Researchers link early exposure to wildfire smoke to early use of upper respiratory medications

Children exposed to wildfire smoke in the first trimester of pregnancy or the first few weeks after birth are more likely to receive upper respiratory medications earlier in life, according to a new study by researchers at UNC-Chapel Hill and the United States Environmental Protection Agency (EPA).

Wildfires are one of the largest sources of air pollution and have a significant impact on respiratory health. In the US, they have increased in frequency and severity over the past two decades due to things like climate change and population growth, especially in Western states. Smoke from these fires contains a dangerous mixture of chemical compounds, particulate matter (PM) and particulate matter (PM2.5) that contribute to ill health, including exacerbation of asthma and reduced lung function in children.

While research has shed light on many of the health effects that come from PM in wildfire smoke, experts are still trying to understand how PM from wildfires may affect children in their earliest developmental stages. The UNC-led study, recently published in Environmental healthsought to investigate whether exposure to wildfire smoke in utero or in the first weeks of life resulted in earlier use of drugs to treat respiratory illnesses.

These medications may include cetirizine (Zyrtec) and mometasone for upper respiratory tract treatment, albuterol for lower respiratory tract treatment, and methylprednisolone, prednisolone, or prednisone for systemic anti-inflammatory treatment.

Results of the study suggest that infants exposed to wildfire smoke during the first trimester or six months of life are at greater risk for upper respiratory illness in early childhood, according to Radhika Dhingra, Ph.D., an adjunct assistant professor of environmental sciences and engineering at UNC Gillings School of Global Public Health and medical student at East Carolina University’s Brody School of Medicine, who is the study’s first author.

Dhingra collaborated on the study with several EPA and UNC colleagues, including Ilona Jaspers, Ph.D., professor of pediatrics, microbiology and immunology at the UNC School of Medicine, environmental sciences and engineering at the Gillings School, and director of the UNC Center for Environmental Medicine, Asthma and Lung Biology (CEMALB); and Ana G. Rappold, Ph.D., Branch Chief of the Clinical Research branch, statistician at EPA, and adjunct associate professor of environmental science and engineering at the Gillings School.

Using data from private insurance claims in an IBM MarketScan database, the research team matched a group of 182,387 live births in Oregon, California, Montana, Nevada and Idaho with wildfire smoke exposure estimates based on data from the Hazard Mapping System Fire and Smoke Product, which is compiled by the U.S. National Oceanic and Atmospheric Administration. They measured exposure to smoke during each trimester and two postnatal periods (0-12 weeks and 13-24 weeks), as well as the time it took to first fill an upper respiratory, lower respiratory or anti-inflammatories prescription, if a child needed one.

The team used this data to produce a statistical measure, called a hazard ratio, that estimated the association between average weekly smoke exposure and time to first prescription fill for each developmental period. Hazard ratios greater than one suggested that a child exposed to wildfire smoke over a period of time was more likely to use a respiratory medication than children who had not been exposed to wildfire smoke over that same time period.

In addition to finding that wildfire smoke exposure in the first trimester and after birth shortened the time to first use of upper respiratory tract medications, researchers found that in utero exposure to wildfire smoke resulted in an increase in the time to first use of lower respiratory tract and anti-inflammatory drugs.

The reason for this unexpected inverse relationship was unclear. Researchers noted that one explanation could be a preference for live births, which is common in perinatal epidemiological studies because the data is limited to live births and cannot include information on pregnancy loss. It could also be a sign of a biological process in response to smoke exposure in the womb.

In addition, the team observed biological sex-related differences in the results. The time to first use of upper respiratory tract medication was shorter in female children exposed to wildfire smoke in the first trimester and first postnatal period of 12 weeks, while it was shorter for male children in the postnatal period of 13-24 weeks. According to the study, these results are consistent with other findings indicating sex differences in lung development and vulnerability to smoke from wildfires.

Jaspers suggested that the difference between the upper and lower respiratory tract results might be related to the difference in how children were exposed to the smoke from wildfires. “The effects measured in the upper respiratory tract were likely caused by infants inhaling wildfire smoke directly through the nasal cavity,” she explained, “while the effects in the first trimester were indirect via maternal exposure. Infants are mandatory nasal breathers and could potentially experience significant nasal exposure during wildfires.”

The upper and lower airways are also structurally and functionally different, which researchers say may influence the effects the study measured.

“The upper respiratory tract includes the nasal cavity, larynx, and pharynx, while the lower respiratory tract is the bronchi and lungs,” Dhingra explained. “The structure, immune protection mechanisms and even the microbiome vary between the two. This variation in physiological and immunological functions may explain why these two parts of the airway do not behave in the same way in response to wildfire smoke.”

To further explore the complexities of these findings, Dhingra and fellow co-author Meghan Rebuli, Ph.D., assistant professor of pediatrics at the School of Medicine and at CEMALB, are currently examining how the microbiome and immune system in the nose (part of the upper respiratory tract) and sputum (a substance produced by the lower respiratory tract) interact as a result of wildfire smoke exposure in adults.

“With this work, we hope to shed some light on the complex relationship between the upper and lower airways,” she said.