Classical Conditioning to Treat Allergic Airway Diseases

Most clinicians who care for patients with inflammatory airway diseases such as allergic
rhinitis and asthma are aware of the negative effects of certain sights, sounds and smells
that can precipitate clinical exacerbations in certain susceptible patients. This is thought
to be due to subconscious associations between these observable stimuli paired and actual
exposure to allergens that induce clinical symptoms. The severity and duration of these
symptoms are typically related to levels of anxiety and/or depression in affected patients.
Classical conditioning of the immune response has been described in many animal and some
human studies in association with administration of immunosuppressive drugs. In successfully
conditioned individuals, subsequent exposure to the conditioning stimulus alone produces
immunosuppressive changes similar to those caused by the drugs themselves. Since disease
exacerbating conditioning appears to be prevalent in allergic patients, these conditions
make an excellent human model for understanding the relationships between classical
conditioning, psychological stress (particularly anxiety and depression) and immune
regulation. Thus this proposal will seek to examine the hypothesis that antiinflammatory
effects of pharmacotherapeutic agents can be classically conditioned and are clinically
effective due to changes in immunoregulatory imbalances known to occur in patients with
allergic airway diseases. The effectiveness of this therapeutic approach will be
significantly affected by levels of psychological stress and individual suggestibility. This
will be investigated with the following Specific Aims: (1). Determine the relative
effectiveness of classical conditioning by a novel gustatory stimulus paired with
immunosuppressive doses of corticosteroid on in vivo and in vitro immune responses (allergen
- specific vs. general) of patients before, during and after classical conditioning
correlated with level of clinical response; (2) Determine the role of neuroendocrine
mechanisms (particularly catecholamines) on the inducibility and duration of the conditioned
immune responses; and (3) Investigate the influence of psychological stress levels
(including anxiety and depression) and/or suggestibility on baseline immune changes, success
and duration of the classical conditioning.

These data will help define parameters for classical conditioning in humans, establish a
model to investigate mechanisms and serve as the basis for development of future
interventional protocols for severe inflammatory diseases involving classical conditioning.