Microbiome networks and change-point analysis reveal key community changes associated with cystic fibrosis pulmonary exacerbations.

Over 90% of cystic fibrosis (CF) patients die due to chronic lung infections leading to respiratory failure. The decline in CF lung function is greatly accelerated by intermittent and progressively severe acute pulmonary exacerbations (PEs). Despite their clinical impact, surprisingly few microbiological signals associated with PEs have been identified.

Penicillin-binding protein 3 is a common adaptive target among Pseudomonas aeruginosa isolates from adult cystic fibrosis patients treated with β-lactams.

Objective: Determining the mechanisms that modulate β-lactam resistance in clinical Pseudomonas aeruginosa (P. aeruginosa) isolates can be challenging, as the molecular profiles identified in mutation-based or expression-based resistance determinant screens may not correlate with in vitro phenotypes. One of the lesser studied resistance mechanisms in P.

A genome-wide association analysis reveals a potential role for recombination in the evolution of antimicrobial resistance in Burkholderia multivorans.

Cystic fibrosis (CF) lung infections caused by members of the Burkholderia cepacia complex, such as Burkholderia multivorans, are associated with high rates of mortality and morbidity. We performed a population genomics study of 111 B. multivorans sputum isolates from one CF patient through three stages of infection including an early incident isolate, deep sampling of a one-year period of chronic infection occurring weeks before a lung transplant, and deep sampling of a post-transplant infection.

The Meanings of Helping: An Analysis of Cystic Fibrosis Patients' Reasons for Participating in Biomedical Research.

Research participants often report wanting to help as a reason for participation, but who they want to help and why is rarely explored. We examined meanings associated with helping among 21 adults with cystic fibrosis (CF)-a group with high participation in research. Meanings included helping to advance research, helping others with CF, helping as their job, helping themselves, helping because they are special, and helping to give back.

Clinical Outcomes Associated with Achromobacter Species Infection in Patients with Cystic Fibrosis.

Rationale: Achromobacter species are increasingly identified in individuals with cystic fibrosis (CF), but the clinical outcomes in these patients remain poorly understood.

Objectives: We aimed to determine the association of Achromobacter infection on clinical outcomes in pediatric and adult patients with CF.

Methods: A cohort study of pediatric and adult patients with CF was conducted from 1997 to 2014 in Toronto, Ontario, Canada.

Navigating social and ethical challenges of biobanking for human microbiome research.

Background: Biobanks are considered to be key infrastructures for research development and have generated a lot of debate about their ethical, legal and social implications (ELSI). While the focus has been on human genomic research, rapid advances in human microbiome research further complicate the debate.

Discussion: We draw on two cystic fibrosis biobanks in Toronto, Canada, to illustrate our points.

Continuous alternating inhaled antibiotics for chronic pseudomonal infection in cystic fibrosis.

Background: Inhaled antibiotics are standard of care for treating chronic pseudomonal respiratory infections in cystic fibrosis patients, initially approved for intermittent administration. However, use of continuous inhaled antibiotic regimens of differing combinations is growing.

Methods: This double-blind trial compared continuous alternating therapy (CAT) to an intermittent treatment regimen.

Conducting Effective Physician Performance Feedback: A Primer for Healthcare Leaders.

Physician performance feedback (PPF) can help physicians gain insight into their practice, to identify areas for improvement, and to implement changes to improve care. There is increasing interest in the use of PPF in Canada. However, little is known about the different types of PPF methods and whether PPF can lead to improved physician performance and patient outcomes.

Global Analysis of the Fungal Microbiome in Cystic Fibrosis Patients Reveals Loss of Function of the Transcriptional Repressor Nrg1 as a Mechanism of Pathogen Adaptation.

The microbiome shapes diverse facets of human biology and disease, with the importance of fungi only beginning to be appreciated. Microbial communities infiltrate diverse anatomical sites as with the respiratory tract of healthy humans and those with diseases such as cystic fibrosis, where chronic colonization and infection lead to clinical decline. Although fungi are frequently recovered from cystic fibrosis patient sputum samples and have been associated with deterioration of lung function, understanding of species and population dynamics remains in its infancy.

Selective Sweeps and Parallel Pathoadaptation Drive Pseudomonas aeruginosa Evolution in the Cystic Fibrosis Lung.

Unlabelled: Pulmonary infections caused by Pseudomonas aeruginosa are a recalcitrant problem in cystic fibrosis (CF) patients. While the clinical implications and long-term evolutionary patterns of these infections are well studied, we know little about the short-term population dynamics that enable this pathogen to persist despite aggressive antimicrobial therapy. Here, we describe a short-term population genomic analysis of 233 P.

Effects of Recipient Age and Diagnosis on Health-related Quality-of-Life Benefit of Lung Transplantation.

Rationale: The average age of lung transplant recipients is increasing, and the mix of recipient indications for transplantation is changing.

Objectives: To determine whether the health-related quality-of-life (HRQL) benefit of lung transplantation differs by recipient age and diagnosis.

Methods: In this prospective cohort study, we obtained serial HRQL measurements in adults with advanced lung disease who subsequently underwent lung transplantation (2004-2012).

Inhaled aztreonam for chronic Burkholderia infection in cystic fibrosis: a placebo-controlled trial.

Background: Individuals with Burkholderia spp. infection have historically been excluded from efficacy trials of inhaled antibiotics, including aztreonam for inhalation solution (AZLI).

Methods: A double-blind, placebo-controlled, 24-week trial of continuous AZLI/placebo treatment was undertaken in individuals with cystic fibrosis (CF) and chronic Burkholderia spp.

Analysis of the cystic fibrosis lung microbiota via serial Illumina sequencing of bacterial 16S rRNA hypervariable regions.

The characterization of bacterial communities using DNA sequencing has revolutionized our ability to study microbes in nature and discover the ways in which microbial communities affect ecosystem functioning and human health. Here we describe Serial Illumina Sequencing (SI-Seq): a method for deep sequencing of the bacterial 16S rRNA gene using next-generation sequencing technology. SI-Seq serially sequences portions of the V5, V6 and V7 hypervariable regions from barcoded 16S rRNA amplicons using an Illumina short-read genome analyzer.

Pulmonary bacterial communities in surgically resected noncystic fibrosis bronchiectasis lungs are similar to those in cystic fibrosis.

Background. Recurrent bacterial infections play a key role in the pathogenesis of bronchiectasis, but conventional microbiologic methods may fail to identify pathogens in many cases. We characterized and compared the pulmonary bacterial communities of cystic fibrosis (CF) and non-CF bronchiectasis patients using a culture-independent molecular approach.

Feasibility of internet-based health-related quality of life data collection in a large patient cohort.

Background: Patient registries are commonly used to track survival and medical outcomes in large cohorts. However, large-scale collection of health-related quality of life (HRQOL) data is more challenging because such data must be collected directly from patients. Internet-based HRQOL questionnaires are a potential solution, allowing home data collection with immediate storage in a central database.

Survival of lung transplant patients with cystic fibrosis harboring panresistant bacteria other than Burkholderia cepacia, compared with patients harboring sensitive bacteria.

Background: The impact of panresistant bacteria, other than Burkholderia cepacia, on the survival after lung transplantation in patients with cystic fibrosis (CF) remains controversial.

Methods: To determine the impact of panresistant bacteria in CF patients on survival after lung transplantation a retrospective multicenter study was performed. All lung transplant recipients with a pre-transplant diagnosis of CF, at the University of Toronto (n = 53) and Duke University (n = 50), were included.

Amiloride-insensitive nasal potential difference varies with the menstrual cycle in cystic fibrosis.

Rationale: There is no adequate explanation for gender-based differences in rates of mortality and of deterioration in pulmonary function in cystic fibrosis (CF) patients. One potential explanation is that gender hormones (sex steroids) may modulate the severity of CF lung disease, the principal cause of mortality in CF, by altering respiratory transepithelial ion transport.

Objective: To determine whether respiratory epithelial ion transport varied during the menstrual cycle of CF females.

Clinical manifestations of cystic fibrosis among patients with diagnosis in adulthood.

Objective: To define the clinical characteristics and diagnostic parameters of patients with cystic fibrosis (CF) diagnosed in adulthood.

Design: Retrospective cohort study.

Setting: Tertiary care center.

The repeatability of forced expiratory volume measurements in adults with cystic fibrosis.

Study Objective: To determine the repeatability of measurements of FEV(1) in adults with lung disease due to cystic fibrosis (CF).

Design: Single cohort study nested within a randomized controlled trial.

Setting: Adult CF of a university teaching hospital.

Airway inflammation and infection in congenital bilateral absence of the vas deferens.

In cystic fibrosis (CF), airway disease begins early in life. Bacteria and elevated levels of neutrophils and inflammatory mediators have been detected in bronchoalveolar lavage (BAL) fluid from infants with CF. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) are common in men with congenital bilateral absence of the vas deferens (CBAVD) and it has been suggested that this syndrome represents a mild form of CF.

Pregnancy in cystic fibrosis. Fetal and maternal outcome.

Objective: To assess the effect of pregnancy on pulmonary function and survival in women with cystic fibrosis (CF) and to assess the fetal outcome.

Design: Cohort study. The data analyzed were collected from the Toronto CF database, chart review, and patient questionnaire.

Pulmonary hypertension and cardiac function in adult cystic fibrosis: role of hypoxemia.

Study Objectives: To determine (1) the prevalence of pulmonary hypertension and cardiac dysfunction in adult cystic fibrosis (CF) patients with severe lung disease, (2) the relationship between these cardiovascular abnormalities and hypoxemia, and (3) the impact of subclinical pulmonary hypertension on survival.

Design: Single-blind, cross-sectional study.

Setting: Ambulatory clinic of the Adult CF program at a tertiary-level hospital.

Comparison of culture and PCR for detection of Burkholderia cepacia in sputum samples of patients with cystic fibrosis.

We investigated the utility of PCR to detect Burkholderia cepacia directly in sputum samples at two cystic fibrosis (CF) centers serving children and adults. Following liquefaction of the sputa by using N-acetyl-L-cysteine, DNA was isolated and analyzed by PCRs with three different primer pairs directed toward bacterial rRNA loci. Two primer pairs were putatively specific for B.