Controlled Allergen Challenge Facilities and Their Unique Contributions to Allergic Rhinitis Research

Current Allergy and Asthma Reports

Volumn 15, Issue 4, 2015, Pages

  North, Michelle L ^a,b   Soliman, Mena ^a,b   Walker, Terry ^b   Steacy, Lisa M ^b   Ellis, Anne K ^a,b  

^a QUEEN S UNIVERSITY   (Canada)

^b KINGSTON GENERAL HOSPITAL   (Canada)

Author keywords

Allergic rhinitis; Antihistamine; Controlled allergen challenge facilities; Immunotherapy; Nasal steroid; Pollen

Indexed keywords

ANTIALLERGIC AGENT; ASTEMIZOLE; AZELASTINE; BILASTINE; BUDESONIDE; CETIRIZINE; CETIRIZINE PLUS PSEUDOEPHEDRINE; CHEMOATTRACTANT RECEPTOR HOMOLOGOUS MOLECULE 2 ANTAGONIST; CICLESONIDE; DESLORATADINE; FEXOFENADINE; FEXOFENADINE PLUS PSEUDOEPHEDRINE; FLUTICASONE; FLUTICASONE FUROATE; FLUTICASONE PROPIONATE; LEVOCETIRIZINE; LORATADINE; LORATADINE PLUS MONTELUKAST; MOMETASONE FUROATE; MONTELUKAST; OLOPATADINE; PHENYLEPHRINE; PLACEBO; PSEUDOEPHEDRINE; RAGWEED ANTIGEN; RUPATADINE; TERFENADINE; TRIAMCINOLONE ACETONIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VANILLOID RECEPTOR 1 ANTAGONIST; ALLERGEN;

ALLERGIC RHINITIS; DRUG EFFICACY; EXPERIMENTAL THERAPY; GRASS POLLEN; HUMAN; IMMUNOTHERAPY; NONHUMAN; NOSE OBSTRUCTION; PEAK NASAL INSPIRATORY FLOW; PERENNIAL RHINITIS; PHARMACODYNAMICS; POLLEN ALLERGY; QUALITY OF LIFE; REVIEW; RHINOCONJUNCTIVITIS; RHINOMANOMETRY; ANIMAL; ENVIRONMENTAL EXPOSURE; IMMUNOLOGY; POLLEN;

ALLERGENS; ANIMALS; ANTI-ALLERGIC AGENTS; ENVIRONMENTAL EXPOSURE; HUMANS; IMMUNOTHERAPY; POLLEN; RHINITIS, ALLERGIC;

EID: 84933505315     PISSN: 15297322     EISSN: 15346315     Source Type: Journal    
DOI: 10.1007/s11882-015-0514-4     Document Type: Review

References (98)

1. Bousquet J, Van Cauwenberge P, Khaltaev N. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol. 2001;108:S147–334. Seminal paper describing the symptoms and pathophysiology of allergic rhinitis and its impact on comorbid asthma.
2. Day JH, Horak F, Briscoe MP, Canonica GW, Fineman SM, Krug N, et al. The role of allergen challenge chambers in the evaluation of anti-allergic medication: an international consensus paper. Clin Exp Allergy Rev. 2006;6:31–59. A consensus paper on CACF models in allergic rhinitis research.
3. Horak F, Jager S. The Vienna challenge chamber (VCC)—a new method for allergen exposition tests. Wien Klin Wocheschr. 1987;99:509–10. Validation of the Vienna challenge chamber (VCC).
4. Pross HF, Day JH, Clark RH, Lees RE. Immunologic studies of subjects with asthma exposed to formaldehyde and urea-formaldehyde foam insulation (UFFI) off products. J Allergy Clin Immunol. 1987;79:797–810.
5. Day JH, Lees RE, Clark RH, Pattee PL. Respiratory response to formaldehyde and off-gas of urea formaldehyde foam insulation. Can Med Assoc J. 1984;131:1061–5.
6. Ellis AK, North ML, Walker T, Steacy LM. Environmental exposure unit: a sensitive, specific, and reproducible methodology for allergen challenge. Ann Allergy Asthma Immunol. 2013;111:323–8.
7. Ronborg SM, Mosbech H, Johnsen CR, Poulsen LK. Exposure chamber for allergen challenge. The development and validation of a new concept. Allergy. 1996;51:82–8. Validation of an allergen exposure facility in Copenhagen, Denmark, for use with house-dust mite allergen.
8. Krug N, Hohlfeld JM, Larbig M, Buckendahl A, Badorrek P, Geldmacher H, et al. Validation of an environmental exposure unit for controlled human inhalation studies with grass pollen in patients with seasonal allergic rhinitis. Clin Exp Allergy. 2003;33:1667–74. Validation of the Fraunhofer Institute Environmental Challenge Chamber (ECC) in Hannover, Germany.
9. Berkowitz RB, Woodworth GG, Lutz C, Weiler K, Weiler J, Moss M, et al. Onset of action, efficacy, and safety of fexofenadine 60 mg/pseudoephedrine 120 mg versus placebo in the Atlanta allergen exposure unit. Ann Allergy Asthma Immunol. 2002;89:38–45.
10. Wilken JA, Berkowitz R, Kane R. Decrements in vigilance and cognitive functioning associated with ragweed-induced allergic rhinitis. Ann Allergy Asthma Immunol. 2002;89:372–80.
11. Berkowitz RB, McCafferty F, Lutz C, Bazelmans D, Godfrey P, Meeves S, et al. Onset of action of fexofenadine hydrochloride 60 mg/pseudoephedrine hydrochloride 120 mg in subjects aged 12 years with moderate to severe seasonal allergic rhinitis: a pooled analysis of two single-dose, randomized, double-blind, placebo-controlled allergen exposure unit studies. Clin Ther. 2006;28:1658–69.
12. Patel P, D’Andrea C, Sacks HJ. Onset of action of azelastine nasal spray compared with mometasone nasal spray and placebo in subjects with seasonal allergic rhinitis evaluated in an environmental exposure chamber. Am J Rhinol. 2007;21:499–503.
13. Patel P, Salapatek AM. Pollinex Quattro: a novel and well-tolerated, ultra short-course allergy vaccine. Expert Rev Vaccines. 2006;5:617–29.
14. Ramirez DA JR, Andrews CP. Uniperus asheii (mountain cedar) pollen utilized as an antigen in the biogenics chamber: comparison of natural and controlled exposures. J Allergy Clin Immunol. 2011;127:AB19.
15. Jacobs RL, Ramirez DA, Andrews CP. Validation of the biogenics research chamber for Juniperus ashei (mountain cedar) pollen. Ann Allergy Asthma Immunol. 2011;107:133–8.
16. Crampton H.J., Gomes, P. A Pilot Study Evaluating the Signs and Symptoms of Seasonal Allergic Rhinitis and Conjunctivitis Following Allergen Exposure in the Allergen BioCube. ClinicalTrials.gov 2009; identifier: NCT00985075.
17. Hamasaki S, Okamoto Y, Yonekura S, Okuma Y, Sakurai T, Iinuma T, et al. Characteristics of the Chiba environmental challenge chamber. Allergol Int. 2014;63:41–50. Validation of the Chiba environmental challenge chamber in Japan.
18. Ito K, Terada T, Yuki A, Ichihara T, Hyo S, Kawata R, et al. Preliminary study of a challenge test to the patients with Japanese cedar pollinosis using an environmental exposure unit. Auris Nasus Larynx. 2010;37:694–9.
19. Yang WH, Yang J, Perrins R, Kelly S, Karsh J. Computer-aided design of an allergen challenge theatre. J Allergy Clin Immunol. 2014;133:AB187.
20. Muradil M, Okamoto Y, Yonekura S, Chazono H, Hisamitsu M, Horiguchi S, et al. Reevaluation of pollen quantitation by an automatic pollen counter. Allergy Asthma Proc. 2010;31:422–7.
21. Chervinsky P, Philip G, Malice MP, Bardelas J, Nayak A, Marchal JL, et al. Montelukast for treating fall allergic rhinitis: effect of pollen exposure in 3 studies. Ann Allergy Asthma Immunol. 2004;92:367–73.
22. Akerlund A, Andersson M, Leflein J, Lildholdt T, Mygind N. Clinical trial design, nasal allergen challenge models, and considerations of relevance to pediatrics, nasal polyposis, and different classes of medication. J Allergy Clin Immunol. 2005;115:S460–82.
23. Day JH, Ellis AK, Rafeiro E, Ratz JD, Briscoe MP. Experimental models for the evaluation of treatment of allergic rhinitis. Ann Allergy Asthma Immunol. 2006;96:263–77. quiz 277–8, 315.
24. U.S. Food and Drug Administration Center for Biologics Evaluation and Research: Allergenic Products Advisory Committee. Transcript, Capital Reporting Company 2011. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/AllergenicProductsAdvisoryCommittee/UCM258587.pdf Accessed 10 Dec 2014.
25. Bernstein JA. Correlation between a pollen challenge chamber and a natural allergen exposure study design for eliciting ocular and nasal symptoms: early evidence supporting a paradigm shift in drug investigation? J Allergy Clin Immunol. 2012;130:128–9.
26. Devillier P, Le Gall M, Horak F. The allergen challenge chamber: a valuable tool for optimizing the clinical development of pollen immunotherapy. Allergy. 2011;66:163–9.
27. Committee for Medicinal Products for Human Use (CHMP). Guideline on the Clinical Development of Products for Specific Immunotherapy for the Treatment of Allergic Diseases. Doc. Ref. CHMP/EWP/18504/2006. 2008. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003605.pdf Accessed 10 Dec 2014.
28. Horak F, Stubner UP, Zieglmayer R, Harris AG. Effect of desloratadine versus placebo on nasal airflow and subjective measures of nasal obstruction in subjects with grass pollen-induced allergic rhinitis in an allergen-exposure unit. J Allergy Clin Immunol. 2002;109:956–61.
29. Horak F, Stubner P, Zieglmeyer R, Harris AG. Comparison of the effects of desloratadine 5-mg daily and placebo on nasal airflow and seasonal allergic rhinitis symptoms induced by grass pollen exposure. Allergy. 2003;58:481–5.
30. Day JH, Briscoe M, Rafeiro E, Chapman D, Kramer B. Comparative onset of action and symptom relief with cetirizine, loratadine, or placebo in an environmental exposure unit in subjects with seasonal allergic rhinitis: confirmation of a test system. Ann Allergy Asthma Immunol. 2001;87:474–81.
31. Day JH, Briscoe M, Widlitz MD. Cetirizine, loratadine, or placebo in subjects with seasonal allergic rhinitis: effects after controlled ragweed pollen challenge in an environmental exposure unit. J Allergy Clin Immunol. 1998;101:638–45.
32. Connell JT. Quantitative intranasal pollen challenges. 3. The priming effect in allergic rhinitis. J Allergy. 1969;43:33–44. Seminal work on the priming effect.
33. Yuki A, Terada T, Ichihara T, Fujii K, Hyo S, Kawata R, et al. Evaluating the effects of testing period on pollinosis symptoms using an allergen challenge chamber. Allergol Int. 2011;60:533–9.
34. Ellis AK, Ratz JD, Day AG, Day JH. Factors that affect the allergic rhinitis response to ragweed allergen exposure. Ann Allergy Asthma Immunol. 2010;104:293–8. Important paper that demonstrated common individual participant factors that affect symptom response in CACF studies.
35. Jacobs, R.L., Andrews, C.P., Ramirez, D.A., Rather, C.G., Harper, N., Jimenez, F, et al. Symptom dynamics during repeated serial allergen challenge chamber exposures to house dust mite. J Allergy Clin Immunol. 2014. in press.
36. Ellis AK, Rafeiro E, Day JH. Quality of life indices may be predictive of placebo and medication response to treatment for allergic rhinitis. Ann Allergy Asthma Immunol. 2001;86:393–6.
37. Ellis AK, Day JH, Lundie MJ. Impact on quality of life during an allergen challenge research trial. Ann Allergy Asthma Immunol. 1999;83:33–9. Work that demonstrated quality of life effects that result from participation in CACF trials.
38. Badorrek P, Dick M, Hecker H, Schaumann F, Sousa AR, Murdoch R, et al. Anti-allergic drug testing in an environmental challenge chamber is suitable both in and out of the relevant pollen season. Ann Allergy Asthma Immunol. 2011;106:336–41. Important paper that demonstrated CACF studies may be conducted both in and out of season.
39. Hohlfeld JM, Holland-Letz T, Larbig M, Lavae-Mokhtari M, Wierenga E, Kapsenberg M, et al. Diagnostic value of outcome measures following allergen exposure in an environmental challenge chamber compared with natural conditions. Clin Exp Allergy. 2010;40:998–1006.
40. Jacobs RL, Harper N, He W, Andrews CP, Rather CG, Ramirez DA, et al. Responses to ragweed pollen in a pollen challenge chamber versus seasonal exposure identify allergic rhinoconjunctivitis endotypes. J Allergy Clin Immunol. 2012;130:122–7 e8. Demonstration of concordance between symptoms generated in a CACF model compared to the natural season.
41. Jacobs RL, Harper N, He W, Andrews CP, Rather CG, Ramirez DA, et al. Effect of confounding cofactors on responses to pollens during natural season versus pollen challenge chamber exposure. J Allergy Clin Immunol. 2014;133:1340–6.
42. Soliman, M., Ellis, A.K. Phenotyping Allergic Rhinitis Responses using the Environmental Exposure Unit (EEU). Ann Allergy Asthma Immunol. 2015. in press.
43. Smit MJ, Timmerman H, Alewijnse AE, Leurs R. From histamine H2 receptor regulation to reclassification of H2 antagonists; inverse agonism as the basis for H2 receptor upregulation. Receptors Channels. 1998;5:99–102.
44. Bakker RA, Wieland K, Timmerman H, Leurs R. Constitutive activity of the histamine H(1) receptor reveals inverse agonism of histamine H(1) receptor antagonists. Eur J Pharmacol. 2000;387:R5–7.
45. Wu RL, Anthes JC, Kreutner W, Harris AG, West Jr RE. Desloratadine inhibits constitutive and histamine-stimulated nuclear factor-kappaB activity consistent with inverse agonism at the histamine H1 receptor. Int Arch Allergy Immunol. 2004;135:313–8.
46. Monczor F, Fernandez N, Fitzsimons CP, Shayo C, Davio C. Antihistaminergics and inverse agonism: potential therapeutic applications. Eur J Pharmacol. 2013;715:26–32.
47. Day JH, Briscoe MP, Clark RH, Ellis AK, Gervais P. Onset of action and efficacy of terfenadine, astemizole, cetirizine, and loratadine for the relief of symptoms of allergic rhinitis. Ann Allergy Asthma Immunol. 1997;79:163–72. Important investigation of second-generation antihistamines using a CACF model.
48. Stubner P, Zieglmayer R, Horak F. A direct comparison of the efficacy of antihistamines in SAR and PAR: randomised, placebo-controlled studies with levocetirizine and loratadine using an environmental exposure unit - the Vienna Challenge Chamber (VCC). Curr Med Res Opin. 2004;20:891–902.
49. Day JH, Briscoe MP, Rafeiro E, Ratz JD. Comparative clinical efficacy, onset and duration of action of levocetirizine and desloratadine for symptoms of seasonal allergic rhinitis in subjects evaluated in the Environmental Exposure Unit (EEU). Int J Clin Pract. 2004;58:109–18.
50. Horak F, Zieglmayer PU, Zieglmayer R, Kavina A, Lemell P. Levocetirizine has a longer duration of action on improving total nasal symptoms score than fexofenadine after single administration. Br J Clin Pharmacol. 2005;60:24–31.
51. Day JH, Briscoe MP, Welsh A, Smith JN, Clark A, Ellis AK, et al. Onset of action, efficacy, and safety of a single dose of fexofenadine hydrochloride for ragweed allergy using an environmental exposure unit. Ann Allergy Asthma Immunol. 1997;79:533–40.
52. Day JH, Briscoe MP, Rafeiro E, Ratz JD, Ellis AK, Frankish CW, et al. Comparative efficacy of cetirizine and fexofenadine for seasonal allergic rhinitis, 5–12 hours postdose, in the environmental exposure unit. Allergy Asthma Proc. 2005;26:275–82.
53. Day JH, Briscoe MP, Rafeiro E, Hewlett Jr D, Chapman D, Kramer B. Randomized double-blind comparison of cetirizine and fexofenadine after pollen challenge in the Environmental Exposure Unit: duration of effect in subjects with seasonal allergic rhinitis. Allergy Asthma Proc. 2004;25:59–68. Demonstration of a longer duration of action for cetirizine compared to fexofenadine.
54. Horak F, Zieglmayer P, Zieglmayer R, Lemell P. The effects of bilastine compared with cetirizine, fexofenadine, and placebo on allergen-induced nasal and ocular symptoms in patients exposed to aeroallergen in the Vienna Challenge Chamber. Inflamm Res. 2010;59:391–8. Demonstration of longer durations of action for bilastine and cetirizine compared to fexofenadine.
55. Yonekura S, Okamoto Y, Yamamoto H, Sakurai T, Iinuma T, Sakurai D, et al. Randomized double-blind study of prophylactic treatment with an antihistamine for seasonal allergic rhinitis. Int Arch Allergy Immunol. 2013;162:71–8. Demonstration that prophylactic treatment with antihistamine is not superior to single treatment.
56. Stuebner P, Horak F, Zieglmayer R, Arnaiz E, Leuratti C, Perez I, et al. Effects of rupatadine vs placebo on allergen-induced symptoms in patients exposed to aeroallergens in the Vienna Challenge Chamber. Ann Allergy Asthma Immunol. 2006;96:37–44.
57. Ellis AK, Zhu Y, Steacy LM, Walker T, Day JH. A four-way, double-blind, randomized, placebo controlled study to determine the efficacy and speed of azelastine nasal spray, versus loratadine, and cetirizine in adult subjects with allergen-induced seasonal allergic rhinitis. Allergy Asthma Clin Immunol. 2013;9:16.
58. Patel P, Roland PS, Marple BF, Benninger PJ, Margalias H, Brubaker M, et al. An assessment of the onset and duration of action of olopatadine nasal spray. Otolaryngol Head Neck Surg. 2007;137:918–24.
59. Horak F, Zieglmayer UP, Zieglmayer R, Kavina A, Marschall K, Munzel U, et al. Azelastine nasal spray and desloratadine tablets in pollen-induced seasonal allergic rhinitis: a pharmacodynamic study of onset of action and efficacy. Curr Med Res Opin. 2006;22:151–7.
60. Day JH, Buckeridge DL, Clark RH, Briscoe MP, Phillips R. A randomized, double-blind, placebo-controlled, controlled antigen delivery study of the onset of action of aerosolized triamcinolone acetonide nasal spray in subjects with ragweed-induced allergic rhinitis. J Allergy Clin Immunol. 1996;97:1050–7. The first evaluation of a nasal corticosteroid in a CACF model that revealed an earlier onset of action than was anticipated.
61. Day JH, Briscoe MP, Rafeiro E, Ellis AK, Pettersson E, Akerlund A. Onset of action of intranasal budesonide (Rhinocort aqua) in seasonal allergic rhinitis studied in a controlled exposure model. J Allergy Clin Immunol. 2000;105:489–94.
62. Couroux P, Kunjibettu S, Hall N, Wingertzahn MA. Onset of action of ciclesonide once daily in the treatment of seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2009;102:62–8.
63. Patel P, Patel D, Kunjibettu S, Hall N, Wingertzahn MA. Onset of action of ciclesonide once daily in the treatment of seasonal allergic rhinitis. Ear Nose Throat J. 2008;87:340–53.
64. Zieglmayer P, Zieglmayer R, Bareille P, Rousell V, Salmon E, Horak F. Fluticasone furoate versus placebo in symptoms of grass-pollen allergic rhinitis induced by exposure in the Vienna challenge chamber. Curr Med Res Opin. 2008;24:1833–40.
65. Salapatek AM, Patel P, Gopalan G, Varghese ST. Mometasone furoate nasal spray provides early, continuing relief of nasal congestion and improves nasal patency in allergic patients. Am J Rhinol Allergy. 2010;24:433–8.
66. Patel D, Garadi R, Brubaker M, Conroy JP, Kaji Y, Crenshaw K, et al. Onset and duration of action of nasal sprays in seasonal allergic rhinitis patients: olopatadine hydrochloride versus mometasone furoate monohydrate. Allergy Asthma Proc. 2007;28:592–9.
67. Yamamoto H, Yonekura S, Sakurai D, Katada K, Inamine A, Hanazawa T, et al. Comparison of nasal steroid with antihistamine in prophylactic treatment against pollinosis using an environmental challenge chamber. Allergy Asthma Proc. 2012;33:397–403.
68. Salapatek AM, Lee J, Patel D, D’Angelo P, Liu J, Zimmerer Jr RO, et al. Solubilized nasal steroid (CDX-947) when combined in the same solution nasal spray with an antihistamine (CDX-313) provides improved, fast-acting symptom relief in patients with allergic rhinitis. Allergy Asthma Proc. 2011;32:221–9.
69. Simons FE. Comparative pharmacology of H1 antihistamines: clinical relevance. Am J Med. 2002;113(Suppl 9A):38S–46.
70. del Cuvillo A, Mullol J, Bartra J, Davila I, Jauregui I, Montoro J, et al. Comparative pharmacology of the H1 antihistamines. J Investig Allergol Clin Immunol. 2006;16 Suppl 1:3–12.
71. Nathan RA, Meltzer EO, Derebery J, Campbell UB, Stang PE, Corrao MA, et al. The prevalence of nasal symptoms attributed to allergies in the United States: findings from the burden of rhinitis in an America survey. Allergy Asthma Proc. 2008;29:600–8. Important work on the prevalence and impact of AR in the USA.
72. Djukanovic R, Wilson SJ, Howarth PH. Pathology of rhinitis and bronchial asthma. Clin Exp Allergy. 1996;26 Suppl 3:44–51.
73. Chervinsky P, Nayak A, Rooklin A, Danzig M. Efficacy and safety of desloratadine/pseudoephedrine tablet, 2.5/120 mg two times a day, versus individual components in the treatment of patients with seasonal allergic rhinitis. Allergy Asthma Proc. 2005;26:391–6.
74. Moinuddin R, de Tineo M, Maleckar B, Naclerio RM, Baroody FM. Comparison of the combinations of fexofenadine-pseudoephedrine and loratadine-montelukast in the treatment of seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2004;92:73–9.
75. Zieglmayer UP, Horak F, Toth J, Marks B, Berger UE, Burtin B. Efficacy and safety of an oral formulation of cetirizine and prolonged-release pseudoephedrine versus budesonide nasal spray in the management of nasal congestion in allergic rhinitis. Treat Respir Med. 2005;4:283–7.
76. Horak F, Zieglmayer P, Zieglmayer R, Lemell P, Yao R, Staudinger H, et al. A placebo-controlled study of the nasal decongestant effect of phenylephrine and pseudoephedrine in the Vienna Challenge Chamber. Ann Allergy Asthma Immunol. 2009;102:116–20. Important work on the relative efficacy of pseudoephedrine and phenylephrine.
77. Day JH, Briscoe MP, Ratz JD, Danzig M, Yao R. Efficacy of loratadine-montelukast on nasal congestion in patients with seasonal allergic rhinitis in an environmental exposure unit. Ann Allergy Asthma Immunol. 2009;102:328–38.
78. Badorrek P, Dick M, Schauerte A, Hecker H, Murdoch R, Luettig B, et al. A combination of cetirizine and pseudoephedrine has therapeutic benefits when compared to single drug treatment in allergic rhinitis. Int J Clin Pharmacol Ther. 2009;47:71–7. Important comparison of the efficacy of antihistamine vs. pseudoephedrine alone and in combination.
79. Empey DW, Young GA, Letley E, John GC, Smith P, McDonnell KA, et al. Dose–response study of the nasal decongestant and cardiovascular effects of pseudoephedrine. Br J Clin Pharmacol. 1980;9:351–8.
80. North ML, Walker T, Steacy LM, Hobsbawn BG, Allan RJ, Hackman F, et al. Double blind randomized crossover trial of PF-03654764 + fexofenadine in the environmental exposure unit (EEU). Allergy Asthma Clin Immunol. 2014;10:A68.
81. Daley-Yates P, Ambery C, Sweeney L, Watson J, Oliver A, McQuade B. The efficacy and tolerability of two novel H(1)/H(3) receptor antagonists in seasonal allergic rhinitis. Int Arch Allergy Immunol. 2012;158:84–98.
82. Barchuk WT, Salapatek AM, Ge T, D’Angelo P, Liu X. A proof-of-concept study of the effect of a novel H3-receptor antagonist in allergen-induced nasal congestion. J Allergy Clin Immunol. 2013;132:838–46. e1-6.
83. Wager TT, Pettersen BA, Schmidt AW, Spracklin DK, Mente S, Butler TW, et al. Discovery of two clinical histamine H(3) receptor antagonists: trans-N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidinylmethyl)phenyl]cyclobutanecarbox amide (PF-03654746) and trans-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]-N-(2-methylpropyl)cyclobutanecarboxamide (PF-03654764). J Med Chem. 2011;54:7602–20.
84. Weisler RH, Pandina GJ, Daly EJ, Cooper K, Gassmann-Mayer C. Randomized clinical study of a histamine H3 receptor antagonist for the treatment of adults with attention-deficit hyperactivity disorder. CNS Drugs. 2012;26:421–34.
85. Small P, Kim H. Allergic rhinitis. Allergy Asthma Clin Immunol. 2011;7 Suppl 1:S3.
86. Day JH, Briscoe MP, Ratz JD. Efficacy of levocetirizine compared with montelukast in subjects with ragweed-induced seasonal allergic rhinitis in the Environmental Exposure Unit. Allergy Asthma Proc. 2008;29:304–12. Comparison of the antileukotriene montelukast to the antihistamine levocetirizine.
87. Patel P, Patel D. Efficacy comparison of levocetirizine vs montelukast in ragweed sensitized patients. Ann Allergy Asthma Immunol. 2008;101:287–94.
88. Day JH, Briscoe MP, Ratz JD, Ellis AK, Yao R, Danzig M. Onset of action of loratadine/montelukast in seasonal allergic rhinitis subjects exposed to ragweed pollen in the environmental exposure unit. Allergy Asthma Proc. 2009;30:270–6.
89. Horak F, Zieglmayer P, Zieglmayer R, Lemell P. Onset of action of loratadine/montelukast in seasonal allergic rhinitis patients exposed to grass pollen. Arzneimittelforschung. 2010;60:249–55.
90. Donovan JP, Buckeridge DL, Briscoe MP, Clark RH, Day JH. Efficacy of immunotherapy to ragweed antigen tested by controlled antigen exposure. Ann Allergy Asthma Immunol. 1996;77:74–80. Important evaluation of the efficacy of standard immunotherapy.
91. Ellis AK. Environmental exposure units for specific immunotherapy trials. Arb Paul Ehrlich Inst Bundesinstitut Impfstoffe Biomed Arzneim Langen Hess. 2013;97:91–4.
92. Patel P, Holdich T, Fischer von Weikersthal-Drachenberg KJ, Huber B. Efficacy of a short course of specific immunotherapy in patients with allergic rhinoconjunctivitis to ragweed pollen. J Allergy Clin Immunol. 2014;133:121–9 e1-2.
93. Patel D, Couroux P, Hickey P, Salapatek AM, Laidler P, Larche M, et al. el d 1-derived peptide antigen desensitization shows a persistent treatment effect 1 year after the start of dosing: a randomized, placebo-controlled study. J Allergy Clin Immunol. 2013;131:103–9 e1-7.
94. Horak F, Zieglmayer P, Zieglmayer R, Lemell P, Devillier P, Montagut A, et al. Early onset of action of a 5-grass-pollen 300-IR sublingual immunotherapy tablet evaluated in an allergen challenge chamber. J Allergy Clin Immunol. 2009;124:471–7, 477 e1.
95. Jordakieva G, Wallmann J, Schmutz R, Lemell P, Wegmann M, Nittke T, et al. Peripheral erythrocytes decrease upon specific respiratory challenge with grass pollen allergen in sensitized mice and in human subjects. PLoS One. 2014;9:e86701.
96. Horak F, Zieglmayer P, Zieglmayer R, Lemell P, Collins LP, Hunter MG, et al. The CRTH2 antagonist OC000459 reduces nasal and ocular symptoms in allergic subjects exposed to grass pollen, a randomised, placebo-controlled, double-blind trial. Allergy. 2012;67:1572–9.
97. Krug N, Gupta A, Badorrek P, Koenen R, Mueller M, Pivovarova A, et al. Efficacy of the oral chemoattractant receptor homologous molecule on TH2 cells antagonist BI 671800 in patients with seasonal allergic rhinitis. J Allergy Clin Immunol. 2014;133:414–9.
98. Bareille P, Murdoch RD, Denyer J, Bentley J, Smart K, Yarnall K, et al. The effects of a TRPV1 antagonist, SB-705498, in the treatment of seasonal allergic rhinitis. Int J Clin Pharmacol Ther. 2013;51:576–84.