TY - JOUR
T1 - Fetal nicotine exposure increases airway responsiveness and alters airway wall composition in young lambs
AU - Sandberg, Kenneth L.
AU - Pinkerton, Kent E
AU - Poole, Stanley D.
AU - Minton, Patricia A.
AU - Sundell, Håkan W.
PY - 2011/4/30
Y1 - 2011/4/30
N2 - To test the hypotheses that fetal nicotine exposure alters airway wall composition and enhances the airway response to inhaled methacholine (MCh), lambs were exposed during the last fetal trimester to (1) a low dose (LN) (n= 13, 0.5. mg/kg/d (maternal weight) of free base nicotine, (2) a moderate dose (MN) (n= 10, 1.5. mg/kg/d) or (3) saline (n= 14). Studies were performed at postnatal days 12, 26 and 52. Prenatal nicotine exposure induced a dose- and age-related hyper-responsiveness to MCh in the proximal airways. Moment analysis of nitrogen decay curves showed no nicotine or MCh effects on ventilation homogeneity or gas-mixing efficiency in the distal airways during MCh inhalations suggesting a bimodal response. Fetal nicotine exposure increased epithelial mucosubstance volume in central (LN, MN) and distal bronchi (LN), increased smooth muscle volume in distal bronchi and bronchioles (LN) and decreased bronchiolar diameter (MN). In conclusion, third trimester nicotine exposure causes hyperreactive proximal airways and alters proximal airway wall composition associated with airflow limitation.
AB - To test the hypotheses that fetal nicotine exposure alters airway wall composition and enhances the airway response to inhaled methacholine (MCh), lambs were exposed during the last fetal trimester to (1) a low dose (LN) (n= 13, 0.5. mg/kg/d (maternal weight) of free base nicotine, (2) a moderate dose (MN) (n= 10, 1.5. mg/kg/d) or (3) saline (n= 14). Studies were performed at postnatal days 12, 26 and 52. Prenatal nicotine exposure induced a dose- and age-related hyper-responsiveness to MCh in the proximal airways. Moment analysis of nitrogen decay curves showed no nicotine or MCh effects on ventilation homogeneity or gas-mixing efficiency in the distal airways during MCh inhalations suggesting a bimodal response. Fetal nicotine exposure increased epithelial mucosubstance volume in central (LN, MN) and distal bronchi (LN), increased smooth muscle volume in distal bronchi and bronchioles (LN) and decreased bronchiolar diameter (MN). In conclusion, third trimester nicotine exposure causes hyperreactive proximal airways and alters proximal airway wall composition associated with airflow limitation.
KW - Lung morphology
KW - Maternal exposure
KW - Nicotine
KW - Respiratory mechanics
KW - Sheep
KW - Tobacco smoke pollution
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UR - http://www.scopus.com/inward/citedby.url?scp=79952452809&partnerID=8YFLogxK
U2 - 10.1016/j.resp.2010.12.015
DO - 10.1016/j.resp.2010.12.015
M3 - Article
C2 - 21195212
AN - SCOPUS:79952452809
VL - 176
SP - 57
EP - 67
JO - Respiratory Physiology and Neurobiology
JF - Respiratory Physiology and Neurobiology
SN - 1569-9048
IS - 1-2
ER -