Pharmacologic improvement of CFTR function rapidly decreases sputum pathogen density, but lung infections generally persist.

BackgroundLung infections are among the most consequential manifestations of cystic fibrosis (CF) and are associated with reduced lung function and shortened survival. Drugs called CF transmembrane conductance regulator (CFTR) modulators improve activity of dysfunctional CFTR channels, which is the physiological defect causing CF. However, it is unclear how improved CFTR activity affects CF lung infections.

Elexacaftor/tezacaftor/ivacaftor and gastrointestinal outcomes in cystic fibrosis: Report of promise-GI.

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) improves pulmonary disease in people with cystic fibrosis (PwCF), but its effect on gastrointestinal symptoms, which also affect quality of life, is not clear.

Methods: PROMISE is a 56-center prospective, observational study of ETI in PwCF >12 years and at least one F508del allele. Gastrointestinal symptoms, evaluated by validated questionnaires: Patient Assessment of Upper Gastrointestinal Disorders-Symptom (PAGI-SYM), Patient Assessment of Constipation-Symptom (PAC-SYM), Patient Assessment of Constipation-Quality of Life (PAC-QOL)), fecal calprotectin, steatocrit and elastase-1 were measured before and 6 months after ETI initiation.

Antipseudomonal treatment decisions during CF exacerbation management.

Background: Cystic fibrosis (CF) pulmonary exacerbation (PEx) treatment guidelines suggest that Pseudomonas aeruginosa (Pa) airway infection be treated with two antipseudomonal agents.

Methods: We retrospectively studied treatment responses for STOP2 PEx treatment trial (NCT02781610) participants with a history of Pa infection. Mean lung function and symptom changes from intravenous (IV) antimicrobial treatment start to Visit 2 (7 to 10 days later) were compared between those receiving one, two, and three+ antipseudomonal classes before Visit 2 by ANCOVA.

Impact of azithromycin on serum inflammatory markers in children with cystic fibrosis and new Pseudomonas.

Chronic azithromycin improves outcomes in cystic fibrosis (CF), but its mechanism of action is unclear. The OPTIMIZE trial demonstrated improvement in time to first pulmonary exacerbation in children with new Pseudomonas treated with azithromycin. Azithromycin effect on systemic markers of inflammation over 18 months was assessed by change from baseline for high-sensitivity C-reactive protein, myeloperoxidase, calprotectin and absolute neutrophil count in the OPTIMIZE population.

C-reactive protein (CRP) as a biomarker of pulmonary exacerbation presentation and treatment response.

Background: C-reactive protein (CRP) has been proposed as a biomarker for pulmonary exacerbation (PEx) diagnosis and treatment response. CRP >75mg/L has been associated with increased risk of PEx treatment failure. We have analyzed CRP measures as biomarkers for clinical response during the STOP2 PEx study (NCT02781610).

Association of site of treatment with clinical outcomes following intravenous antimicrobial treatment of a pulmonary exacerbation.

Background: In the STOP2 (Standardized Treatment of Pulmonary Exacerbations-2) study, intravenous (IV) antimicrobial treatment duration for adults with cystic fibrosis (CF) experiencing pulmonary exacerbations (PEx) was determined based on initial treatment response. The impact of home vs hospital care remains an important clinical question in CF. Our hypothesis was that STOP2 participants treated at home would have less improvement in lung function compared to those treated in the hospital.

A Randomized Clinical Trial of Antimicrobial Duration for Cystic Fibrosis Pulmonary Exacerbation Treatment.

People with cystic fibrosis (CF) experience acute worsening of respiratory symptoms and lung function known as pulmonary exacerbations. Treatment with intravenous antimicrobials is common; however, there is scant evidence to support a standard treatment duration. To test differing durations of intravenous antimicrobials for CF exacerbations.

The effect of oral and intravenous antimicrobials on pulmonary exacerbation recovery in cystic fibrosis.

Background: Retrospective studies indicate that more cystic fibrosis (CF) pulmonary exacerbations (PEx) are treated with oral (PO) than with intravenous (IV) antimicrobials despite little knowledge of the relative effects of PO treatment on lung function recovery or long-term impacts on lung disease progression. Previous studies have suggested that PO treatment may be associated with slower lung function recovery compared with IV treatment. We used longitudinal home spirometry data from the eICE study (NCT01104402) to compare PO versus IV antimicrobial treatment responses for PEx diagnosed by home spirometry and symptom assessment.

Measuring the impact of CFTR modulation on sweat chloride in cystic fibrosis: Rationale and design of the CHEC-SC study.

Background: The Characterizing CFTR Modulated Changes in Sweat Chloride and their Association with Clinical Outcomes (CHEC-SC) study is a large epidemiologic study designed to determine the relationship between sweat chloride response and clinical outcomes in people with cystic fibrosis (CF) on commercially approved CFTR modulators. A challenge to study feasibility was capturing sweat chloride measurements before modulator initiation. We tested the hypothesis that historic sweat chloride approximated contemporary pre-modulator values to estimate CFTR modulator-induced changes, allowing a single-visit study design.

Changes in symptom scores as a potential clinical endpoint for studies of cystic fibrosis pulmonary exacerbation treatment.

Introduction: Symptom improvement was assessed as changes in the Chronic Respiratory Infection Symptom Score (CRISS) during intravenous antimicrobial exacerbation treatments among subjects from study NCT02109822.

Methods: Median daily CRISS reduction (i.e.

Pulmonary Outcomes Associated with Long-Term Azithromycin Therapy in Cystic Fibrosis.

Chronic azithromycin is commonly used in cystic fibrosis based on short controlled clinical trials showing reductions in pulmonary exacerbations and improved FEV. Long-term effects are unknown. Examine pulmonary outcomes among chronic azithromycin users compared with matched controls over years of use and consider combined azithromycin use in cohorts using chronic inhaled tobramycin or aztreonam.

Pancreatic Enzyme Replacement Therapy Use in Infants With Cystic Fibrosis Diagnosed by Newborn Screening.

Objectives: The aim of the study is to describe pancreatic enzyme practices during the first year of life in infants with cystic fibrosis (CF) and evaluate associations between dosing and outcomes, including growth and gastrointestinal (GI) symptoms.

Methods: We analyzed data from a subset of infants who were in a prospective cohort study conducted at 28 US CF centers. Anthropometric measurements and medications were recorded at each visit.

Absence of rebound from diltiazem therapy in Prinzmetal's variant angina.

To determine the frequency of rebound anginal symptoms on abrupt withdrawal of calcium channel blocking agents, anginal symptoms were retrospectively examined in patients with Prinzmetal's variant angina abruptly withdrawn from diltiazem therapy as part of the design of a placebo-controlled multiple crossover trial. Rebound was defined as a return of anginal symptoms to levels exceeding those of the pretreatment baseline state. Values for daily frequency of angina were compared (after subtracting corresponding baseline values) between placebo periods following diltiazem periods and placebo periods following placebo periods.