Pulmonary hypertension and chronic obstructive pulmonary disease: a case for treatment.
Current pharmacotherapy for chronic obstructive pulmonary disease (COPD) relieves symptoms and reduces exacerbation through improving airflow limitation. Such drugs do not effectively improve exercise tolerance due in part to pulmonary hypertension associated with severe COPD, nor impact on its increased morbidity and mortality. Exercise intolerance is often improved (temporarily) by lung volume reduction surgery and pulmonary rehabilitation. Ambulatory oxygen is the most effective treatment of exercise limitation. Chronic cigarette smoking is the principal cause of COPD. An early change in smokers' lungs is pulmonary artery intimal thickening and vessel narrowing, which, as COPD develops, is correlated with both the severity of emphysema and bronchiolitis. This may be the consequence of combined smoking-induced apoptosis, inflammation, and imperfect repair. End-stage bronchiolitis and emphysema are likely to limit the effectiveness of bronchodilators and corticosteroids. There are effective treatments for idiopathic and scleroderma pulmonary arterial hypertension, which increase exercise tolerance and improve survival. Because idiopathic and COPD pulmonary hypertension share a common vascular intimal thickening, excess endothelin receptor expression, and plasma endothelin-1, an important therapeutic question to address is whether an oral endothelin-1 antagonist can improve exercise tolerance in severe COPD.
Higenbottam
Tim
T
Clinical Science, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, Leicestershire LE11 5RH, UK. tim.higenbottam@astrazeneca.com
D000222:Adaptation, Physiological; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D017209:Apoptosis; D001993:Bronchodilator Agents / Q000627:therapeutic use; D004417:Dyspnea / Q000503:physiopathology; D005081:Exercise Therapy; D017079:Exercise Tolerance / Q000502:physiology*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D018763:Muscle Fatigue / Q000502:physiology; D010102:Oxygen Inhalation Therapy; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D012307:Risk Factors; D016540:Smoking Cessation
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents