The goal of this exploratory method-development study is to to establish and evaluate novel non-invasive methods to monitor airway inflammation induced by allergen challenge (both by instillation during bronchoscopy and by inhalation) in patients with mild allergic asthma.
The investigator wants to further profile and develop the allergen challenge model by investigating the utility of various non-invasive monitoring methods. The hypothesis of the project is that local inflammatory changes in the lung induced by allergen can be captured by gas-enhanced magnetic resonance imaging (MRI) and analysis of exhaled breath.
The validation of cellular outcome measures and non-invasive inflammometry can be used in future clinical trials for proof of concept of novel anti-inflammatory medications.
Participants will undergo
* methacholine challenge * 2 inhaled allergen challenges * 2 MRI with hyperpolarized xenon and gadolinium based contrast agent * 2 bronchoscopies with bronchoalveolar lavage (BAL) * segmental allergen challenge during the first bronchoscopy * spirometry * skin prick test and skin prick dilution tests * measurement of particles in exhaled air * nasal filter * nasal lavage * sputum induction * peak flow meter tests * exhaled NO (nictric oxide) * blood sampling (in total approx. 190 ml)
Able and willing to give written informed consent.
Not pregnant, as confirmed by pregnancy test (see assessment schedule), and not nursing.
Of non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre-menarcheal or post-menopausal, with documented proof of hysterectomy or tubal ligation, or meets clinical criteria for menopause and has been amenorrhoeic for more than 1 year prior to the Screening Visit).
Of childbearing potential and using a highly effective method of contraception during the entire study (vasectomised partner, sexual abstinence, implants, injectables, combined oral contraceptives, hormonal Intrauterine Devices (IUDs) or double-barrier methods, i.e. any double combination of IUD, condom with spermicidal gel, diaphragm, sponge, and cervical cap).
Any clinically relevant abnormal findings in physical examination, clinical chemistry, hematology, urinalysis, vital signs, lung function or ECG at Screening Visit, which, in the opinion of the investigator, may either put the subject at risk because of participation in the study or may influence the results of the study, or the subject's ability to participate in the study.
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, metabolic disease (asymptomatic Gilbert's syndrome is allowed), endocrine disease (stable and asymptomatic hypothyroidism with or without hormone replacement therapy (HRT) is allowed), or pulmonary disease (including but not confined to chronic bronchitis, emphysema, tuberculosis, bronchiectasis or cystic fibrosis).
Regular intake of any prescribed or over the counter medication. Exceptions include paracetamol for pain relief, contraceptive medication, hormonal replacement therapy, dietary and vitamin supplements.
Specific Immunotherapy (SIT) within three years prior to the study.