Clinical validation of controlled grass pollen challenge in the Environmental Exposure Unit (EEU)

Abstract

RationaleThe Environmental Exposure Unit (EEU), a controlled allergen exposure model of allergic rhinitis (AR), has traditionally utilized ragweed pollen. We sought to clinically validate the use of grass pollen in the EEU.MethodsHealthy volunteers with a history of AR symptoms during grass pollen season and supportive skin test responses attended the EEU for 3 hrs of rye grass pollen exposure (Lolium Perenne). Non-atopic controls were also recruited. Participants assessed individual rhinoconjunctivitis symptoms to generate Total Nasal Symptom Score (TNSS; max 12) and Total Symptom Score (TSS; max 24) and recorded Peak Nasal Inspiratory Flow (PNIF) q30min while in the EEU. Participants returned the following day for an additional 3 hrs of pollen exposure. Two separate groups allowed for the exploration of lower vs. higher pollen concentrations and subsequent effects on symptoms.Results78 participants were screened, of whom 39 were eligible and attended the 2x3h EEU visits, plus 8 non-atopic controls. Mean TSS, TNSS and PNIF values amongst participants in the higher pollen concentration group (target 3500 grains/m3) after the first 3 hr exposure were 18.9, 9.7 and 68 L/min, respectively. In comparison, mean TSS, TNSS and PNIF values in the lower pollen concentration (2500 grains/m3) group were only 13.3, 7.6, and 82 L/min, respectively. The subsequent day of pollen exposure did not appreciably alter the maximal TSS/TNSSs, but rather resulted in a more rapid onset of symptomatology, with higher mean scores at the 30 min, 60 min and 90 min timepoints. The non-atopic controls remained asymptomatic.ConclusionsThis study provides clinical validation of the ability to generate allergic rhinoconjunctivitis symptoms amongst grass-allergic individuals in the EEU.

Method for a homogeneous distribution of pollens in an environmental exposure chamber

“…All of this made it possible to reproduce typical symptoms of seasonal AR out-of-season during the Danish winter. Consistent with findings from other EECs [16,21], the participants' symptoms rose throughout the exposure period.…”

“…At 3500 pollens/m 3 and after 3 h of exposure, a mean TNSS of 9.7 was seen , and the TNSS maximum is 12. At 2500 pollens/m 3 , the mean TNSS was 7.6 . However, an earlier study using a different grass pollen ( Dactylis glomerata ) and a concentration of 4000 ± 300 pollens/m 3 found a mean TNSS of 4.5 after 4 h of exposure , quite similar to this current study's finding of a mean TNSS of 4.71 at 3½ h. The reason for the discrepancies between exposure levels and symptom severity remains unexplained.…”

“…However, even though a number of different facilities for AR trials exist, for example ceiling-based pollen feeding systems [7,13,14] or pollen dispersion via a laminar air stream [15], to date, no international standards have been established for validating such facilities [16]. Thus, to compare research methods and results from different EECs, detailed information on each EEC's system is needed [7,13].…”

Technical and clinical validation of the Allergen BioCube® for timothy grass

“…While mean TNSS responses were somewhat lower at Visits 4 and 5 than at Visits 2 and 3, the general trend was repeated at these later visits and was typical of EEU exposures : a sharp initial increase in allergy symptoms, with continued but less steep increases throughout, or a leveling off or slight decrease towards the end of the 3‐h Biocube allergen exposure at each study visit. It is interesting to note that in the BioCube study, some of the highest individual subject TNNS occurred at later BioCube grass exposure sessions (Visits 3 through 5).…”

A metabolomic, geographic, and seasonal analysis of the contribution of pollen-derived adenosine to allergic sensitization

“…The P2 model uses a factor of 10 to exaggerate the effect. For comparison, environmental exposure units generally target 3.5 × 10 3 grains/m 3 for grass and weed pollens, (Ellis et al 2015; Ellis et al 2013) so the P2 model using 10 5 , 10 4 , and 10 4 for tree, grass, and weed, respectively, is rather high. The third model (EX) uses the same peak pollen count, but assumes exercise for 1 hour that increases the volume of air 7 fold, (Berry et al 1996) which we consider a rather extreme exposure model.…”