scholarly journals Untargeted Metagenomic Investigation of the Airway Microbiome of Cystic Fibrosis Patients with Moderate-Severe Lung Disease

2020 ◽  
Vol 8 (7) ◽  
pp. 1003 ◽  
Author(s):  
Giovanni Bacci ◽  
Giovanni Taccetti ◽  
Daniela Dolce ◽  
Federica Armanini ◽  
Nicola Segata ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Temporal Dynamics ◽  
Clinical Status ◽  
Antibiotic Resistance Genes ◽  
Lower Airway ◽  
Metagenomic Sequencing ◽  
Taxonomic Profiling ◽  
Shotgun Metagenomic Sequencing ◽  
Airway Microbiome

Although the cystic fibrosis (CF) lung microbiota has been characterized in several studies, little is still known about the temporal changes occurring at the whole microbiome level using untargeted metagenomic analysis. The aim of this study was to investigate the taxonomic and functional temporal dynamics of the lower airway microbiome in a cohort of CF patients. Multiple sputum samples were collected over 15 months from 22 patients with advanced lung disease regularly attending three Italian CF Centers, given a total of 79 samples. DNA extracted from samples was subjected to shotgun metagenomic sequencing allowing both strain-level taxonomic profiling and assessment of the functional metagenomic repertoire. High inter-patient taxonomic heterogeneity was found with short-term compositional changes across clinical status. Each patient exhibited distinct sputum microbial communities at the taxonomic level, and strain-specific colonization of both traditional and atypical CF pathogens. A large core set of genes, including antibiotic resistance genes, were shared across patients despite observed differences in clinical status, and consistently detected in the lung microbiome of all subjects independently from known antibiotic exposure. In conclusion, an overall stability in the microbiome-associated genes was found despite taxonomic fluctuations of the communities.

scholarly journals The lower airway microbiota in early cystic fibrosis lung disease: a longitudinal analysis

Thorax ◽  
2017 ◽  
Vol 72 (12) ◽  
pp. 1104-1112 ◽  
Author(s):  
Katherine B Frayman ◽  
David S Armstrong ◽  
Rosemary Carzino ◽  
Thomas W Ferkol ◽  
Keith Grimwood ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Longitudinal Analysis ◽  
Cystic Fibrosis Lung ◽  
Lower Airway ◽  
Cystic Fibrosis Lung Disease

scholarly journals Fungal Infection and Inflammation in Cystic Fibrosis

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 618
Author(s):  
T. Spencer Poore ◽  
Gina Hong ◽  
Edith T. Zemanick
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Clinical Outcomes ◽  
Fungal Infections ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Lower Airway ◽  
Future Research ◽  
Isolation And Identification ◽  
Helper Cell Type

Fungi are frequently recovered from lower airway samples from people with cystic fibrosis (CF), yet the role of fungi in the progression of lung disease is debated. Recent studies suggest worsening clinical outcomes associated with airway fungal detection, although most studies to date are retrospective or observational. The presence of fungi can elicit a T helper cell type 2 (Th-2) mediated inflammatory reaction known as allergic bronchopulmonary aspergillosis (ABPA), particularly in those with a genetic atopic predisposition. In this review, we discuss the epidemiology of fungal infections in people with CF, risk factors associated with development of fungal infections, and microbiologic approaches for isolation and identification of fungi. We review the spectrum of fungal disease presentations, clinical outcomes after isolation of fungi from airway samples, and the importance of considering airway co-infections. Finally, we discuss the association between fungi and airway inflammation highlighting gaps in knowledge and future research questions that may further elucidate the role of fungus in lung disease progression.

scholarly journals Respiratory infection rates differ between geographically distant paediatric cystic fibrosis cohorts

2016 ◽  
Vol 2 (3) ◽  
pp. 00014-2016 ◽  
Author(s):  
Kathryn A. Ramsey ◽  
Emily Hart ◽  
Lidija Turkovic ◽  
Marc Padros-Goossens ◽  
Stephen M. Stick ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Respiratory Infections ◽  
Age Groups ◽  
Similar Rate ◽  
Lower Airway ◽  
Annual Review ◽  
Respiratory Pathogens ◽  
Geographical Differences ◽  
Old Patients

Respiratory infections are a major cause of pulmonary decline in children with cystic fibrosis (CF). We compared the prevalence of infection in early life at geographically distant CF treatment centres participating in the same surveillance programme in Australia.Lower airway microbiology, inflammation and structural lung disease at annual review were evaluated for 260 children 0–8 years old with CF at 1032 visits to CF treatment centres in Melbourne or Perth.Melbourne patients were more likely to be culture-positive for common respiratory pathogens at all age groups (odds ratio (OR) 1.85, 95% CI 1.33–2.58). Subjects <2 years old in Melbourne were also more likely to have neutrophil elastase present (OR 3.11, 95% CI 1.62–5.95). Bronchiectasis (OR 2.02, 95% CI 1.21–3.38) and air trapping (OR 2.53, 95% CI 1.42–4.51) in subjects 2–5 years old was more common in Melbourne subjects. The severity of structural lung disease was also worse in Melbourne patients >5 years old. Patients at both centres had a similar rate of hospitalisations and prescribed antibiotics.No procedural differences were identified that could explain the disparity between pathogen prevalence. Geographical differences in early acquisition of infection may contribute to variability in outcomes between CF centres.

scholarly journals The clinical significance of oropharyngeal cultures in young children with cystic fibrosis

2018 ◽  
Vol 51 (5) ◽  
pp. 1800238 ◽  
Author(s):  
Oded Breuer ◽  
Daan Caudri ◽  
Lauren Akesson ◽  
Sarath Ranganathan ◽  
Stephen M. Stick ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Cystic Fibrosis ◽  
Lung Disease ◽  
Neutrophil Elastase ◽  
Lung Inflammation ◽  
Interleukin 8 ◽  
Lower Airway ◽  
Increased Risk ◽  
Post Test ◽  
Respiratory Exacerbations

In children with cystic fibrosis (CF) the associations between oropharyngeal swabs (OPSs) for detection of Pseudomonas and lung disease have not been evaluated.OPS and bronchoalveolar lavage (BAL) samples were obtained annually in children with CF from 2005 to 2017. OPS test characteristics were calculated using BAL as “gold standard”. Results were related to lung inflammation (BAL neutrophil elastase and interleukin-8), structural lung disease (chest computed tomography PRAGMA-CF (Perth–Rotterdam Annotated Grid Morphometric Analysis for CF) scores), respiratory exacerbations and future detection of Pseudomonas on BAL.From 181 patients, 690 paired OPS–BAL cultures were obtained. Prevalence of Pseudomonas in BAL was 7.4%. OPS sensitivity was 23.0% and specificity was 91.4%, reducing the post-test probability for a positive BAL following a negative OPS to 6.3%. Pseudomonas on OPS was not associated with lung inflammation or respiratory exacerbations, but was weakly associated with current PRAGMA-CF %Disease score (p=0.043). Pseudomonas on BAL was associated with positive neutrophil elastase (OR 4.17, 95% CI 2.04–8.53; p<0.001), increased interleukin-8 (p<0.001), increased all baseline PRAGMA computed tomography scores (p<0.001), progression of PRAGMA computed tomography scores (p<0.05) and increased risk of respiratory exacerbations (incidence rate ratio 2.11, 95% CI 1.15–3.87; p=0.017).In children with CF OPSs only marginally change the probability of detecting lower airway Pseudomonas and are not associated with lung disease indices nor exacerbations risk.

scholarly journals Upper versus lower airway microbiome and metagenome in children with cystic fibrosis and their correlation with lung inflammation

PLoS ONE ◽  
2019 ◽  
Vol 14 (9) ◽  
pp. e0222323 ◽  
Author(s):  
Mariana E. Kirst ◽  
Dawn Baker ◽  
Eric Li ◽  
Mutasim Abu-Hasan ◽  
Gary P. Wang
Keyword(s):  
Cystic Fibrosis ◽  
Lung Inflammation ◽  
Lower Airway ◽  
Airway Microbiome

Ceramide Is Increased in the Lower Airway Epithelium of People with Advanced Cystic Fibrosis Lung Disease

2010 ◽  
Vol 182 (3) ◽  
pp. 369-375 ◽  
Author(s):  
Malcolm Brodlie ◽  
Michael C. McKean ◽  
Gail E. Johnson ◽  
Joe Gray ◽  
Andrew J. Fisher ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Airway Epithelium ◽  
Cystic Fibrosis Lung ◽  
Lower Airway ◽  
Cystic Fibrosis Lung Disease

scholarly journals Taxonomic variability over functional stability in the microbiome of Cystic Fibrosis patients chronically infected by Pseudomonas aeruginosa

2019 ◽  
Author(s):  
Giovanni Bacci ◽  
Giovanni Taccetti ◽  
Daniela Dolce ◽  
Federica Armanini ◽  
Nicola Segata ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Antibiotic Treatment ◽  
Clinical Status ◽  
Patient Specific ◽  
Metagenomic Sequencing ◽  
Antibiotic Exposure ◽  
Large Core ◽  
Microbial Composition ◽  
Lung Microbiome ◽  
Core Set

AbstractAlthough the cystic fibrosis (CF) lung microbiome has been characterized in several studies, little is still known about the functions harboured by those bacteria, and how they change with disease status and antibiotic treatment. The aim of this study was to investigate the taxonomic and functional temporal dynamics of airways microbiome in a cohort of CF patients. Multiple sputum samples were collected over 15 months from 22 patients with chronic P. aeruginosa infection, for a total of 79 samples. DNA extracted from samples was subjected to shotgun metagenomic sequencing allowing either strain-level taxonomic profiling and assessment of the functional metagenomic repertoire. High inter-patient taxonomic heterogeneity was found with short-term compositional changes during exacerbations and following antibiotic treatment. Each patient exhibited distinct sputum microbial communities at the taxonomic level, and strain-specific colonization of traditional CF pathogens, including P. aeruginosa, and emerging pathogens. Sputum microbiome was found to be extraordinarily resilient following antibiotic treatment, with rapid recovery of taxa and metagenome-associated gene functions. In particular, a large core set of genes, including antibiotic resistance genes, were shared across patients despite observed differences in clinical status or antibiotic treatment, and constantly detected in the lung microbiome of all subjects independently from known antibiotic exposure, suggesting an overall microbiome-associated functions stability despite taxonomic fluctuations of the communities.IMPORTANCEWhile the dynamics of CF sputum microbial composition were highly patient-specific, the overall sputum metagenome composition was stable, showing a high resilience along time and antibiotic exposure. The high degree of redundancy in the CF lung microbiome could testifies ecological aspects connected to the disease that were never considered so far, as the large core-set of genes shared between patients despite observed differences in clinical status or antibiotic treatment. Investigations on the actual functionality (e.g. by metatranscriptomics) of the identified core-set of genes could provide clues on genetic function of the microbiome to be targeted in future therapeutic treatments.

scholarly journals Cystic fibrosis microbiome: analysis of nasal middle meatus and sputum in different lung disease stages

2020 ◽  
Vol 3 (3) ◽  
pp. 225-237
Author(s):  
F.G.O. Maestrali ◽  
R.R.M. Pilan ◽  
R. Athanazio ◽  
L.G. Sparvoli ◽  
R.V. Cortez ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Advanced Disease ◽  
Respiratory Infections ◽  
Middle Meatus ◽  
Culture Methods ◽  
Microbiome Composition ◽  
Conventional Culture ◽  
Culture Independent ◽  
Airway Microbiome

BACKGROUND: Culture independent methods of molecular detection of microbiome have shown the polymicrobial nature of respiratory infections in cystic fibrosis, with pathogenic agents undetectable in conventional culture methods. Composition and diversity of the airway microbiome are still poorly understood. METHODOLOGY: This study evaluated the airway microbiome in 31 adult cystic fibrosis patients via the analysis of 16S rRNA se- quences by next generation sequencing. RESULTS: Staphylococcus, Streptococcus and Corynebacterium were the most abundant genera in the middle meatus, and Pseudo- monas, Haemophilus and Prevotella were the most abundant in sputum. In patients with advanced disease (FEV1< 50%), there was an increase in the prevalence of Pseudomonas in both sample types when studied separately. In each patient, in a paired analysis, the sputum and middle meatus showed similar microbiome composition in mild or moderate disease (FEV1≥ 50%). In patients with severe lung disease, the relative abundance of Pseudomonas had a positive correlation in both collection sites. CONCLUSIONS: This is the first Brazilian study to evaluate the airway microbiome in cystic fibrosis patients. Our findings agree with those in the international literature and indicate the role of Pseudomonas in the sputum and middle meatus in patients with advanced disease.

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