Comparison of microbial composition of cough swabs and sputum for pathogen detection in patients with cystic fibrosis

Fenn, Dominic; Abdel‐Aziz, Mahmoud I.; Brinkman, Paul; R, Kós; Neerincx, Anne H.; Altenburg, Josje; Weersink, Els J.M.; Haarman, Eric G.; Terheggen-Lagro, Suzanne; Zee, Anke‐Hilse Maitland‐van der; Bos, Lieuwe D. J.

doi:10.1016/j.jcf.2021.08.031

Cited by 7 publications

(4 citation statements)

References 39 publications

(50 reference statements)

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“…Duplicate PCRs of the 16s rRNA gene region V4–V5 were performed as described before [ 24 , 25 ]. In brief, the PowerFecal DNA Kit (Qiagen, Venlo, Netherlands) was used for DNA extraction of BALF before PCR amplification using the Illumina MiSeq platform (CGEB-Integrated Microbiome Resource, Halifax, Canada) and primer pair 515F/926R was performed [ 26 , 27 ].…”

Section: Reference Standard and Pathogen Selectionmentioning

confidence: 99%

Composition and diversity analysis of the lung microbiome in patients with suspected ventilator-associated pneumonia

et al. 2022

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Background Ventilator-associated pneumonia (VAP) is associated with high morbidity and health care costs, yet diagnosis remains a challenge. Analysis of airway microbiota by amplicon sequencing provides a possible solution, as pneumonia is characterised by a disruption of the microbiome. However, studies evaluating the diagnostic capabilities of microbiome analysis are limited, with a lack of alignment on possible biomarkers. Using bronchoalveolar lavage fluid (BALF) from ventilated adult patients suspected of VAP, we aimed to explore how key characteristics of the microbiome differ between patients with positive and negative BALF cultures and whether any differences could have a clinically relevant role. Methods BALF from patients suspected of VAP was analysed using 16s rRNA sequencing in order to: (1) differentiate between patients with and without a positive culture; (2) determine if there was any association between microbiome diversity and local inflammatory response; and (3) correctly identify pathogens detected by conventional culture. Results Thirty-seven of 90 ICU patients with suspected VAP had positive cultures. Patients with a positive culture had significant microbiome dysbiosis with reduced alpha diversity. However, gross compositional variance was not strongly associated with culture positivity (AUROCC range 0.66–0.71). Patients with a positive culture had a significantly higher relative abundance of pathogenic bacteria compared to those without [0.45 (IQR 0.10–0.84), 0.02 (IQR 0.004–0.09), respectively], and an increased interleukin (IL)-1β was associated with reduced species evenness (rs = − 0.33, p < 0.01) and increased pathogenic bacteria presence (rs = 0.28, p = 0.013). Untargeted 16s rRNA pathogen detection was limited by false positives, while the use of pathogen-specific relative abundance thresholds showed better diagnostic accuracy (AUROCC range 0.89–0.998). Conclusion Patients with positive BALF culture had increased dysbiosis and genus dominance. An increased caspase-1-dependent IL-1b expression was associated with a reduced species evenness and increased pathogenic bacterial presence, providing a possible causal link between microbiome dysbiosis and lung injury development in VAP. However, measures of diversity were an unreliable predictor of culture positivity and 16s sequencing used agnostically could not usefully identify pathogens; this could be overcome if pathogen-specific relative abundance thresholds are used.

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Section: Reference Standard and Pathogen Selectionmentioning

confidence: 99%

Composition and diversity analysis of the lung microbiome in patients with suspected ventilator-associated pneumonia

et al. 2022

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“…Cough swabs are easy to collect and have long been used as a pediatric surveillance tool [ 20 , 21 ]. Recently, paired cough swabs and sputum samples from a cohort of pediatric and adult pwCF were assessed for microbiome composition and validity between testing modalities [ 22 ]. Despite similar diversity measures, poor concordance between swabs and sputum to discern CF pathogens was observed.…”

Section: Evaluation Of the Cf Microbiome: Evolving Sampling Strategiesmentioning

confidence: 99%

Exploring the Cystic Fibrosis Lung Microbiome: Making the Most of a Sticky Situation

Thornton

Acosta

Surette

et al. 2022

Journal of the Pediatric Infectious Diseases Society

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Chronic lower respiratory tract infections are a leading contributor to morbidity and mortality in persons with cystic fibrosis (pwCF). Traditional respiratory tract surveillance culturing has focused on a limited range of classic pathogens; however, comprehensive culture and culture-independent molecular approaches have demonstrated complex communities highly unique to each individual. Microbial community structure evolves through the lifetime of pwCF and is associated with baseline disease state and rates of disease progression including occurrence of pulmonary exacerbations. While molecular analysis of the airway microbiome has provided insight into these dynamics, challenges remain including discerning not only “who is there” but “what they are doing” in relation to disease progression. Moreover, the microbiome can be leveraged as a multi-modal biomarker for both disease activity and prognostication. In this article, we review our evolving understanding of the role these communities play in pwCF and identify challenges in translating microbiome data to clinical practice.

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“…However, detection of P. aeruginosa is especially challenging in children who often cannot expectorate sputum. Additional tools for detecting organisms such as P. aeruginosa may improve treatment strategies (Fenn et al, 2021). Laryngeal aspirates could potentially play a part in this; however, these are not routinely performed in many centers (Crowley, Holgersen, & Nielsen, 2019; Hanshew, Jetté, Tadayon, & Thibeault, 2017).…”

Section: Discussionmentioning

confidence: 99%

Primary ciliary dyskinesia in Volendam: Diagnostic and phenotypic features in patients with a CCDC114 mutation

Israëls

Gogh

et al. 2022

American J of Med Genetics Pt C

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Primary ciliary dyskinesia (PCD) is a heterogeneous disease, with impaired mucociliary clearance causing respiratory tract infections. A founding CCDC114 mutation has led to a relatively homogeneous and large Dutch PCD population in Volendam. Our aim was to describe their phenotype. Therefore, all Volendam PCD patients seen at the Amsterdam UMC were included in this study. Data were collected on lung function, microbiology, radiology, and ear-nose-throat (ENT) symptoms. A mixed effects model estimated lung function decline in %point per year (95% confidence interval [CI]). Thirty-three (60%) out of approximately 56 Volendam PCD patients were treated at our center and included in this study. Only 30% of patients had situs inversus. FEV 1 declined in children (À1.43%/year, CI: À1.80/À1.05), but not in adults (0.01%/year, CI: À0.36/0.38). Pseudomonas aeruginosa was cultured in 21% of children and 60% of adults, respectively. Patients who have been infected at some point with P. aeruginosa had a steeper decline in FEV 1 as compared to patients that have never been infected. Neonatal symptoms (79%) and ENT problems (94%) were common; fertility issues however, were not (11%) common. Compared to other PCD cohorts, the Volendam/CCDC114 patients have a moderately severe phenotype with lung function decline predominantly occurring in childhood.

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Comparison of microbial composition of cough swabs and sputum for pathogen detection in patients with cystic fibrosis

Cited by 7 publications

References 39 publications

Composition and diversity analysis of the lung microbiome in patients with suspected ventilator-associated pneumonia

Composition and diversity analysis of the lung microbiome in patients with suspected ventilator-associated pneumonia

Exploring the Cystic Fibrosis Lung Microbiome: Making the Most of a Sticky Situation

Primary ciliary dyskinesia in Volendam: Diagnostic and phenotypic features in patients with a CCDC114 mutation

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