Launched in 2007, the Urban Environment and Childhood Asthma (URECA) study evaluated pregnant women in central urban areas of Baltimore, Boston, New York City, and St. Louis, and followed their children from birth through age 17 years to identify risk factors associated with development of asthma and asthma severity. As a result of this research, in 2019, the URECA investigators described five distinct respiratory phenotypes based on patterns of wheezing, allergic sensitization, and pulmonary function measured longitudinally at age 7.
“We looked at several factors potentially related to the development of asthma, including lung function, wheezing trajectories, obesity, and maternal depression,” says Meyer Kattan, MD, Director of the Pediatric Pulmonary Division at NewYork-Presbyterian/Columbia and one of the URECA investigators. The study team identified five patterns of wheezing during the seven-year study period:
- Low wheeze, low atopy
- Low wheeze, high atopy
- Transient wheeze and low atopy, in which the wheeze disappeared early on within the first three years
- High wheeze, low atopy
- High wheeze, high atopy
Drawing on these findings, a subsequent study was undertaken to determine whether these distinct respiratory phenotypes are associated with early-life upper respiratory microbiota development and environmental microbial exposures. “This current investigation followed a cohort of children from the URECA study with a family history of allergies or asthma,” says Dr. Kattan, who is a member of the National Institute of Allergy and Infectious Diseases-sponsored Childhood Asthma in Urban Settings Consortium, which conducted the study. “Nasal samples were collected from 120 children at 12 months and 142 children at 36 months. We also studied dust from the living rooms of their homes when the children were three months old to identify any bacteria. When we compared the bacteria in the home environment with the nasal microbiome, we found that certain bacteria were associated with different wheezing phenotypes.”
Specifically, the results of the study, which were published in The Journal of Allergy and Clinical Immunology, showed:
- Nasal microbiota increased in diversity between 12 and 36 months of age
- Age-related changes in microbiota evenness differed significantly by respiratory phenotypes, increasing most in the transient-wheeze group
- At 12 months, respiratory illness and dominant bacterial genus explained the variance in nasal microbiota composition
- Enrichment of Moraxella and Haemophilus members was associated with both transient- and high-wheeze phenotypes
- By 36 months, nasal microbiota were significantly associated with respiratory phenotypes and Moraxella-dominated microbiota specifically linked to atopy-associated respiratory phenotypes
The Role of Bacteria in Certain Respiratory Phenotypes
The study uncovered that the bacteria Moraxella and Haemophilus were enriched in children with the wheezing phenotypes as compared to those with the non-wheezing phenotypes. They also were associated with the high wheeze, high allergy cluster. “The types of bacteria that reside in the noses of young children may be related to the likelihood of having continued wheezing and to whether allergies are present,” notes Dr. Kattan.
The study authors suggest that these findings provide the potential for changing the bacterial environment to alter the outcome of respiratory illnesses. “Exposing children to good bacteria or eliminating bad bacteria may have an influence on who develops asthma in high-risk patients,” says Dr. Kattan. “Determining that certain wheezing phenotypes have different bacterial compositions offers us an opportunity to alter the trajectory of certain illnesses by interfering or modifying the bacterial environment and prevent wheezing illnesses. And, in fact, we are pursuing another NIH-funded study (Oral Bacterial Extract for the Prevention of Wheezing Lower Respiratory Tract Illness) in which we are giving lyophilized bacteria for two years to high-risk children beginning in their first year of life with the goal of preventing them from developing wheezing and asthma.”
