Exposure to neonatal cigarette smoke causes durable lung changes but does not potentiate cigarette smoke–induced chronic obstructive pulmonary disease in adult mice

Abstract

The impact of early childhood cigarette smoke (CS) exposure on CS-induced chronic obstructive pulmonary disease (COPD) is unknown. This study was performed to evaluate the individual and combined effects of neonatal and adult CS exposure on lung structure, function, and gene expression in adult mice. To model a childhood CS exposure, neonatal C57/B6 mice were exposed to 14 days of CS (Neo CS). At 10 weeks of age, Neo CS and control mice were exposed to 4 months of CS. Pulmonary function tests, bronchoalveolar lavage, and lung morphometry were measured and gene expression profiling was performed on lung tissue. Mean chord lengths and lung volumes were increased in neonatal and/or adult CS-exposed mice. Differences in immune, cornified envelope protein, muscle, and erythrocyte genes were found in CS-exposed lung. Neonatal CS exposure caused durable structural and functional changes in the adult lung but did not potentiate CS-induced COPD changes. Cornified envelope protein gene expression was decreased in all CS-exposed mice, whereas myosin and erythrocyte gene expression was increased in mice exposed to both neonatal and adult CS, suggesting an adaptive response. Additional studies may be warranted to determine the utility of these genes as biomarkers of respiratory outcomes.

Early Postnatal Secondhand Smoke Exposure Disrupts Bacterial Clearance and Abolishes Immune Responses in Muco-Obstructive Lung Disease

“…Immune-cell recruitment, a key component of host defense against inhaled insults, has been shown to be increased in acute smoke-exposed adults (28,29) as well as in neonatal mice (30). In agreement with these studies, as compared with FA-WT mice, the SHS-WT mice in our study had significantly increased neutrophil counts.…”

“…In agreement with these studies, as compared with FA-WT mice, the SHS-WT mice in our study had significantly increased neutrophil counts. In contrast, however, perhaps due to a significantly low dose of smoke exposure levels (TSP = 10 mg/m 3 ) adopted in our study as compared with previous reports (28)(29)(30), macrophage counts were comparable between FA-and SHS-WT mice (Fig. 1C-E).…”