Acute viral infection does not appear to be a primary cause of acute exacerbation of idiopathic pulmonary fibrosis (IPF), a progressive, deadly disease resulting in thickening and scarring of the lungs, according to a study conducted by researchers from the U.S., Korea and Japan.

Previous studies had suggested viral infection might cause exacerbation of IPF in a majority of patients who have the condition, which occurs most often in people between 50 and 70 years of age...

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Neutrophil influx into the airways is an important mechanism in the pathophysiology of the inflammatory process in the airways of patients with chronic obstructive pulmonary disease (COPD). Previously it was shown that anticholinergic drugs reduce the release of non-neuronal paracrine mediators, which modulate inflammation in the airways.

On this basis, we investigated the ability of the long-acting anticholinergic tiotropium bromide to inhibit a) alveolar macrophage (AM)-mediated chemotaxis of neutrophils, and b) cellular release of reactive oxygen species (ROS).MethodAM and neutrophils were collected from 71 COPD patients. Nanomolar concentrations of tiotropium bromide were tested in AM cultured up to 20 h with LPS (1 ug/ml). AM supernatant was tested for TNFalpha, IL8,...

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The environmental, genetic, and/or age-related changes in proteostasis induce inflammation, oxidative stress, and apoptosis. We quantified the correlation of protein expression of critical proteostasis mediators to severity of chronic lung disease using lung tissue samples from control and chronic obstructive pulmonary disease (COPD) subjects (GOLD stage 0-IV) and cigarette smoke (CS)-induced murine model. The human bronchial epithelial cells, HEK-293, and Beas2B cells were used for in vitro experiments to verify the mechanisms.

Our data verifies the correlation of higher expression of valosin-containing protein (VCP) retrograde translocation complex (VCP-Rma1-gp78) with severity of emphysema in COPD lung tissues and over-expression of inflammatory, ER stress and apoptotic mediators like NFκB, GADD-153/CHOP, and p-eIF2α. Moreover, subjects with severe emphysema had a higher accumulation of ubiquitinated proteins and deubiquitinating enzyme, UCHL-1, indicating towards the aggregation of misfolded or damaged proteins. The modulation of both protein degradation and synthesis rates by CS-extract substantiates the pathogenetic role of proteostasis-imbalance in emphysema and COPD. We identified that VCP also mediates proteasomal degradation of HDAC2 and Nrf2, as a potential mechanism for increased oxidative stress and corticosteroid resistance in COPD subjects with emphysema. Next, we confirmed that higher VCP expression associates with increased inflammation and apoptosis using in vitro and murine models.

Our data clearly shows aberrant proteostasis in COPD subjects with severe emphysema. In addition, we evaluate therapeutic efficacy of salubrinal (ER stress inhibitor) to correct the proteostasis-imbalance based on its ability to control VCP expression and ubiquitin accumulation. Overall, our data demonstrate for the first time the critical role of proteostasis-imbalance in pathogenesis of severe emphysema.

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Peer review has been widely used within the National Health Service to facilitate health quality improvement but evaluation has been limited particularly over the longer-term. Change within the National Health Service (NHS) can take a prolonged period - 1-2 years - to occur. We report here a 3-year evaluation of the largest randomized trial of peer review ever conducted in the UK.

Aim : To evaluate whether targeted mutual peer review of respiratory units brings about improvements in services for chronic obstructive pulmonary disease (COPD) over 3 years. Methods  The peer review intervention was a reciprocal supportive exercise that included clinicians, hospital management, commissioners and patients, which focused on the quality of the provision of four specific evidence-based aspects of COPD care.

Results : Follow-up at 36 months demonstrated limited significant quantitative differences in the quality of services offered in the two groups but a strong trend in favour of intervention sites. Qualitative data suggested many benefits of peer review in most but not all intervention units and some control teams. The data identify factors that promote and obstruct change.

Conclusion : The findings demonstrate significant change in service provision over 3 years in both control and intervention sites with great variability in both groups. The combined quantitative and qualitative findings indicate that targeted mutual peer review is associated with improved quality of care, improvements in service delivery and with changes within departments that promote and are precursors to quality improvement. The generic findings of this study have potential implications for the application of peer review throughout the NHS.

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