Close monitoring and early intervention: management principles for cystic fibrosis in Denmark.

Cystic fibrosis (CF) care in Denmark has been characterized by close monitoring and pre-emptive treatment of lung disease and other CF-related complications. Continuous evaluation through data collection and commitment to clinical research has incrementally improved outcomes. This approach has been in line with best practices set forth by European Standards of Care but has also gone beyond Society standards particularly pertaining to early treatment with high-dose combination antimicrobial therapy.

The impact of caring on caregivers of patients with life-threatening organ failure.

Objectives: This study aimed at characterizing 3 populations of family/friend caregivers of patients with different life-threatening organ failure regarding health-related quality of life, caregiver burden, and dyadic coping.

Methods: Three cross-sectional (population) studies were conducted at a tertiary hospital in Denmark (2019-2020). Patients with renal failure (RF), cystic fibrosis (CF), and intestinal failure (IF) were asked to designate the closest person with ≥18 years old involved in the care (caregiver) to participate in this study.

Bacterial Re-Colonization Occurs Early after Lung Transplantation in Cystic Fibrosis Patients.

Most cystic fibrosis (CF) patients referred for lung transplantation are chronically infected with Gram-negative opportunistic pathogens. It is well known that chronic infections in CF patients have a significant impact on lung-function decline and survival before transplantation. The rate and timing of re-colonization after transplantation have been described, but the impact on survival after stratification of bacteria is not well elucidated.

Autologous fibrin sealant co-delivered with antibiotics is a robust method for topical antibiotic treatment after sinus surgery.

Background: Most patients with cystic fibrosis have the risk of pathogenic bacteria being exchanged between their sinuses and lungs.

Aims: A method for topical application of antibiotics where the antibiotics persist for a long period of time is needed.

Material And Methods: Ten patients with cystic fibrosis and bacterial sinusitis were included.

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

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.

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

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.

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

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.

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

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.

Seasonal fluctuation of lung function in cystic fibrosis: A national register-based study in two northern European populations.

Background: Many risk factors for lung disease in cystic fibrosis (CF) display a seasonal pattern yet it is unclear whether this is reflected in seasonal fluctuations in lung function.

Methods: We conducted a longitudinal study using CF registries in Denmark and the UK. 471 individuals with a median of 104 FEV measurements per person and 7586 individuals with a median of nine FEV measures per person were included from Denmark and the UK respectively.

Impact of cystic fibrosis on birthweight: a population based study of children in Denmark and Wales.

Background: Poor growth during infancy and childhood is a characteristic feature of cystic fibrosis (CF). However, the impact of CF on intrauterine growth is unclear. We studied the effect of CF on birth weight in Denmark and Wales, and assessed whether any associations are due to differences in gestational age at birth.

The effect of time-of-day and chest physiotherapy on multiple breath washout measures in children with clinically stable cystic fibrosis.

Background: In this pilot study we investigated daytime variation of multiple breath nitrogen washout (N2MBW) measures in children with clinically stable cystic fibrosis. To our knowledge the effect of time-of-day on multiple breath washout measures in patients with cystic fibrosis has not previously been reported. Furthermore, we assessed the influence of chest physiotherapy on N2MBW measures.

Prevalence and characteristics of chronic kidney disease among Danish adults with cystic fibrosis.

Background: With improved prognosis of CF, comorbidities including chronic kidney disease (CKD) are becoming increasingly important. Identification of those at highest CKD risk is hence a priority.

Methods: In this cross-sectional study, adults with CF attending the Copenhagen CF Centre at Rigshospitalet with ≥2 measurements of serum creatinine from 2013 to 2015 were included.

Association between spirometry controlled chest CT scores using computer-animated biofeedback and clinical markers of lung disease in children with cystic fibrosis.

: Computed tomography (CT) of the lungs is the gold standard for assessing the extent of structural changes in the lungs. Spirometry-controlled chest CT (SCCCT) has improved the usefulness of CT by standardising inspiratory and expiratory lung volumes during imaging. This was a single-centre cross-sectional study in children with cystic fibrosis (CF).

Boosting joint models for longitudinal and time-to-event data.

Joint models for longitudinal and time-to-event data have gained a lot of attention in the last few years as they are a helpful technique clinical studies where longitudinal outcomes are recorded alongside event times. Those two processes are often linked and the two outcomes should thus be modeled jointly in order to prevent the potential bias introduced by independent modeling. Commonly, joint models are estimated in likelihood-based expectation maximization or Bayesian approaches using frameworks where variable selection is problematic and that do not immediately work for high-dimensional data.

Sinus surgery can improve quality of life, lung infections, and lung function in patients with primary ciliary dyskinesia.

Background: Chronic rhinosinusitis (CRS) and bacterial sinusitis are ubiquitous in patients with primary ciliary dyskinesia (PCD). From the sinuses, Pseudomonas aeruginosa can infect the lungs.

Methods: We studied the effect of endoscopic sinus surgery (ESS) on symptoms of CRS and lower airway infections in PCD patients in a prospective single-arm intervention study of ESS with adjuvant therapy using nasal irrigation with saline, topical nasal steroids, and 2 weeks of systemic antibiotics.

Phenotypic shift in Pseudomonas aeruginosa populations from cystic fibrosis lungs after 2-week antipseudomonal treatment.

Background: The influence of suppressive therapy on the different P. aeruginosa phenotypes harbored in the lungs of cystic fibrosis (CF) patients remains unclear. Our aim was to investigate the phenotypic changes (mucoidy, hypermutability, antibiotic resistance, transcriptomic profiles and biofilm) in P.

Comparing the harmful effects of nontuberculous mycobacteria and Gram negative bacteria on lung function in patients with cystic fibrosis.

Background: To better understand the relative effects of infection with nontuberculous mycobacteria and Gram negative bacteria on lung function decline in cystic fibrosis, we assessed the impact of each infection in a Danish setting.

Methods: Longitudinal registry study of 432 patients with cystic fibrosis contributing 53,771 lung function measures between 1974 and 2014. We used a mixed effects model with longitudinally structured correlation, while adjusting for clinically important covariates.

Serodiagnosis of Mycobacterium abscessus complex infection in cystic fibrosis.

Early signs of pulmonary disease with Mycobacterium abscessus complex (MABSC) can be missed in patients with cystic fibrosis (CF). A serological method could help stratify patients according to risk. The objective of this study was to test the diagnostic accuracy of a novel method for investigating IgG activity against MABSC.

Urine lipoarabinomannan point-of-care testing in patients affected by pulmonary nontuberculous mycobacteria--experiences from the Danish Cystic Fibrosis cohort study.

Background: The urine lipoarabinomannan (LAM) strip test has been suggested as a new point-of-care test for active tuberculosis (TB) among human immunodeficiency virus (HIV) infected individuals. It has been questioned if infections with nontuberculous mycobacteria (NTM) affect assay specificity. We set forth to investigate if the test detects LAM in urine from a Danish cystic fibrosis (CF) population characterized by a high NTM prevalence and negligible TB exposure.

Epidemiology of nontuberculous mycobacteria among patients with cystic fibrosis in Scandinavia.

Background: Nontuberculous mycobacteria (NTM) are an emerging threat to cystic fibrosis (CF) patients but their epidemiology is not well described.

Methods: In this retrospective observational study we identified all Scandinavian CF patients with a positive NTM culture from airway secretions from 2000 to the end of 2012 and used national CF databases to describe microbiological and clinical characteristics.

Results: During the 13-year period 157 (11%) CF patients were culture positive for NTM at least once.

Shifting paradigms of nontuberculous mycobacteria in cystic fibrosis.

Important paradigms of pulmonary disease with nontuberculous mycobacteria (NTM) are currently shifting based on an increasing attention within the field of cystic fibrosis (CF). These shifts are likely to benefit the management of all patients with pulmonary NTM, regardless of underlying pathology. Currently several key areas are being revised: The first outbreak of human NTM transmission has been proven and new evidence of biofilm growth in vivo has been demonstrated.