Lipoxin A4 and interleukin-8 levels in cystic fibrosis sputum after antibiotherapy

AbstractAntibiotics are largely prescribed for cystic fibrosis (CF) respiratory exacerbations. Effects of antibiotics on the inflammatory profile of the patients have been shown but remain controversial. Lipoxin A4 (LXA4) is a lipid mediator, reported to play a central role in resolving airway inflammation. The aim of the study was to investigate the consequences of antibiotherapy on LXA4 and IL-8 levels in CF patients' airways.MethodsEighteen CF patients (7 females, median age 20, range 8 to 47 years) consecutively admitted at the CF center of Montpellier for antibiotics during pulmonary exacerbation, were enrolled. Before and after antibiotics, all patients underwent spirometry (FEV1 and FVC), bacterial cultures and cell counts in sputa. IL-8 and LXA4 concentrations were determined in sputum samples by the median of immunometric assays.ResultsAs previously reported, after antibiotics therapy, FEV1 and FVC significantly improved. While neutrophil cell counts and IL-8 levels decreased, the LXA4 levels significantly increased after antibiotics therapy and were inversely correlated with IL-8 levels.In conclusion, we reported a correlation between antibiotics treatments and inflammatory markers in CF sputum. Our data provide evidences for a novel effect of antibiotics increasing the concentration of the anti-inflammatory lipid mediator LXA4

Looking back, looking forward: Methodological challenges and future directions in research on persons with profound intellectual and multiple disabilities

Within the context of the Special Interest Research Group (SIRG) on Persons with Profound Intellectual and Multiple Disabilities (PIMD), researchers often discuss the methodological problems and challenges they are confronted with. The aim of the current article was to give an overview of these challenges. The challenges are centred on six topics. These reflect the main components of a study's design: (a) participant demarcation, (b) participant recruitment, (c) data collection and instruments, (d) data analysis, (e) ethics/including the “voice” of persons with PIMD and (f) theoretical models. Next, to describing the specific challenges, possible solutions and pathways to address them are discussed. These are illustrated by recent studies by the authors and other researchers in the field. The current contribution wants to stimulate further discussion and ex-change of ideas, and the development of creative research techniques

Antiviral TRIMs: friend or foe in autoimmune and autoinflammatory disease?

The concept that viral sensing systems, via their ability to drive pro-inflammatory cytokine and interferon production, contribute to the development of autoimmune and autoinflammatory disease is supported by a wide range of clinical and experimental observations. Recently, the tripartite motif-containing proteins (TRIMs) have emerged as having key roles in antiviral immunity — either as viral restriction factors or as regulators of pathways downstream of viral RNA and DNA sensors, and the inflammasome. Given their involvement in these pathways, we propose that TRIM proteins contribute to the development and pathology of autoimmune and autoinflammatory conditions, thus making them potential novel targets for therapeutic manipulation

Plasma cell-free DNA testing of patients with EGFR mutant non–small-cell lung cancer: Droplet digital PCR versus next-generation sequencing compared with tissue-based results

PURPOSE To compare the results of plasma cell-free DNA (cfDNA) droplet digital PCR (ddPCR) and next-generation sequencing (NGS) on detection of epidermal growth factor receptor (EGFR) primary activating mutations and p.T790M with results of tissue analysis in patients with EGFR mutated non–small-cell lung cancer. METHODS All patients with EGFR mutated non–small cell lung cancer for which a pathology and a plasma specimen were available upon progression between November 2016 and July 2018 were selected. Concordance, Cohen’s κ, and intraclass correlation coefficients were calculated. RESULTS Plasma cfDNA and pathology specimens of 36 patients were analyzed. Agreement between ddPCR and NGS was 86% (κ = 0.63) for the primary activating mutation and 94% (κ = 0.89) for the p.T790M detection. Allele ratios were comparable, with an intraclass correlation coefficient of 0.992 and 0.997, respectively. Discrepancies of some degree were found in 15 patients (41.7%). In six patients (16.7%), no mutations were detected in cfDNA. In three patients (8.3%), p.T790M was detected in plasma but not in the pathology specimen, whereas in three other patients (8.3%), p.T790M was demonstrated in the pathology specimen but not in plasma. Concordance of cfDNA and pathology for the primary activating mutation was 69% for ddPCR and 83% for NGS. For the detection of p.T790M, this was 75% (κ = 0.49) for ddPCR as well as for NGS. CONCLUSION Mutual agreement is high between NGS and ddPCR in cfDNA on the level of a specific mutation, with comparable ratio results. Plasma testing of EGFR primary activating mutations and p.T790M shows high concordance with pathology results, for NGS as well as for ddPCR, depending on the extent of the panel used. In NGS, more genetic aberrations can be investigated at once