Ex Vivo Effect of Surfactant Protein D on Pulmonary Cells in Patients With Asthma and Pilot Study to Assess Local Inflammation Induced by Segmental Allergen Challenge by Magnetic Resonance Imaging

This is an interventional basic science trial for Mild Intermittent Asthma (Gina 1) Read More

Inclusion Criteria:

• Able and willing to give written informed consent
• Physician diagnosis of mild asthma according to GINA guidelines (1;7)
• Nonsmokers with a history of less than 1 pack a year having been nonsmokers for at least the last five years
• FEV1 80% of predicted
• Positive skin prick test for grass mix or D. pteronyssinus at or within 12 months prior to the screening visit
• Positive response to an incremental inhaled allergen challenge with house dust mite allergen or grass pollen allergen

• Women will be considered for inclusion if they are:

  • Not pregnant, as confirmed by pregnancy test, and not nursing
  • Of non-child bearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is pre-menarchial or post-menopausal, with documented proof of hysterectomy or tubal ligation, or meet clinical criteria for menopause and has been amenorrhoeic for more than 1 year prior to the screening visit)o of childbearing potential and using a highly effective method of contraception during the entire study (vasectomized partner, sexual abstinence
  • The lifestyle of the female should be such that there is complete abstinence from intercourse from two weeks prior to the study until at least 72 hours after the end of the study
  • Implants, injectables, combined oral contraceptives, hormonal IUDs, or double barrier methods (i.e. any double combination of IUD, condom with spermicidal gel,diaphragm, sponge, and cervical cap)

Exclusion Criteria:

• History of upper or lower respiratory tract infection four weeks prior to the informed consent visit
• Past or present disease, which as judged by the investigator, may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, hematological disease, neurological disease, psychiatric disease, endocrine disease, infectious disease, inflammatory disease, or pulmonary disease (including but not confined to chronic bronchitis, emphysema, tuberculosis, bronchiectasis or cystic fibrosis).
• Clinically significant pathological findings in safety laboratory tests
• Regular intake of any medication other than short acting inhaled beta agonists, paracetamol for pain relief, birth control medication, hormonal replacement therapy, dietary and vitamin supplements
• Specific Immunotherapy (SIT) within two years prior to the study
• Use of anti-inflammatory medication including systemic or inhaled corticosteroid within the last four weeks
• Any history of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures.
• Suspected hypersensitivity to any ingredients of the medication in line with bronchoscopy (bronchodilators, sedatives and local anesthetics)
• Conditions or factors, which would make the subject unlikely to be able to undergo bronchoscopy or incremental allergen challenge
• Conditions or factors, which would make the subject unable to undergo MRI such as metal containing implants, remainders of shell splinters or bullets, or claustrophobia.
• History of drug or alcohol abuse
• Suspected inability to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study.
• Participation in a clinical trial 30 days prior to enrollment
• Segmental allergen challenge three months prior to treatment
• Risk of non-compliance with study procedures
• Calculated GFR <30 ml/min/1.73 m2
• Known allergy to MRI based contrast agents
• Donation of more than 500 ml of blood in the preceding 9 weeks before the trial examination
• Hb Hemoglobin below lower limit of normal value

Additional Inclusion Criteria for healthy control subjects:

• Healthy subjects with no clinical evidence of allergic rhinitis and respiratory disease (e.g. asthma)
• Negative skin prick test for grass mix or D. pteronyssinus at or within 12 months prior to the screening visit
• Negative response to an incremental metacholine challenge (PC20 ≥ 8mg/ml)
• Total IgE (Immunglobulin E) <100 IU/ml