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.

Insulin sensitivity, disposition index and insulin clearance in cystic fibrosis: a cross-sectional study.

Aims/hypothesis: The aim of this study was to investigate insulin secretion, insulin sensitivity, disposition index and insulin clearance by glucose tolerance status in individuals with cystic fibrosis (CF) and exocrine pancreatic insufficiency.

Methods: In a cross-sectional study, we conducted an extended (ten samples) OGTT in individuals with pancreatic-insufficient CF (PI-CF). Participants were divided into normal glucose tolerance (NGT), early glucose intolerance (EGI), impaired glucose tolerance (IGT) and CF-related diabetes (CFRD) groups.

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.

Widespread alterations in systemic immune profile are linked to lung function heterogeneity and airway microbes in cystic fibrosis.

Background: Excessive inflammation and recurrent airway infections characterize people with cystic fibrosis (pwCF), a disease with highly heterogeneous clinical outcomes. How the overall immune response is affected in pwCF, its relationships with the lung microbiome, and the source of clinical heterogeneity have not been fully elucidated.

Methods: Peripheral blood and sputum samples were collected from 28 pwCF and an age-matched control group.

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.

Decline in HbA1c during the first year of elexacaftor/tezacaftor/ivacaftor treatment in the Danish cystic fibrosis cohort: Short title: Decline in HbA1c after elexacaftor/tezacaftor/ivacaftor treatment.

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) has improved the clinical status of individuals with cystic fibrosis (CF), however, whether ETI impacts glucose tolerance remains unknown. We aimed to study the change in glycated hemoglobin (HbA1c) and CF related diabetes (CFRD) status after initiation of ETI.

Methods: We included individuals ≥12 years treated with ETI in Denmark in a longitudinal observational study.

Characterization of impaired beta and alpha cell function in response to an oral glucose challenge in cystic fibrosis: a cross-sectional study.

Aims: The purpose of the study was to further elucidate the pathophysiology of cystic fibrosis (CF)-related diabetes (CFRD) and potential drivers of hypoglycaemia. Hence, we aimed to describe and compare beta cell function (insulin and proinsulin) and alpha cell function (glucagon) in relation to glucose tolerance in adults with CF and to study whether hypoglycaemia following oral glucose challenge may represent an early sign of islet cell impairment.

Methods: Adults with CF (≥18 years) were included in a cross-sectional study using an extended (-10, -1, 10, 20, 30, 45, 60, 90, 120, 150, and 180 min) or a standard (-1, 30, 60, and 120 min) oral glucose tolerance test (OGTT).

Changes in glucose tolerance in people with cystic fibrosis after initiation of first-generation CFTR modulator treatment.

Background: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have been shown to have a beneficial effect on pulmonary function and nutritional status in patients with cystic fibrosis (CF), but the extent to which they affect glucose tolerance is not fully understood. In the current study, we evaluated the change in glucose tolerance and insulin secretion after first-generation CFTR modulator treatment in adults with CF.

Methods: We performed a longitudinal observational study with an oral glucose tolerance test performed at baseline and after three and a half years of follow-up.

Antibody response following the third and fourth SARS-CoV-2 vaccine dose in individuals with common variable immunodeficiency.

Background: The antibody response after vaccination is impaired in common variable immunodeficiency (CVID).

Objective: We aimed to study the spike receptor-binding domain IgG antibody (anti-S-RBD) levels during a four-dose SARS-CoV-2 vaccination strategy and after monoclonal antibody (mAB) treatment in CVID. Moreover, we assessed the anti-S-RBD levels in immunoglobulin replacement therapy (IgRT) products.

Increased sputum lactate during oral glucose tolerance test in cystic fibrosis.

Blood glucose levels exceeding 8 mM are shown to increase glucose levels in airway surface in cystic fibrosis (CF). Moreover, high levels of endobronchial glucose are proposed to increase the growth of common CF bacteria and feed the neutrophil-driven inflammation. In the infected airways, glucose may be metabolized by glycolysis to lactate by both bacteria and neutrophils.

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.

Correlates of Pancreatic Enzyme Replacement Therapy Intake in Adults with Cystic Fibrosis: Results of a Cross-Sectional Study.

Most people with cystic fibrosis (pwCF) develop pancreatic insufficiency and are treated with pancreatic enzyme replacement therapy (PERT). We aimed to describe the use of PERT and assess the correlates of PERT dose in adult pwCF. In a cross-sectional study at the Copenhagen CF Centre, the participants reported PERT intake, gastrointestinal (GI) symptoms and the use of concomitant treatments.

Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients.

Background: Remdesivir improves clinical outcomes in patients hospitalized with moderate-to-severe coronavirus disease 2019 (Covid-19). Whether the use of remdesivir in symptomatic, nonhospitalized patients with Covid-19 who are at high risk for disease progression prevents hospitalization is uncertain.

Methods: We conducted a randomized, double-blind, placebo-controlled trial involving nonhospitalized patients with Covid-19 who had symptom onset within the previous 7 days and who had at least one risk factor for disease progression (age ≥60 years, obesity, or certain coexisting medical conditions).

Disseminated complex infection in a woman with anti-interferon-γ autoantibodies.

Defects in the interleukin-12/interferon-gamma (IFN-γ) pathway and anti-IFN-γ antibodies have been associated with severe nontuberculous mycobacteria (NTM) infections. Consequently, disseminated NTM infections should prompt investigations for immunodeficiency. Herein, we report a case of a treatment refractory and ultimately disseminated and fatal complex infection in a 71-year-old woman of Thai origin.

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.

Neutrophil count in sputum is associated with increased sputum glucose and sputum L-lactate in cystic fibrosis.

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.

Seasonal variation in child mortality in rural Guinea-Bissau.

Objectives: In many African countries, child mortality is higher in the rainy season than in the dry season. We investigated the effect of season on child mortality by time periods, sex and age in rural Guinea-Bissau.

Methods: Bandim health project follows children under-five in a health and demographic surveillance system in rural Guinea-Bissau.

Development of BCG Scar and Subsequent Morbidity and Mortality in Rural Guinea-Bissau.

Background: Previous studies have found that BCG vaccination has nonspecific beneficial effects on child survival, especially among children who developed a BCG scar. These studies have mostly been done in settings with a high scar frequency. In rural Guinea-Bissau, many children do not develop a scar; we tested the hypothesis that among BCG-vaccinated children, a vaccination scar was associated with lower mortality and fewer hospital admissions.