High-Throughput Surface Liquid Absorption and Secretion Assays to Identify F508del CFTR Correctors Using Patient Primary Airway Epithelial Cultures.

SLAS Discov. 2019 May 20;:2472555219849375

Authors: Berg A, Hallowell S, Tibbetts M, Beasley C, Brown-Phillips T, Healy A, Pustilnik L, Doyonnas R, Pregel M

Abstract
High-throughput screening for drug discovery is increasingly utilizing cellular systems of high physiological relevance, such as patient primary cells and organoid cultures. We used 3D-cultured cystic fibrosis patient bronchial epithelial cells to screen for new small-molecule correctors of the disease-causing F508del mutation in CFTR. Impaired mucociliary clearance due to insufficient airway hydration is a hallmark of cystic fibrosis and we used a simple measure of surface liquid levels to quantify F508del CFTR correction in cultured bronchial epithelial cells. Two robust assay formats were configured and used to screen more than 100,000 compounds as mixtures or individual compounds in 96-well format. The corrector discovery success rate, as measured by the number of hits confirmed by an electrophysiology assay on patient primary bronchial epithelial cells, was superior to screens in cell lines expressing recombinant F508del CFTR. Several novel corrector scaffolds were discovered that when combined with the clinical corrector VX-809 delivered combination responses greater than double that of VX-809 alone. This work exemplifies the advantages of a disease-relevant readout and 3D-cultured patient primary cells for the discovery of new drug candidates.

PMID: 31107611 [PubMed - as supplied by publisher]

Sequence similarity searches for morphine biosynthesis enzymes in bacteria yield putative targets for understanding associations between infection and opiate administration.

J Med Microbiol. 2019 May 20;:

Authors: Zhan SH, French L

Abstract
Exploiting the immunosuppressive, analgesic and highly addictive properties of morphine could increase the success of a bacterial pathogen. Therefore, we performed sequence similarity searches for two morphine biosynthesis demethylases in bacteria. For thebaine 6-O-demethylase and codeine O-demethylase, we found strong alignments to three (Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii) of the six ESKAPE pathogens (Enterococcus faecalis, Staphylococcus aureus, K. pneumoniae, A. baumannii, P. aeruginosa and Enterobacter species) that are commonly associated with drug resistance and nosocomial infections. Expression of the aligned sequence found in P. aeruginosa (NP_252880.1/PA4191) is upregulated in isolates obtained from cystic fibrosis patients. Our findings provide putative mechanistic targets for understanding the role of morphine in pathogenicity.

PMID: 31107204 [PubMed - as supplied by publisher]

Macro- and microvascular functions in cystic fibrosis adults without cardiovascular risk factors: A case-control study.

Monaldi Arch Chest Dis. 2019 May 20;89(2):

Authors: Vizzardi E, Sciatti E, Bonadei I, Cani DS, Menotti E, Prati F, Dallapellegrina L, Metra M, Berlendis M, Poli P, Padoan R

Abstract
Increasing survival from cystic fibrosis show untypical systems involvement, such as cardiocirculatory. In particular, the presence of CFTR in smooth muscle and endothelial cells, systemic inflammation and oxidative stress could explain vascular alterations in these patients. We aimed at noninvasely evaluating macro- and microvascular dysfunction in cystic fibrosis adults without cardiovascular risk factors. Twenty-twoadults affected by cystic fibrosis and 24 healthy volunteers matched for age and sex were enrolled. None had known cardiovascular risk factors. All people underwent blood pressure measurement, microvascular function assessment by EndoPAT-2000 device (calculating RH-PAT index) and macrovascular evaluation by pulse wave velocity (PWV). RH-PAT index was significantly lower in patients than in controls (1.74±0.59 vs 2.33±0.34; p<0.001). Thirteen patients of 22 had a value inferior to the threshold of 1.67 (59.1%), while no controls had (p<0.001). Carotid-femoral PWV did not differ between the two groups (5.2±1.5 m/s vs 5.4±1.1; p=0.9), while brachial-ankle one did (11.0±2.2 m/s vs 10.1±0.8 m/s; p=0.04).Adults patients affected by cystic fibrosis show peripheral endothelial dysfunction, which is the first alteration in atherosclerotic phenomenon. Moreover, arterial stiffness measured by PWV unclearly seems to differ respect of healthy people, perhaps because PWV alterations are typical of above 50 years old people. It is unclear what prognostic role of future developing of atherosclerotic disease these findings could be, but it seems evident that cystic fibrosis directly affects cardiovascular system itself.

PMID: 31107040 [PubMed - in process]

Cystic fibrosis year in review 2018, part 1.

Pediatr Pulmonol. 2019 May 20;:

Authors: Savant AP, McColley SA

Abstract
Cystic fibrosis research and case reports were robust in the year 2018. This report summarizes research and cases related to Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator therapies, inflammation and infection, epidemiology and the physiologic, and imaging assessment of disease.

PMID: 31106528 [PubMed - as supplied by publisher]

Anti-pseudomonad Activity of Manuka Honey and Antibiotics in a Specialized ex vivo Model Simulating Cystic Fibrosis Lung Infection.

Front Microbiol. 2019;10:869

Authors: Roberts AEL, Powell LC, Pritchard MF, Thomas DW, Jenkins RE

Abstract
Pseudomonas aeruginosa causes problematic chronic lung infections in those suffering from cystic fibrosis. This is due to its antimicrobial resistance mechanisms and its ability to form robust biofilm communities with increased antimicrobial tolerances. Using novel antimicrobials or repurposing current ones is required in order to overcome these problems. Manuka honey is a natural antimicrobial agent that has been used for many decades in the treatment of chronic surface wounds with great success, particularly those infected with P. aeruginosa. Here we aim to determine whether the antimicrobial activity of manuka honey could potentially be repurposed to inhibit pulmonary P. aeruginosa infections using two ex vivo models. P. aeruginosa isolates (n = 28) from an international panel were tested for their susceptibility to manuka honey and clinically relevant antibiotics (ciprofloxacin, ceftazidime, and tobramycin), alone and in combination, using conventional antimicrobial susceptibility testing (AST). To increase clinical applicability, two ex vivo porcine lung (EVPL) models (using alveolar and bronchiolar tissue) were used to determine the anti-biofilm effects of manuka honey alone and in combination with antibiotics. All P. aeruginosa isolates were susceptible to manuka honey, however, varying incidences of resistance were seen against antibiotics. The combination of sub-inhibitory manuka honey and antibiotics using conventional AST had no effect on activity against the majority of isolates tested. Using the two ex vivo models, 64% (w/v) manuka honey inhibited many of the isolates where abnormally high concentrations of antibiotics could not. Typically, combinations of both manuka honey and antibiotics had increased antimicrobial activity. These results highlight the potential of manuka honey as a future antimicrobial for the treatment of pulmonary P. aeruginosa isolates, clearing potential infection reservoirs within the upper airway.

PMID: 31105667 [PubMed]

Study of 109 Achromobacter spp. isolates from 9 French CF centres reveals the circulation of a multiresistant clone of A. xylosoxidans belonging to ST 137.

J Cyst Fibros. 2019 May 16;:

Authors: Amoureux L, Sauge J, Sarret B, Lhoumeau M, Bajard A, Tetu J, Bador J, Neuwirth C, MucoMicrobes group

Abstract
We previously reported the distribution of Achromobacter spp. (species and Sequence Types (ST)) in our French Cystic Fibrosis (CF) centre. In the present study we collected 109 Achromobacter isolates (1/patient) from 9 other French CF Centres for species identification, antimicrobial susceptibility testings and Multilocus-Sequence-Typing (MLST) analysis. Ten species were detected, A. xylosoxidans being the most predominant one (73.4% of the isolates). Piperacillin-tazobactam, ceftazidime, imipenem, meropenem and ciprofloxacin were respectively active against 88, 70, 79, 72 and 23% of the isolates. Among the 79 A. xylosoxidans isolates, 46 STs were detected. Interestingly, ST 137, recovered in 4 centres (5 patients), was previously detected in our centre (2 patients). The strains from the 7 patients belonged to the same pulsotype (pulsed-field-gel-electrophoresis analysis) and harboured acquired resistance to meropenem, ceftazidime, ciprofloxacin, and except for 2 isolates, to imipenem and piperacillin-tazobactam. This is the first description in France of a circulating multiresistant A. xylosoxidans strain.

PMID: 31104975 [PubMed - as supplied by publisher]

Pediatric Glittre ADL-test in cystic fibrosis: Physiological parameters and respiratory mechanics.

Physiother Theory Pract. 2019 May 20;:1-8

Authors: Almeida AC, Wamosy RMG, Ludwig Neto N, Mucha FC, Schivinski CIS

Abstract
BACKGROUND: To evaluate the functional capacity in children and adolescents with cystic fibrosis (CF) through the pediatric Glittre ADL-test (TGlittre-P) and its implications for respiratory mechanics, physiological parameters and clinical markers.
METHODS: Impulse oscillometry system (IOS) parameters, vital signs (heart rate, respiratory rate and blood pressure), perception of dyspnea and peripheral oxygen saturation (SpO2) were assessed before and immediately after the TGlittre-P. Test performance was correlated with age, quality of life, disease severity, nutrition, spirometry and IOS parameters.
RESULTS: Twenty-six patients were included thirteen boys, mean age of 9.54 ± 1.94 and FEV1 of 71.45%±22.67%. The mean time to complete the test was 2.94 min, similar to that predicted for healthy children. There was a correlation of time with age, as well as with some IOS parameters. Disease severity, spirometric parameters, nutritional aspects and quality of life (QoL) were correlated with performance in the TGlittre-P. Immediate increase of vital signs and decline in SpO2 were observed after the test, without an impact on IOS parameters.
CONCLUSION: Patients with CF showed similar performance and changes of vital signs at the TGlittre-P compared to reference values for healthy children. There were no immediate changes in parameters for the assessed respiratory mechanics. Also, there was no correlation of time to complete the TGLittre-P test with respiratory mechanics, physiological parameters and clinical markers.

PMID: 31104537 [PubMed - as supplied by publisher]

Diagnosis of Allergic Bronchopulmonary Aspergillosis Exacerbations.

J Allergy Clin Immunol Pract. 2017 Nov - Dec;5(6):1599-1600

Authors: Giavina-Bianchi P, Kalil J

PMID: 29122158 [PubMed - indexed for MEDLINE]

The wait for the waitlist: The next challenge in the lung allocation system.

J Heart Lung Transplant. 2017 03;36(3):250-252

Authors: Englum BR, Hartwig MG

PMID: 28110831 [PubMed - indexed for MEDLINE]

Catalase prevents myeloperoxidase self-destruction in response to oxidative stress.

J Inorg Biochem. 2019 May 04;197:110706

Authors: Ali I, Khan SN, Chatzicharalampous C, Bai D, Abu-Soud HM

Abstract
Catalase (CAT) and myeloperoxiase (MPO) are heme-containing enzymes that have attracted attention for their role in the etiology of numerous respiratory disorders such as cystic fibrosis, bronchial asthma, and acute hypoxemic respiratory failure. However, information regarding the interrelationship and competition between the two enzymes, free iron accumulation, and decreased levels of non-enzymatic antioxidants at sites of inflammation is still lacking. Myeloperoxidase catalyzes the generation of hypochlorous acid (HOCl) from the reaction of hydrogen peroxide (H2O2) and chloride (Cl-). Self-generated HOCl has recently been proposed to auto-inhibit MPO through a mechanism that involves MPO heme destruction. Here, we investigate the interplay of MPO, HOCl, and CAT during catalysis, and explore the crucial role of MPO inhibitors and HOCl scavengers in protecting the catalytic site from protein modification of both enzymes against oxidative damage mediated by HOCl. We showed that CAT not only competes with MPO for H2O2 but also scavenges HOCl. The protective role provided by CAT versus the damaging effect provided by HOCl depends in part on the ratio between MPO/CAT and the affinity of the enzymes towards H2O2 versus HOCl. The severity of such damaging effects mainly depends on the ratio of HOCl to enzyme heme content. In addition to its effect in mediating protein modification and aggregation, HOCl oxidatively destroys the catalytic sites of the enzymes, which contain porphyrin rings and iron. Thus, modulation of MPO/CAT activities may be a fundamental feature of catalysis, and functions to down-regulate HOCl synthesis and prevent hemoprotein heme destruction and/or protein modification.

PMID: 31103890 [PubMed - as supplied by publisher]

Internally Quenched Fluorogenic substrates with unnatural amino acids for cathepsin G investigation.

Biochimie. 2019 May 16;:

Authors: Groborz K, Kołt S, Kasperkiewicz P, Drag M

Abstract
Cathepsin G is one of four members of the neutrophil serine protease family and constitutes an important biological target in various human inflammatory diseases, such as chronic obstructive pulmonary disease, acute respiratory distress syndrome and cystic fibrosis. Many studies have been focused on determining its biological roles, the latest ones concerning its involvement in acute myeloid leukemia, and as such, multiple chemical and biochemical tools were developed to investigate cathepsin G. Nevertheless, most of them lack selectivity or sensitivity and therefore cannot be used in complex systems. Here we present the development of an optimal cathepsin G Internally Quenched Fluorescence (IQF) substrate that incorporates unnatural amino acids causing the increase of its selectivity toward neutrophil elastase and potency in in vitro studies.

PMID: 31103725 [PubMed - as supplied by publisher]

Clustered randomized controlled trial of a clinic-based problem-solving intervention to improve adherence in adolescents with cystic fibrosis.

J Cyst Fibros. 2019 May 15;:

Authors: Quittner AL, Eakin MN, Alpern AN, Ridge AK, McLean KA, Bilderback A, Criado KK, Chung SE, Riekert KA

Abstract
BACKGROUND: In Cystic Fibrosis (CF), adherence to pulmonary medications is about 50% and decreases during adolescence. Effective interventions have not been integrated into CF care. This effectiveness study tested a brief, clinic-based behavioral intervention to improve adherence.
METHODS: iCARE (I Change Adherence and Raise Expectations) was a pragmatic, clustered, 2-arm randomized controlled trial at 18 CF Centers. 607 adolescents with CF, ages 11-20 years, participated. Centers were randomized to IMPACT (n = 9; 300 adolescents), a brief problem-solving + education intervention, or standard care (SC; n = 9; 307 adolescents). IMPACT was delivered during a regularly scheduled clinic visit by a member of the clinical care team. The primary outcome was composite pulmonary medication possession ratio (cMPR); secondary endpoints were lung function, Body Mass Index percentile, courses of IV antibiotics, and health-related quality of life at 12 months.
RESULTS: Effectiveness of the intervention was tested using mixed models, generalized estimating equations comparing IMPACT to SC. Fifty-eight percent of problem-solving sessions targeted barriers to airway clearance, exercise or nutrition, while 18% addressed pulmonary medications. Average intervention fidelity score was 67% (SD = 14%; Range = 25-100%). No significant intervention effects were found for cMPR or any of the secondary outcomes compared to SC.
CONCLUSIONS: The IMPACT intervention did not improve medication adherence or health outcomes over 12 months. Challenges to implementing the intervention as intended during busy clinic visits were identified.
TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01232478; URL: www.clinicaltrials.gov.

PMID: 31103533 [PubMed - as supplied by publisher]

Fertility considerations and attitudes about family planning among women with cystic fibrosis.

Contraception. 2019 May 15;:

Authors: Traxler SA, Chavez V, Hadjiliadis D, Shea JA, Mollen C, Schreiber CA

Abstract
OBJECTIVE: Our objective was to explore knowledge, attitudes, and beliefs about pregnancy and contraceptive decision-making among reproductive-aged women with cystic fibrosis.
STUDY DESIGN: In this qualitative study, we used purposive sampling of reproductive age women enrolled in the Adult Cystic Fibrosis program at Penn Medicine. We conducted semi-structured, one-on-one interviews, lasting 30-60 minutes. Interviews were audio-recorded and transcribed verbatim. Data were analyzed using thematic analysis.
RESULTS: We interviewed 24 women. Participants described shortened life span, personal health status, and impact of cystic fibrosis on a potential child as three factors that were central to family planning. Future pregnancy intentions, perception of fertility including misconceptions, and provider counseling influenced related contraception utilization.
CONCLUSIONS: Women with cystic fibrosis described thoughtful considerations about desired pregnancies to be planned during times of optimal health. Gaps in knowledge may limit a woman's ability to make the most informed family planning decisions. Implications Having CF directly affects women's decisions around pregnancy and family planning. Understanding what motivates women with CF to use or not to use contraception can improve family planning care delivery to this population.

PMID: 31102630 [PubMed - as supplied by publisher]

Cystic Fibrosis Associated Liver Disease in Lung Transplant Recipients.

Liver Transpl. 2019 May 18;:

Authors: Mallea J, Bolan C, Cortese C, Harnois D

Abstract
Cystic fibrosis (CF) is an autosomal recessive disease characterized by mutations in the gene that encodes for the CF transmembrane conductance regulator protein (CFTR). As the life expectancy of individuals with CF continues to increase through improved treatment protocols, the likelihood of multiple organ involvement, particularly liver comorbidities, also increases and requires continued interdisciplinary management. Liver related manifestations of CF include biliary strictures, hepatic steatosis, and cirrhosis, and non-cirrhotic portal hypertension. A better understanding of CF progression in adult patients, consistent diagnostic methodology and criteria for CF-related diseases, as well as subsequent surgical interventions and drug therapies, must be aligned for individualization of treatments across specialties to maximize survival and quality of life in this growing patient population This article is protected by copyright. All rights reserved.

PMID: 31102574 [PubMed - as supplied by publisher]

Successful adjunctive use of bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa infection in a cystic fibrosis patient.

Infection. 2019 May 17;:

Authors: Law N, Logan C, Yung G, Furr CL, Lehman SM, Morales S, Rosas F, Gaidamaka A, Bilinsky I, Grint P, Schooley RT, Aslam S

Abstract
INTRODUCTION: We describe the use of bacteriophage therapy in a 26-year-old cystic fibrosis (CF) patient awaiting lung transplantation.
HOSPITAL COURSE: The patient developed multidrug resistant (MDR) Pseudomonas aeruginosa pneumonia, persistent respiratory failure, and colistin-induced renal failure. We describe the use of intravenous bacteriophage therapy (BT) along with systemic antibiotics in this patient, lack of adverse events, and clinical resolution of infection with this approach. She did not have recurrence of pseudomonal pneumonia and CF exacerbation within 100 days following the end of BT and underwent successful bilateral lung transplantation 9 months later.
CONCLUSION: Given the concern for MDR P. aeruginosa infections in CF patients, BT may offer a viable anti-infective adjunct to traditional antibiotic therapy.

PMID: 31102236 [PubMed - as supplied by publisher]

Antibody-Mediated Rejection in a Multiple Lung Transplant Patient: A Case Report.

Transplant Proc. 2019 May;51(4):1296-1298

Authors: Radeczky P, Ghimessy ÁK, Farkas A, Csende K, Mészáros L, Török K, Fazekas L, Agócs L, Kocsis Á, Bartók T, Dancs T, Tóth KK, Schönauer N, Bogyó L, Bohács A, Madurka I, Elek J, Döme B, Rényi-Vámos F, Lang G, Gieszer B

Abstract
Lung transplant is an effective way to treat many end-stage lung diseases. However, one of the main barriers of allograft organ transplant is still the immunologic rejection of transplanted tissue, which is a response of the HLA molecules. Rejection is a complex process involving both T-cell-mediated delayed-type hypersensitivity reactions and antibody-mediated hypersensitivity reactions to histocompatibility molecules on foreign grafts. We report the case of a 25-year-old female patient with cystic fibrosis who underwent 2 lung transplants because of her initial diagnosis and appearance of bronchiolitis obliterans syndrome after the first transplant. Only 13 months after the second transplant, despite the therapies applied, a new rejection occurred associated with high mean fluorescent intensity donor-specific antibody levels, which resulted later in the death of the patient. The present case draws attention to the importance of matching HLA molecules between donor and recipient in addition to immunosuppressive therapy.

PMID: 31101218 [PubMed - in process]

Testicular Cancer in a Lung Transplant Patient With Cystic Fibrosis: A Case Report.

Transplant Proc. 2019 May;51(4):1293-1295

Authors: Barczi E, Meszaros M, Bohacs A, Geczi L, Vereczkey I, Müller V

Abstract
BACKGROUND: Cystic fibrosis (CF) is one of the most common genetic disorders that develops from a mutation of the cystic fibrosis transmembrane regulator gene. Patients with CF are known to be at risk for malignancies, and lung transplantation-associated immunosuppression further increases this risk.
CASE REPORT: We describe a case of a 29-year-old male patient with CF who developed testicular cancer 14 months after a lung transplantation. Immunosuppressive therapy included antithymocyte globulin induction and tacrolimus, mycophenolate, and prednisolone maintenance therapy as compared to standard alemtuzumab induction, followed by tacrolimus and prednisolone, as used in our center. He underwent semicastration and refused chemotherapy. Immunosuppressive treatment was changed to tacrolimus, everolimus, and prednisolone, which did not influence excellent graft function. This case report highlights the importance of uro-oncological observation of patients with CF following lung transplantations.

PMID: 31101217 [PubMed - in process]

Lung Transplantation in Hungary From Cardiac Surgeons' Perspective.

Transplant Proc. 2019 May;51(4):1263-1267

Authors: Fazekas L, Ghimessy Á, Gieszer B, Radeczky P, Mészáros L, Török K, Bogyó L, Hartyánszky I, Pólos M, Daróczi L, Agócs L, Kocsis Á, Bartók T, Dancs T, Tóth KK, Schönauer N, Madurka I, Elek J, Döme B, Rényi-Vámos F, Lang G, Farkas A

Abstract
Thoracic organ transplantation made a fresh start in Hungary with the first double lung transplant in December 2015. This major leap in Hungarian transplantation was preceded by almost 10 years of preparation, new infrastructure development, and structural changes not only at the organizational level but in human resources as well. In the following years, until recently, altogether 47 lung transplants were performed on 24 men and 23 women. The underlying pathologies were as follows: chronic obstructive pulmonary disease, 25; cystic fibrosis, 11; idiopathic pulmonary fibrosis, 7; as well as other diseases, including bronchiectasis, eosinophilic granuloma, lymphangioleiomyomatosis, and primary pulmonary hypertension in 4 cases. The youngest recipient was 13 and the oldest was 65 years old. Overall survival rates at 30 days and at 1 year were 96% and 82%, respectively. No patients were lost in the cystic fibrosis and other diseases group, whereas the 1-year survival rates of the chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis groups were 73% and 71%, respectively. The results show the robustness and viability of the program, although there is still opportunity for further improvement. In this short paper, we summarize the fields of possible further cooperation of thoracic and cardiac teams as well as future challenges facing the new Hungarian lung transplant program.

PMID: 31101211 [PubMed - in process]

First 3 Years of the Hungarian Lung Transplantation Program.

Transplant Proc. 2019 May;51(4):1254-1257

Authors: Gieszer B, Ghimessy Á, Radeczky P, Farkas A, Csende K, Bogyó L, Fazekas L, Kovács N, Madurka I, Kocsis Á, Agócs L, Török K, Bartók T, Dancs T, Schönauer N, Tóth K, Eszes N, Bohács A, Czebe K, Csiszér E, Mihály S, Kovács L, Müller V, Elek J, Rényi-Vámos F, Lang G

Abstract
In this article we summarize the results of the first 3 years after launching the Hungarian Lung Transplantation Program.
PATIENTS AND METHODS: The first lung transplant in Hungary was carried out on December 12, 2015, with the collaboration of the National Institute of Oncology and the Semmelweis University. Up to December 31, 2018, a total of 62 lung transplants were performed. Data were analyzed retrospectively. Patients were listed for lung transplant after the indication was established by the National Lung Transplantation Committee. Donor lungs were procured from brain-dead donors only.
RESULTS: Within this period our team was involved in 87 lung procurements, 61 of which resulted in bilateral lung transplant and 1 in single-sided transplant. The operative approach was unilateral thoracotomy (n = 1), bilateral thoracotomy (n = 1), or clamshell incision (n = 60) with venoarterial extracorporeal membrane oxygenation support. The underlying disease of the recipients was obstructive lung disease (n = 30), lung fibrosis (n = 11), cystic fibrosis (n = 18), primary pulmonary hypertension (n = 2), histiocytosis-X syndrome (n = 1), bronchiectasis (n = 2), lymphangioleiomyomatosis (n = 1), and retransplant because of bronchiolitis obliterans syndrome (n = 1). The youngest patient was 13 years of age, while the oldest was 65 years. Three patients died in the early postoperative phase. One-year survival was 80%.
DISCUSSION: The number of cases rises steadily in the Hungarian Lung Transplantation Program, which is exceptional compared with the start of other centrums. The incidence of complications and mortality is comparable with those of other experienced centers around the world. Our future goal is to broaden our waiting list, thus increasing the number of lung transplants carried out.

PMID: 31101209 [PubMed - in process]

Development and External Validation of 1- and 2- year Mortality Prediction Models in Cystic Fibrosis.

Eur Respir J. 2019 May 16;:

Authors: Stanojevic S, Sykes J, Stephenson AL, Aaron SD, Whitmore GA

Abstract
INTRODUCTION: We aimed to develop a clinical tool for predicting 1- and 2-year risk of death for patients with cystic fibrosis (CF). The model considers patients' overall health status as well as risk of intermittent shock events in calculating the risk of death.
METHODS: Canadian CF Registry data from 1982 to 2015 were used to develop a predictive risk model using threshold regression. A 2-year risk of death estimated conditional probability of surviving the second year given survival for the first year. UK CF Registry data from 2008 to 2013 were used to externally validate the model.
RESULTS: The combined effect of CF chronic health status and CF intermittent shock risk provided a simple clinical scoring tool for assessing 1-year and 2-year risk of death for an individual CF patient. At a threshold risk of death of 20% or greater, the one-year model had a sensitivity of 74% and specificity of 96%. The area under the receiver operating curve (AUC) for the 2-year mortality model was significantly greater than the AUC for a model that predicted survival based on FEV1 below 30% predicted (AUC 0.95 versus 0.68 respectively, p<0.001). The Canadian-derived model validated well with the UK data and correctly identified 79% of deaths and 95% of survivors in a single year in the UK.
CONCLUSIONS: The prediction models provide an accurate risk of death over a one and two-year time horizon. The models performed equally well when validated in an independent UK CF population.

PMID: 31097523 [PubMed - as supplied by publisher]