Prevalence and subtyping of biofilms present in bronchoalveolar lavage from children with protracted bacterial bronchitis or non-cystic fibrosis bronchiectasis: a cross-sectional study

Summary: Background: Lower airway biofilms are hypothesised to contribute to poor treatment outcomes among children with chronic lung disease; however, data are scarce. We aimed to determine the presence and prevalence of biofilm in bronchoalveolar lavage from children with protracted bacterial bro...

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Main Authors: Robyn L Marsh, PhD, Michael J Binks, PhD, Heidi C Smith-Vaughan, PhD, Maxine Janka, BSc, Sharon Clark, BBioMedSc, Peter Richmond, ProfMD, Anne B Chang, ProfPhD, Ruth B Thornton, PhD
Format: Article
Language:English
Published: Elsevier 2022-03-01
Series:The Lancet Microbe
Online Access:http://www.sciencedirect.com/science/article/pii/S2666524721003001
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author Robyn L Marsh, PhD
Michael J Binks, PhD
Heidi C Smith-Vaughan, PhD
Maxine Janka, BSc
Sharon Clark, BBioMedSc
Peter Richmond, ProfMD
Anne B Chang, ProfPhD
Ruth B Thornton, PhD
author_facet Robyn L Marsh, PhD
Michael J Binks, PhD
Heidi C Smith-Vaughan, PhD
Maxine Janka, BSc
Sharon Clark, BBioMedSc
Peter Richmond, ProfMD
Anne B Chang, ProfPhD
Ruth B Thornton, PhD
author_sort Robyn L Marsh, PhD
collection DOAJ
description Summary: Background: Lower airway biofilms are hypothesised to contribute to poor treatment outcomes among children with chronic lung disease; however, data are scarce. We aimed to determine the presence and prevalence of biofilm in bronchoalveolar lavage from children with protracted bacterial bronchitis (PBB) or bronchiectasis; whether biofilm was associated with signs of lower airway infection; and whether biofilms were consistent with an upper or lower airway origin. Methods: In this cross-sectional study, fluorescent microscopy techniques were used to detect biofilm in archived bronchoalveolar lavage specimens from a paediatric cohort (age <18 years) with PBB or bronchiectasis who were prospectively recruited to observational studies of chronic cough at Royal Children's Hospital (Brisbane, Australia) or Royal Darwin Hospital (Darwin, Australia). Children with cystic fibrosis were excluded. Lower airway infection was defined as bronchoalveolar lavage neutrophil percentage of 15% or more, or a culture of a bacterial pathogen at 104 colony-forming units per mL or more, or both. Biofilms were subtyped as either of lower airway origin (unrelated to squamous epithelial cells) or of upper airway origin (observed in close association with squamous epithelial cells). Bronchoalveolar lavages were considered contaminated with upper airway secretions if the squamous cell proportion was more than ten cells per 1000 nucleated cells (>1%). Primary outcomes were the prevalence of each biofilm subtype among children with PBB compared with children with bronchiectasis. Secondary outcomes were the prevalence of each biofilm subtype among children with signs of lower airway infection compared to children without. Findings: Biofilm testing was performed on 144 bronchoalveolar lavage specimens collected between Jan 1, 2011, and Dec 16, 2014, and preserved at −80°C before biofilm testing (69 children with PBB from Brisbane and 75 children with bronchiectasis from Darwin). The prevalence of lower airway biofilms (unrelated to squamous epithelial cells) was similar among the children with PBB (25 [36%] of 69) and children with bronchiectasis (31 [41%] of 75; odds ratio [OR] 1·24, 95% CI 0·63–2·43), but higher among children with signs of lower airway infection (46 [48%] of 95) than children without (eight [19%] of 43; OR 4·11, 95% CI 1·73–9·78), irrespective of the underlying diagnosis. By contrast, upper airway biofilms (associated with squamous epithelial cells) were more prevalent among children with bronchiectasis (32 [43%] of 75) than children with PBB (16 [23%] of 69; OR 2·47, 95% CI 1·20–5·08) and were unrelated to lower airway infection. Upper airway contamination was uncommon (eight [11%] of 71) and was not evident in 23 (79%) of 29 bronchoalveolar lavages that were positive for upper airway biofilms. Interpretation: Lower airway biofilms are prevalent, but not ubiquitous, in bronchoalveolar lavage from children with PBB or bronchiectasis, suggesting anti-biofilm therapies might be beneficial for some children. Detection of upper airway biofilms in bronchoalveolar lavage that did not have signs of contamination suggests that microaspiration might be important in some children. Specimen quality measures are recommended for future studies to account for the presence of upper airway biofilms. Funding: Financial Markets for Children Project Grant, National Health and Medical Research Council of Australia, Rebecca L Cooper Medical Research Foundation, Queensland Children's Hospital Foundation, and BrightSpark Foundation.
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spelling doaj.art-7b5c8beee47547b8b828a07502f4b5822022-12-22T01:40:42ZengElsevierThe Lancet Microbe2666-52472022-03-0133e215e223Prevalence and subtyping of biofilms present in bronchoalveolar lavage from children with protracted bacterial bronchitis or non-cystic fibrosis bronchiectasis: a cross-sectional studyRobyn L Marsh, PhD0Michael J Binks, PhD1Heidi C Smith-Vaughan, PhD2Maxine Janka, BSc3Sharon Clark, BBioMedSc4Peter Richmond, ProfMD5Anne B Chang, ProfPhD6Ruth B Thornton, PhD7Child Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia; Correspondence to: Dr Robyn Marsh, Child Health Division, Menzies School of Health Research, PO Box 41096, Casuarina, NT 0814, AustraliaChild Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, AustraliaChild Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia; School of Medicine, Griffith University, Gold Coast Campus, Southport, QLD, AustraliaWesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, WA, AustraliaWesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, WA, Australia; School of Medicine, Division of Paediatrics, University of Western Australia, Perth, WA, AustraliaWesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, WA, Australia; School of Medicine, Division of Paediatrics, University of Western Australia, Perth, WA, AustraliaChild Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia; Department of Respiratory and Sleep Medicine, Queensland Children's Hospital and Australian Centre for Health Services Innovation, Queensland University of Technology, Brisbane, QLD, AustraliaWesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, WA, Australia; Centre for Child Health Research, University of Western Australia, Perth, WA, AustraliaSummary: Background: Lower airway biofilms are hypothesised to contribute to poor treatment outcomes among children with chronic lung disease; however, data are scarce. We aimed to determine the presence and prevalence of biofilm in bronchoalveolar lavage from children with protracted bacterial bronchitis (PBB) or bronchiectasis; whether biofilm was associated with signs of lower airway infection; and whether biofilms were consistent with an upper or lower airway origin. Methods: In this cross-sectional study, fluorescent microscopy techniques were used to detect biofilm in archived bronchoalveolar lavage specimens from a paediatric cohort (age <18 years) with PBB or bronchiectasis who were prospectively recruited to observational studies of chronic cough at Royal Children's Hospital (Brisbane, Australia) or Royal Darwin Hospital (Darwin, Australia). Children with cystic fibrosis were excluded. Lower airway infection was defined as bronchoalveolar lavage neutrophil percentage of 15% or more, or a culture of a bacterial pathogen at 104 colony-forming units per mL or more, or both. Biofilms were subtyped as either of lower airway origin (unrelated to squamous epithelial cells) or of upper airway origin (observed in close association with squamous epithelial cells). Bronchoalveolar lavages were considered contaminated with upper airway secretions if the squamous cell proportion was more than ten cells per 1000 nucleated cells (>1%). Primary outcomes were the prevalence of each biofilm subtype among children with PBB compared with children with bronchiectasis. Secondary outcomes were the prevalence of each biofilm subtype among children with signs of lower airway infection compared to children without. Findings: Biofilm testing was performed on 144 bronchoalveolar lavage specimens collected between Jan 1, 2011, and Dec 16, 2014, and preserved at −80°C before biofilm testing (69 children with PBB from Brisbane and 75 children with bronchiectasis from Darwin). The prevalence of lower airway biofilms (unrelated to squamous epithelial cells) was similar among the children with PBB (25 [36%] of 69) and children with bronchiectasis (31 [41%] of 75; odds ratio [OR] 1·24, 95% CI 0·63–2·43), but higher among children with signs of lower airway infection (46 [48%] of 95) than children without (eight [19%] of 43; OR 4·11, 95% CI 1·73–9·78), irrespective of the underlying diagnosis. By contrast, upper airway biofilms (associated with squamous epithelial cells) were more prevalent among children with bronchiectasis (32 [43%] of 75) than children with PBB (16 [23%] of 69; OR 2·47, 95% CI 1·20–5·08) and were unrelated to lower airway infection. Upper airway contamination was uncommon (eight [11%] of 71) and was not evident in 23 (79%) of 29 bronchoalveolar lavages that were positive for upper airway biofilms. Interpretation: Lower airway biofilms are prevalent, but not ubiquitous, in bronchoalveolar lavage from children with PBB or bronchiectasis, suggesting anti-biofilm therapies might be beneficial for some children. Detection of upper airway biofilms in bronchoalveolar lavage that did not have signs of contamination suggests that microaspiration might be important in some children. Specimen quality measures are recommended for future studies to account for the presence of upper airway biofilms. Funding: Financial Markets for Children Project Grant, National Health and Medical Research Council of Australia, Rebecca L Cooper Medical Research Foundation, Queensland Children's Hospital Foundation, and BrightSpark Foundation.http://www.sciencedirect.com/science/article/pii/S2666524721003001
spellingShingle Robyn L Marsh, PhD
Michael J Binks, PhD
Heidi C Smith-Vaughan, PhD
Maxine Janka, BSc
Sharon Clark, BBioMedSc
Peter Richmond, ProfMD
Anne B Chang, ProfPhD
Ruth B Thornton, PhD
Prevalence and subtyping of biofilms present in bronchoalveolar lavage from children with protracted bacterial bronchitis or non-cystic fibrosis bronchiectasis: a cross-sectional study
The Lancet Microbe
title Prevalence and subtyping of biofilms present in bronchoalveolar lavage from children with protracted bacterial bronchitis or non-cystic fibrosis bronchiectasis: a cross-sectional study
title_full Prevalence and subtyping of biofilms present in bronchoalveolar lavage from children with protracted bacterial bronchitis or non-cystic fibrosis bronchiectasis: a cross-sectional study
title_fullStr Prevalence and subtyping of biofilms present in bronchoalveolar lavage from children with protracted bacterial bronchitis or non-cystic fibrosis bronchiectasis: a cross-sectional study
title_full_unstemmed Prevalence and subtyping of biofilms present in bronchoalveolar lavage from children with protracted bacterial bronchitis or non-cystic fibrosis bronchiectasis: a cross-sectional study
title_short Prevalence and subtyping of biofilms present in bronchoalveolar lavage from children with protracted bacterial bronchitis or non-cystic fibrosis bronchiectasis: a cross-sectional study
title_sort prevalence and subtyping of biofilms present in bronchoalveolar lavage from children with protracted bacterial bronchitis or non cystic fibrosis bronchiectasis a cross sectional study
url http://www.sciencedirect.com/science/article/pii/S2666524721003001
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