Search

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 (ppFEVIn 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.

Background People with cystic fibrosis (pwCF) are central in the development of patient-led assessment tools. Qualitative analysis of a frequently used CF-specific patient-reported outcome measure (PROM) sought patient recommendations for development of a new quality of life (QoL) tool. Methods We performed an inventory of PROMs, symptom-report and QoL tools used in clinical trials within the European Cystic Fibrosis Society Clinical Trial Network (ECFS-CTN) and in routine clinical practice among Cystic Fibrosis Europe and ECFS members. A qualitative study using cognitive interviews with pwCF and their caregivers reviewed the Cystic Fibrosis Questionnaire (CFQ), the French initial form of the Cystic Fibrosis Questionnaire-Revised (CFQ-R). Results Survey results from 33 countries revealed over 70 tools used in routine clinical practice, utilized by clinical specialists (n=124), pwCF/parents/carers (n=49) and other allied health professionals (n=60). The CFQ-R was the main PROM used in clinical trials. The qualitative study enrolled 99 pwCF, 6 to 11 years (n=31); 12 to 18 years (n=38); >18 years (n=30) and 26 parents. Inductive thematic analysis based on the CFQ, revealed 19 key themes. Themes common across all cohorts included burden of treatment, impact of disease on day-to-day life, relationships/family, stress/mood, and nutrition. Themes unique to individual groups included, treatment when not symptomatic for the paediatric group; education/studies and planning for the future for adolescents, impact of anxiety and depression on day-to-day life for adults, and for parents, questions addressing anxiety and their role as carers. Conclusions Patient-centeredness is paramount in development of an up-to-date PROM in the era of novel therapies.

Highlights • First feasibility study of respiratory viral detection in Cystic Fibrosis sputum. • High concordance between sputum and nasopharyngeal samples in viral. • Multiplex-PCR performed in 30 paired samples: 83% viral congruency. • Sputum: an optimal non-invasive sample for viral diagnosis in cystic fibrosis., Viruses are important agents in lung function deterioration in Cystic Fibrosis (CF). To date, no standard operating procedures (SOPs) have been established to determine which sampling method is the most effective for an optimal virological diagnosis of respiratory viral infections in CF. Here we investigated the performances of two sampling sites, sputum samples versus nasopharyngeal (NP) swabs, for thirty participants from three CF centres presenting an acute respiratory infection. Sputum and NP samples were simultaneously collected and multiplex PCR targeting 16 to 18 viruses were performed. Viruses were detected for 18/30 patients (60%). A high concordance between the sputum and NP samples was observed in 25 (83%) paired samples of which 13 tested positive and 12 tested negative. These results highlighted the relevance of sputum sampling for diagnostic of respiratory viruses in CF, which is less invasive and better accepted by CF patients than NP, and allows accurate bacterial detection.

Objective To investigate the short-term adverse events and effectiveness of lumacaftor/ivacaftor combination treatment in adults with cystic fibrosis (CF) and severe lung disease in a real life setting. Methods A multicentre observational study investigated adverse events, treatment discontinuation, FEV 1 and body mass index (BMI) one month and three months after lumacaftor/ivacaftor initiation in adults with CF and FEV 1 below 40% predicted. Results Respiratory adverse events (AEs) were reported by 27 of 53 subjects (51%) and 16 (30%) discontinued treatment. The mean absolute change in FEV 1 was +2.06% after one month of treatment ( P =0.086) and +3.19% after 3 months ( P =0.009). BMI was unchanged. Conclusions Treatment with lumacaftor/ivacaftor in patients with CF and severe lung disease was discontinued more frequently than reported in clinical trials, due to respiratory AEs. Nevertheless, the patients who continued treatment had an increase in lung function comparable to what was observed in pivotal trials.

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.

Kidney stones and renal failure are more common in patients with CF compared to general population. Hyperoxaluria caused by fat malabsorption and the lack of intestinal oxalate degrading bacteria Oxalobacter formigenes is known in CF patients. Hyperoxaluria-induced crystal formation is associated with kidney stones and renal failure. However data concerning detection of crystals in CF patients are lacking in the literature. We conducted a prospective study in Pneumology Center, Foch Hospital, during 8 months. Forty cystic fibrosis adult patients were enrolled to have a sample spot urine test on the first morning micturition. Median age was 29 years-old (range 20−55). Sixteen patients were pulmonary transplanted. Thirty-eight (95%) and 24 (61%) patients had exocrine and endocrine pancreas insufficiency, respectively. Three patients had glomerulonephropathy (2 diabetic nephropathy and 1 amyloidosis). The median plasmatic creatinine was 69mmol/l (range 39–400mmol/l). Factors for crystals formation were researched. Thirty-five percent of patients (13/40) had hypercalciuria (>3.5mmol/l), 60% (24/40) had hypershy;oxaluria (>0.3mmol/l) and 72% (28/40) had hypocitraturia (

Objectives Pregnancy after lung transplantation remains rare. This French study deals with maternal and newborn outcomes and change in lung function after a pregnancy. Methods We retrospectively included 39 pregnancies in 35 lung transplant recipients over more than 20 years. Data about patients, course of pregnancies and newborns were collected from nine of the eleven French transplantation centers. Results Mean age at time of pregnancy was 28±5years. Cystic fibrosis affected 71% of our patients. Mean time between transplantation and pregnancy was 63±44 months. Twenty six births occurred (67%) with a mean term of 36±5 weeks gestation and a mean birth weight of 2409±921 g. Prematurity was observed in 11 cases (43%). Forced expiratory volume in one second was measured at 83.9% pred. before pregnancy and at 77.3% pred. 12 months later (p = 0.04). Ten patients developed chronic lung allograft dysfunction, 22.5±14.6 months after delivery. Up to now, nine patients died with a mean time after transplantation of 8.2±7 years and a mean time after pregnancy of 4.6±6.5 years. Conclusion Pregnancy in lung transplant recipients is possible. Maternal and newborn complications are more frequent than in general population. Survival in this cohort appears to be similar to global survival observed in lung transplant recipients. Planned pregnancy and multidisciplinary follow-up are crucial.

Background As a result of prolonged survival, more patients with CF participate in the labour force. The available data on employment in CF have been based on cross-sectional studies. To our knowledge, no cohort study, evaluating the evolution of employment status in CF patients has been conducted so far. In 2009, we assessed occupational levels and risk factors for work disability in 207 patients cared for at our CF centre in Paris. Five years later, we reassessed employment status in the same cohort, with a special focus on lung transplantation recipients. Methods We first reviewed the status of the patients from the 2009 cohort (alive, deceased, lost to follow-up). A self-administered questionnaire, identical to the one used in 2009 on work status and treatment, was submitted to the patients still in the cohort. A section relating to lung transplantation was added when appropriate. In parallel, medical records were reviewed for illness severity indicators. Results Of the 207 initial patients, 16 had died, 7 were lost to follow-up and 184 were still alive (35 of which had received a lung transplantation). To date, data have been collected for 166 patients (80%). In comparison to 2009, 97 (58%) vs 117 (57%) were employed, 14 (8%) vs 13 (6%) were unemployed, 45 (27%) vs 38 (18%) were inactive and 9 (5%) vs 39 (19%) were students. Conclusion The proportion of employed patients was unchanged after 5 years but fewer patients were students. Data collection will be completed for the patients in the cohort who have moved and are no longer followed in our CF center. We plan to analyze employment promoting factors and the impact of lung transplantation on occupational life.

Objectives Portal hypertension (PHT) is the main complication of cystic fibrosis liver disease (CFLD) but severe liver dysfunction occurred only in 0.5% of the patients. The early diagnosis of CFLD is elusive and a gold standard for diagnosis of liver disease is lacking. The aim of this study was to evaluate liver stiffness measurement (LSM) and CT with IV injected contrast medium in CF adult patients. Median LSM in 241 CF patients was 5.9 kPa. Methods 57 CF patients (28F, 33 yrs −18; 51) had LSM and CT done for lung transplant assessement or after lung transplantation. Results LSM was obtained in 53 patients (92%). PHT was evident on CT in 25 patients (portosystemic collaterals 12, splenomegaly 19, proeminent portal vein 25). PHT was present in 60% of the patients when LSM was >5.9 and in 12% when LSM was Conclusion CFLD with PHT could be present in patient with low LSM. Decompensation of PHT is unfrequent even in adults with end stage pulmonary disease or after lung transplantation. Portal venopathy without cirrhosis could explain PHT. The mechanism remains obscure but could explain the rare occurence of hepatocellular deficiency in CFLD.

The prevalence of CF related liver disease (CFLD) ranges from 26% to 45%. The pathogenesis is allegedly related to small bile duct obstruction leading to focal biliary cirrhosis and cirrhosis. Portal hypertension (PHT) without hepatocellular insufficiency is the main presentation of CFLD. The aim of this study was to establish the pathologic pattern in CFLD patients with severe PHT. Patients and Methods In 2 CF centers, all consecutive patients who underwent liver transplantation were retrospectively analysed. Results Eight patients (7 males; 14–32 y) were analysed. All presented with severe PHT: esophageal varices more than grade 2 (bleeding in 2 patients), splenomegaly 18–30 cm, collaterals or ascites. None had signs of hepatocellular insufficiency. Liver tests were less than 1.5 times elevated. Macroscopically, all explants (mean weight 1.6 kg) were dysmorphic with left atrophy and irregular macronodular aspect. There was no thrombosis of the large veins and large bile ducts were normal. Microscopically, all explants showed septal fibrosis without cirrhosis (F2 or F3 Metavir Score, n = 4 each). Diffuse obliterative portal venopathy with sinusoidal dilatation and regenerative nodular hyperplasia was observed in all, associated with frequent ductopenia in small portal tracts, without cholestasis or inflammation. Biliary plugs with ductular reaction were scarce, medium or large biliary ducts were normal. Conclusion According to histological examination of the native livers, CFLD with PHT is not related to biliary cirrhosis but responds to vascular damages as observed in idiopathic non-cirrhotic PHT. The mechanism leading to vascular lesion in CF is unknown.

Objectives PHT is the main manifestation of liver disease in adults CF patients. The risk of hepatic decompensation after isolated LT is unknown. The model for end-stage liver disease (MELD) score is not relevant for the indication to combined lungs-liver transplantation. We presented the postoperative outcome of isolated lung transplantation in CF patients with asymptomatic PHT. Methods From 2008 to 2014, 14 isolated LT (over 299) were proceeded over CF patients with PHT. Results All Patients had asymptomatic liver disease before LT but all had PHT on the CT scan: splenomegaly (14–19 cm) in 10 patients, portosystemic collaterals in 8, all had portal vein dilatation >14 (diameter 17±2.3 mm). The liver stiffness measurement (LMS) was elevated 18±8 kPa when in our adult CF center median LSM was 5.9 kPa in 241 CF patients. Thirteen patients had normal liver and renal function. Gastroesophageal varices were absents in 10 screened patients. After LT, 4 patients required ECMO, 6 developed easy to treat ascites associated with transient renal insufficiency (4) or intestinal complications (2). One developed transient ascitis 7 months after LT associated with sepsis and renal dysfunction. Hepatocellular function remain normal in all patients. Every patient is still alive (mean time 42±22 months). Conclusion Carefully selected CF patients with end-stage lung disease and portal hypertension can tolerate isolated lung transplantation. The non-invasive evaluation of the severity of PHT has to be evaluated. Prospective multicentric study is need to clearly define the indications of combined lung–liver transplantation.