Early Life Exposure To Arsenic And Influenza Has Additive Effects On Lung Function Impairment

RATIONALE: Arsenic exposure via drinking water represents a significant global health issue. Epidemiological data suggest a relationship between early life arsenic exposure and the development of obstructive lung disease. This may be explained by an increased response to early life respiratory insults such as viral infection. We aimed to determine if exposure to arsenic increases the severity of response to early life influenza infection using a mouse model.

METHODS: Pregnant C57BL/6 mice were given drinking water containing 0 (control) or 100 ppb arsenic from gestational day 8 to 2 weeks after birth. Offspring were infected with either influenza A (Mem/1/71, H3N1) or a mock influenza treatment via intranasal inoculation at 1 week of age. Lung volume and lung mechanics were measured in offspring at 2 weeks of age using plethysmography and the forced oscillation technique which partitions lung mechanics into parameters representing the conducting airways (R = airway resistance) and aw lung parenchyma (G = tissue damping; H = tissue elastance).

RESULTS: Parenchymal mechanics adjusted for lung volume were significantly higher in both arsenic (G p = 0.02, H p = 0.02) and influenza (G p = 0.01, H p = 0.005) exposed male offspring compared to male controls. Male offspring exposed to both arsenic and influenza had the greatest deficit in parenchymal mechanics, but there was no significant interaction between the two treatments (G p = 0.41, H p = 0.35). There were no differences in airway resistance between groups of either sex, and no differences in parenchymal mechanics in females.

CONCLUSION: This study provides mechanical evidence for greater structural damage to the lung parenchyma as a result of combined arsenic and influenza exposure, compared to either arsenic or influenza exposure alone. These data also indicate that males have a more severe response to both arsenic and influenza and that the effects were additive. These responses may explain the link between early life arsenic exposure and obstructive lung disease.