Predicting lung function decline in cystic fibrosis: the impact of initiating ivacaftor therapy.

Background: Modulator therapies that seek to correct the underlying defect in cystic fibrosis (CF) have revolutionized the clinical landscape. Given the heterogeneous nature of lung disease progression in the post-modulator era, there is a need to develop prediction models that are robust to modulator uptake.

Methods: We conducted a retrospective longitudinal cohort study of the CF Foundation Patient Registry (N = 867 patients carrying the G551D mutation who were treated with ivacaftor from 2003 to 2018).

Pharmacokinetic modelling to predict risk of ototoxicity with intravenous tobramycin treatment in cystic fibrosis.

Introduction: Further optimization of therapeutic drug monitoring (TDM) for aminoglycosides (AGs) is urgently needed, especially in special populations such as those with cystic fibrosis (CF), >50% of whom develop ototoxicity if treated with multiple courses of IV AGs. This study aimed to empirically test a pharmacokinetic (PK) model using Bayesian estimation of drug exposure in the deeper body tissues to determine feasibility for prediction of ototoxicity.

Materials And Methods: IV doses (n = 3645) of tobramycin and vancomycin were documented with precise timing from 38 patients with CF (aged 8-21 years), including total doses given and total exposure (cumulative AUC).

Patient personalized translational tools in cystic fibrosis to transform data from bench to bed-side and back.

Cystic fibrosis is a deadly multiorgan disorder caused by loss of function mutations in the gene that encodes for the cystic fibrosis transmembrane conductance regulator (CFTR) chloride/bicarbonate ion channel. More than 1,700 genetic variants exist that can cause CF, and majority of these are extremely rare. Because of genetic and environmental influences, CF patients exhibit large phenotypic variation.

Functional Impacts of Aminoglycoside Treatment on Speech Perception and Extended High-Frequency Hearing Loss in a Pediatric Cystic Fibrosis Cohort.

Purpose The purpose of this study is to better understand the prevalence of ototoxicity-related hearing loss and its functional impact on communication in a pediatric and young adult cohort with cystic fibrosis (CF) and individuals without CF (controls). Method We did an observational, cross-sectional investigation of hearing function in children, teens, and young adults with CF ( = 57, = 15.0 years) who received intravenous aminoglycoside antibiotics and age- and gender-matched controls ( = 61, = 14.

Technology-Enabled Health Care Collaboration in Pediatric Chronic Illness: Pre-Post Interventional Study for Feasibility, Acceptability, and Clinical Impact of an Electronic Health Record-Linked Platform for Patient-Clinician Partnership.

Background: Mobile health (mHealth) technology has the potential to support the Chronic Care Model's vision of closed feedback loops and patient-clinician partnerships.

Objective: This study aims to evaluate the feasibility, acceptability, and short-term impact of an electronic health record-linked mHealth platform (Orchestra) supporting patient and clinician collaboration through real-time, bidirectional data sharing.

Methods: We conducted a 6-month prospective, pre-post, proof-of-concept study of Orchestra among patients and parents in the Cincinnati Children's Hospital inflammatory bowel disease (IBD) and cystic fibrosis (CF) clinics.

Characterization of tracheobronchomalacia in infants with hypophosphatasia.

Background: Perinatal and infantile hypophosphatasia (HPP) are associated with respiratory failure and respiratory complications. Effective management of such complications is of key clinical importance. In some infants with HPP, severe tracheobronchomalacia (TBM) contributes to respiratory difficulties.

Improving Detection of Rapid Cystic Fibrosis Disease Progression-Early Translation of a Predictive Algorithm Into a Point-of-Care Tool.

The clinical course of cystic fibrosis (CF) lung disease is marked by acute drops of lung function, defined clinically as rapid decline. As such, lung function is monitored routinely through pulmonary function testing, producing hundreds of measurements over the lifespan of an individual patient. Point-of-care technologies aimed at improving detection of rapid decline have been limited.

Use and Incidence of Adverse Effects of Proton Pump Inhibitors in Patients with Cystic Fibrosis.

Purpose: To evaluate the incidence of adverse effects associated with chronic proton pump inhibitor (PPI) use as well as the dosing, indication, and duration of use of PPIs in the cystic fibrosis (CF) population at a pediatric academic medical center.

Methods: Study design was a retrospective chart review evaluating patients with CF who were prescribed a PPI for at least 6 months (PPI group) or patients with CF who had never been prescribed a PPI (control group) from June 1, 2014, to May 31, 2015.

Results: The study enrolled 126 patients in the PPI group and 49 patients in the control group.

Early Detection of Rapid Cystic Fibrosis Disease Progression Tailored to Point of Care: A Proof-of-Principle Study.

Slowing cystic fibrosis (CF) lung disease progression is crucial to survival, but point-of-care technologies aimed at early detection-and possibly prevention-of rapid lung function decline are limited. This proof-of-principle study leverages a rich national patient registry and follow-up data on a local CF cohort to build an algorithm and prototype prognostic tool aimed at early detection of rapid lung function decline. The algorithm was developed using a novel longitudinal analysis of lung function (measured as forced expiratory volume in 1 s of % predicted, FEV1).

Protocol of a Pilot Study of Technology-Enabled Coproduction in Pediatric Chronic Illness Care.

Background: Pediatric chronic illness care models are traditionally organized around acute episodes of care and may not meet the needs of patients and their families. Interventions that extend the patient-clinician interaction beyond the health care visit, allow for asynchronous and bidirectional feedback loops that span visits and daily life, and facilitate seamless sharing of information are needed to support a care delivery system that is more collaborative, continuous, and data-driven. Orchestra is a mobile health technology platform and intervention designed to transform the management of chronic diseases by optimizing patient-clinician coproduction of care.

Constrictive Bronchiolitis in Cystic Fibrosis Adolescents with Refractory Pulmonary Decline.

Rationale: Refractory lung function decline in association with recurrent pulmonary exacerbations is a common, yet poorly explained finding in cystic fibrosis (CF). To investigate the histopathologic mechanisms of pulmonary deterioration during adolescence and early adulthood, we reviewed clinically-indicated lung biopsy specimens obtained during a period of persistent decline.

Objectives: To determine if peribronchiolar remodeling is prominent in lung biopsy specimens obtained in adolescents with CF refractory to conventional therapy.

Adolescents' Spirituality and Cystic Fibrosis Airway Clearance Treatment Adherence: Examining Mediators.

Objective: Adolescent cystic fibrosis (CF) treatment adherence is a significant multidimensional issue. Using the Theory of Reasoned Action (TRA), this study examined the role of spiritual factors in adherence.

Methods: Forty-five 11-19-year-olds diagnosed with CF completed questionnaires concerning psychosocial, spiritual, and adherence-related constructs and Daily Phone Diaries to calculate treatment adherence.

Decision Making for Children with Obstructive Sleep Apnea without Tonsillar Hypertrophy.

Objective: Evidence-based medicine is the gold standard practice model for patient management. Our aim was to determine whether decisions made by pediatric subspecialists regarding management of obstructive sleep apnea in children without tonsillar hypertrophy adhered to this model or were based on clinical experiences.

Study Design: Single-institution prospective study.

Lumacaftor alone and combined with ivacaftor: preclinical and clinical trial experience of F508del CFTR correction.

Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator protein (CFTR), leading to significant morbidity and mortality. CFTR is a chloride and bicarbonate channel at the epithelial cell membrane. The most common CFTR mutation is F508del, resulting in minimal CFTR at the plasma membrane.

Concentration of fractional excretion of nitric oxide (FENO): A potential airway biomarker of restored CFTR function.

Background: Lower airway biomarkers of restored cystic fibrosis transmembrane conductance regulator (CFTR) function are limited. We hypothesized that fractional excretion of nitric oxide (FENO), typically low in CF patients, would demonstrate reproducibility during CFTR-independent therapies, and increase during CFTR-specific intervention (ivacaftor) in patients with CFTR gating mutations.

Methods: Repeated FENO and spirometry measurements in children with CF (Cohort 1; n=29) were performed during hospital admission for acute pulmonary exacerbations and routine outpatient care.

Obstructive lung disease in children with idiopathic scoliosis.

Objective: To measure the prevalence of obstructive lung disease (OLD) among patients undergoing preoperative pulmonary assessment for idiopathic scoliosis.

Study Design: This was a retrospective, descriptive review from clinical data in a tertiary care pediatric hospital in the US. Patients (n = 176) with idiopathic scoliosis with Cobb angles of ≥ 40 degrees who performed acceptable and repeatable preoperative pulmonary function testing were included.

The impact of transforming healthcare delivery on cystic fibrosis outcomes: a decade of quality improvement at Cincinnati Children's Hospital.

Background: In 2001, Cincinnati Children's Hospital embarked on a journey to improve healthcare delivery to patients with cystic fibrosis (CF). Data from the Cystic Fibrosis Foundation National Patient Registry revealed our below-average clinical outcomes, prompting us to initiate improvement interventions.

Objective: To improve clinical outcomes for patients with CF through a comprehensive quality-improvement approach directed at increasing patient centredness and improving healthcare delivery.

Obstructive lung disease is common in children with syndromic and congenital scoliosis: a preliminary study.

Background: It is well known that restrictive lung disease (RLD) is associated with scoliosis. This study identifies that obstructive lung disease (OLD) is associated with syndromic scoliosis and congenital scoliosis.

Methods: We searched a local database for patients with scoliosis who underwent a pulmonary function testing (PFT) from 2004 to 2009.

A semiparametric approach to estimate rapid lung function decline in cystic fibrosis.

Purpose: Detecting the onset of rapid lung function decline is important to reduce mortality rates in cystic fibrosis (CF) and other lung diseases. The most common approach is conventional linear mixed modeling-estimating a population-level slope of lung function decline and using random effects to address serial correlation-but this ignores nonlinear features of disease progression and distinct sources of variability. The purpose of this article was to estimate patient-specific timing and degree of rapid decline while appropriately characterizing natural progression and variation in CF.

Inhaled tobramycin effectively reduces FEV1 decline in cystic fibrosis. An instrumental variables analysis.

Rationale: The efficacy of inhaled tobramycin on chronic Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF) has been established in clinical trials. However, little is known about its clinical effectiveness on lung function outside randomized controlled trial settings; conventional analysis of existing registry data has heretofore been confounded by treatment selection bias.

Objective: To determine effectiveness of inhaled tobramycin on FEV1 decline in patients with chronic P.

Aortopulmonary collateral flow in cystic fibrosis assessed with phase-contrast MRI.

Background: Cystic fibrosis (CF) is a common genetic disease in Caucasians. Chronic pulmonary disease with progressive destruction of the pulmonary parenchyma is two of the major morbidities, but the relationship between clinical severity of CF and aortopulmonary collateral blood flow has not been assessed.

Objective: The purpose of this study is to measure changes in aortopulmonary collateral blood flow by phase-contrast magnetic resonance imaging (MRI) in children with CF across the spectrum of disease severity as measured by the forced expiratory volume in one second as percent predicted value (FEV1% predicted).

"I honestly believe god keeps me healthy so i can take care of my child": parental use of faith related to treatment adherence.

A limited number of studies address parental faith and its relationship to their children's health. Using cystic fibrosis as a disease exemplar in which religion/spirituality have been shown to play a role and parental health behaviors (adherence to their child's daily recommended home treatments) are important, this study explored whether parents with different levels of adherence would describe use of faith differently. Twenty-five interviews were completed and analyzed using grounded theory methodology.

Is adolescents' religious coping with cystic fibrosis associated with the rate of decline in pulmonary function?-A preliminary study.

Religious coping is associated with health outcomes in adolescents with chronic disease. Identifying potentially modifiable spiritual factors is important for improving health outcomes. The purpose of this study was to determine if associations exist between rate of change in pulmonary function and subsequent religious coping by adolescents with cystic fibrosis (CF).