The impact of cystic fibrosis on work attendance and performance in adults living in rural and remote Western Australia.

J Cyst Fibros. 2017 Jan 18;:

Authors: Wood J, Jenkins S, Mulrennan S, Hill K

PMID: 28109711 [PubMed - as supplied by publisher]

Diagnosis of celiac disease and applicability of ESPGHAN guidelines in Mediterranean countries: a real life prospective study.

BMC Gastroenterol. 2017 Jan 21;17(1):17

Authors: Smarrazzo A, Misak Z, Costa S, Mičetić-Turk D, Abu-Zekry M, Kansu A, Abkari A, Bouziane-Nedjadi K, Ben Hariz M, Roma E, Velmishi V, Legarda Tamara M, Attard T, Djurisic V, Greco L, Magazzù G

Abstract
BACKGROUND: We assessed how the diagnosis of Celiac Disease (CD) is made and how the new ESPGHAN guidelines can be applied in children from countries with different resources.
METHODS: A real life prospective study was performed in 14 centres of 13 different Mediterranean countries. Participants were asked to apply the usual diagnostic work-up for CD according to their diagnostic facilities.
RESULTS: There were 1974 patients enrolled in the study, mean age 4 years, 10 months; 865 male, 1109 female. CD was confirmed in 511 (25.9%) and was unconfirmed in 1391 (70.5%) patients; 14 patients were diagnosed as having CD according to the new ESPGHAN guidelines, 43 patients were classified as having potential CD. In all participating countries the diagnosis of CD relied on histology of duodenal biopsy; in 5 countries, HLA, and in one country endomysial antibodies (EMA) were not available. Symptoms did not add a significant increase to the pre-test probability of serological tests. The positive predictive value of tissue transglutaminase type 2 (tTG) antibodies performed with different kits but all corresponding to those recommended by ESPGHAN was 96.1% (95% CI 94-97.9%) in presence of tTG > 10xULN. In 135 patients with tTG >10xULN, HLA genotyping was performed and in all it was compatible with CD.
CONCLUSIONS: The results of our study show that CD diagnosis still relies on intestinal biopsy in the Mediterranean area. New ESPGHAN criteria are not applicable in 5 countries due to lack of resources needed to perform HLA genotyping and, in one country, EMA assay. Further simplification of the new ESPGHAN guidelines might be made according to what preliminarily the present results suggest if confirmed by new prospective studies.

PMID: 28109250 [PubMed - in process]

Targeted In-Depth Quantification of Signaling Using Label-Free Mass Spectrometry.

Methods Enzymol. 2017;585:245-268

Authors: Cutillas PR

Abstract
Protein phosphorylation encodes information on the activity of kinase-driven signaling pathways that regulate cell biology. This chapter discusses an approach, named TIQUAS (targeted in-depth quantification of signaling), to quantify cell signaling comprehensively and without bias. The workflow-based on mass spectrometry (MS) and computational science-consists of targeting the analysis of phosphopeptides previously identified by shotgun liquid chromatography tandem MS (LC-MS/MS) across the samples that are being compared. TIQUAS therefore takes advantage of concepts derived from both targeted (data-independent) and data-dependent acquisition methods; phosphorylation sites are quantified in all experimental samples regardless of whether or not these phosphopeptides were identified by MS/MS in all runs. As a result, datasets are obtained containing quantitative information on several thousand phosphorylation sites in as many samples and replicates as required in the experimental design, and these rich datasets are devoid of a significant number of missing data points. This chapter discussed the biochemical, analytical, and computational procedures required to apply the approach and for obtaining a biological interpretation of the data in the context of our understanding of cell signaling regulation and kinase-substrate relationships.

PMID: 28109432 [PubMed - in process]

Reannotation of Genomes by Means of Proteomics Data.

Methods Enzymol. 2017;585:201-216

Authors: Armengaud J

Abstract
Omics approaches have become popular in biology as powerful discovery tools, and currently gain in interest for diagnostic applications. Establishing the accurate genome sequence of any organism is easy, but the outcome of its annotation by means of automatic pipelines remains imprecise. Some protein-encoding genes may be missed as soon as they are specific and poorly conserved in a given taxon, while important to explain the specific traits of the organism. Translational starts are also poorly predicted in a relatively important number of cases, thus impacting the protein sequence database used in proteomics, comparative genomics, and systems biology. The use of high-throughput proteomics data to improve genome annotation is an attractive option to obtain a more comprehensive molecular picture of a given organism. Here, protocols for reannotating prokaryote genomes are described based on shotgun proteomics and derivatization of protein N-termini with a positively charged reagent coupled to high-resolution tandem mass spectrometry.

PMID: 28109430 [PubMed - in process]

Parameter estimation in large-scale systems biology models: a parallel and self-adaptive cooperative strategy.

BMC Bioinformatics. 2017 Jan 21;18(1):52

Authors: Penas DR, González P, Egea JA, Doallo R, Banga JR

Abstract
BACKGROUND: The development of large-scale kinetic models is one of the current key issues in computational systems biology and bioinformatics. Here we consider the problem of parameter estimation in nonlinear dynamic models. Global optimization methods can be used to solve this type of problems but the associated computational cost is very large. Moreover, many of these methods need the tuning of a number of adjustable search parameters, requiring a number of initial exploratory runs and therefore further increasing the computation times. Here we present a novel parallel method, self-adaptive cooperative enhanced scatter search (saCeSS), to accelerate the solution of this class of problems. The method is based on the scatter search optimization metaheuristic and incorporates several key new mechanisms: (i) asynchronous cooperation between parallel processes, (ii) coarse and fine-grained parallelism, and (iii) self-tuning strategies.
RESULTS: The performance and robustness of saCeSS is illustrated by solving a set of challenging parameter estimation problems, including medium and large-scale kinetic models of the bacterium E. coli, bakerés yeast S. cerevisiae, the vinegar fly D. melanogaster, Chinese Hamster Ovary cells, and a generic signal transduction network. The results consistently show that saCeSS is a robust and efficient method, allowing very significant reduction of computation times with respect to several previous state of the art methods (from days to minutes, in several cases) even when only a small number of processors is used.
CONCLUSIONS: The new parallel cooperative method presented here allows the solution of medium and large scale parameter estimation problems in reasonable computation times and with small hardware requirements. Further, the method includes self-tuning mechanisms which facilitate its use by non-experts. We believe that this new method can play a key role in the development of large-scale and even whole-cell dynamic models.

PMID: 28109249 [PubMed - in process]

Affordable orphan drugs: A role for not-for-profit organisations.

Br J Clin Pharmacol. 2017 Jan 20;:

Authors: Davies EH, Fulton E, Brook D, Hughes DA

Abstract
The success of the Regulation on Orphan Medicinal Products in the European Union is evidenced by the 127 orphan drugs that have had market authorisation since 2000. However the incentives aimed to stimulate research and development have had the unintended consequence of increasing drug cost, resulting in many orphan drugs not being cost-effective. Orphan drugs command an increasing share of the pharmaceutical market and account for a disproportionate amount of healthcare expenditure. Orphan drug ownership by socially motivated, not-for-profit organisations may facilitate access to more affordable orphan drugs, for the benefit of patients and healthcare systems alike. Using repurposed drugs as a paradigm, this review navigates the regulatory hurdles, describes the legal context and identifies funding opportunities, in a bid to facilitate and encourage not-for-profit organisations to lead on the development of affordable orphan drugs.

PMID: 28109021 [PubMed - as supplied by publisher]

Pharmacophore-based screening and drug repurposing exemplified on glycogen synthase kinase-3 inhibitors.

Mol Divers. 2017 Jan 21;:

Authors: Crisan L, Avram S, Pacureanu L

Abstract
The current study was conducted to elaborate a novel pharmacophore model to accurately map selective glycogen synthase kinase-3 (GSK-3) inhibitors, and perform virtual screening and drug repurposing. Pharmacophore modeling was developed using PHASE on a data set of 203 maleimides. Two benchmarking validation data sets with focus on selectivity were assembled using ChEMBL and PubChem GSK-3 confirmatory assays. A drug repurposing experiment linking pharmacophore matching with drug information originating from multiple data sources was performed. A five-point pharmacophore model was built consisting of a hydrogen bond acceptor (A), hydrogen bond donor (D), hydrophobic (H), and two rings (RR). An atom-based 3D quantitative structure-activity relationship (QSAR) model showed good correlative and satisfactory predictive abilities (training set [Formula: see text]; test set: [Formula: see text]; whole data set: stability [Formula: see text]). Virtual screening experiments revealed that selective GSK-3 inhibitors are ranked preferentially by Hypo-1, but fail to retrieve nonselective compounds. The pharmacophore and 3D QSAR models can provide assistance to design novel, potential GSK-3 inhibitors with high potency and selectivity pattern, with potential application for the treatment of GSK-3-driven diseases. A class of purine nucleoside antileukemic drugs was identified as potential inhibitor of GSK-3, suggesting the reassessment of the target range of these drugs.

PMID: 28108896 [PubMed - as supplied by publisher]

Airway mucus, inflammation and remodeling: emerging links in the pathogenesis of chronic lung diseases.

Cell Tissue Res. 2017 Jan 20;:

Authors: Zhou-Suckow Z, Duerr J, Hagner M, Agrawal R, Mall MA

Abstract
Airway mucus obstruction is a hallmark of many chronic lung diseases including rare genetic disorders such as cystic fibrosis (CF) and primary ciliary dyskinesia, as well as common lung diseases such as asthma and chronic obstructive pulmonary disease (COPD), which have emerged as a leading cause of morbidity and mortality worldwide. However, the role of excess airway mucus in the in vivo pathogenesis of these diseases remains poorly understood. The generation of mice with airway-specific overexpression of epithelial Na(+) channels (ENaC), exhibiting airway surface dehydration (mucus hyperconcentration), impaired mucociliary clearance (MCC) and mucus plugging, led to a model of muco-obstructive lung disease that shares key features of CF and COPD. In this review, we summarize recent progress in the understanding of causes of impaired MCC and in vivo consequences of airway mucus obstruction that can be inferred from studies in βENaC-overexpressing mice. These studies confirm that mucus hyperconcentration on airway surfaces plays a critical role in the pathophysiology of impaired MCC, mucus adhesion and airway plugging that cause airflow obstruction and provide a nidus for bacterial infection. In addition, these studies support the emerging concept that excess airway mucus per se, probably via several mechanisms including hypoxic epithelial necrosis, retention of inhaled irritants or allergens, and potential immunomodulatory effects, is a potent trigger of chronic airway inflammation and associated lung damage, even in the absence of bacterial infection. Finally, these studies suggest that improvement of mucus clearance may be a promising therapeutic strategy for a spectrum of muco-obstructive lung diseases.

PMID: 28108847 [PubMed - as supplied by publisher]

Predictive performance of different kidney function estimation equations in lung transplant patients.

Clin Biochem. 2017 Jan 17;:

Authors: Degen DA, Janardan J, Barraclough KA, Schneider HG, Barber T, Barton H, Snell G, Levvey B, Walker RG

Abstract
BACKGROUND: There has been limited examination of the performance of glomerular filtration rate estimation (eGFR) equations in lung transplant populations. This study aimed to compare the performance of serum creatinine and cystatin C based eGFR equations with Tc-99m diethylenetriaminepentaacetic acid (DTPA) GFR measurements in individuals with end-stage lung disease, either prior to, or following, lung transplantation.
METHODS: In this prospective observational study, participants underwent GFR measurements with Tc-99m Pentetate. Measured results were compared with GFR estimates derived from estimation equations [4-variable Modification of Diet in Renal Disease, Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine, cystatin C and creatinine-cystatin C combined equations].
RESULTS: Ninety-seven individuals were studied (77 post- and 20 wait-listed for transplantation). Median (range) radionucleotide GFR was 56.7ml/min/1.73m(2) (22.8-109.2ml/min/1.73m(2)). In the study cohort as a whole, the CKD-EPI creatinine-cystatin C combined equation showed the highest performance, but was only slightly superior to the CKD-EPI creatinine equation. However, in individuals with cystic fibrosis, low arm muscle mass and/or low body mass index, all of the creatinine-based equations showed unacceptable performance. In these subgroups, improved GFR estimation was seen with the CKD-EPI cystatin C equation, and predictions were better still using the CKD-EPI creatinine-cystatin C combined equation.
CONCLUSIONS: This study shows adequate predictive ability of CKD-EPI creatinine in the cohort as a whole, but unacceptable performance in patients with cystic fibrosis, low arm muscle area and/or low body mass index. Our findings demonstrate that cystatin C may be a preferable filtration marker in these subgroups.

PMID: 28108166 [PubMed - as supplied by publisher]

Adherence to therapies in cystic fibrosis: a targeted literature review.

Expert Rev Respir Med. 2017 Jan 20;:1-17

Authors: Narayanan S, Mainz JG, Gala S, Tabori H, Grossoehme D

Abstract
INTRODUCTION: Cystic fibrosis (CF) is a life-shortening condition with no cure. Available therapies relieving the symptoms of CF are complex and time-consuming. A comprehensive review assessing adherence to different CF therapies, association of adherence with outcomes, and factors influencing adherence could inform optimal patient management strategies. Areas covered: A targeted literature review of studies published from 2010-2016 assessed adherence to CF therapies. Nineteen studies qualified for inclusion. Adherence to CF therapies was sub-optimal, and varied by treatment, mode of treatment administration, age, season, time and method of adherence measurement. Adherence to ivacaftor and inhaled antibiotics were reported higher than dornase alfa or hypertonic saline, oral pancreatic enzyme and vitamin supplements, and airway clearance therapy. Several patient, healthcare provider and treatment related factors influenced adherence. Sub-optimal adherence was shown to impact clinical and economic burden of the disease. Expert commentary: Higher adherence to CF therapies can lower disease burden, and improve patient outcomes. Healthcare providers and policy makers should devise patient-centered and caregiver-enabled interventions to improve adherence. Research on long-term adherence and outcomes associated with promising oral treatments such as CFTR modulators is needed. Identifying ways to overcome key barriers to adherence can positively affect outcomes associated with CF.

PMID: 28107795 [PubMed - as supplied by publisher]

Implementing Genomic Clinical Decision Support for Drug-Based Precision Medicine.

CPT Pharmacometrics Syst Pharmacol. 2017 Jan 20;:

Authors: Freimuth RR, Formea CM, Hoffman JM, Matey E, Peterson JF, Boyce RD

PMID: 28109071 [PubMed - as supplied by publisher]

Integrated omics analysis of specialized metabolism in medicinal plants.

Plant J. 2017 Jan 21;:

Authors: Rai A, Saito K, Yamazaki M

Abstract
Medicinal plants are the rich source of highly diverse specialized metabolites with important pharmacological properties. Until recently, plant biologists were limited in their approach to explore biosynthetic pathways of these metabolites, mainly due to the scarcity of plant genomics resources. Recent advancements in the high-throughput large-scale analytical methods have enabled plant biologists to discover biosynthetic pathways for important plant-based medicinal metabolites. Reduced cost to generate omics datasets, and the development of computational tools for their analysis and integration have led to the elucidation of biosynthetic pathways of several plant origin bio-active metabolites. These discoveries have inspired synthetic biology approaches to develop microbial systems producing plant origin bioactive metabolites, an alternative for sustainable source of medicinally important chemicals. Since the world population is increasing at a rapid pace and so is the demand for medicinal compounds, understanding the complete biosynthesis of specialized metabolites becomes important. Here, we have reviewed the contributions of major omics approaches and their integration towards our understanding of biosynthetic pathways of bioactive metabolites. We have briefly discussed different approaches to integrate omics datasets to extract biological relevant knowledge, and application of omics datasets in the construction and reconstruction of metabolic models. This article is protected by copyright. All rights reserved.

PMID: 28109168 [PubMed - as supplied by publisher]

Systematic analysis of molecular mechanisms for HCC metastasis via text mining approach.

Oncotarget. 2017 Jan 17;:

Authors: Zhen C, Zhu C, Chen H, Xiong Y, Tan J, Chen D, Li J

Abstract
OBJECTIVE: To systematically explore the molecular mechanism for hepatocellular carcinoma (HCC) metastasis and identify regulatory genes with text mining methods.
RESULTS: Genes with highest frequencies and significant pathways related to HCC metastasis were listed. A handful of proteins such as EGFR, MDM2, TP53 and APP, were identified as hub nodes in PPI (protein-protein interaction) network. Compared with unique genes for HBV-HCCs, genes particular to HCV-HCCs were less, but may participate in more extensive signaling processes. VEGFA, PI3KCA, MAPK1, MMP9 and other genes may play important roles in multiple phenotypes of metastasis.
MATERIALS AND METHODS: Genes in abstracts of HCC-metastasis literatures were identified. Word frequency analysis, KEGG pathway and PPI network analysis were performed. Then co-occurrence analysis between genes and metastasis-related phenotypes were carried out.
CONCLUSIONS: Text mining is effective for revealing potential regulators or pathways, but the purpose of it should be specific, and the combination of various methods will be more useful.

PMID: 28108733 [PubMed - as supplied by publisher]

Commentary on EPC Methods: An Exploration of the Use of Text-Mining Software in Systematic Reviews.

J Clin Epidemiol. 2017 Jan 17;:

Authors: Paynter R, Bañez LL, Erinoff E, Matsuura J, Potter S

PMID: 28108352 [PubMed - as supplied by publisher]

A physarum-inspired prize-collecting steiner tree approach to identify subnetworks for drug repositioning.

BMC Syst Biol. 2016 Dec 05;10(Suppl 5):128

Authors: Sun Y, Hameed PN, Verspoor K, Halgamuge S

Abstract
BACKGROUND: Drug repositioning can reduce the time, costs and risks of drug development by identifying new therapeutic effects for known drugs. It is challenging to reposition drugs as pharmacological data is large and complex. Subnetwork identification has already been used to simplify the visualization and interpretation of biological data, but it has not been applied to drug repositioning so far. In this paper, we fill this gap by proposing a new Physarum-inspired Prize-Collecting Steiner Tree algorithm to identify subnetworks for drug repositioning.
RESULTS: Drug Similarity Networks (DSN) are generated using the chemical, therapeutic, protein, and phenotype features of drugs. In DSNs, vertex prizes and edge costs represent the similarities and dissimilarities between drugs respectively, and terminals represent drugs in the cardiovascular class, as defined in the Anatomical Therapeutic Chemical classification system. A new Physarum-inspired Prize-Collecting Steiner Tree algorithm is proposed in this paper to identify subnetworks. We apply both the proposed algorithm and the widely-used GW algorithm to identify subnetworks in our 18 generated DSNs. In these DSNs, our proposed algorithm identifies subnetworks with an average Rand Index of 81.1%, while the GW algorithm can only identify subnetworks with an average Rand Index of 64.1%. We select 9 subnetworks with high Rand Index to find drug repositioning opportunities. 10 frequently occurring drugs in these subnetworks are identified as candidates to be repositioned for cardiovascular diseases.
CONCLUSIONS: We find evidence to support previous discoveries that nitroglycerin, theophylline and acarbose may be able to be repositioned for cardiovascular diseases. Moreover, we identify seven previously unknown drug candidates that also may interact with the biological cardiovascular system. These discoveries show our proposed Prize-Collecting Steiner Tree approach as a promising strategy for drug repositioning.

PMID: 28105946 [PubMed - in process]

Applications of chemogenomic library screening in drug discovery.

Nat Rev Drug Discov. 2017 Jan 20;:

Authors: Jones LH, Bunnage ME

Abstract
The allure of phenotypic screening, combined with the industry preference for target-based approaches, has prompted the development of innovative chemical biology technologies that facilitate the identification of new therapeutic targets for accelerated drug discovery. A chemogenomic library is a collection of selective small-molecule pharmacological agents, and a hit from such a set in a phenotypic screen suggests that the annotated target or targets of that pharmacological agent may be involved in perturbing the observable phenotype. In this Review, we describe opportunities for chemogenomic screening to considerably expedite the conversion of phenotypic screening projects into target-based drug discovery approaches. Other applications are explored, including drug repositioning, predictive toxicology and the discovery of novel pharmacological modalities.

PMID: 28104905 [PubMed - as supplied by publisher]

Apply Resources to Practice: Use Current Genetics and Genomics Content in Oncology.

Clin J Oncol Nurs. 2017 Feb 01;21(1):34-38

Authors: Mahon SM

Abstract
Genetic and genomic science directly affects oncology nursing care. Many resources are available to enable oncology nurses to better understand and deliver competent genomic care to patients and families. This article relays resources for germline genetic testing, tumor profiling, pharmacogenomics, and nursing education.

PMID: 28107338 [PubMed - in process]

Burkholderia cepacia Complex Regulation of Virulence Gene Expression: A Review.

Genes (Basel). 2017 Jan 19;8(1):

Authors: Sousa SA, Feliciano JR, Pita T, Guerreiro SI, Leitão JH

Abstract
Burkholderia cepacia complex (Bcc) bacteria emerged as opportunistic pathogens in cystic fibrosis and immunocompromised patients. Their eradication is very difficult due to the high level of intrinsic resistance to clinically relevant antibiotics. Bcc bacteria have large and complex genomes, composed of two to four replicons, with variable numbers of insertion sequences. The complexity of Bcc genomes confers a high genomic plasticity to these bacteria, allowing their adaptation and survival to diverse habitats, including the human host. In this work, we review results from recent studies using omics approaches to elucidate in vivo adaptive strategies and virulence gene regulation expression of Bcc bacteria when infecting the human host or subject to conditions mimicking the stressful environment of the cystic fibrosis lung.

PMID: 28106859 [PubMed - in process]

Determinants of Serum Glycerophospholipid Fatty Acids in Cystic Fibrosis.

Int J Mol Sci. 2017 Jan 18;18(1):

Authors: Drzymała-Czyż S, Krzyżanowska P, Koletzko B, Nowak J, Miśkiewicz-Chotnicka A, Moczko JA, Lisowska A, Walkowiak J

Abstract
The etiology of altered blood fatty acid (FA) composition in cystic fibrosis (CF) is understood only partially. We aimed to investigate the determinants of serum glycerophospholipids' FAs in CF with regard to the highest number of FAs and in the largest cohort to date. The study comprised 172 CF patients and 30 healthy subjects (HS). We assessed Fas' profile (gas chromatography/mass spectrometry), CF transmembrane conductance regulator (CFTR) genotype, spirometry, fecal elastase-1, body height and weight Z-scores, liver disease, diabetes and colonization by Pseudomonas aeruginosa. The amounts of saturated FAs (C14:0, C16:0) and monounsaturated FAs (C16:1n-7, C18:1n-9, C20:1n-9, C20:3n-9) were significantly higher in CF patients than in HS. C18:3n-6, C20:3n-6 and C22:4n-6 levels were also higher in CF, but C18:2n-6, C20:2n-6 and C20:4n-6, as well as C22:6n-3, were lower. In a multiple regression analysis, levels of seven FAs were predicted by various sets of factors that included age, genotype, forced expiratory volume in one second, pancreatic status and diabetes. FA composition abnormalities are highly prevalent in CF patients. They seem to be caused by both metabolic disturbances and independent clinical risk factors. Further research into the influence of CFTR mutations on fat metabolism and desaturases' activity is warranted.

PMID: 28106773 [PubMed - in process]

Cystic fibrosis physicians' perspectives on the timing of referral for lung transplant evaluation: a survey of physicians in the United States.

BMC Pulm Med. 2017 Jan 19;17(1):21

Authors: Ramos KJ, Somayaji R, Lease ED, Goss CH, Aitken ML

Abstract
BACKGROUND: Prior studies reveal that a significant proportion of patients with cystic fibrosis (CF) and advanced lung disease are not referred for lung transplant (LTx) evaluation. We sought to assess expert CF physician perspectives on the timing of LTx referral and investigate their LTx knowledge.
METHODS: We developed an online anonymous survey that was distributed by the Cystic Fibrosis Foundation (CFF) to the medical directors of all CFF-accredited care centers in the United States in 2015. The survey addressed only adult patients (≥18 years old) and was sent to 119 adult CF physicians, 86 CFF-affiliated CF physicians (who see adults and children, but have smaller program sizes than adult or pediatric centers), and 127 pediatric CF physicians (who see some adults, but mostly children). The focus of the questions was on CFF-care center characteristics, physician experience and indications/contraindications to referral for LTx evaluation.
RESULTS: There were 114/332 (34%) total responses to the survey. The response rates were: 57/119 (48%) adult physicians, 12/86 (14%) affiliate physicians and 43/127 (34%) pediatric physicians; 2 physicians did not include their CFF center type. Despite the poor ability of FEV1 < 30% to predict death within 2 years, 94% of responding CF physicians said they would refer an adult patient for LTx evaluation if the patient's lung function fell to FEV1 < 30% predicted. Only 54% of respondents report that pulmonary hypertension would trigger referral. Pulmonary hypertension is an internationally recommended indication to list a patient for LTx (not just for referral for evaluation). Very few physicians (N = 17, 15%) employed components of the lung allocation score (LAS) to determine the timing of referral for LTx evaluation. Interestingly, patient preference not to undergo LTx was "often" or "always" the primary patient-related reason to defer referral for LTx evaluation for 41% (47/114) of respondents.
CONCLUSIONS: Some potential barriers to timely LTx referral for patients with CF include physician knowledge regarding non-lung function-based recommendations related to timing of referral and listing for LTx, and patient preference not to undergo LTx. Further exploration of physician-level and CF patient-level barriers to timely LTx referral is warranted.

PMID: 28103851 [PubMed - in process]