[Adherence to chest physiotherapy in adults with cystic fibrosis]. / Adhésion à la kinésithérapie respiratoire chez les adultes atteints de mucoviscidose.

INTRODUCTION: Chest-physiotherapy is a key element in treatment of cystic fibrosis and patient adherence is a major issue in global cystic fibrosis care. This study aims to assess adherence to chest physiotherapy in adults with cystic fibrosis who not treated with tritherapy and to analyze the impact of certain factors on adherence. METHODS: Thus is a cross-sectional study, conducted using a questionnaire and a physiotherapy evaluation. Adherence to this treatment was measured in terms of quantitative and qualitative aspects. The impact on adherence of 15 factors was then assessed. RESULTS: Only 47% of patients could be considered as adherent, with a significant disparity between a quantitative and qualitative assessment. Gender, working time, pathology severity, the fact of being regularly followed by a physiotherapist, the perceived benefit of the sessions and their replacement by physical activity, seem associated with adherence to this treatment. CONCLUSIONS: Taking into account the qualitative aspect of the sessions, our study reveals a low rate, in our cohort, of adherence to respiratory physiotherapy, and highlights six factors likely to predominate. Regular follow-up by a physiotherapist seems to be a determining factor in adherence to this treatment.

Human papillomavirus prevalence, persistence and cervical dysplasia in females with cystic fibrosis.

BACKGROUND: A higher risk of human papillomavirus (HPV)-related cervical intra-epithelial neoplasia (CIN) is suspected among females with cystic fibrosis (CF). METHODS: We conducted a single center prospective cohort study among females attending the Lyon adult CF center. We performed a cervical cytology (Hologic Thinprep®) and HPV testing with genotyping (Clinical Arrays Papillomavirus; Genomica, enabling 35 genotype detection, 20 of which are high-risk (HR-HPV)) at inclusion. We followed all females with positive HPV tests at 6, 12 and 24 months to evaluate HPV persistence, and performed a colposcopy in cases of abnormal cytology. RESULTS: We included eighty-five participants, 18 (21%) of whom were lung-transplanted. The mean age at inclusion was 31.9 (range 18-59) years. The prevalence of HPV (all types) was 31.8%. HR-HPV was found in 25.9% of the whole cohort, 44.4% of transplanted patients, and 20.1% of nontransplanted patients. Genotype-specific HR-HPV persistence at 12 months was 43.5% among transplanted and 34.6% among nontransplanted patients. Overall, 17.6% (15/85) of females had an abnormal cytology: 44.4% (8/18) among transplanted and 10.4% (7/67) among nontransplanted patients. CIN was identified in 12 (14.1%) patients (6 low-grade, 6 high-grade). High-grade CIN developed in 4 nontransplanted patients. CONCLUSION: Transplanted females had high HR-HPV, abnormal cervical cytology and CIN prevalence rates compared to large published cohorts in the general non-CF population. Although HR-HPV prevalence and persistence were globally not significantly different in nontransplanted females compared to the general population, we reported high frequencies of abnormal cytology and CIN. Cervical cancer screening and prevention should be promoted among females with CF.

[Human papillomavirus and systemic lupus erythematosus]. / Papillomavirus humain et lupus érythémateux systémique.

Infection with human papillomavirus (HPV) is one of the most widespread sexually transmitted diseases and the main risk factor for cervical cancer. Underlying conditions, like immunosuppression, favour the persistence and the progression of cervical lesions to an aggressive form. Patients with autoimmune diseases, and particularly systemic lupus erythematosus (SLE), may be prone to HPV infection and cervical dysplasia. However, the risk factors for developing persistent HPV-related infection, dysplasia and cancer are not identified for patients with SLE. The existence of an increased risk of cervical cancer compared to the general population remains debated. Thus, HPV vaccine is recommended for SLE patients as well as for the general population. Vaccine coverage of SLE patients is not known in France. Adolescents with chronic health condition seem to be insufficiently vaccinated regarding their vulnerability to infectious diseases. Strategies are required to decrease HPV vaccination barriers.

Twice- or Once-Daily Dosing of Direct Oral Anticoagulants, a systematic review and meta-analysis.

AIM: The direct oral anticoagulants (DOAC) have similar half-lives, but the dosing regimen varies between once daily (QD) or twice daily (BID). For some prescribers, the QD regimen improves compliance. Others prefer BID regimens to promote better stability of plasma concentrations, particularly in the event of missed doses. Limited level of evidence provides guidance about the best treatment strategy. The purpose of this study was to compare the treatment effect of QD vs. BID administration of DOACs in major orthopedic surgery (MOS), non-valvular atrial fibrillation (NVAF), venous thromboembolism (VTE), and acute coronary syndrome (ACS). METHODS: We conducted a systematic review up to April 2020. We included phase II clinical trials comparing DOAC QD vs BID with same daily dose. We extracted data for the occurrence of major thrombosis (proximal deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke) and major hemorrhage (ISTH criteria and recommendations of the European Medicines Agency for surgical patients). Relative risks (RR) were combined using a fixed and random effects weighted meta-analysis. RESULTS: Twelve randomized, controlled, phase II trials were included (10,716 patients), representing 24 dosing regimen comparisons of apixaban, darexaban, edoxaban, rivaroxaban, letaxaban, and dabigatran. There was no difference for major thrombotic event (RRBID/QD = 1.06, 95%IC 0.86-1.30) nor for major bleeding (RRBID/QD = 1.02, 95%IC 0.84-1.23) between the BID vs QD regimens, without heterogeneity (I2 = 0%). CONCLUSION: Our study does not support a global difference in term of efficacy and safety of the BID and QD regimens of DOAC in MOS, NVAF, VTE and ACS.

Sarcoidosis diagnosed in the elderly: a case-control study.

BACKGROUND: Studies on sarcoidosis in elderly patients are scarce and none have specifically evaluated patients aged ≥75 at onset. AIM: We aimed to analyse the characteristics of patients with sarcoidosis diagnosed after 75 and to compare them with those of younger patients. DESIGN: Multicenter case-control study comparing elderly-onset sarcoidosis (EOS) with young-onset sarcoidosis (YOS) seen at Lyon University Hospitals between 2006 and 2018. METHODS: Using our institutional database, we included 34 patients in the EOS group and compared them with 102 controls from the YOS group in a 1:3 ratio. Demographic characteristics, medical history, clinical presentation, laboratory and imaging findings, sites of biopsies, histological analyses, treatments and outcomes were recorded using a comprehensive questionnaire. RESULTS: There were more Caucasians in the EOS group (94.1% vs. 59.8%; P < 0.001), who had significantly more comorbidities (mean, 3.1 ± 2 vs. 1.1 ± 1.6; P < 0.001). In the EOS group, there was less pulmonary involvement (26.5% vs. 49%; P = 0.022), less lymphadenopathy (2.9% vs. 16.7%; P = 0.041), no erythema nodosum (0% vs. 12.8%; P = 0.029) and no arthralgia (0% vs. 25.5%; P = 0.001). Conversely, uveitis was more common in the EOS group (55.9% vs. 20.6%; P < 0.001). Pathological confirmation was obtained significantly less frequently in the EOS group (67.7% vs. 85.3%; P = 0.023). Corticosteroid-related side effects were significantly more common in the EOS group (100% vs. 75.9%; P = 0.030). CONCLUSION: Epidemiology and clinical presentation of EOS differs from YOS, including more comorbidities and more uveitis. Elderly patients are more prone to corticosteroid side effects.

[Tryptase: A practical guide for the physician]. / Dosage de la tryptase : un guide d'utilisation pour le clinicien.

Tryptase is the most abundant endopeptidase released by mast cells degranulation, involved in many pro and anti-inflammatory processes. Normal serum tryptase range is 0-11.4 µg/L. Tryptase is a useful diagnostic tool for anaphylaxis, systemic mastocytosis (SM) and mast cell activation syndrome (MCAS), where specific threshold values must be used. SM diagnosis criteria include evidence of dense mast cell infiltrate either in the bone marrow or the affected organ (such as skin), presence of KIT D816V mutation and elevated serum tryptase level (>20 µg/L). In SM, tryptase level is correlated with the burden of mast cells in bone marrow. MCAS should be considered in case of severe and recurrent typical clinical signs of systemic mast cell activation involving at least two organs, associated with an increase in serum tryptase level of 20% + 2 µg/L from the individual's baseline. Anaphylaxis is the most severe among hypersensitivity reactions. A clonal mast cell disorder is a central question in anaphylaxis and appropriate explorations should be conducted in these patients. Triggers for anaphylactic reactions vary significantly in the general population and in patients with MS or MCAS. Finally, physicians must be aware of the many pathological and physiological situations that affect tryptase levels.

[Functional immunoassays in the setting of infectious risk and immunosuppressive therapy of non-HIV immunocompromised patients]. / Place des tests immunitaires fonctionnels dans la prise en charge du risque infectieux et de la gestion des thérapies immunosuppressives chez les patients immunodéprimés non-VIH.

The holistic approach of the human immune system is based on the study of its components collectively driving a functional response to an immunogenic stimulus. To appreciate a specific immune dysfunction, a condition is mimicked ex vivo and the immune response induced is assessed. The application field of such assays are broad and expanding, from the diagnosis of primary and secondary immunodeficiencies, immunotherapy for cancer to the management of patients at-risk for infections and vaccination. These assays are immune monitoring tools that may contribute to a personalised and precision medicine. The purpose of this review is to describe immune functional assays available in the setting of non-HIV acquired immune deficiency. First, we will address the use of theses assays in the diagnosis of opportunistic infections such as viral reactivation. Secondly, we will report the usefulness of these assays to assess vaccine efficacy and to manage immunosuppressive therapies.

Improvement in contraceptive coverage and gynecological care of adult women with cystic fibrosis following the implementation of an on-site gynecological consultation.

OBJECTIVE: Our study aimed to evaluate the impact of the introduction of a new gynecologic referral service in our adult Cystic Fibrosis (CF) center on contraceptive coverage, gynecological follow-up regularity, and cervical cancer screening coverage. STUDY DESIGN: We implemented an on-site gynecological consultation in our adult CF center in 2015. We compared the results of two surveys conducted successively in 2014 and in 2017 in a cohort of women with CF attending the Lyon CF center. Women completed the same self-report written questionnaire as in 2014. Main outcome measures were the comparisons of contraceptive coverage, gynecological follow-up regularity, and cervical cancer screening coverage between 2014 and 2017. RESULTS: All the 136 women (100%) who attended the clinic in 2017 participated. Contraceptive prevalence rate increased from 69%(CI95%:60.3-78.1) to 86%(CI95%:79.6-92.9) between 2014 and 2017 (p = 0.005). Among transplanted patients, the contraceptive prevalence rate was 92.3%(CI95%:82.0-100) in 2017. Long acting reversible contraceptive use markedly increased from 10% to 21.6% (p = 0.005). The proportion of women that reported an access to gynecological care increased between 2014 and 2017 (74%(CI95%:66.3-82.0) vs 91%(CI95%:86.9-95.4), p < 0.005) and reached 100% among transplanted patients. Cervical cancer screening improved (55%(CI95%:51.2-68.8) vs 85%(CI95%:78.6-90.6) women ever screened) (p < 0.0005) and reached 100% among transplanted patients. CONCLUSIONS: We observed an improvement in contraceptive coverage and gynecological care of adult women with CF following the implementation of a dedicated gynecological consultation in the CF center. IMPLICATIONS: Service linkages and formal links between CF centers and gynecologists can facilitate access to disease-specific contraceptive counseling, adequate gynecological management and cervical cancer screening.

[Quality criteria for the transition to adult care in French CF centers - results from the SAFETIM APP study?] / Critères de qualité pour la transition dans la mucoviscidose en France (suivi des adolescents, des familles et des équipes, pour une transition idéale en mucoviscidose ­ analyse des pratiques professionnelles).

INTRODUCTION: SAFETIM-APP compiled an inventory of professional practice in the 45 French cystic fibrosis reference centres (CFRC), between February 2015 and December 2016, related to the transition of adolescents with cystic fibrosis to adult centres. METHOD: This multicentre cross-sectional study addressed the modalities of the transition in CFRCs and proposed a list of items that could be used to establish quality criteria. Quantitative analysis of the criteria and a qualitative analysis of the transition procedure were carried out. RESULTS: A total of 77% of the CFRCs that were contacted took part. Transition lasted 3 to 5 years and began at around 15 years of age. Nine criteria were described as fundamental, including: collaboration between teams, taking adolescence into account, having a time for adolescents to speak with the physician alone, defining a program including therapeutic education, involving the family, accompanying the parents. Seven additional criteria were noted to be important, including: re-announcing the diagnosis, identifying a common thread (caregiver) accompanying the family, scheduling adult follow-up from paediatrics onwards, visiting the adult department, organizing a formal departure/reception time, initiating the process early enough, identifying indicators to evaluate practices. CONCLUSION: The transition processes in place in CFRCs can be improved by implementing the use of these quality criteria systematically.

[Gynecological management and follow-up in women with cystic fibrosis]. / Suivi et prise en charge gynécologique chez les femmes atteintes de mucoviscidose.

INTRODUCTION: Most women with cystic fibrosis reach adulthood and should have appropriate gynecological follow-up and contraception. BACKGROUND: There is no specific contra-indication to any contraception due to cystic fibrosis itself. Combined estrogen-progesterone contraception can be used in most cases (including transplanted women). In case of transplantation, intra-uterine devices should be used carefully (risk of pelvic inflammatory disease, potential risk of contraceptive failure with copper intra-uterine devices). Hormonal contraceptives may not be effective in women taking corrective treatments aiming to correct the maturation defect of the chloride channel. Screening for cervical cancer is recommended with a pap smear every three years for women aged 25-65, but yearly and starting at a younger age among transplanted women who are at higher risk for cervical dysplasia. Human Papillomavirus vaccination should be offered to all young women. OUTLOOK: Women with cystic fibrosis and health care providers should be better informed on screening and on sexual and reproductive health to avoid unplanned pregnancies, to take into account drug interactions and to prevent cervical disease. CONCLUSION: Regular and specific gynecological management is mandatory in cases of cystic fibrosis.

[Thrombosis during thrombopoietin receptor agonist treatment for immune thrombocytopenia. A French multicentric observational study]. / Thromboses sous agonistes du récepteur de la thrombopoïétine au cours du purpura thrombopénique immunologique. Étude rétrospective multicentrique en France.

INTRODUCTION: Thrombopoietin-receptor agonists (TPO-RA) are marketed for immune thrombocytopenia (ITP). They have been associated to thrombosis occurrence in randomized controlled trials. However, the characteristics of these thromboses in the real-life practice as well as their management are poorly known. The objectives of this study were to determine the risk factors, circumstances and management of thrombosis occurring during exposure to TPO-RA in ITP. METHODS: We carried out a multicentre retrospective study in France. Moreover, all cases reported to the French pharmacovigilance system were also analyzed. RESULTS: Overall, 41 thrombosis (13 arterial) in 36 ITP patients (14 males and 22 females, mean age: 59 years) were recorded between January 2009 and October 2015. Twenty patients were treated with romiplostim, 15 with eltrombopag and 1 was treated by both medications. Thirty-three (92%) of the patients had another risk factor for thrombosis. Ten (28%) had an history of thrombosis and 13 (36%) received immunoglobulin in the month preceding the thrombotic event. Three had antiphospholipid antibodies; congenital low-risk thrombophilia was found in 4 cases; 18 patients (50%) were splenectomized. Median platelet count at the time of thrombosis was 172G/l (1-1049G/l). In 22 patients (56%), a good prognosis was associated with the thrombosis and was not linked with TPO-RA withdrawal. Bleeding events occurred in 14% of the patients treated with antiplatelet or anticoagulant drug, including 5% serious events (1 death of intracranial haemorrhage, 1 death of haemorrhagic shock). CONCLUSIONS: The thrombotic risk may be carefully assessed before starting TPO-RA in ITP patients. The impact of antiphospholipid antibodies and of congenital thrombophilia remains to be defined. Thrombosis evolution seems independent of TPO-RA management. Bleeding manifestations seem rare. Poor prognosis was mainly due to ischemic sequelae.

Reduced bone volumetric density and weak correlation between infection and bone markers in cystic fibrosis adult patients.

UNLABELLED: In our current adult CF population, low BMD prevalence was only 20 %, lower than that historically described. We found a mild increase of serum RANK-L levels, independent from the bone resorption level. The increased fracture risk in CF may be explained by a lower tibial cortical thickness and total vBMD. INTRODUCTION: Bone disease is now well described in cystic fibrosis (CF) adult patients. CF bone disease is multifactorial but many studies suggested the crucial role of inflammation. The objectives of this study were, in a current adult CF population, to assess the prevalence of bone disease, to examine its relationship with infections and inflammation, and to characterize the bone microarchitecture using high resolution peripheral scanner (HR-pQCT). METHODS: Fifty-six patients (52 % men, 26 ± 7 years) were assessed in clinically stable period, during a respiratory infection, and finally 14 days after the end of antibiotic therapy. At each time points, we performed a clinical evaluation, lung function tests, and biochemical tests. Absorptiometry and dorso-lumbar radiographs were also performed. A subgroup of 40 CF patients (63 % men, 29 ± 6 years) underwent bone microarchitecture assessment and was age- and gender-matched with 80 healthy controls. RESULTS: Among the 56 CF patients, the prevalence of low areal BMD (T-score < -2 at any site), was 20 % (95 % CI: [10.2 %; 32.4 %]). After infections, serum RANK-L (+24 %, p = 0.08) and OPG (+13 %, p = 0.04) were increased with a stable ratio. Microarchitectural differences were mostly observed at the distal tibia, with lower total and cortical vBMD and trabecular thickness (respectively -9.9, -3.0, and -5 %, p < 0.05) in CF patients compared to controls, after adjustment for age, gender, weight, and height. CONCLUSIONS: In this study, bone disease among adult CF patients was less severe than that previously described with only 20 % of CF patients with low BMD. We found a mild increase of biological marker levels and an impaired volumetric density of the tibia that may explain the increased fracture risk in CF population.

[Transition from paediatric to adult cystic fibrosis care centre]. / Mucoviscidose : transition du centre pédiatrique au centre adulte.

The number of adolescents and young adults with chronic diseases has increased dramatically over the last decade. This led paediatric teams to organize the transition to adult centres with the aim to ensure the quality of care and prognosis, adherence to survey and treatment. To promote a good work and family life is also a challenge. Several studies have shown the importance of a successful transition in cystic fibrosis (CF) in order to prevent complications and loss monitoring and to improve the perception of patients and their families. In France in 2003, cystic fibrosis centres (CRCM) have been identified and among them of adult CF centres. The regular increase of the adult centre's active file requires improving the transition process. It is necessary to improve the transition process and to prepare the young patient and their family early during adolescence. The process in place should concern the whole aspects of care, i.e., medical, psychological and educational. The transition to adulthood will be successful if it results in a stable state of the disease allowing family and career plans.

[New therapeutic developments in cystic fibrosis]. / Nouvelles thérapeutiques ciblant le canal chlorure dans la mucoviscidose.

Since the discovery of chloride secretion by the Cystic Fibrosis Transport regulator CFTR in 1983, and CFTR gene in 1989, knowledge about CFTR synthesis, maturation, intracellular transfer and function has dramatically expanded. These discoveries have led to the distribution of CF mutations into 6 classes with different pathophysiological mechanisms. In this article we will explore the state of art on CFTR synthesis and its chloride secretion function. We will then explore the consequences of the 6 classes of mutations on CFTR protein function and we will describe the new therapeutic developments aiming at correcting these defects.

Contraceptive practices and cervical screening in women with cystic fibrosis.

STUDY QUESTION: Is gynaecological management of women with cystic fibrosis (CF) adequate? SUMMARY ANSWER: Gynaecological care (frequency of follow-up, cervical screening and contraceptive use among sexually active women) in women with CF fails to reach the recommended level. WHAT IS KNOWN ALREADY: Little is known about gynaecological follow-up and cervical screening in CF. Only few studies have described contraceptive practices in cohorts of CF women. STUDY DESIGN, SIZE, DURATION: We did a cross-sectional study in a cohort of 155 CF women attending the Lyon adult centre. Women attending the CF adult centre in 2014 completed a written questionnaire about their contraceptive choices, frequency of gynaecological follow-up and cervical screening. Other clinical data were collected from the CF adult centre registry. PARTICIPANTS/MATERIALS, SETTING, METHODS: One hundred and twenty women (100%) answered the questionnaire, among whom two were post-menopausal (46 and 59 years of age), and five were pregnant. MAIN RESULTS AND THE ROLE OF CHANCE: Seventy-four per cent of the women declared they had undergone gynaecological follow-up (89% of the women with transplantation), and only 55% reported having at least one previous Pap smear test. Among the transplanted patients, only 58% had had a Pap smear test, despite immunosuppressive treatment. The overall rate of contraception was only 64% and in diabetic women, it was 61%. Among contraception users; 65% used oral contraception, predominantly combined estrogen-progestagen (47%); among diabetic patients, 26% used progestin-only contraception. Intrauterine device accounted for 10% of patients using contraception, and tubal ligation only 4%. LIMITATIONS, REASONS FOR CAUTION: This study is limited by its cross-sectional design. Despite an internal validation of the questionnaire showing an almost perfect agreement, the risk of recall bias has to be taken into account. WIDER IMPLICATIONS OF THE FINDINGS: This study of practices highlights the importance of improved information regarding sexuality, fertility and reproductive health in young women with CF. A regular gynaecological follow-up and cervical screening is mandatory in this population. Better gynaecological care and contraceptive advice would help to avoid unplanned pregnancies, and optimize contraceptive selection in relationship to specific clinical conditions.

FDG-PET/CT findings in systemic mastocytosis: a French multicentre study.

INTRODUCTION: Mastocytosis is a clonal haematological disease characterized by uncontrolled proliferation and the activation of mast cells. The value of FDG-PET/CT (FDG-PET) in mastocytosis has yet to be determined. METHODS: We retrospectively identified patients with an established diagnosis of systemic mastocytosis (SM), according to the WHO criteria, who underwent PET using the French Reference Centre for Mastocytosis database. Semi-quantitative and visual analysis of FDG-PET was performed and compared to the clinico-biological data. RESULTS: Our cohort included 19 adult patients, median age 65 years [range 58-74], including three with smouldering SM (SSM), three with aggressive SM (ASM), 10 with an associated clonal haematological non-mast-cell lineage disease (SM-AHNMD), and three with mast cell sarcoma (MCS). FDG-PET was performed at the time of the SM diagnosis (15/19), to evaluate lymph node (LN) activity (3/19) or the efficacy of therapy (1/19). FDG uptake was observed in the bone marrow (BM) (9/19, 47%), LN (6/19, 32%), spleen (12/19, 63%), or liver (1/19, 5%). No significant FDG uptake was observed in the SSM and ASM patients. A pathological FDG uptake was observed in the BM of 6/10 patients with SM-AHNMD, appearing as diffuse and homogeneous, and in the LN of 5/10 patients. All 3 MCS patients showed intense and multifocal BM pathological uptake, mimicking metastasis. No correlation was found between the FDG-PET findings and serum tryptase levels, BM mast cell infiltration percentage, and CD30 and CD2 expression by mast cells. CONCLUSIONS: FDG uptake does not appear to be a sensitive marker of mast cell activation or proliferation because no significant FDG uptake was observed in most common forms of mastocytosis (notably purely aggressive SM). However, pathological FDG uptake was observed in the SM-AHNMD and in MCS cases, suggesting a role of FDG-PET in their early identification and as a tool of therapeutic assessment in this subgroup of patients.

[Therapeutic update in cystic fibrosis]. / Actualité thérapeutique dans la mucoviscidose.

We present the recent therapeutic advances in the cystic fibrosis care. It concerns improvements in symptomatic treatment with the development of dry powder inhaled antibiotics that improved quality of life, and innovative treatments namely the modulators of the cystic fibrosis transmembrane protein conductance regulator (CFTR), molecules which act specifically at the level of the defective mechanisms implied in the disease. The life expectancy of cystic fibrosis patients born after 2000, is estimated now to be about 50 years. This improvement of survival was obtained with the organization of the care within the specialized centers for cystic fibrosis (Centre de ressource et de compétences de la mucoviscidose) and remains still based on heavy symptomatic treatments. Dry powder inhaled antibiotics constitute a significant time saving for patients to whom all the care can achieve two hours daily. Since 2012, the modulators of CFTR, molecules allowing a pharmacological approach targeted according to the type of the mutations, allows a more specific approach of the disease. Ivacaftor (Kalydeco(®)) which potentialises the function of the CFTR protein expressed on the cellular surface is now available for patients with the G551D mutation. Lumacaftor is going to be tested in association with ivacaftor in patients with the F508del mutation, that is present in at least 75% of the patients. The ataluren which allows the production of a functional protein CFTR in patients with a no sense mutation is the third representing of this new therapeutic class. We presently have numerous symptomatic treatments for the cystic fibrosis care. The development of CFTR modulators, today available to a restricted number of patients treated with ivacaftor represents a very promising therapeutic avenue. It will represent probably the first step to a personalized treatment according to CFTR genotype.