Comparison of allergic rhinitis outcomes of the environmental exposure unit and nasal allergen challenge model

Tenn, Mark W.; Steacy, Lisa M.; Adams, Daniel E.; Walker, Terry; Ellis, Anne K.

doi:10.1016/j.anai.2019.04.003

Cited by 11 publications

(11 citation statements)

References 10 publications

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“…Another study that compared clinical outcomes between NAC and EEC observed good agreement between both challenge modalities with respect to peak and mean symptom scores. 3 It is unclear whether differences in the type/ amount of allergen used in challenges, or simply the small number of participants used in experiments, may explain the lack of agreement with our data. Importantly, in our study, the effects of the 2 challenges on immunologic outcomes and on nasal mucosal transcriptomics show striking similarities and are highly correlated.…”

Section: Discussionmentioning

confidence: 61%

“…2 Direct comparisons of NAC and EEC have occurred in only 1 study; however, immunologic responses were not assessed. 3 Various clinical and physiologic outcomes can be measured in the course of these challenges including standardized symptom scores, such as the total nasal symptom score (TNSS), and objective measures of nasal obstruction such as the peak nasal inspiratory flow (PNIF). The NAC has also been extensively used to conduct mechanistic research and has unveiled many aspects of the pathophysiology of allergic rhinitis including the acute release of mast cell mediators upon allergen exposure, the nasal latephase reaction, the local influx of inflammatory cells, the production of type 2 and other cytokines and chemokines, and the development of nasal hyperrespnsiveness.…”

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confidence: 99%

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Nasal allergen challenge and environmental exposure chamber challenge: A randomized trial comparing clinical and biological responses to cat allergen

Larson

Patel

Salapatek

et al. 2020

Journal of Allergy and Clinical Immunology

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Background: The direct-instillation nasal allergen challenge (NAC) and the environmental exposure chamber (EEC) are 2 methods of conducting controlled allergen provocations. The clinical and biological comparability of these methods has not been thoroughly investigated. Objective: We sought to compare clinical and immunologic responses to cat allergen in NAC versus EEC. Methods: Twenty-four participants were randomized to receive either NAC followed by a 2-day challenge in an EEC or a 2-day challenge in an EEC followed by NAC. Challenges were separated by 28-day washout periods. We measured total nasal symptom scores, peak nasal inspiratory flow, nasal (0-8 hours) and serum cytokines, serum antibodies, peripheral blood antigen-specific T lymphocytes, and gene expression in nasal scrapings. The primary outcome was the total nasal symptom score area under the curve for the first 3 hours after allergen exposure in NAC or after initiation of exposure in EEC. Results: Both challenges increased IL-5 and IL-13 in nasal fluids and serum and resulted in altered nasal cell expression of gene modules related to mucosal biology and transcriptional regulation. Changes in gene modules, more so than cytokine measurements, showed significant associations with total nasal symptom score and peak nasal inspiratory flow. Overall, EEC exposure generated larger responses and more early terminations compared with NAC. Although the 2 challenges did not correlate in symptom magnitude or temporality, striking correlations were observed in cytokine levels. Conclusions: Although clinical outcomes of NAC and EEC were temporally different and nonequivalent in magnitude, immunologic responses were similar. Selection of a particular allergen challenge method should depend on considerations of study objectives and cost.

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Section: Discussionmentioning

confidence: 61%

mentioning

confidence: 99%

Nasal allergen challenge and environmental exposure chamber challenge: A randomized trial comparing clinical and biological responses to cat allergen

Larson

Patel

Salapatek

et al. 2020

Journal of Allergy and Clinical Immunology

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“…[22][23][24] Although few community-based studies have assessed the relationship between outdoor pollen exposure, lung function and airway inflammation, the findings have not been integrated systematically, especially at a detailed mechanistic level. Laboratory challenge studies may not be representative of outdoor pollen exposure because they involve direct introduction of allergens into the nostrils, 25 do not take into account other seasonal factors or environmental co-stimulants 26 and often impose extremely high pollen concentrations that are unlikely to occur in pollen seasons. 27,28 Here, we synthesized the available evidence to determine the strength and magnitude of the association between outdoor pollen exposure and lung function and airway inflammation at the community level.…”

Section: Introductionmentioning

confidence: 99%

Outdoor pollen‐related changes in lung function and markers of airway inflammation: A systematic review and meta‐analysis

Idrose

Walters

Zhang

et al. 2021

Clin Experimental Allergy

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Background Experimental challenge studies have shown that pollen can have early and delayed effects on the lungs and airways. Here, we qualitatively and quantitatively synthesize the evidence of outdoor pollen exposure on various lung function and airway inflammation markers in community‐based studies. Methods Four online databases were searched: Medline, Web of Science, CINAHL and Google Scholar. The search strategy included terms relating to both exposure and outcomes. Inclusion criteria were human‐based studies published in English that were representative of the community. Additionally, we only considered cross‐sectional or short‐term longitudinal studies which investigated pollen exposure by levels or season. Study quality assessment was performed using the Newcastle‐Ottawa scale. Meta‐analysis was conducted using random‐effects models. Results We included 27 of 6551 studies identified from the search. Qualitative synthesis indicated associations between pollen exposure and predominantly type‐2 inflammation in both the upper and lower airways, but little evidence for lung function changes. People with ever asthma and/or seasonal allergic rhinitis (SAR) were at higher risk of such airway inflammation. Meta‐analysis confirmed a positive relationship between pollen season, eosinophilia and eosinophil cationic protein (ECP) in people with ever SAR but the results between studies were highly variable. Heterogeneity was reduced after further subgrouping by age, and the forest plots indicated that eosinophilic airway inflammation to outdoor pollen exposure increased with age. Conclusion Among people with ever asthma and ever SAR, exposure to increased ambient pollen triggers type‐2 upper and lower airway inflammation rather than a non‐specific or innate inflammation. These findings can lead to the formulation of specific pollen immunotherapy for susceptible individuals. Future research should be directed towards investigating lagged associations and effect modifications using larger and more generalized populations. Systematic review registration CRD42020146981 (PROSPERO).

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“…It was demonstrated before that although the different methodologies of allergen challenge yield different clinical responses, immunologic responses are very similar. 49,50 It has been demonstrated that holoBLG selectively nourishes regulatory immune cells with micronutrients, thereby fostering immune resilience and tolerance. 34 BLG is a lipocalin, like many of the major allergens, but acts as a tolerogen in context with its ligands (holoBLG) by increasing intracellular iron, importing retinoic acid (RA) via the RA receptor, and activating the arylhydrocarbon receptor via transport of flavonoids such as quercetin, promoting regulatory pathways in a concerted manner.…”

Section: Discussionmentioning

confidence: 99%

The holo beta‐lactoglobulin lozenge reduces symptoms in cat allergy—Evaluation in an allergen exposure chamber and by titrated nasal allergen challenge

Bergmann

Raab²,

Graessel

et al. 2023

Clinical & Translational All

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Background The allergists´ tool box in cat allergy management is limited. Clinical studies have shown that holo beta‐lactoglobulin (holoBLG) can restore micronutritional deficits in atopic immune cells and alleviate allergic symptoms in a completely allergen‐nonspecific manner. With this study, we aimed to provide proof of principle in cat allergy. Methods A novel challenge protocol for cat allergy in a standardized ECARF allergen exposure chamber (AEC) was developed. In an open pilot study (NCT05455749), patients with clinically relevant cat allergy were provoked with cat allergen for 120 min in the AEC before and after a 3‐month intervention phase (holoBLG lozenge 2x daily). Nasal, conjunctival, bronchial, and pruritus symptoms were scored every 10 min– constituting the total symptom score (TSS). Peak nasal inspiratory flow (PNIF) was measured every 30 min. In addition, a titrated nasal provocation test (NPT) was performed before and after the intervention. Primary endpoint was change in TSS at the end of final exposure compared to baseline. Secondary endpoints included changes in PNIF, NPT, and occurrence of late reactions up to 24 h after exposure. Results 35 patients (mean age: 40 years) completed the study. Compared to baseline, holoBLG supplementation resulted in significant improvement in median TSS of 50% (p < 0.001), as well as in median nasal flow by 20 L/min (p = 0.0035). 20% of patients reported late reactions after baseline exposure, but 0% after the final exposure. Conclusions Cat allergic patients profited from targeted micronutrition with the holoBLG lozenge. As previously seen in other allergies, holoBLG supplementation also induced immune resilience in cat allergies, resulting in significant symptom amelioration.

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Comparison of allergic rhinitis outcomes of the environmental exposure unit and nasal allergen challenge model

Cited by 11 publications

References 10 publications

Nasal allergen challenge and environmental exposure chamber challenge: A randomized trial comparing clinical and biological responses to cat allergen

Nasal allergen challenge and environmental exposure chamber challenge: A randomized trial comparing clinical and biological responses to cat allergen

Outdoor pollen‐related changes in lung function and markers of airway inflammation: A systematic review and meta‐analysis

The holo beta‐lactoglobulin lozenge reduces symptoms in cat allergy—Evaluation in an allergen exposure chamber and by titrated nasal allergen challenge

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