In the JournalsPerspective

Nose, throat microbiome hints at source of LRTIs in children

Photo of Debby Bogaert
Debby Bogaert

The microbiome of children’s nasopharynx very closely resembles the viral and bacterial microbiome observed in deep endotracheal samples, according to findings published in The Lancet Respiratory Medicine. Researchers suggested that nasopharyngeal samples could be used as a proxy for lung microbiota, which could help clinicians better understand the causes of lower respiratory tract infections in children and tailor better treatment.

Debby Bogaert, MD, PhD, a Scottish senior clinical fellow and honorary consultant in pediatric infectious diseases at the University of Edinburgh, told Infectious Diseases in Children that the relationship between the upper and lower respiratory tract has been already established, and that bacteria and viruses that cause lung infections are commonly found in the nose and throat. However, the presence of potentially pathogenic organisms does not necessarily indicate disease.

“Now, with a more sophisticated and nuanced way of studying this, we actually did find a very good correlation between what is in the nose and what is in the lungs at time of a severe infection,” she said. “The clue is that you need to look at everything — the whole ‘ecosystem’ of the nose — not at a single bacteria or virus.”

Bogaert and colleagues first conducted a prospective study that included 29 children aged 4 weeks to 5 years who received care in a pediatric ICU at Wilhelmina Children’s Hospital in Utrecht, the Netherlands. The children were diagnosed with a lower respiratory tract infection (LRTI) that required mechanical ventilation. Nurses collected nasopharyngeal swabs and deep endotracheal aspirates within 4 hours of intubation.

The researchers then conducted a matched case-control study of patients with an LRTI requiring mechanical ventilation (n = 154) at three Dutch teaching hospitals. Nasopharyngeal samples were collected at admission for these cases and during home visits for controls who were selected from the community (n = 307). The researchers used qualitative PCR to establish viral microbiota profiles and 16S rRNA-based sequencing to establish bacterial microbiota profiles.

In the prospective study, Bogaert and colleagues observed similarities between the patients’ viral microbiota profiles (96% agreement; 95% CI, 93%-99%) found in nasopharyngeal and endotracheal samples. The researchers also found similarities between the patients’ bacterial microbiota profiles in the lungs and nasopharynx (58 taxa with a median Pearson’s r = 0.93 [interquartile range, 0.62-0.99]; P < .05 for all 58 taxa).

In the case-control study, the researchers found that they could not successfully distinguish healthy patients from patients with LRTIs by relying on bacterial microbiota (area under the curve [AUC] = 0.77), viral microbiota (AUC = 0.7) and child characteristics (AUC = 0.8) alone. However, they accurately identified patients with LRTIs using a classification model that incorporated all three characteristics (AUC = 0.92).

Based on these findings, the researchers suggested that LRTIs “result from the interplay between microbiota and host characteristics, rather than a single microorganism.”

Bogaert said additional research is needed before their approach can be used in a clinical setting.

“In evidence-based medicine, we never act upon one study alone, so it will be important that other independent groups follow us with these methods to confirm our findings,” she said. “The technology needed to use this type of approach is currently available but not ready to use on individual patients nor to generate results within approximately 24 hours. It is important to make the technology and read-out user-friendly and, preferably, bedside.”

Bogaert’s “optimistic view” is that microbiota-based diagnostics could be used clinically in the next 5 to 10 years. She said she envisions the devices being used in EDs, general wards and ICUs. – by Katherine Bortz

Disclosures: The authors report no relevant financial disclosures.

Photo of Debby Bogaert
Debby Bogaert

The microbiome of children’s nasopharynx very closely resembles the viral and bacterial microbiome observed in deep endotracheal samples, according to findings published in The Lancet Respiratory Medicine. Researchers suggested that nasopharyngeal samples could be used as a proxy for lung microbiota, which could help clinicians better understand the causes of lower respiratory tract infections in children and tailor better treatment.

Debby Bogaert, MD, PhD, a Scottish senior clinical fellow and honorary consultant in pediatric infectious diseases at the University of Edinburgh, told Infectious Diseases in Children that the relationship between the upper and lower respiratory tract has been already established, and that bacteria and viruses that cause lung infections are commonly found in the nose and throat. However, the presence of potentially pathogenic organisms does not necessarily indicate disease.

“Now, with a more sophisticated and nuanced way of studying this, we actually did find a very good correlation between what is in the nose and what is in the lungs at time of a severe infection,” she said. “The clue is that you need to look at everything — the whole ‘ecosystem’ of the nose — not at a single bacteria or virus.”

Bogaert and colleagues first conducted a prospective study that included 29 children aged 4 weeks to 5 years who received care in a pediatric ICU at Wilhelmina Children’s Hospital in Utrecht, the Netherlands. The children were diagnosed with a lower respiratory tract infection (LRTI) that required mechanical ventilation. Nurses collected nasopharyngeal swabs and deep endotracheal aspirates within 4 hours of intubation.

The researchers then conducted a matched case-control study of patients with an LRTI requiring mechanical ventilation (n = 154) at three Dutch teaching hospitals. Nasopharyngeal samples were collected at admission for these cases and during home visits for controls who were selected from the community (n = 307). The researchers used qualitative PCR to establish viral microbiota profiles and 16S rRNA-based sequencing to establish bacterial microbiota profiles.

In the prospective study, Bogaert and colleagues observed similarities between the patients’ viral microbiota profiles (96% agreement; 95% CI, 93%-99%) found in nasopharyngeal and endotracheal samples. The researchers also found similarities between the patients’ bacterial microbiota profiles in the lungs and nasopharynx (58 taxa with a median Pearson’s r = 0.93 [interquartile range, 0.62-0.99]; P < .05 for all 58 taxa).

In the case-control study, the researchers found that they could not successfully distinguish healthy patients from patients with LRTIs by relying on bacterial microbiota (area under the curve [AUC] = 0.77), viral microbiota (AUC = 0.7) and child characteristics (AUC = 0.8) alone. However, they accurately identified patients with LRTIs using a classification model that incorporated all three characteristics (AUC = 0.92).

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Based on these findings, the researchers suggested that LRTIs “result from the interplay between microbiota and host characteristics, rather than a single microorganism.”

Bogaert said additional research is needed before their approach can be used in a clinical setting.

“In evidence-based medicine, we never act upon one study alone, so it will be important that other independent groups follow us with these methods to confirm our findings,” she said. “The technology needed to use this type of approach is currently available but not ready to use on individual patients nor to generate results within approximately 24 hours. It is important to make the technology and read-out user-friendly and, preferably, bedside.”

Bogaert’s “optimistic view” is that microbiota-based diagnostics could be used clinically in the next 5 to 10 years. She said she envisions the devices being used in EDs, general wards and ICUs. – by Katherine Bortz

Disclosures: The authors report no relevant financial disclosures.

    Perspective

    Wing Ho Man and colleagues investigated the complex interplay between bacterial and viral respiratory tract microbiota and host characteristics in children with lower respiratory tract infections. An important finding is that the nasopharyngeal viral and bacterial microbiota can be used as a proxy of the lung microbiota, which is much more difficult to assess and investigate.

    The study supports evidence from previous findings that lower respiratory tract infections cannot be strictly categorized into viral and bacterial infections because there seems to be an overlap between both. This study helps in understanding the complex interplay of respiratory tract microbiota and host factors that contribute to the development of new diagnostic tools and individualized medicine for children with respiratory tract infections.

    • Roland P. Neumann, MD
    • Neonatal consultant
      Department of neonatology
      University Children’s Hospital Basel
      University of Basel, Switzerland

    Disclosures: Neumann reports that he received a research grant from Vifor Pharma AG, Villars-sur-Glâne, Switzerland.