More than 17 million persons in North America suffer from chronic obstructive pulmonary diseases (asthma, chronic bronchitis, emphysema). Neuropsychological dysfunction has been described in 35% of asthmatic children receiving theophylline and up to 40% of patients with COPD in a variety of medical regimens. The consequences of this cognitive morbidity have not been fully elucidated but could be expected to include impaired school or job performance, a negative impact on self-esteem, premature retirement, increased needs for disability benefits and impairments of self-care abilities. Although the cause of this neuropsychological dysfunction are probably multifactorial, the effect of medical therapy upon cerebral function appears to be a central component. Acutely, theophylline globally decreases cerebral blood flow, and, chronically, cigarette smoking also reduces cerebral blood flow. Regional cerebral blood flow and oxygen consumption are closely linked to regional cerebral activity. Disruption of the link between regional cerebral activation and increased blood flow and substrate delivery may have detrimental effects upon cerebral function. The potential roles of bronchodilator therapy or cigarette smoking in the genesis of this cognitive morbidity have not been elucidated. Whether theophylline administration or cigarette smoking impairs the ability of cerebral blood flow to increase in response to an activating cognitive or motor task (rCBF-activation coupling) is not known. Additionally, theophylline is a powerful adenosine antagonist and can alter the release of central neurotransmitters which might also result in impairment of neuropsychological function. The proposed study will enroll 80 asthmatic subjects for the purpose of ascertaining: first, the acute and chronic effects of theophylline on neuropsychological function; second, the acute and chronic effects of theophylline upon changes in rCBF in response to global cerebral activation using a multiple modality behavioral activation procedure; third, the acute and chronic effects of theophylline in cigarette smokers with respect to neuropsychological function and upon changes in rCBF in response to global cerebral activation; and fourth, whether the previously described acute decreases in CBF following theophylline administration are maintained during chronic administration.
|Bowton, D L; Stump, D A; Anderson, R (1994) Effect of chronic theophylline therapy on brain blood flow and function in adult asthmatics. Am J Respir Crit Care Med 150:1002-5|