Lung function improvement on triple modulators: high-resolution, nationwide data from the Danish Cystic Fibrosis Cohort.

Background: People living with cystic fibrosis in Denmark had early, universal access to triple modulator treatment with elexacaftor/tezacaftor/ivacaftor. Close monitoring allowed us to assess the impact of treatment on lung function and progression of lung disease in an unselected nationwide cystic fibrosis population from 6 years of age.

Methods: Data were analysed using linear mixed-effect models to assess changes in levels and annual rates of change (slopes) in percent predicted (pp) forced expiratory volume in 1 s (FEV), forced vital capacity (FVC) and forced expiratory flow at 25-75% of FVC (ppFEF) between the 12 months pre-treatment and treatment periods.

Long-Term Lung Function and Infection in Genotyped Primary Ciliary Dyskinesia.

Primary ciliary dyskinesia is a rare genetic disorder characterized by progressive lung disease. is a major pathogen in this disease, known to impact lung function. Previous genotype-phenotype studies have been limited by cross-sectional designs, isolated adult or pediatric populations, small numbers, or short follow-up durations.

Real-world data confirm elexacftor/tezacaftor/ivacaftor modulators halves sweat chloride concentration in eligible people with cystic fibrosis.

Sweat chloride concentration, a diagnostic feature in cystic fibrosis (CF), reflects CF transmembrane conductance regulator (CFTR) activity. CFTR modulator therapies, especially elexacaftor/tezacaftor/ivacaftor (ETI), has improved CF outcomes. We report nationwide, real-world data on sweat chloride concentration in people with CF (pwCF) with and without modulator therapies.

Education, employment, and income among people living with cystic fibrosis across three decades - A matched cohort study using Danish health registries.

Background: Past and ongoing advancements in cystic fibrosis (CF) care warrant long-term analysis of the societal impact of the condition. This study aims to evaluate changes in key socioeconomic factors across three decades among people living with CF (pwCF), compared with both the general population and an early-onset chronic disease population.

Methods: This nationwide, registry-based, matched cohort study included all pwCF ≥ 18 years in Denmark in the years 1990, 2000, 2010, and 2018.

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.

Implementation of a vaccination clinic for adult solid organ transplant candidates: A single-center experience.

Vaccination is an evidence-based strategy to prevent or reduce the severity of infectious diseases (ID). Here, we aimed to describe the experience of implementing a vaccination clinic specifically targeting liver, heart, lung, and combined dual organ transplantation at a single transplantation center in Denmark. In this cohort of 242 solid organ transplant (SOT) candidates, we investigated seroprotection and the proportion of recommended vaccinations documented before transplantation.

Antimicrobial resistance of Pseudomonas aeruginosa in a cystic fibrosis population after introduction of a novel cephalosporin/β-lactamase inhibitor combination.

Ceftolozane-tazobactam is a new β-lactam/β-lactamase inhibitor combination approved by the U.S. Food and Drug Administration in 2019 for the treatment of hospital-acquired and ventilator-associated pneumonia.

Antimicrobial Strategies for Cystic Fibrosis.

Lung infection is the leading cause of death in cystic fibrosis (CF), and antimicrobial therapies are the backbone of infection management. While many different strategies may be applied, rigorous microbiological surveillance, intensive eradication therapy, and long-term maintenance therapy based on inhaled antibiotics may be considered the main strategy for infection control in individuals with CF. While most of the existing evidence is based on infection with , other important pathogens causing lung inflammation and deterioration exist and should be treated despite the evidence gap.

Adaptive Immune Response to Complex (MABSC) in Cystic Fibrosis and the Implications of Cross-Reactivity.

Background: We aimed to characterise the adaptive immune response to complex (MABSC) and its cross-reactivity with complex (MAC) and (Bacille Calmette-Guérin, BCG) in cystic fibrosis (CF) patients and non-CF controls in terms of lymphocyte proliferation and immunophenotyping, cytokine production and anti-MABSC IgG plasma levels.

Methods: In this cross-sectional analysis, peripheral blood mononuclear cells (PBMC) from CF patients with MABSC (CF/MABSC, n=12), MAC infection history (CF/MAC, n=5), no NTM history (CF/NTM-, n=15), BCG-vaccinated (C/BCG+, n=9) and non-vaccinated controls (C/BCG-, n=8) were cultured for four days under stimulation with an in-house MABSC lysate and we used flow cytometry to assess lymphocyte proliferation (given by lymphoblast formation) and immunophenotypes. Cytokine production was assessed after overnight whole blood stimulation with the same lysate, and anti-MABSC IgG levels were measured in plasma from non-stimulated blood.

Use of inhaled antibiotics among Danish patients with cystic fibrosis.

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.

spp. in a Cohort of Non-Selected Pre- and Post-Lung Transplant Recipients.

is an opportunistic pathogen that mainly causes chronic lung infections in cystic fibrosis (CF) patients and is associated with increased mortality. Little is known about spp. in the lung transplant recipient (LTXr) population.

Bacterial biofilms predominate in both acute and chronic human lung infections.

Background: A basic paradigm of human infection is that acute bacterial disease is caused by fast growing planktonic bacteria while chronic infections are caused by slow-growing, aggregated bacteria, a phenomenon known as a biofilm. For lung infections, this paradigm has been thought to be supported by observations of how bacteria proliferate in well-established growth media in the laboratory-the gold standard of microbiology.

Objective: To investigate the bacterial architecture in sputum from patients with acute and chronic lung infections.

Associations Between Glucose Tolerance, Insulin Secretion, Muscle and Fat Mass in Cystic Fibrosis.

Background: A frequent comorbidity in cystic fibrosis (CF) is CF related diabetes (CFRD) caused by a gradual decline in insulin secretion. The reduction in the anabolic hormone, insulin, might explain the weight loss that precedes onset of CFRD. We investigated the association between muscle and fat mass in relation to glucose tolerance and insulin function.

At-Risk Groups of Men Who Have Sex With Men Can Be Reached Through Community-Based HIV Testing in Denmark.

This study evaluates whether the community-based HIV testing clinic Checkpoint could reach at-risk groups of men who have sex with men (MSM) and link patients to care. A prospective observational study of all Checkpoint visits during 2013-2016 and a retrospective registry study of all MSM diagnosed with HIV in Denmark during the same period were conducted. One percent of the 9,074 tests in Checkpoint were HIV-positive, accounting for 19% of all new HIV diagnoses among MSM in Denmark.

Biofilms of Mycobacterium abscessus Complex Can Be Sensitized to Antibiotics by Disaggregation and Oxygenation.

Pulmonary infection with the multidrug-resistant complex (MABSC) is difficult to treat in individuals with cystic fibrosis (CF). MABSC grows as biofilm aggregates in CF patient lungs, which are known to have anaerobic niches. How aggregation and anoxic conditions affect antibiotic tolerance is not well understood.

Temporal changes in size-at-maturity of black dogfish Centroscyllium fabricii.

By examining the maturity of 283 black dogfish Centroscyllium fabricii from Greenland waters, a shift in size-at-maturity in both sexes over the past 25 years is observed. Size-at-first maturity decreased approximately 10 cm in both sexes, and L and L shifted similarly in males, but not in females. It is argued that bycatch in the Greenland halibut Reinhardtius hippoglossoides fishery has contributed to the observed shift, but also emphasised that such a distinct change could have a methodological component as well as being subject to effects of environmental change.

Mycobacterium brisbanense lung infection facilitated by steroid induced adrenal insufficiency.

Mycobacterium brisbanense is rapid-growing nontuberculous mycobacteria. It was first described in 2004 as a human pathogen and only one case report has previously been published. We report a case of M.

Antibody response against Mycobacterium avium complex in cystic fibrosis patients measured by a novel IgG ELISA test.

Background: Early signs of Mycobacterium avium complex pulmonary disease can be missed in patients with cystic fibrosis due to subclinical infection or delays in mycobacterial culture. The aim of this study was to determine the diagnostic accuracy of a novel enzyme linked immunosorbent assay for immunoglobulin G against Mycobacterium avium complex, which could help stratify patients according to risk.

Methods: A retrospective cross sectional analysis of serum samples from the Copenhagen Cystic Fibrosis Center was performed.

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.

Comparison of the Outcomes of Individuals With Medically Attended Influenza A and B Virus Infections Enrolled in 2 International Cohort Studies Over a 6-Year Period: 2009-2015.

Background: Outcome data from prospective follow-up studies comparing infections with different influenza virus types/subtypes are limited.

Methods: Demographic, clinical characteristics and follow-up outcomes for adults with laboratory-confirmed influenza A(H1N1)pdm09, A(H3N2), or B virus infections were compared in 2 prospective cohorts enrolled globally from 2009 through 2015. Logistic regression was used to compare outcomes among influenza virus type/subtypes.

Diagnosis of biofilm infections in cystic fibrosis patients.

Chronic Pseudomonas aeruginosa biofilm lung infection in cystic fibrosis patients is the best described biofilm infection in medicine. The initial focus can be the paranasal sinuses and then follows repeated colonization and infection of the lungs by aspiration. The matrix of the biofilms is dominated by alginate and the pathogenesis of tissue damage is immune complex-mediated chronic inflammation dominated by polymorphonuclear leukocytes and their products (DNA, oxygen radicals and proteases).