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. 2009 Oct 13;9(6):439–445. doi: 10.1007/s11882-009-0065-7

Asthma phenotypes

Steve Handoyo, Lanny J Rosenwasser 1,✉
PMCID: PMC7089312  PMID: 19814916

Abstract

The many roads leading to the syndrome of asthma have proven to be intricately interconnected. The chronic inflammation of asthma is characterized by airway hyperreactivity and variable reversibility. Past classification systems relied on assessment of daily impairment and the distinction between intrinsic (nonallergic) and extrinsic (allergic). With more precise asthma phenotypes, association studies likely will have greater significance. In addition, patients at higher risk for severe disease can be more effectively managed, and treatments can be directed to responders. In this review, we look at eight identified phenotypes: atopic and nonatopic status, pre-asthma wheezing, inflammatory mediator predominance, aspirin-sensitive, exercise-induced, severe, and flare-prone asthma. Although significant overlap exists among the distinctions, any future phenotype classification system will need to incorporate these eight clinical asthmatic populations.

Keywords: Asthma, Respiratory Syncytial Virus, Asthma Patient, Severe Asthma, Allergy Clin Immunol

References and Recommended Reading

  • 1.National Institutes of Health, National Heart, Lung,Blood Institute. National Asthma EducationPrevention Program. Expert Panel Report 3 . Guidelines for the Diagnosis and Management of Asthma. Bethesda, MD: National Heart, Lung, and Blood Institute; 2007. [Google Scholar]
  • 2.Bouzigon E., Corda E., Aschard H., et al. Effect of 17q21 variants and smoking exposure in early-onset asthma. N Engl J Med. 2008;359:1985–1994. doi: 10.1056/NEJMoa0806604. [DOI] [PubMed] [Google Scholar]
  • 3.Leckie M.J., ten Brinke A., Khan J., et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet. 2000;356:2144–2148. doi: 10.1016/S0140-6736(00)03496-6. [DOI] [PubMed] [Google Scholar]
  • 4.Miranda C., Busacker A., Balzar S., et al. Distinguishing severe asthma phenotypes: role of age at onset and eosinophilic inflammation. J Allergy Clin Immunol. 2004;113:101–108. doi: 10.1016/j.jaci.2003.10.041. [DOI] [PubMed] [Google Scholar]
  • 5.Haldar P., Brightling C.E., Hargadon B., et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med. 2009;360:973–984. doi: 10.1056/NEJMoa0808991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Nair P., Pizzichini M.M., Kjarsgaard M., et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med. 2009;360:985–993. doi: 10.1056/NEJMoa0805435. [DOI] [PubMed] [Google Scholar]
  • 7.Haldar P., Pavord I.D., Shaw D.E., et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med. 2008;178:218–224. doi: 10.1164/rccm.200711-1754OC. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Arbes S.J., Jr, Gergen P.J., Vaughn B., Zeldin D.C. Asthma cases attributable to atopy: results from the Third National Health and Nutrition Examination Survey. J Allergy Clin Immunol. 2007;120:1139–1145. doi: 10.1016/j.jaci.2007.07.056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Ahern D., Lloyd C.M., Robinson D.S. Chemokine responsiveness of CD4+ CD25+ regulatory and CD4+ CD25-T cells from atopic and nonatopic donors. Allergy. 2009;64:1121–1129. doi: 10.1111/j.1398-9995.2008.01962.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Drews AC, Pizzichini MM, Pizzichini E, et al.: Neutrophilic airway inflammation is a main feature of induced sputum in nonatopic asthmatic children. Allergy 2009 Apr 14 (Epub ahead of print). [DOI] [PubMed]
  • 11.Romanet-Manent S., Charpin D., Magnan A., et al. Allergic vs nonallergic asthma: what makes the difference? Allergy. 2002;57:607–613. doi: 10.1034/j.1398-9995.2002.23504.x. [DOI] [PubMed] [Google Scholar]
  • 12.Novak N., Bieber T. Allergic and nonallergic forms of atopic diseases. J Allergy Clin Immunol. 2003;112:252–262. doi: 10.1067/mai.2003.1595. [DOI] [PubMed] [Google Scholar]
  • 13.Turato G., Barbato A., Baraldo S., et al. Nonatopic children with multitrigger wheezing have airway pathology comparable to atopic asthma. Am J Respir Crit Care Med. 2008;178:476–482. doi: 10.1164/rccm.200712-1818OC. [DOI] [PubMed] [Google Scholar]
  • 14.Ownby D.R., Joseph C.L. Should nonatopic asthma get equal attention? J Allergy Clin Immunol. 2007;120:1018–1020. doi: 10.1016/j.jaci.2007.09.028. [DOI] [PubMed] [Google Scholar]
  • 15.Sears M.R., Greene J.M., Willan A.R., et al. A longitudinal, population-based, cohort study of childhood asthma followed to adulthood. N Engl J Med. 2003;349:1414–1422. doi: 10.1056/NEJMoa022363. [DOI] [PubMed] [Google Scholar]
  • 16.Henderson J., Granell R., Heron J., et al. Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airway responsiveness in mid-childhood. Thorax. 2008;63:974–980. doi: 10.1136/thx.2007.093187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Martinez F.D., Wright A.L., Taussig L.M., et al. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med. 1995;332:133–138. doi: 10.1056/NEJM199501193320301. [DOI] [PubMed] [Google Scholar]
  • 18.Strachan D.P., Butland B.K., Anderson H.R. Incidence and prognosis of asthma and wheezing illness from early childhood to age 33 in a national British cohort. BMJ. 1996;312:1195–1199. doi: 10.1136/bmj.312.7040.1195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Haldar P., Pavord I.D. Noneosinophilic asthma: a distinct clinical and pathologic phenotype. J Allergy Clin Immunol. 2007;119:1043–1052. doi: 10.1016/j.jaci.2007.02.042. [DOI] [PubMed] [Google Scholar]
  • 20.Wenzel S.E. Asthma: defining of the persistent adult phenotypes. Lancet. 2006;368:804–813. doi: 10.1016/S0140-6736(06)69290-8. [DOI] [PubMed] [Google Scholar]
  • 21.Borish L., Culp J.A. Asthma: a syndrome composed of heterogeneous diseases. Ann Allergy Asthma Immunol. 2008;101:1–8. doi: 10.1016/S1081-1206(10)60826-5. [DOI] [PubMed] [Google Scholar]
  • 22.Moore W.C., Bleecker E.R., Curran-Everett D., et al. Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute’s Severe Asthma Research Program. J Allergy Clin Immunol. 2007;119:405–413. doi: 10.1016/j.jaci.2006.11.639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.ten Brinke A., Zwinderman A.H., Sterk P.J., et al. “Refractory“ eosinophilic airway inflammation in severe asthma: effect of parenteral corticosteroids. Am J Respir Crit Care Med. 2004;170:601–605. doi: 10.1164/rccm.200404-440OC. [DOI] [PubMed] [Google Scholar]
  • 24.MacDowell A.L., Bacharier L.B. Infectious triggers of asthma. Immunol Allergy Clin North Am. 2005;25:45–66. doi: 10.1016/j.iac.2004.09.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Bisgaard H., Hermansen M.N., Buchvald F., et al. Childhood asthma after bacterial colonization of the airway in neonates. N Engl J Med. 2007;357:1487–1495. doi: 10.1056/NEJMoa052632. [DOI] [PubMed] [Google Scholar]
  • 26.Kraft M., Cassell G.H., Pak J., Martin R.J. Mycoplasma pneumoniae and Chlamydia pneumoniae in asthma: effect of clarithromycin. Chest. 2002;121:1782–1788. doi: 10.1378/chest.121.6.1782. [DOI] [PubMed] [Google Scholar]
  • 27.Stensballe L.G., Simonsen J.B., Thomsen S.F., et al. The causal direction in the association between respiratory syncytial virus hospitalization and asthma. J Allergy Clin Immunol. 2009;123:131.e1–137.e1. doi: 10.1016/j.jaci.2008.10.042. [DOI] [PubMed] [Google Scholar]
  • 28.Lemanske R.F., Jr, Jackson D.J., Gangnon R.E., et al. Rhinovirus illnesses during infancy predict subsequent childhood wheezing. J Allergy Clin Immunol. 2005;116:571–577. doi: 10.1016/j.jaci.2005.06.024. [DOI] [PubMed] [Google Scholar]
  • 29.Kusel M.M., de Klerk N.H., Kebadze T., et al. Early-life respiratory viral infections, atopic sensitization, and risk of subsequent development of persistent asthma. J Allergy Clin Immunol. 2007;119:1105–1110. doi: 10.1016/j.jaci.2006.12.669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Miller E.K., Edwards K.M., Weinberg G.A., et al. A novel group of rhinoviruses is associated with asthma hospitalizations. J Allergy Clin Immunol. 2009;123:98.e1–104.e1. doi: 10.1016/j.jaci.2008.10.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Sutherland E.R., Martin R.J. Asthma and atypical bacterial infection. Chest. 2007;132:1962–1966. doi: 10.1378/chest.06-2415. [DOI] [PubMed] [Google Scholar]
  • 32.Lieberman D., Printz S., Ben-Yaakov M., et al. Atypical pathogen infection in adults with acute exacerbation of bronchial asthma. Am J Respir Crit Care Med. 2003;167:406–410. doi: 10.1164/rccm.200209-996OC. [DOI] [PubMed] [Google Scholar]
  • 33.Johnston S.L., Blasi F., Black P.N., et al. The effect of telithromycin in acute exacerbations of asthma. N Engl J Med. 2006;354:1589–1600. doi: 10.1056/NEJMoa044080. [DOI] [PubMed] [Google Scholar]
  • 34.ten Brinke A., van Dissel J.T., Sterk P.J., et al. Persistent airflow limitation in adult-onset nonatopic asthma is associated with serologic evidence of Chlamydia pneumoniae infection. J Allergy Clin Immunol. 2001;107:449–454. doi: 10.1067/mai.2001.113047. [DOI] [PubMed] [Google Scholar]
  • 35.Schroder N.W., Crother T.R., Naiki Y., et al. Innate immune responses during respiratory tract infection with a bacterial pathogen induce allergic airway sensitization. J Allergy Clin Immunol. 2008;122:595.e5–602.e5. doi: 10.1016/j.jaci.2008.06.038. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Mascia K., Haselkorn T., Deniz Y.M., et al. Aspirin sensitivity and severity of asthma: evidence for irreversible airway obstruction in patients with severe or difficult-to-treat asthma. J Allergy Clin Immunol. 2005;116:970–975. doi: 10.1016/j.jaci.2005.08.035. [DOI] [PubMed] [Google Scholar]
  • 37.Szczeklik A., Stevenson D.D. Aspirin-induced asthma: advances in pathogenesis, diagnosis, and management. J Allergy Clin Immunol. 2003;111:913–921. doi: 10.1067/mai.2003.1487. [DOI] [PubMed] [Google Scholar]
  • 38.Kawagishi Y., Mita H., Taniguchi M., et al. Leukotriene C4 synthase promoter polymorphism in Japanese patients with aspirin-induced asthma. J Allergy Clin Immunol. 2002;109:936–942. doi: 10.1067/mai.2002.124466. [DOI] [PubMed] [Google Scholar]
  • 39.Sousa A.R., Parikh A., Scadding G., et al. Leukotriene-receptor expression on nasal mucosal inflammatory cells in aspirin-sensitive rhinosinusitis. N Engl J Med. 2002;347:1493–1499. doi: 10.1056/NEJMoa013508. [DOI] [PubMed] [Google Scholar]
  • 40.Shaker M., Lobb A., Jenkins P., et al. An economic analysis of aspirin desensitization in aspirin-exacerbated respiratory disease. J Allergy Clin Immunol. 2008;121:81–87. doi: 10.1016/j.jaci.2007.06.047. [DOI] [PubMed] [Google Scholar]
  • 41.Weiler J.M., Bonini S., Coifman R., et al. American Academy of Allergy, Asthma & Immunology Work Group report: exercise-induced asthma. J Allergy Clin Immunol. 2007;119:1349–1358. doi: 10.1016/j.jaci.2007.02.041. [DOI] [PubMed] [Google Scholar]
  • 42.Fitch K.D., Sue-Chu M., Anderson S.D., et al. Asthma and the elite athlete: summary of the International Olympic Committee’s consensus conference, Lausanne, Switzerland, January 22–24, 2008. J Allergy Clin Immunol. 2008;122:254–260. doi: 10.1016/j.jaci.2008.07.003. [DOI] [PubMed] [Google Scholar]
  • 43.Lessard A., Turcotte H., Cormier Y., Boulet L.P. Obesity and asthma: a specific phenotype? Chest. 2008;134:317–323. doi: 10.1378/chest.07-2959. [DOI] [PubMed] [Google Scholar]
  • 44.Brinke T. Risk factors of frequent exacerbations in difficult-to-treat asthma. Eur Respir J. 2005;26:812–818. doi: 10.1183/09031936.05.00037905. [DOI] [PubMed] [Google Scholar]
  • 45.Carroll C.L., Schramm C.M., Zucker A.R. Severe exacerbations in children with mild asthma: characterizing a pediatric phenotype. J Asthma. 2008;45:513–517. doi: 10.1080/02770900802017751. [DOI] [PubMed] [Google Scholar]
  • 46.Bai T.R., Vonk J.M., Postma D.S., Boezen H.M. Severe exacerbations predict excess lung function decline in asthma. Eur Respir J. 2007;30:452–456. doi: 10.1183/09031936.00165106. [DOI] [PubMed] [Google Scholar]
  • 47.ten Brinke A., Sterk P.J., Masclee A.A., et al. Risk factors of frequent exacerbations in difficult-to-treat asthma. Eur Respir J. 2005;26:812–818. doi: 10.1183/09031936.05.00037905. [DOI] [PubMed] [Google Scholar]
  • 48.Miller M.K., Lee J.H., Miller D.P., Wenzel S.E. Recent asthma exacerbations: a key predictor of future exacerbations. Respir Med. 2007;101:481–489. doi: 10.1016/j.rmed.2006.07.005. [DOI] [PubMed] [Google Scholar]
  • 49.Tattersfield A.E., Postma D.S., Barnes P.J., et al. Exacerbations of asthma: a descriptive study of 425 severe exacerbations. The FACET International Study Group. Am J Respir Crit Care Med. 1999;160:594–599. doi: 10.1164/ajrccm.160.2.9811100. [DOI] [PubMed] [Google Scholar]
  • 50.Sykes A., Johnston S.L. Etiology of asthma exacerbations. J Allergy Clin Immunol. 2008;122:685–688. doi: 10.1016/j.jaci.2008.08.017. [DOI] [PubMed] [Google Scholar]
  • 51.Murray C.S., Poletti G., Kebadze T., et al. Study of modifiable risk factors for asthma exacerbations: virus infection and allergen exposure increase the risk of asthma hospital admissions in children. Thorax. 2006;61:376–382. doi: 10.1136/thx.2005.042523. [DOI] [PMC free article] [PubMed] [Google Scholar]

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