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ETS effects on breathing patterns

Institution: University of California, Davis
Investigator(s): Jesse Joad, M.D.
Award Cycle: 2000 (Cycle 9) Grant #: 9RT-0010 Award: $590,780
Subject Area: Pulmonary Disease
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
Children raised with exposure to environmental tobacco smoke (ETS) have increased cough, wheeze, airway obstruction, phlegm, asthma, and sudden infant death. The central C-fiber reflex consists of the C-fiber nerves in the lungs which sense irritation and send nerve activity to an area of the brain where the information is processed and then sent on to other areas of the brain to cause cough, narrowing of the airways, phlegm production, and breath holding. Our studies have shown that exposing guinea pigs to sidestream smoke during the equivalent of human childhood increases the number of C-fiber nerve branches in lung, enhances the activity of lung C-fiber nerves, enhances the activity of brain C-fiber neurons, and lengthens breath holding. Lacking is an understanding of the mechanism by which sidestream smoke exposure increases C-fiber nerves in the lung, and the mechanism by which sidestream smoke exposure enhances brain processing, transforming signals from lung C-fiber nerves into changes in breathing and lung function.

We propose that chronic ETS exposure during childhood increases the amount of neurotrophins in the lungs which causes C-fiber nerves to make more substance P (a neurotransmitter). Then when C-fiber nerves are stimulated, more substance P is released into the brain and the changes in breathing and lung function are greater.

If our hypothesis is correct, our findings will suggest that children raised in homes of smokers have more airway obstruction, phlegm, and cough because of changes in their C-fiber nerves and brain. Although we do not know the reason for sudden infant death, a possible explanation is breath holding. Our findings will suggest that a possible reason why infants raised in the homes have smokers have more sudden infant death is because changes in their C-fiber nerves and brain cause longer breath holding.

Possible applications of these findings are 1) to use drugs which block neurotrophins or substance P in children raised with ETS exposure, 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.
Publications

Effect of respiratory pattern on ozone injury to the airways of isolated rat lung
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

Smoking and pediatric respiratory health
Periodical: Clinics in Chest Medicine Index Medicus:
Authors: Joad JP ART
Yr: 2000 Vol: 21 Nbr: 1 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: 2001 Vol: 108 Nbr: Suppl. 3 Abs: Pg: 457-462

Three-dimensional mapping of ozone-induced acute cytotoxicity in tracheobronchial airways of isolated perfused rat lung
Periodical: American Journal of Respiratory Cell and Molecular Biology Index Medicus:
Authors: Postlethwait EM, Joad JP, Hyde DM ART
Yr: 2000 Vol: 22 Nbr: Abs: Pg: 191-199

Chronic passive cigarette smoke exposure augments bronchopulmonary c-fibre inputs to nucleus tractus solitarii neurons and reflex ouput in young guinea-pigs
Periodical: Journal of Physiology Index Medicus:
Authors: Mutoh T, Joad JP, Bonham AC ART
Yr: 2000 Vol: 523 Nbr: 1 Abs: Pg: 223-233

Substance P in the nucleus of the solitary tract augments bronchopulmonary C fiber reflex output
Periodical: American Journal of Physiology Index Medicus:
Authors: Mutoh T, Bonham AC, Joad JP ART
Yr: 2000 Vol: 279 Nbr: Abs: Pg: R1215-R1223

Lung C-fiber CNS reflex: Role in the respiratory consequences of extended environmental tobacco smoke exposure in young guinea pigs.
Periodical: Environmental Health Perspectives Index Medicus:
Authors: Bonham AC, Chen CY, Mutoh T, and Joad JP ART
Yr: 2001 Vol: 4 Nbr: 109 Suppl Abs: Pg: 573-578

Substance P depresses synaptic responses of second-order neurons to tracheobronchial sensory input in guinea pigs.
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: Sekizawa S-i, Bonham AC and Joad JP ABS
Yr: 2002 Vol: 165 Nbr: Abs: Pg: 720

Environmental tobacco smoke exposure causes neuroplastic changes in NTS second-order neurons in lung afferent pathways in young guinea pigs.
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: Sekizawa S-I, Bonham AC, Joad JP ABS
Yr: 2003 Vol: 167 Nbr: Abs: Pg: 147

Substance P presynaptically depresses the transmission of sensory input to bronchopulmonary neurons in the guinea pig nucleus tractus solitarii.
Periodical: Journal of Physiology Index Medicus:
Authors: Sekizawa S, Joad JP, Bonham AC ART
Yr: 2003 Vol: 522 Nbr: 2 Abs: Pg: 547-559

Passive smoke effects on cough and airways in young guinea pigs. Role of brainstem substance P.
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: Joad JP, Munch PA, Bric JM, Evans SJ, Pinkerton KE, Chen C-Y, Bonham AC ART
Yr: 2004 Vol: 169 Nbr: Abs: Pg: 499-504

Effect of chronically exposing young guinea pigs to environmental tobacco smoke on cough and bronchoconstriction, role of NK-1 receptors in the nucleus tractus solitarius.
Periodical: Journal of Allergy and Clinical Immunology Index Medicus:
Authors: Joad, JP, Munch PA, Bric JM, Evans SJ, Pinkerton KE, Chen C-Y, Bonham AC ABS
Yr: 2004 Vol: 113 Nbr: Abs: Pg: S271

Environmental tobacco smoke (ETS) exposure recruits neuropeptidergic synaptic transmission in nucleus tractus solitarius (NTS) second-order lung afferent neurons in young guinea pigs.
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: Sekizawa S, Bonham AC, Joad JP ABS
Yr: 2004 Vol: 169 Nbr: Abs: Pg: A182