Standardisation of cardiopulmonary exercise testing in chronic lung diseases: summary of key findings from the ERS task force.

Eur Respir J. 2019 Dec;54(6):

Authors: Radtke T, Vogiatzis I, Urquhart DS, Laveneziana P, Casaburi R, Hebestreit H, European Respiratory Society Task Force on Standardisation of Cardiopulmonary Exercise Testing in Chronic Lung Diseases

PMID: 31857385 [PubMed - in process]

A web-based intervention to promote physical activity in adolescents and young adults with cystic fibrosis: protocol for a randomized controlled trial.

BMC Pulm Med. 2019 Dec 19;19(1):253

Authors: Cox NS, Eldridge B, Rawlings S, Dreger J, Corda J, Hauser J, Button BM, Bishop J, Nichols A, Middleton A, Ward N, Dwyer T, Tomlinson OW, Denford S, Barker AR, Williams CA, Kingsley M, O'Halloran P, Holland AE, Youth Activity Unlimited – A Strategic Research Centre of the UK Cystic Fibrosis Trust

Abstract
BACKGROUND: Regular participation in physical activity by people with cystic fibrosis (CF) promotes positive clinical and health outcomes including reduced rate of decline in lung function, fewer hospitalizations and greater wellbeing. However adherence to exercise and activity programs is low, in part due to the substantial daily therapy burden for young people with CF. Strict infection control requirements limit the role of group exercise programs that are commonly used in other clinical groups. Investigation of methods to promote physical activity in this group has been limited. The Active Online Physical Activity in Cystic fibrosis Trial (ActionPACT) is an assessor-blinded, multi-centre, randomized controlled trial designed to compare the efficacy of a novel web-based program (ActivOnline) compared to usual care in promoting physical activity participation in adolescents and young adults with CF.
METHODS: Adolescents and young adults with CF will be recruited on discharge from hospital for a respiratory exacerbation. Participants randomized to the intervention group will have access to a web-based physical activity platform for the 12-week intervention period. ActivOnline allows users to track their physical activity, set goals, and self-monitor progress. All participants in both groups will be provided with standardised information regarding general physical activity recommendations for adolescents and young adults. Outcomes will be assessed by a blinded assessor at baseline, after completion of the intervention, and at 3-months followup. Healthcare utilization will be assessed at 12 months from intervention completion. The primary outcome is change in moderate-to-vigorous physical activity participation measured objectively by accelerometry. Secondary outcomes include aerobic fitness, health-related quality of life, anxiety and depression and sleep quality.
DISCUSSION: This trial will establish whether a web-based application can improve physical activity participation more effectively than usual care in the period following hospitalization for a respiratory exacerbation. The web-based application under investigation can be made readily and widely available to all individuals with CF, to support physical activity and exercise participation at a time and location of the user's choosing, regardless of microbiological status.
TRIAL REGISTRATION: Clinical trial registered on July 13, 2017 with the Australian and New Zealand Clinical Trials Register at (ACTRN12617001009303).

PMID: 31856791 [PubMed - in process]

Risk factors for neo-osteogenesis in cystic fibrosis and non-cystic fibrosis chronic rhinosinusitis.

Int Forum Allergy Rhinol. 2019 Dec 19;:

Authors: Karempelis P, Karp E, Rubin N, Hunter R, Dunitz J, Boyer H

Abstract
BACKGROUND: The purpose of this retrospective review was to determine how patient-related factors and culture data affect neo-osteogenesis in patients with chronic rhinosinusitis (CRS) and patients with cystic fibrosis (CF) with CRS.
METHODS: Information from a database associated with a large tertiary medical center was used to assess adult patients with CF CRS and non-CF CRS (total, n = 102; CF CRS, n = 31; non-CF CRS, n = 71). Radiologic evidence of neo-osteogenesis was measured using the Global Osteitis Scoring Scale (GOSS), and mucosal disease was assessed using the Lund-Mackay score (LMS) by 2 independent reviewers who were blinded to the patient's disease state. Bacterial cultures were obtained endoscopically. Multiple logistic regression models were used to evaluate the effect of age, sex, number of previous surgeries, CF, and culture species on the odds of neo-osteogenesis.
RESULTS: Fifty-one of the 102 patients (50%) met radiologic criteria for neo-osteogenesis. Sixty-nine patients (67.6%) with CF CRS and non-CF CRS had culture data. In the multiple logistic regression model, male gender was significantly associated with neo-osteogenesis (odds ratio [OR], 5.2; 95% confidence interval [CI], 1.68-17.86; p = 0.006). Pseudomonas aeruginosa was not associated with neo-osteogenesis (OR, 3.12; 95% CI, 0.84-12.80; p = 0.097). Age, number of surgeries, CF, Staphylococcus aureus, and coagulase-negative Staphylococcus were not statistically significant.
CONCLUSION: To our knowledge, this is the first study to assess risk factors associated with neo-osteogenesis and patients with CF CRS. Interestingly, male gender was the only significant predictor of neo-osteogenesis.

PMID: 31856378 [PubMed - as supplied by publisher]

Dynamic perfluorinated gas MRI reveals abnormal ventilation despite normal FEV1 in cystic fibrosis.

JCI Insight. 2019 Dec 19;:

Authors: Goralski JL, Chung SH, Glass TM, Ceppe AS, Akinnagbe-Zusterzeel EO, Trimble AT, Boucher RC, Soher BJ, Charles HC, Donaldson SH, Lee YZ

Abstract
BACKGROUND: We hypothesized that dynamic perfluorinated gas magnetic resonance imaging (19F MRI) would sensitively detect mild cystic fibrosis (CF) lung.
METHODS: This prospective study enrolled 20 healthy volunteers and 24 stable subjects with CF, including a subgroup of subjects with normal FEV1 (>80% predicted, n = 9). Dynamic 19F MRI images were acquired during sequential breath holds while breathing perfluoropropane (PFP) and during gas wash-out. Outcomes included the fraction of lung without significant ventilation (ventilation defect percent, VDP) and time constants that described PFP wash-in and wash-out kinetics.
RESULTS: VDP values (mean ± SD) of healthy controls (3.87% ± 2.7%) were statistically different from moderate CF subjects (19.5% ± 15.5%, P = 0.001) but not from mild CF subjects (10.4% ± 9.9%, P = 0.24) . The fractional lung volume with slow gas wash-out was elevated both in subjects with mild (9.61% ± 4.87%; P = 0.0066) and moderate CF (16.01% ± 5.01%; P = 0.0002) when compared to healthy controls (3.84% ± 2.16%).
CONCLUSION: 19F MRI detected significant ventilation abnormalities in subjects with cystic fibrosis. Assessment of gas wash-out kinetics was more sensitive to mild CF lung disease than quantitation of steady state ventilation defects making 19F MRI a potentially valuable method for the characterization of early lung disease in CF.

PMID: 31855577 [PubMed - as supplied by publisher]

Clinical Development of Sphingosine as Anti-Bacterial Drug: Inhalation of Sphingosine in Mini Pigs has no Adverse Side Effects.

Cell Physiol Biochem. 2019;53(6):1015-1028

Authors: Carstens H, Schumacher F, Keitsch S, Kramer M, Kühn C, Sehl C, Soddemann M, Wilker B, Herrmann D, Swaidan A, Kleuser B, Verhaegh R, Hilken G, Edwards MJ, Dubicanac M, Carpinteiro A, Wissmann A, Becker KA, Kamler M, Gulbins E

Abstract
BACKGROUND/AIMS: Pulmonary infections with Pseudomonas aeruginosa (P. aeruginosa) or Staphylococcus aureus (S. aureus) are of utmost clinical relevance in patients with cystic fibrosis, chronic obstructive pulmonary disease, after trauma and burn, upon ventilation or in immuno-compromised patients. Many P. aeruginosa and S. aureus strains are resistant to many known antibiotics and it is very difficult or often impossible to eradicate the pathogens in patient´s lungs. We have recently shown that the sphingoid base sphingosine very efficiently kills many pathogens, including for instance P. aeruginosa, S. aureus or Acinetobacter baumannii, in vitro. In vivo experiments of our group on cystic fibrosis mice indicated that inhalation of sphingosine prevents or eliminates existing acute or chronic pneumonia with P. aeruginosa or S. aureus in these mice. We also demonstrated that sphingosine is safe to use for inhalation up to high doses, at least in mice. To facilitate development of sphingosine to an anti-bactericidal drug that can be used in humans for inhalation, safety data on non-rodents, larger animals are absolutely required.
METHODS: Here, we inhaled mini pigs with increasing doses of sphingosine for 10 days and analyzed the uptake of sphingosine into epithelial cells of bronchi as well as into the trachea and lung and the systemic circulation. Moreover, we measured the generation of ceramide and sphingosine 1-phosphate that potentially mediate inflammation, the influx of leukocytes, epithelial cell death and disruption of the epithelial cell barrier.
RESULTS: We demonstrate that inhalation of sphingosine results in increased levels of sphingosine in the luminal membrane of bronchi and the trachea, but not in systemic accumulation. Inhaled sphingosine had no side effects up to very high doses.
CONCLUSION: In summary, we demonstrate that inhalation of sphingosine results in an increase of sphingosine concentrations in the luminal plasma membrane of tracheal and bronchial epithelial cells. The inhalation has no systemic or local side effects.

PMID: 31854953 [PubMed - in process]

Diagnostics of CFTR-negative patients with congenital bilateral absence of vas deferens: which mutations are of most interest?

Expert Rev Mol Diagn. 2019 Dec 19;:

Authors: Ferlin A, Stuppia L

PMID: 31854215 [PubMed - as supplied by publisher]

Detection of the sickle hemoglobin allele using a surface plasmon resonance based biosensor.

Sens Actuators B Chem. 2019 Oct 01;296:126604

Authors: Breveglieri G, D'Aversa E, Cosenza LC, Boutou E, Balassopoulou A, Voskaridou E, Gambari R, Borgatti M

Abstract
Sickle Cell Disease (SCD) is a monogenic hereditary blood disorder caused by a single point mutation (βS) in the β globin gene resulting in an abnormal hemoglobin (HbS) that can polymerize within the erythrocytes, inducing their characteristic sickle shape. This causes hemolytic anemia and occlusive vessels for the most severe clinical status. Molecular analysis is crucial for fast and precise diagnosis of different forms of SCD, and, on the basis of underlying genotype, for supporting the most appropriate treatment options. In this context, we describe a simple and reproducible protocol for the molecular identification of the βS mutation based on surface plasmon resonance (SPR) using the Biacore™ X100 affinity biosensor. This technology has already demonstrated its diagnostic suitability for the identification of point mutations responsible for genetic diseases such as cystic fibrosis and β thalassemia, using a protocol based on immobilization of PCR products on the sensor chip. On the contrary, in this work we applied a SPR strategy based on an innovative interaction format, recently developed in our group also for β thalassemia mutations. In particular, we correctly detected the βS mutation responsible for SCD, both in homozygous and heterozygous states, after hybridization of two oligonucleotide probes (normal and mutated) for the βS mutation, immobilized on sensor chip, with unbalanced PCR products obtained from 53 genomic DNAs carrying different βS allele combinations.

PMID: 31853166 [PubMed]

ERS statement on standardisation of cardiopulmonary exercise testing in chronic lung diseases.

Eur Respir Rev. 2019 Dec 31;28(154):

Authors: Radtke T, Crook S, Kaltsakas G, Louvaris Z, Berton D, Urquhart DS, Kampouras A, Rabinovich RA, Verges S, Kontopidis D, Boyd J, Tonia T, Langer D, De Brandt J, Goërtz YMJ, Burtin C, Spruit MA, Braeken DCW, Dacha S, Franssen FME, Laveneziana P, Eber E, Troosters T, Neder JA, Puhan MA, Casaburi R, Vogiatzis I, Hebestreit H

Abstract
The objective of this document was to standardise published cardiopulmonary exercise testing (CPET) protocols for improved interpretation in clinical settings and multicentre research projects. This document: 1) summarises the protocols and procedures used in published studies focusing on incremental CPET in chronic lung conditions; 2) presents standard incremental protocols for CPET on a stationary cycle ergometer and a treadmill; and 3) provides patients' perspectives on CPET obtained through an online survey supported by the European Lung Foundation. We systematically reviewed published studies obtained from EMBASE, Medline, Scopus, Web of Science and the Cochrane Library from inception to January 2017. Of 7914 identified studies, 595 studies with 26 523 subjects were included. The literature supports a test protocol with a resting phase lasting at least 3 min, a 3-min unloaded phase, and an 8- to 12-min incremental phase with work rate increased linearly at least every minute, followed by a recovery phase of at least 2-3 min. Patients responding to the survey (n=295) perceived CPET as highly beneficial for their diagnostic assessment and informed the Task Force consensus. Future research should focus on the individualised estimation of optimal work rate increments across different lung diseases, and the collection of robust normative data.

PMID: 31852745 [PubMed - in process]

Year-round treatment initiation for a 6-grasses pollen allergoid in specific immunotherapy of allergic rhinoconjunctivitis and asthma.

Immunotherapy. 2019 Dec 19;:

Authors: Mahler V, Zielen S, Rosewich M

Abstract
Aim: Allergen immunotherapy (AIT) is an effective treatment for allergic diseases. We investigate whether treatment-initiation during the pollen season is safe. Methods: RCT-IIIb-trial of 6-grass-pollen-allergoid (Allergovit®) in grass pollen-allergic patients (18-65 years) with moderate-severe rhinitis/rhinoconjunctivitis (± controlled asthma), randomized 2:1 to treatment-initiation during (Group-A) versus outside the pollen season (Group-B). Results: Of 240 patients (32.8 ± 9.9 years, 19.5% asthma) treated, 84.9% (Group-A) and 86.6% (Group-B) reached maintenance dose without delay. Treatment-emergent adverse events occurred in 108 (68.4%/Group-A) and 41 patients (56.2%/Group-B) leading to premature trial-termination in 11 patients (7%/A) versus 3 (4.1%/B). Across groups, physicians (for 190 patients; 85.2%) and patients (192; 86.1%) rated the tolerability as 'very good'-'good'. Phleum pratense-specific IgG4 increased in both groups (p < 0.0001). Conclusion: Year-round allergen immunotherapy-initiation with this preparation is safe.

PMID: 31852355 [PubMed - as supplied by publisher]

Refinement of metabolite detection in cystic fibrosis sputum reveals heme correlates with lung function decline.

PLoS One. 2019;14(12):e0226578

Authors: Glasser NR, Hunter RC, Liou TG, Newman DK, Mountain West CF Consortium Investigators

Abstract
The bacterial growth environment within cystic fibrosis (CF) sputum is complex, dynamic, and shaped by both host and microbial processes. Characterization of the chemical parameters within sputum that stimulate the in vivo growth of airway pathogens (e.g. Pseudomonas aeruginosa) and their associated virulence factors may lead to improved CF treatment strategies. Motivated by conflicting reports of the prevalence and abundance of P. aeruginosa-derived metabolites known as phenazines within CF airway secretions, we sought to quantify these metabolites in sputum using quadrupole time-of-flight mass spectrometry. In contrast to our previous work, all phenazines tested (pyocyanin (PYO), phenazine-1-carboxylic acid (PCA), phenazine-1-carboxamide, and 1-hydroxyphenazine) were below detection limits of the instrument (0.1 μM). Instead, we identified a late-eluting compound that shared retention time and absorbance characteristics with PCA, yet generated mass spectra and a fragmentation pattern consistent with ferriprotoporphyrin IX, otherwise known as heme B. These data suggested that UV-vis chromatographic peaks previously attributed to PCA and PYO in sputum were mis-assigned. Indeed, retrospective analysis of raw data from our prior study found that the heme B peak closely matched the peaks assigned to PCA, indicating that the previous study likely uncovered a positive correlation between pulmonary function (percent predicted forced expiratory volume in 1 second, or ppFEV1) and heme B, not PCA or any other phenazine. To independently test this observation, we performed a new tandem mass-spectrometry analysis of 71 additional samples provided by the Mountain West CF Consortium Sputum Biomarker study and revealed a positive correlation (ρ = -0.47, p<0.001) between sputum heme concentrations and ppFEV1. Given that hemoptysis is strongly associated with airway inflammation, pulmonary exacerbations and impaired lung function, these new data suggest that heme B may be a useful biomarker of CF pathophysiology.

PMID: 31851705 [PubMed - in process]

Hematopoietic Stem Cell Transplantation Restores Naïve T-Cell Populations in Atm-Deficient Mice and in Preemptively Treated Patients With Ataxia-Telangiectasia.

Front Immunol. 2019;10:2785

Authors: Duecker R, Baer PC, Buecker A, Huenecke S, Pfeffermann LM, Modlich U, Bakhtiar S, Bader P, Zielen S, Schubert R

Abstract
Background: Ataxia-telangiectasia (A-T) is a multisystem disorder with progressive cerebellar ataxia, immunodeficiency, chromosomal instability, and increased cancer susceptibility. Cellular immunodeficiency is based on naïve CD4+ and CD8+ T-cell lymphopenia. Hematopoietic stem cell transplantation (HSCT) offers a potential to cure immunodeficiency and cancer due to restoration of the lymphopoietic system. The aim of this investigation was to analyze the effect of HSCT on naïve CD4+ as well as CD8+ T-cell numbers in A-T. Methods: We analyzed total numbers of peripheral naïve (CD45RA+CD62L+) and memory (CD45RO+CD62L-) CD4+ and CD8+ T-cells of 32 A-T patients. Naïve (CD62LhighCD44low) and memory (CD62LlowCD44high) T-cells were also measured in Atm-deficient mice before and after HSCT with GFP-expressing bone marrow derived hematopoietic stem cells. In addition, we analyzed T-cells in the peripheral blood of two A-T patients after HLA-identic allogeneic HSCT. Results: Like in humans, naïve CD4+ as well as naïve CD8+ lymphocytes were decreased in Atm-deficient mice. HSCT significantly inhibited thymic lymphomas and increased survival time in these animals. Donor cell chimerism increased up to more than 50% 6 months after HSCT accompanied by a significant increase of naïve CD4 and CD8 T-cell subpopulations, but not of memory T-cells. This finding was also identified in the blood of the A-T patients after HSCT. Conclusion: HSCT seems to be a feasible strategy to overcome immunodeficiency and might be a conceivable strategy to avoid T-cell driven cancer in A-T at higher risk for malignancy. Naïve CD4 and CD8 T-cells counts are suitable markers for monitoring immune reconstitution post-HSCT. However, risks and benefits of HSCT in A-T have to be properly weighted.

PMID: 31849966 [PubMed - in process]

Multidrug-Resistant and Clinically Relevant Gram-Negative Bacteria Are Present in German Surface Waters.

Front Microbiol. 2019;10:2779

Authors: Falgenhauer L, Schwengers O, Schmiedel J, Baars C, Lambrecht O, Heß S, Berendonk TU, Falgenhauer J, Chakraborty T, Imirzalioglu C

Abstract
Water is considered to play a role in the dissemination of antibiotic-resistant Gram-negative bacteria including those encoding Extended-spectrum beta-lactamases (ESBL) and carbapenemases. To investigate the role of water for their spread in more detail, we characterized ESBL/Carbapenemase-producing bacteria from surface water and sediment samples using phenotypic and genotypic approaches. ESBL/Carbapenemase-producing isolates were obtained from water/sediment samples. Species and antibiotic resistance were determined. A subset of these isolates (n = 33) was whole-genome-sequenced and analyzed for the presence of antibiotic resistance genes and virulence determinants. Their relatedness to isolates associated with human infections was investigated using multilocus sequence type and cgMLST-based analysis. Eighty-nine percent of the isolates comprised of clinically relevant species. Fifty-eight percent exhibited a multidrug-resistance phenotype. Two isolates harbored the mobile colistin resistance gene mcr-1. One carbapenemase-producing isolate identified as Enterobacter kobei harbored bla VIM- 1. Two Escherichia coli isolates had sequence types (ST) associated with human infections (ST131 and ST1485) and a Klebsiella pneumoniae isolate was classified as hypervirulent. A multidrug-resistant (MDR) Pseudomonas aeruginosa isolate encoding known virulence genes associated with severe lung infections in cystic fibrosis patients was also detected. The presence of MDR and clinically relevant isolates in recreational and surface water underlines the role of aquatic environments as both reservoirs and hot spots for MDR bacteria. Future assessment of water quality should include the examination of the multidrug resistance of clinically relevant bacterial species and thus provide an important link regarding the spread of MDR bacteria in a One Health context.

PMID: 31849911 [PubMed]

Editorial: Emerging Therapeutic Approaches for Cystic Fibrosis.

Front Pharmacol. 2019;10:1440

Authors: Lopes-Pacheco M, Pedemonte N, Kicic A

PMID: 31849681 [PubMed]

Universal strategy for preimplantation genetic testing for cystic fibrosis based on next-generation sequencing.

J Assist Reprod Genet. 2019 Dec 17;:

Authors: Chamayou S, Sicali M, Lombardo D, Alecci C, Ragolia C, Maglia E, Liprino A, Cardea C, Storaci G, Romano S, Guglielmino A

Abstract
PURPOSE: We developed and applied a universal strategy for preimplantation genetic testing for all cystic fibrosis gene mutations (PGT-CF) based on next-generation sequencing (NGS).
METHODS: A molecular protocol was designed to diagnose all CF mutations at preimplantation stage. The detection of CF mutations was performed by direct gene sequencing and linkage strategy testing 38 specific SNPs located upstream and inside the gene for PGT-CF. Seventeen couples at risk of CF transmission decided to undergo PGT-CF. Trophectoderm cell biopsies were performed on days 5-6 blastocysts. PGT for aneuploidy (PGT-A) was performed from the same samples. Tested embryos were transferred on further natural cycles.
RESULTS: PGT was performed on 109 embryos. Fifteen CF mutations were tested. PGT-CF and PGT-A were conclusive for, respectively, 92.7% and 95.3% of the samples. A mean of 24.1 SNPs was informative per couple. After single embryo transfer on natural cycle, 81.3% of the transferred tested embryos implanted.
CONCLUSIONS: The present protocol based on the entire CFTR gene sequencing together with informative SNPs outside and inside the gene can be applied to diagnose all CF mutations at preimplantation stage.

PMID: 31848897 [PubMed - as supplied by publisher]

Lumacaftor/ivacaftor reduces exacerbations in adults homozygous for Phe508del mutation with severe lung disease.

J Cyst Fibros. 2019 Dec 15;:

Authors: Tong K, Barker D, France M, Burr L, Greville H, Visser S, Middleton P, Wainwright C, Dorahy D, Wark P

Abstract
BACKGROUND: Lumacaftor/ivacaftor (LUM/IVA) improves outcomes in cystic fibrosis (CF) patients homozygous for Phe508del with ppFEV1 > 40%. There is limited safety or efficacy data in patients with ppFEV1 < 40%. We determined whether LUM/IVA in patients with ppFEV1 < 40 would reduce the rate of pulmonary exacerbations.
METHODS: This was a case control study performed on patients > 12 years, homozygous for Phe508del CFTR mutation and with ppFEV1 < 40%. Control subjects were matched for age, sex and ppFEV1, and had mutations ineligible for LUM/IVA. We assessed the rate of pulmonary exacerbations requiring intravenous antibiotics, the mean rate of change in ppFEV1 over 12 months and all adverse events.
RESULTS: Data was collected from 7 Australian CF centres on 105 patients; 72 on LUM/IVA and 33 controls. LUM/IVA demonstrated a large reduction in exacerbations with an incident rate ratio of 0.455 (95%CI; 0.306 - 0.676), p <  0.001 after adjusting for the number of exacerbations in the previous 12 months. LUM/IVA prolonged the time to first exacerbation and reduced the rate of decline in ppFEV1 over 12 months. Adverse events were common; chest tightness or dyspnoea was experienced by 55% and resulted in cessation of treatment in 32%.
CONCLUSIONS: Treatment with LUM/IVA resulted in a substantially lower rate of pulmonary exacerbations, prolonged time to first exacerbation and slowed the rate of decline of ppFEV1 in participants with severe lung disease. Adverse reactions to LUM/IVA however were unacceptably frequent, and resulted in a very high discontinuation rate.

PMID: 31848044 [PubMed - as supplied by publisher]

Salivary Biomarkers and Oral Microbial Load in Relation to the Dental Status of Adults with Cystic Fibrosis.

Microorganisms. 2019 Dec 13;7(12):

Authors: Pawlaczyk-Kamieńska T, Borysewicz-Lewicka M, Batura-Gabryel H

Abstract
The mutation of cystic fibrosis transmembrane conductance regulator (CFTR) can modify the physical and chemical properties of saliva, which in turn can affect the oral microflora and oral health in patients with cystic fibrosis (CF). The aim of the study was to examine oral health status, salivary properties, and total oral bacteria count in CF adults. Dental status was assessed using the decayed missing filled surfaces (DMF-S) index, and oral clearness using the approximal plaque index (API). The Saliva-Check BUFFER test was used to assess saliva, and real-time polymerase chain reaction (PCR) test to determine the total oral bacteria count. CF patients in comparison to healthy controls showed a higher level of examined clinical indices, higher total oral bacteria count, lower salivary flow rate, lower salivary pH, and increased viscosity. Conclusions: In CF patients, saliva properties, accompanied by insufficient dental care, might be an essential dental caries risk factor. In CF patients, among the etiological factors for dental caries, the bacterial agent seems to be less significant. The frequent and long-term infectious pharmacotherapy can probably explain that. A great deal of the information collected on the oral environment in CF patients, which has helped us understand the etiological conditions for inflammation and infection in this area of the body, indicates that proper dental care can mostly counteract these pathologies.

PMID: 31847106 [PubMed]

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Females with Cystic Fibrosis Demonstrate a Differential Response Profile to Ivacaftor Compared to Males.

Am J Respir Crit Care Med. 2019 Dec 16;:

Authors: Secunda KE, Guimbellot JS, Jovanovic B, Heltshe SL, Sagel SD, Rowe SM, Jain M

PMID: 31841644 [PubMed - as supplied by publisher]

Universal antibiotic tolerance arising from antibiotic-triggered accumulation of pyocyanin in Pseudomonas aeruginosa.

PLoS Biol. 2019 Dec 16;17(12):e3000573

Authors: Zhu K, Chen S, Sysoeva TA, You L

Abstract
Pseudomonas aeruginosa is an opportunistic pathogen that often infects open wounds or patients with cystic fibrosis. Once established, P. aeruginosa infections are notoriously difficult to eradicate. This difficulty is in part due to the ability of P. aeruginosa to tolerate antibiotic treatment at the individual-cell level or through collective behaviors. Here, we describe a new phenomenon by which P. aeruginosa tolerates antibiotic treatment. In particular, treatment of P. aeruginosa with sublethal concentrations of antibiotics covering all major classes promoted accumulation of the redox-sensitive phenazine pyocyanin (PYO). PYO in turn conferred general tolerance against diverse antibiotics for both P. aeruginosa and other gram-negative and gram-positive bacteria. This property is shared by other redox-active phenazines produced by P. aeruginosa. Our discovery sheds new insights into the physiological functions of phenazines and has implications for designing effective antibiotic treatment protocols.

PMID: 31841520 [PubMed - as supplied by publisher]

Treatment of dental complications in sickle cell disease.

Cochrane Database Syst Rev. 2019 Dec 16;12:CD011633

Authors: Mulimani P, Ballas SK, Abas AB, Karanth L

Abstract
BACKGROUND: Sickle cell disease is the most common single gene disorder and the commonest haemoglobinopathy found with high prevalence in many populations across the world. Management of dental complications in people with sickle cell disease requires special consideration for three main reasons. Firstly, dental and oral tissues are affected by the blood disorder resulting in several oro-facial abnormalities. Secondly, living with a haemoglobinopathy and coping with its associated serious consequences may result in individuals neglecting their oral health care. Finally, the treatment of these oral complications must be adapted to the systemic condition and special needs of these individuals, in order not to exacerbate or deteriorate their general health. Guidelines for the treatment of dental complications in this population who require special care are unclear and even unavailable in many aspects. Hence this review was undertaken to provide a basis for clinical care by investigating and analysing the existing evidence in the literature for the treatment of dental complications in people with sickle cell disease. This is an update of a previously published review.
OBJECTIVES: To assess methods of treating dental complications in people with sickle cell disease.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Review Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 01 August 2019. Additionally, we searched nine online databases (PubMed, Google Scholar, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Literature in the Health Sciences in Latin America and the Caribbean database, African Index Medicus, Index Medicus for South East Asia Region, Index Medicus for the Eastern Mediterranean Region, Indexing of Indian Medical Journals). We also searched the reference lists of relevant articles and reviews and contacted haematologists, experts in fields of dentistry, organizations, pharmaceutical companies and researchers working in this field. Date of last search: 07 November 2019.
SELECTION CRITERIA: We searched for published or unpublished randomised controlled studies of treatments for dental complications in people with sickle cell disease.
DATA COLLECTION AND ANALYSIS: Two review authors intended to independently extract data and assess the risk of bias of the included studies using standard Cochrane methodologies; however, no studies were identified for inclusion in the review.
MAIN RESULTS: No randomised controlled studies were identified.
AUTHORS' CONCLUSIONS: This Cochrane Review did not identify any randomised controlled studies assessing interventions for the treatment of dental complications in people with sickle cell disease. There is an important need for randomised controlled studies in this area, so as to identify the most effective and safe method for treating dental complications in people with sickle cell disease.

PMID: 31841224 [PubMed - in process]