• Measure : 6 minutes walk distance [ Time Frame: before treatment; at one month and two months of treatment ] [ Designated as safety issue: Yes ]
  

• VO2 max [ Time Frame: before treatment, at one month and two months ] [ Designated as safety issue: Yes ]
  
• MRC Dyspnea score [ Time Frame: before treatment, at one month and two months ] [ Designated as safety issue: Yes ]
  
• St George quality of life score [ Time Frame: before treatment and at two months of treatment ] [ Designated as safety issue: Yes ]
  
• Inflammation biological parameters [ Time Frame: before treatment and at two months of treatment ] [ Designated as safety issue: Yes ]
  

The development of anemia in patients with chronic obstructive pulmonary disease (COPD) is now taken as a predictor of increased morbidity and mortality. Preliminary data from patients investigated in our department indicate a negative correlation between anemia severity and 6-minute walking distance. Our working hypothesis is that hemoglobin level correction by erythropoietin therapy will improve the effort capacity of patients with COPD and anemia. Our objective is to conduct a pilot study of the efficacy of darbepoetin alfa.

The study will include about 15 patients with COPD recruited at three pulmonology centers based on two selection criteria: COPD stage II or III or IV according to GOLD criteria and hemoglobin level less than 12 g/dL. Effort capacity will be evaluated chiefly by performing a 6-minute walking test and by measuring VO2 at maximum exertion on a bicycle ergometer with increasing loads. Darbepoetin alfa will be given for 2 months. If the hemoglobin increase is less than 1 g/dL after 1 month, the dosage will be increased by 25%.

Effort parameters will be measured at baseline and after 1 and 2 months of treatment. Among secondary objectives, we will evaluate functional ergospirometric parameters and laboratory tests for inflammation. Total study duration will not exceed 18 months.

Inclusion Criteria:

• Male and female aged 40-75 years
• Diagnosis of a moderate to very severe COPD (stage II, III or IV according to GOLD criteria):
• a ratio of post-bronchodilator FEV1 to forced vital capacity (FVC) < 70%
• a FEV1 < 80% of the predicted value
• Hemoglobin level less than 12 g/dL.
• Peak VO2 less than 80% of predict value and 6-min walk test distance less than 500 meters

Exclusion Criteria:

• Hemorrhagic anemia
• Iron deficiency anemia (ferritin < 30 ng/ml)
• Folate and Vitamin B12 deficiency anemia
• Myelodysplastic Syndrome
• Chronic disease associated with anemia : renal insufficiency, inflammatory disease, neoplastic disease, left ventricular insufficiency (Ejection Fraction<40%)
• Chronic disease likely to interfere with dyspnea or exercise testing (cardiac insufficiency, neurologic disease, claudication)
• Acute exacerbation of COPD within the last 4 weeks
• History of thromboembolic disease
• Contraindications for cardiopulmonary exercise testing
• Contraindications for darbepoetin alfa treatment:
• uncontrolled arterial hypertension
• Hypersensitivity reaction to darbepoetin alfa
• Pregnancy or breast-feeding. Women of reproductive potential should use adequate birth control measures during the whole duration of study treatment.