A retrospective cohort study to evaluate the relationship of airway hyperresponsiveness to type 2 biomarkers in persistent asthma

Authors

  • Rory Chan Scottish Centre for Respiratory Research, Ninewells Hospital and Medical School, University of Dundee, Scotland, DD1 9SY, UK
  • Chris RuiWen Kuo Scottish Centre for Respiratory Research, Ninewells Hospital and Medical School, University of Dundee, Scotland, DD1 9SY, UK
  • Brian Lipworth Scottish Centre for Respiratory Research, Ninewells Hospital and Medical School, University of Dundee, Scotland, DD1 9SY, UK

DOI:

https://doi.org/10.29328/journal.aaai.1001023

Keywords:

Airway hyperresponsiveness, Asthma, Allergy, Type 2 inflammation, FeNO

Abstract

Airway hyperresponsiveness (AHR) is a hallmark of persistent asthma measured using direct or indirect airway bronchial challenge testing. The purpose of this study is to investigate the putative relationships between type 2 inflammatory biomarkers, airway geometry (FEV1 and FEF25-75) and specific IgE (RAST or skin prick) to AHR. We performed a retrospective analysis of our database (n = 131) of patients with asthma. Of these subjects, 75 had a histamine challenge and 56 had a mannitol challenge. Fractional exhaled nitric oxide (FeNO) and specific immunoglobulin E (IgE) but not blood eosinophils were significantly higher in patients with AHR to either histamine or mannitol. FEV1 % and FEF25 - 75 % were significantly lower in patients with AHR. Elevated Type 2 biomarkers including FeNO and specific IgE but not blood eosinophils were associated with AHR. Highlights: FeNO and specific IgE but not blood eosinophils are raised in patients with airway hyperresponsiveness. Abbreviations: AHR: Airway Hyperresponsiveness; AMP: Adenosine Monophosphate; AUC: Area Under Curve; EOS: Eosinophils; FeNO: Fractional exhaled Nitric Oxide; FEV1: Forced Expiratory volume in 1 Second; FEF25-75: Forced mid Expiratory Flow Rate Between 25% and 75% of Forced Vital Capacity (FVC); ICS: Inhaled Corticosteroid; IgE: Immunoglobulin E; µg: microgram; Mg/Ml: Milligrams per millilitre; PD15: Provocative Dose of Mannitol Resulting in 15% Drop in FEV1; PC20: Provocative Concentration of Histamine Resulting in 20% Drop in FEV1 ; Ppb: Parts per billion; RAST: Radioallergosorbent Testing for Specific IgE; ROC: Receiver Operator Characteristics; SEM: Standard Error of Means; T2: Type 2 Inflammation

References

Joos GF, O'Connor B, Anderson SD, Chung F, Cockcroft DW, et al. Indirect airway challenges. Eur Respir J. 2003; 21: 1050-1068. PubMed: https://pubmed.ncbi.nlm.nih.gov/12797503/

Anderson SD. Bronchial challenge tests: usefulness, availability and limitations. Breathe. 2011; 8: 53-60.

O'Byrne PM, Inman MD. Airway hyperresponsiveness. Chest. 2003; 123(3 Suppl): 411s-416s. PubMed: https://pubmed.ncbi.nlm.nih.gov/12629006/

Busse WW. The relationship of airway hyperresponsiveness and airway inflammation: Airway hyperresponsiveness in asthma: its measurement and clinical significance. Chest. 2010; 138(2 Suppl): 4s-10s. PubMed: https://pubmed.ncbi.nlm.nih.gov/20668012/

Laprise C, Laviolette M, Boutet M, Boulet L. Asymptomatic airway hyperresponsiveness: relationships with airway inflammation and remodelling. Eur Respir J. 1999; 14: 63-73. PubMed: https://pubmed.ncbi.nlm.nih.gov/10489830/

Schwartz N, Grossman A, Levy Y, Schwarz Y. Correlation between Eosinophil Count and Methacholine Challenge Test in Asymptomatic Subjects. J Asthma. 2012; 49: 336-341. PubMed: https://pubmed.ncbi.nlm.nih.gov/22715867/

Jatakanon A, Lim S, Kharitonov SA, Chung KF, Barnes PJ. Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthma. Thorax. 1998; 53: 91-95. PubMed: https://pubmed.ncbi.nlm.nih.gov/9624291/

Juniper EF, Frith PA, Hargreave FE. Airway responsiveness to histamine and methacholine: relationship to minimum treatment to control symptoms of asthma. Thorax. 1981; 36: 575-579. PubMed: https://pubmed.ncbi.nlm.nih.gov/7031972/

Peat JK, Woolcock AJ, Cullen K. Rate of decline of lung function in subjects with asthma. Eur J Respir Dis. 1987; 70: 171-179. PubMed: https://pubmed.ncbi.nlm.nih.gov/3569449/

Fowler SJ, Dempsey OJ, Sims EJ, Lipworth BJ. Screening for bronchial hyperresponsiveness using methacholine and adenosine monophosphate. Relationship to asthma severity and beta(2)receptor genotype. Am J Respir Crit Care Med. 2000; 162: 1318-1322. PubMed: https://pubmed.ncbi.nlm.nih.gov/11029338/

Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. Standardisation of spirometry. Eur Respir J. 2005; 26: 319-338. PubMed: https://pubmed.ncbi.nlm.nih.gov/16055882/

Heinzerling L, Mari A, Bergmann KC, Bresciani M, Burbach G, et al. The skin prick test – European standards. Clin Transl Allergy. 2013; 3: 3. PubMed: https://pubmed.ncbi.nlm.nih.gov/23369181/

ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med. 2005; 171: 912-930. PubMed: https://pubmed.ncbi.nlm.nih.gov/15817806/

Currie GP, Haggart K, Brannan JD, Lee DKC, Anderson SD, et al. Relationship between airway hyperresponsiveness to mannitol and adenosine monophosphate. Allergy. 2003; 58: 762-766. PubMed: https://pubmed.ncbi.nlm.nih.gov/12859555/

Manoharan A, Lipworth BJ, Craig E, Jackson C. The potential role of direct and indirect bronchial challenge testing to identify overtreatment of community managed asthma. Clin Exp Allergy. 2014; 44: 1240-1245. PubMed: https://pubmed.ncbi.nlm.nih.gov/24912796/

Wilson AM, Lipworth BJ. Dose-response evaluation of the therapeutic index for inhaled budesonide in patients with mild-to-moderate asthma. Am J Med. 2000; 108: 269-275. PubMed: https://pubmed.ncbi.nlm.nih.gov/11014718/

Currie GP, Fowler SJ, Lipworth BJ. Dose response of inhaled corticosteroids on bronchial hyperresponsiveness: A meta-analysis. Ann Allergy Asthma Immunol. 2003; 90: 194-198. PubMed: https://pubmed.ncbi.nlm.nih.gov/12602665/

Zietkowski Z, Bodzenta-Lukaszyk A, Tomasiak MM, Skiepko R, Szmitkowski M. Comparison of exhaled nitric oxide measurement with conventional tests in steroid-naive asthma patients. J Investig Allergol Clin Immunol. 2006; 16: 239-246. PubMed: https://pubmed.ncbi.nlm.nih.gov/16889281/

Sverrild A, Porsbjerg C, Thomsen SF, Backer V. Airway hyperresponsiveness to mannitol and methacholine and exhaled nitric oxide: a random-sample population study. J Allergy Clin Immunol. 2010; 126: 952-958. PubMed: https://pubmed.ncbi.nlm.nih.gov/20934208/

Lipworth BJ, Short PM, Williamson PA, Clearie KL, Fardon TC, et al. A randomized primary care trial of steroid titration against mannitol in persistent asthma: STAMINA trial. Chest. 2012; 141: 607-615. PubMed: https://pubmed.ncbi.nlm.nih.gov/21998259/

Jabbal S, Lipworth BJ. Blood eosinophils: The forgotten man of inhaled steroid dose titration. Clin Exp Allergy. 2018; 48: 93-95. PubMed: https://pubmed.ncbi.nlm.nih.gov/29117628/

Chan R, RuiWen Kuo C, Lipworth B. Pragmatic Clinical Perspective on Biologics for Severe Refractory Type 2 Asthma. J Allergy Clin Immunol Pract. 2020; 8: 3363-3370. PubMed: https://pubmed.ncbi.nlm.nih.gov/32673880/

Meurs H, Gosens R, Zaagsma J. Airway hyperresponsiveness in asthma: lessons from in vitro model systems and animal models. Eur Respir J. 2008; 32: 487-502. PubMed: https://pubmed.ncbi.nlm.nih.gov/18669789/

Sont JK, Willems LN, Bel EH, van Krieken JH, Vandenbroucke JP, Sterk PJ. Clinical control and histopathologic outcome of asthma when using airway hyperresponsiveness as an additional guide to long-term treatment. The AMPUL Study Group. Am J Respir Crit Care Med. 1999; 159: 1043-1051. PubMed: https://pubmed.ncbi.nlm.nih.gov/10194144/

Britton J, Hanley SP, Garrett HV, Hadfield JW, Tattersfield AE. Dose related effects of salbutamol and ipratropium bromide on airway calibre and reactivity in subjects with asthma. Thorax. 1988; 43: 300-305. PubMed: https://pubmed.ncbi.nlm.nih.gov/2970125/

Suh DI, Koh YY. Relationship between atopy and bronchial hyperresponsiveness. Allergy Asthma Immunol Res. 2013; 5: 181-188. PubMed: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695231/

Lipworth BJ, Jabbal S. Un-diagnosing persistent adult asthma. Eur Respir J. 2017; 50: 1701433. PubMed: https://pubmed.ncbi.nlm.nih.gov/29097435/

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Published

2021-02-17

How to Cite

Chan, R., Kuo, C. R., & Lipworth, B. (2021). A retrospective cohort study to evaluate the relationship of airway hyperresponsiveness to type 2 biomarkers in persistent asthma. Archives of Asthma, Allergy and Immunology, 5(1), 008–013. https://doi.org/10.29328/journal.aaai.1001023

Issue

Vol. 5 No. 1 (2021)

Section

Research Articles

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Copyright (c) 2021 Chan R, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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