T lymphocyte insensitivity to corticosteroids in chronic obstructive pulmonary disease

<p>Abstract</p> <p>Background</p> <p>There are increased numbers of activated lymphocytes in the lungs of chronic obstructive pulmonary disease (COPD) patients. The clinical benefits of corticosteroids in COPD patients are limited. Our hypothesis is that lymphocytes play a role in this corticosteroid insensitivity.</p> <p>Objectives</p> <p>To investigate the effects of the corticosteroid dexamethasone on lung lymphocyte cytokine production from patients with COPD compared to controls.</p> <p>Methods</p> <p>Cultured airway lymphocytes obtained by bronchoscopy from healthy non-smokers (HNS), smokers (S) and COPD patients were stimulated with phytohaemagglutinin (PHA) & phorbol myristate acetate (PMA), +/- dexamethasone. Supernatants were assayed for interleukin (IL)-2 and interferon (IFN)γ. Immunofluoresence was used to analyse changes in CD8 glucocorticoid receptor (GRα and GRβ) expression.</p> <p>Results</p> <p>The inhibition of PHA/PMA stimulated IFNγ production by dexamethasone was reduced in COPD patients compared to HNS (<it>p </it>< 0.05 at concentrations from 0.1-1 μM). There was also a significant reduction (<it>p </it>< 0.05) in the mean inhibitory effect at 1 μM in COPD patients (54.1%) compared to smokers (72.1%), and in smokers compared to HNS (85.5%). There was a numerically reduced effect of dexamethasone on IL-2 production that did not reach statistical significance. There was no difference in GRα and GRβ expression in follicular CD8 cells between COPD patients (50.9% and 30.4% respectively) and smokers (52.9% and 29.7% respectively).</p> <p>Conclusions</p> <p>IFNγ production from COPD airway lymphocytes is corticosteroid insensitive. This phenomenon may be important in the poor clinical response often observed with corticosteroids.</p

Prevalence of haemoglobinopathies in the diabetic population served by Connolly Hospital

Introduction: Small shifts in glycaemic control are associated with significant effects on clinical complications in patients with diabetes. Measurement of glycosylated haemoglobin, called HbA1c, is well established as the gold standard for measurement of long-term glycaemic control. However, variations in haemoglobin may alter the validity of HbA1c. Aim: To determine the percentage of HbA1c tests performed on patients with haemoglobinopathies at Connolly Hospital, with consideration of the possible need for fructosamine measurement in those patients. Methods: A retrospective chart review covering all patients tested for HbA1c at Connolly Hospital between January 1, 2014, and July 1, 2014. Results: Some 28 patients out of a total of 3,920 (0.71%) were automatically flagged in laboratory records as demonstrating abnormal haemoglobins upon HbA1c measurement, with 36 HbA1c tests in total (including repeats on individuals) run on these patients over the study period. Nine (four female, five male) had previous records of specific haemoglobin screening tests, all of which were consistent with sickle cell trait. Conclusion: The number of patients having HbA1c tested at Connolly Hospital who have haemoglobinopathies warrants interpreting their HbA1c results with caution. It is worth considering the need to perform fructosamine measurements regularly in house as an alternative.</p

Primary spontaneous pneumothorax:a diffuse disease of the pleura

Primary spontaneous pneumothorax (PSP) is by definition not associated with any underlying lung disease. However, this does not mean that there is no underlying pathological process. It has become increasingly apparent over recent years that PSP is associated with diffuse and often bilateral abnormalities within the pleura and is not simply a disease caused by ruptured blebs/bullae. The pathological process includes emphysema-like changes, pleural porosity and inflammation. In this review, we summarise the recent advances in our understanding of the pathogenesis of PSP and discuss how this relates to management strategies for patients with PSP.</jats:p

Down regulation of T cell receptor expression in COPD pulmonary CD8 cells.

CD8 cells may contribute towards an autoimmune process in COPD. Down regulation of T cell receptor (TCR) signalling molecules occurs in autoimmune diseases with consequent T cell dysfunction. We hypothesise that TCR signalling is abnormal in COPD pulmonary CD8 cells. Micro-array gene expression analysis of blood and pulmonary COPD CD8 samples was performed and compared to pulmonary CD8 cells from smoker controls (S). We focused on the TCR signalling pathway, with validation of key findings using polymerase chain reaction and immunofluorescence. TCR signalling molecules in COPD pulmonary CD8 cells were down regulated compared to blood CD8 cells (CD247: fold change (FC) -2.43, Q = 0.001; LCK: FC -2.25, Q = 0.01). Micro-array analysis revealed no significant differences between COPD and S pulmonary CD8 cells. However, PCR revealed significantly lower gene expression levels of CD247 (FC -1.79, p = 0.04) and LCK (FC -1.77, p = 0.01) in COPD compared to S pulmonary CD8 cells. CD247 down regulation in COPD CD8 cells was confirmed by immunofluorescent staining of bronchoalveolar lavage cells: Significantly fewer COPD CD8 cells co-expressed CD247 compared to healthy non-smoker CD8 cells (mean 88.9 vs 75.2%,

Impact of haemoglobin variants on the use of haemoglobin A1c for the diagnosis and monitoring of diabetes: a contextualised review

HbA1c is the established test for monitoring glycaemic control in diabetes, and intervention trials studying the impact of treatment on glycaemic control and risk of complications focus predominantly on this parameter in terms of evaluating the glycaemic outcomes. It is also the main parameter used when targets for control are being individualised, and more recently, it has been used for the diagnosis of type 2 diabetes. For laboratories performing this test and clinicians utilising it in their decision-making process, a thorough understanding of factors that can impact on the accuracy, and appropriate interpretation of the test is essential. The changing demographic in the Irish population over the last two decades has brought this issue sharply into focus. It is therefore timely to review the utility, performance and interpretation of the HbA1c test to highlight factors impacting on the results, specifically the impact of haemoglobin variants, and the impact of these factors on its utilisation in clinical practice. </p

Additional file 2: Figure S1. of Additive anti-inflammatory effects of corticosteroids and phosphodiesterase-4 inhibitors in COPD CD8 cells

Effect of GSK256066, Roflumilast and Forskolin on release of IL-2 in peripheral blood CD8 cells. Peripheral blood CD8 cells from healthy non-smokers (n = 2) were pre-treated with stated concentrations of GSK256066 (A), Roflumilast (B) or Forskolin (C) for 1 h prior to stimulation with anti-CD2/3/28 beads for 24 h. Supernatants were harvested and interleukin 2 (IL-2) was measured by ELISA. Data presented as mean ± SE % inhibition of IL-2. (PNG 43 kb

Additional file 1: of Additive anti-inflammatory effects of corticosteroids and phosphodiesterase-4 inhibitors in COPD CD8 cells

Supplementary data and Tables S1 & S2. (DOCX 20 kb

Self-management for non-cystic fibrosis bronchiectasis: Cochrane Systematic Review

BackgroundThe aims of therapeutic management for non-cystic fibrosis (non-CF) bronchiectasis are: preservation of lung function, reduction of symptoms and exacerbations, minimise complications, and improve quality of life. Self-management interventions are beneficial in the management of other airways diseases and has been identified as a research priority for bronchiectasis. ObjectivesTo assess the efficacy, cost-effectiveness and adverse effects of self-management interventions for adults and children with non-CF bronchiectasis. MethodsCochrane Airways Group's Specialised Register, ClinicalTrials.gov and the World Health Organization trials portal were searched. We included all parallel and cluster-randomised controlled trials which included adults and children with non-CF bronchiectasis assessing self-management interventions delivered in any form (e.g. mobile device, face-to-face). Two reviewers independently assessed studies for eligibility and quality, and extracted data. ResultsWe identified 53 records and included 2 studies. A total of 84 patients with bronchiectasis were randomised: one RCT of early rehabilitation in adults in two centres in England and one proof-of-concept RCT of an expert patient programme in adults in a single regional respiratory centre in Northern Ireland. Data aggregation was not possible. For primary outcomes, health-related quality of life was reported in both studies but showed no significant benefit. One study reported more deaths in the intervention group compared to the control group, (Intervention: 4 of 8, Control: 2 of 12), though small numbers limit interpretation. Neither study reported data on exacerbations requiring antibiotic therapy. For secondary outcomes, frequency of hospital admissions was reported in one study but was not significantly different between groups. Both studies reported lung function in terms of FEV1 but there were no significant differences between groups (P>0.05). One study reported data on self-efficacy and showed evidence of benefit. Neither study reported data on respiratory symptoms, economic costs or adverse events. Using GRADE guidelines, the outcomes included were judged as very low quality. No trials in children were identified.  ConclusionsThere is insufficient evidence to determine whether self-management has benefits in adults and children with non-CF bronchiectasis. Future studies should more clearly define self-management interventions, control for sources of variability, be adequately powered, measure clinically important outcomes, and include children