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

Fraunhofer-Institute of Toxicology and Experimental Medicine

Status

Completed

Conditions

Mild Intermittent Asthma (Gina 1)

Treatments

Other: Bronchoscopy

Study type

Interventional

Funder types

Other

Identifiers

NCT01378624

10-07 ZAP2

Details and patient eligibility

About

Ex vivo effect of fragments and modified forms of surfactant protein D on pulmonary immune cells derived from bronchoalveolar lavage after segmental allergen challenge in patients with asthma and pilot study to assess local inflammation induced by segmental allergen challenge by magnetic resonance imaging.

Full description

The effect of surfactant protein D under native and altered conditions will be investigated in immune cells that are derived from bronchoalveolar lavage in patients with allergic asthma following segmental allergen challenge. The goal of this study is to elucidate the pro- versus anti-inflammatory function of SP-D molecules and to identify motifs of SP-D that have treatment potential in allergic asthma and to assess local inflammation induced by segmental allergen challenge by magnetic resonance imaging.

In addition to the patients with allergic asthma a subgroup of five healthy subjects will be included into the study to elucidate the specificity of the SP-D (surfactant protein-D) effect on the allergic inflammation in the invitro models.

The primary objective of this study is to isolate BAL cells for different invitro experiments and to assess local inflammation after segmental allergen challenge by MRI in response to the applied allergen dose.

Therefore, following a baseline BAL, allergen (2× individual dose, 1× one tenth of individual dose) and saline (1×) will be instilled into four different lung segments during a first bronchoscopy. After 24 hours during a second bronchoscopy BAL will be collected in these challenged segments to harvest invaded cells for invitro experimentation. In addition, bronchial biopsies and epithelial brushes will be taken to assess the degree of local inflammation in bronchial mucosa and to study the activation of airway epithelium following allergen challenge.

Enrollment

15 patients

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

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