Researchers find distinct microbiomes in airway, gastrointestinal systems of children with chronic cough

Jul 26 2018

Different respiratory diseases associated with chronic cough create distinct microbial imbalances in the lower airways of children, according to a study led by researchers at NYU School of Medicine. The study, published online this month in Pediatric Pulmonology, is the first to assess the bacterial population of the airway and gastrointestinal systems of children with chronic cough using bacterial DNA sequencing.

Up to 20% of preschool-aged children experience a recurring cough lasting longer than four weeks. Unlike an acute cough, which typically lasts fewer than two weeks and is frequently associated with a respiratory tract infection, chronic cough is often related to an underlying respiratory or gastrointestinal issue such as asthma, upper airway disorders, or gastroesophageal reflux disease (GERD).

"Chronic cough can have a significant negative impact on a child's quality of life, and in order to effectively treat it you must accurately identify the cause," says lead author Mikhail Kazachkov, MD, clinical professor in the Department of Pediatrics and director of the Division of Pediatric Pulmonology at Hassenfeld Children's Hospital at NYU Langone. "This first-of-its-kind study could improve assessment and treatment for children with chronic cough by allowing clinicians to better understand the underlying condition."

In current practice, clinicians collect fluid or tissue samples and enable bacteria from the sample to grow in a dish to gather information about the airway's bacterial population and make a diagnosis. With this newer method of 16S ribosomal RNA gene sequencing, researchers were able to capture the presence of key bacterial species in the children's upper and lower airway and digestive system that were missed by the traditional culture method.

"The disparity between the results of the traditional method of testing and the more unbiased DNA sequencing method further highlights our incomplete knowledge of the microbial populations living in the human body," says senior author Leopoldo N. Segal, MD, assistant professor in NYU Langone's Division of Pulmonary, Critical Care, and Sleep Medicine.

The study consisted of 36 children seen at the Pediatric Aerodigestive Center at Hassenfeld Children's Hospital who had suffered from daily cough for more than eight weeks. Children were assigned to one of four groups after clinical evaluation: asthma, protracted bacterial bronchitis (PBB), neurologically impaired children fed orally, and neurologically impaired children fed through a tube. Neurologically impaired children are more likely to experience respiratory problems due to a condition's effect on a child's muscle strength, breathing, and swallowing.

Researchers collected a total of 354 samples from the children's airways to their gastrointestinal tracts. They then used genomic and cutting-edge bioinformatic techniques to analyze the millions of pieces of bacterial DNA in the samples, identifying distinct microbial features that were not detectable using the conventional culture method.

Significantly, the microbiomes of neurologically impaired children were strikingly different from children with asthma and bronchitis. The lower airways of orally-fed neurologically impaired children were enriched with Veillonella, bacteria usually found in the mouth, which may point to this bacterium as a marker for aspiration.

In neurologically impaired children, aspiration of food, mucus, or saliva into the lungs is common, and can cause rapid development of severe lung disease. This is a growing concern for clinicians, as rates of children with aspiration have risen in recent years due to higher survival rates for children with severe neurological and genetic disorders.

"It is extremely difficult to diagnose aspiration with certainty, but the data give us hope that in the future we can diagnose aspiration-related lung disease using certain microbial signatures, and provide the appropriate treatment to prevent lung damage," says Dr. Kazachkov.

Researchers also noted that across diagnoses, inflammation of the lower airway was associated with similarity between the lower airway microbiota and the upper airway microbiota. Researchers suggest that inflammation and associated abundant airway secretions impair the body's natural microbial clearance, allowing more bacteria to invade the lower airway and further increase its inflammation.

"The characterization of these distinct microbial features is an exciting step toward more personalized targeted therapies for children with varying causes of chronic cough," says Dr. Segal.

Researchers acknowledge a limitation of the study is the lack of a control group of healthy children-;ethical concerns making it impossible to perform unnecessary invasive procedures such as bronchoscopy-;and note that further longitudinal studies with larger cohorts are warranted.