PRenatal mOdulator treatment to PrEvent CF complicaTions (PROTECT) workshop report.

Background: Data from cystic fibrosis (CF) animal models and case studies suggests that in utero administration of CF transmembrane conductance regulator (CFTR) modulators (variant specific therapies, VST) can rescue CFTR-related pathophysiology in the fetus. Use of VST during pregnancy to prevent disease in infants has not been systematically studied. Through stakeholder engagement, we sought to determine if formal research evaluation is warranted.

A Phase IIa, Single-Blind, Placebo-Controlled, Parallel-Group Study to Assess Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of Brensocatib in Adults with Cystic Fibrosis.

Background And Objectives: Brensocatib, an oral, competitive, and reversible inhibitor of dipeptidyl peptidase 1 (DPP1), reduces exacerbations and lung function decline in non-cystic fibrosis bronchiectasis (NCFBE). This study aimed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of brensocatib in adults with cystic fibrosis (CF), comparing these findings with data from previous trials in healthy adults and in those with NCFBE to inform dose selection for future clinical trials.

Methods: A phase IIa, single-blind, randomized, placebo-controlled trial was conducted to assess the PK, PD, safety, and tolerability of brensocatib in adults with CF.

Cannabinoid receptor 2 agonist, lenabasum, for the treatment of pulmonary exacerbations in cystic fibrosis.

Background: Lenabasum is a cannabinoid receptor 2 (CB2) agonist under development for cystic fibrosis (CF), targeting inflammation. We evaluated the efficacy and safety of lenabasum in people with CF (pwCF).

Methods: We conducted a global, 28-week, randomized, double-blind, placebo-controlled Phase 2b trial.

The Aging Patient with Cystic Fibrosis.

Cystic fibrosis (CF) is an inherited condition that leads to multiorgan dysfunction, especially in the respiratory, gastrointestinal, and reproductive tracts, with associated conditions including persistent pulmonary infection, liver disease, pancreatic insufficiency, and infertility. Historically, people with CF (pwCF) suffered a shortened lifespan due to complications of the condition, namely respiratory. The emphasis on center-based, multidisciplinary care and the widespread introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy has resulted in pwCF living longer and healthier lives.

Trial Conduct, Baseline Characteristics, and Symptom Burden of Patients in the ARISE Study.

Introduction: ARISE was a global clinical trial designed to generate evidence demonstrating the utility of the patient-reported outcome instruments Quality of Life-Bronchiectasis (QOL-B) [Respiratory Domain (RD) only] and Patient-Reported Outcomes Measurement Information System Short Form v1.0-Fatigue 7a (PROMIS F SF-7a) in patients with newly diagnosed or recurrent Mycobacterium avium complex lung disease (MACLD). Here, we describe trial conduct, patient characteristics, and patient-reported symptoms at baseline among patients enrolled in ARISE.

Relationship between culture conversion and clinical outcomes in nontuberculous mycobacterial pulmonary disease: Narrative review.

Purpose: Nontuberculous mycobacterial pulmonary disease (NTMPD) is a chronic, often progressive condition associated with a significant symptom burden and increased mortality. Goals of NTMPD treatment include microbiological eradication, symptom reduction, improved quality of life (QoL), and preventing disease progression. Antibiotics are used to reduce microbial burden, and cultures of sputum are used to guide treatment.

Roles of immunoglobulin GM and KM allotypes and Fcγ receptor 2 A genotypes in humoral immunity to a conserved microbial polysaccharide in pulmonary diseases.

Immunoglobulin GM (γ marker) and KM (κ marker) allotypes-encoded by immunoglobulin heavy chain G (IGHG) and immunoglobulin κ constant (IGKC) genes-have been shown to be associated with immune responsiveness to a variety of self and nonself antigens. The aim of the present investigation was to determine whether allelic variation at the GM and KM loci was associated with antibody responsiveness to poly-N-acetyl-D-glucosamine (PNAG), a broadly-conserved surface polysaccharide expressed by many microbial pathogens. In addition, we wished to determine whether Fcγ receptor 2 A (FCGR2A) genotypes, which have been shown to be risk factors for some pathogens, also influenced antibody responses to PNAG.

Targeting neutrophil serine proteases in bronchiectasis.

Persistent neutrophilic inflammation is a central feature in both the pathogenesis and progression of bronchiectasis. Neutrophils release neutrophil serine proteases (NSPs), such as neutrophil elastase (NE), cathepsin G and proteinase 3. When chronically high levels of free NSP activity exceed those of protective antiproteases, structural lung destruction, mucosal-related defects, further susceptibility to infection and worsening of clinical outcomes can occur.

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.

Cystic fibrosis foundation position paper: Redefining the cystic fibrosis care team.

Interdisciplinary teams care for people with cystic fibrosis (pwCF) at specialized treatment centers. These teams have laid the foundation for the cystic fibrosis (CF) care model responsible for gains in health outcomes and quality of life within the CF community. However, the landscape of CF care is transforming, invigorated by new technologies, accessibility of cystic fibrosis transmembrane conductance regulator (CFTR) therapies, and increased utilization of telemedicine.

The impact of switching to race-neutral reference equations on FEV percent predicted among people with cystic fibrosis.

Rationale: The American Thoracic Society recommended switching to race-neutral spirometry reference equations, as race is a social construct and to avoid normalizing disparities in lung function due to structural racism. Understanding the impact of the race-neutral equations on percent predicted forced expiratory volume in one second (ppFEV) in people with cystic fibrosis (PwCF) will help prepare patients and providers to interpret pulmonary function test results.

Objective(s): To quantify the impact of switching from Global Lung Initiative (GLI) 2012 race-specific to GLI 2022 Global race-neutral reference equations on the distribution of ppFEV among PwCF of different races.

Adjunctive Systemic Corticosteroids for Pulmonary Exacerbations of Cystic Fibrosis.

Pulmonary exacerbations (PEx) remain the most common cause of morbidity, recurrent hospitalization, and diminished survival in people with cystic fibrosis (PWCF) and are characterized by excess inflammation. Corticosteroids are potent, widely available antiinflammatory drugs. However, corticosteroid efficacy data from randomized controlled trials in PWCF are limited.

Prevalence and Clinical Impact of Respiratory Viral Infections from the STOP2 Study of Cystic Fibrosis Pulmonary Exacerbations.

Rates of viral respiratory infection (VRI) are similar in people with cystic fibrosis (CF) and the general population; however, the associations between VRI and CF pulmonary exacerbations (PEx) require further elucidation. To determine VRI prevalence during CF PEx and evaluate associations between VRI, clinical presentation, and treatment response. The STOP2 (Standardized Treatment of Pulmonary Exacerbations II) study was a multicenter randomized trial to evaluate different durations of intravenous antibiotic therapy for PEx.

Characteristics associated with cystic fibrosis-related pulmonary exacerbation treatment location.

Previous studies indicate that hospital rather than home treatment of pulmonary exacerbations (PEx) in people with cystic fibrosis (CF) can improve outcomes. We evaluated characteristics of adult participants from the Standardized Treatment of Pulmonary Exacerbations (STOP2) trial with two separate comparisons: (1) those who were treated initially in hospital (N = 768) to those treated initially at home (N = 214) and (2) those treated only in hospital (N = 328) to those who were treated only at home or both at home and in hospital (N = 654). Participants who had Medicaid insurance, were treated for shorter duration, and traveled longer to reach treatment centers were more likely to have been treated initially in the hospital.

Experiences of cystic fibrosis newborn screening and genetic counseling.

The South Carolina cystic fibrosis (CF) newborn screening (NBS) program changed in 2019 to include CFTR genotyping for babies with top 4% immunoreactive trypsinogen, which improves sensitivity and timeliness but increases carrier detection. Carrier identification has genetic implications for the family and parents of NBS+ babies have increased emotional distress. Genetic counseling (GC) may increase parent understanding and reduce anxiety yet is not uniformly offered at CF centers.

Preparing clinicians to be site investigators in multicenter clinical trials: A training program at an academic medical center.

Clinical trials are essential in the translation of biomedical discoveries to new clinical interventions and therapeutics. Successful multisite clinical trials require qualified site investigators with an understanding of the full spectrum of processes and requirements from trial identification through closeout. New site investigators may be deterred by competing demands on their time, the complexity of administrative and regulatory processes for trial initiation and conduct, and limited access to experienced mentor networks.

Long-term Safety and Tolerability of Omadacycline for the Treatment of Infections.

Background: is a virulent human pathogen. Treatment is complex and often poorly tolerated with suboptimal rates of eradication, highlighting the need for improved therapeutics. This study reports clinical experience with omadacycline for treatment of infections at five large nontuberculous mycobacterial (NTM) disease clinics across the United States to better understand long-term safety and tolerability.

Impact of lumacaftor/ivacaftor and tezacaftor/ivacaftor on treatment response in pulmonary exacerbations of F508del/F508del cystic fibrosis.

Background: Pulmonary exacerbations (PEx) remain a major cause of morbidity and mortality in people with cystic fibrosis (PWCF). Although the combination cystic fibrosis transmembrane conductance regulator (CFTR) modulators lumacaftor/ivacaftor and tezacaftor/ivacaftor have been shown to reduce PEx frequency, their influence on clinical and biochemical responses to acute PEx treatment is unknown.

Methods: We performed a secondary analysis of STOP2, a large multicenter randomized controlled trial of antimicrobial treatment durations for adult PWCF presenting with PEx.

Pulmonary exacerbations in insured patients with bronchiectasis over 2 years.

Background: Patients with bronchiectasis experience persistent symptoms and frequent pulmonary exacerbations; this study investigated the frequency of exacerbations and all-cause hospitalisation.

Methods: This longitudinal, retrospective, claims database study (IBM® MarketScan®) identified patients aged ≥18 years from 1 July 2015 through 30 September 2018. Exacerbations were identified by bronchiectasis inpatient claim or a healthcare interaction, followed by antibiotic prescription within 7 days.

Role of hyperglycemia in cystic fibrosis pulmonary exacerbations.

Background: Hyperglycemia could affect treatment response during cystic fibrosis (CF) exacerbations. We aimed to evaluate the prevalence and associations of hyperglycemia with exacerbation outcomes. We also evaluated feasibility of continuous glucose monitoring (CGM) during exacerbations.

Reporting Standards for Diagnostic Testing: Guidance for Authors From Editors of Respiratory, Sleep, and Critical Care Journals.

Diagnostic testing is fundamental to medicine. However, studies of diagnostic testing in respiratory medicine vary significantly in terms of their methodology, definitions, and reporting of results. This has led to often conflicting or ambiguous results.

Association between unplanned pregnancies and maternal exacerbations in cystic fibrosis.

Introduction: Following availability of the highly effective cystic fibrosis (CF) transmembrane conductance regulator modulator, elexacaftor/tezacaftor/ivacaftor, there was a near doubling of pregnancies reported in the United States (US) in people with CF. We sought to determine health impacts of planned (PP) versus unplanned pregnancies (UP).

Methods: We collected retrospective pregnancy data from January 2010-December 2020 from 11 US CF centers.

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.