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Environmental tobacco smoke effects on lung surfactant

Institution: University of California, Santa Barbara
Investigator(s): Joseph Zasadzinski, Ph.D.
Award Cycle: 2002 (Cycle 11) Grant #: 11RT-0222 Award: $406,444
Subject Area: Pulmonary Disease
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
Quantifying the risks that environmental tobacco smoke (ETS) might pose to non-smokers is an important public health and policy concern. A clear association between ETS exposure and lung cancer appears to exist, and nonsmokers married to smokers have a statistically significant risk of developing lung cancer. In addition to lung cancer, associatinos have been found between passive smoking at the workplace and chronic respiratory symptoms such as wheezing and cough; the severity of which depends on the extent of exposure. Respiratory effects of ETS are especially significant in infants and children exposed to parental smoking. Epidemiological studies have clearly shown that children raised in homes with smokers have more coughing, wheezing, and respiratory illness compared with children raised in homes without smoking. However, epidemiological studies cannot provide a detailed explanation for the actual physiological effects of ETS on specific organs, tissues, etc. in a systematic and controlled fashion.

This continuation proposal is designed to determine the effects of controlled exposure to environmental tobacco smoke on the chemical and morphological features of human lung surfactants. The surfactant lining of the alveolus plays an important part in proper lung function including minimizing the work of breathing, ensuring uniform lung inflation, and reducing chemical and particulate damage to the deep lungs. Lung surfactant achieves these multiple goals by forming a single molecule layer thick film at the fluid-air interface of the alveolus that lowers the surface tension as the available interfacial area changes during respiration. The surfactant monolayer must be capable of maintaining a near zero surface tension at the contracting alveolus interface during exhalation to minimize the work of breathing. The surfactant monolayer must also respread to cover the expanding interface during in halation in order to prepare for the next breath. Normal lung surfactant consists of a complex mixture of saturated phosphatidylcholines, unsaturated phosphatidylcholines and phosphatidylglycerols, fatty acids and surfactant specific proteins that act synergistically to achieve these necessary physiological functions.

We have previously found that ETS exposure significantly degrades the performance of the lipids in lung surfactants. The main features of this degradation are an increase in the minimum surface tension on inhalation and a decrease in the respreading of the surfactant over the alveolar surfaces on inhalation. In this continuation proposal, we will examine the effects of the lung surfactant specific proteins and how they are affected by ETS. We plan to use in vitro measurements of surfactant performance such as minimum surface tension, monolayer morphology and monolayer viscosity to determine the effects of ETS on lung surfactants. To do this, we will expose a buffered saline solution (that is imilar to the alveolar lining fluid) to various concentratin of side-stream smoke using a system developed at the Institute of Toxicology and Environmental Health at UC Davis. Lung surfactant monolayers will be spread over this "smoke-conditioned" fluid and the suface tension, viscosity, phase behavior, and morphology of the monolayers will be compared to control monolayers. Variations in these parameters will be quantified and related to changes in the chemical composition and concentrations of the components of lung surfactant. These alterations can then be related to the physiological effects known to occur in passive smoking. We hope to be able to provide direct information on the effects of ETS lung surfactant system, and how these changes can lead to changes in respiratory health.
Publications

Nanostructural changes in lung surfactant monolayers induced by interactions between POPG and surfactant protein SP-B.
Periodical: Langmuir Index Medicus:
Authors: Ding J, Doudevski I, Warriner HE, Zasadzinski J ART
Yr: 2003 Vol: 19 Nbr: Abs: Pg: 1539-1550

Environmental tobacco smoke effects on the primary lipids of lung surfactant.
Periodical: Langmuir Index Medicus:
Authors: Bringezu F, Pinkerton K, Zasadzinski J ART
Yr: 2003 Vol: 19 Nbr: Abs: Pg: 1900-1907

Electrostatic barrier to recovery of dipalmitoylphosphatidylglycerol monolayers after collapse
Periodical: Biophysical Journal Index Medicus:
Authors: Alig TF, Warriner HE, Lee L, Zasadzinski J ART
Yr: 2004 Vol: 86 Nbr: Abs: Pg: 897-904

Linear dependence of surface drag on surface viscosity
Periodical: Physical Review Letters Index Medicus:
Authors: Alonso C, Zasadzinski J ART
Yr: 2004 Vol: 69 Nbr: 021602 Abs: Pg: 1-6

Exogenous lung surfactant survanta in vitro function-composition relationship
Periodical: Langmuir Index Medicus:
Authors: Alonso C, Alig T, Zasadzinski J ART
Yr: 2004 Vol: Nbr: Abs: Pg:

Keeping ling surfactants where it belongs, protein regulation of surfactant viscosity April 25, 2005
Periodical: Biophysical Journal Index Medicus:
Authors: Joseph Zasadzinski ART
Yr: 0 Vol: Nbr: Abs: Pg:

Modifying calf lung surfactant by Hexadecanol 1028-1035, 2005
Periodical: Langmuir Index Medicus:
Authors: Zasadzinski,J ABS
Yr: 2005 Vol: 21 Nbr: Abs: Pg: 1028 - 1035

More than a Monolayer, Relating Lung Surfactant Structure and Mechanics to Composition 4188-4202
Periodical: Biophysical Journal Index Medicus:
Authors: Zasadzinski, J ART
Yr: 2004 Vol: 87 Nbr: Abs: Pg: 4188 - 4202

Linear Dependence of Surface Drag on Surface Viscossity, 2004
Periodical: Physical Review Letters Index Medicus:
Authors: J. Zasadzinski ART
Yr: 2004 Vol: 69 Nbr: Abs: Pg: 021602 - 1.6

Inhibition of Pulmonary Surfactant Adsorption by Serum and the Mechanisms of Reversal by Hydrophilic polymers Therory
Periodical: Biophysical Journal Index Medicus:
Authors: Joseph Zasadzinski ART
Yr: 2005 Vol: 89 Nbr: Abs: Pg: 1621-1629