Search

Rationale Targeted cystic fibrosis (CF) therapy with lumacaftor/ivacaftor partly restores chloride channel function and improves epithelial fluid transport in the airways. Consequently, changes may occur in the microbiome, which is adapted to CF lungs. Objectives To investigate the effects of lumacaftor/ivacaftor on respiratory microbial composition and microbial metabolic activity by repeatedly sampling the lower respiratory tract. Methods This was a single-centre longitudinal observational cohort study in adult CF patients with a homozygous Phe508del mutation. Lung function measurements and microbial cultures of sputum were performed as part of routine care. An oral and nasal wash, and a breath sample, were collected before and every 3 months after starting therapy, for up to 12 months. Results Twenty patients were included in this study. Amplicon 16S RNA and metagenomics sequencing revealed that Pseudomonas aeruginosa was most abundant in sputum and seemed to decrease after 6 months of treatment, although this did not reach statistical significance after correction for multiple testing. Two types of untargeted metabolomics analyses in sputum showed a change in metabolic composition between 3 and 9 months that almost returned to baseline levels after 12 months of treatment. The volatile metabolic composition of breath was significantly different after 3 months and remained different from baseline until 12 months follow-up. Conclusions After starting CF transmembrane conductance regulator (CFTR) modulating treatment in CF patients with a homozygous Phe508del mutation, a temporary and moderate change in the lung microbiome is observed, which is mainly characterised by a reduction in the relative abundance of Pseudomonas aeruginosa., Lumacaftor/ivacaftor in adult cystic fibrosis patients with homozygous Phe508del results in temporal and moderate changes in lung microbiome and metabolome, that are mainly characterised by a reduction in the relative abundance of Pseudomonas aeruginosa https://bit.ly/3pcPUfX

Recently, endogenous glucocorticoid excess has been identified as a risk factor for VTE. Whether exogenous use of glucocorticoids is associated with an increased risk of VTE is unclear. We aimed to quantify the risk of symptomatic pulmonary embolism (PE) in patients using corticosteroids. A case-control study using the PHARMO Record Linkage System, a Dutch population-based pharmacy registry, was conducted. Cases were 4,495 patients with a first hospital admission for PE between 1998 and 2008. Control subjects were 16,802 sex- and age-matched subjects without a history of PE. International Classification of Diseases codes for hospitalization were used to retrieve information on underlying conditions. The risk of PE was highest in the first 30 days of glucocorticoid exposure (adjusted OR, 5.9; 95% CI, 2.3-3.9) and gradually decreased with increasing duration of use (OR, 1.9; 95% CI, 1.3-2.9) for long-term users (> 1 year). Low-dose glucocorticoid use (prednisolone daily dose equivalent < 5 mg) carried a twofold increased risk of PE (OR, 1.8; 95% CI, 1.3-2.4), whereas a 10-fold increased risk was observed for the highest dose of glucocorticoids (prednisolone > 30 mg) (OR, 9.6; 95% CI, 4.3-20.5). Stratification for both duration and dose of glucocorticoid showed the highest risk of PE in recently started users compared with long-term users at the time of PE, irrespective of the dose. Patients treated with oral glucocorticoids may be at an increased risk of PE, especially during the first month of exposure. This hypothesis requires confirmation in future studies

Background: Patients with lung cancer (LC) are at increased risk of venous and arterial thrombosis due to cancer itself and its treatment. Although some studies have assessed the incidence of venous thrombosis among LC patients, data on the occurrence of specific venous and arterial thrombotic events is scarce. Objectives: To study the rate of myocardial infarction (MI), ischemic stroke (IS) and pulmonary embolism (PE) before and after LC diagnosis compared with cancer-free controls. Methods: Patients with LC during 2000-2007 were selected from PALGA, the Dutch nationwide registry of histo-and cytopathology, and linked to the PHARMO RLS, including drug use and hospitalizations of approximately three million inhabitants in the Netherlands. Included LC patients were matched 1:10 by age and gender to cancer-free controls. The occurrence of MI, IS and PE were assessed in the 12 months before and after LC diagnosis. Results: This study included 3,717 LC patients, with a mean (±SD) age of 59 (±14) years and 69% males. LC patients were six times as likely as their cancer-free controls to have had a hospitalization for PE in the 12 months before diagnosis, though prevalence was