Qualitative understanding of experiences of people with cystic fibrosis in a treatment discontinuation trial: The QUEST study.

Background: As people with cystic fibrosis (PWCF) live longer due to the breakthrough drug elexacaftor-tezacaftor-ivacaftor (ETI), they have questioned whether other CF therapies could be safely discontinued. SIMPLIFY was the first prospective, randomized trial to evaluate non-inferiority of discontinuing versus continuing two therapies. The QUEST (Qualitative Understanding of Experiences in the SIMPLIFY Trial) study was conducted to understand experiences of PWCF enrolled in SIMPLIFY, including why they joined, perceptions of randomization, decision-making around study withdrawal, and considerations for future discontinuation studies.

Self-reported chronic therapy use after 24-weeks of follow-up by participants who completed the simplify randomized, controlled trial.

Background: Highly effective CFTR modulator therapy (HEMT) has improved the health of many people with cystic fibrosis (pwCF), offering opportunities to discontinue burdensome therapies. SIMPLIFY included randomized, controlled trials that confirmed non-inferiority of discontinuing versus continuing dornase alfa (DA) or hypertonic saline (HS) for 6 weeks in pwCF on HEMT. In this study of post-trial treatment use by SIMPLIFY participants, we hypothesized that randomization to discontinue DA or HS during the trial would be associated with a higher likelihood of non-use of each medication during follow-up.

Impact of Discontinuing Both Hypertonic Saline and Dornase Alfa after Elexacaftor-Tezacaftor-Ivacaftor in Cystic Fibrosis.

Evaluating approaches to reduce treatment burden is a research priority among people with cystic fibrosis on highly effective modulators, including elexacaftor-tezacaftor-ivacaftor (ETI). We sought to evaluate the impact of discontinuing both hypertonic saline (HS) and dornase alfa (DA) versus continuing both therapies among a subgroup of participants in the SIMPLIFY study who sequentially participated in trials evaluating the independent clinical effects of discontinuing HS and DA. SIMPLIFY participants ≥12 years old on ETI and constituting a subgroup using both HS and DA at study entry were randomized to the HS or DA trial and then randomized 1:1 to continue or discontinue the applicable therapy for 6 weeks.

Association between CFTR modulators and changes in iron deficiency markers in cystic fibrosis.

Background: Iron deficiency (ID) is a common extrapulmonary manifestation in cystic fibrosis (CF). CF transmembrane conductance regulator (CFTR) modulator therapies, particularly highly-effective modulator therapy (HEMT), have drastically improved health status in a majority of people with CF. We hypothesize that CFTR modulator use is associated with improved markers of ID.

The effect of discontinuing hypertonic saline or dornase alfa on mucociliary clearance in elexacaftor/tezacaftor/ivacaftor treated people with cystic fibrosis: The SIMPLIFY-MCC Study.

Many people with CF (pwCF) desire a reduction in inhaled treatment burden after initiation of elexacaftor/tezacaftor/ivacaftor. The randomized, open-label SIMPLIFY study showed that discontinuing hypertonic saline (HS) or dornase alfa (DA) was non-inferior to continuation of each treatment with respect to change in lung function over a 6-week period. In this SIMPLIFY substudy, we used gamma scintigraphy to determine whether discontinuation of either HS or DA was associated with deterioration in the rate of in vivo mucociliary clearance (MCC) in participants ≥12 years of age.

The cost of simplifying treatments for cystic fibrosis: Implications of the SIMPLIFY trial.

Background: Dornase alfa and hypertonic saline are mucoactive therapies that can improve respiratory symptoms in people with cystic fibrosis (CF). A recent randomized control trial showed that participants with well-preserved pulmonary function taking elexacaftor + tezacaftor + ivacaftor (ETI) who discontinued dornase alfa or hypertonic saline for 6 weeks had no clinically meaningful decline in lung function. This may prompt discussions with care providers regarding ongoing use of these medications.

Chronic daily respiratory care needs in people with cystic fibrosis treated with highly effective cystic fibrosis transmembrane conductance regulator modulators.

Purpose Of Review: Cystic fibrosis is a genetic disease that increases risk of death from respiratory failure because of impairment in mucociliary clearance. Complex daily care regimens including medications and airway clearance techniques (ACTs) aim to preserve lung function and alleviate symptoms for people with cystic fibrosis (pwCF). The success of highly effective modulator therapy (HEMT) permits evaluation of treatment simplification.

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.

Update on Clinical Outcomes of Highly Effective Modulator Therapy.

Based on the cystic fibrosis transmembrane conductance regulator (CFTR) genotype, approximately 90% of people with cystic fibrosis (CF) are candidates for highly effective modulator therapy (HEMT). Clinical trials conducted over the last 11 years have shown that these oral therapies substantially restore CFTR function, leading to improvements in lung function, nutritional status, and health-related quality of life. Here, we review safety and efficacy data from phase 3 clinical trials and observational studies which support the use of HEMT in most adults and children with CF.

Discontinuation versus continuation of hypertonic saline or dornase alfa in modulator treated people with cystic fibrosis (SIMPLIFY): results from two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials.

Background: Reducing treatment burden is a priority for people with cystic fibrosis, whose health has benefited from using new modulators that substantially increase CFTR protein function. The SIMPLIFY study aimed to assess the effects of discontinuing nebulised hypertonic saline or dornase alfa in individuals using the CFTR modulator elexacaftor plus tezacaftor plus ivacaftor (ETI).

Methods: The SIMPLIFY study included two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials at 80 participating clinics across the USA in the Cystic Fibrosis Therapeutics Development Network.

Evaluating barriers to and promoters of telehealth during the COVID-19 pandemic at U.S. cystic fibrosis programs.

Background: Cystic fibrosis (CF) care programs in the United States rapidly adopted telehealth during the COVID-19 pandemic. Understanding factors that promote or impede telehealth will inform planning for future telehealth-enabled care models.

Methods: Adult, pediatric, and affiliate CF care programs in the United States (n = 287) were surveyed twice eight months apart in 2020-2021 about telehealth use.

Calprotectin-Mediated Zinc Chelation Inhibits Pseudomonas aeruginosa Protease Activity in Cystic Fibrosis Sputum.

Pseudomonas aeruginosa induces pathways indicative of low zinc availability in the cystic fibrosis (CF) lung environment. To learn more about P. aeruginosa zinc access in CF, we grew P.

Use of proton pump inhibitors is associated with lower hemoglobin levels in people with cystic fibrosis.

Background: Proton pump inhibitors (PPIs) and histamine H2-receptor antagonists (H2RAs) are commonly prescribed to people with cystic fibrosis (PwCF) to treat gastroesophageal reflux disease (GERD) and/or protect pancreatic enzymes from degradation in the stomach. Acid suppressive medications (ASMs) could theoretically reduce hemoglobin (Hgb) levels by restricting enteral iron absorption, but evidence of an association between use of ASMs and lower Hgb levels is lacking in PwCF.

Methods: We used unadjusted and covariate-adjusted generalized linear mixed models (GLMMs) to estimate the fixed effects of using versus never using ASMs on annual Hgb levels of PwCF in the U.

A pilot study of cystic fibrosis exacerbation response phenotypes reveals contrasting serum and sputum iron trends.

The cystic fibrosis (CF) community seeks to explain heterogeneous outcomes of pulmonary exacerbation (PEX) treatment. Serum and sputum inflammatory mediators may identify people with CF (PwCF) at risk for suboptimal responses. However, lack of an established association between response phenotypes and these mediators limits clinical application.

Evaluating the Impact of Stopping Chronic Therapies after Modulator Drug Therapy in Cystic Fibrosis: The SIMPLIFY Clinical Trial Study Design.

The care for individuals with cystic fibrosis (CF) with at least one F508del mutation will greatly change as a result of the unparalleled clinical benefits observed with the new triple-combination CFTR (CF transmembrane regulator)-modulator therapy elexacaftor/tezacaftor/ivacaftor (ETI). Incorporating ETI into the standard of care creates new motivation and opportunity to consider reductions in overall treatment burden and evaluate whether other chronic medications can now be safely discontinued without loss of clinical benefit. SIMPLIFY is a master protocol poised to test the impact of discontinuing versus continuing two commonly used chronic therapies in people with CF who are at least 12 years of age or older and stable on ETI therapy.

Formative evaluation of a dashboard to support coproduction of healthcare services in cystic fibrosis.

Background: Healthcare coproduction engages patients and clinicians to design and execute services, yet little is known about tools that facilitate coproduction. Our objective was to understand uptake, experiences, benefits, and limitations of a dashboard to support patient-clinician partnerships within the cystic fibrosis (CF) community.

Methods: People living with CF (PwCF) and clinicians co-designed a dashboard that displayed patient-reported and clinical data.

Answering the call to address cystic fibrosis treatment burden in the era of highly effective CFTR modulator therapy.

Background: We recognize an unprecedented opportunity to study the effects of withdrawing one or more chronic treatments in people with CF (PwCF) who benefit greatly from CFTR modulator therapy, but feasibility and acceptance of such a study within the community is unknown.

Methods: We surveyed PwCF, their families, and their acquaintances between November 16, 2018, and December 2, 2018, and CF clinicians between December 19, 2018, and January 2, 2019, about treatment withdrawal research. We sought feedback from these groups about their level of interest in this research, the consistency with which they were taking modulator and non-modulator treatments, the ways in which they conceptualized health changes, and what chronic non-modulator treatments they were most interested in stopping.

Availability of Zinc Impacts Interactions between Streptococcus sanguinis and Pseudomonas aeruginosa in Coculture.

Airway infections associated with cystic fibrosis (CF) are polymicrobial. We reported previously that clinical isolates of promote the growth of a variety of streptococcal species. To explore the mechanistic basis of this interaction, we performed a genetic screen to identify mutants of SK36 whose growth was no longer enhanced by PAO1.

CFTR Modulator Use Is Associated with Higher Hemoglobin Levels in Individuals with Cystic Fibrosis.

Rationale: Understanding how cystic fibrosis transmembrane conductance regulator (CFTR) modulators influence comorbid conditions like anemia is of great interest to the cystic fibrosis community.

Objectives: To test the hypothesis that CFTR modulators are associated with higher hemoglobin (Hgb) levels.

Methods: Annualized Hgb and other laboratory, demographic, and anthropometric data were abstracted from the U.

The epidemiology of idiopathic pulmonary fibrosis and interstitial lung diseases at risk of a progressive-fibrosing phenotype.

The availability of epidemiological data relating to interstitial lung diseases (ILDs) has increased over recent years, but information on the prevalence and incidence of ILDs of different aetiologies remains limited. Despite global distribution, the proportion of patients who develop a progressive phenotype across different ILDs is not well known. Disease behaviour is well documented in idiopathic pulmonary fibrosis but idiosyncratic in other ILDs that may present a progressive fibrosing phenotype.