The impact of persistent bacterial bronchitis on the pulmonary microbiome of children

Cuthbertson, Leah; Craven, Vanessa; Bingle, Lynne; Cookson, Woc; Everard, Mark L.; Moffatt, Miriam F.

doi:10.1101/181982

Cited by 5 publications

(11 citation statements)

References 26 publications

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“…Our findings are in contrast to a study that found lower alpha diversity in children with PBB (compared with control patients) that was associated with dominance by Haemophilus and Neisseria. 12 The reasons for our contrasting results are unclear, but may reflect specimen and cohort differences. The former study 12 analyzed protected brush specimens that sample less airway surface than BAL 31 and may be less affected by inadvertent upper airway flora contamination.…”

Section: Discussionmentioning

confidence: 90%

“…12 The reasons for our contrasting results are unclear, but may reflect specimen and cohort differences. The former study 12 analyzed protected brush specimens that sample less airway surface than BAL 31 and may be less affected by inadvertent upper airway flora contamination. It is possible that detection of H influenzae at clinically significant levels but low relative abundance in most BALs in our study may reflect contamination by upper respiratory flora; however, this is considered unlikely because a comparison of protected brush, BAL, and oral specimens found that upper airway flora had a minimal effect on BAL microbiota profiles.…”

Section: Discussionmentioning

confidence: 90%

“…16 No studies have examined relationships between alpha diversity and inflammation in children with PBB; however, one study found the respiratory microbiota of children with PBB had lower alpha diversity compared with control patients because of dominance by Haemophilus and Neisseria species. 12 Furthermore, the dominant bacteria in the respiratory microbiota of 37% of children with PBB were not detected by culture. 12 Better understanding of relationships between alpha diversity and lower airway inflammation is important in determining the role of the respiratory microbiota in PBB pathogenesis and in whether microbiota profiling could be used to identify children at risk of recurrent or more severe lung disease.…”

mentioning

confidence: 99%

“…12 Furthermore, the dominant bacteria in the respiratory microbiota of 37% of children with PBB were not detected by culture. 12 Better understanding of relationships between alpha diversity and lower airway inflammation is important in determining the role of the respiratory microbiota in PBB pathogenesis and in whether microbiota profiling could be used to identify children at risk of recurrent or more severe lung disease.…”

mentioning

confidence: 99%

“…1 Important roles for other bacteria are suggested by culture-independent studies that have identified a complex lower airway microbiota that include multiple taxa that are not detected using standard methods, including anaerobic bacteria. [10][11][12] The role of anaerobes in the pathogenesis of chronic respiratory infections is unclear; however, cystic fibrosis (CF) studies report a potentially important role for Prevotella in moderating treatment responses. 13,14 Determining whether the respiratory microbiota contribute to lower airway inflammation or moderate treatment response is potentially important to identifying treatments that can effectively prevent recurrent PBB.…”

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confidence: 99%

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Multiple Respiratory Microbiota Profiles Are Associated With Lower Airway Inflammation in Children With Protracted Bacterial Bronchitis

Marsh

Smith‐Vaughan

Chen

et al. 2019

Chest

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BACKGROUND: Effective management of protracted bacterial bronchitis (PBB) is needed to prevent chronic disease (eg, bronchiectasis). Understanding the contributions of ongoing airway infection and inflammation is important to achieving optimal PBB treatments. The aim of this study was to compare BAL microbiota, bacterial biomass, and inflammatory markers in children with PBB and age-matched control patients.METHODS: BAL was prospectively collected from 28 children with PBB (median age, 1.7 years; range, 0.6-7.4) and 8 control patients (median age, 1.9 years; range, 0.4-4.7). BAL microbiology was determined using culture, 16S ribosomal RNA gene sequencing and bacterial biomass quantification. BAL inflammatory cells, IL-8, and IL-1b were used to assess lower airway inflammation.RESULTS: Bacterial biomass, neutrophil percentage, IL-8, and IL-1b levels were significantly higher in children with PBB compared with control patients. BAL microbiota in children with PBB was significantly different to that of control patients (permutational multivariate analysis of variance P ¼ .001) and clustered into four distinct profiles that were either dominated by a respiratory pathogen or contained a more diverse microbiota including Prevotella species. Alpha diversity was unrelated to bacterial biomass, culture of recognized respiratory pathogens, or inflammatory markers.CONCLUSIONS: Neutrophilic inflammation in children with PBB was associated with multiple BAL microbiota profiles. Significant associations between inflammatory markers and bacterial biomass, but not alpha diversity, suggest that inflammation in children with PBB is not driven by single pathogenic species. Understanding the role of the entire respiratory microbiota in PBB pathogenesis may be important to determining whether bacteria other than the recognized pathogens contribute to disease recurrence and progression to bronchiectasis.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 90%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Multiple Respiratory Microbiota Profiles Are Associated With Lower Airway Inflammation in Children With Protracted Bacterial Bronchitis

Marsh

Smith‐Vaughan

Chen

et al. 2019

Chest

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Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection

Habibi

Thwaites

Chang

et al. 2020

Science

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135

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The variable outcome of viral exposure is only partially explained by known factors. We administered respiratory syncytial virus (RSV) to 58 volunteers, of whom 57% became infected. Mucosal neutrophil activation before exposure was highly predictive of symptomatic RSV disease. This was associated with a rapid, presymptomatic decline in mucosal interleukin-17A (IL-17A) and other mediators. Conversely, those who resisted infection showed presymptomatic activation of IL-17– and tumor necrosis factor–related pathways. Vulnerability to infection was not associated with baseline microbiome but was reproduced in mice by preinfection chemokine-driven airway recruitment of neutrophils, which caused enhanced disease mediated by pulmonary CD8+ T cell infiltration. Thus, mucosal neutrophilic inflammation at the time of RSV exposure enhances susceptibility, revealing dynamic, time-dependent local immune responses before symptom onset and explaining the as-yet unpredictable outcomes of pathogen exposure.

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Seasonal Azithromycin Use in Paediatric Protracted Bacterial Bronchitis Does Not Promote Antimicrobial Resistance but Does Modulate the Nasopharyngeal Microbiome

Hardman,

Shackley,

Ugonna

et al. 2023

IJMS

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Protracted bacterial bronchitis (PBB) causes chronic wet cough for which seasonal azithromycin is increasingly used to reduce exacerbations. We investigated the impact of seasonal azithromycin on antimicrobial resistance and the nasopharyngeal microbiome. In an observational cohort study, 50 children with PBB were enrolled over two consecutive winters; 25/50 at study entry were designated on clinical grounds to take azithromycin over the winter months and 25/50 were not. Serial nasopharyngeal swabs were collected during the study period (12–20 months) and cultured bacterial isolates were assessed for antimicrobial susceptibility. 16S rRNA-based sequencing was performed on a subset of samples. Irrespective of azithromycin usage, high levels of azithromycin resistance were found; 73% of bacteria from swabs in the azithromycin group vs. 69% in the comparison group. Resistance was predominantly driven by azithromycin-resistant S. pneumoniae, yet these isolates were mostly erythromycin susceptible. Analysis of 16S rRNA-based sequencing revealed a reduction in within-sample diversity in response to azithromycin, but only in samples of children actively taking azithromycin at the time of swab collection. Actively taking azithromycin at the time of swab collection significantly contributed to dissimilarity in bacterial community composition. The discrepancy between laboratory detection of azithromycin and erythromycin resistance in the S. pneumoniae isolates requires further investigation. Seasonal azithromycin for PBB did not promote antimicrobial resistance over the study period, but did perturb the microbiome.

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The impact of persistent bacterial bronchitis on the pulmonary microbiome of children

Cited by 5 publications

References 26 publications

Multiple Respiratory Microbiota Profiles Are Associated With Lower Airway Inflammation in Children With Protracted Bacterial Bronchitis

Multiple Respiratory Microbiota Profiles Are Associated With Lower Airway Inflammation in Children With Protracted Bacterial Bronchitis

Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection

Seasonal Azithromycin Use in Paediatric Protracted Bacterial Bronchitis Does Not Promote Antimicrobial Resistance but Does Modulate the Nasopharyngeal Microbiome

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