Allergic sensitization and exposure to ambient air pollution beginning early in life lead to a COPD-like phenotype in young adult mice

Ecotoxicol Environ Saf. 2022 Aug:241:113821. doi: 10.1016/j.ecoenv.2022.113821. Epub 2022 Jul 4.

Abstract

The perinatal period and early infancy are considered critical periods for lung development. During this period, adversities such as environmental exposures, allergic sensitization, and asthma are believed to impact lung health in adulthood. Therefore, we hypothesized that concomitant exposure to allergic sensitization and urban-derived fine particulate matter (PM2.5) in the early postnatal period of mice would cause more profound alterations in lung alveolarization and growth and differently modulate lung inflammation and gene expression than either insult alone in adult life. BALB/c mice were sensitized with ovalbumin (OVA) and exposed to PM2.5 from the fifth day of life. Then, we assessed lung responsiveness, inflammation in BALF, lung tissue, and alveolarization by stereology. In addition, we performed a transcriptomic analysis of lung tissue on the 40th day of life. Our results showed that young adult mice submitted to allergic sensitization and exposure to ambient PM2.5 since early life presented decreased lung growth with impaired alveolarization, a mixed neutrophilic-eosinophilic pattern of lung inflammation, increased airway responsiveness, and increased expression of genes linked to neutrophil recruitment when compared to animals that were OVA-sensitized or PM2.5 exposed only. Both, early life allergic sensitization and PM2.5 exposure, induced inflammation and impaired lung growth, but concomitant exposure was associated with worsened inflammation parameters and caused alveolar enlargement. Our experimental data provide pathological support for the hypothesis that allergic or environmental insults in early life have permanent adverse consequences for lung growth. In addition, combined insults were associated with the development of a COPD-like phenotype in young adult mice. Together with our data, current evidence points to the urgent need for healthier environments with fewer childhood disadvantage factors during the critical windows of lung development and growth.

Keywords: Air pollution; Allergic sensitization; Alveolarization; Asthma; Particulate matter.

MeSH terms

  • Air Pollutants* / analysis
  • Air Pollution* / adverse effects
  • Animals
  • Bronchoalveolar Lavage Fluid
  • Inflammation / chemically induced
  • Lung
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin
  • Particulate Matter / analysis
  • Phenotype
  • Pneumonia* / chemically induced
  • Pulmonary Disease, Chronic Obstructive*

Substances

  • Air Pollutants
  • Particulate Matter
  • Ovalbumin