Maximising opportunity for therapeutic success: sequential participation in cystic fibrosis nucleic acid-based therapy trials.

Identifying safe and effective therapies that target the underlying cause of cystic fibrosis remains a key priority for the cystic fibrosis community. CFTR modulators are first-in-class, regulatory-approved therapies that improve the function of the protein encoded by the CFTR gene and are associated with dramatic and sustained clinical benefits. Although approximately 90% of the population with cystic fibrosis could benefit from these therapies based on genetic eligibility, a crucial unmet need remains: developing CFTR-directed therapies for the ultra-rare population with cystic fibrosis who are not candidates for CFTR modulators due to either ineligibility or intolerance.

Addressing Sex as a Biological Variable in Preclinical Models of Lung Disease: An Official American Thoracic Society Research Statement.

Pulmonary diseases have sex-specific predilections across the lifespan. The rigor of preclinical research is paramount to ensure the reproducibility and applicability of findings to clinical studies. The overarching goal was to identify current research gaps and the need for consideration of sex as a biological variable (SABV) in preclinical pulmonary research.

Investigating the Interplay Between Having Cystic Fibrosis and Being a Member of the LGBTQIA+ Community: Protocol for the PRIDE CF Study.

The impact of the intersectional lived experience of having a chronic health condition and identifying as lesbian, gay, bisexual, transgender, queer, intersex, asexual or another sexual or gender minority (LGBTQIA+) on health and wellbeing is largely unknown. In this article, we describe the development and structure of PRIDE CF, an innovative, large-scale epidemiologic study using a mixed-methods team science approach to understand the experiences and health outcomes of people with cystic fibrosis (PwCF) who identify as a gender or sexual minority. Our four separate but symbiotic projects utilize the PRIDE CF cohort (n ~ 300) with the shared goal of better understanding the needs of LGBTQIA+ PwCF.

Fertility and family-building experiences and perspectives of males with cystic fibrosis.

Background: Nearly all males with cystic fibrosis (MwCF) are infertile and, thus, require the use of assisted reproductive technology (ART) to have biologic children. This study aims to describe the fertility and family-building knowledge, experiences, and care utilization of this population and to compare these findings to the general United States (US) population.

Methods: We conducted an anonymous cross-sectional study of self-reported survey data compared to data from the 2017-2019 US National Survey for Family Growth (NSFG).

Menopause in Cystic Fibrosis: Special Considerations for Bone Health, Menopausal Symptoms, and Treatment.

Cystic fibrosis (CF) is a multisystem autosomal recessive disease arising from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Dysfunction of the CFTR protein leads to progressive pulmonary disease, pancreatic exocrine insufficiency, and nutritional deficiencies. Survival has significantly increased over the last several decades due to improved pulmonary and nutritional management, including CFTR modulator therapy.

Personalized inhaled bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa in cystic fibrosis.

Bacteriophage (phage) therapy, which uses lytic viruses as antimicrobials, is a potential strategy to address the antimicrobial resistance crisis. Cystic fibrosis, a disease complicated by recurrent Pseudomonas aeruginosa pulmonary infections, is an example of the clinical impact of antimicrobial resistance. Here, using a personalized phage therapy strategy that selects phages for a predicted evolutionary trade-off, nine adults with cystic fibrosis (eight women and one man) of median age 32 (range 22-46) years were treated with phages on a compassionate basis because their clinical course was complicated by multidrug-resistant or pan-drug-resistant Pseudomonas that was refractory to prior courses of standard antibiotics.

Discrepancy in efficiency scores due to sampling error in data envelopment analysis methodology: evidence from the banking sector.

Background: Data Envelopment Analysis (DEA) methodology is considered the most suitable approach for relative performance efficiency calculation for banks as it is believed to be superior to traditional ratio-based analysis and other conventional performance evaluations. This study provides statistical evidence on the sampling error that can creep into performance evaluation studies using the DEA methodology. Inferences are drawn based on samples, and various preventive measures must be taken to eliminate or avoid sampling errors and misleading results.

Real-world association between ivacaftor initiation and lung function variability: A registry study.

Background: Increased variability in forced expiratory volume in 1 s of % predicted (FEVpp) has been associated with accelerated lung function decline in individuals with cystic fibrosis (CF). Lung function variability is a leading predictor of decline, but the association between ivacaftor initiation and FEVpp variability has not been characterized.

Methods: We utilized the Cystic Fibrosis Foundation Patient Registry (2008-2020) to quantify this association and identify risk factors of increased variability.

Contraceptive use and pregnancy in cystic fibrosis: Survey findings from 10 cystic fibrosis centers.

Background: Reproductive life planning is key, now that people with cystic fibrosis (pwCF) may live into their 60s. This study explores contraceptive use, pregnancy trends, and whether concomitant cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy reduces contraceptive effectiveness.

Methods: Females with CF aged 18-45 years from 10 U.

Development of metabolic syndrome in people with Cystic Fibrosis one year after exposure to elexacaftor-tezacaftor-ivacaftor.

Background: The constellation of hypertension, truncal obesity, impaired fasting glucose, low high-density lipoprotein, and hypertriglyceridemia is known as metabolic syndrome (MetSyn) and is associated with cardiovascular and other diseases. Elexacaftor-tezacaftor-ivacaftor (ETI) in people with cystic fibrosis (pwCF) is associated with weight gain but effects on cardiovascular risk are unknown. This study sought to investigate ETI exposure and risk for development of MetSyn in pwCF.

Impact of Cystic Fibrosis Transmembrane Conductance Regulator Modulators on Maternal Outcomes During and After Pregnancy.

Background: Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators are available to the majority of people with CF in the United States; little is known about pregnancy outcomes with modulator use. The aim of this retrospective study was to determine the impact of CFTR modulators on maternal outcomes.

Research Question: Does pregnancy differentially affect outcomes in female individuals with CF with and without CFTR modulator exposure?

Study Design And Methods: Data on pregnancies from 2010 to 2021 were collected from 11 US adult CF centers.

Lentiviral Gene Therapy for Cystic Fibrosis: A Promising Approach and First-in-Human Trial.

Cystic fibrosis (CF) is a genetic disease caused by mutations in the (cystic fibrosis transmembrane conductance regulator) gene. Although CF is a multiorgan disease, the leading causes of morbidity and mortality are related to progressive lung disease. Current understanding of the effects of the broad spectrum of mutations on CFTR function has allowed for the development of CFTR modulator therapies.

Glucagon-like-peptide-1 agonist therapy in adults with cystic fibrosis.

Glucagon-like-peptide-1 (GLP-1) agonists are commonly used to improve glycemic control and promote weight loss in individuals with type 2 diabetes mellitus (T2DM) and/or obesity. However, there is a paucity of evidence regarding GLP-1 agonist use in people with cystic fibrosis (pwCF). We present 11 people with CF (males: 3, females: 7; age range 24-47; BMI range 25.

Assessing the health impacts of parenthood on people with cystic fibrosis: the HOPeCF prospective cohort protocol.

Introduction: People with cystic fibrosis (CF) are living longer and healthier lives with a growing number considering and pursuing parenthood. The decision of whether to become a parent is complex for people with CF, and CF is a major factor in reproductive decision-making. Unfortunately, in people with CF who become parents, there are no prospective studies of disease trajectory, no data on the impact of parenthood on mental health, disease self-management, or quality of life, and no research regarding non-genetic parenthood.

Pregnancy and fertility in people with cystic fibrosis following lung transplantation.

Purpose Of Review: The purpose of this review is to summarize available data on fertility, fertility preservation, pregnancy and parenthood following lung transplantation for people with cystic fibrosis (pwCF).

Recent Findings: In the era of cystic fibrosis transmembrane conductance regulator (CFTR) modulator use, oral therapies that positively impact fundamental CFTR protein abnormalities, the number of pregnancies has increased dramatically with a concomitant decrease in lung transplantation. Nonetheless, some pwCF still require lung transplantation as a life-saving measure, and a fraction of those individuals desires parenthood.

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.

Forced Expiratory Volume in 1 Second Variability Predicts Lung Transplant or Mortality in People with Cystic Fibrosis in the United States.

Declines in percent predicted forced expiratory volume in 1 second (ppFEV) are an important marker of clinical progression of cystic fibrosis (CF). We examined ppFEV variability in relation to a combined outcome of lung transplant or death. We estimated the association between ppFEV variability and the combined outcome of lung transplant or death.

In vivo editing of lung stem cells for durable gene correction in mice.

In vivo genome correction holds promise for generating durable disease cures; yet, effective stem cell editing remains challenging. In this work, we demonstrate that optimized lung-targeting lipid nanoparticles (LNPs) enable high levels of genome editing in stem cells, yielding durable responses. Intravenously administered gene-editing LNPs in activatable tdTomato mice achieved >70% lung stem cell editing, sustaining tdTomato expression in >80% of lung epithelial cells for 660 days.