Modulation, microbiota and inflammation in the adult CF gut: A prospective study.

BACKGROUND: Cystic Fibrosis (CF) has prominent gastrointestinal and pancreatic manifestations. The aim of this study was to determine the effect of Cystic fibrosis transmembrane conductance regulator (CFTR) modulation on, gastrointestinal inflammation, pancreatic function and gut microbiota composition in people with cystic fibrosis (CF) and the G551D-CFTR mutation. METHODS: Fourteen adult patients with the G551D-CFTR mutation were assessed clinically at baseline and for up to 1 year after treatment with ivacaftor. The change in gut inflammatory markers (calprotectin and lactoferrin), exocrine pancreatic status and gut microbiota composition and structure were assessed in stool samples. RESULTS: There was no significant change in faecal calprotectin nor lactoferrin in patients with treatment while all patients remained severely pancreatic insufficient. There was no significant change in gut microbiota diversity and richness following treatment. CONCLUSION: There was no significant change in gut inflammation after partial restoration of CFTR function with ivacaftor, suggesting that excess gut inflammation in CF is multi-factorial in aetiology. In this adult cohort, exocrine pancreatic function was irreversibly lost. Longer term follow-up may reveal more dynamic changes in the gut microbiota and possible restoration of CFTR function.

Ultra-low-dose thoracic CT with model-based iterative reconstruction (MBIR) in cystic fibrosis patients undergoing treatment with cystic fibrosis transmembrane conductance regulators (CFTR).

AIM: To assess the utility of a volumetric low-dose computed tomography (CT) thorax (LDCTT) protocol at a dose equivalent to a posteroanterior (PA) and lateral chest radiograph for surveillance of cystic fibrosis (CF) patients. MATERIALS AND METHODS: A prospective study was undertaken of 19 adult patients with CF that proceeded to LDCTT at 12 and 24 months following initiation of ivacaftor. A previously validated seven-section, low-dose axial CT protocol was used for the 12-month study. A volumetric LDCTT protocol was developed for the 24-month study and reconstructed with hybrid iterative reconstruction (LD-ASIR) and pure iterative reconstruction (model-based IR [LD-MBIR]). Radiation dose was recorded for each scan. Image quality was assessed quantitatively and qualitatively, and disease severity was assessed using a modified Bhalla score. Statistical analysis was performed and p-values of <0.05 were considered statistically significant. RESULTS: Volumetric LD-MBIR studies were acquired at a lower radiation dose than the seven-section studies (0.08 ± 0.01 versus 0.10 ± 0.02 mSv; p=0.02). LD-MBIR and seven-section ASIR images had significantly lower levels of image noise compared with LD-ASIR images (p<0.0001). Diagnostic acceptability scores and depiction of bronchovascular structures were found to be acceptable for axial and coronal LD-MBIR images. LD-MBIR images were superior to LD-ASIR images for all qualitative parameters assessed (p<0.0001). No significant change was observed in mean Bhalla score between 1-year and 2-year studies (p=0.84). CONCLUSIONS: The use of a volumetric LDCTT protocol (reconstructed with pure IR) enabled acquisition of diagnostic quality CT images, which were considered extremely useful for surveillance of CF patients, at a dose equivalent to a PA and lateral chest radiograph.

A pilot study demonstrating the altered gut microbiota functionality in stable adults with Cystic Fibrosis.

Cystic Fibrosis (CF) and its treatment result in an altered gut microbiota composition compared to non-CF controls. However, the impact of this on gut microbiota functionality has not been extensively characterised. Our aim was to conduct a proof-of-principle study to investigate if measurable changes in gut microbiota functionality occur in adult CF patients compared to controls. Metagenomic DNA was extracted from faecal samples from six CF patients and six non-CF controls and shotgun metagenomic sequencing was performed on the MiSeq platform. Metabolomic analysis using gas chromatography-mass spectrometry was conducted on faecal water. The gut microbiota of the CF group was significantly different compared to the non-CF controls, with significantly increased Firmicutes and decreased Bacteroidetes. Functionality was altered, with higher pathway abundances and gene families involved in lipid (e.g. PWY 6284 unsaturated fatty acid biosynthesis (p = 0.016)) and xenobiotic metabolism (e.g. PWY-5430 meta-cleavage pathway of aromatic compounds (p = 0.004)) in CF patients compared to the controls. Significant differences in metabolites occurred between the two groups. This proof-of-principle study demonstrates that measurable changes in gut microbiota functionality occur in CF patients compared to controls. Larger studies are thus needed to interrogate this further.

A Study To Assess The Prevalence Of Exercise-Induced Bronchoconstriction In Inter-County Hurling.

Exercise-Induced Bronchoconstriction (EIB) is an acute, transient airway narrowing occurring after exercise which may impact athletic performance. Studies report 10% of the general population and up to 90% of asthmatics experience EIB. Ninety-two players from three elite hurling squads underwent a spirometric field-based provocation test with real-time heart rate monitoring and lactate measurements to ensure adequate exertion. Players with a new diagnosis of EIB and those with a negative field-test but with a previous label of EIB or asthma underwent further reversibility testing and if negative, methacholine challenge. Eight (8.7%) of players had EIB, with one further athlete having asthma with a negative field test. Interestingly, only three out of 12 players who had previously been physician-labelled with EIB or asthma had their diagnosis objectively confirmed. Our study highlights the role of objective testing in EIB.