Cystic fibrosis: NHS England strikes deal to offer triple combination treatment.

BMJ. 2020 Jul 01;370:m2643

Authors: Iacobucci G

PMID: 32611555 [PubMed - in process]

Macrocyclic Transmembrane Anion Transporters via a One-Pot Condensation Reaction.

Org Lett. 2020 Jul 02;22(13):5104-5108

Authors: Saha P, Madhavan N

Abstract
Synthetic chloride transporters are potential therapeutic agents for cystic fibrosis and cancer. Reported herein are macrocyclic transmembrane chloride transporters prepared by a one-pot condensation reaction. The most efficient macrocycle possesses a fine balance of hydrophobicity for membrane permeation and hydrophilicity for ion recognition. The macrocycle transports chloride ions by forming channels in the membrane. Hydrogen bonds and anion-π interactions assist chloride transport.

PMID: 32610925 [PubMed - in process]

CFTR Regulates the Proliferation, Migration and Invasion of Cervical Cancer Cells by Inhibiting the NF-κB Signalling Pathway.

Cancer Manag Res. 2020;12:4685-4697

Authors: Wu Z, Li J, Zhang Y, Hu L, Peng X

Abstract
Background: The cystic fibrosis transmembrane conductance regulator (CFTR) and nuclear factor κB (NF-κB) signalling pathways are currently regarded as co-regulators of the occurrence of cervical cancer. However, the detailed mechanism of CFTR- and NF-κB-mediated effects in cervical cancer remains to be elucidated. This study aimed to investigate the mechanism by which CFTR and NF-κB influence the development of cervical cancer.
Patients and Methods: CFTR ΔF508 mutation and CFTR promoter methylation were detected in cervical tissue samples. NF-κB p65 and IκBα protein levels were tested in HeLa cells with CFTR overexpression and knockdown by Western blotting. The effects of CFTR on cell proliferation, migration, and invasion were examined in HeLa cells by WST-1 and soft agar assays, cell wound scratch assay, and Matrigel invasion assays, respectively. The protein-protein interaction (PPI) network was constructed by using GeneMANIA. GeneCoDis3 was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis on genes in the PPI network.
Results: CFTR mutation and CFTR promoter methylation were not associated with the occurrence of cervical cancer. NF-κB p65 protein levels were decreased in CFTR overexpression lines and increased in CFTR knockdown lines, and IκBα levels were affected in the opposite manner, indicating that CFTR inhibited the NF-κB signalling pathway. CFTR also regulated the cell proliferation, migration, and invasion ability of cervical cancer cells. When CFTR was overexpressed, cell proliferation, migration, and invasion ability were decreased. There were 20 genes that interacted with CFTR. KEGG pathway analysis showed enrichment in the gastric acid secretion, chemokine signalling, bile secretion and apoptosis pathways.
Conclusion: CFTR plays an important role in cancer cell proliferation, migration and invasion by inhibiting the NF-κB signalling pathway in cervical cancer.

PMID: 32606960 [PubMed]

CFTR Functions as a Tumor Suppressor and Is Regulated by DNA Methylation in Colorectal Cancer.

Cancer Manag Res. 2020;12:4261-4270

Authors: Liu C, Song C, Li J, Sun Q

Abstract
Purpose: Cystic fibrosis transmembrane conductance regulator (CFTR) was shown to be downregulated or silenced in carcinomas and acts as a candidate tumor suppressor gene. However, the function of CFTR gene in colorectal cancer (CRC) is still unclear. This aim of this study was to investigate the CFTR promoter methylation status and its impact on the expression and functional role of CFTR in CRC development.
Patients and Methods: CFTR expression in CRC tissues and CRC cell lines was detected via quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The promoter methylation status of CFTR was measured using methylation-specific PCR (MSP). colony formation, transwell, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were used to evaluate the effect of CFTR overexpression in CRC cell lines.
Results: qRT-PCR and IHC results indicated that CFTR expression was downregulated in the CRC tissues compared to the adjacent normal tissues. The promoter methylation status of CFTR was further analyzed in 70 CRC specimens. MSP validation showed methylation of CFTR promoter in 62.2% (45/70) of CRC tissues. The methylation of CFTR promoter was significantly associated with age (P=0.013) and lymph node metastasis (P=0.026) in CRC tissues. Results of transwell, MTT, and colony formation assays showed that CFTR overexpression inhibited the migration, invasion, and proliferation of CRC cells.
Conclusion: CFTR expression was downregulated in CRC and promoter methylation may be responsible for this downregulation. Overexpression of CFTR may suppress CRC tumor growth by inhibiting the proliferation, migration, and invasion of CRC cells. CFTR promoter methylation was significantly correlated with lymph node metastasis; thus, CFTR may be a potential marker for lymph node metastasis of CRC.

PMID: 32606923 [PubMed]

Activated L-Arginine/Nitric Oxide Pathway in Pediatric Cystic Fibrosis and Its Association with Pancreatic Insufficiency, Liver Involvement and Nourishment: An Overview and New Results.

J Clin Med. 2020 Jun 26;9(6):

Authors: Brinkmann F, Hanusch B, Ballmann M, Mayorandan S, Bollenbach A, Chobanyan-Jürgens K, Jansen K, Schmidt-Choudhury A, Derichs N, Tsikas D, Lücke T

Abstract
Cystic fibrosis (CF; OMIM 219700) is a rare genetic disorder caused by a chloride channel defect, resulting in lung disease, pancreas insufficiency and liver impairment. Altered L-arginine (Arg)/nitric oxide (NO) metabolism has been observed in CF patients' lungs and in connection with malnutrition. The aim of the present study was to investigate markers of the Arg/NO pathway in the plasma and urine of CF patients and to identify possible risk factors, especially associated with malnutrition. We measured the major NO metabolites nitrite and nitrate, Arg, a semi-essential amino acid and NO precursor, the NO synthesis inhibitor asymmetric dimethylarginine (ADMA) and its major urinary metabolite dimethylamine (DMA) in plasma and urine samples of 70 pediatric CF patients and 78 age-matched healthy controls. Biomarkers were determined by gas chromatography-mass spectrometry and high-performance liquid chromatography. We observed higher plasma Arg (90.3 vs. 75.6 µM, p < 0.0001), ADMA (0.62 vs. 0.57 µM, p = 0.03), Arg/ADMA ratio (148 vs. 135, p = 0.01), nitrite (2.07 vs. 1.95 µM, p = 0.03) and nitrate (43.3 vs. 33.1 µM, p < 0.001) concentrations, as well as higher urinary DMA (57.9 vs. 40.7 µM/mM creatinine, p < 0.001) and nitrate (159 vs. 115 µM/mM creatinine, p = 0.001) excretion rates in the CF patients compared to healthy controls. CF patients with pancreatic sufficiency showed plasma concentrations of the biomarkers comparable to those of healthy controls. Malnourished CF patients had lower Arg/ADMA ratios (p = 0.02), indicating a higher NO synthesis capacity in sufficiently nourished CF patients. We conclude that NO production, protein-arginine dimethylation, and ADMA metabolism is increased in pediatric CF patients. Pancreas and liver function influence Arg/NO metabolism. Good nutritional status is associated with higher NO synthesis capacity and lower protein-arginine dimethylation.

PMID: 32604946 [PubMed]

Evaluation of the psychological status of mothers of children with cystic fibrosis and the relationship between children's clinical status.

J Paediatr Child Health. 2020 Jul 01;:

Authors: Unal Yuksekgonul A, Aslan AT, Sismanlar Eyuboglu T, Soysal S, Budakoglu II

Abstract
AIM: In this study, we aimed to determine the psychosocial status of primary care givers of children with cystic fibrosis (CF) and its relationship with the clinical scores of children with CF.
METHODS: Thirty-six patients with CF and their primary care givers were assessed. A personal information form, as well as the Parent Attitude Research Instrument, Maslach Burnout Inventory, Beck Depression Scale and modified Shwachman-Kulczycki Score, were used for data collection.
RESULTS: All the CF children's primary care givers were their mothers. The mothers' occupation and educational level affected their child-rearing attitudes (P < 0.05). Furthermore, the frequency of hospital visits and hospitalizations was associated with increased emotional exhaustion, depression and negative attitudes towards child-rearing (P < 0.05). Higher levels of emotional exhaustion in mothers were associated with increased depersonalization and depression, while personal accomplishment was associated with lower levels of depression (P < 0.05). Depression was present in 69.4% of mothers, and its severity was correlated with their children having a poor clinical status. Moreover, increased depression was associated with increased negative attitudes towards child-rearing (P < 0.05).
CONCLUSION: The rate of depression is high in mothers of children with CF. These mothers displayed a negative attitude towards child-rearing, along with the disease, which was more severe in their children. These mothers should undergo routine psychosocial screening, and support should be given to those in need.

PMID: 32610373 [PubMed - as supplied by publisher]

Enhancing Care for Individuals with Advanced Cystic Fibrosis Lung Disease.

Pediatr Pulmonol. 2020 Jul 01;:

Authors: Kapnadak SG, Ramos KJ, Dellon EP

Abstract
While remarkable advances in cystic fibrosis (CF) care have led to improvements in survival and quality of life, many individuals with CF are living with advanced cystic fibrosis lung disease (ACFLD) and others will face continued disease progression and its associated complex treatments and choices. This review will provide a summary of recently published guidelines for ACFLD care and lung transplant referral and highlight ongoing work to enhance care of those with ACFLD through improvements in medical and psychosocial care, palliative care, and care around lung transplantation. This article is protected by copyright. All rights reserved.

PMID: 32609949 [PubMed - as supplied by publisher]

Novel Therapies for Treatment of Resistant and Refractory Nontuberculous Mycobacterial Infections in Patients with Cystic Fibrosis.

Pediatr Pulmonol. 2020 Jul 01;:

Authors: Laudone TW, Garner L, Kam CW, Esther CR, McKinzie CJ

Abstract
Respiratory infections caused by non-tuberculous mycobacteria (NTM) are a major cause of morbidity for patients living with cystic fibrosis (CF), as NTM pulmonary disease (NTM-PD) is challenging to both diagnose and eradicate. Despite the lengthy courses of the established regimens recommended by the Cystic Fibrosis Foundation (CFF) and European Cystic Fibrosis Society (ECFS) consensus guidelines, only about 50-60% of patients achieve culture conversion, and treatment regimens are often complicated by antibiotic resistance and toxicities. Since publication of the CFF/ECFS guidelines, several new or alternative antibiotic regimens have been described for patients with CF who have NTM-PD. These regimens offer new options for patients who do not clear NTM with standard therapies or cannot utilize the usual regimens due to toxicities or drug-drug interactions This article is protected by copyright. All rights reserved.

PMID: 32609433 [PubMed - as supplied by publisher]

The Dance of Cystic Fibrosis: Experiences of Living with Cystic Fibrosis as an Adult.

J Clin Nurs. 2020 Jul 01;:

Authors: Varilek BM, Isaacson MJ

Abstract
AIM: This study sought to understand the experience of living with cystic fibrosis as an adult.
BACKGROUND: Cystic fibrosis is one of the most difficult chronic diseases to manage long-term because of numerous challenges faced on a day-to-day basis. The majority of studies focus on improving symptom response to new treatment regimens with the hope of prolonging life. Yet few qualitative studies explore the experience of adults with cystic fibrosis. What is missing from the current literature are the voices of people living with cystic fibrosis, especially as they age.
DESIGN: This study follows a hermeneutic phenomenology design guided by Martin Heidegger's philosophy.
METHODS: Semi-structured interviews were conducted with 9 adults living with cystic fibrosis. Hermeneutic phenomenology guided the data interpretation. This manuscript follows COREQ reporting guidelines.
RESULTS: Hermeneutic analysis revealed the overarching theme The Dance of Cystic Fibrosis which is supported by five themes: 1) The Paradox of Control, 2) Living Deaths, 3) Dancing with Death, 4) Relearning to Dance, and 5) Role of the Dance Partner.
CONCLUSIONS: The experience of living with cystic fibrosis as an adult is multidimensional and unique to each person. Despite the uniqueness, there is a shared experience that manifested as The Dance of Cystic Fibrosis. As life expectancy continues to increase for persons with cystic fibrosis, it is essential that researchers and healthcare professionals intentionally consider the life prolonging effects of the treatment regimen alongside the persons' experience with those effects.
RELEVANCE TO CLINICAL PRACTICE: Nurses at all levels of practice should be prepared to address the multifaceted experience of living with cystic fibrosis through thoughtful incorporation of open-ended questions. This allows patients to share their experience with nurses, augmenting their practice of delivering holistic care.

PMID: 32608531 [PubMed - as supplied by publisher]

The Use of Exaggerative Language in News Articles About Cystic Fibrosis Therapies : Exaggerative Language Describing Cystic Fibrosis Therapies.

J Gen Intern Med. 2020 Jun 30;:

Authors: Wenger D, Ottwell R, Johnson AL, Torgerson T, Vassar M

PMID: 32607933 [PubMed - as supplied by publisher]

Identifying patients' priorities for quality survivorship: conceptualizing a patient-centered approach to survivorship care.

J Cancer Surviv. 2020 Jun 30;:

Authors: Mead KH, Raskin S, Willis A, Arem H, Murtaza S, Charney L, Pratt-Chapman M

Abstract
PURPOSE: This study explored cancer survivors' experiences with and priorities for cancer survivorship care to describe a patient-centered approach to quality survivorship care.
METHODS: We conducted 22 focus groups with 170 adult survivors of breast, prostate, and colorectal cancer from six cities across the country and online. We used thematic analysis to identify participants' principles and priorities for quality survivorship care.
RESULTS: Based on our analysis of a limited group of cancer survivors, we identified two core principles that underlie participants' expectations for survivorship care and 11 practice priorities that reflect opportunities to improve patient-centeredness at the individual, interpersonal, and organizational levels. The principles reflect participants' desire to be better prepared for and equipped to accept and manage their chronic care needs post-cancer treatment. The priorities reflect practices that patients, providers, and cancer centers can engage in to ensure survivors' goals for post-treatment care are met.
CONCLUSIONS: Results from the study suggest the need to expand conceptualization of high-quality survivorship care. The survivor principles and practice priorities identified in this study challenge the field to organize a more patient-centered survivorship care system that empowers and respects patients and provides a holistic approach to survivors' chronic and long-term needs.
IMPLICATIONS FOR CANCER SURVIVORS: Quality cancer survivorship care must reflect patients' priorities. The findings from this study can be used to develop a patient-centered framework for survivorship care that can be used in conjunction with quality guidelines to ensure survivorship care is organized to achieve both clinical and patient-centered outcomes.

PMID: 32607715 [PubMed - as supplied by publisher]

The Use of Amikacin Liposome Inhalation Suspension (Arikayce) in the Treatment of Refractory Nontuberculous Mycobacterial Lung Disease in Adults.

Drug Des Devel Ther. 2020;14:2287-2294

Authors: Khan O, Chaudary N

Abstract
Nontuberculous mycobacteria (NTM) can cause and perpetuate chronic inflammation and lung infection. Despite having the diagnostic criteria, as defined by the American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA), clinicians find it challenging to diagnose and treat NTM-induced lung disease. Inhaled antibiotics are suitable for patients with lung infection caused by Pseudomonas aeruginosa and other organisms, but until recently, their utility in NTM-induced infection was not established. The most common NTM pathogens identified are the slow-growing Mycobacterium avium complex (MAC) and the rapid-growing M. abscessus complex (MABSC), both of which include several subspecies. Other less commonly isolated species include M. kansasii, M. simiae, and M. fortuitum. NTM strains are frequently more resistant than what is found in bacterial sputum cultures. Until recently, there was no approved inhaled antibiotic therapy for patients who were culture positive for pulmonary NTM infection. Of late, inhaled amikacin has been under investigation for the treatment of NTM-induced pulmonary infection. The FDA approved Arikayce (amikacin liposome inhalation suspension or ALIS) based on results from the ongoing Phase 3 CONVERT trial. In this study, the use of Arikayce met its primary endpoint of sputum culture conversion by the sixth month of treatment. The addition of Arikayce to guideline-based therapy led to negative sputum cultures for NTM by month 6 in 29% of patients compared to 8.9% of patients treated with guideline-based therapy alone. The effectiveness of Arikayce holds promise. However, due to limited data on Arikayce's safety, it is currently useful only for a specific population, particularly patients with refractory NTM-induced lung disease. Future trials must verify the target group and endorse the clinical benefits of Arikayce.

PMID: 32606598 [PubMed - in process]

The changing demography of the cystic fibrosis population: forecasting future numbers of adults in the UK.

Sci Rep. 2020 Jun 30;10(1):10660

Authors: Keogh RH, Tanner K, Simmonds NJ, Bilton D

Abstract
Improvements in management of cystic fibrosis (CF) through specialist centres in the UK have been associated with a step-change in life expectancy. With increasing numbers of adult patients there is a need to review health care provision to ensure it is sufficient to meet future needs. We used UK CF Registry data to project the number of patients aged 16-17 and 18 and older  up to 2030, and numbers therefore requiring specialist adult CF care. Survival modelling was used to estimate age-specific mortality rates. New-diagnosis rates were estimated using diagnoses observed in the Registry and national population figures. Uncertainty in projections was captured through 95% prediction intervals (PI). The number of adults (aged 18 and older) is expected to increase by 28% from 6,225 in 2017 to 7,988 in 2030 (95% PI 7,803-8,169), assuming current mortality rates. If mortality rates improve at the rate seen over recent years, the projected number increases to 8,579 (95% PI 8,386-8,764). The age distribution is also expected to change, with 36% of CF adults being over 40 in 2030, versus 21% in 2017. There is an urgent requirement to review adult CF health care provision, due to both increasing numbers and the changing care needs of an older population.

PMID: 32606329 [PubMed - in process]

COVID-19 meets Cystic Fibrosis: for better or worse?

Genes Immun. 2020 Jul 01;:

Authors: Peckham D, McDermott MF, Savic S, Mehta A

Abstract
Cystic fibrosis (CF) is one of the most common autosomal recessive life-limiting conditions affecting Caucasians. The resulting defect in the cystic fibrosis transmembrane conductance regulator protein (CFTR) results in defective chloride and bicarbonate secretion, as well as dysregulation of epithelial sodium channels (ENaC). These changes bring about defective mucociliary clearance, reduced airway surface liquid and an exaggerated proinflammatory response driven, in part, by infection. In this short article we explore the overlap in the pathophysiology of CF and COVID-19 infection and discuss how understanding the interaction between both diseases may shed light on future treatments.

PMID: 32606316 [PubMed - as supplied by publisher]

COVID-19: protecting the medically vulnerable.

Br J Nurs. 2020 06 25;29(12):660

Authors: Wood C

PMID: 32579456 [PubMed - indexed for MEDLINE]

A Pancreatic Enzyme Medication Self-Management Initiative.

Am J Nurs. 2020 05;120(5):58-62

Authors: Gallagher-Ford L, Tucker SJ, Gettis M, Dye BA

Abstract
This is the seventh article in a new series about evidence-based practice (EBP) that builds on AJN's award-winning previous series-Evidence-Based Practice, Step by Step-published between 2009 and 2011 (to access the series, go to http://links.lww.com/AJN/A133). This follow-up series features exemplars illustrating the various strategies that can be used to implement EBP changes-one of the most challenging steps in the EBP process.

PMID: 32332369 [PubMed - indexed for MEDLINE]

27 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

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23 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2020/07/01

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Technical validity and usability of a novel smartphone connected spirometry device for pediatric patients with asthma and cystic fibrosis.

Pediatr Pulmonol. 2020 Jun 27;:

Authors: Kruizinga MD, Essers E, Stuurman FE, Zhuparris A, van Eik N, Janssens HM, Groothuis I, Sprij AJ, Nuijsink M, Cohen AF, Driessen G

Abstract
BACKGROUND: Diagnosis and follow-up of respiratory diseases traditionally rely on pulmonary function tests (PFT), which are currently performed in hospitals and require trained personnel. Smartphone connected spirometers, like the Air Next spirometer, have been developed to aid in the home-monitoring of patients with pulmonary disease. The aim of this study was to investigate the technical validity and usability of the Air Next spirometer in pediatric patients.
METHODS: Device variability was tested with a calibrated syringe. 90 subjects aged 6-16 were included in a prospective cohort study. 58 subjects performed conventional spirometry and subsequent Air Next spirometry. The bias and the limits of agreement between the measurements were calculated. Furthermore, subjects used the device for 28 days at home and completed a subject satisfaction questionnaire at the end of the study period.
RESULTS: Inter-device variability was 2.8% and intra-device variability was 0.9%. The average difference between the Air Next and conventional spirometry was 40 mL for FEV1 and 3 mL for FVC. The limits of agreement were -270 mL and +352 mL for FEV1 and -403 mL and +397 mL for FVC. 45% of FEV1 measurements and 41% of FVC measurements at home were acceptable and reproducible according to ATS/ERS criteria. Parents scored difficulty, usefulness and reliability 1.9, 3.5 and 3.8 out of 5, respectively.
CONCLUSION: The Air Next device shows validity for the measurement of FEV1 and FVC in a pediatric patient population. This article is protected by copyright. All rights reserved.

PMID: 32592537 [PubMed - as supplied by publisher]

Novel Imaging Techniques for Cystic Fibrosis Lung Disease.

Pediatr Pulmonol. 2020 Jun 27;:

Authors: Goralski JL, Stewart NJ, Woods JC

Abstract
With an increasing number of patients with cystic fibrosis (CF) receiving highly effective CFTR modulator therapy, particularly at a young age, there is an increasing need to identify imaging tools that can detect and regionally visualize mild CF lung disease and subtle changes in disease state. In this review, we discuss the latest developments in imaging modalities for both structural and functional imaging of the lung available to CF clinicians and researchers, from the widely-available, clinically-utilized imaging methods for assessing CF lung disease - chest radiography and computed tomography - to newer techniques poised to become the next phase of clinical tools - structural/functional proton and hyperpolarized gas magnetic resonance imaging (MRI). Finally, we provide a brief discussion of several newer lung imaging techniques that are currently available only in selected research settings, including chest tomosynthesis, and fluorinated gas MRI. We provide an update on the clinical and/or research status of each technique, with a focus on sensitivity, early disease detection, and possibilities for monitoring treatment efficacy. This article is protected by copyright. All rights reserved.

PMID: 32592531 [PubMed - as supplied by publisher]