Publications by authors named "Marianne Skov"

83 Publications

Use of inhaled antibiotics among Danish patients with cystic fibrosis.

Pediatr Pulmonol 2022 Apr 28. Epub 2022 Apr 28.

Department of Infectious Diseases, University Hospital of Copenhagen, Cystic Fibrosis Centre, Copenhagen, Denmark.

Background: Inhaled antibiotics are an important part of cystic fibrosis (CF) airway disease management and should be individualized to fit the microorganism and match patient needs. To investigate the implementation of personalized treatment, this study mapped the use of different types of inhaled antibiotics and adherence patterns.

Methods: We performed individual structured interviews in a cross-sectional study at the CF Centre in Copenhagen, Denmark. Patients with CF older than 15 years attending clinical consultations were included. Clinical data were obtained from centralized databases.

Results: Among 149 participants, 107 (72%) had indication for treatment with inhaled antibiotics. In this group, 97 (91%) reported the use of inhaled antibiotics within the last 12 months. Change from one inhaled antibiotic to another during that period was reported by 31 (29%), and 17 (25%) with Pseudomonas aeruginosa had used off-label antibiotics. Adherence to a minimum of one daily dose of antibiotic was reported by 78%, while adherence to all daily doses was 28 percentage points lower. Skipping inhalations was due to side effects and doubt about the effect in less than 5% of cases.

Conclusion: Change of inhaled antibiotics and use of off-label antibiotics for inhalation were common and side effects were a rare cause of nonadherence. This suggests satisfactory implementation of the principle of tailored antibiotic inhalation prescription in the Copenhagen CF population. Adherence to at least one daily inhalation dose was markedly higher than adherence to multiple daily inhalations.
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http://dx.doi.org/10.1002/ppul.25942DOI Listing
April 2022

National multi-centre study found a low prevalence of severely impaired lung function in children and adolescents.

Acta Paediatr 2022 May 31;111(5):1044-1051. Epub 2022 Jan 31.

Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Aim: As no data to our knowledge exist, the aim of the study was to describe the national prevalence and characteristics of Danish children and adolescents with severely impaired lung function.

Methods: We performed a descriptive, cross-sectional Danish multi-centre study. Children and adolescents between 6 and 18 years old demonstrating severely impaired lung function from 2015 to 2018, defined by forced expiratory volume in 1 second (FEV ) <60% or who had lung transplantation, were eligible for inclusion.

Results: This study included 113 children with a mean age (standard deviation) of 12.9 years (3.5 years). The prevalence of severely impaired lung function was approximately 13 in 100,000. The mean (standard deviation) FEV was 46.1% (10.1%) of predicted, and z-score was -4.5 (0.8). The most frequent diagnosis was cystic fibrosis (20.4%), followed by asthma (19.5%) and bronchiolitis obliterans (16.8%), while almost 25% had different elements of airway malformations or non-pulmonary conditions. Two adolescents with cystic fibrosis underwent lung transplantation.

Conclusion: The estimated prevalence of severely impaired lung function in Danish children and adolescents was low, and extremely, few children underwent lung transplantation. The most frequent diagnosis was cystic fibrosis, while almost 25% had different elements of airway malformations or non-pulmonary conditions, which may require clinical attention.
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http://dx.doi.org/10.1111/apa.16262DOI Listing
May 2022

Contemporary N and SF multiple breath washout in infants and toddlers with cystic fibrosis.

Pediatr Pulmonol 2022 04 25;57(4):945-955. Epub 2022 Jan 25.

Danish Paediatric Pulmonary Service, CF Centre Copenhagen, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Introduction: Multiple breath washout (MBW) is used for early detection of cystic fibrosis (CF) lung disease, with SF MBW commonly viewed as the reference method. The use of N MBW in infants and toddlers has been questioned for technical and physiological reasons, but a new correction of the N signal has minimized the technical part. The present study aimed to assess the remaining differences and the contributing mechanisms for the differences between SF and N MBW,corrected-such as tidal volume reduction during N washout with pure O .

Method: This was a longitudinal multicenter cohort study. SF MBW and N MBW were performed prospectively at three CF centers in the same visits on 154 test occasions across 62 children with CF (mean age: 22.7 months). Offline analysis using identical algorithms to the commercially available program provided outcomes of N and N for comparison with SF MBW.

Results: Mean functional residual capacity, FRC was 14.3% lower than FRC , and 1.0% different from FRC . Lung clearance index, LCI was 25.2% lower than LCI , and 7.3% higher than LCI . Mean (SD) tidal volume decreased significantly during N MBW , compared to SF MBW (-13.1 ml [-30.7; 4.6], p < 0.0001, equal to -12.0% [-25.7; 1.73]), but this tidal volume reduction did not correlate to the differences between LCI and LCI . The absolute differences in LCI increased significantly with higher LCI (0.63/LCI ) and (0.23/LCI ), respectively, for N and N , but the relative differences were stable across disease severity for N , but not for N .

Conclusion: Only minor residual differences between FRC and FRC remained to show that the two methods measure gas volumes very similar in this age range. Small differences in LCI were found. Tidal volume reduction during N MBW did not affect differences. The corrected N MBW can now be used with confidence in young children with CF, although not interchangeably with SF .
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http://dx.doi.org/10.1002/ppul.25830DOI Listing
April 2022

Rectally shed SARS-CoV-2 in COVID-19 inpatients is consistently lower than respiratory shedding and lacks infectivity.

Clin Microbiol Infect 2022 Feb 9;28(2):304.e1-304.e3. Epub 2021 Nov 9.

Department of Clinical Microbiology, Odense University Hospital and Research Unit of Clinical Microbiology, University of Southern Denmark, Odense, Denmark. Electronic address:

Objectives: Assessment of whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been propagated during intestinal passage and infectivity is conserved when shed rectally by hospitalized individuals.

Methods: An exploratory cohort study including 28 inpatients with coronavirus disease 2019 with estimation of RNA levels by RT-PCR and of viral infectivity by culturing of viral material sampled concomitantly and identically from pharynx and rectum.

Results: SARS-CoV-2 RNA was detected more frequently (91%, 30/33 versus 42%, 14/33, p <0.0001) and at higher concentrations (median levels 2 190 186 IU/mL versus 13 014 IU/mL, p <0.0001) in the pharyngeal swabs than in the rectal swabs. For all sample pairs (n = 33) the rectal swabs contained undetectable or lower SARS-CoV-2 RNA concentrations than their paired pharyngeal swabs. Replicative virus was found in 37% (11/30) of the PCR-positive pharyngeal swabs, whereas none of the PCR-positive rectal swabs could be cultured (0%, 0/14) despite containing SARS-CoV-2 RNA concentrations up to 1 544 691 IU/mL.

Conclusions: Our data draw into question whether SARS-CoV-2 is transmitted readily from faeces.
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http://dx.doi.org/10.1016/j.cmi.2021.10.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575534PMC
February 2022

Impact of timing of PERT on gastrointestinal symptoms in Danish children and adolescents with CF.

Acta Paediatr 2022 Feb 28;111(2):432-439. Epub 2021 Oct 28.

Rigshospitalet, CF Center Copenhagen, Department of Pediatrics and Adolescent Medicine, Copenhagen, Denmark.

Aim: Gastrointestinal (GI) symptoms are often reported by CF patients. Despite a proven relation to exocrine pancreatic insufficiency (PI), it remains unclear whether GI symptoms are related to the timing of pancreatic enzyme replacement therapy (PERT). Whereas most international recommendations suggest administration of PERT at the beginning of meals, it has not been studied whether such a proceeding is associated with lower burden of symptoms.

Methods: Thirty CF patients aged 0-17 years of age with PI were randomised to four weeks of PERT prior to meals followed by four weeks of PERT after meals or vice versa. Using the CF-specific validated CFAbd-Score, abdominal pain, dysfunctional bowel habits and Quality of Life (QoL) related to GI symptoms were assessed in relation to the timing of PERT. Data were analysed using a linear mixed model.

Results: There was no significant difference regarding abdominal pain, bowel habits or QoL related to GI symptoms when timing of PERT was changed from prior to after meals.

Conclusion: No significant difference was found when administration mode of PERT changed from prior to after meals or vice versa. However, after an individual assessment, some patients may profit from changing administration mode of PERT from prior to after meals.
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http://dx.doi.org/10.1111/apa.16143DOI Listing
February 2022

Prolonged viral shedding of SARS-CoV-2 in two immunocompromised patients, a case report.

BMC Infect Dis 2021 Aug 3;21(1):743. Epub 2021 Aug 3.

Department of Infectious Diseases, Odense University Hospital, J.B Winsløws Vej 4, 5000, Odense C, Denmark.

Background: The duration of viable Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) shedding in immunocompromised patients is still unknown. This case report describes the duration of viable SARS-CoV-2 in two immunocompromised patients with completely different clinical courses and further addresses the immunological aspects.

Case Presentations: Oropharyngeal swaps were collected continuously during hospitalization for two immunocompromised patients infected with SARS-CoV-2 and sent for analysis to real time reverse transcription polymerase chain reaction (RT-PCR), viral culture assessed by plaque assay and full genome sequencing. Blood samples for flow cytometry and further immunological analysis were taken once during admission. One patient was without symptoms of Coronavirus disease 2019 (COVID-19) whereas the other had severe respiratory symptoms requiring a stay at an intensive care unit (ICU) and treatment with remdesivir and dexamethasone. Despite their difference in clinical courses, they both continuously shed SARS-CoV-2 with high viral loads in culture. Both patients had undetectable anti SARS-CoV-2 IgG levels about 2 weeks after the first positive real time RT-PCR test of SARS-CoV-2, marked expansions of virus reactive CD8+ T cells but cellular markers indicative of attenuated humoral immunity.

Conclusions: Our case illustrates the importance of distinguishing isolation guidelines for patients infected with SARS-CoV-2 according to their immunological status. Furthermore, it demonstrates the need for immune markers relating to viral shedding in immunocompromised patients.
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http://dx.doi.org/10.1186/s12879-021-06429-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330202PMC
August 2021

Phenol-chloroform-based RNA purification for detection of SARS-CoV-2 by RT-qPCR: Comparison with automated systems.

PLoS One 2021 24;16(2):e0247524. Epub 2021 Feb 24.

Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic levels. Sufficient testing for SARS-CoV-2 has remained essential for tracking and containing the virus. SARS-CoV-2 testing capabilities are still limited in many countries. Here, we explore the use of conventional RNA purification as an alternative to automated systems for detection of SARS-CoV-2 by RT-qPCR. 87 clinical swab specimens were extracted by conventional phenol-chloroform RNA purification and compared to commercial platforms for RNA extraction and the fully integrated Cobas®6800 diagnostic system. Our results show that the conventional RNA extraction is fully comparable to modern automated systems regarding analytical sensitivity and specificity with respect to detection of SARS-CoV-2 as evaluated by RT-qPCR. Moreover, the method is easily scalable and implemented in conventional laboratories as a low cost and suitable alternative to automated systems for the detection of SARS-CoV-2.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247524PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904160PMC
March 2021

Withdrawal of dornase alfa increases ventilation inhomogeneity in children with cystic fibrosis.

J Cyst Fibros 2021 11 19;20(6):949-956. Epub 2021 Feb 19.

CF Centre Copenhagen, Paediatric Pulmonary Service, Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. Electronic address:

Background: The lung clearance index (LCI) is increasingly used as an outcome in clinical trials of patients with mild cystic fibrosis (CF) lung disease. Yet, understanding the impact of standard CF respiratory therapy on LCI is needed. We assessed to what degree withdrawal of nebulised dornase alfa affected LCI in school-age children with CF not receiving CFTR modulators or hydrator therapy.

Methods: A single-centre, randomised, controlled, parallel group study to determine effects of one month's withdrawal of nebulised dornase alfa (intervention) in 5-18 years old children with CF. Remaining chronic maintenance therapy stayed unchanged. Outcome measures were assessed at two visits one month apart. Primary outcome was absolute change in LCI. Secondary outcomes were FEV, FEF and CF Questionnaire-revised (CFQ-R) respiratory symptom score. Possible harmful effects were assessed by comparing the occurrence of pulmonary exacerbations between groups.

Results: Twenty-eight children (median age 10.4 [interquartile range: 7.6; 13.5] years) with CF received standard care (n = 14) or intervention (n = 14). Compared with the control group, LCI increased (worsened) 1.74 (95% confidence interval: 0.62; 2.86) during withdrawal of dornase alfa, while FEV (-6.8% predicted) and FEF (-13.1% predicted) decreased significantly. Change in CFQ-R respiratory symptom score and the occurrence of pulmonary exacerbations did not differ significantly between groups.

Conclusions: One month's withdrawal of dornase alfa caused increasing ventilation inhomogeneity and deteriorating FEV and FEF in school-age children with mild CF. Hence, adherence to dornase alfa optimally needs to be addressed when using LCI and spirometric parameters as endpoints, even in short-term clinical trials.
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http://dx.doi.org/10.1016/j.jcf.2021.02.004DOI Listing
November 2021

Using core genome multilocus sequence typing (cgMLST) for vancomycin-resistant Enterococcus faecium isolates to guide infection control interventions and end an outbreak.

J Glob Antimicrob Resist 2021 03 19;24:418-423. Epub 2021 Feb 19.

Research Unit for Department of Clinical Microbiology, Odense University Hospital, University of Southern Denmark, Odense, Denmark.

Objectives: Until July 2016, vancomycin-resistantEnterococcus faecium (VREfm) was sporadically detected in Odense University Hospital, Denmark. After July 2016, the number of VREfm cases increased. This study aimed to apply a core genome multilocus sequence typing (cgMLST) scheme for E. faecium to type and analyse VREfm isolates collected at a single Danish hospital and to compare the results with cgMLST data from other regions of Denmark to trace transmission.

Methods: A total of 38 VREfm clinical isolates from inpatients at the hospital in the period January 2014 through June 2017 were included in the study and analysed using whole-genome sequencing. Use of SeqSphere + software was initiated from the beginning of June 2017 to obtain MLST, cgMLST and epi curves. Admission histories were incorporated and national surveillance data on cgMLST were used to identify transmission routes.

Results: Six different sequence types (STs) were identified, the most frequent being ST80, ST117 and ST203. cgMLST subdivided the 38 isolates into 18 different complex types (CTs) with 13 isolates (34%) belonging to ST80-CT993. Epi curves indicated transmission of ST80-CT993 in several departments. Transmission from patients transferred from other hospitals was not identifiable. Infection control interventions launched in one department ended the outbreak.

Conclusion: The high resolution of cgMLST allowed for detailed interpretation with evidence of nosocomial transmission of specific CTs. cgMLST made it easy to compare our local isolates with national findings, thereby clarifying transmission routes. Supplemented with admission histories, cgMLST targeted the epidemiological investigation and delineated the expensive and time-consuming infection control interventions.
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http://dx.doi.org/10.1016/j.jgar.2021.02.007DOI Listing
March 2021

Potential anti-EBV effects associated with elevated interleukin-21 levels: a case report.

BMC Infect Dis 2020 Nov 23;20(1):878. Epub 2020 Nov 23.

Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.

Background: Germinal center derived memory B cells and plasma cells constitute, in health and during EBV reactivation, the largest functional EBV reservoir. Hence, by reducing germinal center derived formation of memory B cells and plasma cells, EBV loads may be reduced. Animal and in-vitro models have shown that IL-21 can support memory B and plasma cell formation and thereby potentially contribute to EBV persistence. However, IL-21 also displays anti-viral effects, as mice models have shown that CD4 T cell produced IL-21 is critical for the differentiation, function and survival of anti-viral CD8 T cells able to contain chronic virus infections.

Case Presentation: We present immunological work-up (flow-cytometry, ELISA and genetics) related to a patient suffering from a condition resembling B cell chronic active EBV infection, albeit with moderately elevated EBV copy numbers. No mutations in genes associated with EBV disease, common variable immunodeficiency or pertaining to the IL-21 signaling pathway (including hypermorphic IL-21 mutations) were found. Increased (> 5-fold increase 7 days post-vaccination) CD4 T cell produced (p < 0.01) and extracellular IL-21 levels characterized our patient and coexisted with: CD8 lymphopenia, B lymphopenia, hypogammaglobulinemia, compromised memory B cell differentiation, absent induction of B-cell lymphoma 6 protein (Bcl-6) dependent peripheral follicular helper T cells (pT, p = 0.01), reduced frequencies of peripheral CD4 Bcl-6 T cells (p = 0.05), compromised plasmablast differentiation (reduced protein vaccine responses (p < 0.001) as well as reduced Treg frequencies. Supporting IL-21 mediated suppression of pT formation, pT and CD4 IL-21 frequencies were strongly inversely correlated, prior to and after vaccination, in the patient and in controls, Spearman's rho: - 0.86, p < 0.001.

Conclusions: To the best of our knowledge, this is the first report of elevated CD4 IL-21 T cell frequencies in human EBV disease. IL-21 overproduction may, apart from driving T cell mediated anti-EBV responses, disrupt germinal center derived memory B cell and plasma cell formation, and thereby contribute to EBV disease control.
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http://dx.doi.org/10.1186/s12879-020-05609-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685648PMC
November 2020

Extended Screening for Cystic Fibrosis-related Liver Disease Including Elastography in Children and Adolescents.

J Pediatr Gastroenterol Nutr 2020 11;71(5):663-668

Copenhagen Cystic Fibrosis Center, Rigshospitalet.

Objectives: Advances in treatment of cystic fibrosis (CF) have increased survival and thereby prevalence of patients with liver disease, making chronic liver disease one of the major complications of CF. We describe the prevalence of liver fibrosis, portal hypertension, and liver decompensation by extended screening for cystic fibrosis-related liver disease (CFLD) including ultrasound, elastography, and an extended panel of biochemical markers.

Methods: A cross sectional study of CFLD in all pediatric CF patients (1-18 years) from the Copenhagen CF Center. Screening for liver disease included physical examination, biochemical analysis, Vibration-Controlled Transient Elastography (FibroScan), conventional ultrasound, and Real-Time Shear Wave elastography (SWE). Patients were scored according to Williams ultrasound scoring scale (WUSS) within 6 months.

Results: A total of 84 consecutive patients (male sex 46.4%, median age 10.4 years) were included. Eight patients (9.5%) had both ≥2 abnormal results of sonographic methods and ≥2 abnormal biochemical results and were in this study categorized as having manifest CFLD. Manifest CFLD patients were significantly older and had a higher mean value of APRI, but no differences in gender, z-height, z-weight, z-BMI, FEV1%, or mean value of bilirubin or albumin were found.

Conclusions: In total, 8 patients (9.5%) in this pediatric CF population were categorized as having CFLD according to both biochemical and sonographic tests. Consistency was found among the results of FibroScan and SWE. We suggest WUSS and either FibroScan or SWE, combined with GGT as diagnostic markers for CFLD.
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http://dx.doi.org/10.1097/MPG.0000000000002872DOI Listing
November 2020

Omics-based tracking of persistence in "eradicated" cystic fibrosis patients.

Eur Respir J 2021 04 8;57(4). Epub 2021 Apr 8.

The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.

Whenever is cultured from cystic fibrosis (CF) patient airways, the primary goal is eradication by antibiotic therapy. Success is defined by ≥6 months of negative bacterial airway cultures. However, we suspect that persists in airways without clinical detection for long periods.Out of 298 -infected Copenhagen CF patients, we identified 80 with complete monitoring records and measured their maximum -free eradication periods (MEP). Isolates from 72 patients were whole-genome sequenced (n=567) and clone typed. Select isolate relatedness was examined through phylogenetic analysis and phenotypic multivariate modelling.69 (86%) patients exhibited eradication in the monitoring period (2002-2018). Sequenced isolates bridged the MEP of 42 patients, and the same clone type persisted over the MEP in 18 (43%) patients. Patients with failed eradication were on average treated more intensively with antibiotics, but this may be linked to their more severe pre-MEP infection trajectories. Of the 42 patients, 26 also had sinus surgery; the majority (n=15) showed MEPs adjacent to surgery, and only five had persisting clone types. Importantly, combined phylogenetic-phenomic evaluation suggests that persisting clone types are a result of re-emergence of the same strain rather than re-infection from the environment, and similar relatedness is exhibited by paired lower and upper airway samples and in transmission cases.In conclusion, nearly half of CF patients with supposed eradication may not truly be cleared of their original bacteria according to omics-based monitoring. This distinct cohort that is persistently infected would probably benefit from tailored antibiotic therapy.
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http://dx.doi.org/10.1183/13993003.00512-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8029213PMC
April 2021

Prospective longitudinal association between repeated multiple breath washout measurements and computed tomography scores in children with cystic fibrosis.

J Cyst Fibros 2021 07 4;20(4):632-640. Epub 2020 Oct 4.

Danish PCD & chILD Centre, CF Centre Copenhagen, Paediatric Pulmonary Service, ERN Accredited, Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Denmark. Electronic address:

Background: Progression of structural lung disease (SLD) is a major risk factor for morbidity in patients with cystic fibrosis (CF). We studied changes in SLD and correlations with spirometry and nitrogen multiple breath washout (NMBW) outcomes to explore associations in contemporary evolution between structural and functional abnormalities in CF lung disease.

Methods: Spirometry-controlled chest-CTs using PRAGMA-CF for scoring extent of SLD, spirometry, and NMBW were performed at two-year intervals in school-age children with CF.

Results: Fifty-seven children aged 6-18 years were included. No significant progression in mean PRAGMA-CF scores was observed. Half of the children showed improvement in the proportion of bronchiectasis (%Bx). Lung Clearance Index (LCI) and the second moment ratio (M2) increased significantly and baseline values correlated significantly with SLD at follow-up (p ≤ 0.0002). The correlation between the change in M2 (∆M2) and the change in total SLD was R = 0.27 (p = 0.048). We found high negative predictive values (100%) for ∆M2<10% to exclude progression in SLD. For stable or improving values of LCI and M2, the predicted probability for progression in SLD was 16% and 14%, respectively (upper 95% confidence limit: 33%). Evolution in NMBW and CT outcomes was discordant in half of the children.

Conclusions: We found no progression in SLD over 2 years in school-age children with CF, in contrast to both LCI and M2, which along with discordant outcomes in half of the children underlines that NMBW and CT assess different aspects of CF lung disease. However, stable outcomes from NMBW were associated with stable structural lung disease.
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http://dx.doi.org/10.1016/j.jcf.2020.09.010DOI Listing
July 2021

Azole-Resistant Among Danish Cystic Fibrosis Patients: Increasing Prevalence and Dominance of TR/L98H.

Front Microbiol 2020 13;11:1850. Epub 2020 Aug 13.

Unit of Mycology, Statens Serum Institut, Copenhagen, Denmark.

Azole-resistant (azole-R) is an increasing challenge worldwide. Patients with cystic fibrosis (CF) are at risk of colonization and disease due to a favorable lung environment for microorganisms. We performed a nationwide study in 2018 of azole-non-susceptible in CF patients and compared with data from two prior studies. All airway samples with mold isolates from patients monitored at the two CF centers in Denmark (RH, Jan-Sept and AUH, Jan-Jun) were included. Classical species identification (morphology and thermo-tolerance) was performed and MALDI-TOF/β-tubulin sequencing was performed if needed. Susceptibility was determined using EUCAST E.Def 10.1, and E.Def 9.3.2. sequencing and STR genotyping were performed for azole-non-susceptible isolates and relevant sequential isolates. In total, 340 mold isolates from 159 CF patients were obtained. The most frequent species were (266/340, 78.2%) and (26/340, 7.6%). Azole-R was cultured from 7.3% (10/137) of patients, including 9.5% (9/95) of patients at RH and 2.4% at AUH (1/42), respectively. In a 10-year perspective, azole-non-susceptibility increased numerically among patients at RH (10.5% in 2018 vs 4.5% in 2007-2009). Cyp51A resistance mechanisms were found in nine azole-R from eight CF patients. Five were of environmental origin (TR/L98H), three were human medicine-driven (two M220K and one M220R), and one was novel (TR /L98H) and found in a patient who also harbored a TR/L98H isolate. STR genotyping identified 27 unique genotypes among 45 isolates and ≥2 genotypes in 8 of 12 patients. This included one patient carrying two unique TR/L98H isolates, a rare phenomenon. Genotyping of sequential TR /L98H and TR/L98H isolates from the same patient showed only minor differences in 1/9 markers. Finally, azole-R was found in three patients including two with Cyp51A alterations (M217I and G51A, respectively). Azole-R is increasing among CF patients in Denmark with the environmentally associated resistance TR/L98H mechanism being dominant. Mixed infections (wildtype/non-wildtype and several non-wildtypes) and a case of potential additional tandem repeat acquisition were found. However, similar genotypes were identified from another patient (and outside this study), potentially suggesting a predominant TR/L98H clone in DK. These findings suggest an increasing prevalence and complexity of azole resistance in .
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http://dx.doi.org/10.3389/fmicb.2020.01850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438406PMC
August 2020

Patients with cystic fibrosis and advanced lung disease benefit from lumacaftor/ivacaftor treatment.

Pediatr Pulmonol 2020 12 19;55(12):3364-3370. Epub 2020 Sep 19.

Cystic Fibrosis Center, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Background: Several studies have assessed safety and efficacy outcomes for lumacaftor/ivacaftor therapy. We report on lumacaftor/ivacaftor's impact on lung function, physical performance, and health-related quality of life (HRQOL) in a subpopulation of Danish people with Cystic Fibrosis (CF; PWCF) with advanced pulmonary disease who would not fulfill inclusion criteria for these studies.

Methods: This follow-up study examined lumacaftor/ivacaftor's effect in a highly selected CF population. Inclusion criteria included low percent predicted forced expiratory volume in one second (ppFEV ), fast deteriorating ppFEV , low body mass index (BMI), and difficult-to-treat infections. Primary endpoints included change in ppFEV slope, cardiopulmonary exercise testing (CPET), and all domains of the Cystic Fibrosis Questionnaire-Revised (CFQ-R). Secondary outcomes included change in ppFEV , BMI Z-score, and sweat chloride concentration.

Results: A total of 21 patients homozygous for the F508del mutation and a median ppFEV of 38.7 were included. We found significant improvements in ppFEV (+4.2 p < .01, +5.8 p < .01, +4.8 p < .01 and +3.8 p = .03 ppFEV after 3, 6, 9, and 12 months of treatment compared to baseline), ppFEV slope (+6.84 ppFEV /year between the year before and the year after treatment initiation; p = .02), and saturation at CPET initiation (+1.4%, p < .02) and termination (+2.6%, p < .01) after 6 months of treatment. Finally, HRQOL improved significantly in all CFQ-R domains except Emotion and Treat.

Conclusions: Our findings suggest that lumacaftor/ivacaftor reduces lung function decline, improves lung function, physical performance, and HRQOL to a greater extent in PWCF with severe lung disease than previously recognized.
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http://dx.doi.org/10.1002/ppul.25059DOI Listing
December 2020

Lung clearance index-triggered intervention in children with cystic fibrosis - A randomised pilot study.

J Cyst Fibros 2020 11 21;19(6):934-941. Epub 2020 Jun 21.

CF Centre Copenhagen, Paediatric Pulmonary Service, Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark. Electronic address:

Hypothesis: Using increase in the lung clearance index (LCI) as a trigger for bronchoalveolar lavage (BAL) and associated antimicrobial treatment might benefit clinical outcomes in children with cystic fibrosis (CF).

Methods: A 2-year, longitudinal, interventional, randomized, controlled pilot study with quarterly visits in 5-18 years old children with CF. LCI and z-scores for the forced expired volume in 1 s (zFEV) and body mass index (zBMI) were obtained at every visit, CF Questionnaire-revised (CFQ-R) yearly and BAL and chest computed tomography at first and last visit. Children in the intervention group had BAL performed if LCI increased >1 unit from a fixed baseline value established at first visit. If the presence of a pathogen was documented in the BAL fluid, treatment was initiated/altered accordingly.

Results: Twenty-nine children with CF were randomized to the control (n = 14) and intervention group (n = 15). The median (interquartile range) number of BAL procedures per child was 2.5 (2.0; 3.0) and 6.0 (4.0; 7.0) in the control and intervention group, respectively. There was no significant difference between groups in slope for the primary outcome LCI; difference was 0.21 (95% confidence interval: -0.45; 0.88) units/year. Likewise, there was no significant difference between groups in slope for the secondary outcomes zFEV, zBMI, CFQ-R respiratory symptom score and the proportion of total disease and trapped air on chest computed tomography.

Conclusions: LCI-triggered BAL and associated antimicrobial treatment did not benefit clinical outcomes in a small cohort of closely monitored school-age children with CF.
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http://dx.doi.org/10.1016/j.jcf.2020.06.010DOI Listing
November 2020

What it takes to implement regular longitudinal multiple breath washout tests in infants with cystic fibrosis.

J Cyst Fibros 2020 11 30;19(6):1027-1028. Epub 2020 Apr 30.

CF Centre Copenhagen, Paediatric Pulmonary Service, Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. Electronic address:

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http://dx.doi.org/10.1016/j.jcf.2020.04.002DOI Listing
November 2020

A Chlamydia trachomatis 23S rRNA G1523A variant escaping detection in the Aptima Combo 2 assay (Hologic) was widespread across Denmark in July-September 2019.

APMIS 2020 Jun 4;128(6):440-444. Epub 2020 May 4.

Department for Bacteria, Parasites and Fungi, Infectious Diseases Preparedness, Statens Serum Institut, Copenhagen, Denmark.

Chlamydia trachomatis infection is the most common bacterial sexually transmitted infection globally, and nucleic acid amplification tests (NAATs) are recommended for highly sensitive and specific diagnosis. In early 2019, the Finnish new variant of Chlamydia trachomatis (FI-nvCT) was identified. The FI-nvCT has a C1515T mutation in the 23S rRNA gene, making it escaping detection in the Aptima Combo 2 (AC2; Hologic) NAAT, and the FI-nvCT has been subsequently reported in Sweden and Norway. In the present study, we investigated the presence of the FI-nvCT and other AC2 diagnostic-escape CT mutants in July-September 2019 in Denmark. The FI-nvCT was present but rare in Denmark. However, another AC2 diagnostic-escape CT mutant (with a 23S rRNA G1523A mutation) was found to be widespread across Denmark, accounting for 95% (76/80) of AC2 diagnostic-escape nvCT samples from five Danish CT-diagnostic laboratories. This nvCT-G1523A has previously only been detected in one single sample in the United Kingdom and Norway, respectively. It is vital to monitor the continued stability of the NAAT targets in local, national and international settings and monitor as well as appropriately analyse incidence, unexplained shifts in diagnostics rates and/or annual collections of samples diagnosed as negative/equivocal using NAATs with different target(s). Furthermore, diagnostic CT NAATs with dual target sequences are crucial, and fortunately, an updated Hologic AC2 assay including one additional target sequence is in advanced development.
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http://dx.doi.org/10.1111/apm.13043DOI Listing
June 2020

Cystic fibrosis newborn screening in Denmark: Experience from the first 2 years.

Pediatr Pulmonol 2020 02 4;55(2):549-555. Epub 2019 Nov 4.

Department of Clinical Genetics, Molecular Genetics Laboratory, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Background: In Denmark, newborn screening (NBS) for cystic fibrosis (CF) was introduced on 1 May 2016. The implementation and results from the first 2 years of the national newborn CF screening program are presented.

Methods: The screening included immunoreactive trypsinogen (IRT), followed by evaluation for the F508del mutation when a value at or above the 50 ng/mL cutoff was present. In cases with a single F508del mutation or a very high IRT value above 145 ng/mL, next-generation sequencing of the CF transmembrane conductance regulator gene (CFTR) was performed.

Results: Of 126 522 newborn infants 126 338 were tested (99.85%), and 4730 samples (3.7%) were assessed for CFTR mutations. Twenty-six infants were screen-positive and referred for diagnostic follow-up of whom 22 were confirmed to have a CF diagnosis, four had one known and one CFTR allele with unknown pathogenicity, classified as cystic fibrosis screening positive inconclusive diagnosis (CFSPID), PPV 84.6%. One of the four children classified as CFSPID was later found to carry the two identified CFTR variants in cis and was reclassified as a carrier of CF. We found two false negatives; one exhibited an IRT level above the 50 ng/mL cutoff but was below the 145 ng/mL very high cutoff and with no F508del mutation present. The second false-negative fell below the 50 ng/mL IRT cutoff but was diagnosed shortly after birth on the basis of meconium ileus. Screening sensitivity, 91.7%. Two hundred thirty-two children were identified as carriers of CF, which is twofold above the estimated annual number of carriers. All but one carrier were heterozygous for the F508del CFTR mutation. Sixteen percent of the sequenced samples revealed rare CFTR variants, which were classified as nonpathogenic in relation to CF.

Conclusions: During the first 2 years of NBS CF screening in Denmark, we identified close to the expected number of infants with CF using an algorithm based on IRT, presence of F508del mutation and comprehensive genetic analysis. CFSPID accounted for only a small minority, despite comprehensive CFTR sequencing, whereas more carriers than initially expected were identified.
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http://dx.doi.org/10.1002/ppul.24564DOI Listing
February 2020

Late diagnosis and poor nutrition in cystic fibrosis diagnosed before implementation of newborn screening.

Acta Paediatr 2019 12 12;108(12):2241-2245. Epub 2019 Jul 12.

Department of Pediatrics, Copenhagen University Hospital, Copenhagen, Denmark.

Aim: Denmark has a high standard cystic fibrosis care. However, newborn screening was not implemented until 2016. This article describes the clinical status of cystic fibrosis patients at time of diagnosis prior to newborn screening.

Methods: Patients diagnosed with cystic fibrosis in Denmark in 2010-2014 were reviewed using the Danish Cystic Fibrosis Registry as well as patient files. Parameters collected were age at diagnosis, gender, weight, height, forced expiratory volume at 1 second, cystic fibrosis transmembrane regulator-genotype, lung bacteriology at diagnosis and previous diagnoses.

Results: A total of 63 patients were diagnosed in the study period. The most typical pre-cystic fibrosis diagnoses were asthma and pneumonia. The median age at diagnosis was 1.4 years for the pancreatic insufficient and 27.3 years for the pancreatic sufficient patients. Of the pancreatic insufficient patients, 21% had moderate to severe malnutrition with BMI below minus 2 SD and 40% had moderate to severe stunting with height below minus 2 SD.

Conclusion: Diagnosis was delayed considerably compared to diagnosis by newborn screening in other countries. Many cystic fibrosis patients diagnosed due to clinical symptoms were moderately to severely underweight or stunted at diagnosis.
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http://dx.doi.org/10.1111/apa.14908DOI Listing
December 2019

Markers of bone turnover are reduced in patients with CF related diabetes; the role of glucose.

J Cyst Fibros 2019 05 28;18(3):436-441. Epub 2019 Mar 28.

Copenhagen Cystic Fibrosis Center, Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK2100 Copenhagen, Denmark.

Background: Cystic fibrosis(CF) related diabetes(CFRD) and osteoporosis are prevalent in adult patients with CF. We aimed to evaluate if CFRD and markers of glucose metabolism and inflammation are associated with bone turnover in CF.

Methods: Cross sectional study at the adult section at the Copenhagen CF Center from January-October 2017. Fasting blood samples, including bone turnover markers(BTMs) and cytokines, Dual-x-ray absorptiometry scan and oral glucose tolerance test were performed. Lung-transplanted participants and patients in antiosteoporotic treatment were excluded from analyses.

Results: 102 patients were included of whom 19 had a prior CFRD diagnosis. CFRD patients had lower procollagen type 1 N-terminal propeptide(P1NP) and C-Terminal cross-linked Telopeptide(CTX) levels compared to CF patients without diabetes (median[IQR]) 49.5 μg/l [29.6,57.1] vs 56.9 μg/l [38.2,74.3], p = .03 and 0.2 μg/l [0.1,0.3] vs 0.4 μg/l [0.3,0.6], p < .01, respectively. Fasting plasma glucose(FPG) was negatively associated with the bone formation markers P1NP and osteocalcin and bone resorption marker CTX. In multivariate linear regression FPG remained a significant predictor of P1NP -1.07 [-1.09;-0.01] and CTX -1.13 [-1.21;-1.06]. Bone mineral density Z-score was not different between patients with and without CFRD but FPG was negatively associated with hip and femoral neck Z-score. There was no consistent association between inflammatory cytokines and BTMs.

Conclusions: Bone turnover markers are reduced in CF patients with CFRD and negatively associated with glucose levels. Extra attention towards frequent hyperglycemia in CF patients should be taken when evaluating decreased BMD. Glycemia may be a future target for improving outcome in CFBD.
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http://dx.doi.org/10.1016/j.jcf.2019.01.004DOI Listing
May 2019

Optimization of colistin dosing regimen for cystic fibrosis patients with chronic Pseudomonas aeruginosa biofilm lung infections.

Pediatr Pulmonol 2019 05 25;54(5):575-580. Epub 2019 Feb 25.

Department of Clinical Microbiology, Rigshospitalet, University of Copenhagen, Denmark.

Objective: The present study was performed to explore dosing regimens of colistin in patients of cystic fibrosis (CF) with Pseudomonas aeruginosa chronic biofilm lung infection.

Methods: Ten CF patients were involved. One dose colistimethate sodium (CMS) of 6 MIU (million international units) and 9 MIU were administered by intravenous infusion over 45 and 90 min. Venous blood was collected at different time points after the infusion of CMS. Pharmacokinetic parameters of colistin were calculated. Minimum inhibitory concentration for planktonic P. aeruginosa, minimum biofilm inhibitory concentration and minimum biofilm eradication concentration of P. aeruginosa were determined. Monte Carlo simulation was performed to determine the clinical probability of target attainment of different dosing regimens of colistin in CF patients.

Results: For 90 min (6 MIU), 45 min (6 MIU), and 45 min (9 MIU) intravenous infusion of colistin, C was 8.9 ± 1.8, 15 ± 5.5, and 31.7 ± 5.3 μg/mL, respectively; T was 1.2 ± 0.4, 0.7 ± 0.2, and 0.8 ± 0.2 h, respectively; AUC were 31 ± 3.8, 34 ± 10, and 135 ± 31mg · h/L, respectively; t was 2.1 ± 0.4, 2 ± 0.3, and 3.3 ± 0.4 h, respectively. MBIC and MBEC of colistin on biofilms at 24 h period treatment were 16-128 μg/mL for non-mucoid and mucoid biofilms of P. aeruginosa. For 90 min (6 MIU), 45 min (6 MIU) and 45 min iv infusion (9 MIU) with one dose colistin, PTA was 49.8%, 53.8%, 99.4% for planktonic infection, and 11.3%, 14.6%, 65.3%, respectively for biofilm infection.

Conclusions: colistin treatment using 45 min iv infusion is better than 90 min iv infusion in this study. Colistin dosage of 9 MIU is better than 6 MIU on both planktonic and biofilm infections of P. aeruginosa in this study.
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http://dx.doi.org/10.1002/ppul.24269DOI Listing
May 2019

Cystic fibrosis - an example of personalized and precision medicine.

APMIS 2019 May 14;127(5):352-360. Epub 2019 Feb 14.

Cystic Fibrosis Center, Rigshospitalet, Copenhagen, Denmark.

Cystic fibrosis (CF) is a severe, monogenic, autosomal recessive disease caused by mutations in the CFTR (cystic fibrosis transmembrane regulator) gene, where disturbed chloride and bicarbonate transportation in epithelial cells results in a multiorgan disease with primarily pulmonary infections and pancreatic insufficiency. In 1968, the Copenhagen CF Center was established, and centralized care of CF patients with monthly control was introduced. Close monitoring and treatment of Pseudomonas lung infection as well as segregation of patients with different infection status improved the clinical outcome as well as survival. Prophylactic basic treatment as well as infection treatments follow specific algorithms. A variety of comorbidities have all along the pulmonary infection control necessitated personalized care, adjusted to the patients' phenotype. With the introduction of CFTR modulators, the treatment has shifted from prophylactic, symptomatic type toward a new era of precision medicine targeting the basic defect according to the patients' CFTR genotype. Future directions will focus on further improvement of the CFTR modulators and gene therapy, as well as modifier genes and CF phenotype.
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http://dx.doi.org/10.1111/apm.12915DOI Listing
May 2019

Use of Loop-Mediated Isothermal Amplification in a Resource-Saving Strategy for Primary Malaria Screening in a Non-Endemic Setting.

Am J Trop Med Hyg 2019 03;100(3):566-571

Department of Clinical Microbiology, Odense University Hospital, Odense, Denmark.

Malaria is traditionally diagnosed by blood smear microscopy, which requires continuous resource-demanding training. In areas with only a few cases of malaria, a simple and rapid test that can reliably exclude malaria could significantly reduce the need for microscopy and training. We evaluated whether loop-mediated isothermal amplification (LAMP) for screening malaria parasites could reduce the workload in the diagnosis of malaria. Loop-mediated isothermal amplification was used to analyze 38 ethylene-diamine-tetraacetic acid (EDTA) blood samples from 23 patients who had previously been tested for malaria by microscopy, antigen-based rapid diagnostic test (antigen-RDT), and in-house real-time polymerase chain reaction (RT-PCR). The samples included blood with low-level parasitaemia and samples with discrepancies between the results of the different methods. Loop-mediated isothermal amplification detected malaria parasites in 27 of 28 samples that were positive according to in-house RT-PCR. There were negative microscopy results in 10 of these and negative antigen-RDT results in 11. The sample with a negative LAMP result and positive in-house RT-PCR result was from a patient who had recently been treated for low-level malaria parasitaemia. We found LAMP to be reliable for malaria screening and suitable for replacing microscopy without loss of performance. The low number of LAMP-positive samples needing microscopy can be handled by a limited number of trained microscopists. The time saved on training and documentation was estimated to be 520 working hours yearly in our laboratory. Using LAMP for primary screening of patient samples, we have made a diagnostic workflow that ensures more reliable, faster, and less resource-demanding diagnosis of malaria.
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http://dx.doi.org/10.4269/ajtmh.18-0496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402892PMC
March 2019

Can secretory immunoglobulin A in saliva predict a change in lung infection status in patients with cystic fibrosis? A prospective pilot study.

Health Sci Rep 2018 Aug 12;1(8):e52. Epub 2018 Jul 12.

Department of Clinical Microbiology Rigshospitalet Denmark.

Background: Chronic lung infection with is the main cause of mortality in patients with cystic fibrosis (CF). Sinus colonization with P. aeruginosa often precedes intermittent lung colonization, and intermittent colonization precedes chronic infection.When P. aeruginosa colonizes the sinuses, elevated immunoglobulin A (IgA) levels specific against P. aeruginosa can be detected in saliva. Therefore, we hypothesized that increasing levels of IgA in saliva can be detected before P. aeruginosa lung colonization.

Methods: Forty-nine CF patients free from lung colonization with P. aeruginosa or other Gram-negative bacteria (GNB) were included in this prospective study. Saliva and serum samples were collected and examined for IgA antibodies against P. aeruginosa with at least 6-month intervals between sequential samples.

Results: A total of 110 measurements of IgA in saliva were included. During a median of 8.5-month follow-up, 25 patients changed their lung infection status. We were able to construct a statistical model that for a given value of IgA in saliva, could predict the probability of a change in lung infection status within the next 8.5 months (median):  = 1 / (1 + exp(-(-0.9582 + 1.6518*IgA)). The model includes a prediction band where 95% of new measurements are predicted to fall within. The model, however, failed to reach statistical significance ( = 0.056 1-tailed), probably because of lack of power.

Conclusion: The saliva IgA model may predict a worsening in lung infection status presumably acting as a surrogate marker of P. aeruginosa bacterial sinusitis. The model may identify patients at risk of subsequent lung colonization and, thus, be a helpful clinical tool, but it should be tested in studies with larger sample sizes to evaluate its utility.
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http://dx.doi.org/10.1002/hsr2.52DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266372PMC
August 2018

The importance of early diagnosis of Mycobacterium abscessus complex in patients with cystic fibrosis.

APMIS 2018 Dec;126(12):885-891

Cystic Fibrosis Center Copenhagen, Rigshospitalet, Copenhagen, Denmark.

Mycobacterium abscessus complex can cause severe lung infections and has proven to be a serious threat to patients with cystic fibrosis and a challenge for clinicians due to difficulties in timely diagnosis and complex multidrug treatment regimes. Mycobacterial culture is the gold standard for diagnosis, but in most cystic fibrosis centers it is performed less frequently than culture for other pathogens. Consensus today recommends just one annual mycobacterial culture for asymptomatic patients with cystic fibrosis, a strategy likely to lead to diagnostic delays. Postponement of diagnosis might be the deciding factor in whether an early colonization turns into chronic infection. This review highlights the latest developments in knowledge about the pathogenicity and clinical consequences of M. abscessus complex pulmonary disease, addressing the central theme of why pulmonary infection requires early identification and aggressive antibiotic treatment. The window of opportunity, before M. abscessus complex transforms from a mucosal colonizer to a chronic biofilm infection, is where microbial eradication is most likely to be successful, making early diagnosis essential for improved outcomes.
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http://dx.doi.org/10.1111/apm.12903DOI Listing
December 2018

Osteoporosis Is Associated with Deteriorating Clinical Status in Adults with Cystic Fibrosis.

Int J Endocrinol 2018 26;2018:4803974. Epub 2018 Mar 26.

Department of Medicine, Endocrine Division, Zealand University Hospital, Lykkebaekvej 1, 4600 Koege, Denmark.

Background: Cystic fibrosis (CF) patients are in increased risk of osteoporosis. We aimed to determine the osteoporosis prevalence in an adult CF cohort and investigate calcium metabolic parameters and clinical status' association with bone mineral density evaluated by dual X-ray absorptiometry scan.

Methods: We performed a cross section database study of adults at a tertiary CF Center. scores were applied for patients < 50 years of age and scores for patients > 50 years of age.

Results: One hundred twenty-five patients were included. Compared to nonosteoporotic patients, osteoporotic patients (15%) had significantly lower percent predicted forced expiratory volume in 1 second (ppFEV1), lower body mass index, higher frequency of CF-related diabetes and chronic lung infection, and higher high-sensitive C-reactive protein and glycated hemoglobin levels. Vitamin D was not associated with any outcome. In multivariate analyses, only ppFEV1 and female gender were independently associated with scores.

Conclusions: Osteoporosis in CF occurs with deteriorating clinical status while the role of calcium metabolism seems minor. Gender specific and dysglycemic impact on bone status should be investigated further.
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http://dx.doi.org/10.1155/2018/4803974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892249PMC
March 2018

Living with cystic fibrosis - a qualitative study of a life coaching intervention.

Patient Prefer Adherence 2018 19;12:585-594. Epub 2018 Apr 19.

Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark.

Background: Cystic fibrosis (CF) is a chronic, life-shortening disease with a significant treatment burden. To support young adults with CF in their everyday life, we previously conducted a life coaching feasibility trial (published elsewhere). The aim of the current study was to explore how life coaching was experienced by study participants within the context of their lives with CF.

Methods: A qualitative study using individual interviews. Respondents (n=14) were recruited from the intervention group after participation in life coaching. Data were analyzed from a phenomenologic-hermeneutical perspective, inspired by Ricoeur's theory.

Findings: Periodic exacerbations of CF led to worry about disease progression, and interrupted the respondents' ability to fulfill daily life roles satisfactory. The treatment burden demanded self-discipline and this was sometimes at the expense of social life or career. The young adults rarely spoke to others about their situation; therefore, they valued opening up to a professional coach about life and concerns. We identified three themes: 1) living an unpredictable life; 2) the conflict between freedom and the constraints of illness; and 3) the value of telling one's story. In relation to all three themes, coaching promoted reflection over life situations, reframed thoughts, and facilitated finding new ways to manage everyday life.

Conclusion: Life coaching is an intervention that is valued for those who feel challenged by their CF disease. Coaching programs should be designed to include the participants, when they feel a need for coaching and are open for change. Screening parameters to identify persons who will most likely benefit from life coaching are needed.
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http://dx.doi.org/10.2147/PPA.S159306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916455PMC
April 2018
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