We performed a multicenter prevalence study of nontuberculous mycobacteria (NTM) involving 1,582 patients (mean age, 18.9 years; male/female ratio, 1.06) with cystic fibrosis in France. The overall ...NTM prevalence (percentage of patients with at least one positive culture) was 6.6% (104/1,582 patients), with prevalences ranging from 3.7% (in the east of France) to 9.6% (in the greater Paris area). Mycobacterium abscessus complex (MABSC; 50 patients) and Mycobacterium avium complex (MAC; 23 patients) species were the most common NTM, and the only ones associated with fulfillment of the American Thoracic Society bacteriological criteria for NTM lung disease. The "new" species, Mycobacterium bolletii and Mycobacterium massiliense, accounted for 40% of MABSC isolates. MABSC species were isolated at all ages, with a prevalence peak between 11 and 15 years of age (5.8%), while MAC species reached their highest prevalence value among patients over 25 years of age (2.2%).
Pseudomonas aeruginosa is the main cause of chronic airway infection in cystic fibrosis (CF). However, for unclear reasons some patients are never colonized by P. aeruginosa. The objectives of this ...study were to better define the clinical, genetic, and microbiological characteristics of such a subpopulation and to identify predictive factors of non-colonization with P. aeruginosa. The French CF patient registry 2013-2014 was used to identify CF patients aged ≥ 20 years. The clinical outcomes, CF Transmembrane conductance Regulator (CFTR) genotypes, and microbiological data of patients reported positive at least once for P. aeruginosa ("Pyo" group, n = 1,827) were compared to those of patients with no history of P. aeruginosa isolation ("Never" group, n = 303). Predictive factors of non-colonization by P. aeruginosa were identified by multivariate logistic regression model with backward selection. Absence of aspergillosis (odds ratio (OR) 95% CI = 1.64 1.01-2.66), absence of diabetes (2.25 1.21-4.18), pancreatic sufficiency (1.81 1.30-2.52), forced expiratory volume 1 (FEV1) ≥ 80% (3.03 2.28-4.03), older age at CF diagnosis (1.03 1.02-1.04), and absence of F508del/F508del genotype (2.17 1.48-3.19) were predictive clinical factors associated with absence of infection ("Never" group). Microbiologically, this same group was associated with more frequent detection of Haemophilus influenzae and lower rates of Stenotrophomonas maltophilia, Achromobacter xylosoxidans and Aspergillus spp. (all p<0.01) in sputum. This study strongly suggests that the absence of pulmonary colonization by P. aeruginosa in a minority of CF adults (14.2%) is associated with a milder form of the disease. Recent progress in the development of drugs to correct CFTR deficiency thus may be decisive in the control of P. aeruginosa lung infection.
Abstract 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/m2 , 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.
Viral 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 (
= 19, 61.3%), and a mild lung disease (
= 19, 65%, with percent-predicted forced expiratory volume in 1 s (ppFEV
) > 70). Three (10%) patients remained asymptomatic. For the 28 (90%) patients who displayed symptoms, most common symptoms at admission were fever (
= 22, 78.6%), fatigue (
= 14, 50%), and increased cough (
= 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.
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.
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.
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).
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.
Rare diseases (RD) patient registries are powerful instruments that help develop clinical research, facilitate the planning of appropriate clinical trials, improve patient care, and support ...healthcare management. They constitute a key information system that supports the activities of European Reference Networks (ERNs) on rare diseases. A rapid proliferation of RD registries has occurred during the last years and there is a need to develop guidance for the minimum requirements, recommendations and standards necessary to maintain a high-quality registry. In response to these heterogeneities, in the framework of RD-Connect, a European platform connecting databases, registries, biobanks and clinical bioinformatics for rare disease research, we report on a list of recommendations, developed by a group of experts, including members of patient organizations, to be used as a framework for improving the quality of RD registries. This list includes aspects of governance, Findable, Accessible, Interoperable and Reusable (FAIR) data and information, infrastructure, documentation, training, and quality audit. The list is intended to be used by established as well as new RD registries. Further work includes the development of a toolkit to enable continuous assessment and improvement of their organizational and data quality.
Life expectancy for people with cystic fibrosis (CF) varies considerably both within and between countries. The objective of this study was to compare survival among countries with single-payer ...healthcare systems while accounting for markers of disease severity.
This cohort study used data from established national CF registries in Australia, Canada, France and New Zealand from 2015 to 2019. Median age of survival for each of the four countries was estimated using the Kaplan-Meier method. A Cox proportional hazards model was used to compare risk of death between Canada, France and Australia after adjusting for prognostic factors. Due to low number of deaths, New Zealand was not included in final adjusted models.
Between 2015 and 2019, a total of 14 842 people (3537 Australia, 4434 Canada, 6411 France and 460 New Zealand) were included. The median age of survival was highest in France 65.9 years (95% CI: 59.8 to 76.0) versus 53.3 years (95% CI: 48.9 to 59.8) for Australia, 55.4 years (95% CI: 51.3 to 59.2) for Canada and 54.8 years (95% CI: 40.7 to not available) for New Zealand. After adjusting for individual-level factors, the risk of death was significantly higher in Canada (HR 1.85, 95% CI: 1.48 to 2.32; p<0.001) and Australia (HR 2.08, 95% CI: 1.64 to 2.64; p<0.001) versus France.
We observed significantly higher survival in France compared with countries with single-payer healthcare systems. The median age of survival in France exceeded 60 years of age despite having the highest proportion of underweight patients which may be due to differences in availability of transplant.
•ETI is approved for pwCF and eligible CFTR mutations.•Initiation of ETI provided clinical improvement in lung transplant candidates.•Lung transplantation could be safely deferred in most ...patients.•ETI should be initiated in transplant candidates prior to transplant listing.
Elexacaftor-tezacaftor-ivacaftor induces rapid clinical improvement in patients with cystic fibrosis (CF) and advanced pulmonary disease, often leading to suspend the indication for lung transplantation. Yet no long-term data is available in lung transplant candidates.
Lung transplant candidates (defined as being waitlisted for lung transplantation or considered for listing within 3 months) who have initiated elexacaftor-tezacaftor-ivacaftor were identified in the French cohort of patients with CF and advanced pulmonary disease. Patients were prospectively followed to evaluate treatment safety and effectiveness from initiation to July 20th, 2021.
Among the 331 patients with advanced CF pulmonary disease who initiated elexacaftor-tezacaftor-ivacaftor, 65 were lung transplant candidates (17 listed for transplantation, 48 considered for listing within 3 months). Median IQR follow-up time was 363 329; 377 days. At the end of the follow-up period, two patients were transplanted five and 11 days following treatment initiation, two were listed for transplantation, and 61 no longer met transplantation criteria. Improvement in percent predicted forced expiratory volume in 1 s (ppFEV1) at one month was +13.4% (95% confidence interval, 10.3%-16.5%; P < 0.0001) and remained stable thereafter. Treatment burden decreased substantially, with an 86% decrease in the need for intravenous antibiotics, 59% for oxygen therapy and 62% for non-invasive ventilation.
In lung transplant candidates eligible for elexacaftor-tezacaftor-ivacaftor, the rapid improvement following initiation of treatment persisted over one year with a reduction in treatment burden and lung transplantation could be safely deferred in most patients.
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