Early Life Wildfire Smoke Exposure Is Associated with Immune Dysregulation and Lung Function Decrements in Adolescence

Abstract

The long-term health effects of wildfire smoke exposure in pediatric populations are not known. The objectives of this study were to determine if early life exposure to wildfire smoke can affect parameters of immunity and airway physiology that are detectable with maturity. We studied a mixed-sex cohort of rhesus macaque monkeys that were exposed as infants to ambient wood smoke from a series of Northern California wildfires in the summer of 2008. Peripheral blood mononuclear cells (PBMCs) and pulmonary function measures were obtained when animals were approximately 3 years of age. PBMCs were cultured with either LPS or flagellin, followed by measurement of secreted IL-8 and IL-6 protein. PBMCs from a subset of female animals were also evaluated by Toll-like receptor (TLR) pathway mRNA analysis. Induction of IL-8 protein synthesis with either LPS or flagellin was significantly reduced in PBMC cultures from wildfire smoke-exposed female monkeys. In contrast, LPS- or flagellin-induced IL-6 protein synthesis was significantly reduced in PBMC cultures from wildfire smoke-exposed male monkeys. Baseline and TLR ligand-induced expression of the transcription factor, RelB, was globally modulated in PBMCs from wildfire smoke-exposed monkeys, with additional TLR pathway genes affected in a ligand-dependent manner. Wildfire smoke-exposed monkeys displayed significantly reduced inspiratory capacity, residual volume, vital capacity, functional residual capacity, and total lung capacity per unit of body weight relative to control animals. Our findings suggest that ambient wildfire smoke exposure during infancy results in sex-dependent attenuation of systemic TLR responses and reduced lung volume in adolescence.

Early life exposure to coal mine fire smoke emissions and altered lung function in young children

“…The only comparable study, in terms of exposure, was conducted in monkeys but not in humans. The California fires of 2008 caused degraded air quality for a period of 3 weeks in a primate research facility soon after the birth of 50 rhesus macaque monkeys, and their lung function was evaluated in adolescence . Unlike our results, these authors found moderate reductions in airway resistance in the exposed animals compared with the unexposed indicating better lung function.…”

Wildfire smoke exposure and human health: Significant gaps in research for a growing public health issue

“…Animal models of lung development suggest a strong oxidant exposure in early life changes lung function by altering the pattern and timing of alveolarization and distal airway development (Avdalovic et al, 2012; Fanucchi et al, 2006). This is consistent with animal studies showing altered lung volumes in nonhuman primates exposed to wildfire smoke during infancy (Black et al, 2017). A mechanism explaining the health effects of wildfire smoke would help to predict how wildfire smoke interacts with the developing lung and other long-term health considerations in specific populations.…”

“…A study of these animals performed 3 years later (as juveniles) found that compared to age-matched peers, these animals had reduced lung volumes. Furthermore, stimulation of peripheral blood mononuclear cells collected from the animals produced lower levels of inflammatory cytokines in response to Toll-like receptor ligands compared to age-matched controls that were not exposed to wildfire smoke as infants (Black et al, 2017). …”

The impact of prescribed fire versus wildfire on the immune and cardiovascular systems of children

“…We focus on children given their reduced lung size, increased metabolic rates, higher respiratory rate, and developing immune systems, 5 and because in macaque monkeys who are exposed to wildfire smoke in infancy, there is associated immune dysregulation and decreased lung function in adolescence. 6 We hypothesize that the health impacts of a prescribed fire are less detrimental to the respiratory and cardiovascular systems than a wildfire in school-aged children and…”