Effect of intravenous recombinant human APC on coagulation and inflammation in house dust mite and lipopolysaccharide induced allergic asthma

INTERVENTION: Intravenous rhAPC treatment and bronchoscopy allergen challenge and lavage. At 05:00 asthma patients will start on intravenous rhAPC treatment or placebo treatment. At 09:00 patients are challenged with housedustmite+LPS in one lungsegment and Saline in a lung segment of the contralateral lung. At 16.00 intravenous treatment is halted and at 17:00 a second bronchoscopy is done to lavage the segments. CONDITION: ; House dust mite allergy, Allergic asthma, Lung inflammation, Coagulation ; ; PRIMARY OUTCOME: Influx, differentiation and possible phenotype differences of inflammatory cells. SECONDARY OUTCOME: Eight hours after instillation of HDM and LPS (t = 8 hours) a second bronchoscopy will be performed and the challenged segments will be lavaged. In BAL fluid and blood, obtained directly before bronchoscopies, leukocyte responses, the response of alveolar macrophages, activation of the cytokine and chemokine network, complement and activation of coagulation and fibrinolysis will be determined. INCLUSION CRITERIA: 1. Intermittent to mild asthmatics between 18 and 45 years of age according to the Global Initiative for Asthma (GINA) criteria; 2. Allergy for HDM documented by a positive RAST and a positive skin prick test; 3. No clinically significant findings during physical examination and hematological and biochemical screening; 4. At spirometry FEV1 more than 70% of predicted value; 5. Able to communicate well with the investigator and to comply with the requirements of the study; 6. Stable asthma without the use of asthma medication 2 weeks prior to the study day; 7. Written informed consent; 8. No current smoking for at least 1 year and less than 10 pack years of smoking history; 9. Both male and female subjects are eligible for the study. Female subjects of child bearing potential will use adequate anti‐conceptive precautions and will be tested for pregnancy.