Lung transplant referral practice patterns: a survey of cystic fibrosis physicians and general pulmonologists.

Background: Many individuals with cystic fibrosis (CF) die from respiratory failure without referral for lung transplant. Physician practices that may expedite, delay, or preclude referral, are poorly understood.

Methods: Two parallel, web-based surveys focusing on lung transplant referral triggers and barriers, as well as pre-referral evaluation, were emailed to pulmonologists practicing in the New England region.

US pediatric pulmonology workforce.

Aim: Children with respiratory conditions benefit from care provided by pediatric pulmonologists. As these physicians are a small portion of the overall pediatric workforce, it is necessary to understand the practices and career plans of these specialists.

Methods: An internet survey was developed by the American Academy of Pediatrics Division of Workforce and Medical Education Policy and sent to members of the American Academy of Pediatrics and American College of Chest Physicians who identified as pediatric pulmonary physicians.

Ciprofloxacin DPI: a randomised, placebo-controlled, phase IIb efficacy and safety study on cystic fibrosis.

Background: Treatment of infective bronchitis involving Pseudomonas aeruginosa is a cornerstone of care in patients with cystic fibrosis (CF). This phase IIb, randomised, double-blind, placebo-controlled study assessed the efficacy and safety of ciprofloxacin dry powder for inhalation (DPI) in this population.

Methods: Patients with CF, ≥12 years of age (N=286), were randomised to ciprofloxacin DPI (32.

Inhaled alpha1-proteinase inhibitor therapy in patients with cystic fibrosis.

Background: Inhaled alpha1-proteinase inhibitor (PI) is known to reduce neutrophil elastase burden in some patients with CF. This phase 2a study was designed to test inhaled Alpha-1 HC, a new aerosolized alpha1-PI formulation, in CF patients.

Methods: We performed a randomized, double-blind, placebo-controlled study and evaluated the safety of 100 or 200mg of inhaled Alpha-1 HC once daily for 3 weeks in subjects with CF.

Congenital pulmonary malformations in pediatric patients: review and update on etiology, classification, and imaging findings.

Congenital pulmonary malformations represent a heterogeneous group of developmental disorders affecting the lung parenchyma, the arterial supply to the lung, and the lung's venous drainage. In both asymptomatic and symptomatic pediatric patients with congenital pulmonary malformations, the diagnosis of such malformations usually requires imaging evaluation, particularly in cases of surgical lesions for preoperative assessment. The goal of this article is to review the current imaging techniques for evaluating congenital pulmonary malformations and their characteristic imaging findings, which can allow differentiation among various congenital pulmonary malformations in pediatric patients.

Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for the F508del-CFTR mutation.

Background: VX-809, a cystic fibrosis transmembrane conductance regulator (CFTR) modulator, has been shown to increase the cell surface density of functional F508del-CFTR in vitro.

Methods: A randomised, double-blind, placebo-controlled study evaluated the safety, tolerability and pharmacodynamics of VX-809 in adult patients with cystic fibrosis (n=89) who were homozygous for the F508del-CFTR mutation. Subjects were randomised to one of four VX-809 28 day dose groups (25, 50, 100 and 200 mg) or matching placebo.

Cystic fibrosis newborn screening: using experience to optimize the screening algorithm.

Newborn screening (NBS) for cystic fibrosis (CF) offers the opportunity for early diagnosis and improved outcomes in patients with CF and has been universally available in the state of Massachusetts since 1999 using an immunoreactive trypsinogen (IRT)-DNA algorithm. Ideally, CF NBS is incorporated as part of an integrated NBS system that allows for comprehensive and coordinated education, laboratory screening, clinical follow-up, and evaluation so that evidence-based data can be used to maximize quality improvements and optimize the screening algorithm. The New England Newborn Screening Program (NENSP) retrospectively analyzed Massachusetts's CF newborn screening data that yielded decisions to eliminate a screen-positive category, maintain the IRT cutoff value that prompts the second tier DNA testing, and communicate CF relative risk to primary care providers (PCPs) based on categorization of positive CF NBS results.

Repeated aerosolized AAV-CFTR for treatment of cystic fibrosis: a randomized placebo-controlled phase 2B trial.

Previous studies have demonstrated that delivery of a recombinant adeno-associated virus (AAV) vector encoding the complete human cystic fibrosis transmembrane regulator (CFTR) cDNA (tgAAVCF) to the nose, sinus, and lungs of subjects with cystic fibrosis (CF) was safe and well tolerated. In a small randomized, double-blind study of three doses of aerosolized tgAAVCF or placebo at 30-day intervals, encouraging but non-significant trends in pulmonary function and induced sputum interleukin 8 (IL-8) levels were seen at early time points. This larger study was conducted to verify these trends.

Early pulmonary manifestation of cystic fibrosis in children with the DeltaF508/R117H-7T genotype.

We report 3 cystic fibrosis newborn screen-positive infants with the DeltaF508/R117H-7T genotype who had Pseudomonas aeruginosa detected in oropharyngeal cultures early in life and a fourth who had pulmonary symptoms and Gram-negative growth on multiple oropharyngeal cultures. All 4 patients were followed prospectively from the time of genetic diagnosis. As many regions implement newborn screening for cystic fibrosis, there is concern regarding which mutations should be included in genetic panels used to make the cystic fibrosis diagnosis.

Communications systems and their models: Massachusetts parent compliance with recommended specialty care after positive cystic fibrosis newborn screening result.

Objective: To evaluate compliance with recommendations for sweat testing/specialty evaluation and genetic counseling after a positive cystic fibrosis newborn screening (CF NBS) result.

Study Design: All infants with positive CF NBS results require a diagnostic sweat test at a CF center. Results that were "screen positive and diagnosis negative" prompted family genetic counseling.

Challenges in implementing a successful newborn cystic fibrosis screening program.

Objective: To identify necessary components of a successful cystic fibrosis (CF) newborn screening (NBS) program.

Study Design: The approach to CF NBS used by the Massachusetts NBS program was examined.

Results: Several key components were identified that should be addressed when a state has made the decision to screen, and well in advance of actual implementation.

Sweat testing infants detected by cystic fibrosis newborn screening.

Objective: Describe and define limitations of early pilocarpine iontophoresis (sweat testing) for cystic fibrosis (CF) newborn screening (NBS).

Study Design: Population-based results from follow-up of CF NBS-positive newborns.

Results: Insufficient quantity of sweat is more likely if the sweat test is done too early, but testing is generally successful after 2 weeks of age.

Species-specific bacteria identification using differential mobility spectrometry and bioinformatics pattern recognition.

As bacteria grow and proliferate, they release a variety of volatile compounds that can be profiled and used for speciation, providing an approach amenable to disease diagnosis through quick analysis of clinical cultures as well as patient breath analysis. As a practical alternative to mass spectrometry detection and whole cell pyrolysis approaches, we have developed methodology that involves detection via a sensitive, micromachined differential mobility spectrometer (microDMx), for sampling headspace gases produced by bacteria growing in liquid culture. We have applied pattern discovery/recognition algorithms (ProteomeQuest) to analyze headspace gas spectra generated by microDMx to reliably discern multiple species of bacteria in vitro: Escherichia coli, Bacillus subtilis, Bacillus thuringiensis, and Mycobacterium smegmatis.

Population-based newborn screening for genetic disorders when multiple mutation DNA testing is incorporated: a cystic fibrosis newborn screening model demonstrating increased sensitivity but more carrier detections.

Objectives: Newborn screening for cystic fibrosis (CF) provides a model to investigate the implications of applying multiple-mutation DNA testing in screening for any disorder in a pediatric population-based setting, where detection of affected infants is desired and identification of unaffected carriers is not. Widely applied 2-tiered CF newborn screening strategies first test for elevated immunoreactive trypsinogen (IRT) with subsequent analysis for a single CFTR mutation (DeltaF508), systematically missing CF-affected infants with any of the >1000 less common or population-specific mutations. Comparison of CF newborn screening algorithms that incorporate single- and multiple-mutation testing may offer insights into strategies that maximize the public health value of screening for CF and other genetic disorders.

Genetic counseling after implementation of statewide cystic fibrosis newborn screening: Two years' experience in one medical center.

Purpose: To study the follow-up of genetic counseling performed in families with a newborn detected with one cystic fibrosis (CF) mutation in a statewide newborn screening pilot program.

Methods: Newborns in Massachusetts with an elevated trypsinogen level on newborn screen who are found to have one mutation for CF on a selected mutation assay undergo sweat testing for CF, and their families receive genetic counseling. The genetic counseling focuses on carrier risk for the parents of the newborn and offers carrier testing.

Aerosol and lobar administration of a recombinant adenovirus to individuals with cystic fibrosis. II. Transfection efficiency in airway epithelium.

A phase I clinical trial was conducted in which recombinant adenovirus containing the cystic fibrosis trans-membrane regulator (CFTR) (Ad2/CFTR) was administered by bronchoscopic instillation or aerosolization to the lungs of cystic fibrosis (CF) patients. In this paper, we evaluate the efficiency of Ad2/CFTR-mediated transduction of bronchial airway cells. The ability of an Ad2/CFTR vector to transduce airway cells was first evaluated in patients to whom the vector was administered by bronchoscopic instillation.

Aerosol and lobar administration of a recombinant adenovirus to individuals with cystic fibrosis. I. Methods, safety, and clinical implications.

Cystic fibrosis (CF), an autosomal recessive disorder resulting from mutations in the cystic fibrosis trans-membrane conductance regulator (CFTR) gene, is the most common lethal genetic illness in the Caucasian population. Gene transfer to airway epithelium, using adenoviruses containing normal CFTR cDNA, leads to transient production of CFTR mRNA and, in some studies, to correction of the airway epithelial ion transport defect caused by dysfunctional CFTR. Inflammatory responses to the adenoviral vector have been reported, particularly at high viral titers.

Practice of pediatric pulmonology: results of the Future of Pediatric Education Project (FOPE).

In 1996, the Future of Pediatric Education (FOPE) Project of the American Academy of Pediatrics (AAP) developed surveys to describe the nature of pediatric practices, recent trends in clinical practice, and anticipated workforce needs for both pediatric generalists and pediatric sub-specialists. A survey was specifically developed to describe the features of pediatric pulmonology as self-reported by pediatric pulmonologists. The survey was distributed to members of the AAP Pulmonology Section, the Pediatric Assembly of the American Thoracic Society, and certified pediatric pulmonologists recognized by the American Board of Pediatrics.

Safety of repeated intermittent courses of aerosolized recombinant human deoxyribonuclease in patients with cystic fibrosis.

Objectives: To determine the effect of repeated doses of aerosolized recombinant human deoxyribonuclease (rhDNase) on the development of anti-rhDNase antibodies, acute allergic reactions, and pulmonary function in patients with cystic fibrosis.

Design: A multicenter, open-label study in which 184 patients received 10 mg aerosolized rhDNase twice a day for 14 days followed by a 14-day washout period for a total of 6 treatment cycles. Serial determinations of anti-rhDNase antibodies and pulmonary functions were performed.

Interpretation of respiratory input impedance in healthy infants.

Respiratory input impedance (Zin) is a potentially informative test of pulmonary function in infants who are unable to perform standard tests commonly performed in children and adults Analysis of Zin in dogs using the six-element model of DuBois et al. (J Appl Physiol 8:587, 1956) provides estimates of airways resistance separate from tissue resistance, as well as an estimate of thoracic gas volume. However, reliable estimates of these parameters can only be obtained when Zin displays a distinct antiresonance that is associated with the tissue inertance and alveolar gas compression compliance.

Elastin and collagen degradation products in urine of patients with cystic fibrosis.

Elastin degradation has been reported to be increased in patients with cystic fibrosis (CF). In order to further explore evidence for elastin degradation in a group of 18 patients with CF with a wide range of disease severity, we used an isotope dilution method to measure urinary desmosine (DES) and isodesmosine (IDES), amino acids derived exclusively from cross-linked elastin, and hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), amino acids derived exclusively from cross-linked collagen. Urinary DES and IDES (mean +/- SD) were 23.

Correction of the cystic fibrosis defect by gene complementation in human intrahepatic biliary epithelial cell lines.

Background/aims: Hepatobiliary disease is the second most common cause of mortality in patients with cystic fibrosis (CF). In the liver, only the intrahepatic biliary epithelial (IBE) cells express cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. The aim of this study was to determine whether human CF-derived IBE cells can be infected with adenovirus and the CF phenotype complemented.

Efficacy and safety of short-term administration of aerosolized recombinant human deoxyribonuclease in patients with cystic fibrosis.

Chronic endobronchial bacterial infection evokes purulent airway secretions in patients with CF. The viscoelastic properties of these secretions is primarily due to the presence of polymerized DNA from degenerating leukocytes. Recombinant human DNase I (rhDNase) reduces the viscosity of CF sputum in vitro.