Advertisement

Race is associated with differences in airway inflammation in patients with asthma

Published:January 06, 2017DOI:https://doi.org/10.1016/j.jaci.2016.10.024

      Background

      African American subjects have a greater burden from asthma compared with white subjects. Whether the pattern of airway inflammation differs between African American and white subjects is unclear.

      Objective

      We sought to compare sputum airway inflammatory phenotypes of African American and white subjects treated or not with inhaled corticosteroids (ICSs; ICS+ and ICS−, respectively).

      Methods

      We performed a secondary analysis of self-identified African American and white subjects with asthma enrolled in clinical trials conducted by the National Heart, Lung, and Blood Institute–sponsored Asthma Clinical Research Network and AsthmaNet. Demographics, clinical characteristics, and sputum cytology after sputum induction were examined. We used a sputum eosinophil 2% cut point to define subjects with either an eosinophilic (≥2%) or noneosinophilic (<2%) inflammatory phenotype.

      Results

      Among 1018 participants, African American subjects (n = 264) had a lower FEV1 percent predicted (80% vs 85%, P < .01), greater total IgE levels (197 vs 120 IU/mL, P < .01), and a greater proportion with uncontrolled asthma (43% vs 28%, P < .01) compared with white subjects (n = 754). There were 922 subjects in the ICS+ group (248 African American and 674 white subjects) and 298 subjects in the ICS− group (49 African American and 249 white subjects). Eosinophilic airway inflammation was not significantly different between African American and white subjects in either group (percentage with eosinophilic phenotype: ICS+ group: 19% vs 16%, P = .28; ICS− group: 39% vs 35%, P = .65; respectively). However, when adjusted for confounding factors, African American subjects were more likely to exhibit eosinophilic airway inflammation than white subjects in the ICS+ group (odds ratio, 1.58; 95% CI, 1.01-2.48; P = .046) but not in the ICS− group (P = .984).

      Conclusion

      African American subjects exhibit greater eosinophilic airway inflammation, which might explain the greater asthma burden in this population.

      Key words

      Abbreviations used:

      ACQ (Asthma Control Questionnaire), ACRN (Asthma Clinical Research Network), ACT (Asthma Control Test), BMI (Body mass index), ICS (Inhaled corticosteroid), SLIMSIT (Salmeterol and Leukotriene Modifiers vs. Salmeterol and ICS Treatment), SMOG (Smoking Modulates Outcomes of Glucocorticoid Therapy in Asthma), SOCS (Salmeterol Off Corticosteroids)
      To read this article in full you will need to make a payment

      References

        • Moorman J.E.
        • Rudd R.A.
        • Johnson C.A.
        • King M.
        • Minor P.
        • Bailey C.
        • et al.
        National surveillance for asthma—United States, 1980-2004.
        MMWR Surveill Summary. 2007; 56: 1-54
        • Akinbami L.
        Asthma prevalence, health care use and mortality: United States 2003-05.
        CDC National Center for Health Statistics, 2006 (Available at:) (Accessed October 21, 2015)
        • Grant E.N.
        • Lyttle C.S.
        • Weiss K.B.
        The relation of socioeconomic factors and racial/ethnic differences in US asthma mortality.
        Am J Public Health. 2000; 90: 1923-1925
        • Joseph C.L.M.
        • Ownby D.R.
        • Peterson E.L.
        • Johnson C.C.
        Racial differences in physiologic parameters related to asthma among middle-class children.
        Chest. 2000; 117: 1336-1344
        • Stewart K.A.
        • Higgins P.C.
        • McLaughlin C.G.
        • Williams T.V.
        • Granger E.
        • Croghan T.W.
        Differences in prevalence, treatment, and outcomes of asthma among a diverse population of children with equal access to care: findings from a study in the military health system.
        Arch Pediatr Adolesc Med. 2010; 164: 720-726
        • Nishimura K.K.
        • Galanter J.M.
        • Roth L.A.
        • Oh S.S.
        • Thakur N.
        • Nguyen E.A.
        • et al.
        Early-life air pollution and asthma risk in minority children: the GALA II and SAGE II studies.
        Am J Respir Crit Care Med. 2013; 188: 309-318
        • Thakur N.
        • Oh S.S.
        • Nguyen E.A.
        • Martin M.
        • Roth L.A.
        • Galanter J.
        • et al.
        Socioeconomic status and childhood asthma in urban minority youths: the GALA II and SAGE II studies.
        Am J Respir Crit Care Med. 2013; 188: 1202-1209
        • Akinbami L.J.
        • Moorman J.E.
        • Simon A.E.
        • Schoendorf K.C.
        Trends in racial disparities for asthma outcomes among children 0 to 17 years, 2001-2010.
        J Allergy Clin Immunol. 2014; 134: 547-553.e5
        • Zoratti E.M.
        • Havstad S.
        • Rodriguez J.
        • Robens-Paradise Y.
        • Lafata J.E.
        • McCarthy B.
        Health service use by African Americans and Caucasians with asthma in a managed care setting.
        Am J Respir Crit Care Med. 1998; 158: 371-377
        • Boudreaux E.D.
        • Emond S.D.
        • Clark S.
        • Camargo C.A.
        Race/ethnicity and asthma among children presenting to the emergency department: differences in disease severity and management.
        Pediatrics. 2003; 111: E615-E621
        • Ford J.G.
        • McCaffrey L.
        Understanding disparities in asthma outcomes among African Americans.
        Clin Chest Med. 2006; 27: 423-430
        • Haselkorn T.
        • Lee J.H.
        • Mink D.R.
        • Weiss S.T.
        TENOR Study Group. Racial disparities in asthma-related health outcomes in severe or difficult-to-treat asthma.
        Ann Allergy Asthma Immunol. 2008; 101: 256-263
        • Wechsler M.E.
        • Castro M.
        • Lehman E.
        • Chinchilli V.M.
        • Sutherland E.R.
        • Denlinger L.
        • et al.
        Impact of race on asthma treatment failures in the Asthma Clinical Research Network.
        Am J Respir Crit Care Med. 2011; 184: 1247-1253
        • Chan M.T.
        • Leung D.Y.
        • Szefler S.J.
        • Spahn J.D.
        Difficult-to-control asthma: clinical characteristics of steroid-insensitive asthma.
        J Allergy Clin Immunol. 1998; 101: 594-601
        • Ortega V.E.
        • Meyers D.A.
        Pharmacogenetics: implications of race and ethnicity on defining genetic profiles for personalized medicine.
        J Allergy Clin Immunol. 2014; 133: 16-26
        • Drazen J.M.
        • Arm J.P.
        • Austen K.F.
        Sorting out the cytokines of asthma.
        J Exp Med. 1996; 183: 1-5
        • Spanevello A.
        • Confalonieri M.
        • Sulotto F.
        • Romano F.
        • Balzano G.
        • Migliori G.B.
        • et al.
        Induced sputum cellularity—reference values and distribution in normal volunteers.
        Am J Respir Crit Care Med. 2000; 162: 1172-1174
        • Belda J.
        • Leigh R.
        • Parameswaran K.
        • O'Byrne P.M.
        • Sears M.R.
        • Hargreave F.E.
        Induced sputum cell counts in healthy adults.
        Am J Respir Crit Care Med. 2000; 161: 475-478
        • Szefler S.J.
        • Wenzel S.
        • Brown R.
        • Erzurum S.C.
        • Fahy J.V.
        • Hamilton R.G.
        • et al.
        Asthma outcomes: biomarkers.
        J Allergy Clin Immunol. 2012; 129: S9-S23
        • McGrath K.W.
        • Icitovic N.
        • Boushey H.A.
        • Lazarus S.C.
        • Sutherland E.R.
        • Chinchilli V.M.
        • et al.
        A large subgroup of mild-to-moderate asthma is persistently non-eosinophilic.
        Am J Respir Crit Care Med. 2012; 185: 612-619
        • Iwamoto H.
        • Yokoyama A.
        • Shiota N.
        • Shoda H.
        • Haruta Y.
        • Hattori N.
        • et al.
        Tiotropium bromide is effective for severe asthma with noneosinophilic phenotype.
        Eur Respir J. 2008; 31: 1379-1380
        • Sutherland E.R.
        • Busse W.W.
        Designing clinical trials to address the needs of childhood and adult asthma: the National Heart, Lung, and Blood Institute's AsthmaNet.
        J Allergy Clin Immunol. 2014; 133: 34-38.e1
        • Lazarus S.C.
        • Boushey H.A.
        • Fahy J.V.
        • Chinchilli V.M.
        • Lemanske Jr., R.F.
        • Sorkness C.A.
        • et al.
        Long-acting 2-agonist monotherapy vs continued therapy with inhaled corticosteroids in patients with persistent asthma: a randomized controlled trial.
        JAMA. 2001; 285: 2583-2593
        • Szefler S.J.
        • Martin R.J.
        • King T.S.
        • Boushey H.A.
        • Cherniack R.M.
        • Chinchilli V.M.
        • et al.
        Significant variability in response to inhaled corticosteroids for persistent asthma.
        J Allergy Clin Immunol. 2002; 109: 410-418
        • Boushey H.A.
        • Sorkness C.A.
        • King T.S.
        • Sullivan S.D.
        • Fahy J.V.
        • Lazarus S.C.
        • et al.
        Daily versus as-needed corticosteroids for mild persistent asthma.
        N Engl J Med. 2005; 352: 1519-1528
        • Martin R.J.
        • Szefler S.J.
        • King T.S.
        • Kraft M.
        • Boushey H.A.
        • Chinchilli V.M.
        • et al.
        The Predicting Response to Inhaled Corticosteroid Efficacy (PRICE) trial.
        J Allergy Clin Immunol. 2007; 119: 73-80
        • Lazarus S.C.
        • Chinchilli V.M.
        • Rollings N.J.
        • Boushey H.A.
        • Cherniack R.
        • Craig T.J.
        • et al.
        Smoking affects response to inhaled corticosteroids or leukotriene receptor antagonists in asthma.
        Am J Respir Crit Care Med. 2007; 175: 783-790
        • Deykin A.
        • Wechsler M.E.
        • Boushey H.A.
        • Chinchilli V.M.
        • Kunselman S.J.
        • Craig T.J.
        • et al.
        Combination therapy with a long-acting beta-agonist and a leukotriene antagonist in moderate asthma.
        Am J Respir Crit Care Med. 2007; 175: 228-234
        • Peters S.P.
        • Kunselman S.J.
        • Icitovic N.
        • Moore W.C.
        • Pascual R.
        • Ameredes B.T.
        • et al.
        Tiotropium bromide step-up therapy for adults with uncontrolled asthma.
        N Engl J Med. 2010; 363: 1715-1726
        • Sutherland E.R.
        • King T.S.
        • Icitovic N.
        • Ameredes B.T.
        • Bleecker E.
        • Boushey H.A.
        • et al.
        A trial of clarithromycin for the treatment of suboptimally controlled asthma.
        J Allergy Clin Immunol. 2010; 126: 747-753
        • Calhoun W.J.
        • Ameredes B.T.
        • King T.S.
        • Icitovic N.
        • Bleecker E.R.
        • Castro M.
        • et al.
        Comparison of physician-, biomarker-, and symptom-based strategies for adjustment of inhaled corticosteroid therapy in adults with asthma: the BASALT randomized controlled trial.
        JAMA. 2012; 308: 987-997
        • Castro M.
        • King T.S.
        • Kunselman S.J.
        • Cabana M.D.
        • Denlinger L.
        • Holguin F.
        • et al.
        Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: the VIDA randomized clinical trial.
        JAMA. 2014; 311: 2083-2091
        • National Asthma Education and Prevention Program
        Full report of the expert panel: guidelines for the diagnosis and management of asthma.
        (EPR-3; Source Document). National Heart, Lung and Blood Institute, 2007 (Available at:) (Accessed October 21, 2015)
        • Simpson J.L.
        • Powell H.
        • Boyle M.J.
        • Scott R.J.
        • Gibson P.G.
        Clarithromycin targets neutrophilic airway inflammation in refractory asthma.
        Am J Respir Crit Care Med. 2008; 177: 148-155
        • Pizzichini E.
        • Leff J.A.
        • Reiss T.F.
        • Hendeles L.
        • Boulet L.P.
        • Wei L.X.
        • et al.
        Montelukast reduces airway eosinophilic inflammation in asthma: a randomized, controlled trial.
        Eur Respir J. 1999; 14: 12-18
        • Minoguchi K.
        • Kohno Y.
        • Minoguchi H.
        • Kihara N.
        • Sano Y.
        • Yasuhara H.
        • et al.
        Reduction of eosinophilic inflammation in the airways of patients with asthma using montelukast.
        Chest. 2002; 121: 732-738
        • Juniper E.F.
        • O'Byrne P.M.
        • Guyatt G.H.
        • Ferrie P.J.
        • King D.R.
        Development and validation of a questionnaire to measure asthma control.
        Eur Respir J. 1999; 14: 902-907
        • Nathan R.A.
        • Sorkness C.A.
        • Kosinski M.
        • Schatz M.
        • Li J.T.
        • Marcus P.
        • et al.
        Development of the asthma control test: a survey for assessing asthma control.
        J Allergy Clin Immunol. 2004; 113: 59-65
        • Naqvi M.
        • Choudhry S.
        • Tsai H.J.
        • Thyne S.
        • Navarro D.
        • Nazario S.
        • et al.
        Association between IgE levels and asthma severity among African American, Mexican, and Puerto Rican patients with asthma.
        J Allergy Clin Immunol. 2007; 120: 137-143
        • Tran T.N.
        • Khatry D.B.
        • Ke X.
        • Ward C.K.
        • Goassage D.
        High blood eosinophil count is associated with more frequent asthma attacks in asthma patients.
        Ann Allergy Asthma Immunol. 2014; 113: 19-24
        • Wagener A.H.
        • de Nijs S.B.
        • Lutter R.
        • Sousa A.R.
        • Weersink E.J.
        • Bel E.H.
        • et al.
        External validation of blood eosinophils, FE(NO) and serum periostin as surrogates for sputum eosinophils in asthma.
        Thorax. 2015; 70: 115-120
        • Martin R.J.
        • Kephart D.K.
        • Dyer A.M.
        • Fahy J.V.
        • Kraft M.
        • Asthma Clinical Research Network
        Quality control within the Asthma Clinical Research Network.
        Control Clin Trials. 2001; 22: 207S-221S
        • Gershman N.H.
        • Wong H.H.
        • Liu J.T.
        • Mahlmeister M.J.
        • Fahy J.V.
        Comparison of two methods of collecting induced sputum in asthmatic subjects.
        Eur Respir J. 1996; 9: 2448-2453
        • Simpson J.L.
        • Scott R.
        • Boyle M.J.
        • Gibson P.G.
        Inflammatory subtypes in asthma: assessment and identification using induced sputum.
        Respirology. 2006; 11: 54-61
        • Woodruff P.G.
        • Khashayar R.
        • Lazarus S.C.
        • Janson S.
        • Avila P.
        • Boushey H.A.
        • et al.
        Relationship between airway inflammation, hyperresponsiveness, and obstruction in asthma.
        J Allergy Clin Immunol. 2001; 108: 753-758
        • Wenzel S.E.
        Asthma: defining of the persistent adult phenotypes.
        Lancet. 2006; 368: 804-813
        • Green R.H.
        • Brightlung C.E.
        • Woltmann G.
        • Parker D.
        • Wardlaw A.J.
        • Pavord I.D.
        Analysis of induced sputum in adults with asthma: identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticosteroids.
        Thorax. 2002; 57: 875-879
        • Hastie A.T.
        • Moore W.C.
        • Meyers D.A.
        • Vestal P.L.
        • Li H.S.
        • Peters S.P.
        • et al.
        Analyses of asthma severity phenotypes and inflammatory proteins in subjects stratified by sputum granulocytes.
        J Allergy Clin Immunol. 2010; 125: 1028-1036.e13
        • Kumar R.
        • Seibold M.A.
        • Aldrich M.C.
        • Williams L.K.
        • Reiner A.P.
        • Colangelo L.
        • et al.
        Genetic ancestry in lung-function predictions.
        N Engl J Med. 2010; 363: 321-330
        • Goleva E.
        • Li L.B.
        • Eves P.T.
        • Strand M.J.
        • Martin R.J.
        • Leung D.Y.M.
        Increased glucocorticoid receptor beta alters steroid response in glucocorticoid-insensitive asthma.
        Am J Respir Crit Care Med. 2006; 173: 607-616
        • Federico M.J.
        • Covar R.A.
        • Brown E.E.
        • Leung D.Y.M.
        • Spahn J.D.
        Racial differences in T-lymphocyte response to glucocorticoids.
        Chest. 2005; 127: 571-578
        • Sutherland E.R.
        • Goleva E.
        • Strand M.
        • Beuther D.A.
        • Leung D.Y.M.
        Body mass and glucocorticoid response in asthma.
        Am J Respir Crit Care Med. 2008; 178: 682-687
        • Goleva E.
        • Li L.B.
        • Leung D.Y.M.
        IFN-gamma reverses IL-2- and IL-4-mediated T-cell steroid resistance.
        Am J Respir Cell Mol Biol. 2009; 40: 223-230
        • Li L.B.
        • Leung D.Y.M.
        • Martin R.J.
        • Goleva E.
        Inhibition of histone deacetylase 2 expression by elevated glucocorticoid receptor beta in steroid-resistant asthma.
        Am J Respir Crit Care Med. 2010; 182: 877-883
        • Peters-Golden M.
        • Swern A.
        • Bird S.S.
        • Hustad C.M.
        • Grant E.
        • Edelman J.M.
        Influence of body mass index on the response to asthma controller agents.
        Eur Respir J. 2006; 27: 495-503
        • Dixon A.E.
        • Holguin F.
        • Sood A.
        • Salone C.M.
        • Pratley R.E.
        • Beuther D.A.
        • et al.
        An official American Thoracic Society Workshop report: obesity and asthma.
        Proc Am Thorac Soc. 2010; 7: 325-335
        • Schatz M.
        • Zeiger R.S.
        • Yang S.J.
        • Chen W.
        • Sajjan S.
        • Allen-Ramey F.
        • et al.
        Prospective study on the relationship of obesity to asthma impairment and risk.
        J Allergy Clin Immunol Pract. 2015; 3: 560-565.e1
        • Camargo Jr., C.A.
        • Boulet L.P.
        • Sutherland E.R.
        • Busse W.W.
        • Yancey S.W.
        • Emmett A.H.
        • et al.
        Body mass index and response to asthma therapy: fluticasone propionate/salmeterol versus montelukast.
        J Asthma. 2010; 47: 76-82
        • Nyenhuis S.N.
        • Du J.
        • Ackerman S.J.
        • Krishnan J.A.
        • Kittles R.
        Impact of self-identified race and genetic ancestry on airway inflammation in asthma.
        J Allergy Clin Immunol. 2015; 135 ([abstract]): AB86
        • Pizzichini E.
        • Pizzichini M.M.
        • Efthimiadia A.
        • Dolovich J.
        • Hargreave F.E.
        Measuring airway inflammation in asthma: eosinophils and eosinophilic cationic protein in induced sputum compared with peripheral blood.
        J Allergy Clin Immunol. 1997; 99: 539-544
        • Smith A.D.
        • Cowan J.O.
        • Filsell S.
        • McLachlan C.
        • Monti-Sheehan G.
        • Jackson P.
        • et al.
        Diagnosing asthma: comparisons between exhaled nitric oxide measurements and conventional tests.
        Am J Respir Crit Care Med. 2004; 169: 473-478
        • Korevaar D.A.
        • Westerhof G.A.
        • Wang J.
        • Cohen J.F.
        • Spijker R.
        • Sterk P.J.
        • et al.
        Diagnostic accuracy of minimally invasive markers for detection of airway eosinophilia in asthma: a systematic review and meta-analysis.
        Lancet Respir Med. 2015; 3: 290-300
        • Malka J.
        • Mauger D.T.
        • Covar R.
        • Rabinovitch N.
        • Lemanske Jr., R.F.
        • Spahn J.D.
        • et al.
        Eczema and race as combined determinants for differential response to step-up asthma therapy.
        J Allergy Clin Immunol. 2014; 134: 483-485