Biomedical subjects

J M Drazen

Publications and source records attributed to J M Drazen.

328 records · Page 19Linked to original sources

PubMedDate not supplied

Effect of polymorphism of the beta(2)-adrenergic receptor on response to regular use of albuterol in asthma.

BACKGROUND: Regular use of inhaled beta-adrenergic agonists may have adverse effects in some asthma patients. Polymorphisms of the beta(2)-adrenergic receptor (beta(2)-AR) can affect its regulation; however, results of smaller studies of the effects of such polymorphisms on response to beta-agonist therapy have been inconsistent. METHODS: We examined the possible effects of polymorphisms at codons 16 (beta(2)-AR-16) and 27 (beta(2)-AR-27) on response to albuterol by genotyping 190 asthmatics who had participated in a trial of regular versus as-needed albuterol use. RESULTS: During the 16-week treatment period, patients homozygous for arginine (Arg/Arg) at beta(2)-AR-16 who used albuterol regularly had a small decline in morning peak expiratory flow (AM PEF). This effect was magnified during a 4-week run-out period, when all patients returned to as-needed albuterol only. By the end of the study, Arg/Arg subjects who had used albuterol regularly had an AM PEF 30.5 +/- 12.1 liters/min lower (p = 0.012) than Arg/Arg patients who had used albuterol as needed only. Subjects homozygous for glycine at beta(2)-AR-16 showed no such decline. Evening PEF also declined in the Arg/Arg regular but not in as-need albuterol users. No significant differences between regular and as-needed treatment were associated with polymorphisms at beta(2)-AR-27. CONCLUSIONS: Polymorphisms of the beta(2)-AR may influence airway responses to regular inhaled beta-agonist treatment.

Adolescent↗

PubMedDate not supplied

Treatment of chronic stable asthma with drugs active on the 5-lipoxygenase pathway.

It is now established that 5-lipoxygenase products are synthesized and released in the airway during asthmatic reactions. The importance of these products in the asthmatic response has been established through study of the effects of 5-lipoxygenase inhibitors and leukotriene D4 receptor antagonists in patients with chronic stable asthma. In this study we review the data demonstrating that chronic administration of zileuton, an inhibitor of 5-lipoxygenase, is associated with improved airway function, decreased asthma symptoms and decreased need for asthma medication use in patients with mild to moderate asthma.

Adrenergic beta-Agonists↗

PubMedDate not supplied

High-frequency ventilation: a promising new approach to mechanical ventilation.

Adequate pulmonary ventilation can be achieved in experimental animals and in humans using tidal volumes on the order of the anatomic dead space volume applied at very high ventilatory frequencies (3-30 Hz). Classical mechanism of gas exchange cannot account for these paradoxical observations, but theories based on the concept of augmented diffusion may provide an adequate explanation for this phenomenon. Even though the exact mechanisms accounting for gas exchange are not well understood, a number of successful ventilators have been designed and tested based on the concept of small volume/high frequency ventilation. The differences among these various ventilators are compared and contrasted and possible clinical uses of the technique are discussed.

Animals↗

PubMedDate not supplied

Pharmacology of leukotriene receptor antagonists and 5-lipoxygenase inhibitors in the management of asthma.

The leukotrienes (LTs), a family of inflammatory mediators arising from the metabolism of arachidonic acid via the 5-lipoxygenase pathway, are prominently implicated in the pathobiology of asthma. Two classes of LTs, the cysteinyl LTs (LTC4, LTD4, and LTE4) and the dihydroxy-LT (LTB4) have been identified, with each class acting via distinct receptors. Inhibition of LT-mediated inflammation can be achieved by either interruption of 5-lipoxygenase action, thereby preventing formation of the LTs, or inhibition at specific LT receptor sites in the airway. Both the 5-lipoxygenase inhibitors and the cysLT receptor antagonists have thus far demonstrated the capacity to improve pulmonary function and reduce symptoms in clinical models of asthma, such as exercise-, aspirin-, or antigen-induced bronchoconstriction, and to improve pulmonary function in patients with mild-to-moderate, chronic stable asthma. The LTs are therefore critical effector molecules in some patients with asthma and important targets in the pharmacologic management of this disease.

Asthma↗