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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: Mycobacterium massiliense is closely related to Mycobacterium abscessus and is also a frequent cause of mycobacterial lung disease in patients with cystic fibrosis (CF). There has been no previous investigation of possible differences between M. massiliense and M. abscessus infections in the setting of CF., Methods: We studied a prospective cohort of 16 M. massiliense and 27 M. abscessus lung infection cases with CF, with a mean follow-up of 6 years., Results: M. massiliense cases were younger than M. abscessus cases (mean age: 12.8 vs 17.1 years; p=0.02) at the time of the first mycobacterial isolation and also had lower body mass index values (mean: 16.4 vs 19.3 kg/m(2), p=0.002). All M. massiliense cases, except one, had negative BMI Z-score values at the time of the first mycobacterial isolation (11/12 vs 16/23 M. abscessus cases, p=0.04). Clarithromycin-based combination therapies led to mycobacterial eradication in 100% of M. massiliense cases but only in 27% of M. abscessus cases (p=0.009)., Conclusion: Our data show a particular link between M. massiliense and malnutrition specifically in CF patients. Unlike M. abscessus, the bacteriological response of M. massiliense to combination antibiotic therapies containing clarithromycin was excellent. Distinguishing between M. massiliense and M. abscessus has major clinical implications for CF patients., (Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Catheter venous thrombosis may result in life-threatening embolic complications. Recently, a thrombophilic tendency was described in cystic fibrosis (CF), the significance of which remains unclear. The aims of this study were to (1) document the frequency of catheter venous thrombosis detected by colour-Doppler-ultrasound (Doppler-US), (2) assess genetic and acquired thrombophilia risk factors for catheter venous thrombosis and hypercoagulability status and (3) provide recommendations on laboratory screening when considering insertion of a totally implantable vascular access device (TIVAD) in CF patients., Methods: We designed a multicentre prospective study in patients selected at the time of catheter insertion. Doppler-US was scheduled at 1 and 6months after insertion and before insertion in case of a previous central line. Blood samplings were drawn at insertion and at 1 and 6months later., Results: One-hundred patients received a TIVAD and 90 completed the 6-month study. Prevalence of thrombophilia abnormalities and hypercoagulability was found in 50% of the cohorts. Conversely, catheter venous thrombosis frequency was low (6.6%)., Conclusion: Our data do not support biological screening at the time of a TIVAD insertion. We emphasise the contribution of a medical history of venous thromboembolism and prospective Doppler-US for identifying asymptomatic catheter venous thrombosis to select patients who may benefit from biological screening and possible anticoagulant therapy., (Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

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.

Pulmonary function tests have rarely been assessed in preschool children with cystic fibrosis (CF). The objective of this multicenter study was to compare pulmonary function in 39 preschool children with CF (height, 90-130 cm; 16 homozygous Delta F508) and in 79 healthy control children. Functional residual capacity (helium dilution technique) and expiratory interrupter resistance (Rint(exp)) (interrupter technique) were measured. As compared with control children, children with CF had significantly higher Rint(exp), expressed as absolute values and as Z-scores (1.05 +/- 0.36 versus 0.80 +/- 0.20 kPa.L(-1). second, p < 0.0001; and 1.31 +/- 1.72 versus 0.19 +/- 0.97, p < 0.0001), and significantly lower specific expiratory interrupter conductance (1.29 +/- 0.34 versus 1.63 +/- 0.43 kPa(-1). second, p < 0.0001). The effect of the bronchodilator salbutamol on Rint(exp) was not significantly different between children with CF and control children. Rint(exp) Z-scores were significantly higher in children with CF who were exposed to passive smoke (n = 8) (p < 0.03). Children with CF and with a history of respiratory symptoms (n = 31) had significantly higher functional residual capacity Z-scores (p < 0.02) and lower specific expiratory interrupter conductance Z-scores (p < 0.04). Genotype did not influence the data. We conclude that Rint(exp) and functional residual capacity measurements may help to follow young children with CF who are unable to perform reproducible forced expiratory maneuvers.

Introduction: Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator that has demonstrated clinical benefits in phase 3 trials. We report results from a real-world study (BRIO) to assess the effectiveness of ivacaftor in people with cystic fibrosis (pwCF) in France. Methods: BRIO was an observational study conducted at 35 centers in France. Both pwCF initiating ivacaftor treatment and those already taking ivacaftor were included and prospectively followed for 24 months. The primary objective was to evaluate the effect of ivacaftor on percent predicted forced expiratory volume in 1 s (ppFEV1); secondary objectives were evaluating the effect of ivacaftor on clinical effectiveness, healthcare resource utilization (HCRU), and safety. Results: A total of 129 pwCF were enrolled; 58.9% were aged < 18 years; 64.3% had a G551D-CFTR allele. Mean age at ivacaftor initiation was 19.1 years (range, 2–64 years); ppFEV1 increased by a least squares mean of 8.49 percentage points in the first 6 months and was sustained through 36 months of ivacaftor use. Growth metrics increased during the first 12 months post-ivacaftor and remained stable. The rate of pulmonary exacerbations (PEx) decreased during the 12 months post-ivacaftor compared with the 12 months pre-ivacaftor; estimated rate ratios (95% CI) were 0.57 (0.43–0.75) for PEx events and 0.25 (0.13–0.48) for PEx requiring hospitalization. No new safety concerns were identified; no deaths occurred. Conclusions: The results from this real-world study of ivacaftor usage in France were consistent with prior clinical trial outcomes, confirming the clinical effectiveness of ivacaftor, as well as an associated reduction in HCRU. [ABSTRACT FROM AUTHOR]

Lung infections play a critical role in cystic fibrosis (CF) pathogenesis. CF respiratory tract is now considered to be a polymicrobial niche and advances in high-throughput sequencing allowed to analyze its microbiota and mycobiota. However, no NGS studies until now have characterized both communities during CF pulmonary exacerbation (CFPE). Thirty-three sputa isolated from patients with and without CFPE were used for metagenomic high-throughput sequencing targeting 16S and ITS2 regions of bacterial and fungal rRNA. We built inter-kingdom network and adapted Phy-Lasso method to highlight correlations in compositional data. The decline in respiratory function was associated with a decrease in bacterial diversity. The inter-kingdom network revealed three main clusters organized around Aspergillus, Candida, and Scedosporium genera. Using Phy-Lasso method, we identified Aspergillus and Malassezia as relevantly associated with CFPE, and Scedosporium plus Pseudomonas with a decline in lung function. We corroborated in vitro the cross-domain interactions between Aspergillus and Streptococcus predicted by the correlation network. For the first time, we included documented mycobiome data into a version of the ecological Climax/Attack model that opens new lines of thoughts about the physiopathology of CF lung disease and future perspectives to improve its therapeutic management. [ABSTRACT FROM AUTHOR]