AIRWAY RESPONSE--MECHANICAL DETERMINANTS AND MA TURATION

Project: Research project

Description

The long term objectives of this project are to understand the mechanisms
that contribute to the decline in airway reactivity between infancy and
adolescence, and the presence of heightened airway reactivity in infants
and older children following lung injury early in life. Normal infants
and adult asthmatics demonstrate greater maximal airway narrowing in
response to bronchoconstrictors than do normal adults. Mechanical forces
in the airways and the lung parenchyma, and the interdependence between
these forces, are significant determinants of the decrease in airway
caliber that occurs in response to bronchoconstrictors. We hypothesize
that the balance between these forces change with the maturation of the
lung, and that an alteration of these forces early in life results in
heightened airway reactivity in older children and adults. The specific
aims of this project are 1) to determine the extent of age-related
differences in the responses of airway resistance and tissue resistance
to methacholine using an animal model, 2) to compare airway-parenchymal
interdependence in the immature and mature animal, 3) to determine the
effects of parenchymal lung injury early in life on airway reactivity in
the mature animal, and 4) to compare the static and the dynamic
contractile properties of immature and mature rabbit airway smooth
muscle. An alveolar capsule technique will be used to partition
pulmonary resistance into airway and tissue components. Physiologic
measurements in mature and immature animals will be correlated with
morphometric assessments of airway caliber, airway wall thickness,
quantity of airway smooth muscle, elastin, and alveolar size and shape.
Airway-parenchymal interdependence will be evaluated through physiologic
and morphometric assessments of airway narrowing at different lung
volumes. Parenchymal injury in the immature animal will be produced with
intra-tracheal elastase and collagenase, and when the animals are mature,
physiologic and morphometric measurements will be obtained.
StatusFinished
Effective start/end date8/13/923/31/18

Funding

  • National Institutes of Health: $424,911.00
  • National Institutes of Health: $316,938.00
  • National Institutes of Health
  • National Institutes of Health: $307,706.00
  • National Institutes of Health
  • National Institutes of Health: $347,978.00
  • National Institutes of Health: $359,212.00
  • National Institutes of Health: $385,061.00
  • National Institutes of Health: $431,382.00
  • National Institutes of Health: $293,521.00
  • National Institutes of Health: $349,764.00
  • National Institutes of Health
  • National Institutes of Health: $412,416.00
  • National Institutes of Health: $353,194.00
  • National Institutes of Health: $390,598.00
  • National Institutes of Health: $391,561.00
  • National Institutes of Health: $240,214.00
  • National Institutes of Health: $431,382.00
  • National Institutes of Health: $388,499.00
  • National Institutes of Health: $348,294.00
  • National Institutes of Health: $398,929.00

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Lung
Smooth Muscle
Asthma
Continuous Positive Airway Pressure
Bronchoconstrictor Agents
Muscles
Bronchoconstriction
Cytoskeletal Proteins
Interleukin-13
Inflammation
Cellular Mechanotransduction
Rabbits
Airway Resistance
Allergens
Airway Remodeling
Lung Injury
Respiration
Growth
Therapeutics
Actin Cytoskeleton

ASJC

  • Medicine(all)