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et al.With the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in coronavirus disease 2019 (COVID-19), corporate entities, federal, state, county, and city governments, universities, school districts, places of worship, prisons, health care facilities, assisted living organizations, daycares, homeowners, and other building owners and occupants have an opportunity to reduce the potential for transmission through built environment (BE)-mediated pathways. Over the last decade, substantial research into the presence, abundance, diversity, function, and transmission of microbes in the BE has taken place and revealed common pathogen exchange pathways and mechanisms. In this paper, we synthesize this microbiology of the BE research and the known information about SARS-CoV-2 to provide actionable and achievable guidance to BE decision makers, building operators, and all indoor occupants attempting to minimize infectious disease transmission through environmentally mediated pathways. We believe this information is useful to corporate and public administrators and individuals responsible for building operations and environmental services in their decision-making process about the degree and duration of social-distancing measures during viral epidemics and pandemics. Copyright © 2020 Dietz et al.Since the turn of the century, technological advances have made it possible to obtain the molecular profile of any tissue in a cost-effective manner. Among these advances are sophisticated high-throughput assays that measure the relative abundances of microorganisms, RNA molecules, and metabolites. While these data are most often collected to gain new insights into biological systems, they can also be used as biomarkers to create clinically useful diagnostic classifiers. How best to classify high-dimensional -omics data remains an area of active research. However, few explicitly model the relative nature of these data and instead rely on cumbersome normalizations. This report (i) emphasizes the relative nature of health biomarkers, (ii) discusses the literature surrounding the classification of relative data, and (iii) benchmarks how different transformations perform for regularized logistic regression across multiple biomarker types. Clofarabine DNA inhibitor We show how an interpretable set of log contrasts, called balances, can pre we developed an entirely normalization-free classification procedure that reduces the feature space and improves the interpretability, without sacrificing classifier performance. Copyright © 2020 Quinn and Erb.Microorganisms from the environment can enter the dairy supply chain at multiple stages, including production, milk collection, and processing, with potential implications for quality and safety. The ability to track these microorganisms can be greatly enhanced by the use of high-throughput DNA sequencing (HTS). Here HTS, both 16S rRNA gene amplicon and shotgun metagenomic sequencing were applied to investigate the microbiomes of fresh mid- and late-lactation milk collected from farm bulk tanks, collection tankers, milk silos, skimmed milk silos, a cream silo, and powder samples to investigate the microbial changes throughout a skim milk powder manufacturing process. 16S rRNA gene analysis established that the microbiota of raw milks from farm bulk tanks and in collection tankers were very diverse but that psychrotrophic genera associated with spoilage, Pseudomonas and Acinetobacter, were present in all samples. Upon storage within the whole-milk silo at the processing facility, the species Pseudomonas fluoreentify microorganisms along the processing chain. In addition, it demonstrates that the populations of microbes change from raw milk to the end product. Routine implementation of high-throughput sequencing would elucidate the factors that influence population dynamics. This will enable a manufacturer to adopt control measures specific to each stage of processing and respond in an effective manner, which would ultimately lead to increased food safety and quality. Copyright © 2020 McHugh et al.Severe respiratory consequences of the COVID-19 pandemic have prompted urgent need for novel therapies. Cell-based approaches, primarily using mesenchymal stem (stromal) cells (MSCs), have demonstrated safety and possible efficacy in patients with the acute respiratory distress syndrome (ARDS), although not as yet well studied in respiratory virus-induced ARDS. Limited pre-clinical data suggest that systemic MSC administration can significantly reduce respiratory virus (Influenza strains H5N1 and H9N2)-induced lung injury, however, there are no available data in models of coronavirus respiratory infection.There are a rapidly increasing number of clinical investigations of cell-based therapy approaches for COVID-19. These utilise a range of different cell sources, doses, dosing strategies, and targeted patient populations. To provide a rationale strategy to maximise potential therapeutic use, it is critically important to understand the relevant pre-clinical studies and postulated mechanisms of MSC actions in respiratory virus-induced lung injuries. These are presented along with consideration of current clinical investigations. Copyright ©ERS 2020.INTRODUCTION Inhaled antibiotics may improve symptom scores but it is not known which specific symptoms improve with therapy. Item-level analysis of questionnaire data may allow us to identify which specific symptoms respond best to treatment. METHODS Post-hoc analysis of the AIR-BX1 and 2 trials of inhaled aztreonam versus placebo in bronchiectasis. Individual items from the quality of life bronchiectasis respiratory symptom scale (QOL-B) were extracted, as representing severity of 9 distinct symptoms. Generalised linear models were used to evaluate changes in symptoms with treatment versus placebo from baseline to end of first on treatment cycle and mixed models used to evaluate changes across the full 16 week trial. RESULTS Aztreonam improved cough (difference 0.22; 95%CI 0.08-0.37, p=0.002), sputum production (0.30; 95%CI 0.15-0.44, p less then 0.0001) and sputum colour (0.29; 95%CI 0.15-0.43 p less then 0.0001) versus placebo equating to a 20% improvement in cough and 25% improvement in sputum production and colour respectively. Similar results were observed for cough, sputum production and sputum purulence across the trial duration (all p less then 0.05). Patients with higher sputum production and sputum colour scores had a greater response on the overall QOL-B (difference 4.82; 95%CI 1.12-8.53, p=0.011) for sputum production and 5.02; 95%CI 1.19-8.86, p=0.01 for sputum colour. In contrast, treating patients who had lower levels of bronchitic symptoms resulted in shorter time to next exacerbations (HR 1.83; 95%CI 1.02-3.28, p=0.042). CONCLUSION Baseline bronchitic symptoms predict response to inhaled aztreonam in bronchiectasis. More sensitive tools to measure bronchitic symptoms may be useful to enrich for inhaled antibiotic responders and to evaluate patient response to treatment. Copyright ©ERS 2020.Idiopathic Pulmonary Fibrosis (IPF) is thought to result from aberrant tissue repair processes in response to chronic or repetitive lung injury. The origin and nature of the injury, as well as its cellular and molecular targets, are likely heterogeneous, which complicates accurate pre-clinical modeling of the disease and makes therapeutic targeting a challenge. Efforts are underway to identify central pathways in fibrogenesis which may allow targeting of aberrant repair processes regardless of the initial injury stimulus. Dysregulated endothelial permeability and vascular leak have long been studied for their role in acute lung injury and repair. Evidence that these processes are of importance to the pathogenesis of fibrotic lung disease is growing. Endothelial permeability is increased in non-fibrosing lung diseases, but it resolves in a self-limited fashion in conditions such as bacterial pneumonia and acute respiratory distress syndrome (ARDS). In progressive fibrosing diseases such as IPF, permeability appears to persist however and may also predict mortality. In this hypothesis-generating review, we summarise available data on the role of endothelial permeability in IPF and focus on the deleterious consequences of sustained endothelial hyperpermeability in response to and during pulmonary inflammation and fibrosis. We propose that persistent permeability and vascular leak in the lung have the potential to establish and amplify the pro-fibrotic environment. Therapeutic interventions aimed at recognising and "plugging" the leak may therefore be of significant benefit for preventing the transition from lung injury to fibrosis and should be areas for future research. Copyright ©ERS 2020.BACKGROUND The role of bronchoalveolar lavage fluid (BAL) lymphocyte% to diagnose chronic hypersensitivity pneumonitis (CHP) is unclear. We conducted a systematic review and meta-analysis of BAL lymphocyte% in the diagnosis of CHP. METHODS We searched Medline, Embase and Cochrane library from inception to August 2019. Individual patient data were obtained to test performance characteristics of BAL lymphocyte% at different thresholds. Random-effects models were used for pooled estimates, with comparisons made between CHP and non-CHP interstitial lung diseases (ILD). RESULTS Fifty-three studies were included in the systematic review and 42 in the meta-analysis. The pooled estimate for BAL lymphocyte% was 42.8% (95%CI 37.7-47.8, I2=95.3%) in CHP, 10.0% (95%CI 6.9-13.1, I2=91.2%) in idiopathic pulmonary fibrosis (IPF), 23.1% (95% CI 3.0-43.2, I2=85.2%) in non-IPF idiopathic interstitial pneumonia (IIP), 23.4% (95%CI 11.0-35.9, I2=45.7%) in connective-tissue disease ILD (CTD-ILD), and 31.2% (95% CI 17.6-44.8, I2=95.2%) in sarcoidosis. Results differed between CHP and IPF (p20% provided sensitivity of 68.1% and specificity of 64.8% for CHP. Higher thresholds provided lower sensitivity with higher specificity. Older age and ever having smoked were associated with lower lymphocyte% in CHP. CONCLUSIONS BAL lymphocyte% is higher in CHP compared to IPF and other IIP, with higher thresholds providing improved specificity at the cost of sensitivity. However, parent studies are at risk of incorporation bias, and prospective studies should evaluate the additive discriminate value of BAL lymphocyte% to accurately diagnose CHP. Copyright ©ERS 2020.In January 2019, a European Respiratory Society (ERS) Research Seminar entitled "Targeting the detrimental effects of sleep disturbances and disorders" was held in Dublin, Ireland. It provided the opportunity to critically review the current evidence of pathophysiological responses of sleep disturbances, such as sleep deprivation, sleep fragmentation or circadian misalignment and of abnormalities in physiological gases such as oxygen and carbon dioxide which are frequently occurring in respiratory conditions during sleep. A specific emphasis of the seminar was placed on the evaluation of the current state of knowledge of the pathophysiology of cardiovascular and metabolic diseases in obstructive sleep apnoea (OSA). Identification of the detailed mechanisms of these processes is of major importance to the field and this seminar offered an ideal platform to exchange knowledge, to discuss pitfalls of current models and the design of future collaborative studies. We also debated the limitations of current treatment strategies for cardiometabolic complications in OSA and discussed potentially valuable alternative approaches.