On the relationship between anion binding and chloride conductance in the CFTR anion channel.

Biochim Biophys Acta Biomembr. 2021 Jan 11;:183558

Authors: Linsdell P

Abstract
Mutations at many sites within the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel pore region result in changes in chloride conductance. Although chloride binding in the pore - as well as interactions between concurrently bound chloride ions - is thought to be important facets of the chloride permeation mechanism, little is known about the relationship between anion binding and chloride conductance. The present work presents a comprehensive investigation of a number of anion binding properties in different pore mutants with differential effects on chloride conductance. When multiple pore mutants are compared, conductance appears best correlated with the ability of anions to bind to the pore when it is already occupied by chloride ions. In contrast, conductance was not correlated with biophysical measures of anion:anion interactions inside the pore. Although these findings suggest anion binding is required for high conductance, mutations that strengthened anion binding had very little effect on conductance, especially at high chloride concentrations, suggesting that the wild-type CFTR pore is already close to saturated with chloride ions. These results are used to support a revised model of chloride permeation in CFTR in which the overall chloride occupancy of multiple loosely-defined chloride binding sites results in high chloride conductance through the pore.

PMID: 33444622 [PubMed - as supplied by publisher]

Exercise as a substitute for traditional airway clearance in cystic fibrosis: a systematic review.

Thorax. 2020 Dec 22;:

Authors: Ward N, Morrow S, Stiller K, Holland AE

Abstract
BACKGROUND: Exercise and traditional airway clearance techniques (ACTs) are both routinely recommended for people with cystic fibrosis (CF), with some people using exercise as a substitute for traditional ACTs. The effectiveness of this is unclear. We systematically reviewed the evidence for using exercise as a substitute for traditional ACTs in people with CF.
METHODS: A systematic database and literature search were undertaken of studies comparing exercise to rest or traditional ACTs. Primary outcomes were respiratory function, respiratory exacerbations and health-related quality of life. Secondary outcomes included mucociliary clearance (MCC), sputum weight and ease of expectoration. Data are mean difference (95% CI).
RESULTS: A total of 12 studies (15 reports) were included, all of short duration (single session to 2 weeks). In crossover trials, exercise did not improve forced expiratory volume in one second in comparison to rest, but peak expiratory flow was increased during treadmill exercise (mean difference (MD) range 1.00-1.16 L/s) and cycle ergometry (1.19 (0.96 to 1.42) L/s). Treadmill exercise improved MCC (2.6 (1.6 to 3.6)%) and ease of expectoration (MD range 1.3-1.8 cm) compared with rest. No consistent differences in respiratory function were evident when exercise was compared with traditional ACTs (four crossover studies). There was no significant difference in MCC or sputum weight in studies where forced expirations were included in the exercise intervention.
CONCLUSIONS: Exercise improves ease of expectoration and sputum clearance compared with rest. Exercise, incorporating forced expirations, may have similar effects to traditional ACTs over the short term. There are no data comparing exercise to traditional ACTs over the longer term.
PROSPERO REGISTRATION NUMBER: CRD42018102780.

PMID: 33443204 [PubMed - as supplied by publisher]

Influence of relevant cystic fibrosis bacteria on Scedosporium apiospermum and Scedosporium boydii growth and viability.

Braz J Microbiol. 2021 Jan 13;:

Authors: Marques AJ, Rollin-Pinheiro R, Xisto MIDDS, Dos Santos ALS, Barreto-Bergter E, Liporagi-Lopes LC

Abstract
Cystic fibrosis (CF) causes a variety of symptoms in different organs, but the majority of the morbidity and mortality of CF is related with pulmonary conditions. Primary infections are usually bacterial, and when treated with antibiotics, yeast infections appear or become more evident. Studies show that different microorganisms can co-inhabit the same environment and the interactions could be synergistic or antagonistic. Using techniques including viable and non-viable cell-to-cell interactions, mixed culture in liquid, and solid media sharing or not the supernatant, this study has evaluated interactions between the fungal species Scedosporium apiospermum and Scedosporium boydii with the bacterial species Staphylococcus aureus, Pseudomonas aeruginosa, and Burkholderia cepacia. Cell-to-cell interactions in liquid medium showed that P. aeruginosa and B. cepacia were able to reduce fungal viability but only in the presence of alive bacteria. Interactions without cell contact using a semi-permeable membrane showed that all bacteria were able to inhibit both fungal growths/viabilities. Cell-free supernatants from bacterial growth reduced fungal viability in planktonic fungal cells as well as in some conditions for preformed fungal biomass. According to the chemical analysis of the bacterial supernatants, the predominant component is protein. In this work, we verified that bacterial cells and their metabolites, present in the supernatants, can play anti-S. apiospermum and anti-S. boydii roles on fungal growth and viability.

PMID: 33442865 [PubMed - as supplied by publisher]

Surgery for Ampullary Cancer in a Patient with Pancreatic Lipomatosis Caused by Cystic Fibrosis.

Case Rep Gastroenterol. 2020 Sep-Dec;14(3):695-701

Authors: Vuurberg NE, Bakker I, van den Boom AL, de Haas RJ, Duiker EW, van den Heuvel MC, Klaase JM

Abstract
A patient with cystic fibrosis (CF) with pancreatic insufficiency presented with jaundice due to an ampullary tumour. CF is known for a higher incidence of gastrointestinal malignancies. The patient suffered from pancreatic insufficiency. At computed tomography (CT), pancreatic lipomatosis with absence of the pancreatic duct was seen. This is uncommon, also in patients with CF. During surgery, a total pancreatectomy was performed, because there was no possibility to construct a duct to mucosa anastomosis due to the absence of the pancreatic duct and more importantly the pancreas was already afunctional. The presence of lipomatosis increases the risk of leakage at the pancreaticojejunal anastomosis. Therefore, it is important to take this phenomenon, in this case already visible on the preoperative CT scan, into account during the workup for surgery.

PMID: 33442351 [PubMed]

Methods and feasibility study for exome sequencing as a universal second-tier test in newborn screening.

Genet Med. 2021 Jan 13;:

Authors: Ruiz-Schultz N, Sant D, Norcross S, Dansithong W, Hart K, Asay B, Little J, Chung K, Oakeson KF, Young EL, Eilbeck K, Rohrwasser A

Abstract
PURPOSE: Newborn screening disorders increasingly require genetic variant analysis as part of second-tier or confirmatory testing. Sanger sequencing and gene-specific next-generation sequencing (NGS)-based tests, the current methods of choice, are costly and lack scalability when expanding to new conditions. We describe a scalable, exome sequencing-based NGS pipeline with a priori analysis restriction that can be universally applied to any NBS disorder.
METHODS: De-identified abnormal newborn screening specimens representing severe combined immune deficiency (SCID), cystic fibrosis (CF), VLCAD deficiency, metachromatic leukodystrophy (MLD), and in silico sequence read data sets were used to validate the pipeline. To support interpretation and clinical decision-making within the bioinformatics pipeline, variants from multiple databases were curated and validated.
RESULTS: CFTR variant panel analysis correctly identified all variants. Concordance compared with diagnostic testing results for targeted gene analysis was between 78.6% and 100%. Validation of the bioinformatics pipeline with in silico data sets revealed a 100% detection rate. Varying degrees of overlap were observed between ClinVar and other databases ranging from 3% to 65%. Data normalization revealed that 11% of variants across the databases required manual curation.
CONCLUSION: This pipeline allows for restriction of analysis to variants within a single gene or multiple genes, and can be readily expanded to full exome analysis if clinically indicated and parental consent is granted.

PMID: 33442025 [PubMed - as supplied by publisher]

Modulation of cAMP metabolism for CFTR potentiation in human airway epithelial cells.

Sci Rep. 2021 Jan 13;11(1):904

Authors: Nguyen JP, Bianca M, Huff RD, Tiessen N, Inman MD, Hirota JA

Abstract
Cystic fibrosis (CF) is a genetic disease characterized by CF transmembrane regulator (CFTR) dysfunction. With over 2000 CFTR variants identified, in addition to known patient to patient variability, there is a need for personalized treatment. The discovery of CFTR modulators has shown efficacy in certain CF populations, however there are still CF populations without valid therapeutic options. With evidence suggesting that single drug therapeutics are insufficient for optimal management of CF disease, there has been an increased pursuit of combinatorial therapies. Our aim was to test cyclic AMP (cAMP) modulation, through ATP Binding Cassette Transporter C4 (ABCC4) and phosphodiesterase-4 (PDE-4) inhibition, as a potential add-on therapeutic to a clinically approved CFTR modulator, VX-770, as a method for increasing CFTR activity. Human airway epithelial cells (Calu-3) were used to test the efficacy of cAMP modulation by ABCC4 and PDE-4 inhibition through a series of concentration-response studies. Our results showed that cAMP modulation, in combination with VX-770, led to an increase in CFTR activity via an increase in sensitivity when compared to treatment of VX-770 alone. Our study suggests that cAMP modulation has potential to be pursued as an add-on therapy for the optimal management of CF disease.

PMID: 33441643 [PubMed - in process]

Gasdermin D restricts Burkholderia cenocepacia infection in vitro and in vivo.

Sci Rep. 2021 Jan 13;11(1):855

Authors: Estfanous S, Krause K, Anne MNK, Eltobgy M, Caution K, Abu Khweek A, Hamilton K, Badr A, Daily K, Carafice C, Baetzhold D, Zhang X, Li T, Wen H, Gavrilin MA, Haffez H, Soror S, Amer AO

Abstract
Burkholderia cenocepacia (B. cenocepacia) is an opportunistic bacterium; causing severe life threatening systemic infections in immunocompromised individuals including cystic fibrosis patients. The lack of gasdermin D (GSDMD) protects mice against endotoxin lipopolysaccharide (LPS) shock. On the other hand, GSDMD promotes mice survival in response to certain bacterial infections. However, the role of GSDMD during B. cenocepacia infection is not yet determined. Our in vitro study shows that GSDMD restricts B. cenocepacia replication within macrophages independent of its role in cell death through promoting mitochondrial reactive oxygen species (mROS) production. mROS is known to stimulate autophagy, hence, the inhibition of mROS or the absence of GSDMD during B. cenocepacia infections reduces autophagy which plays a critical role in the restriction of the pathogen. GSDMD promotes inflammation in response to B. cenocepacia through mediating the release of inflammasome dependent cytokine (IL-1β) and an independent one (CXCL1) (KC). Additionally, different B. cenocepacia secretory systems (T3SS, T4SS, and T6SS) contribute to inflammasome activation together with bacterial survival within macrophages. In vivo study confirmed the in vitro findings and showed that GSDMD restricts B. cenocepacia infection and dissemination and stimulates autophagy in response to B. cenocepacia. Nevertheless, GSDMD promotes lung inflammation and necrosis in response to B. cenocepacia without altering mice survival. This study describes the double-edged functions of GSDMD in response to B. cenocepacia infection and shows the importance of GSDMD-mediated mROS in restriction of B. cenocepacia.

PMID: 33441602 [PubMed - in process]

Cystic Fibrosis: Quality of Life and Radiological Monitoring.

Arch Bronconeumol. 2020 Dec 30;:

Authors: Diab Cáceres L, Girón Moreno RM, Caballero Sánchez-Robles P

PMID: 33441238 [PubMed - as supplied by publisher]

The biofilm of Burkholderia cenocepacia H111 contains an exopolysaccharide composed of l-rhamnose and l-mannose: Structural characterization and molecular modelling.

Carbohydr Res. 2020 Dec 30;499:108231

Authors: Bellich B, Jou IA, Buriola C, Ravenscroft N, Brady JW, Fazli M, Tolker-Nielsen T, Rizzo R, Cescutti P

Abstract
Burkholderia cenocepacia belongs to the Burkholderia Cepacia Complex, a group of 22 closely related species both of clinical and environmental origin, infecting cystic fibrosis patients. B. cenocepacia accounts for the majority of the clinical isolates, comprising the most virulent and transmissible strains. The capacity to form biofilms is among the many virulence determinants of B. cenocepacia, a characteristic that confers enhanced tolerance to some antibiotics, desiccation, oxidizing agents, and host defenses. Exopolysaccharides are a major component of biofilm matrices, particularly providing mechanical stability to biofilms. Recently, a water-insoluble exopolysaccharide produced by B. cenocepacia H111 in biofilm was characterized. In the present study, a water-soluble exopolysaccharide was extracted from B. cenocepacia H111 biofilm, and its structure was determined by GLC-MS, NMR and ESI-MS. The repeating unit is a linear rhamno-tetrasaccharide with 50% replacement of a 3-α-L-Rha with a α-3-L-Man. [2)-α-L-Rhap-(1→3)-α-L-[Rhap or Manp]-(1→3)-α-L-Rhap-(1→2)-α-L-Rhap-(1→]n Molecular modelling was used to obtain information about local structural motifs which could give information about the polysaccharide conformation.

PMID: 33440288 [PubMed - as supplied by publisher]

Metformin slows liver cyst formation and fibrosis in experimental model of polycystic liver disease.

Am J Physiol Gastrointest Liver Physiol. 2021 Jan 13;:

Authors: Sato Y, Qiu J, Hirose T, Miura T, Sato Y, Kohzuki M, Ito O

Abstract
Background Polycystic liver disease (PLD) is hereditary liver disease in which the number of cysts increases over time, causing various abdominal symptoms and a poor quality of life. Although effective treatment for PLD has not been established, we recently reported that long-term exercise ameliorated liver cyst formation and fibrosis with activation of AMP-activated protein kinase (AMPK) in polycystic kidney (PCK) rats, a PLD model. Therefore, the aim of this study was to investigate whether metformin, an indirect AMPK activator, was effective in PCK rats. Methods PCK rats were randomly divided into a control (Con) group and a metformin group (Met group). The Met group was treated orally with metformin in drinking water. After 12 weeks, liver function, histology and signaling cascades of PLD were examined in the groups. Results Metformin did not affect body weight or liver weight, but it reduced liver cyst formation, fibrosis and Ki-67-positive cells around the cyst. Metformin increased the phosphorylation of AMPK and decreased the phosphorylation of mammalian target of rapamycin and extracellular signal-regulated kinase and the expression of cystic fibrosis transmembrane conductance regulator, aquaporin I, transforming growth factor-β and type 1 collagen in the liver. Conclusions Metformin slows the development of cyst formation and fibrosis with activation of AMPK and inhibition of signaling cascades responsible for cellular proliferation and fibrosis in the liver of PCK rats.

PMID: 33439105 [PubMed - as supplied by publisher]

The GENDULF algorithm: mining transcriptomics to uncover modifier genes for monogenic diseases.

Mol Syst Biol. 2020 Dec;16(12):e9701

Authors: Auslander N, Ramos DM, Zelaya I, Karathia H, Crawford TO, Schäffer AA, Sumner CJ, Ruppin E

Abstract
Modifier genes are believed to account for the clinical variability observed in many Mendelian disorders, but their identification remains challenging due to the limited availability of genomics data from large patient cohorts. Here, we present GENDULF (GENetic moDULators identiFication), one of the first methods to facilitate prediction of disease modifiers using healthy and diseased tissue gene expression data. GENDULF is designed for monogenic diseases in which the mechanism is loss of function leading to reduced expression of the mutated gene. When applied to cystic fibrosis, GENDULF successfully identifies multiple, previously established disease modifiers, including EHF, SLC6A14, and CLCA1. It is then utilized in spinal muscular atrophy (SMA) and predicts U2AF1 as a modifier whose low expression correlates with higher SMN2 pre-mRNA exon 7 retention. Indeed, knockdown of U2AF1 in SMA patient-derived cells leads to increased full-length SMN2 transcript and SMN protein expression. Taking advantage of the increasing availability of transcriptomic data, GENDULF is a novel addition to existing strategies for prediction of genetic disease modifiers, providing insights into disease pathogenesis and uncovering novel therapeutic targets.

PMID: 33438800 [PubMed - in process]

Azole resistance in Aspergillus isolates by different types of patients and correlation with environment - An Italian prospective multicentre study (ARiA study).

Mycoses. 2021 Jan 12;:

Authors: Prigitano A, Esposto MC, Grancini A, Biffi A, Innocenti P, Cavanna C, Lallitto F, Mollaschi EMG, Bandettini R, Oltolini C, Passera M, De Lorenzis G, Sargolzaei M, Crespan M, Cogliati M, Tortorano AM, Romanò L

Abstract
BACKGROUND: A wide range of frequency of azole-resistance in A. fumigatus in different patient populations worldwide was observed threatening to reduce therapeutic options.
OBJECTIVES: Estimate the prevalence of azole-resistance, investigate the molecular mechanisms of resistance, compare the genotypes of resistant clinical isolates with those from the surrounding environment.
METHODS: Aspergillus isolates were collected by seven Italian hospital microbiology laboratories. Strains were isolated from different clinical samples from unselected patients. The azole-resistance was evaluated using screening test and microdilution EUCAST method. The molecular mechanism of resistance was performed sequencing the cyp51A gene. Resistant isolates were genotyped by microsatellite analysis and their profiles compared with those of azole-resistant isolates from previous Italian studies.
RESULTS: 425 Aspergillus isolates from 367 patients were analysed. The azole-resistance rates were 4.9% and 6.6% considering all Aspergillus spp. isolates and the A. fumigatus sensu stricto, respectively. All resistant isolates except one were from a single hospital. Two rare azole-resistant species were identified: A. thermomutatus and A. lentulus. The predominant resistance mechanism was TR34 /L98H. No correlation between the clinical resistant strains and environmental isolates from patients' home/work/ward was observed. The analysis of the molecular correlation between the resistant clinical strains collected in the present study and those of environmental and clinical origin collected in previous Italian studies reveals a progressive diversification of azole-resistant genotypes starting from a founder azole-resistant genotype.
CONCLUSIONS: This study confirms the trend of azole-resistance rate in Italy, showing a geographical difference. Data reinforces the importance of surveillance programs to monitor the local epidemiological situation.

PMID: 33438319 [PubMed - as supplied by publisher]

Korean Red Ginseng aqueous extract improves markers of mucociliary clearance by stimulating chloride secretion.

J Ginseng Res. 2021 Jan;45(1):66-74

Authors: Cho DY, Skinner D, Zhang S, Lazrak A, Lim DJ, Weeks CG, Banks CG, Han CK, Kim SK, Tearney GJ, Matalon S, Rowe SM, Woodworth BA

Abstract
Background: Abnormal chloride (Cl-) transport has a detrimental impact on mucociliary clearance in both cystic fibrosis (CF) and non-CF chronic rhinosinusitis. Ginseng is a medicinal plant noted to have anti-inflammatory and antimicrobial properties. The present study aims to assess the capability of red ginseng aqueous extract (RGAE) to promote transepithelial Cl- secretion in nasal epithelium.
Methods: Primary murine nasal septal epithelial (MNSE) [wild-type (WT) and transgenic CFTR-/-], fisher-rat-thyroid (FRT) cells expressing human WT CFTR, and TMEM16A-expressing human embryonic kidney cultures were utilized for the present experiments. Ciliary beat frequency (CBF) and airway surface liquid (ASL) depth measurements were performed using micro-optical coherence tomography (μOCT). Mechanisms underlying transepithelial Cl- transport were determined using pharmacologic manipulation in Ussing chambers and whole-cell patch clamp analysis.
Results: RGAE (at 30μg/mL of ginsenosides) significantly increased Cl- transport [measured as change in short-circuit current (ΔISC = μA/cm2)] when compared with control in WT and CFTR-/- MNSE (WT vs control = 49.8±2.6 vs 0.1+/-0.2, CFTR-/- = 33.5±1.5 vs 0.2±0.3, p < 0.0001). In FRT cells, the CFTR-mediated ΔISC attributed to RGAE was small (6.8 ± 2.5 vs control, 0.03 ± 0.01, p < 0.05). In patch clamp, TMEM16A-mediated currents were markedly improved with co-administration of RGAE and uridine 5-triphosphate (8406.3 +/- 807.7 pA) over uridine 5-triphosphate (3524.1 +/- 292.4 pA) or RGAE alone (465.2 +/- 90.7 pA) (p < 0.0001). ASL and CBF were significantly greater with RGAE (6.2+/-0.3 μm vs control, 3.9+/-0.09 μm; 10.4+/-0.3 Hz vs control, 7.3 ± 0.2 Hz; p < 0.0001) in MNSE.
Conclusion: RGAE augments ASL depth and CBF by stimulating Cl- secretion through CaCC, which suggests therapeutic potential in both CF and non-CF chronic rhinosinusitis.

PMID: 33437158 [PubMed]

Peptide-Conjugated Phosphorodiamidate Morpholino Oligomers Retain Activity against Multidrug-Resistant Pseudomonas aeruginosa In Vitro and In Vivo.

mBio. 2021 Jan 12;12(1):

Authors: Moustafa DA, Wu AW, Zamora D, Daly SM, Sturge CR, Pybus C, Geller BL, Goldberg JB, Greenberg DE

Abstract
Most antimicrobials currently in the clinical pipeline are modifications of existing classes of antibiotics and are considered short-term solutions due to the emergence of resistance. Pseudomonas aeruginosa represents a major challenge for new antimicrobial drug discovery due to its versatile lifestyle, ability to develop resistance to most antibiotic classes, and capacity to form robust biofilms on surfaces and in certain hosts such as those living with cystic fibrosis (CF). A precision antibiotic approach to treating Pseudomonas could be achieved with an antisense method, specifically by using peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs). Here, we demonstrate that PPMOs targeting acpP (acyl carrier protein), lpxC (UDP-(3-O-acyl)-N-acetylglucosamine deacetylase), and rpsJ (30S ribosomal protein S10) inhibited the in vitro growth of several multidrug-resistant clinical P. aeruginosa isolates at levels equivalent to those that were effective against sensitive strains. Lead PPMOs reduced established pseudomonal biofilms alone or in combination with tobramycin or piperacillin-tazobactam. Lead PPMO dosing alone or combined with tobramycin in an acute pneumonia model reduced lung bacterial burden in treated mice at 24 h and reduced morbidity up to 5 days postinfection. PPMOs reduced bacterial burden of extensively drug-resistant P. aeruginosa in the same model and resulted in superior survival compared to conventional antibiotics. These data suggest that lead PPMOs alone or in combination with clinically relevant antibiotics represent a promising therapeutic approach for combating P. aeruginosa infections.IMPORTANCE Numerous Gram-negative bacteria are becoming increasingly resistant to multiple, if not all, classes of existing antibiotics. Multidrug-resistant Pseudomonas aeruginosa bacteria are a major cause of health care-associated infections in a variety of clinical settings, endangering patients who are immunocompromised or those who suffer from chronic infections, such as people with cystic fibrosis (CF). Herein, we utilize antisense molecules that target mRNA of genes essential to bacterial growth, preventing the formation of the target proteins, including acpP, rpsJ, and lpxC We demonstrate here that antisense molecules targeted to essential genes, alone or in combination with clinically relevant antibiotics, were effective in reducing biofilms and protected mice in a lethal model of acute pneumonia.

PMID: 33436433 [PubMed - in process]

Same Game, Different Players: Emerging Pathogens of the CF Lung.

mBio. 2021 Jan 12;12(1):

Authors: Gannon AD, Darch SE

Abstract
The survival rates of individuals with cystic fibrosis (CF) have significantly increased as a result of improved therapies, such as the inclusion of cystic fibrosis transmembrane conductance regulator (CFTR) modulators for some mutations. However, microbial infection of the airways remains a significant clinical problem. The well-known pathogens Pseudomonas aeruginosa and Staphylococcus aureus continue to establish difficult-to-treat infections in the CF lung. However, in recent years, there has been an increased prevalence of both Aspergillus fumigatus (Af) and non-tuberculous mycobacteria (NTM) species isolated from CF patient sputa. The emergence of these pathogens opens an important area of discussion about multikingdom infections, specifically, how interspecies interactions have the potential to shape the course of infection, such as tolerance to host immune defenses and antimicrobial therapies. Their ability to establish themselves in an existing polymicrobial environment suggests to us that microbial interactions play a significant role, and characterizing these mechanisms and understanding their implications will be critical to the future development of better antimicrobial therapies. With this minireview, we hope to inspire conversations about and demonstrate the merit of more research in this area.IMPORTANCE Incidences of non-tuberculous mycobacteria (NTM) and Aspergillus fumigatus have increased around the world over the past decade and have become a significant health threat to immunocompromised individuals such as those with cystic fibrosis (CF). CF is characterized by the buildup of mucus in the lungs which become chronically infected by a myriad of pathogens. The emergence of these pathogens in established infection sites raises many questions about the microbial ecosystems they become a part of, specifically how changes in these ecosystems impact disease outcomes. Understanding how microbial communities establish and maintain themselves despite medical treatment and host immune defenses will be critical for the development of improved therapeutic strategies.

PMID: 33436426 [PubMed - in process]

COVID-19 rapid guideline: cystic fibrosis

Book. 2020 10 07

Authors:

Abstract
The purpose of this guideline is to maximise the safety of patients with cystic fibrosis and make the best use of NHS resources, while protecting staff from infection. This guideline focuses on what you need to stop or start doing during the pandemic. Follow the usual professional guidelines, standards and laws (including those on equalities, safeguarding, communication and mental capacity), as described in making decisions using NICE guidelines. On 7 October 2020, we withdrew our recommendations on reducing or deprioritising cystic fibrosis registry data entry, limiting transplant services and deferring transition to adult services because these emergency measures are no longer needed. This guideline is for: health and care practitioners; health and care staff involved in planning and delivering services; commissioners. The recommendations bring together: existing national and international guidance and policies; advice from specialists working in the NHS from across the UK. These include people with expertise and experience of treating patients with cystic fibrosis during the current COVID-19 pandemic. NICE has also produced a COVID-19 rapid guideline on arranging planned care in hospitals and diagnostic services, which should be read alongside this guideline. We developed this guideline using the interim process and methods for developing rapid guidelines on COVID-19 in response to the rapidly evolving situation. We will review and update the recommendations as the knowledge base develops using the interim process and methods for guidelines developed in response to health and social care emergencies.

PMID: 33439587

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20 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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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.

17 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 2021/01/12

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.

Untapped potential: Therapeutically targeting eicosanoids and endocannabinoids in the lung.

Clin Pharmacol Ther. 2021 Jan 10;:

Authors: Yonker LM, Barrios J, Mou H, Hurley BP

Abstract
Inflammation of the airway involves the recruitment of highly active immune cells to combat and clear microbes and toxic factors, however this inflammatory response can result in unintended damage to lung tissue. Tissue damage resulting from inflammation is often mitigated by resolving factors that limit the scope and duration of the inflammatory response. Both inflammatory and resolving processes require the actions of a vast array of lipid mediators that can be rapidly synthesized through a variety of airway resident and infiltrating immune cells. Eicosanoids and endocannabinoids represent two major classes of lipid mediators that share synthetic enzymes and have diverse and overlapping functions. This review seeks to provide a summary of the major bioactive eicosanoids and endocannabinoids, challenges facing researchers that study them, as well as their roles in modulating inflammation and resolution. With a special emphasis on cystic fibrosis, a variety of therapeutics are discussed that have been explored for their potential anti-inflammatory or pro-resolving impact toward alleviating excessive airway inflammation and improving lung function.

PMID: 33423293 [PubMed - as supplied by publisher]