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European Respiratory Journal 01/24/2020 06:56
Pulmonary fibrosis is considered to result from recurrent alveolar epithelial injury coupled with dysfunctional alveolar wound healing mechanisms, some of which have a genetic background. Pulmonary fibrosis in the adult has not been previously associated with prolidase deficiency, an innate deficiency of aminoacids metabolism.
European Respiratory Journal 01/24/2020 06:56
Bodyweight and fat distribution may be related to Chronic obstructive pulmonary disease (COPD) risk. Limited prospective evidence linked COPD to abdominal adiposity. We investigated the association of body mass index (BMI) and measures of abdominal adiposity with COPD risk in a prospective cohort study. The China Kadoorie Biobank (CKB) recruited participants aged 30–79 years from ten areas across China. Anthropometric indexes were objectively measured at the baseline survey during 2004–2008. After exclusion of participants with prevalent COPD and major chronic diseases, 452 259 participants were included and followed up through the end of 2016. We used Cox models to estimate adjusted hazard ratios relating adiposity to risk of COPD hospital.
European Respiratory Journal 01/24/2020 06:56
The World Health Organization (WHO) has listed moxifloxacin and linezolid among the preferred "Group A" drugs in the treatment of multidrug-resistant tuberculosis (MDR-TB) [1]. Therapeutic drug monitoring (TDM) could potentially optimise MDR-TB therapy, since moxifloxacin and linezolid show large pharmacokinetic variability [1–4]. TDM of moxifloxacin focuses on identifying patients with low drug exposure who are at risk of treatment failure and acquired fluoroquinolone resistance [5, 6].
European Respiratory Journal 01/24/2020 06:56
While immunoglobulin E is a prominent biomarker for early-onset, its levels are often elevated in non-allergic late-onset asthma. However, the pattern of IgE expression in the latter is mostly polyclonal, with specific IgEs low or below detection level albeit an increased total IgE. In late-onset severe asthma patients, specific IgE to Staphylococcal enterotoxins (se-IgE) can frequently be detected in serum, and has been associated with asthma, with severe asthma defined by hospitalisations, oral steroid use and decrease in lung function. Recently, se-IgE was demonstrated to even predict the development into severe asthma with exacerbations over the next decade. S. aureus manipulates the airway mucosal immunology at various levels via its p.
European Respiratory Journal 01/24/2020 06:56
Background. Beyond the major gene BMPR2 , several new genes predisposing to PAH have been identified during the last decade. Recently, preliminary evidence of the involvement of the KDR gene was found in a large genetic association study. Methods. We prospectively analysed the KDR gene by targeted panel sequencing in a series of 311 PAH patients referred to a clinical molecular laboratory for genetic diagnosis of PAH. Results. Two index cases with severe PAH from two different families were found to carry a loss-of-function mutation in the KDR gene. These two index cases were clinically characterised by low diffusing capacity for carbon monoxide adjusted for hemoglobin (DLCOc) and interstitial lung disease. In one family, segregation analysis
European Respiratory Journal 01/24/2020 06:56
Increasing bacterial burden in the lower airways of patients with idiopathic pulmonary fibrosis confers an increased risk of disease progression and mortality. However, it remains unclear whether this increased bacterial burden directly influences progression of fibrosis or simply reflects the magnitude of the underlying disease extent or severity. We prospectively recruited 193 patients who underwent bronchoscopy and received a multidisciplinary diagnosis of idiopathic pulmonary fibrosis. Quantification of the total bacterial burden in bronchoalveolar lavage fluid was performed by 16S rRNA gene qPCR. Imaging was independently evaluated by two readers assigning quantitative scores for extent, severity and topography of radiographic changes
European Respiratory Journal 01/24/2020 06:56
Background. Clinical trials suggest less hepatotoxicity and better adherence with 4 months rifampin (4R) versus 9 months isoniazid (9H) for treating latent tuberculosis infection (LTBI). Our objectives were to compare frequencies of severe hepatic adverse events and treatment completion, and direct health system costs of LTBI regimens 4R and 9H, in the general population of the province of Quebec, Canada, using provincial health administrative data. Methods. Our retrospective cohort included all patients starting rifampin or isoniazid regimens between 2003 and 2007. We estimated hepatotoxicity from hospitalisation records, treatment completion from community pharmacy records, and direct costs from billing records and fee schedules. We compare.
European Respiratory Journal 01/24/2020 06:56
The presence of a systemic autoimmune rheumatic disease (ARD) is a well-known risk factor for interstitial lung disease (ILD). For example, 33% of adults with rheumatoid arthritis (RA) have subclinical ILD [1]. Higher serum levels of IgM rheumatoid factor (RF), IgA RF, and anti-cyclic citrullinated peptide antibody 2 are associated with subclinical ILD in community-dwelling adults [2]. It is unknown whether this relationship between autoimmunity and subclinical ILD is limited to RA-related autoantibodies, or extends more broadly to other epitopes. High attenuation areas (HAA) and interstitial lung abnormalities (ILA) are validated quantitative and qualitative subclinical ILD phenotypes, respectively.
European Respiratory Journal 01/23/2020 03:05
Bronchiectasis is a chronic and often progressive disease, which frequently is associated with significant symptom burden, requiring intensive treatment. Regardless of the multiple potential underlying aetiologies, the vicious cycle of airway inflammation, structural airway damage, impaired mucus clearance and airway pathogen acquisition is the crucial pathogenic pathway for the progression of disease [1].
European Respiratory Journal 01/23/2020 03:05
Marie Curie is a legendary figure: her research had huge impact on medicine, and she was the first woman to receive a Nobel Prize. In fact, she received two, one in Physics in 1903, and one in Chemistry in 1911, and so early in the history of Nobel Prizes (they were first awarded in 1901) a woman was a laureate. This was before women's suffrage in most parts of the world, and before any notion of gender equality, when few women had a chance to follow a career in science or medicine or get any education, and Marie Curie showed that it was possible. She was admired, respected and a role model for women in science. But still, more than 100 years later, few women have followed her footsteps: Between 1901 and 2018, there have been 902 Nobel laur.
European Respiratory Journal 01/23/2020 03:05
We read with interest the report of the results of the COPE-III trial by Lenferink et al. [1]. This large randomised trial continues on from the authors’ earlier COPE-II study [1], with personalised exacerbation action plans based on associated comorbidities. The action plans were detailed, and designed to determine symptom changes and the signs of an ensuing exacerbation. The study was negative for its primary endpoint (COPD exacerbation days) and no improvement in quality of life was found using the self-management intervention.
European Respiratory Journal 01/23/2020 03:05
The gender imbalance in medicine has been a topic of increasing interest and discussion. There are increasing proportions of graduating female medical students globally, with 41.1% of Australian doctors, 47% of UK doctors and 46% of medical residents in the USA being female [1, 2]. However, in positions of influence, the proportions change, such that in the USA only 21% of medical professors and 16% of medical deans are female [3]. Postulated reasons for this include implicit and unconscious gender bias and fewer promotion opportunities available to women.
European Respiratory Journal 01/23/2020 03:05
The Fleischner Society white paper and the American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) guidelines recently redefined the computed tomography (CT) scanning patterns of usual interstitial pneumonia (UIP) [1, 2].
European Respiratory Journal 01/23/2020 03:05
Management of progressive fibrotic interstitial lung diseases (ILDs) has long been limited to compensatory oxygen therapy and/or corticosteroids, but work in recent years has established the efficacy of new antifibrotic treatments in slowing the decline of patients with idiopathic pulmonary fibrosis [1].
European Respiratory Journal 01/23/2020 03:05
Background. Airway obstruction and wheezing in preschool children with recurrent viral infections are a major clinical problem, and are recognised as a risk factor for the development of chronic asthma. We aimed to analyse whether gene expression profiling provides evidence for pathways that delineate distinct groups of children with wheeze, and in combination with clinical information could contribute to diagnosis and prognosis of disease development. Methods. We analysed leukocyte transcriptomes from preschool children (6 months–3 years) at acute wheeze (n=107), and at a revisit 2–3 months later, comparing them to age-matched healthy controls (n=66). RNA-sequencing applying GlobinLock was used. The cases were followed clinically until age 7.
European Respiratory Journal 01/23/2020 03:05
Rationale. The lung mesenchyme gives rise to multiple distinct lineages of cells in the mature respiratory system, including smooth muscle cells of the airway and vasculature. However, a thorough understanding of the specification and mesenchymal cell diversity in the human lung is lacking. Methods. We completed single-cell RNA sequencing analysis of fetal human lung tissues. Canonical correlation analysis, clustering, cluster marker gene identification and t-distributed stochastic neighbour embedding representation was performed in Seurat. Cell populations were annotated using ToppFun. Immunohistochemistry and in situ hybridisation were used to validate spatiotemporal gene expression patterns for key marker genes. Results. We identified molec.

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