Biomarker-based Asthma Phenotypes of Corticosteroid Response

Overview

Journal J Allergy Clin Immunol

Specialty Allergy & Immunology

Date 2014 Dec 10

PMID 25488689

Citations 45

Authors

Douglas C Cowan

D Robin Taylor

Laura E Peterson

Jan O Cowan

Rochelle Palmay

Avis Williamson

Jef Hammel

Serpil C Erzurum

Stanley L Hazen

Suzy A A Comhair

Affiliations

Soon will be listed here.

Abstract

Background: Asthma is a heterogeneous disease with different phenotypes. Inhaled corticosteroid (ICS) therapy is a mainstay of treatment for asthma, but the clinical response to ICSs is variable.

Objective: We hypothesized that a panel of inflammatory biomarkers (ie, fraction of exhaled nitric oxide [Feno], sputum eosinophil count, and urinary bromotyrosine [BrTyr] level) might predict steroid responsiveness.

Methods: The original study from which this analysis originates comprised 2 phases: a steroid-naive phase 1 and a 28-day trial of ICSs (phase 2) during which Feno values, sputum eosinophil counts, and urinary BrTyr levels were measured. The response to ICSs was based on clinical improvements, including a 12% or greater increase in FEV1, a 0.5-point or greater decrease in Asthma Control Questionnaire score, and 2 doubling dose or greater increase in provocative concentration of adenosine 5'-monophosphate causing a 20% decrease in FEV1 (PC20AMP). Healthy control subjects were also evaluated in this study for comparison of biomarkers with those seen in asthmatic patients.

Results: Asthmatic patients had higher than normal Feno values, sputum eosinophil counts, and urinary BrTyr levels during the steroid-naive phase and after ICS therapy. After 28-day trial of ICSs, Feno values decreased in 82% of asthmatic patients, sputum eosinophil counts decreased in 60%, and urinary BrTyr levels decreased in 58%. Each of the biomarkers at the steroid-naive phase had utility for predicting steroid responsiveness, but the combination of high Feno values and high urinary BrTyr levels had the best power (13.3-fold, P < .01) to predict a favorable response to ICS therapy. However, the magnitude of the decrease in biomarker levels was unrelated to the magnitude of clinical response to ICS therapy.

Conclusion: A noninvasive panel of biomarkers in steroid-naive asthmatic patients predicts clinical responsiveness to ICS therapy.

Citing Articles

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References

Pavord I, Brightling C, Woltmann G, Wardlaw A . Non-eosinophilic corticosteroid unresponsive asthma. Lancet. 1999; 353(9171):2213-4. DOI: 10.1016/S0140-6736(99)01813-9. View

Brown H . Treatment of chronic asthma with prednisolone; significance of eosinophils in the sputum. Lancet. 1958; 2(7059):1245-7. DOI: 10.1016/s0140-6736(58)91385-0. View

Deykin A, Lazarus S, Fahy J, Wechsler M, Boushey H, Chinchilli V . Sputum eosinophil counts predict asthma control after discontinuation of inhaled corticosteroids. J Allergy Clin Immunol. 2005; 115(4):720-7. DOI: 10.1016/j.jaci.2004.12.1129. View

. 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(8):912-30. DOI: 10.1164/rccm.200406-710ST. View

Juniper E, Svensson K, Mork A, Stahl E . Measurement properties and interpretation of three shortened versions of the asthma control questionnaire. Respir Med. 2005; 99(5):553-8. DOI: 10.1016/j.rmed.2004.10.008. View

Berry M, Shaw D, Green R, Brightling C, Wardlaw A, Pavord I . The use of exhaled nitric oxide concentration to identify eosinophilic airway inflammation: an observational study in adults with asthma. Clin Exp Allergy. 2005; 35(9):1175-9. DOI: 10.1111/j.1365-2222.2005.02314.x. View

Zeiger R, Szefler S, Phillips B, Schatz M, Martinez F, Chinchilli V . Response profiles to fluticasone and montelukast in mild-to-moderate persistent childhood asthma. J Allergy Clin Immunol. 2006; 117(1):45-52. DOI: 10.1016/j.jaci.2005.10.012. View

Bacci E, Cianchetti S, Bartoli M, Dente F, Di Franco A, Vagaggini B . Low sputum eosinophils predict the lack of response to beclomethasone in symptomatic asthmatic patients. Chest. 2006; 129(3):565-72. DOI: 10.1378/chest.129.3.565. View

Lemiere C, Ernst P, Olivenstein R, Yamauchi Y, Govindaraju K, Ludwig M . Airway inflammation assessed by invasive and noninvasive means in severe asthma: eosinophilic and noneosinophilic phenotypes. J Allergy Clin Immunol. 2006; 118(5):1033-9. DOI: 10.1016/j.jaci.2006.08.003. View

10.

Michils A, Baldassarre S, Van Muylem A . Exhaled nitric oxide and asthma control: a longitudinal study in unselected patients. Eur Respir J. 2007; 31(3):539-46. DOI: 10.1183/09031936.00020407. View

11.

Puckett J, George S . Partitioned exhaled nitric oxide to non-invasively assess asthma. Respir Physiol Neurobiol. 2008; 163(1-3):166-77. PMC: 2642931. DOI: 10.1016/j.resp.2008.07.020. View

12.

Haldar P, Brightling C, Hargadon B, Gupta S, Monteiro W, Sousa A . Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med. 2009; 360(10):973-84. PMC: 3992367. DOI: 10.1056/NEJMoa0808991. View

13.

Reddel H, Taylor D, Bateman E, Boulet L, Boushey H, Busse W . An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med. 2009; 180(1):59-99. DOI: 10.1164/rccm.200801-060ST. View

14.

Scott M, Raza A, Karmaus W, Mitchell F, Grundy J, Kurukulaaratchy R . Influence of atopy and asthma on exhaled nitric oxide in an unselected birth cohort study. Thorax. 2010; 65(3):258-62. PMC: 2890070. DOI: 10.1136/thx.2009.125443. View

15.

Cowan D, Cowan J, Palmay R, Williamson A, Taylor D . Effects of steroid therapy on inflammatory cell subtypes in asthma. Thorax. 2009; 65(5):384-90. DOI: 10.1136/thx.2009.126722. View

16.

Wedes S, Khatri S, Zhang R, Wu W, Comhair S, Wenzel S . Noninvasive markers of airway inflammation in asthma. Clin Transl Sci. 2010; 2(2):112-7. PMC: 2838203. DOI: 10.1111/j.1752-8062.2009.00095.x. View

17.

Dweik R, Sorkness R, Wenzel S, Hammel J, Curran-Everett D, Comhair S . Use of exhaled nitric oxide measurement to identify a reactive, at-risk phenotype among patients with asthma. Am J Respir Crit Care Med. 2010; 181(10):1033-41. PMC: 2874447. DOI: 10.1164/rccm.200905-0695OC. View

18.

Wedes S, Wu W, Comhair S, McDowell K, DiDonato J, Erzurum S . Urinary bromotyrosine measures asthma control and predicts asthma exacerbations in children. J Pediatr. 2011; 159(2):248-55.e1. PMC: 3354913. DOI: 10.1016/j.jpeds.2011.01.029. View

19.

Wegmann M . Targeting eosinophil biology in asthma therapy. Am J Respir Cell Mol Biol. 2011; 45(4):667-74. DOI: 10.1165/rcmb.2011-0013TR. View

20.

Fleming L, Wilson N, Regamey N, Bush A . Use of sputum eosinophil counts to guide management in children with severe asthma. Thorax. 2011; 67(3):193-8. DOI: 10.1136/thx.2010.156836. View