Validated allergen exposure chamber is plausible tool for the assessment of house dust mite-triggered allergic rhinitis

Abstract

Background: Allergen exposure chamber (AEC) is a clinical facility that allows exposure to allergenic airborne particles in controlled environment. Although AECs offer stable levels of airborne allergens, the validation of symptoms and other endpoints induced by allergen challenge is key for their recommendation as a plausible tool for the assessment of patients, especially in clinical research. This study aimed to demonstrate the reproducibility of defined clinical endpoints after AEC house dust mite (HDM) challenge under optimal conditions in patients with allergic rhinitis (AR).

Method: HDM was distributed at different concentrations. The assessment was subjective by the patients: total nasal symptom score (TNSS), visual analog scale (VAS), and objective by the investigator: acoustic rhinometry, peak nasal inspiratory flow (PNIF), and nasal secretion weight. Safety was assessed clinically and by peak expiratory flow rate (PEFR) and forced expiratory volume in the first second (FEV₁ ).

Results: Constant environment: temperature, humidity, and carbon dioxide (CO₂ ) concentration were maintained during all challenges. The concentration of HDM on average remained stable within the targeted values: 1000, 3000, 5000, 7000 particles (p)/m³ . Most symptoms were observed at concentrations 3000 p/m³ or higher. The symptoms severity and other endpoints results were reproducible. 5000 p/m³ , and challenge duration of 120 min were found optimal. The procedure was safe with no lung function abnormalities due to challenge.

Conclusion: HDM challenge in ALL-MED AEC offers a safe and reliable method for inducing symptoms in AR patients for the use in controlled clinical studies including allergen immunotherapy.

Keywords: acoustic rhinometry; allergen challenge; allergen exposure chamber; allergic rhinitis; house dust mite.

FIGURE 1

Structure of AEC. (A) Schematic AEC layout. Capacity 15–20 people. The circulation and direction of air and distributed particles are shown in pink. In the front viewing window, and control table with a computer‐controlled feeder, LPC, and a microphone for communication. (B) Photograph of AEC with subjects during the trial. Abbreviation: AEC, allergen exposure chamber; LPC, laser particle counter.

FIGURE 2

Environmental stability during HDM AEC challenges. (A) HDM particle concentration was measured by LPC in the range of 0–20 μm/m³. Each value measured by the LPC counter during the studies consists of the target concentration plus about 100 p/m³ (particle influx by subjects). The concentration of HDM 5000 p/m³ is shown twice to demonstrate reproducibility, data from two trials. (B) One representative data of CO₂ concentration, (C) temperature, and (D) humidity are shown. (E) The minimal and maximal values, mean ± SD of HDM concentrations during different trials. Abbreviations: °C, degrees Celsius; CO₂, carbon dioxide; HDM, house dust mite; LPC, laser particle counter; m, meter; min, minute(s); p, particles; ppm, parts per million; SE, standard deviation; temp., temperature.

FIGURE 3

Endpoints during AEC challenges in HDM‐allergic and non‐allergic subjects (ctrl), at different HDM concentrations. HMD triggered‐allergy subjects were exposed to different concentrations of HDM distributed in AEC during five trials: no HDM, 1000, 3000, 5000, 7000 p/m³. Non‐allergic subjects were exposed to 5000 p/m³ of HDM. (A) TNSS, (B) VAS, (C) MCA in acoustic rhinometry, (D) PNIF, and (E) nasal secretion weight were evaluated. The results are shown as mean ± SEM. Statistical significance between concentration 5000 p/m³ (as the optimal chosen concentrations) and “no HDM” and the “ctrl” group is shown; **p < .01; ***p < .001, ****p < .0001. Abbreviations: AEC, allergen exposure chamber; HDM, house dust mite; g, gram(s); MCA, minimal cross‐sectional area; p, particles; PNIF, peak nasal inspiratory flow; SEM, standard error of the mean; TNSS, total nasal symptom score; VAS, visual analog scale.

FIGURE 4

Repeatability of subjective and objective parameters in separate trials in HDM‐allergic subjects during AEC challenges with 5000 p/m ³ of HDM. (A) TNSS, (B) VAS, (C) MCA in acoustic rhinometry, (D) PNIF, and (E) nasal secretion weight were evaluated. Results are shown as mean ± SEM. No statistical differences between groups were found. Abbreviations: AEC, allergen exposure chamber; HDM, house dust mite; g, gram(s); MCA, minimal cross‐sectional area; p, particles; PNIF, peak nasal inspiratory flow; SEM, standard error of the mean; TNSS, total nasal symptom score; VAS, visual analog scale.