Peak nasal inspiratory flow as outcome for provocation studies in allergen exposure chambers: a GA2LEN study

Georg Boelke, Uwe Berger, Karl-Christian Bergmann, Carsten Bindslev-Jensen, Jean Bousquet, Julia Gildemeister, Marek Jutel, Oliver Pfaar, Torsten Sehlinger, Torsten Zuberbier, Georg Boelke, Uwe Berger, Karl-Christian Bergmann, Carsten Bindslev-Jensen, Jean Bousquet, Julia Gildemeister, Marek Jutel, Oliver Pfaar, Torsten Sehlinger, Torsten Zuberbier

Abstract

Background: The GA2LEN chamber has been developed as a novel mobile allergen exposure chamber (AEC) allowing standardized multicenter trials in allergy. Hitherto, subjective nasal symptom scores have been the most often used outcome parameter, but in standardized modern trials objective parameters are preferred. Despite its practicability, the objective parameter peak nasal inspiratory flow (PNIF) has been rarely used for allergy trials in the setting of allergen exposure chambers. This study aims to evaluate PNIF as an outcome parameter for provocation studies in AECs.

Methods: In a randomized controlled blinded setting subjects suffering from allergic rhinitis were exposed to grass pollen, birch pollen, house dust mite and/or placebo in the GA2LEN chamber. Different allergen concentrations were used to evaluate symptom severities. Patients had to perform PNIF before and every 30 min during a challenge using a portable PNIF meter.

Results: 86 subjects participated in 203 challenges, altogether. House dust mite provocations caused the greatest reduction in PNIF values, followed by grass pollen and birch pollen. Provocations with every allergen or pollen concentration led to a significant decrease (p < 0.05) in PNIF compared to baseline. Furthermore, positive correlations were obtained between PNIF and peak expiratory flow, height and weight, and inverse correlations between PNIF and total nasal symptom score, nasal congestion score and visual analog scale of overall subjective symptoms.

Conclusion: PNIF is a helpful and feasible tool for conducting provocation trials with allergens, especially grass pollen and house dust mite, in an AEC.

Keywords: Allergen exposure chamber (AEC); Allergy trial; GA2LEN chamber; Peak nasal inspiratory flow (PNIF); Provocation study.

Figures

Fig. 1
Fig. 1
Reduction of PNIF during exposure with grass pollen in the GA2LEN chamber. PNIF development during exposure with Phleum pratense. A hash marks a reduction compared to baseline p < 0.001, a dagger a reduction compared to baseline p < 0.01. Outliers are presented as degree sign, extreme outliers as asterisk. PNIF% from both actively exposed groups (4000 and 8000 grains/m3) is significantly lower (p < 0.05) than in the placebo group at every associated time of measurement. PNIF% is displayed as medians and boxplots
Fig. 2
Fig. 2
Reduction of PNIF during exposure with birch pollen in the GA2LEN chamber. PNIF development during exposure with Betula pendula. A hash marks a reduction compared to baseline p < 0.001, a dagger a reduction compared to baseline p < 0.01 and a double dagger a reduction compared to baseline p < 0.05. Outliers are presented as degree sign, extreme outliers as asterisk. PNIF% is displayed as medians and boxplots
Fig. 3
Fig. 3
Reduction of PNIF during exposure with house dust mite (Der p 1) in the GA2LEN chamber. PNIF development during exposure with house dust mite material. A hash marks a reduction compared to baseline p < 0.001, a dagger a reduction compared to baseline p < 0.01. Outliers are presented as degree sign. PNIF% from the actively exposed group (250 µg/m3) is significantly lower (p < 0.05) than in the placebo group at every associated time of measurement. PNIF% is displayed as medians and boxplots
Fig. 4
Fig. 4
Correlations between peak nasal inspiratory flow (PNIF) and oral peak expiratory flow (PEF) (a), height (b), and weight (c) with n = 86, and relative peak nasal inspiratory flow compared to baseline (PNIF%) and mean VAS change from baseline (d), mean Total Nasal Symptom Score (TNSS) (e), and mean nasal congestion score (f) with n = 203

References

    1. Pefura-Yone EW, Kengne AP, Balkissou AD, Boulleys-Nana JR, Efe-de-Melingui NR, Ndjeutcheu-Moualeu PI, Mbele-Onana CL, Kenmegne-Noumsi EC, Kolontchang-Yomi BL, Theubo-Kamgang BJ, et al. Prevalence of asthma and allergic rhinitis among adults in Yaounde, Cameroon. PLoS ONE. 2015;10:e0123099. doi: 10.1371/journal.pone.0123099.
    1. Pols DH, Wartna JB, Moed H, van Alphen EI, Bohnen AM, Bindels PJ. Atopic dermatitis, asthma and allergic rhinitis in general practice and the open population: a systematic review. Scand J Prim Health Care. 2016;34:143–150. doi: 10.3109/02813432.2016.1160629.
    1. Bauchau V, Durham SR. Prevalence and rate of diagnosis of allergic rhinitis in Europe. Eur Respir J. 2004;24:758–764. doi: 10.1183/09031936.04.00013904.
    1. Salo PM, Arbes SJ, Jaramillo R, Calatroni A, Weir CH, Sever ML, Hoppin JA, Rose KM, Liu AH, Gergen PJ, et al. Prevalence of allergic sensitization in the United States: results from the National Health and Nutrition Examination Survey (NHANES) 2005–2006. J Allergy Clin Immunol. 2014;134:350–359. doi: 10.1016/j.jaci.2013.12.1071.
    1. Bergmann KC, Heinrich J, Niemann H. Current status of allergy prevalence in Germany: Position paper of the Environmental Medicine Commission of the Robert Koch Institute. Allergo J Int. 2016;25:6–10. doi: 10.1007/s40629-016-0092-6.
    1. Wheatley LM, Togias A. Clinical practice. Allergic rhinitis. N Engl J Med. 2015;372:456–463. doi: 10.1056/NEJMcp1412282.
    1. D’Amato G, Cecchi L, Bonini S, Nunes C, Annesi-Maesano I, Behrendt H, Liccardi G, Popov T, van Cauwenberge P. Allergenic pollen and pollen allergy in Europe. Allergy. 2007;62:976–990. doi: 10.1111/j.1398-9995.2007.01393.x.
    1. Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, Zuberbier T, Baena-Cagnani CE, Canonica GW, van Weel C, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen) Allergy. 2008;63(Suppl 86):8–160. doi: 10.1111/j.1398-9995.2007.01620.x.
    1. McCrory DC, Williams JW, Dolor RJ, Gray RN, Kolimaga JT, Reed S, Sundy J, Witsell DL. Management of allergic rhinitis in the working-age population. Evid Rep Technol Assess (Summ) 2003;67:1–4.
    1. Meltzer EO, Bukstein DA. The economic impact of allergic rhinitis and current guidelines for treatment. Ann Allergy Asthma Immunol. 2011;106:S12–S16. doi: 10.1016/j.anai.2010.10.014.
    1. Small M, Piercy J, Demoly P, Marsden H. Burden of illness and quality of life in patients being treated for seasonal allergic rhinitis: a cohort survey. Clin Transl Allergy. 2013;3:33. doi: 10.1186/2045-7022-3-33.
    1. Day JH, Horak F, Briscoe MP, Canonica GW, Fineman SM, Krug N, Leynadier F, Lieberman P, Quirce S, Takenaka H, Cauwenberge P. The role of allergen challenge chambers in the evaluation of anti-allergic medication an international consensus paper. Clin Exp Allergy Rev. 2006;6(2):31–59. doi: 10.1111/j.1365-2222.2005.00099.x.
    1. Rosner-Friese K, Kaul S, Vieths S, Pfaar O. Environmental exposure chambers in allergen immunotherapy trials: current status and clinical validation needs. J Allergy Clin Immunol. 2015;135:636–643. doi: 10.1016/j.jaci.2014.10.045.
    1. Zuberbier T, Abelson MB, Akdis CA, Bachert C, Berger U, Bindslev-Jensen C, Boelke G, Bousquet J, Canonica GW, Casale TB, et al. Validation of the Global Allergy and Asthma European Network (GA(2)LEN) chamber for trials in allergy: innovation of a mobile allergen exposure chamber. J Allergy Clin Immunol. 2017;139:1158–1166. doi: 10.1016/j.jaci.2016.08.025.
    1. Starling-Schwanz R, Peake HL, Salome CM, Toelle BG, Ng KW, Marks GB, Lean ML, Rimmer SJ. Repeatability of peak nasal inspiratory flow measurements and utility for assessing the severity of rhinitis. Allergy. 2005;60:795–800. doi: 10.1111/j.1398-9995.2005.00779.x.
    1. Nathan RA, Eccles R, Howarth PH, Steinsvåg SK, Togias A. Objective monitoring of nasal patency and nasal physiology in rhinitis. J Allergy Clin Immunol. 2005;115:S442–S459. doi: 10.1016/j.jaci.2004.12.015.
    1. Tsounis M, Swart KM, Georgalas C, Markou K, Menger DJ. The clinical value of peak nasal inspiratory flow, peak oral inspiratory flow, and the nasal patency index. Laryngoscope. 2014;124:2665–2669. doi: 10.1002/lary.24810.
    1. Ottaviano G, Fokkens WJ. Measurements of nasal airflow and patency: a critical review with emphasis on the use of peak nasal inspiratory flow in daily practice. Allergy. 2016;71:162–174. doi: 10.1111/all.12778.
    1. Scadding GW, Eifan AO, Lao-Araya M, Penagos M, Poon SY, Steveling E, Yan R, Switzer A, Phippard D, Togias A, et al. Effect of grass pollen immunotherapy on clinical and local immune response to nasal allergen challenge. Allergy. 2015;70:689–696. doi: 10.1111/all.12608.
    1. Pfaar O, Demoly P, Gerth van Wijk R, Bonini S, Bousquet J, Canonica GW, Durham SR, Jacobsen L, Malling HJ, Mösges R, et al. Recommendations for the standardization of clinical outcomes used in allergen immunotherapy trials for allergic rhinoconjunctivitis: an EAACI Position Paper. Allergy. 2014;69:854–867. doi: 10.1111/all.12383.
    1. Stjärne P, Mösges R, Jorissen M, Passàli D, Bellussi L, Staudinger H, Danzig M. A randomized controlled trial of mometasone furoate nasal spray for the treatment of nasal polyposis. Arch Otolaryngol Head Neck Surg. 2006;132:179–185. doi: 10.1001/archotol.132.2.179.
    1. Bachert C, Mannent L, Naclerio RM, Mullol J, Ferguson BJ, Gevaert P, Hellings P, Jiao L, Wang L, Evans RR, et al. Effect of subcutaneous dupilumab on nasal polyp burden in patients with chronic sinusitis and nasal polyposis: a randomized clinical trial. JAMA. 2016;315:469–479. doi: 10.1001/jama.2015.19330.
    1. Nizankowska-Mogilnicka E, Bochenek G, Mastalerz L, Swierczyńska M, Picado C, Scadding G, Kowalski ML, Setkowicz M, Ring J, Brockow K, et al. EAACI/GA2LEN guideline: aspirin provocation tests for diagnosis of aspirin hypersensitivity. Allergy. 2007;62:1111–1118. doi: 10.1111/j.1398-9995.2007.01409.x.
    1. Benichou AC, Armanet M, Bussière A, Chevreau N, Cardot JM, Tétard J. A proprietary blend of quail egg for the attenuation of nasal provocation with a standardized allergenic challenge: a randomized, double-blind, placebo-controlled study. Food Sci Nutr. 2014;2:655–663. doi: 10.1002/fsn3.147.
    1. Bermüller C, Kirsche H, Rettinger G, Riechelmann H. Diagnostic accuracy of peak nasal inspiratory flow and rhinomanometry in functional rhinosurgery. Laryngoscope. 2008;118:605–610. doi: 10.1097/MLG.0b013e318161e56b.
    1. Menger DJ, Swart KM, Nolst Trenité GJ, Georgalas C, Grolman W. Surgery of the external nasal valve: the correlation between subjective and objective measurements. Clin Otolaryngol. 2014;39:150–155. doi: 10.1111/coa.12243.
    1. de Souza-Campos-Fernandes S, Ribeiro de Andrade C, da Cunha Ibiapina C. Application of Peak Nasal Inspiratory Flow reference values in the treatment of allergic rhinitis. Rhinology. 2014;52:133–136.
    1. Hox V, Bobic S, Callebaux I, Jorissen M, Hellings PW. Nasal obstruction and smell impairment in nasal polyp disease: correlation between objective and subjective parameters. Rhinology. 2010;48:426–432.
    1. Teixeira RU, Zappelini CE, Alves FS, da Costa EA. Peak nasal inspiratory flow evaluation as an objective method of measuring nasal airflow. Braz J Otorhinolaryngol. 2011;77:473–480. doi: 10.1590/S1808-86942011000400011.
    1. Ottaviano G, Scadding GK, Iacono V, Scarpa B, Martini A, Lund VJ. Peak nasal inspiratory flow and peak expiratory flow. Upright and sitting values in an adult population. Rhinology. 2016;54:160–163.
    1. Bouzgarou MD, Ben Saad H, Chouchane A, Cheikh IB, Zbidi A, Dessanges JF, Tabka Z. North African reference equation for peak nasal inspiratory flow. J Laryngol Otol. 2011;125:595–602. doi: 10.1017/S0022215111000181.
    1. Akerlund A, Millqvist E, Oberg D, Bende M. Prevalence of upper and lower airway symptoms: the Skövde population-based study. Acta Otolaryngol. 2006;126:483–488. doi: 10.1080/00016480500416835.
    1. Ottaviano G, Scadding GK, Coles S, Lund VJ. Peak nasal inspiratory flow; normal range in adult population. Rhinology. 2006;44:32–35.
    1. Klossek JM, Lebreton JP, Delagranda A, Dufour X. PNIF measurement in a healthy French population. A prospective study about 234 patients. Rhinology. 2009;47:389–392.
    1. Potter PC, Group S Levocetirizine is effective for symptom relief including nasal congestion in adolescent and adult (PAR) sensitized to house dust mites. Allergy. 2003;58:893–899. doi: 10.1034/j.1398-9995.2003.00171.x.
    1. Caillaud D, Martin S, Segala C, Besancenot JP, Clot B, Thibaudon M, Network FA. Effects of airborne birch pollen levels on clinical symptoms of seasonal allergic rhinoconjunctivitis. Int Arch Allergy Immunol. 2014;163:43–50. doi: 10.1159/000355630.
    1. Pfaar O, Calderon MA, Andrews CP, Angjeli E, Bergmann KC, Bønløkke JH, de Blay F, Devillier P, Ellis AK, Gerth van Wijk R, et al. Allergen exposure chambers: harmonizing current concepts and projecting the needs for the future—an EAACI Position Paper. Allergy. 2017;72:1035–1042. doi: 10.1111/all.13133.
    1. Ellis AK, Steacy LM, Hobsbawn B, Conway CE, Walker TJ. Clinical validation of controlled grass pollen challenge in the Environmental Exposure Unit (EEU) Allergy Asthma Clin Immunol. 2015;11:5. doi: 10.1186/s13223-015-0071-3.
    1. Ellis AK, Soliman M, Steacy LM, Adams DE, Hobsbawn B, Walker TJ. Clinical validation of controlled exposure to birch pollen in the Environmental Exposure Unit (EEU) Allergy Asthma Clin Immunol. 2016;12:53. doi: 10.1186/s13223-016-0156-7.
    1. Blomgren K, Simola M, Hytönen M, Pitkäranta A. Peak nasal inspiratory and expiratory flow measurements-practical tools in primary care? Rhinology. 2003;41:206–210.
    1. Phagoo SB, Watson RA, Pride NB. Use of nasal peak flow to assess nasal patency. Allergy. 1997;52:901–908. doi: 10.1111/j.1398-9995.1997.tb01249.x.
    1. Ottaviano G, Lund VJ, Coles S, Staffieri A, Scadding GK. Does peak nasal inspiratory flow relate to peak expiratory flow? Rhinology. 2008;46:200–203.
    1. Ibiapina CC, de Andrade CR, Godinho R, Alvim CG, Cruz Á. Correlation between peak nasal inspiratory flow and peak expiratory flow in children and adolescents. Rhinology. 2012;50:381–385.
    1. Wilson AM, Sims EJ, Orr LC, Coutie WJ, White PS, Gardiner Q, Lipworth BJ. Effects of topical corticosteroid and combined mediator blockade on domiciliary and laboratory measurements of nasal function in seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2001;87:344–349. doi: 10.1016/S1081-1206(10)62250-8.
    1. Scadding GW, Calderon MA, Bellido V, Koed GK, Nielsen NC, Lund K, Togias A, Phippard D, Turka LA, Hansel TT, et al. Optimisation of grass pollen nasal allergen challenge for assessment of clinical and immunological outcomes. J Immunol Methods. 2012;384:25–32. doi: 10.1016/j.jim.2012.06.013.

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