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ETS effects on pulmonary breathing patterns

Institution: University of California, Davis
Investigator(s): Jesse Joad, M.D.
Award Cycle: 1997 (Cycle 6) Grant #: 6RT-0024 Award: $446,954
Subject Area: Pulmonary Disease
Award Type: Research Project Awards

Initial Award Abstract
Children exposed to environmental tobacco smoke (ETS) have problems with cough, phlegm, and respiratory illnesses. C-fibers are nerves in the lung which, when stimulated, cause chest discomfort, cough, phlegm, and airway narrowing; these responses are thought to protect the lung from damage from noxious substances. C-fibers are known to be stimulated by mainstream smoke. Thus if ETS also stimulates C-fibers, some of the symptoms experienced by children such as cough and phlegm may be due to ETS directly stimulating C-fibers. However, this would not explain the increased respiratory illnesses in children exposed to ETS. We suggest that the initial vigorous reflex response to ETS declines with continued ETS exposure resulting in impaired pulmonary protective responses. If such is the case, there are two important consequences: 1) other injurious agents such as ozone and respiratory viruses may be able to cause more damage to the lungs of ETS-exposed children than to the lungs of children not exposed to ETS, and 2) children of smokers are more likely to become smokers themselves since their first exposure to mainstream smoke may be less uncomfortable.

Final Report
C-fibers are nerves which sense irritants in the lungs and when stimulated cause rapid shallow breathing, narrowing of airways, mucous secretion, and breath holding. Many of these same symptoms are reported in children who live in the homes with exposure to environmental tobacco smoke (ETS). The original proposal was to examine the overall hypothesis that extended sidestream smoke exposure to the developing organism induces damage to the lung by decreasing the responsiveness of the bronchopulmonary C-fiber system leaving the lung more vulnerable to other noxious agents. We proposed to test this hypothesis by determining if extended exposure to sidestream smoke during the equivalent of human childhood 1) decreases the nerve activity of stimulated C-fibers, 2) increases the activity of a chemical which eliminates several of the neurotransmitters of C-fibers, 3) diminishes C-fiber nerves in airway muscle, and 4) results in lungs which because of diminished function of their C-fibers are more vulnerable to further damage produced by an acute exposure to ozone or mainstream smoke. Upon completion of our studies, we found, however, that at least for part of the C-fiber reflex, quite the opposite was the case. In general, several aspects of the C-fiber reflex were enhanced by exposure to sidestream smoke. We now believe that chronic sidestream smoke exposure enhances the central C-fiber reflex. Specifically we found that exposing guinea pigs to sidestream smoke during the equivalent of human childhood 1) increased the nerve activity of stimulated C-fibers, 2) increased the nerves (or the chemical content of the nerves) of the airways, 3) increased the activity of neurons in the brain which receive signals from stimulated C-fibers, and 4) lengthened the breath holding produced by stimulating C-fibers. Since we found that a chemical found in C-fibers, substance P, was increased in the airways, we proposed that it might also be increased in the brain. We found that substance P is capable of increasing the transmission of nerve activity from the lung C-fibers to the neurons in the brain. Finally, we studied the function of C-fibers by showing that C-fibers protect the airways from damage from ozone, an effect which is greater in the bigger airways than in the smaller ones. These studies suggest that an increase in the responsiveness of C-fibers may explain some of the respiratory symptoms (cough, bronchoconstriction, mucous secretion) and sudden infant death (due to long breath holds) that occurs in children raised with exposure to ETS. Possible applications of these findings are 1) to use drugs which block substance P in children raised with ETS exposure, and 2) to document the cellular, biochemical, and physiological changes produced by ETS exposure thereby providing powerful evidence which may convince parents not to smoke around their children.

Chronic exposure to sidestream tobacco smoke augments bronchopulmonary C-fiber responsiveness in young guinea pigs
Periodical: Journal of Applied Physiology Index Medicus:
Authors: Mutoh T, Bonham AC, Kott KS, Joad JP ART
Yr: 1999 Vol: 87 Nbr: Abs: Pg: 757-768

Smoking and pediatric respiratory health
Periodical: Clinics in Chest Medicine Index Medicus:
Authors: Joad JP ART
Yr: 2000 Vol: 21 Nbr: Abs: Pg: 37-46

The mammalian respiratory system and critical windows of exposure for children's health
Periodical: Environmental Health Perspectives Index Medicus:
Authors: Pinkerton KE, Joad JP ART
Yr: 2000 Vol: 108 Nbr: 3 Abs: Pg: 457-462

Chronic passive cigarette smoke exposure augments bronchopulmonary C-fiber inputs to nucleus tractus neurones and reflex output in young guinea pigs
Periodical: Journal of Physiology Index Medicus:
Authors: Mutoh T, Joad JP, Bonham AC ART
Yr: 2000 Vol: 523 Nbr: Abs: Pg: 223-233

Effect of respiratory pattern on ozone injury to the airways of isolated rat lungs
Periodical: Toxicology and Applied Pharmacology Index Medicus:
Authors: Joad JP, Bric JM, Weir AJ, et al ART
Yr: 2000 Vol: 169 Nbr: Abs: Pg: 26-32