Vanzacaftor-tezacaftor-deutivacaftor versus elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older (SKYLINE Trials VX20-121-102 and VX20-121-103): results from two randomised, active-controlled, phase 3 trials.

Background: The goal of cystic fibrosis transmembrane conductance regulator (CFTR) modulators is to reach normal CFTR function in people with cystic fibrosis. Vanzacaftor-tezacaftor-deutivacaftor restored CFTR function in vitro and in phase 2 trials in participants aged 18 years and older resulting in improvements in CFTR function, as measured by sweat chloride concentrations and lung function as measured by spirometry. We aimed to evaluate the efficacy and safety of vanzacaftor-tezacaftor-deutivacaftor compared with standard of care elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older.

Safety of non-cuffed tunneled central venous catheters in adults with cystic fibrosis.

Background: Peripherally inserted central catheters (PICCs) are the most common route of intravenous (I.V.) access for treatment of cystic fibrosis (CF) pulmonary exacerbations, but repeated PICC placement can result in upper extremity peripheral venous stenosis.

Complications and Practice Variation in the Use of Peripherally Inserted Central Venous Catheters in People With Cystic Fibrosis: The Prospective Study of Peripherally Inserted Venous Catheters in People With Cystic Fibrosis Study.

Background: Peripherally inserted central catheters (PICCs) are used commonly to administer antibiotics to people with cystic fibrosis (CF), but their use can be complicated by venous thrombosis and catheter occlusion.

Research Question: Which participant-, catheter-, and catheter management-level attributes are associated with increased risk of complications of PICCs among people with CF?

Study Design And Methods: This was a prospective observational study of adults and children with CF who received PICCs at 10 CF care centers in the United States. The primary end point was defined as occlusion of the catheter resulting in unplanned removal, symptomatic venous thrombosis in the extremity containing the catheter, or both.

High-Frequency Percussive Ventilation in Cystic Fibrosis Patients With Acute Respiratory Failure: A Case Series.

Acute respiratory failure in cystic fibrosis carries a high risk of mortality. The optimal mode of mechanical ventilation (MV) in this population is not well established. In this case series, we identified patients with cystic fibrosis who were ventilated with high-frequency percussive ventilation (HFPV) at our institution and describe their characteristics and outcomes.

Physical Activity Level and Perception of Exercise in Cystic Fibrosis.

Background: More patients with cystic fibrosis (CF) are living longer, and lifestyle-related behavior is becoming increasingly important for improving morbidity and mortality. Declining levels of exercise leads to low cardiorespiratory fitness, which is a strong, independent predictor of mortality in patients with CF. As a result, exercise training has become a commonly accepted form of treatment for patients with CF.

Aztreonam Lysine Inhalation Solution in Cystic Fibrosis.

Patients with cystic fibrosis (CF) develop pulmonary disease secondary to airway infection and dysregulated inflammation. Therapeutic innovations such as nebulized antimicrobial therapy targeting specific pathogens have resulted in improvements in quality of life and life expectancy. Aztreonam lysine for inhalation (AZLI) solution was initially approved to improve respiratory symptoms in CF patients with (PA) in 2010 by the Food and Drug Administration.

Chasing Zero: Increasing Infection Control Compliance on an Inpatient Cystic Fibrosis Unit.

Patients with cystic fibrosis have increased risk of pulmonary infections, and reducing spread of microorganisms is critical. To improve hospital-staff adherence to infection control guidelines, we implemented brightly colored Safe Zone floor decals, staff compliance contracts, and an infection control in-service video. Audits of staff adherence conducted pre and postintervention demonstrated an increased and sustainable improvement among each group (P < .

Quality improvement initiative to reduce deep vein thrombosis associated with peripherally inserted central catheters in adults with cystic fibrosis.

Rationale: Peripherally inserted central catheters (PICCs) are common in the treatment of patients with cystic fibrosis (CF). Previous reports suggest that patients with CF are at increased risk for PICC-associated deep vein thrombosis (DVT).

Objectives: We assessed potential risk factors for symptomatic PICC-associated DVT with subsequent implementation of a quality improvement (QI) initiative to reduce PICC-associated DVT in patients with CF.

HIV-1/cocaine induced oxidative stress disrupts tight junction protein-1 in human pulmonary microvascular endothelial cells: role of Ras/ERK1/2 pathway.

Intravenous drug use (IVDU) is the major risk factor in the development of HIV-related pulmonary arterial hypertension (HRPAH); however, the pathogenesis of HRPAH in association with IVDU has yet to be characterized. Endothelial injury is considered to be an initiating factor for pulmonary vascular remodeling in animal models of PAH. Our previous study shows that simultaneous exposure to HIV-Trans-activator of transcription (Tat) and cocaine exacerbates both disruption of tight junction proteins and permeability of human pulmonary artery endothelial cells compared with either treatment alone.

NanoCluster budesonide formulations enable efficient drug delivery driven by mechanical ventilation.

Agglomerates of budesonide nanoparticles (also known as 'NanoClusters') are fine dry powder aerosols that were hypothesized to enable drug delivery through ventilator circuits. These engineered powders were delivered via a Monodose inhaler or a novel device, entrained through commercial endotracheal tubes, and analyzed by cascade impaction. Inspiration flow rates and other parameters such as inspiration patterns and inspiration volumes were controlled by a ventilator.

HMG-CoA Reductase Inhibitors for Prevention and Treatment of Severe Sepsis.

HMG-CoA reductase inhibitors, or statins, are among the most commonly prescribed pharmaceuticals in the world, especially among the elderly. The remarkable conjuncture of this fact with the rising incidence of severe sepsis among people over age 65 could prove to be of serendipitous benefit, because numerous actions of the statins make them of potential use in the prevention and treatment of severe sepsis. Severe sepsis continues to be a highly lethal condition, for which there are, as yet, no effective pharmacological treatments, save antibiotics.

Hypoxia-inducible factor-1 α/platelet derived growth factor axis in HIV-associated pulmonary vascular remodeling.

Background: Human immunodeficiency virus (HIV) infected patients are at increased risk for the development of pulmonary arterial hypertension (PAH). Recent reports have demonstrated that HIV associated viral proteins induce reactive oxygen species (ROS) with resultant endothelial cell dysfunction and related vascular injury. In this study, we explored the impact of HIV protein induced oxidative stress on production of hypoxia inducible factor (HIF)-1α and platelet-derived growth factor (PDGF), critical mediators implicated in the pathogenesis of HIV-PAH.

Body mass index is associated with reduced exhaled nitric oxide and higher exhaled 8-isoprostanes in asthmatics.

Background: Recently, it has been shown that increasing body mass index (BMI) in asthma is associated with reduced exhaled NO. Our objective in this study was to determine if the BMI-related changes in exhaled NO differ across asthmatics and controls, and to determine if these changes are related to increased airway oxidative stress and systemic levels of leptin and adiponectin.

Methods: Observational study of the association of BMI, leptin, and adiponectin with exhaled nitric oxide (NO) and exhaled 8-isoprostanes in 67 non-smoking patients with moderate to severe persistent asthma during baseline conditions and 47 controls.