Cat allergen exposure in a naturalistic exposure chamber: A prospective observational study in cat-allergic subjects.

BACKGROUND: To determine the proportion and reproducibility of cat-allergic mild asthmatics with early asthmatic response (EAR) during cat allergen exposure in a naturalistic exposure chamber (NEC). METHODS: This was a prospective, observational study in 30 cat-allergic mild asthmatics who received two 180-min cat-allergen (Felis domesticus allergen 1 [Fel d 1]) challenges 27 days apart in an NEC. RESULTS: An EAR (≥20% reduction from baseline in forced expiratory volume in 1 s [FEV1]) was observed in 67% and 52% of subjects at first and second NEC exposure, respectively, with similar median time to EAR; 44% of subjects had an EAR on days 1 and 28. Late asthmatic response (≥15% reduction in FEV1 within 24 h of NEC exit) was observed in 33% of subjects following either exposure. Average FEV1 and total nasal symptom score during NEC exposure were highly correlated within subjects between NEC exposures (r = 0.91, p < 0.0001; r = 0.73, p < 0.001), but total ocular symptom score was not. Time to EAR, but not average FEV1, was significantly associated with NEC Fel d 1 concentration, which was variable. There were no serious adverse events; 12/30 subjects experienced 20 adverse events (including asthma, 10%; headache, 10%). CONCLUSIONS: The NEC model demonstrates that average FEV1 change is highly reproducible and has a low correlation with cat allergen levels. However, time to EAR and incidence of EAR are less reproducible and are highly correlated with NEC allergen levels. Average FEV1, rather than incidence of EAR or time to EAR, could be considered as an endpoint for interventional trials testing cat-specific anti-allergy therapies using an NEC.

Technical standards in allergen exposure chambers worldwide - an EAACI Task Force Report.

Allergen exposure chambers (AECs) can be used for controlled exposure to allergenic and non-allergenic airborne particles in an enclosed environment, in order to (i) characterize the pathological features of respiratory diseases and (ii) contribute to and accelerate the clinical development of pharmacological treatments and allergen immunotherapy for allergic disease of the respiratory tract (such as allergic rhinitis, allergic rhinoconjunctivitis, and allergic asthma). In the guidelines of the European Medicines Agency for the clinical development of products for allergen immunotherapy (AIT), the role of AECs in determining primary endpoints in dose-finding Phase II trials is emphasized. Although methodologically insulated from the variability of natural pollen exposure, chamber models remain confined to supporting secondary, rather than primary, endpoints in Phase III registration trials. The need for further validation in comparison with field exposure is clearly mandated. On this basis, the European Academy of Allergy and Clinical Immunology (EAACI) initiated a Task Force in 2015 charged to gain a better understanding of how AECs can generate knowledge about respiratory allergies and can contribute to the clinical development of treatments. Researchers working with AECs worldwide were asked to provide technical information in eight sections: (i) dimensions and structure of the AEC, (ii) AEC staff, (iii) airflow, air processing, and operating conditions, (iv) particle dispersal, (v) pollen/particle counting, (vi) safety and non-contamination measures, (vii) procedures for symptom assessments, (viii) tested allergens/substances and validation procedures. On this basis, a minimal set of technical requirements for AECs applied to the field of allergology is proposed.

Effects of red blood cell aggregation on microparticle wall adhesion in circular microchannels.

The wall adhesion of 1 µm microparticles in human blood was studied in circular microchannels. The level of particle wall adhesion was measured for varying levels of shear rate and varying degrees of red blood cell aggregation, which was modulated by the addition of macromolecule dextran 500. The blood preparations were injected into PDMS microfluidic devices that were modified to have circular channels, better matching the geometry of physiological microcirculation compared to square channels or Couette flow systems. The circular walls of the microchannels were embedded with biotinylated phospholipids to which marginating microspheres coated with streptavidin bound. The particle wall adhesion was evaluated by counting the particles adhering to the channel wall after flushing the channel. Blood preparations of five dextran concentrations (including baseline case of 0%) were tested for four flow velocities, to quantify the effects of aggregation for varying shear rate. It was found that the level of particle wall adhesion was positively correlated with the level of RBC aggregation, particularly at low shear rates, when aggregation was enhanced. The particle adhesion was especially enhanceat aggregation levels in the range of physiological aggregation levels of whole blood, suggesting that RBC aggregation plays an important role in the dynamic of platelets and leukocytes in vivo.