Health care resource utilization preceding death or lung transplantation in people with cystic fibrosis: HCRU before transplant or death in cystic fibrosis.

BACKGROUND: We studied the health care resource utilization (HCRU) and associated costs in the year preceding LT in pwCF or death without LT, and we estimated the overall cost of LT. METHODS: We performed a linkage between 2006 and 2017 data from the French CF Registry (FCFR) and the French health claims database (Système National des Données de Santé; SNDS). The HCRU and associated costs were described the year before LT or before death without LT, and two years after LT. RESULTS: Among the 7,671 patients included in the FCFR, 6,187 patients (80.7 %) were successfully matched to patients in the SNDS (males (m): 51.9 %, mean±SD age at the end of follow-up: 24.6 ± 13.6). Overall, 166 patients died without LT (m: 47.6 %, age at death: 30.4 ± 14.5) and 767 patients with primary LT (m: 48.2 %, age at transplantation: 28.0 ± 9.1) were identified. HCRU was lower among patients who died without receiving LT, with marked differences in the cost of hospital stays. The mean total cost per patient was €66,759 ± 38,249 in the year before death, €149,374 ± 62,678 in the year preceding LT, €63,919 ± 35,399 in the first year following LT, and €42,813 ± 39,967 in the second year of follow-up. CONCLUSION: Our results indicate that HCRU was two times lower in the year before death in non-transplant pwCF than in the year before LT, which may reflect inappropriate care of CF in patients who died without receiving LT. It also shows the cost associated with LT.

A Participatory Approach Involving Patients with Cystic Fibrosis and Healthcare Professionals for the Co-Design of an Adherence-Enhancing Intervention Toolkit.

Purpose: Cystic fibrosis (CF) is an inherited life-shortening disease involving a significant treatment burden. Few interventions have been proven effective in improving adherence, and of these fewer have been adopted for implementation. Patient participation in research is increasingly desired in developing relevant health care services. A participatory approach was implemented in an adult CF center to co-design an adherence-enhancing intervention toolkit. We aimed to report on the participatory process and the results regarding the co-designed intervention. Patients and Methods: Two focus group sessions and four working sessions were conducted at 4-week intervals with three healthcare professionals (HCP; physician, nurse, physiotherapist), eight patients, and two researchers (sociologist, public health pharmacist). The two initial focus group sessions were dedicated to the collection of narratives about CF treatment experiences to identify drivers of adherence. The next four working sessions were dedicated to the reflection on solutions that could alleviate the difficulties identified and be used in current clinical practice. The researchers observed during all sessions the interactions between participants, group dynamics, and process of implementation of the collective reflection. Results: The process facilitated an active participation of patients and HCP, who contributed equally to the intervention development. The co-design adherence-enhancing intervention toolkit consisted in a self-questionnaire to be completed by patients before the medical consultation and used as a communication support during the consultation, plus a toolkit of solutions to be proposed by the HCP for each barrier identified by patients, and to be followed up during the next consultation. Conclusion: This study demonstrated that a participatory approach involving CF patients and HCP lead to the development of an adherence-enhancing intervention toolkit, using a 6-session format; the benefits of the co-designed intervention on the medication adherence have yet to be tested in a multicenter, open-label study in 3 centers in France.

Screening strategies for glucose tolerance abnormalities and diabetes in people with cystic fibrosis.

The increase in life expectancy of patients with cystic fibrosis has come with new comorbidities, particularly diabetes. The gradual development of glucose tolerance abnormalities means that 30 to 40% of adults will be diabetic. Cystic fibrosis-related diabetes is a major challenge in the care of these patients because it is a morbidity and mortality factor at all stages of the disease. Early glucose tolerance abnormalities observed from childhood, before the stage of diabetes, are also associated with a poor pulmonary and nutritional outcome. The long asymptomatic period justifies systematic screening with an annual oral glucose tolerance test from the age of 10 years. However, this strategy does not take into account the new clinical profiles of patients with cystic fibrosis, recent pathophysiological knowledge of glucose tolerance abnormalities, and the emergence of new diagnostic tools in diabetology. In this paper, we summarise the challenges of screening in the current context of new patient profiles - patients who are pregnant, have transplants, or are being treated with fibrosis conductance transmembrane regulator modulators - and put forward an inventory of the various screening methods for cystic fibrosis-related diabetes, including their applications, limitations and practical implications.

Reproductive health after thoracic transplantation: An ISHLT expert consensus statement.

Pregnancy after thoracic organ transplantation is feasible for select individuals but requires multidisciplinary subspecialty care. Key components for a successful pregnancy after lung or heart transplantation include preconception and contraceptive planning, thorough risk stratification, optimization of maternal comorbidities and fetal health through careful monitoring, and open communication with shared decision-making. The goal of this consensus statement is to summarize the current evidence and provide guidance surrounding preconception counseling, patient risk assessment, medical management, maternal and fetal outcomes, obstetric management, and pharmacologic considerations.

[Therapeutic advances in cystic fibrosis: from genetics to treatment personalized]. / Avancées thérapeutiques dans la mucoviscidose : de la génétique au traitement personnalisé.

THERAPEUTIC ADVANCES IN CYSTIC FIBROSIS: FROM GENETICS TO TREATMENT PERSONALIZED. Cystic fibrosis is a severe monogenic disease that affects around 7 300 patients in France. Mutations (> 2 000) in CFTR, the gene encoding for an epithelial ion channel that normally transports chloride and bicarbonate ions, lead to mucus dehydration and impaired bronchial clearance and pancreatic functions. Systematic neonatal screening in France has allowed early diagnosis since 2002. Although highly restrictive, supportive treatments including daily chest physiotherapy, inhaled aerosol therapy, frequent antibiotic courses, nutritional and pancreatic extracts have improved the prognosis. Median age at death is now beyond 30 years of age. Ivacaftor was the first CFTR potentiator found to both reduce sweat chloride concentrations and improve pulmonary function. Then, combinations of a potentiator and various correctors such as lumacaftor + ivacaftor or tezacaftor + ivacaftor have been tested. Finally, the triple association ivacaftor + tezacaftor + elexacaftor was recently shown to normalize sweat chloride concentration, significantly improve pulmonary function testing, reduce the need for antibiotic treatments, and ultimately improve the quality of life in patients with at least oneF508del mutation (83% of patients in France).

AVANCÉES THÉRAPEUTIQUES DANS LA MUCOVISCIDOSE : DE LA GÉNÉTIQUE AU TRAITEMENT PERSONNALISÉ. La mucoviscidose est une maladie monogénique affectant environ 7 300 patients en France. Plus de 2 000 mutations dans le gène CFTR codant pour la protéine CFTR, canal épithélial qui transporte les ions chlorure et bicarbonate, conduisent à la production d'un mucus déshydraté et visqueux qui altère les fonctions respiratoire et pancréatique. Le dépistage néonatal est systématique en France depuis 2002. Bien que très contraignants, les traitements symptomatiques ont permis de porter l'âge médian au décès au-delà de 30 ans. L'ivacaftor, un potentiateur de la fonction CFTR, a été le premier médicament à faire la preuve de son efficacité, avec une diminution nette des symptômes. Puis ont été testées les combinaisons d'un potentiateur et de correcteurs de la protéine CFTR : lumacaftor-ivacaftor ou tezacaftor-ivacaftor. Enfin, la triple association ivacaftor-tezacaftor- elexacaftor a permis de normaliser la teneur en chlorure sudoral (biomarqueur de la fonction protéique CFTR au niveau des glandes sudorales), d'améliorer durablement la fonction respiratoire (VEMS), de diminuer les exacerbations pulmonaires et la consommation d'antibiotiques chez les patients homozygotes ou hétérozygotes composites pour la mutation F508del (83 % des patients en France).

Cancer incidence and prevalence in cystic fibrosis patients with and without a lung transplant in France.

Background: Cystic fibrosis (CF) care and the life expectancy of affected patients have substantially improved in recent decades, leading to an increased number of patients being diagnosed with comorbidities, including cancers. Our objective was to characterize the epidemiology of cancers between 2006 and 2017 in CF patients with and without a lung transplant. Methods: Medical records of CF patients from 2006 to 2016 in the French CF Registry were linked to their corresponding claims data (SNDS). The annual prevalence and incidence rates of cancers were estimated from 2006 to 2017 in CF patients without lung transplant and in those with lung transplant after transplantation. Results: Of the 7,671 patients included in the French CF Registry, 6,187 patients (80.7%) were linked to the SNDS; among them, 1,006 (16.3%) received a lung transplant. The prevalence of any cancer increased between 2006 and 2017, from 0.3 to 1.0% and from 1.3 to 6.3% in non-transplanted and transplanted patients, respectively. When compared to the general population, the incidence of cancer was significantly higher in both non-transplanted [Standardized Incidence Ratio (SIR) = 2.57, 95%CI 2.05 to 3.17] and transplanted (SIR = 19.76, 95%CI 16.45 to 23.55) patients. The median time between transplant and the first cancer was 3.9 years. Among the 211 incident cancer cases, the most frequent malignant neoplasms were skin neoplasm (48 cases), lung cancers (31 cases), gastro-intestinal (24 cases), and hematologic cancers (17 cases). Conclusion: The overall burden of cancer in CF patients is high, particularly following lung transplantation. Therefore, specific follow-up, screening and cancer prevention for CF patients with transplants are necessary.

Anakinra for the Treatment of Hemophagocytic Lymphohistiocytosis: 21 Cases.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening cytokine storm syndrome. There are no definitive guidelines for the management of secondary HLH (sHLH). A recent report by a National Health Service (NHS) clinical panel has recommended anakinra as a treatment option. We aimed to analyse the efficacy and safety of anakinra for the treatment of all-cause sHLH. We conducted a multicentric retrospective study in two French University hospitals and included all patients who had a diagnosis of sHLH and who received anakinra. Among 21 patients (median age, 45 years), 13 were men. Anakinra was used as first-line therapy in 10 patients, and as monotherapy in 5 patients. We found that anakinra was effective in 19/21 patients (90.5%), with fever resolution in 19 patients (90.5%) within a median of 1.0 day (1, 2). At the Day 7 assessment, the mean CRP concentration decreased significantly (p < 0.001), as did the mean ferritin (p = 0.011). Anakinra was generally safe and well tolerated and was discontinued for side effects in only three patients (14.3%). Anakinra is an efficient and safe treatment to control sHLH of various causes. These data, together with the recent report of the NHS panel, call for the rapid conduct of prospective randomized clinical trials.

Implementation of Model-Based Dose Adjustment of Tobramycin in Adult Patients with Cystic Fibrosis.

Therapeutic drug monitoring (TDM) of tobramycin is widely performed in patients with cystic fibrosis (CF), but little is known about the value of model-informed precision dosing (MIPD) in this setting. We aim at reporting our experience with tobramycin MIPD in adult patients with CF. We analyzed data from adult patients with CF who received IV tobramycin and had model-guided TDM during the first year of implementation of MIPD. The predictive performance of a pharmacokinetic (PK) model was assessed. Observed maximal (Cmax) and minimal (Cmin) concentrations after initial dosing were compared with target values. We compared the initial doses and adjusted doses after model-based TDM, as well as renal function at the beginning and end of therapy. A total of 78 tobramycin courses were administered in 61 patients. After initial dosing set by physicians (mean, 9.2 ± 1.4 mg/kg), 68.8% of patients did not achieve the target Cmax ≥ 30 mg/L. The PK model fit the data very well, with a median absolute percentage error of 4.9%. MIPD was associated with a significant increase in tobramycin doses (p < 0.001) without significant change in renal function. Model-based dose suggestions were wellaccepted by the physicians and the expected target attainment for Cmax was 83%. To conclude, the implementation of MIPD was effective in changing prescribing practice and was not associated with nephrotoxic events in adult patients with CF.

A New Pathogenic Missense Variant in a Consanguineous North-African Family Responsible for a Highly Variable Aceruloplasminemia Phenotype: A Case-Report.

Aceruloplasminemia is a rare autosomal recessive inherited disorder. Mutations in the ceruloplasmin gene cause depressed ferroxidase activity leading to iron accumulation. The clinical phenotype is highly variable: anemia, retinopathy, diabetes mellitus, psychiatric disorders, and neurological symptoms including parkinsonian disorders and dementia are the main features of this disease. Characterized by high serum ferritin with low transferrin saturation, aceruloplasminemia uniquely combines brain, liver and systemic iron overload. We report here four new cases of aceruloplasminemia in a consanguineous North-African family. Genetic sequencing revealed a homozygous missense variant c.656T>A in exon 4 of the ceruloplasmin gene, which had been described previously as of "unknown significance" in the dbSNP database and never associated with ACP in the HGMD database. Ferroxidase activity was strongly depressed. Clinical manifestations varied among cases. The proband exhibited mild microcytic anemia, diabetes mellitus, psychosis and parkinsonism, whereas the other cases were asymptomatic or mildly anemic, although high serum ferritin and brain iron deposition were documented in all of them. Therapeutic management was complex. The proband started deferoxamine treatment when already symptomatic and he rapidly declined. In the asymptomatic cases, the treatment was associated with poor tolerance and was discontinued due to anemia requiring red blood cell transfusion. Our series illustrates the need for new therapeutic approaches to aceruloplasminemia.

Prevalence of Post-Glucose Challenge Hypoglycemia in Adult Patients With Cystic Fibrosis and Relevance to the Risk of Cystic Fibrosis-Related Diabetes.

OBJECTIVES: The clinical relevance of fasting and postprandial hypoglycemia in patients with cystic fibrosis (CF) is poorly characterized. Our aim in this study was to characterize the prevalence of hypoglycemia in adult patients during oral glucose tolerance test (OGTT) screening and determine its impact on the risk of developing CF-related diabetes (CFRD). METHODS: We analyzed 2 cohorts of pancreatic insufficient patients with CF exposed to comparable treatment recommendations in France (Lyon CF cohort [DIAMUCO]) and Canada (Montréal CF cohort [MCFC]). Patients were classified into 3 groups based on hypoglycemia absence or presence as well as its severity at baseline. We defined the groups as follows: level 2 hypoglycemia (L2H; plasma glucose [PG]<3.0 mmol/L), level 1 hypoglycemia (L1H; PG 3.0 to <4.0 mmol/L) and no hypoglycemia (NH) during an OGTT. RESULTS: A total of 153 MCFC and 114 DIAMUCO subjects were included in the study. In total, 22% of the patients experienced hypoglycemia, with 5% having it on 2 or more OGTTs. The L1H and L2H groups tended to have a lower 2-hour glucose and higher early-phase insulin secretion (insulin area under the curve at 0 to 30 minutes) compared with NH patients. In both cohorts, a greater proportion of men and patients with normal glucose tolerance had hypoglycemia. Over a 5-year period, there were no cases of CFRD in the L2H group, whereas 4 subjects in the L1H group and 36 in the NH group developed CFRD. CONCLUSIONS: Patients with hypoglycemia were at lower risk of developing CFRD, but at higher risk of early-phase insulin secretion and unsuppressed insulin secretion. This could potentially lead to further hypoglycemia after the 2-hour OGTT, suggesting high clinical relevance.

Clinical practice versus guidelines for the screening of cystic fibrosis-related diabetes: A French survey from the 47 centers.

This study aimed to analyze clinical practices concerning cystic fibrosis-related diabetes (CFRD) screening in France. A web-based questionnaire was distributed between December 1, 2020 and January 31, 2021 among 47 cystic fibrosis centers including pediatric, adult, and mixed units. In accordance with guidelines, 92.8% of CF centers performed annual oral glucose tolerance tests (OGTT). Overall, 86.3% of CF centers performed 1- and 2-hour blood glucose determinations following OGTT. The OGTT was conducted before 10 years of age in 73% of pediatric centers. Continuous glucose monitoring (CGM) and laboratory glycated hemoglobin were employed for CFRD screening in 86.5% and 50% of centers, respectively. CGM was carried out in 69% of centers after glucose tolerance abnormalities had been detected in OGTT. Most CF centers used OGTT and CGM for CFRD screening. Studies are required to assess CGM usefulness as a validated tool in CFRD screening.

Cumulative Incidence and Risk Factors for Severe Coronavirus Disease 2019 in French People With Cystic Fibrosis.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are closely monitored in people with cystic fibrosis (pwCF), especially severe cases. Previous studies used hospitalization rates as proxy for severity. METHODS: We evaluated data from coronavirus disease 2019 (COVID-19) cases diagnosed in French pwCF over the first pandemic year. Objective criteria were applied for defining severity (eg, respiratory failure and/or death). Data were compared to all French pwCF using the National Registry. RESULTS: As of 30 April 2021, 223 pwCF were diagnosed with COVID-19, with higher risks in adults (odds ratio [OR], 2.52 [95% confidence interval {CI}, 1.82-3.48]) and transplant recipients (OR, 2.68 [95% CI, 1.98-3.63]). Sixty (26.9%) patients were hospitalized, with increased risk in transplant recipients (OR, 4.74 [95% CI, 2.49-9.02]). In 34 (15%) cases, COVID-19 was considered severe; 28 (46.7%) hospitalizations occurred without objective criteria of severity. Severe cases occurred mostly in adult (85.3%) and posttransplant pwCF (61.8%; OR, 6.02 [95% CI, 2.77-13.06]). In nontransplanted pwCF, risk factors for severity included low lung function (median percentage of predicted forced expiratory volume in 1 second, 54.6% vs 75.1%; OR, 1.04 [95% CI, 1.01-1.08]) and CF-related diabetes (OR, 3.26 [95% CI, 1.02-10.4]). While 204 cases fully recovered, 16 were followed for possible sequelae, and 3 posttransplant females died. CONCLUSIONS: Severe COVID-19 occurred infrequently during the first pandemic year in French pwCF. Nontransplanted adults with severe respiratory disease or diabetes and posttransplant individuals were at risk for severe COVID-19. Thus, specific preventive measures should be proposed.

Iron Deficiency in Cystic Fibrosis: A Cross-Sectional Single-Centre Study in a Referral Adult Centre.

Iron deficiency (ID) diagnosis in cystic fibrosis (CF) is challenging because of frequent systemic inflammation. We aimed to determine the prevalence and risk factors of ID in adult patients with CF. We conducted a single-centre prospective study in a referral centre. ID was defined by transferrin saturation ≤16% or ferritin ≤20 (women) or 30 (men) µg/L, or ≤100 µg/L in the case of systemic inflammation. Apparent exacerbation was an exclusion criterion. We included 165 patients (78 women), mean age­31.1 ± 8.9 years. ID prevalence was 44.2%. ID was significantly associated with female gender (58.9% vs. 38%), lower age (29.4 ± 8.5 vs. 32.5 ± 9.1), lower body mass index (20.5 ± 2.2 vs. 21.3 ± 2.5), and Pseudomonas aeruginosa colonization (70.8% vs. 55.1%). Diabetes mellitus, antiacid drug use and low pulmonary function were more frequent in patients with ID with no statistical significance. The use of CFTR correctors was not associated with ID. In the multivariate analysis, ID was associated with female gender (OR 2.64, CI95% 1.31−5.31), age < 30 years (OR 2.30, CI95% 1.16−4.56), and P. aeruginosa (OR 2.09, CI95% 1.04−4.19).

HOMA indices as screening tests for cystic fibrosis-related diabetes.

BACKGROUND: We assessed the diagnostic performances of homeostasis model assessment indices (HOMA) of ß-cell function (HOMA-%ß) 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-%ß and HOMA-IR. HOMA-%ß <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-%ß 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-%ß and 42%, 48%, 91% and 6% for HOMA-IR in the pooled data of children; and 83%, 18%, 90% and 10% for HOMA-%ß, and 39%, 80%, 92% and 18% for HOMA-IR in the pooled data of adults. Combining HOMA-%ß and HOMA-IR did not improve performances. CONCLUSION: Within both age groups, HOMA-%ß <100 provided good sensitivity and NPV. HOMA-IR >1 had low sensitivity. Calculation of the HOMA-%ß 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-%ß<100 does not support the diagnosis of CFRD and should be complemented by OGTT.

Temporal trends in healthcare resource use and associated costs of patients with cystic fibrosis.

BACKGROUND: Better insights into the natural course of cystic fibrosis (CF) have led to treatment approaches that have improved pulmonary health and increased the life expectancy of affected individuals. This study evaluated how the combination of modified demographics and changes in CF management impacted resource consumption and the cost of care. METHODS: Medical records of CF patients from 2006 to 2016 in the French CF Registry were linked to their corresponding claims data (SNDS). Medications, medical visits, procedures, hospitalisations, and indirect costs were annualized by calendar year from 2006 to 2017. RESULTS: Of the 7,671 patients included in the French CF Registry, 6,187 patients (80.7%) were linked to the SNDS (51.9% male, mean age = 24.7 years). The average cost per patient was €14,174 in 2006, €21,920 in 2011 and €44,585 in 2017. Costs associated with hospital stays increased from €3,843 per patient in 2006 to €6,741 in 2017. In 2017, the mean cost per CF patient was allocated as follows: 72% for medications (of which 51% for modulator therapies), 15% for hospital stays, 7% for medical visits, 3% for indirect costs, 2% for medical devices, 1% for outpatient medical procedures. CONCLUSION: There was a strong increase in the mean annual cost per CF patient between 2006 and 2017, mostly due to the cost of therapy after the introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulators. The combination of an increase in the number of CF patients - particularly adult patients - and an increase in the annual cost per patient led to a substantial increase in the total cost of CF disease care for the health systems.

Combined Indeterminate and Impaired Glucose Tolerance Is a Novel Group at High Risk of Cystic Fibrosis-Related Diabetes.

BACKGROUND: Indeterminate glycemia (INDET) and impaired glucose tolerance (IGT) are independently associated with cystic fibrosis-related diabetes (CFRD) risk. We determined whether patients meeting both criteria have increased risk of diabetes in 2 separate adult cohorts. METHODS: The Montreal Cystic Fibrosis Cohort (MCFC; n = 293 baseline and 198 for prospective analysis excluding subjects identified with incident CFRD at baseline) and the Lyon cystic fibrosis cohort [Determination of the Predictive Factors in the Reversibility or the Aggravation in the Disorders of the Glucose Metabolism in Cystic Fibrosis Patients (DIAMUCO); n = 144/105] are prospective observational cohorts. RESULTS: In the MCFC and DIAMUCO cohorts, mean age was 25.5 ±â€…7.7 and 25.0 ±â€…8.6 years; body mass index, 21.7 ±â€…3.0 and 20.2 ±â€…2.2 kg/m2; percentage of forced expiratory volume expired in 1 sec, 73.2 ±â€…22.1 and 62.5 ±â€…21.9; and follow-up, 6.9 ±â€…3.8 and 2.4 ±â€…1.2 years, respectively. In the MCFC cohort, the IGT only and combined INDET and IGT (INDET + IGT) groups had greater risk of CFRD (P = 0.0109). In the DIAMUCO cohort, there was lower diabetes-free survival in the INDET + IGT group (P = 0.0105). In both cohorts, CFRD risk ranged from 17% in normal glucose tolerance patients up to 42% to 56% in patients with INDET + IGT. CONCLUSION: Patients who meet combined criteria have a higher risk of developing diabetes probably justifying closer follow-up.

Glycated Hemoglobin as a First-line Screening Test for Cystic Fibrosis‒Related Diabetes and Impaired Glucose Tolerance in Children With Cystic Fibrosis: A Validation Study.

OBJECTIVES: Our aims in this study were to document the screening rate for cystic fibrosis‒related diabetes (CFRD) in children followed at a cystic fibrosis (CF) clinic in Canada and to evaluate the accuracy of various glycated hemoglobin (A1C) cutoffs to screen for CFRD and impaired glucose tolerance (IGT) in a pediatric CF population. METHODS: The CFRD screening rate was calculated over a follow-up period of up to 8 years among children who attended the CF clinic between 1993 and 2018. Test performance of A1C at various thresholds ranging from 5.5% to 6.2% was compared with the oral glucose tolerance test (OGTT) as the reference method. Children with CF aged ≥10 years with an OGTT performed within 120 days of A1C measurement were included in the analysis. RESULTS: The overall CFRD screening rate was 53.0%. A total of 256 children were included for the A1C performance analysis, of whom 8.6% had an OGTT-confirmed CFRD diagnosis. An A1C threshold of 5.8% demonstrated an optimal balance between sensitivity (90.9%) and specificity (60.7%) for CFRD screening, leading to a potential reduction of 56.3% of the annual required OGTTs. A1C demonstrated poor accuracy for identifying children with IGT. CONCLUSIONS: An A1C threshold ≥5.8% allows for identification of children requiring further CFRD investigations, which may reduce the clinical burden of children with CF without compromising the ability of early CFRD diagnosis.

A formalized transition program for cystic fibrosis: A 10-year retrospective analysis of 97 patients in Lyon.

INTRODUCTION: The prognosis of people diagnosed with cystic fibrosis (CF) has dramatically improved over the past decade in France, largely due to advances in CF care management, including an emphasis on chronic maintenance medications. Currently, the majority of French CF patients are adults, which means that they went through a transition process from receiving care at a pediatric CF center to receiving care at an adult CF center. To determine the impact of the transfer on clinical evolution, we report the transition procedure of our CF center in Lyon. MATERIALS AND METHODS: From January 2006 to December 2016, 97 CF patients underwent a standardized process of transitioning from the pediatric to the adult CF center in Lyon. We compared the clinical evolution of these patients during three periods, starting the year before transition and ending the year after transition. Clinical data taken into account were forced expiratory volume in 1 s (FEV1 in liters), body mass index (BMI in kg/m2 ), pulmonary colonization, number of antibiotic courses, number of days of hospitalization per year, and outpatient visits per year. RESULTS: No significant differences were observed between respiratory and nutritional status, respiratory microbiome, number of antibiotic courses, or number of hospitalizations or visits when comparing the threeperiods of observation around transition (the year before, the first year after, and the second year after transfer). CONCLUSION: The standardized transition procedure used in Lyon is associated with the clinical stability of our CF patients.

Impact of 1h oral glucose tolerance test on the clinical status of adult cystic fibrosis patients over a 4-year period.

OBJECTIVE: To report the clinical profile associated with G60 and I60 over a 4-year prospective observational period in 2 large cohorts of adult patients with CF. METHODS: 319 patients were included (210 Canadian and 119 French) and classified according to their inclusion G60 (≥ or < 11.1 mmol/L) and the median inclusion I60 (≥ or < 24 mU/I). Forced expiratory volume in 1 second (FEV1), body mass index (BMI) were collected on OGTT days. Linear mixed regression models were used to assess the effect of G60 and I60. RESULTS: High G60 was not associated to a lower FEV1 at inclusion and the follow-up decline was not higher in the high G60 group (Coefficient [95% CI]: -3.4 [-7.4;0.6], p = 0.0995.). There was no significant association between BMI and G60. Patients with high I60 tended to have a higher mean BMI (+0.5 kg/m2 [0.0 to 1.1], p = 0.05) but no interaction over time was observed. CONCLUSIONS: High G60 is not associated with a lower lung function at inclusion nor its decline over a 4-year follow-up. High I60 is slightly associated to a higher weight at inclusion, but not with BMI evolution over time in adult patients.

Risk factors for nontuberculous mycobacterial isolation in patients with cystic fibrosis: A meta-analysis.

BACKGROUND: To better understand the mechanisms of infection with nontuberculous mycobacteria (NTM) in patients with cystic fibrosis (CF), we explore different risk factors associated with NTM positivity in a meta-analysis. METHODS: Studies published before 31 July 2019 were selected from MEDLINE. Combined odds ratios (ORs) were calculated by pooling the ORs of each study. The weighted mean difference (WMD) was used for continuous numerical measurements. Summary data were pooled using fixed- or random-effects models according to the presence of heterogeneity (P < .1 or I2 > 50%). RESULTS: Nineteen studies with a total of 23 418 patients, of whom 1421 (6%) were diagnosed as NTM positive, were included. Older age was significantly associated with NTM positivity (WMD = 2.12, 95% confidence interval [CI]: 1.11-3.13; P < .01, fixed-effects model). The OR for Staphylococcus aureus colonization was 1.66 (95% CI: 1.21-2.26; P = .001) in 11 studies (8091 patients), the OR for Aspergillus fumigatus colonization was 3.59 (95% CI: 3.05-4.23; P < .001) in 11 studies (20 480 patients), and the OR for Stenotrophomonas maltophilia colonization was 3.41 (95% CI: 2.66-4.39; P < .01) in seven studies (14 935 patients). Oral corticosteroids were significantly associated with NTM positivity (OR = 1.98, 95% CI: 1.24-3.16; P < .01, 6 studies, 1936 patients). No other factor showed a significant association. CONCLUSION: Older age, S. aureus, S. maltophilia, and A. fumigatus chronic colonization, and oral corticosteroids were significantly associated with an increased risk of NTM positivity. CF patients with more severe conditions should be closely monitored for NTM.