.5. The service was rated as excellent by the eight patients who completed the survey. The health professional team gave positive feedback on the experience of delivering the intervention. Delivery of a breathlessness service for COPD outpatients with refractory breathlessness appears feasible, easy to implement in a respiratory outpatient clinic, and has the potential to be effective. A randomized controlled clinical trial is needed to test effectiveness and cost-effectiveness in this context.

OBJECTIVES: The aim of this study was to determine associations between lung function, bronchial hyperresponsiveness (BHR), and atopy with exposure to fire smoke among firefighters. METHODS: The study was comprised of 402 firefighters, a randomly chosen subset of a previous survey among firefighters in the Netherlands. Subjects underwent spirometry and methacholine provocation, and blood samples were taken to assess atopy. Exposure to fire smoke was registered by a questionnaire. RESULTS: Hyperresponsiveness expressed as dose–response slope (DRS) was positively and significantly associated with the number of fires fought in the last 12 months with and without adjustments for smoking, gender, atopy, age, and exposure in the main job held. Limiting the analysis to firefighters without exposure within 7 days of testing did not change any of the associations. The association between the number of fires and the DRS was stronger among atopics, and hyperresponsiveness expressed as PD_20 was also significantly associated, indicating that atopics are at higher risk of developing BHR as a result of smoke exposure. Respiratory protection devices were not optimally used. CONCLUSIONS: It is recommended that awareness be heightened among firefighters to avoid exposure to all fire smoke and that management be sensitive to the adequate use of self-contained breathing apparatuses by their personnel.

Erik Bathoorn1, Huib Kerstjens1, Dirkje Postma1, Wim Timens2, William MacNee31Groningen Research Institute for Asthma and COPD (GRIAC), Department of Pulmonology, 2Department of Pathology, University Medical Center Groningen, University of Groningen, the Netherlands; 3Edinburgh Lung and the Environment Group Initiative/Colt Research Laboratories, Medical School, University of Edinburgh, Edinburgh, Scotland, United KingdomIntroduction: Inflammation is a core feature of acute chronic obstructive pulmonary disease (COPD) exacerbations. It is important to focus on inflammation since it gives insight into the pathological changes causing an exacerbation, thereby possibly providing directions for future therapies which modify inflammation.Objectives: To provide a cell-by-cell overview of the inflammatory processes during COPD exacerbations. To evaluate cell activation, and cytokine production, cellular interactions, damaging effects of inflammatory mediators to tissue, and the relation to symptoms at the onset of COPD exacerbations. To speculate on future therapeutic options to modify inflammation during COPD exacerbations.Results: During COPD exacerbations, there is increased airway wall inflammation, with pathophysiological influx of eosinophils, neutrophils, and lymphocytes. Although links have been suggested between the increase in eosinophils and lymphocytes and a viral etiology of the exacerbation, and between the increase in neutrophils and a bacterial aetiology, these increases in both inflammatory cell types are not limited to the respective aetiologies and the underlying mechanisms remain elusive.Conclusion: Further research is required to fully understand the inflammatory mechanisms in the onset and development of COPD exacerbations. This might make inflammatory pathway-specific intervention possible, resulting in a more effective treatment of COPD exacerbations with fewer side effects.Keywords: COPD, exacerbation, inflammation, therapy