Abstract
There is compelling evidence that prenatal nicotine exposure permanently alters lung development and airway function. The aim of this study was to determine how prenatal nicotine exposure alters proximal and distal airway function. Thirteen lambs were continuously exposed during the last fetal trimester to low-dose nicotine (LN) and 12 to a moderate dose (MN) (maternal s.c. dose: 0.5 and 1.5 mg/kg/d, respectively). Ten lambs served as controls (C). Proximal airway function was measured by lung mechanics. A multiple-breath N2 washout technique was used to measure lung volume (functional residual capacity) and efficiency of gas mixing in distal airways, i.e. terminal respiratory units (moment ratio and nitrogen clearance). In comparison with C, both LN and MN had significantly reduced specific airway conductance to the same extent at a median study age of 12, 25, and 51 d, indicating signs of proximal airway obstruction. Distal airway function showed significant improvement in LN. Ventilation and functional residual capacity were unaffected. In summary, prenatal nicotine exposure induced airway obstruction in proximal airways and improved gas mixing in distal airways, possibly reflecting restriction in proximal airway growth and accelerated maturation of the acinar part of the lung, respectively. We speculate that prenatal nicotine exposure has a disparate impact on airway development and function. The effect on the distal airways seemed to be inversely related to dose, which was not the case in the large airways. The altered airway function persisted during the study period, indicating that the effects of prenatal nicotine exposure might be permanent.
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Abbreviations
- C:
-
control
- M0:
-
zero moment
- Cdyn:
-
dynamic lung compliance
- M1:
-
first moment
- FRC:
-
functional residual capacity
- NC:
-
nitrogen clearance
- LN:
-
low-dose nicotine
- Rl:
-
lung resistance
- MN:
-
moderate-dose nicotine
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Acknowledgements
The authors thank Patricia A. Minton, R.N., Rao Gaddipati, M.S., and Charles A. Dematteo, Jr., for skilled technical assistance, Dr. Neal Benowitz for performing nicotine and cotinine determinations, Dr. Beverly Mellen for performing the randomization procedure, and Dr. James Sheller for his helpful advice.
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Supported by grants from the Smokeless Tobacco Research Council (#0765). K.S. was in part supported by The Research Fund at the Queen Silvia Children's Hospital, Göteborg, Sweden.
These results were presented in part at the annual meeting of the American Pediatric Society and Society for Pediatric Research 2002.
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Sandberg, K., Poole, S., Hamdan, A. et al. Altered Lung Development after Prenatal Nicotine Exposure in Young Lambs. Pediatr Res 56, 432–439 (2004). https://doi.org/10.1203/01.PDR.0000136276.52104.61
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DOI: https://doi.org/10.1203/01.PDR.0000136276.52104.61
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