The Airway Microbiota in Cystic Fibrosis: A Complex Fungal and Bacterial Community—Implications for Therapeutic Management

International audienceBackground Given the polymicrobial nature of pulmonary infections in patients with cystic fibrosis (CF), it is essential to enhance our knowledge on the composition of the microbial community to improve patient management. In this study, we developed a pyrosequencing approach to extensively explore the diversity and dynamics of fungal and prokaryotic populations in CF lower airways. Methodology and Principal Findings Fungi and bacteria diversity in eight sputum samples collected from four adult CF patients was investigated using conventional microbiological culturing and high-throughput pyrosequencing approach targeting the ITS2 locus and the 16S rDNA gene. The unveiled microbial community structure was compared to the clinical profile of the CF patients. Pyrosequencing confirmed recently reported bacterial diversity and observed complex fungal communities, in which more than 60% of the species or genera were not detected by cultures. Strikingly, the diversity and species richness of fungal and bacterial communities was significantly lower in patients with decreased lung function and poor clinical status. Values of Chao1 richness estimator were statistically correlated with values of the Shwachman-Kulczycki score, body mass index, forced vital capacity, and forced expiratory volume in 1 s (p = 0.046, 0.047, 0.004, and 0.001, respectively for fungal Chao1 indices, and p = 0.010, 0.047, 0.002, and 0.0003, respectively for bacterial Chao1 values). Phylogenetic analysis showed high molecular diversities at the sub-species level for the main fungal and bacterial taxa identified in the present study. Anaerobes were isolated with Pseudomonas aeruginosa, which was more likely to be observed in association with Candida albicans than with Aspergillus fumigatus

Etude des patients adultes hospitalisés au CHRU de Lille pour suspicion de grippe A(H1N1)v pendant la pandémie 2009

LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

Variabilitätsmodellierung in Software Produktlinien Drei Lösungsansätze im Fokus

INTRODUCTION: The aim of this study was to gain insight into the physiological changes occurring in subjects with cystic fibrosis (CF) after autogenic drainage (AD). Changes in respiratory system resistance (Rrs), reactance (Xrs), and spirometry were analyzed in adult CF subjects after a single AD physiotherapy session. METHODS: This prospective observational study was conducted during the annual check-up of adult CF subjects in stable condition. Spirometry and Rrs and Xrs measurements using the forced oscillations technique at 5, 11, and 19 hertz (Hz) were performed before and 30 min after a 20-min AD session. Control CF subjects were tested at baseline and 50 min without AD. Results are expressed as mean ± standard deviation or median [interquartile range]. RESULTS: Thirty subjects were included in the physiotherapy group (age 29 [25-34] years, forced expiratory volume in 1 s (FEV1) 40.3 [30.1-57.9]% predicted) and 11 in the control group (age 31 [28.5-36.5] years, FEV1 43.6 [31.1-51.9] % predicted). No significant changes in any parameter were observed in the control group. AD modestly but significantly increased the forced vital capacity (FVC) and FEV1 (p<0.001). Inspiratory resistance was also significantly improved by AD: Rrs5 from 5.74±2.39 to 5.24±2.17 cmH2O/L/s, p<0.05; Rrs11 from 4.83±1.98 to 4.32±1.7 cmH2O/L/s, p = 0.003; and Rrs19 from 4.18 [3.46-5.07] to 3.86 [2.76-4.98] cmH2O/L/s, p<0.001. In contrast, AD had no significant effects on frequency dependence of resistance (Rrs5-Rrs19) or expiratory resistance. Inspiratory Xrs5, but not ΔXrs5 (expiratory-inspiratory Xrs), was improved by AD (p<0.05). Moderate correlations were detected between the improvement in FEV1 and FVC and inspiratory resistance (r = 0.53, p = 0.005 and r = 0.44, p = 0.02, respectively). CONCLUSION: A single session of AD improved inspiratory airway resistance, except in the distal airways. The forced oscillations technique provides a new tool for understanding the pathophysiological effects of airway clearance physiotherapy in CF

Influence of the nitric oxide donor glyceryl trinitrate on apoptotic pathways in human colon cancer cells

International audienc

Characteristics of the cystic fibrosis patients.

<p>Characteristics of the cystic fibrosis patients.</p

An educational intervention about the classification of penicillin allergies: effect on the appropriate choice of antibiotic therapy in pregnant women

International audienceBACKGROUND: Most pregnant women who self-report penicillin allergy are not truly penicillin-allergic and this misunderstanding often leads to administration of inappropriate antibiotic therapy. Decision algorithms have been developed to guide antibiotic selection but major discrepancies have been reported between guidelines and clinical practice. We aimed to optimize the prescription of antibiotics for pregnant women who self-reported penicillin allergy, using an educational intervention about the classification of penicillin allergies that targeted gynecologists, anesthesiologists and midwives.METHODS: This quasi-experimental study assessed the effect of an educational intervention about the classification of penicillin allergy. For six months, a combination of two strategies was used, namely dissemination of printed educational materials and group education. The principal study endpoint was the appropriateness of the antibiotic therapy, defined in advance for each level of allergic risk.RESULTS: The pre-intervention phase included 903 women; one year after its conclusion, the post-intervention phase began and included 892 women. The prevalence of self-reported penicillin allergy was stable over the two periods (6.8% before vs 5.4% after, P=0.24). The clinical classification of penicillin allergies was more often used after the educational intervention (68% vs 100%, P<0.001). The appropriateness of the antibiotic therapy prescribed to self-reported penicillin allergic-women increased significantly between the two periods, from 5/29 (17.2%) to 18/27 (66.7%, P<0.001).CONCLUSIONS: An educational intervention about penicillin allergy classification was associated with an improvement in the choice of appropriate antibiotic therapy among women who had reported penicillin allergy

Individual values of inspiratory resistances before and after autogenic drainage in 30 CF patients.

<p>A, Rrs_5; B, Rrs_11; C, Rrs_19; D, Rrs₅–Rrs₁₉.</p

First Wave of COVID-19 in French Patients with Cystic Fibrosis

International audienceViral infections are known to lead to serious respiratory complications in cystic fibrosis (CF) patients. Hypothesizing that CF patients were a population at high risk for severe respiratory complications from SARS-CoV-2 infection, we conducted a national study to describe the clinical expression of COVID-19 in French CF patients. This prospective observational study involves all 47 French CF centers caring for approximately 7500 CF patients. Between March 1st and June 30th 2020, 31 patients were diagnosed with COVID-19: 19 had positive SARS-CoV-2 RT-PCR in nasopharyngeal swabs; 1 had negative RT-PCR but typical COVID-19 signs on a CT scan; and 11 had positive SARS-CoV-2 serology. Fifteen were males, median (range) age was 31 (9–60) years, and 12 patients were living with a lung transplant. The majority of the patients had CF-related diabetes (n = 19, 61.3%), and a mild lung disease (n = 19, 65%, with percent-predicted forced expiratory volume in 1 s (ppFEV1) > 70). Three (10%) patients remained asymptomatic. For the 28 (90%) patients who displayed symptoms, most common symptoms at admission were fever (n = 22, 78.6%), fatigue (n = 14, 50%), and increased cough (n = 14, 50%). Nineteen were hospitalized (including 11 out of the 12 post-lung transplant patients), seven required oxygen therapy, and four (3 post-lung transplant patients) were admitted to an Intensive Care Unit (ICU). Ten developed complications (including acute respiratory distress syndrome in two post-lung transplant patients), but all recovered and were discharged home without noticeable short-term sequelae. Overall, French CF patients were rarely diagnosed with COVID-19. Further research should establish whether they were not infected or remained asymptomatic upon infection. In diagnosed cases, the short-term evolution was favorable with rare acute respiratory distress syndrome and no death. Post-lung transplant patients had more severe outcomes and should be monitored more closely. View Full-Tex

Rarefaction curves.

<p>These curves are representing the numbers of OTUs with respect to the number of pyrosequence reads obtained from each patient at different sampling times and using the two set of primers targeting prokaryotic 16S rDNA (A) and fungal ITS2 (B) loci.</p

Clinical response to lumacaftor-ivacaftor in patients with cystic fibrosis according to baseline lung function

International audienceBackground: Phase 3 trials have demonstrated the safety and efficacy of lumacaftor-ivacaftor (LUMA-IVA) in patients with cystic fibrosis (CF) homozygous for the Phe508del CFTR mutation and percent predicted forced expiratory volume in 1 s (ppFEV1) between 40 and 90. Marketing authorizations have been granted for patients at all levels of ppFEV1.Methods: To evaluate the safety and effectiveness of LUMA-IVA over the first year of treatment in patients with ppFEV1<40 or ppFEV1≥90 in comparison with those with ppFEV1 [40-90[. Analysis of data collected during a real world study, which included all patients aged ≥12 years who started LUMA-IVA in 2016 across all 47 French CF centers.Results: 827 patients were classified into 3 subgroups according to ppFEV1 at treatment initiation (ppFEV1<40, n = 121; ppFEV1 [40-90[, n = 609; ppFEV1≥90, n = 97). Treatment discontinuation rate was higher in ppFEV1<40 patients (28.9%) than in those with ppFEV1 [40-90[(16.4%) or ppFEV1≥90 (17.5%). In patients with uninterrupted treatment, significant increase in ppFEV1 occurred in the ppFEV1 [40-90[subgroup (+2.9%, P<0.001), and in those ppFEV1<40 (+0.5%, P = 0.03) but not in those with ppFEV1≥90 (P = 0.46). Compared with the year prior to initiation, the number of days of intravenous antibiotics were reduced in all subgroups, although 72% of patients with ppFEV1<40 still experienced at least one exacerbation/year under LUMA-IVA. Comparable increase in body mass index was seen in the three subgroups.Conclusion: Phe508del homozygous CF patients benefit from LUMA-IVA at all levels of baseline lung function, but the characteristics and magnitude of the response vary depending on ppFEV1 at baseline