DEFENSE FUNCTIONS IN THE DEVELOPING RESPIRATORY SYSTEM

Project: Research project

Description

Epidemiologic and clinical studies suggest that acute airway injury during
postnatal lung growth can lead to chronic bronchitis, asthma or recurrent
respiratory infections extending into adulthood. However, the underlying
mechanisms have not been identified. The overall objective of this
proposal is therefore to establish a link between airway damage during
early life and chronic airway disease by using an animal model with lung
anatomy resembling that of man, and focusing on the role of mucociliary
dysfunction in this sequence of events. The specific aims are to 1)
establish a relationship between airway morphology and mucociliary function
during postnasal lung growth, 2) investigate the possibility that
mechanical and chemical mucosal damage shortly after birth produce
permanent mucociliary dysfunction, and 3) determine if this defect leads to
impaired bacterial clearance in, and thus bacterial colonization and
possible recurrent infection of the airways. Lambs will be studied
longitudinally between birth and six months of age (full maturation).
Mucosal injury shortly after birth will be produced by O3, or airway
manipulation simulating ventilatory support for respiratory insufficiency.
Three aspects of the respiratory system will be investigated: Mucociliary
function, airway function and airway morphology. For the first, in vivo
tracheal mucous transport rates and lung mucociliary clearance will be
measured by using a radiographic technique and an inhaled insoluble
radioaerosol, respectively. In addition, the clearance of an inhaled
bacterial aerosol will also be determined. The component functions of
mucociliary clearance will be measured in vitro by determination of mucus
secretion, ion and water transport as well as ciliary beat frequency.
Airway function will be assessed by the measurement of pulmonary resistance
and gas distribution by the single-breath nitrogen test. Routine light
microscopy will be used for the histologic studies. These observations are
expected to provide valuable new information on the pathogenesis of chronic
airway disease occurring following acute airway injury in newborns.
StatusFinished
Effective start/end date9/30/839/29/86

Funding

  • National Institutes of Health

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Respiratory System
Parturition
Lung
Mucociliary Clearance
Breath Tests
Chronic Bronchitis
Ion Transport
Wounds and Injuries
Lung Injury
Growth
Infection
Aerosols
Respiratory Insufficiency
Epidemiologic Studies
Chronic Disease
Nitrogen
Asthma
Animal Models
Gases
Newborn Infant

ASJC

  • Medicine(all)