16S rRNA-Based Microbiota Profiling Assists Conventional Culture Analysis of Airway Samples from Pediatric Cystic Fibrosis Patients.

16S-based sequencing provides broader information on the respiratory microbial community than conventional culturing. However, it (often) lacks species- and strain-level information. To overcome this issue, we used 16S rRNA-based sequencing results from 246 nasopharyngeal samples obtained from 20 infants with cystic fibrosis (CF) and 43 healthy infants, which were all 0 to 6 months old, and compared them to both standard (blind) diagnostic culturing and a 16S-sequencing-informed "targeted" reculturing approach.

Factors in childhood associated with lung function decline to adolescence in cystic fibrosis.

Background: Despite improvements in general health and life expectancy in people with cystic fibrosis (CF), lung function decline continues unabated during adolescence and early adult life.

Methods: We examined factors present at age 5-years that predicted lung function decline from childhood to adolescence in a longitudinal study of Australasian children with CF followed from 1999 to 2017.

Results: Lung function trajectories were calculated for 119 children with CF from childhood (median 5.

Lung inflammation and simulated airway resistance in infants with cystic fibrosis.

Cystic fibrosis (CF) is characterized by small airway disease; but central airways may also be affected. We hypothesized that airway resistance estimated from computational fluid dynamic (CFD) methodology in infants with CF was higher than controls and that early airway inflammation in infants with CF is associated with airway resistance. Central airway models with a median of 51 bronchial outlets per model (interquartile range 46,56) were created from chest computed tomography scans of 18 infants with CF and 7 controls.

Development of the gut microbiota in early life: The impact of cystic fibrosis and antibiotic treatment.

Objectives: Patients with Cystic Fibrosis (CF) suffer from pancreatic insufficiency, lipid malabsorption and gastrointestinal complaints, next to progressive pulmonary disease. Altered mucosal homoeostasis due to malfunctioning chloride channels results in an adapted microbial composition of the gastrointestinal and the respiratory tract. Additionally, antibiotic treatment has the potential to distort resident microbial communities dramatically.

Efficacy and safety of tobramycin inhalation powder in bronchiectasis patients with P. aeruginosa infection: Design of a dose-finding study (iBEST-1).

In patients with bronchiectasis (BE), infection with Pseudomonas aeruginosa (Pa) results in disease progression, frequent pulmonary exacerbations and lung function decline. However, at present, no inhaled antibiotics have been approved for the treatment of these patients. Tobramycin inhalation powder (TIP), approved for treatment of Pa infection in cystic fibrosis, could be a promising candidate.

Concordance between upper and lower airway microbiota in infants with cystic fibrosis.

Nasopharyngeal and oropharyngeal samples are commonly used to direct therapy for lower respiratory tract infections in non-expectorating infants with cystic fibrosis (CF).We aimed to investigate the concordance between the bacterial community compositions of 25 sets of nasopharyngeal, oropharyngeal and bronchoalveolar lavage (BAL) samples from 17 infants with CF aged ∼5 months (n=13) and ∼12 months (n=12) using conventional culturing and 16S-rRNA sequencing.Clustering analyses demonstrated that BAL microbiota profiles were in general characterised by a mixture of oral and nasopharyngeal bacteria, including commensals like , , and spp.

Maximum inspiratory pressure as a clinically meaningful trial endpoint for neuromuscular diseases: a comprehensive review of the literature.

Respiratory muscle strength is a proven predictor of long-term outcome of neuromuscular disease (NMD), including amyotrophic lateral sclerosis, Duchenne muscular dystrophy, and spinal muscular atrophy. Maximal inspiratory pressure (MIP), a sensitive measure of respiratory muscle strength, one of several useful tests of respiratory muscle strength, is gaining interest as a therapeutic clinical trial endpoint for NMD. In this comprehensive review we investigate the use of MIP as a measure of respiratory muscle strength in clinical trials of therapeutics targeting respiratory muscle, examine the correlation of MIP with survival, quality of life, and other measures of pulmonary function, and outline the role of MIP as a clinically significantly meaningful outcome measure.

The fate of inhaled antibiotics after deposition in cystic fibrosis: How to get drug to the bug?

Background: Chronic airway infections in patients with cystic fibrosis (CF) are most often treated with inhaled antibiotics of which deposition patterns have been extensively studied. However, the journey of aerosol particles does not end after deposition within the bronchial tree.

Objectives: To review how local conditions affect the clinical efficacy of antibiotic aerosol particles after deposition in the airways of patients with CF.

Automatic airway-artery analysis on lung CT to quantify airway wall thickening and bronchiectasis.

Purpose: Bronchiectasis and airway wall thickening are commonly assessed in computed tomography (CT) by comparing the airway size with the size of the accompanying artery. Thus, in order to automate the quantification of bronchiectasis and wall thickening following a similar principle, there is a need for methods that automatically segment the airway and vascular trees, measure their size, and pair each airway branch with its accompanying artery.

Methods: This paper combines and extends existing techniques to present a fully automated pipeline that, given a thoracic chest CT, segments, measures, and pairs airway branches with the accompanying artery, then quantifies airway wall thickening and bronchiectasis by measuring the wall-artery ratio (WAR) and lumen and outer wall airway-artery ratio (AAR).

Quantification of Diaphragm Mechanics in Pompe Disease Using Dynamic 3D MRI.

Background: Diaphragm weakness is the main reason for respiratory dysfunction in patients with Pompe disease, a progressive metabolic myopathy affecting respiratory and limb-girdle muscles. Since respiratory failure is the major cause of death among adult patients, early identification of respiratory muscle involvement is necessary to initiate treatment in time and possibly prevent irreversible damage. In this paper we investigate the suitability of dynamic MR imaging in combination with state-of-the-art image analysis methods to assess respiratory muscle weakness.

Objective airway artery dimensions compared to CT scoring methods assessing structural cystic fibrosis lung disease.

Background: CF-CT and PRAGMA-CF are commonly used scoring methods to quantify the severity of bronchiectasis (BE) and airway wall thickening (AWT) on chest CTs of children with cystic fibrosis (CF). We aimed to validate CF-CT and PRAGMA-CF sub-scores for BE and AWT against quantitative airway–artery (AA) dimensions.

Methods: This is a retrospective study with 23 spirometer guided inspiratory chest CTs (11 CF, 12 controls; age range 6 to 16 years old) included.

Spirometer guided chest imaging in children: It is worth the effort!

Purpose: Computed tomography (CT) and magnetic resonance imaging (MRI) scans are used to assess and monitor several pediatric lung diseases. It is well recognized that lung volume at the moment of acquisition has a major impact on the appearance of lung parenchyma and airways. Importantly, the sensitivity of chest CT and MRI to detect bronchiectasis and gas trapping is highly dependent on adequate volume control during the image acquisition.

Lung CT imaging in patients with bronchopulmonary dysplasia: A systematic review.

Background: Bronchopulmonary dysplasia (BPD) is a common respiratory complication of preterm birth and associated with long-term respiratory sequelae. Chest computed tomography (CT) is a sensitive tool to obtain insight in structural lung abnormalities and may be a predictor for later symptoms.

Objectives: To give an overview of chest CT scoring methods that are used to evaluate chest CT scans of BPD patients.

The development of bronchiectasis on chest computed tomography in children with cystic fibrosis: can pre-stages be identified?

Objective: Bronchiectasis is an important component of cystic fibrosis (CF) lung disease but little is known about its development. We aimed to study the development of bronchiectasis and identify determinants for rapid progression of bronchiectasis on chest CT.

Methods: Forty-three patients with CF with at least four consecutive biennial volumetric CTs were included.

Multicentre chest computed tomography standardisation in children and adolescents with cystic fibrosis: the way forward.

Progressive cystic fibrosis (CF) lung disease is the main cause of mortality in CF patients. CF lung disease starts in early childhood. With current standards of care, respiratory function remains largely normal in children and more sensitive outcome measures are needed to monitor early CF lung disease.

Daily Observations of Nebuliser Use and Technique (DONUT) in children with cystic fibrosis.

Background: Cystic fibrosis (CF) caregivers focus on correct inhalation technique for nebulisers as this is essential to optimize efficacy of inhaled drugs. However, little is known on this nebuliser technique of patients at home.

Methods: Three "hidden" video registrations were made of 32 children with CF (6-18years) nebulising at home.

Diffusion weighted imaging in cystic fibrosis disease: beyond morphological imaging.

Objectives: To explore the feasibility of diffusion-weighted imaging (DWI) to assess inflammatory lung changes in patients with Cystic Fibrosis (CF) METHODS: CF patients referred for their annual check-up had spirometry, chest-CT and MRI on the same day. MRI was performed in a 1.5 T scanner with BLADE and EPI-DWI sequences (b = 0-600 s/mm).

Morphometric Analysis of Explant Lungs in Cystic Fibrosis.

Rationale: After repeated cycles of lung infection and inflammation, patients with cystic fibrosis (CF) evolve to respiratory insufficiency. Although histology and imaging have provided descriptive information, a thorough morphometric analysis of end-stage CF lung disease is lacking.

Objectives: To quantify the involvement of small and large airways in end-stage CF.

Development of the Nasopharyngeal Microbiota in Infants with Cystic Fibrosis.

Rationale: Cystic fibrosis (CF) is characterized by early structural lung disease caused by pulmonary infections. The nasopharynx of infants is a major ecological reservoir of potential respiratory pathogens.

Objectives: To investigate the development of nasopharyngeal microbiota profiles in infants with CF compared with those of healthy control subjects during the first 6 months of life.

Pulmonary ventilation and micro-structural findings in congenital diaphragmatic hernia.

Background: With increasing survival of patients with more severe forms of congenital diaphragmatic hernia (CDH) and risk of long-term respiratory morbidity, studies on lung morphology are needed. We used hyperpolarised (3) He MRI and anatomical (1) H MRI in a cohort of young adult CDH patients to image regional lung ventilation and microstructure, focusing on morphological and micro-structural (alveolar) abnormalities.

Methods: Nine patients with left-sided CDH, born 1975-1993, were studied.

Validating chest MRI to detect and monitor cystic fibrosis lung disease in a pediatric cohort.

Background: Computed Tomography (CT) is the gold standard to assess bronchiectasis and trapped air in cystic fibrosis (CF) lung disease, but has the disadvantage of radiation exposure. Magnetic Resonance Imaging (MRI) is a radiation free alternative.

Objective: To validate MRI as outcome measure by: correlating MRI scores for bronchiectasis and trapped air with clinical parameters, and by comparing those MRI scores with CT scores.

Magnetic resonance imaging in children: common problems and possible solutions for lung and airways imaging.

Pediatric chest MRI is challenging. High-resolution scans of the lungs and airways are compromised by long imaging times, low lung proton density and motion. Low signal is a problem of normal lung.

Respiratory tract exacerbations revisited: ventilation, inflammation, perfusion, and structure (VIPS) monitoring to redefine treatment.

For cystic fibrosis (CF) patients older than 6 years there are convincing data that suggest respiratory tract exacerbations (RTE) play an important role in the progressive loss of functional lung tissue. There is a poor understanding of the pathobiology of RTE and whether specific treatment of RTE reduces lung damage in the long term. In addition, there are limited tools available to measure the various components of CF lung disease and responses to therapy.

Assessment of CF lung disease using motion corrected PROPELLER MRI: a comparison with CT.

Objectives: To date, PROPELLER MRI, a breathing-motion-insensitive technique, has not been assessed for cystic fibrosis (CF) lung disease. We compared this technique to CT for assessing CF lung disease in children and adults.

Methods: Thirty-eight stable CF patients (median 21 years, range 6-51 years, 22 female) underwent MRI and CT on the same day.