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Introduction: Fibroblastic foci represent the cardinal pathogenic lesion in idiopathic pulmonary fibrosis (IPF) and comprise activated fibroblasts and myofibroblasts, the key effector cells responsible for dysregulated extracellular matrix deposition in multiple fibrotic conditions. The aim of this study was to define the major transcriptional programmes involved in fibrogenesis in IPF by profiling unmanipulated myofibroblasts within fibrotic foci in situ by laser capture microdissection.Methods: The challenges associated with deriving gene calls from low amounts of RNA and the absence of a meaningful comparator cell type were overcome by adopting novel data mining strategies and by using weighted gene co-expression network analysis (WGCNA), as well as an eigengene-based approach to identify transcriptional signatures, which correlate with fibrillar collagen gene expression.Results: WGCNA identified prominent clusters of genes associated with cell cycle, inflammation/differentiation, translation and cytoskeleton/cell adhesion. Collagen eigengene analysis revealed that transforming growth factor β1 (TGF-β1), RhoA kinase and the TSC2/RHEB axis formed major signalling clusters associated with collagen gene expression. Functional studies using CRISPR-Cas9 gene-edited cells demonstrated a key role for the TSC2/RHEB axis in regulating TGF-β1-induced mechanistic target of rapamycin complex 1 activation and collagen I deposition in mesenchymal cells reflecting IPF and other disease settings, including cancer-associated fibroblasts.Conclusion: These data provide strong support for the human tissue-based and bioinformatics approaches adopted to identify critical transcriptional nodes associated with the key pathogenic cell responsible for fibrogenesis in situ and further identify the TSC2/RHEB axis as a potential novel target for interfering with excessive matrix deposition in IPF and other fibrotic conditions. [ABSTRACT FROM AUTHOR]

Background: People aged 85 years and older are the fastest growing age group worldwide. This study assessed respiratory health, prevalence of respiratory disease and use of spirometry in respiratory diagnosis in a population-based cohort of 85 year olds to better understand respiratory health and disease in this sector of society.Methods: A single year birth-cohort of 85 year olds participated in a respiratory assessment at their home or residential institution including self-reporting of symptoms and measurement of spirometry. General practice medical records were reviewed for respiratory diagnoses and treatments.Findings: In the 845 participants, a substantial burden of respiratory disease was seen with a prevalence of COPD in medical records of 16.6% (n=140). A large proportion of the cohort had environmental exposures through past or current smoking (64.2%, n=539) and occupational risk factors (33.6%, n=269). Spirometry meeting reliability criteria was performed in 87% (n=737) of participants. In the subgroup with a diagnosis of COPD (n=123), only 75.6% (n=93) satisfied Global Initiative in Obstructive Lung Disease (GOLD) criteria for airflow obstruction, and in a healthy subgroup without respiratory symptoms or diagnoses (n=151), 44.4% (n=67) reached GOLD criteria for airflow obstruction and 43.3% (n=29) National Institute of Health and Care Excellence criteria for at least moderate COPD.Interpretation: Spirometry can be successfully performed in the very old, aged 85 years, and may help identify respiratory diseases such as COPD. However interpretation in this age group using current definitions of COPD based on spirometry indices may be difficult and lead to overdiagnosis in a healthy group with transient symptoms. [ABSTRACT FROM AUTHOR]

Background We conducted a placebo-controlled trial of azithromycin therapy in bronchiolitis obliterans syndrome (BOS) post lung transplantation. Methods We compared azithromycin (250 mg alternate days, 12 weeks) with placebo. Primary outcome was FEV1 change at 12 weeks. Results 48 patients were randomised; (25 azithromycin, 23 placebo). It was established, post randomisation that two did not have BOS. 46 patients were analysed as intention to treat (ITT) with 33 'Completers'. ITT analysis included placebo patients treated with open-label azithromycin after study withdrawal. Outcome The ITT analysis (n=46, 177 observations) estimated mean difference in FEV1 between treatments (azithromycin minus placebo) was 0.035 L, with a 95% CI of -0.112 L to 0.182 L (p=0.6). Five withdrawals, who were identified at the end of the study as having been randomised to placebo (four with rapid loss in FEV1, one withdrawn consent) had received rescue openlabel azithromycin, with improvement in subsequent FEV1 at 12 weeks. Study Completers showed an estimated mean difference in FEV1 between treatment groups (azithromycin minus placebo) of 0.278 L, with 95% CI for the mean difference: 0.170 L to 0.386 L (p=<0.001). Nine of 23 ITT patients in the azithromycin group had ≤10% gain in FEV1 from baseline. No patients in the placebo group had ≤10% gain in FEV1 from baseline while on placebo (p=0.002). Seven serious adverse events, three azithromycin, four in the placebo group, were deemed unrelated to study medication. Conclusions Azithromycin therapy improves FEV1 in patients with BOS and appears superior to placebo. This study strengthens evidence for clinical practice of initiating azithromycin therapy in BOS. [ABSTRACT FROM AUTHOR]

This review highlights new developments in scientific and clinical research presented at the British Thoracic Society Winter Scientific Meeting held from 5 to 7 December 2012. Although a wide spectrum of respiratory research was presented at the meeting the content of the review focuses specifically on the key themes of pleural disease, interstitial lung disease and future therapies in respiratory medicine. Advances in clinical and translational respiratory research presented in the major symposia and spoken sessions related to these areas are summarised. Additional sessions covering lifestyle dilemmas in the context of respiratory disease and the early career investigator awards are also highlighted. [ABSTRACT FROM AUTHOR]

A review is presented on articles published in Thorax between 2008 and 2010 relating to lung transplantation and pulmonary hypertension. [ABSTRACT FROM AUTHOR]

This is the second annual review of the British Thoracic Society Winter Scientific Meeting held from 7-9 December 2011, which was attended by over 2000 delegates. Although a wide spectrum of respiratory research was presented at the meeting, the content of the review focuses specifically on three key themes: cystic fibrosis, pulmonary vascular disease and thoracic oncology. Advances in clinical and translational respiratory research presented within the major symposia and spoken sessions related to these areas are summarised. Additional sessions recognising topics relevant to the forthcoming 2012 London Olympics are also highlighted. [ABSTRACT FROM AUTHOR]

The authors reflect on the importance of the guidelines from the British Thoracic Society for the identification of those at risk after an acute pulmonary embolism. They argue that stratification of risk in patients who present with acute pulmonary embolism is less clear. They claim that manifestation of right ventricular dysfunction on either echocardiography or spiral high-resolution computed tomography (HRCT) scanning of the chest is an indicator of those requiring more treatment.

Background: Lung transplantation is the only treatment modality that provides a survival advantage in pulmonary fibrosis, but many patients deemed suitable will die awaiting lung transplantation. While donor organ shortage undoubtedly contributes to this, late referral to the transplant centre may also play a role. This study investigates factors influencing the chance of patients with pulmonary fibrosis reaching lung transplantation.Methods: A single-centre retrospective review of patient demographic data, assessment investigations and subsequent clinical outcomes was performed for patients with pulmonary fibrosis assessed for lung transplantation over a 5-year period.Results: Between March 1999 and March 2004, 129 patients with pulmonary fibrosis underwent formal transplant assessment. Sixty-nine were accepted and listed for lung transplantation. Of these, 17 were transplanted, 37 died while waiting, 4 were removed from the list and 11 were still waiting at the conclusion of the study. The median waiting time on the list for those transplanted was 103 days (range 6-904) compared with 125 days (range 2-547) for those who died while on the list (p = 0.65). There was no significant difference in age, spirometry, total lung capacity, gas transfer measures or 6 min walk distance between those who died waiting and those transplanted. However, time from onset of symptoms to transplant assessment was significantly shorter in those who died on the waiting list (median 29 months (range 2-120)) than in those transplanted (median 46 months (range 6-204), p = 0.037).Conclusion: Patients with pulmonary fibrosis who died awaiting transplantation had similar disease severity at assessment as those who achieved transplantation. However, the interval between symptom onset and transplant referral was significantly shorter in those who died while on the waiting list, suggesting they had more rapidly progressive disease. The rate of disease progression appears to be a more sensitive indicator for transplantation referral than any single physiological measure of disease severity and should act as an important trigger for early transplant referral. [ABSTRACT FROM AUTHOR]

Two letters to the editor are presented in response to the article "Identification of Those at Risk After Acute Pulmonary Embolism" by A. J. Fisher and P. A. Corris in a previous issue.

This review presents the inaugural report of the British Thoracic Society Winter Scientific Meeting held from 1st-3rd December 2010. Although a wide spectrum of respiratory research was presented at the meeting the content of the review focuses specifically on three key themes of inflammation and lung injury, airways disease and respiratory infection. Advances in both clinical and translational respiratory research presented within the major symposia and spoken sessions related to these themes are summarised. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Effect of azithromycin on primary bronchial epithelial cells derived from stable lung allografts" which is published in the previous issue of the periodical.