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Background: Pulmonary alveolar proteinosis (PAP) is a rare syndrome caused by several distinct diseases leading to progressive dyspnoea, hypoxemia, risk of respiratory failure and early death due to accumulation of proteinaceous material in the lungs. Diagnostic strategies may include computed tomography (CT) of the lungs, bronchoalveolar lavage, evaluation of antibodies against granulocyte macrophage colony stimulating factor (GM-CSF), genetic testing, and, eventually, lung biopsy. The management options are focused at removing the proteinaceous material by whole lung lavage (WLL), augmentation therapy with GM-CSF, rituximab, plasmapheresis, and lung transplantation. The presented diagnostic and management guideline aim to provide guidance to physicians managing patients with PAP., Methods: A European Respiratory Society Task Force committee composed of clinicians, methodologists, and patients with experience in PAP developed recommendations in accordance with the ERS Handbook for Clinical Practice Guidelines and the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach. This included a systematic review of the literature and application of the GRADE approach to assess the certainty of the evidence and strength of recommendations. The committee formulated five PICO (Patients, Intervention, Comparison, Outcomes) questions, and two narrative questions to develop specific evidence-based recommendations., Results: The Task Force committee developed recommendations for five PICOs. These included management of PAP with WLL, GM-CSF augmentation therapy, rituximab, plasmapheresis, and lung transplantation. Also, the committee made recommendations regarding the use of GM-CSF antibody testing, diagnostic bronchoalveolar lavage (BAL) and biopsy based on narrative questions.In addition to the recommendations, the committee provided information on the hierarchy of diagnostic interventions and therapy., Conclusions: The diagnosis of PAP is based on CT and BAL cytology or lung histology, whereas diagnosis of specific PAP-causing diseases requires GM-CSF antibody testing or genetic analysis. There are several therapies including WLL and augmentation therapy with GM-CSF available to treat PAP, but supporting evidence is still limited., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Screening for lung cancer with low radiation dose computed tomography has a strong evidence base, is being introduced in several European countries and is recommended as a new targeted cancer screening programme. The imperative now is to ensure that implementation follows an evidence-based process that will ensure clinical and cost effectiveness. This European Respiratory Society (ERS) task force was formed to provide an expert consensus for the management of incidental findings which can be adapted and followed during implementation., Methods: A multi-European society collaborative group was convened. 23 topics were identified, primarily from an ERS statement on lung cancer screening, and a systematic review of the literature was conducted according to ERS standards. Initial review of abstracts was completed and full text was provided to members of the group for each topic. Sections were edited and the final document approved by all members and the ERS Science Council., Results: Nine topics considered most important and frequent were reviewed as standalone topics (interstitial lung abnormalities, emphysema, bronchiectasis, consolidation, coronary calcification, aortic valve disease, mediastinal mass, mediastinal lymph nodes and thyroid abnormalities). Other topics considered of lower importance or infrequent were grouped into generic categories, suitable for general statements., Conclusions: This European collaborative group has produced an incidental findings statement that can be followed during lung cancer screening. It will ensure that an evidence-based approach is used for reporting and managing incidental findings, which will mean that harms are minimised and any programme is as cost-effective as possible., Competing Interests: Conflict of interest: All declarations are outside the submitted work. Unless otherwise stated, authors do not make any relevant disclosures. A. Brunelli declares honoraria from AstraZeneca, Ethicon, Medtronic, MSD and Roche. J. Chorostowska declares honoraria from AstraZeneca, MSD, Pfizer, Takeda, Amgen, Grifols, CSL Behring, Novartis, Chiesi, Celon Pharma, Adamed and Mero Biopharma. A. Devaraj declares consulting fees from Boehringer Ingelheim, Roche, Vicore and Brainomix, and personal stock/options in Brainomix. D. Deruysscher declares grants/honoraria from AstraZeneca, BMS, Beigne and Philips. H. Prosch declares grants and honoraria from Boehringer Ingelheim, AstraZeneca, Siemens and MSD. A. Kerpel-Fronius declares honoraria from MSD and Boehringer Ingelheim, and conference expenses from Roche and Bracco. W. van Geffen is local PI for trials funded by MSD and Roche. H-U. Kauczor declares honoraria and grants from Boehringer Ingelheim, Philips, Siemens and MSD, and honoraria from Sanofi. P.M. Putora declares grants to his institution from AstraZeneca and Bayer. M-P. Revel declares honoraria from MSD, Boehringer Ingelheim, GE Healthcare, Bracco and Gleamer, grants from the French Ministry of Health and French Cancer Institute, and software from Aidence, Mevis, Coreline and Gleamer. R. Vliegenthart declares honoraria from Siemens Healthineers and Bayer, and research grants from the Dutch Cancer Foundation, Siemens Heathineers, the Dutch Heart Foundation and the Netherlands Organisation for Scientific Research. A. Snoeckx declares grants from the Foundation Agaist Cancer and the Flemish Cancer Society, and advisory board work for Agfa. G. Veronesi declares honoraria from AstraZeneca, Medtronic and Roche, and grants from INAIL and IARC. D.R. Baldwin declares honoraria for speaking from Roche, MSD and AstraZeneca, and research grants from CRUK, NIHR, Innovate UK, Small Business Research Initiative, NHS Digital, NHS England, Roy Castle Lung Foundation, European Commission Horizon and Yourshire Cancer; and is advisor to the UK National Screening Committee., (This article has been co-published with permission in the European Journal of Cardio-Thoracic Surgery and in the European Respiratory Journal. Copyright © The authors 2023. Published by the European Respiratory Society. All rights reserved. For reproduction rights and permissions contact permissions@ersnet.org. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Either citation can be used when citing this article.)

Lymphangioleiomyomatosis (LAM) is a diffuse cystic lung disease. There are two main types of LAM: sporadic, and LAM associated with the tuberous sclerosis complex (TSC), which is caused by mutations in the TSC1 and TSC2 genes. LAM is characterised by cystic lung disease resulting in progressive dyspnoea, renal angiomyolipomas and lymphatic complications. Pneumothorax occurs frequently (70%) and definitive management with pleurodesis is recommended as the risk of recurrence is high. Characteristic thin-walled cysts are seen on computed tomography and the presence of elevated serum levels of a vascular endothelial growth factor-D has good diagnostic specificity. Currently, no single clinical or serological factor has been shown to predict prognosis. However, over the past decade, significant advances in our understanding of the pathophysiology of LAM has led to improved recognition of this rare disease and identification of treatment options. Mechanistic target of rapamycin inhibitors slow the rate of lung function decline and can resolve chylous effusion and regress angiomyolipomas. Life expectancy in patients with LAM is favourable, with a mean transplant-free survival >20 years from the time of diagnosis. Continued advances in understanding the molecular basis of LAM will lead to improved therapeutic targets and the development of more robust prognostic indicators., Educational Aims: To illustrate the clinical features, common presentations and radiological features of LAMTo outline the diagnostic approach to LAM, including the role of VEGF-DTo review the current prognostic indicators in LAM, and outline the impact of lung function, hormonal status, VEGF-D and clinical presentation on outcomeTo inform clinicians on the management options for LAM both pharmacological and nonpharmacological., Competing Interests: Conflict of interest: A.M. O'Mahony has nothing to disclose. Conflict of interest: E. Lynn has nothing to disclose Conflict of interest: D.J. Murphy has nothing to disclose. Conflict of interest: A. Fabre has nothing to disclose. Conflict of interest: C. McCarthy has nothing to disclose., (Copyright ©ERS 2020.)

Obstructive sleep apnoea (OSA) is increasingly associated with insulin resistance. The underlying pathophysiology remains unclear but intermittent hypoxia (IH)-mediated inflammation and subsequent dysfunction of the adipose tissue has been hypothesised to play a key role.We tested this hypothesis employing a comprehensive translational approach using a murine IH model of lean and diet-induced obese mice, an innovative IH system for cell cultures and a tightly controlled patient cohort.IH led to the development of insulin resistance in mice, corrected for the degree of obesity, and reduced insulin-mediated glucose uptake in 3T3-L1 adipocytes, associated with inhibition of the insulin-signalling pathway and downregulation of insulin-receptor substrate-1 mRNA. Providing mechanistic insight, IH induced a pro-inflammatory phenotype of visceral adipose tissue in mice with pro-inflammatory M1 macrophage polarisation correlating with the severity of insulin resistance. Complimentary in vitro analysis demonstrated that IH led to M1 polarisation of THP1-derived macrophages. In subjects without comorbidities (n=186), OSA was independently associated with insulin resistance. Furthermore, we found an independent correlation of OSA severity with the M1 macrophage inflammatory marker sCD163.This study provides evidence that IH induces a pro-inflammatory phenotype of the adipose tissue, which may be a crucial link between OSA and the development of insulin resistance., Competing Interests: Conflict of interest: None declared., (Copyright ©ERS 2017.)

The aim of this study was to evaluate the risk factors for and outcomes of acute exacerbations in patients with advanced idiopathic pulmonary fibrosis (IPF), and to examine the relationship between disease severity and neovascularisation in explanted IPF lung tissue. 55 IPF patients assessed for lung transplantation were divided into acute (n=27) and non-acute exacerbation (n=28) groups. Haemodynamic data was collected at baseline, at the time of acute exacerbation and at lung transplantation. Histological analysis and CD31 immunostaining to quantify microvessel density (MVD) was performed on the explanted lung tissue of 13 transplanted patients. Acute exacerbations were associated with increased mortality (p=0.0015). Pulmonary hypertension (PH) at baseline and acute exacerbations were associated with poor survival (p<0.01). PH at baseline was associated with a significant risk of acute exacerbations (HR 2.217, p=0.041). Neovascularisation (MVD) was significantly increased in areas of cellular fibrosis and significantly decreased in areas of honeycombing. There was a significant inverse correlation between mean pulmonary artery pressure and MVD in areas of honeycombing. Acute exacerbations were associated with significantly increased mortality in patients with advanced IPF. PH was associated with the subsequent development of an acute exacerbation and with poor survival. Neovascularisation was significantly decreased in areas of honeycombing, and was significantly inversely correlated with mean pulmonary arterial pressure in areas of honeycombing.