Search

Objectives: Lumacaftor-ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator known to improve clinical status in people with cystic fibrosis (CF). The aim of this study was to assess lung structural changes after 1 year of lumacaftor-ivacaftor treatment and to use unsupervised machine learning to identify morphological phenotypes of lung disease that are associated with response to lumacaftor-ivacaftor., Methods: Adolescents and adults with CF from a French multicentre real-world prospective observational study evaluating the first year of treatment with lumacaftor-ivacaftor were included if they had pre-therapeutic and follow-up chest computed tomography (CT) scans available. CT scans were visually scored using a modified Bhalla score. A k-means clustering method was performed based on 120 radiomics features extracted from unenhanced pre-therapeutic chest CT scans., Results: In total, 283 patients were included. The Bhalla score significantly decreased after 1 year of lumacaftor-ivacaftor (-1.40±1.53 points compared with pre-therapeutic CT, p<0.001). This finding was related to a significant decrease in mucus plugging (-0.58±0.88 points, p<0.001), bronchial wall thickening (-0.35±0.62 points, p<0.001) and parenchymal consolidations (-0.24±0.52 points, p<0.001). Cluster analysis identified three morphological clusters. Patients from cluster C were more likely to experience an increase in per cent predicted forced expiratory volume in 1 s (FEV 1 % pred) ≥5% under lumacaftor-ivacaftor than those in the other clusters (54% of responders versus 32% and 33%; p=0.02)., Conclusion: 1-year treatment with lumacaftor-ivacaftor was associated with a significant visual improvement of bronchial disease on chest CT. Radiomics features on pre-therapeutic CT scans may help to predict lung function response under lumacaftor-ivacaftor., Competing Interests: Conflict of interest: A. Campredon has nothing to disclose. Conflict of interest: E. Battistella has nothing to disclose. Conflict of interest: C. Martin reports lecture payments or honoraria from Chiesi and Zambon, outside the submitted work. Conflict of interest: I. Durieu has nothing to disclose. Conflict of interest: L. Mely has nothing to disclose. Conflict of interest: C. Marguet reports consulting fees from Gleamer; lecture payments or honoraria from Vertex, Viatis and Zambon; support for attending meetings and/or travel from Zambon; and participation on a Data Safety Monitoring Board or Advisory Board for Zambon and Viatis; outside the submitted work. Conflict of interest: C. Belleguic has nothing to disclose. Conflict of interest: M. Murris-Espin has nothing to disclose. Conflict of interest: R. Chiron has nothing to disclose. Conflict of interest: A. Fanton has nothing to disclose. Conflict of interest: S. Bui reports payment for expert testimony for inhaled antibiotics for Zambon, outside the submitted work. Conflict of interest: M. Reynaud-Gaubert has nothing to disclose. Conflict of interest: P. Reix has nothing to disclose. Conflict of interest: T-N. Hoang-Thi has nothing to disclose. Conflict of interest: M. Vakalopoulou has nothing to disclose. Conflict of interest: M-P. Revel has nothing to disclose. Conflict of interest: J. Da Silva has nothing to disclose. Conflict of interest: P-R. Burgel reports grants or contracts from Vertex and GSK; consulting fees from AstraZeneca, Chiesi, GSK, Insmed, Vertex and Zambon; and lecture payments or honoraria from Pfizer and Novartis; outside the submitted work. Conflict of interest: G. Chassagnon reports lecture payments or honoraria from Chiesi, outside the submitted work., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: We assessed the diagnostic performances of homeostasis model assessment indices (HOMA) of β-cell function (HOMA-%β) and of insulin resistance (HOMA-IR) for cystic fibrosis related diabetes (CFRD) screening., Methods: Data were collected from a prospective cohort of 228 patients with CF (117 adults and 111 children). Fasting insulin and glucose levels were measured to calculate HOMA-%β and HOMA-IR. HOMA-%β <100 indicated insulin secretion deficiency and HOMA-IR >1 insulin resistance. Both were used to calculate sensitivity, specificity, and positive and negative predictive values (PPV and NPV). Two-hour oral glucose tolerance tests (2h-OGTT) defined CFRD. Analyses were conducted separately for children and adults. Performances of HOMA-%β and HOMA-IR were calculated at inclusion, for each year of follow-up and for pooled data over the follow-up period., Results: Sensitivity, specificity, NPV and PPV were respectively: 88%, 45%, 98% and 11% for HOMA-%β and 42%, 48%, 91% and 6% for HOMA-IR in the pooled data of children; and 83%, 18%, 90% and 10% for HOMA-%β, and 39%, 80%, 92% and 18% for HOMA-IR in the pooled data of adults. Combining HOMA-%β and HOMA-IR did not improve performances., Conclusion: Within both age groups, HOMA-%β <100 provided good sensitivity and NPV. HOMA-IR >1 had low sensitivity. Calculation of the HOMA-%β could be an interesting first-line screening approach to exclude CFRD and thus avoid unnecessary OGTT in patients for whom value is ≥100. However, HOMA-%β<100 does not support the diagnosis of CFRD and should be complemented by OGTT., Competing Interests: Declaration of Competing Interest None, (Copyright © 2021. Published by Elsevier B.V.)

Background: Adult patients with cystic fibrosis (CF) experience daily physical symptoms and disabilities that can be challenging to address for health care teams., Methods: We sought to identify the most frequent topics that CF adults need to discuss with health care teams using a custom questionnaire including 62 items., Results: Fifty patients were included, 70% men, mean age 27.6 years, with a mean body mass index of 21.8 kg/m 2 . Mean FEV 1 % was 64% of predicted value. Forty-two percent of patients selected at least one topic. The most frequently selected topics were fatigue (20%), professional or scholar worries (18%), procreation (16%), physical activities (16%) and evolution of CF disease (16%). Women were more frequently concerned about fatigue, procreation and profession/school., Conclusions: Using a custom questionnaire, we identified that CF adults express various unmet needs that extend beyond usual respiratory and nutritional concerns or treatment adherence. The interest of this questionnaire by health care team for improving therapeutic management of CF patients remains to be validated., Trial Registration: The study was registered on ClinicalTrials.gov (NCT02924818) on 5th October 2016., (© 2021. The Author(s).)

The transition from childhood to adulthood means physical and psychological upheaval. The Safetim study, in a multi-professional team, is looking at the ideal transition for cystic fibrosis patients. Synthesis of the literature on the subject., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: Cystic fibrosis (CF) is a life-shortening genetic condition that usually affects several organs and involves significant treatment burden. Adherence to medication is important for successful CF management., Objective: To describe medication adherence according to age, therapeutic class, and pharmaceutical form in adults and children followed in four regional CF centers in France., Methods: We conducted a cross-sectional study with non-transplanted patients followed in two adult and two pediatric centers during 2015 who were covered by the French National Health Insurance (NHI). Sociodemographic, clinical, hospitalization, and prescription data were collected from patient medical records. Medication dispensations were extracted from the regional French NHI database. Adherence was calculated over 12 months using continuous medication availability (CMA) accounting for dose adjustments and hospitalizations. Drug-specific CMA was computed in R with the AdhereR package for each medication prescribed more than 3 months, which was averaged to obtain a composite CMA score (cCMA) for all treatments and per therapeutic class as well as pharmaceutical form for each patient., Results: A total of 228 patients were included. The number of chronic medications increased with age ( r =0.50, p <0.001): a median of 7 medications per patient were prescribed. The mean±SD cCMA was significantly different between age groups ( p =0.0098): it was 0.71±0.20 for the 0-5 years age group, 0.73±0.16 for 6-11 years, 0.64±0.17 for 12-17 years, 0.57±0.23 for 18-25 years, and 0.65±0.20 for the over 25 years age group. cCMA varied significantly according to pharmaceutical forms: the mean±SD cCMA was 0.70±0.21 for oral medications and 0.54±0.28 for inhaled medications ( p <0.001)., Conclusion: This study suggests that adherence to medication regimens in CF patients remains suboptimal and varies substantially between age groups and pharmaceutical forms. These variations in adherence should be considered when developing effective strategies to improve adherence., Competing Interests: Alexandra Lelia Dima report grants and non-financial support from Respiratory Effectiveness Group, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2019 Rouzé et al.)

Fungal respiratory colonization of cystic fibrosis (CF) patients emerges as a new concern; however, the heterogeneity of mycological protocols limits investigations. We first aimed at setting up an efficient standardized protocol for mycological analysis of CF sputa that was assessed during a prospective, multicenter study: "MucoFong" program (PHRC-06/1902). Sputa from 243 CF patients from seven centers in France were collected over a 15-month period and submitted to a standardized protocol based on 6 semi-selective media. After mucolytic pretreatment, sputa were plated in parallel on cycloheximide-enriched (ACT37), erythritol-enriched (ERY37), benomyl dichloran-rose bengal (BENO37) and chromogenic (CAN37) media incubated at 37 °C and on Sabouraud-chloramphenicol (SAB27) and erythritol-enriched (ERY27) media incubated at 20-27 °C. Each plate was checked twice a week during 3 weeks. Fungi were conventionally identified; time for detection of fungal growth was noted for each species. Fungal prevalences and media performances were assessed; an optimal combination of media was determined using the Chi-squared automatic interaction detector method. At least one fungal species was isolated from 81% of sputa. Candida albicans was the most prevalent species (58.8%), followed by Aspergillus fumigatus (35.4%). Cultivation on CAN37, SAB27, ACT37 and ERY27 during 16 days provided an optimal combination, detecting C. albicans, A. fumigatus, Scedosporium apiospermum complex and Exophiala spp. with sensitivities of 96.5, 98.8, 100 and 100%. Combination of these four culture media is recommended to ensure the growth of key fungal pathogens in CF respiratory specimens. The use of such consensual protocol is of major interest for merging results from future epidemiological studies.

Allergic bronchopulmonary aspergillosis (ABPA) is a frequent complication in cystic fibrosis patients. The diagnosis remains difficult and requires a combination of clinical, radiological, biological, and mycological criteria. The aim of this study was to analyze the added value of two recombinant antigens, rAspf4 and rAspf6, associated with the detection of specific IgG; precipitins; total IgE; and Aspergillus fumigatus in sputum for the diagnosis of ABPA. In a retrospective study, we determined the specific IgE responses to these recombinants in 133 sera of 65 cystic fibrosis patients. We selected an average of five serum samples from each of the 17 patients with ABPA (13 proven and 4 probable ABPA) and from 3 patients with Aspergillus bronchitis and rhinosinusitis. One serum sample for the 45 patients without ABPA was tested. The sensitivity of specific IgE detection against rAspf4 calculated per patient (92.3%) was significantly higher (P < 0.05) than that of rAspf6 (53.8%). When rAspf4 IgE detection was associated with anti-Aspergillus IgG enzyme-linked immunosorbent assay (ELISA) and precipitin detection, the sensitivity rose to 100%. The specificities of rAspf4 and rAspf6 IgE detection were 93.7% and 91.6%, respectively. Other diagnostic criteria had slightly lower specificities (87.5% for anti-Aspergillus IgG ELISA, 89.6% for precipitins, 84.4% for total IgE, and 85.0% for positive A. fumigatus culture in sputum). In conclusion, this retrospective study showed the relevance of rAspf4 IgE detection, in combination with other biological markers (Aspergillus IgG ELISA, precipitins, and total IgE), for improving the biological diagnosis of ABPA.