Evaluation of elexacaftor-tezacaftor-ivacaftor treatment in individuals with cystic fibrosis and CFTR in the USA: a prospective, multicentre, open-label, single-arm trial.

Background: CFTR modulators are approved for approximately 90% of people with cystic fibrosis in the USA and provide substantial clinical benefit. N1303K (Asn1303Lys), one of the most common class 2 CFTR defects, has not been approved for these therapies by any regulatory agency. Preclinical investigation by our laboratories showed N1303K CFTR activation with elexacaftor-tezacaftor-ivacaftor (ETI).

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.

Validation of the Integrated Palliative Care Outcome Scale (IPOS) in adults with cystic fibrosis.

Background: A primary palliative care model for cystic fibrosis (CF) recommends using the Integrated Palliative Care Outcome Scale (IPOS) for screening. Validation of the IPOS is needed.

Methods: This secondary analysis utilized baseline data from a multisite trial of the palliative care model, Improving Life with CF.

Palliative care needs among outpatient adults with cystic fibrosis: Baseline data from the Improving Life with CF trial.

Background: Little is known about the burden of illness experienced by people with cystic fibrosis (pwCF) since the advent of CF transmembrane conductance regulator (CFTR) modulator therapies. Studies that characterize the nature of illness burden are needed to inform the development and implementation of palliative care programs that can serve this population and address quality of life concerns.

Methods: Adults with CF treated at five U.

Long-term safety and efficacy of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis and at least one allele: 144-week interim results from a 192-week open-label extension study.

Background: In two pivotal phase 3 trials, up to 24 weeks of treatment with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was efficacious and safe in patients with cystic fibrosis (CF) ≥12 years of age who have at least one allele. The aim of this study is to assess long-term safety and efficacy of ELX/TEZ/IVA in these patients.

Methods: In this phase 3, open-label, single-arm extension study, participants with -minimal function (from a 24-week parent study; n=399) or - (from a 4-week parent study; n=107) genotypes receive ELX/TEZ/IVA at the same dose (ELX 200 mg once daily, TEZ 100 mg once daily and IVA 150 mg every 12 h).

Diagnostic challenges in CFTR-related metabolic syndrome: Where the guidelines fall short.

Newborn screening (NBS) for cystic fibrosis (CF) has enabled earlier diagnosis and has improved nutritional and growth-related outcomes in children with CF. For those with a positive NBS for CF that do not meet the diagnostic criteria for CF, the clinical entity called CFTR-Related Metabolic Syndrome (CRMS) or CF Screen- Positive, Inconclusive Diagnosis (CFSPID) is used. Although most children with CRMS remain relatively asymptomatic, studies have shown that between 11% and 48% of these patients may eventually progress to a diagnosis of CF over time.

Development of a Cystic Fibrosis Primary Palliative Care Intervention: Qualitative Analysis of Patient and Family Caregiver Preferences.

To prevent or mitigate chronic illness burden, people with cystic fibrosis (pwCF) and their family caregivers need primary (generalist-level) palliative care from the time of diagnosis forward. We used qualitative methods to explore their preferences about a screening-and-triage model ("") developed to standardize this care. We purposively sampled and interviewed 14 pwCF and caregivers from 5 study sites.

EFFECT OF ELEXACAFTOR/TEZACAFTOR/IVACAFTOR ON ANNUAL RATE OF LUNG FUNCTION DECLINE IN PEOPLE WITH CYSTIC FIBROSIS.

Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be safe and efficacious in people with cystic fibrosis (CF) with ≥ 1 F508del-CFTR allele in Phase 3 clinical trials. ELX/TEZ/IVA treatment led to improved lung function, with increases in percent predicted forced expiratory volume in 1 second (ppFEV) and Cystic Fibrosis Questionnaire-Revised respiratory domain score. Here, we evaluated the impact of ELX/TEZ/IVA on the rate of lung function decline over time by comparing changes in ppFEV in participants from the Phase 3 trials with a matched group of people with CF from the US Cystic Fibrosis Foundation Patient Registry not eligible for cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy.

Serum anti-PAD4 autoantibodies are present in cystic fibrosis children and increase with age and lung disease severity.

Cystic fibrosis (CF) lung disease begins early in childhood and is characterized by neutrophilic inflammation of the airways. Neutrophil extracellular traps (NETs) represent one mechanism by which neutrophils contribute to lung damage. The enzyme peptidylarginine deiminase 4 (PAD4) is required for NET formation.

Trajectories of oral glucose tolerance testing in cystic fibrosis.

Introduction: Annual oral glucose tolerance testing (OGTT) is the recommended screening modality for cystic fibrosis-related diabetes (CFRD) in patients with cystic fibrosis (CF). This study aimed to determine if there were patterns of progression of worsening glucose homeostasis in pediatric CF patients and to explore any relationship to lung function.

Methods: We conducted a retrospective cohort study of CF patients, ages 10-18 years, without CFRD and with ≥3 OGTT from 2013 to 2016.

Improving lung function in adolescents with CF by tracking annual rate of lung function decline.

Background: For patients with cystic fibrosis (CF), sustaining lung function through the adolescent years is crucial to slow the progressive decline that leads to significant morbidity and early mortality. This holds true for patients with high per cent predicted forced expiratory volume in 1 s (ppFEV), as they may receive less vigilant monitoring and treatment. Early identification of lung function decline followed by aggressive treatment can lead to preservation of lung function.

Use of the NINJA (Nephrotoxic Injury Negated by Just-in-Time Action) Program to Identify Nephrotoxicity in Pediatric Patients with Cystic Fibrosis.

Objective: This study aims to use and evaluate the Nephrotoxic Injury Negated by Just-in-time Action (NINJA) program in hospitalized patients with cystic fibrosis (CF) at Children's Healthcare of Atlanta.

Methods: This was a single-center study evaluating patients with CF who were hospitalized and admitted to the pulmonary service 4 months pre- and post-NINJA implementation. Postimplementation patients with high nephrotoxic medication (NTMx) exposure were identified using an electronic reporting tool that triggered the pharmacist to alert the medical team and recommend Monday/Wednesday/Friday serum creatinine (SCr) monitoring.

Transition Planning for Chronic Illnesses in the Time of COVID-19.

Transition from pediatric to adult care for those with chronic illnesses must have special considerations during the COVID-19 pandemic. The SARS-CoV-2 coronavirus has significantly disrupted social, economic, and health care practices globally. Young adults with special health care needs are at increased risk for poor outcomes during this unprecedented time.

IgA autoantibodies directed against self DNA are elevated in cystic fibrosis and associated with more severe lung dysfunction.

Although extracellular host DNA (ecDNA) levels in CF airways were linked to airflow obstruction and recombinant DNAse therapy is beneficial for CF patients, it remains incompletely understood whether ecDNA also leads to an autoimmune response. Here we hypothesized that chronic presence of DNA in CF airways triggers the production of autoantibodies targeting host human DNA. We measured the levels of IgA autoantibodies recognising host double-stranded (ds) DNA in the blood and sputum samples of CF patients and only sera of controls subjects and patients suffering from rheumatoid arthritis and systemic lupus erythematosus (SLE) that served as non-CF, autoimmune disease cohorts.

Maternal Fish Consumption in Pregnancy Is Associated with a -Dominant Microbiome Profile in Infants.

National guidelines suggest that pregnant women consume 2-3 servings of fish weekly and often focus exclusively on limiting mercury exposure. We examined if meeting this recommendation in the third trimester of pregnancy was associated with differences in infant fecal microbiota composition and diversity. We used multinomial regression to analyze data from 114 infant-mother dyads.

Effects of a primary palliative care intervention on quality of life and mental health in cystic fibrosis.

Background: Despite the significant impact of chronic symptoms on quality of life with cystic fibrosis (CF), the role of palliative care in management of this disease is not well defined. The coping, goal assessment, and relief from evolving CF symptoms (CF-CARES) model is a primary palliative care intervention designed to provide chronic symptom management at all stages of the disease. The goal of this pilot study was to estimate the effectiveness of the CF-CARES intervention on improving chronic symptoms and quality of life for people living with CF.

Advance Care Planning Experiences and Preferences among People with Cystic Fibrosis.

Background: Advance care planning (ACP) is recommended for people with cystic fibrosis (CF), yet guidance for optimal implementation is lacking.

Objective: To assess ACP-related thoughts, comfort level, and preferences among people with CF to guide evidence-based routine implementation of ACP in the CF clinic.

Design: A cross-sectional survey assessed ACP-related experiences and preferences.

Sphingolipid metabolism potential in fecal microbiome and bronchiolitis in infants: a case-control study.

Objective: Emerging evidence demonstrated that the structure of fecal microbiome is associated with the likelihood of bronchiolitis in infants. However, no study has examined functional profiles of fecal microbiome in infants with bronchiolitis. In this context, we conducted a case-control study.

The CF-CARES primary palliative care model: A CF-specific structured assessment of symptoms, distress, and coping.

Background: Current palliative care tools do not address distressing chronic symptoms that are most relevant to cystic fibrosis.

Methods: A CF-specific structured assessment based on a primary palliative care framework was administered to 41 adolescents and adults with CF. Descriptive and correlational analyses were conducted.

Nasal Airway Microbiota Profile and Severe Bronchiolitis in Infants: A Case-control Study.

Background: Little is known about the relationship of airway microbiota with bronchiolitis in infants. We aimed to identify nasal airway microbiota profiles and to determine their association with the likelihood of bronchiolitis in infants.

Methods: A case-control study was conducted.

Household siblings and nasal and fecal microbiota in infants.

Background: Early-life exposure to older siblings is associated with a lower risk of asthma. To date, no study has addressed the impact of having siblings on both the airway and fecal microbiota during infancy. The aim of this study was therefore to profile the nasal airway and fecal microbiota in infants, and to examine the association between having siblings and microbiota profile.

Cohort Study of Severe Bronchiolitis during Infancy and Risk of Asthma by Age 5 Years.

Background: Severe bronchiolitis (ie, bronchiolitis requiring hospital admission) is thought to markedly increase asthma risk, with 30%-50% developing asthma by age 5 years. To date, studies of this association are small, and most are from outside the United States.

Objective: The objective of this study was to investigate the association between severe bronchiolitis and risk of asthma in a US birth cohort.

The Fecal Microbiota Profile and Bronchiolitis in Infants.

Background: Little is known about the association of gut microbiota, a potentially modifiable factor, with bronchiolitis in infants. We aimed to determine the association of fecal microbiota with bronchiolitis in infants.

Methods: We conducted a case-control study.

Pre-birth cohort study of atopic dermatitis and severe bronchiolitis during infancy.

Background: Infants hospitalized for bronchiolitis (i.e. severe bronchiolitis) are at increased risk of childhood asthma.