Specialized examinations
Medaimun specializes in the following time-consuming and complex examinations:
Overview of our special examinations
1. Allergen provocation
1.1 Oral allergen provocation
The double-blind oral food challenge is an established procedure in which a food or placebo, to which you might be allergic, is administered in increasing amounts under medical supervision in order to diagnose or rule out a food allergy.
Medaimun is an expert in the double-blind oral peanut challenge. Medaimun has successfully participated in several clinical studies, including Phase 2 and Phase 3 trials.
References:
- AR101 Oral Immunotherapy for Peanut Allergy Clinical Trial. N Engl J Med. 2018 Nov 22;379(21):1991-2001. doi: 10.1056/NEJMoa1812856. PALISADE Group of Clinical Investigators; Vickery BP, Vereda A, Casale TB, Beyer K,.. Blumchen K, Zielen S et al.
1.2 Conjunctival and nasal allergen provocation
Conjunctival and nasal allergen exposure are established procedures in which an allergen or placebo, to which the patient may be allergic, is administered in increasing doses into the eye or nose under medical supervision in order to verify a pollen allergy. We have an SOP according to the label for both conjunctival and nasal provocation. Both methods are used primarily in Phase 2 studies used for dose finding in allergen-specific immunotherapy.
Medaimun is an expert in Phase 2 studies in specific allergen immunotherapy (AIT). Over the past 10 years, Medaimun has successfully participated in several clinical studies:
References:
- Strong dose response after immunotherapy with PQ grass using conjunctival provocation testing. Zielen S, Kuna P, Aberer W, Lassmann S, Pfaar O, Klimek L, Wade A, Kluehr K, Raab J, Wessiepe D, Lee D, Kramer MF, Gunawardena K, Higenbottam T, Heath MD, Skinner MA, de Kam PJ. World Allergy Organ J. 2019 Oct 25;12(11):100075. doi: 10.1016/j.waojou.2019.100075.
- Nasal IgE in subjects with allergic and non-allergic rhinitis. Eckrich J, Hinkel J, Fischl A, Herrmann E, Holtappels G, Bachert C, Zielen S. World Allergy Organ J. 2020 Jun 23;13(6):100129. doi: 10.1016/j.waojou.2020.100129.
- Randomized controlled trials define shape of dose response for Pollinex Quattro Birch allergoid immunotherapy. Worm M, Higenbottam T, Pfaar O, Mösges R, Aberer W, Gunawardena K, Wessiepe D, Lee D, Kramer MF, Skinner M, Lees B, Zielen S.Allergy. 2018 Sep;73(9):1812-1822. doi: 10.1111/all.13478
1.3 Bronchial Allergen Provocation
Bronchial allergen exposure has become a well‑established procedure in Phase 2 “proof‑of‑concept” studies.
The allergen solution is nebulized using a Medic Aid nebulizer and administered with the aid of the Aerosol Provocation System APS® (VIASYS Healthcare GmbH, Hoechberg, Germany).
Specific bronchial hyperreactivity (BHR) is defined by the cumulative dose of the allergen at which the FEV₁ decreases by 20% compared to baseline (PD20FEV₁).
The provocation can be performed as a single-step or multi-step challenge.
(1) Download
Low-dose allergen challenge
This method is based on the inhalation of a low dose of allergen that triggers a 5% decrease in FEV1 (PD5FEV1). The method is ideal for generating an inflammatory situation through repeated allergen exposure. The low-dose allergen provocation model is a perfect tool for studying anti-inflammatory drugs and substances, such as functional foods.
(2) Download
High-dose allergen challenge
The high-dose allergen provocation is a newly established method in Frankfurt, where subjects are repeatedly exposed to allergens (4 provocations of PD20FEV1 within one week). This provocation not only leads to changes in lung function (decrease in FEV1) but also triggers asthmatic symptoms. The high-dose allergen challenge can only be conducted under partial inpatient monitoring of the patients.
(3) Download
Medaimun has its own SOP and has participated in several clinical studies involving bronchial allergen provocation (5–6)
References:
- Bronchial allergen challenge using the Medicaid dosimeter. Schulze J, Rosewich M, Dressler M, Riemer C, Rose MA, Zielen S. Int Arch Allergy Immunol. 2012;157(1):89-97. doi: 10.1159/000324473.
- Effect of n-3 polyunsaturated fatty acids in asthma after low-dose allergen challenge. Schubert R, Kitz R, Beermann C, Rose MA, Lieb A, Sommerer PC, Moskovits J, Alberternst H, Böhles HJ, Schulze J, Zielen S. Int Arch Allergy Immunol. 2009;148(4):321-9. doi: 10.1159/000170386.
- Airway responses and inflammation in subjects with asthma after four days of repeated high-single-dose allergen challenge. Schulze J, Voss S, Zissler U, Rose MA, Zielen S, Schubert R. Respir Res. 2012 Sep 19;13(1):78. doi: 10.1186/1465-9921-13-78.
- EAACI position paper on the clinical use of the bronchial allergen challenge: Unmet needs and research priorities. Agache I, Antolin-Amerigo D, … et al., Zielen S, Eguiluz-Gracia I. Allergy. 2022 Jun;77(6):1667-1684. doi: 10.1111/all.15203.
- Omalizumab protects against allergen-induced bronchoconstriction in allergic (immunoglobulin E-mediated) asthma. Zielen S, Lieb A, De La Motte S, Wagner F, de Monchy J, Fuhr R, Munzu C, Koehne-Voss S, Rivière GJ, Kaiser G, Erpenbeck VJ. Int Arch Allergy Immunol. 2013;160(1):102-10. doi: 10.1159/000339243.
- The late asthmatic reaction is in part independent from the early asthmatic reactions. Zielen S, Alemdar O, Wimmers A, Gronau L, Duecker R, Hutter M, Trischler J, Monchy JG, Schubert R. Int J Mol Sci. 2025 Feb 27;26(5):2088. doi: 10.3390/ijms26052088.
2. Bronchitis Model: LPS‑Induced Inflammation
J Endotoxin Res. 2006;12(6):367-74. (Download)
- Kitz R, Rose MA, Placzek K, Schulze J, Zielen S, Schubert R. LPS inhalation challenge: a new tool to characterize the inflammatory response in humans.
Med Microbiol Immunol. 2008 Mar;197(1):13-9. (Download) - Lipopolysaccharide challenge: immunological effects and safety in humans. Zielen S, Trischler J, Schubert R. Expert Rev Clin Immunol. 2015 Mar;11(3):409-18. doi: 10.1586/1744666X.2015.1012158.
3. Serial Lung Function Measurement
Medaimun has extensive expertise in the field of lung function measurement:
- Spirometry
- Body Plethysmography with Diffusion Measurement
- Oscilloresistometry
Medaimun has an inpatient unit and has participated as a study site in various overnight studies (Phase II) involving serial lung function measurements and pharmacokinetic studies.
Medaimun has two very comfortable overnight rooms and several state‑of‑the‑art lung function testing devices.
4. Sputum Examinations
Medaimun is an expert in sputum analysis. Induced sputum is an important procedure for characterizing bronchial inflammation in greater detail. An in‑house SOP for the collection and processing of induced sputum has been established, and the results have been published in numerous clinical studies.
References:
- Sputum biomarker profiles in cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) and association between pulmonary function. Eickmeier O, Huebner M, Herrmann E, Zissler U, Rosewich M, Baer PC, Buhl R, Schmitt-Grohé S, Zielen S, Schubert R.Cytokine. 2010 May;50(2):152-7. doi: 10.1016/j.cyto.2010.02.004.
- Mucolytic Effectiveness of Tyloxapol in Chronic Obstructive Pulmonary Disease – A Double-Blind, Randomized Controlled Trial. Randomized Controlled Trial PLoS One . 2016 Jun 16;11(6):e0156999. doi: 10.1371/journal.pone.0156999. Koppitz M, Eschenburg E, Salzmann E, Rosewich R, Schubert R, Zielen S.
- Cell distribution and cytokine levels in induced sputum from healthy subjects and patients with asthma after using different nebulizer techniques. Koc-Günel S, Schubert R, Zielen S, Rosewich M. BMC Pulm Med. 2018 Jul 13;18(1):115. doi: 10.1186/s12890-018-0683-8.
- Bronchial inflammation biomarker patterns link humoral immunodeficiency with bronchiectasis-related small airway dysfunction. Zissler UM, Thron A, Eckrich J, Bakhtiar S, Schubert R, Zielen S. Clin Exp Allergy. 2022 Jun;52(6):760-773. doi: 10.1111/cea.14140.
- Proinflammatory pattern in the lower airways of non-asthmatic obese adolescents. Gutmann D, Dressler M, Eickmeier O, Herrmann E, Kirwil M, Schubert R, Zielen S, Zissler UM. Cytokine. 2024 Jan;173:156452. doi: 10.1016/j.cyto.2023.156452.
5. Biomarker and Pharmacokinetics (PK) Laboratory Analyses
Biomarkers are biological characteristics that are measured and assessed in blood, urine, cerebrospinal fluid, or in nasal or sputum samples, as well as in exhaled air. Biomarkers indicate pathological changes. In asthma, the measurement of exhaled nitric oxide (eNO) in the breath is an established marker that reflects bronchial inflammation. eNO values between 5–30 ppb are considered normal, while values >30 ppb are elevated. In allergic asthma and house dust mite (HDM) allergy, a value of >46 ppb not only indicates bronchial inflammation. Such a value is associated with a 100% likelihood of bronchial obstruction in a cold-air challenge (1).
Pharmacokinetics (PK) describes the behavior of a drug or biomarker within the human body. This is usually assessed through serial blood sampling in the context of Phase 1 and Phase 2 studies. Medaimun has more than 10 years of experience in conducting blood draws and performing PK laboratory analyses and biomarker measurements.
References:
- Exhaled NO as a predictor of exercise-induced asthma in cold air. Dreßler M, Salzmann-Manrique E, Zielen S, Schulze J. Nitric Oxide. 2018 Jun 1;76:45-52. doi: 10.1016/j.niox.2018.03.004. Epub 2018 Mar 8.
- Dogmas, challenges, and promises in phase III allergen immunotherapy studies. De Kam PJ, Kramer MF, Shamji MH, Oluwayi K, Heath MD, Jensen-Jarolim E, Berger MH, Berger UE, Graessel A, Sellwood F, Zielen S, Vogelberg C, Zieglmayer P, Mösges R, Klimek L, DuBuske LM, Shreffler WG, Bernstein JA, Kündig TM, Skinner MA. World Allergy Organ J. 2021 Sep 28;14(9):100578. doi: 10.1016/j.waojou.2021.100578.
- Altered Cerebrospinal Fluid (CSF) in Children with Ataxia Telangiectasia. Woelke S, Schrewe R, Donath H, Theis M, Kieslich M, Duecker R, Auburger G, Schubert R, Zielen S. Cerebellum. 2021 Feb;20(1):31-40. doi: 10.1007/s12311-020-01175-x.
