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  1. Article ; Online: Review of recombinant human deoxyribonuclease (rhDNase) in the management of patients with cystic fibrosis

    Tacjana Pressler

    Biologics: Targets & Therapy, Vol 2008, Iss Issue 4, Pp 611-

    2008  Volume 617

    Abstract: Tacjana PresslerCF Centre, Dept. of Pediatrics, Rigshospitalet, University of Copenhagen DenmarkAbstract: The most important problem in cystic fibrosis (CF) lung disease is chronic airway inflammation and infection, which starts early in life. To prevent ...

    Abstract Tacjana PresslerCF Centre, Dept. of Pediatrics, Rigshospitalet, University of Copenhagen DenmarkAbstract: The most important problem in cystic fibrosis (CF) lung disease is chronic airway inflammation and infection, which starts early in life. To prevent severe lung damage, it is important to mobilize as much sputum as possible from the lung on a daily basis. RhDNase is an enzyme that breaks down DNA strands in airway secretions, hydrolyzes the DNA present in sputum/mucus of CF patients, reducing viscosity in the lungs and promoting secretion clearance. Several well performed trials have proven its efficacy in young CF patients with mild disease as well as in older patients with more advanced lung disease. Daily inhalation of this agent slows down lung function decline and decreases the frequency of respiratory exacerbations. The drug is well tolerated by most patients independent of the severity of lung disease.Keywords: cystic fibrosis, lung disease, recombinant human deoxyribonuclease
    Keywords Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2008-09-01T00:00:00Z
    Publisher Dove Medical Press
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Nationwide lung function monitoring from infancy in newborn-screened children with cystic fibrosis

    Rikke M. Sandvik / Marika N. Schmidt / Christian M. Voldby / Frederik F. Buchvald / Hanne V. Olesen / Jørgen Olsen / Maja V. Kragh / Sune L.M. Rubak / Tacjana Pressler / Paul D. Robinson / Per M. Gustafsson / Marianne Skov / Kim G. Nielsen

    ERJ Open Research, Vol 9, Iss

    2023  Volume 5

    Abstract: Background Cystic fibrosis (CF) lung disease starts in infancy and can be assessed for structural lung abnormalities using computed tomography or magnetic resonance scans, or for lung function impairment using multiple breath washout (MBW). However, in ... ...

    Abstract Background Cystic fibrosis (CF) lung disease starts in infancy and can be assessed for structural lung abnormalities using computed tomography or magnetic resonance scans, or for lung function impairment using multiple breath washout (MBW). However, in infancy these two methods are not well correlated. Trajectories of CF lung disease assessed by MBW in infants and toddlers remain poorly described, which is why we aimed to 1) describe the trajectory of lung function, 2) explore risk factors for progression and 3) explore the real-life effect of lumacaftor/ivacaftor. Methods This was a nationwide observational cohort study (2018–2021) using data collected as part of the routine clinical surveillance programme (including MBW and monthly endo-laryngeal suction sampling for bacterial pathogens) in children born after implementation of newborn screening for CF (May 2016). Lumacaftor/ivacaftor commenced from age 2 years in children homozygous for F508del. Ventilation distribution efficiency (VDE), recently described to have advantages over lung clearance index (LCI), was reported as the primary MBW outcome after z-score calculations based on published reference data. Mixed effect linear regression models were the main statistical analyses performed in this study. Results 59 children, aged 2–45 months, contributed with 211 MBW occasions (median (interquartile range (IQR)) 3 (2–5) MBW occasions per child) with a median (IQR) follow-up time of 10.8 (5.2–22.3) months. An overall mean annual deterioration rate of −0.50 (95% CI −0.78– −0.22) z-VDE was observed, starting from an estimated mean z-VDE of −1.68 (95% CI −2.15– −1.22) at age 0.0 years (intercept). Pseudomonas aeruginosa “ever” (n=14, MBWs 50) had a significantly worse z-VDE trajectory versus P. aeruginosa “never” (mean difference 0.53 (95% CI 0.16–0.89) per year; p=0.0047) and lumacaftor/ivacaftor treatment (n=22, MBWs 46) significantly improved the trajectory of z-VDE (mean difference 1.72 (95% CI 0.79–2.66) per year; p=0.0004), leading to a stable mean z-VDE ...
    Keywords Medicine ; R
    Subject code 610
    Language English
    Publishing date 2023-10-01T00:00:00Z
    Publisher European Respiratory Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Neutrophil count in sputum is associated with increased sputum glucose and sputum L-lactate in cystic fibrosis.

    Bibi Uhre Nielsen / Mette Kolpen / Peter Østrup Jensen / Terese Katzenstein / Tacjana Pressler / Christian Ritz / Inger Hee Mabuza Mathiesen / Daniel Faurholt-Jepsen

    PLoS ONE, Vol 15, Iss 9, p e

    2020  Volume 0238524

    Abstract: Background Markers of lung inflammation measured directly in expectorated sputum have the potential of improving the timing of antibiotic treatment in cystic fibrosis (CF). L-Lactate might be a marker of inflammation, as it is produced from glucose by ... ...

    Abstract Background Markers of lung inflammation measured directly in expectorated sputum have the potential of improving the timing of antibiotic treatment in cystic fibrosis (CF). L-Lactate might be a marker of inflammation, as it is produced from glucose by polymorphonuclear neutrophils (PMNs) in CF lungs. We aimed to investigate changes in and associations between PMNs, glucose and L-lactate in sputum during antibiotic treatment. In addition, the effect of hemoglobin A1c and plasma glucose on these biomarkers were investigated. Methods We sampled non-induced sputum at day 0, 7, 14 and 42 in 27 chronically infected CF patients electively treated with 14 days of intravenous antibiotic. To analyze sputum samples, we used flowcytometry to count PMNs and colorimetric assays to estimate lactate and glucose. Results No changes in levels of PMNs, glucose and lactate were detected in sputum during the antibiotic treatment. Sputum PMNs were positively associated with both glucose (log coefficient = 0.20, p = 0.01) and L-lactate (log coefficient = 0.34, p<0.001). In multivariate analyses, hemoglobin A1c was negatively associated with sputum PMNs (log coefficient = -1.68, p<0.001) and plasma glucose was negatively associated with sputum glucose (log coefficient = -0.09, p = 0.02). Conclusions In CF sputum PMNs, glucose and lactate were unchanged during elective antibiotic treatment. However, sputum PMNs were associated with both sputum glucose and sputum lactate. Surprisingly, hyperglycemia seemed to be associated with less PMNs infiltration and less glucose in CF sputum.
    Keywords Medicine ; R ; Science ; Q
    Subject code 670
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Neutrophil count in sputum is associated with increased sputum glucose and sputum L-lactate in cystic fibrosis

    Bibi Uhre Nielsen / Mette Kolpen / Peter Østrup Jensen / Terese Katzenstein / Tacjana Pressler / Christian Ritz / Inger Hee Mabuza Mathiesen / Daniel Faurholt-Jepsen / Monica Cartelle Gestal

    PLoS ONE, Vol 15, Iss

    2020  Volume 9

    Abstract: Background Markers of lung inflammation measured directly in expectorated sputum have the potential of improving the timing of antibiotic treatment in cystic fibrosis (CF). L-Lactate might be a marker of inflammation, as it is produced from glucose by ... ...

    Abstract Background Markers of lung inflammation measured directly in expectorated sputum have the potential of improving the timing of antibiotic treatment in cystic fibrosis (CF). L-Lactate might be a marker of inflammation, as it is produced from glucose by polymorphonuclear neutrophils (PMNs) in CF lungs. We aimed to investigate changes in and associations between PMNs, glucose and L-lactate in sputum during antibiotic treatment. In addition, the effect of hemoglobin A1c and plasma glucose on these biomarkers were investigated. Methods We sampled non-induced sputum at day 0, 7, 14 and 42 in 27 chronically infected CF patients electively treated with 14 days of intravenous antibiotic. To analyze sputum samples, we used flowcytometry to count PMNs and colorimetric assays to estimate lactate and glucose. Results No changes in levels of PMNs, glucose and lactate were detected in sputum during the antibiotic treatment. Sputum PMNs were positively associated with both glucose (log coefficient = 0.20, p = 0.01) and L-lactate (log coefficient = 0.34, p<0.001). In multivariate analyses, hemoglobin A1c was negatively associated with sputum PMNs (log coefficient = -1.68, p<0.001) and plasma glucose was negatively associated with sputum glucose (log coefficient = -0.09, p = 0.02). Conclusions In CF sputum PMNs, glucose and lactate were unchanged during elective antibiotic treatment. However, sputum PMNs were associated with both sputum glucose and sputum lactate. Surprisingly, hyperglycemia seemed to be associated with less PMNs infiltration and less glucose in CF sputum.
    Keywords Medicine ; R ; Science ; Q
    Subject code 670
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Bacterial persisters in long-term infection

    Jennifer A Bartell / David R Cameron / Biljana Mojsoska / Janus Anders Juul Haagensen / Tacjana Pressler / Lea M Sommer / Kim Lewis / Søren Molin / Helle Krogh Johansen

    PLoS Pathogens, Vol 16, Iss 12, p e

    Emergence and fitness in a complex host environment.

    2020  Volume 1009112

    Abstract: Despite intensive antibiotic treatment, Pseudomonas aeruginosa often persists in the airways of cystic fibrosis (CF) patients for decades, and can do so without antibiotic resistance development. Using high-throughput screening assays of bacterial ... ...

    Abstract Despite intensive antibiotic treatment, Pseudomonas aeruginosa often persists in the airways of cystic fibrosis (CF) patients for decades, and can do so without antibiotic resistance development. Using high-throughput screening assays of bacterial survival after treatment with high concentrations of ciprofloxacin, we have determined the prevalence of persisters in a large patient cohort using 460 longitudinal isolates of P. aeruginosa from 39 CF patients. Isolates were classed as high persister variants (Hip) if they regrew following antibiotic treatment in at least 75% of the experimental replicates. Strain genomic data, isolate phenotyping, and patient treatment records were integrated in a lineage-based analysis of persister formation and clinical impact. In total, 19% of the isolates were classified as Hip and Hip emergence increased over lineage colonization time within 22 Hip+ patients. Most Hip+ lineages produced multiple Hip isolates, but few Hip+ lineages were dominated by Hip. While we observed no strong signal of adaptive genetic convergence within Hip isolates, they generally emerged in parallel or following the development of ciprofloxacin resistance and slowed growth. Transient lineages were majority Hip-, while strains that persisted over a clinically diagnosed 'eradication' period were majority Hip+. Patients received indistinguishable treatment regimens before Hip emergence, but Hip+ patients overall were treated significantly more than Hip- patients, signaling repeated treatment failure. When subjected to in vivo-similar antibiotic dosing, a Hip isolate survived better than a non-Hip in a structured biofilm environment. In sum, the Hip phenotype appears to substantially contribute to long-term establishment of a lineage in the CF lung environment. Our results argue against the existence of a single dominant molecular mechanism underlying bacterial antibiotic persistence. We instead show that many routes, both phenotypic and genetic, are available for persister formation and consequent increases ...
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2020-12-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Dietary intake and nutritional status in a Scandinavian adult cystic fibrosis-population compared with recommendations

    Inger E. Moen / Kristina Nilsson / Anna Andersson / Morten W. Fagerland / Gjermund Fluge / Annika Hollsing / Marita Gilljam / Lena Mared / Tacjana Pressler / Henriette Santi / Olav-Trond Storrøsten / Lena Hjelte

    Food & Nutrition Research, Vol 55, Iss 0, Pp 1-

    2011  Volume 9

    Abstract: Malnutrition is a well-known complication in cystic fibrosis (CF). There is good evidence that maintaining a normal body-weight correlates well with improved survival in CF. Energy intake in excess of 120% of the estimated average requirement (EAR) has ... ...

    Abstract Malnutrition is a well-known complication in cystic fibrosis (CF). There is good evidence that maintaining a normal body-weight correlates well with improved survival in CF. Energy intake in excess of 120% of the estimated average requirement (EAR) has been advised since 1980s.To investigate the nutritional intake and status in the adult Scandinavian CF-population.A cross-sectional multi-centre study was used to investigate the nutritional status of 456 adult CF-patients (2003 2006). Height and weight were measured and body mass index (BMI) and z-scores were calculated. Pulmonary function was examined by dynamic spirometry. A 7-day pre-coded food record (FR) obtained energy and nutrient intake data in 180 patients.The mean energy intake was 114 (SD 30.0)% of EAR and thus significantly lower than the target of 120% EAR (p< 0.001) for patients with pancreatic insufficiency (PI) (n=136). Mean BMI was 22.0 (SD 2.9), the prevalence of BMI <18 was 13% and the prevalence of BMI ≥25 was 15% (n = 136). Mean BMI was 20.8 (SD 2.4) in PI-patients with FEV1 <70% and 23.2% (SD 3.0), in PI-patients with FEV1 ≥70%, mean difference 2.4, (95% CI: 1.5, 3.3) (p<0.001), but there was no difference in energy intake. BMI ≥18.5 and a reported energy intake <120% were revealed in 54% of the PI-patients.The energy intake did not reach the recommended 120% EAR, but the prevalence of underweight was lower than reported in other studies. The recommendation may exceed the requirement for a number of CF-patients. The nutritional status must still be closely monitored and nutritional advice and intervention should be individualised and adjusted to actual needs.
    Keywords cystic fibrosis ; adult ; body mass index ; energy intake ; nutritional requirement ; forced expiratory volume ; Nutrition. Foods and food supply ; TX341-641 ; Home economics ; TX1-1110 ; Technology ; T ; DOAJ:Nutrition and Food Sciences ; DOAJ:Agriculture and Food Sciences
    Subject code 610
    Language English
    Publishing date 2011-11-01T00:00:00Z
    Publisher Co-Action Publishing
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Inhaled dry powder alginate oligosaccharide in cystic fibrosis

    Silke van Koningsbruggen-Rietschel / Jane C. Davies / Tacjana Pressler / Rainald Fischer / Gordon MacGregor / Scott H. Donaldson / Knut Smerud / Nils Meland / Jann Mortensen / Marie Ø. Fosbøl / Damian G. Downey / Astrid H. Myrset / Hugo Flaten / Philip D. Rye / The following investigators and their teams (in alphabetical order) conducted this study. / Mary Carroll / Jane Davies / Carsten Schwarz / Nico Derichs /
    Damian Downey / Olaf Eickmeier / Pal Leyell Finstad / Marie Øbro Fossbøl / Marita Gilljam / Lena Hjelte / Alan Knox / Susanne Nährig / Joachim Riethmüller / Felix C. Ringshausen / AS AlgiPharma / Laura Gow / Joy Conway / William Bennett

    ERJ Open Research, Vol 6, Iss

    a randomised, double-blind, placebo-controlled, crossover phase 2b study

    2020  Volume 4

    Abstract: Background OligoG is a low molecular-weight alginate oligosaccharide that improves the viscoelastic properties of cystic fibrosis (CF) mucus and disrupts biofilms, thereby potentiating the activity of antimicrobial agents. The efficacy of inhaled OligoG ... ...

    Abstract Background OligoG is a low molecular-weight alginate oligosaccharide that improves the viscoelastic properties of cystic fibrosis (CF) mucus and disrupts biofilms, thereby potentiating the activity of antimicrobial agents. The efficacy of inhaled OligoG was evaluated in adult patients with CF. Methods A randomised, double-blind, placebo-controlled multicentre crossover study was used to demonstrate safety and efficacy of inhaled dry powder OligoG. Subjects were randomly allocated to receive OligoG 1050 mg per day (10 capsules three times daily) or matching placebo for 28 days, with 28-day washout periods following each treatment period. The primary end-point was absolute change in percentage predicted forced expiratory volume in 1 s (FEV1) at the end of 28-day treatment. The intention-to-treat (ITT) population (n=65) was defined as randomised to treatment with at least one administration of study medication and post-dosing evaluation. Results In this study, 90 adult subjects were screened and 65 were randomised. Statistically significant improvement in FEV1 was not observed in the ITT population. Adverse events included nasopharyngitis, cough and pulmonary exacerbation. The number and proportions of patients with adverse events and serious adverse events were similar between OligoG and placebo group. Conclusions Inhalation of OligoG-dry powder over 28 days was safe in adult CF subjects. Statistically significant improvement of FEV1 was not reached. The planned analyses did not indicate a significant treatment benefit with OligoG compared to placebo. Post hoc exploratory analyses showed subgroup results that indicate that further studies of OligoG in this patient population are justified.
    Keywords Medicine ; R
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher European Respiratory Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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