Targeting Bronchoconstriction , Mucus Secretion , and Pulmonary Hypertension

Chronic obstructive pulmonary disease (COPD) is initiated by exposure to a noxious stimulus, which, in susceptible individuals, initiates an inflammatory response in the lower airways leading to emphysema and mucus hypersecretion. Numerous therapies to address different aspects of the COPD disease process—the inflammatory component as well as bronchoconstriction, mucus hypersecretion, and pulmonary hypertension—are in various stages of development. Long-acting bronchodilators are one area of current interest. The US Food and Drug Administration has recently approved tiotropium and (R,R)-formoterol is in phase 3 clinical trials. Other types of drugs under evaluation are mucolytic agents and vasodilators. Anabolic steroids are being tested to address some of the systemic effects of COPD. Current therapeutic strategies target a subset of pathogenic mechanisms, so any single treatment is only addressing a portion of the disease process. Future “rational treatment” will aim to match the appropriate drug(s) with the pathophysiological process(es). Current challenges to reaching this level of treatment include the need for better understanding of the pathophysiological processes, the need for appropriate clinical trials for COPD (particularly if exacerbations and survival are assessed), the lack of a surrogate marker for COPD to provide an expedited assessment of any treatment benefit, and the limitations of animal models of COPD. Another aspect of COPD treatment that has been under-recognized and underutilized is palliative care delivered at end-stage disease. During the last year of life, COPD patients are incapacitated by severely reduced forced expiratory volume in 1 second and performance status; multiple hospitalizations; numerous comorbidities; neuropsychiatric disorders such as depression, anxiety, and panic; insomnia; and cognitive impairment, and they typically live alone. Although it can be an uncomfortable subject, palliative care, including hospice, offers the clinician the chance to relieve the patient of pain and to reinforce the commitment of the healthcare team to care for the patient throughout the entire disease process. (Adv Stud Med. 2004;4(10A):S767-S772)