PATHOPHYSIOLOGY OF BRONCHIAL ASTHMA

Project: Research project

Description

Bronchial asthma is characterized by the triad of airway smooth
muscle contraction, mucociliary dysfunction and edema. Two of
these manifestations involve the mucosa. During the previous and
current grant periods, we conducted a series of experiments in an
attempt to characterized airway mucociliary function in a sheep
model of allergic bronchoconstriction. Those studies have
demonstrated that antigen challenge leads to an impairment of
mucociliary clearance which is related to chemical mediators of
anaphylaxis, is caused by abnormal airway secretory functions,
and persists for several days. The overall objective of the present
proposal is to extend those observations to other aspects of
mucosal function and to assess the role of inflammation in the
demonstrated defects. Specifically, we will determine if, in the
same sheep model, 1) the sustained mucociliary dysfunction after
antigen challenge is causally related to inflammation, 2) the depth
and distribution of airway mucus influences the bronchial
responsiveness to inhaled bronchoconstrictor aerosols, 3) the
allergic airway is characterized by an inappropriate adaptation in
epithelial water transport to osmotic stimuli and this abnormality
is caused by inflammatory cell products, and 4) thermal stress
produces differential vascular responses in allergic and non-
allergic airways due to differences in mediator generation of
autonomic responsiveness. The in vitro techniques will include
the measurement of tracheal mucus velocity, respiratory
mechanics, aerosol deposition, tracheal mucosal blood flow and
tissue volume. In vitro techniques will include the measurement
of mucus glycoprotein, ion, water fluxes and hydraulic
conductivity in tracheal tissue, and determination of the
interaction among ciliary beat frequency, mucus depth, mucus
rheology and mucus transport rate. These physiologic parameters
will be correlated with histopathologic and humoral indices (RIA
and HPLC) of inflammation. Most of the proposed in vivo and in
vitro methods have been previously used and validated in this and
other laboratories. We expect to show that in the allergic airway,
mucosal defects re involved in the abnormal airway responses to
physical and pharmacologic stimuli and are related to
inflammation. The results may form the basis for new treatment
strategies in patients with bronchial asthma.
StatusFinished
Effective start/end date4/1/788/31/97

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $177,499.00
  • National Institutes of Health: $210,120.00
  • National Institutes of Health

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Asthma
Mucus
Glycoconjugates
Bacterial Adhesion
Sheep
Organized Financing
Inflammation
Smooth Muscle
Glycocalyx
Antigens
Oxygen
Microvessels
Anaphylaxis
Aerosols
Architectural Accessibility
Myristic Acid
Phagocytes
Lectins
Bronchoconstrictor Agents
Water

ASJC

  • Medicine(all)