Introduction to Asthma and Phenotyping

  • Regina A. Pillai
  • William J. CalhounEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 795)


Asthma is a heterogeneous disease process that is characterized by three cardinal features: (1) chronic inflammation of the airways leading to (2) variable airflow obstruction and (3) airway hyperresponsiveness (NHLBI 2007). Over the past two decades, there has been a rise in asthma prevalence, such that about 8 % of the population in 2010 and more than 25 million Americans are affected (Akinbami et al. 2012). The clinical presentation varies in degree of severity, but common symptoms include wheezing, shortness of breath, and cough (NHLBI 2007). There has been a steady increase in asthma prevalence from 2001 to 2010 which is particularly marked in the pediatric population; children have required increased emergency room visits and hospitalizations (Akinbami et al. 2012). Despite the overwhelming prevalence of asthma worldwide, extensive healthcare costs and immense economic burden, a detailed understanding of the underlying pathophysiology of asthma, particularly those features leading to variable expression of disease (recognized as clinical phenotypes) remains to be developed (Bousquet and Khaltaev 2007). Asthma affects industrialized nations as well underdeveloped countries, and similar phenotypes have been recognized across these borders (Weiss et al. 1992). Recent investigations have noted distinct clinical asthma phenotypes, but the characteristics that separate these phenotypes overlap significantly, including those factors that contribute to the difficulty in clinical management of these patients (Calhoun et al. 2003).


Asthma Heterogeneity Clinical phenotypes Clusters Physiology Treatment Molecular phenotype Induced phenotype 


  1. Abbas AK, Murphy KM, Sher A (1996) Functional diversity of helper T lymphocytes. Nature 383:787PubMedCrossRefGoogle Scholar
  2. Akinbami LJ, Moorman JE, Bailey C et al (2012) Trends in asthma prevalence, health care use, and mortality in the United States, 2001–2010. NCHS data brief, no 94. National Center for Health Statistics, Hyattsville, MDGoogle Scholar
  3. American Thoracic Society (ATS) (2000) Proceedings of the ATS workshop on refractory asthma: current understanding, recommendations, and unanswered questions. American Thoracic Society. Am J Respir Crit Care Med 162:2341–2351Google Scholar
  4. Anderson SD, Daviskas E (1999) Airway drying and exercise induced asthma. In: McFadden ER (ed) Exercise induced asthma—lung biology in health and disease. Marcel Dekker, New York, pp 77–113Google Scholar
  5. Anderson SD, Daviskas E (2000) The mechanism of exercise-induced asthma is…. J Allergy Clin Immunol 106:453–459PubMedCrossRefGoogle Scholar
  6. Balzar S, Fajt ML, Comhair SA, Erzurum SC, Bleecker E, Busse WW et al (2011) Mast cell phenotype, location, and activation in severe asthma: data from the severe asthma research program. Am J Respir Crit Care Med 183(3):299–309PubMedCrossRefGoogle Scholar
  7. Berry M, Morgan A, Shaw M et al (2007) Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma. Thorax 62(12):1043–1049PubMedCrossRefGoogle Scholar
  8. Bhavnani SK, Victor S, Calhoun WJ, Busse WW, Bleecker E, Castro M, Ju H, Pillai R, Oezguen N, Bellala G, Brasier AR (2011) How cytokines co-occur across asthma patients: from bipartite network analysis to a molecular-based classification. J Biomed Inform 44(Suppl):S24–S30PubMedCrossRefGoogle Scholar
  9. Bhavsar P, Hew M, Khorasani N, Torrego A, Barnes PJ, Adcock I, Chung KF (2008) Relative corticosteroid insensitivity of alveolar macrophages in severe asthma compared with non-severe asthma. Thorax 63:784–790PubMedCrossRefGoogle Scholar
  10. Bousquet J, Khaltaev N (2007) Global surveillance, prevention and control of chronic respiratory diseases: a comprehensive approach. Global alliance against chronic respiratory disease. World Health Organization, GenevaGoogle Scholar
  11. Bousquet J, Chanez P, Lacoste JY, Barneon G, Ghavanian N, Enander I, Venge P, Ahlstedt S, Simony-Lafontaine J, Godard P et al (1990) Eosinophilic inflammation in asthma. N Engl J Med 323:1033–1039PubMedCrossRefGoogle Scholar
  12. Brasier AR, Victor S, Boetticher G, Ju H, Lee C, Bleecker ER, Castro M, Busse WW, Calhoun WJ (2008) Molecular phenotyping of severe asthma using pattern recognition of bronchoalveolar lavage-derived cytokines. J Allergy Clin Immunol 121:30–37PubMedCrossRefGoogle Scholar
  13. Brasier AR, Victor S, Ju H, Busse WW, Curran-Everett D, Bleecker E, Castro M, Chung KF, Gaston B, Israel E, Wenzel SE, Erzurum SC, Jarjour NN, Calhoun WJ (2010) Predicting intermediate phenotypes in asthma using bronchoalveolar lavage-derived cytokines. Clin Transl Sci 3:147–157PubMedCrossRefGoogle Scholar
  14. Busse WW, Calhoun WF, Sedgwick JD (1993) Mechanism of airway inflammation in asthma. Am Rev Respir Dis 147:S20–S24PubMedCrossRefGoogle Scholar
  15. Calhoun WJ, Sutton LB, Emmett A et al (2003) Asthma variability in patients previously treated with B2 agonists alone. J Allergy Clin Immunol 112:1088–1094PubMedCrossRefGoogle Scholar
  16. Edmunds AT, Tooley M, Godfrey S (1978) The refractory period after exercise-induced asthma: its duration and relation to the severity of exercise. Am Rev Respir Dis 117(2):247–254PubMedGoogle Scholar
  17. Fahy JV, Kim KW, Liu J, Boushey HA (1995) Prominent neutrophilic inflammation in sputum from subjects with asthma exacerbation. J Allergy Clin Immunol 95:843–852PubMedCrossRefGoogle Scholar
  18. Fahy JV, Fleming HE, Wong HH et al (1997) The effect of an anti-IgE monoclonal antibody on the early- and late-phase responses to allergen inhalation in asthmatic subjects. Am J Respir Crit Care Med 155:1828–1834PubMedCrossRefGoogle Scholar
  19. Gauvreau GM, Boulet LP, Cockcroft DW et al (2011) Effects of interleukin-13 blockade on allergen-induced airway responses in mild atopic asthma. Am J Respir Crit Care Med 183(8):1007–1014PubMedCrossRefGoogle Scholar
  20. Global Strategy for Asthma Management and Prevention Update (2011) Global initiative for asthma.
  21. Green RH, Brightling CE, Woltmann G, Parker D, Wardlaw AJ, Pavord ID (2002) Analysis of induced sputum in adults with asthma: identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticoids. Thorax 57:875–879PubMedCrossRefGoogle Scholar
  22. Hallstrand TS, Curtis JR, Koepsell TD et al (2002) Effectiveness of screening examinations to detect unrecognized exercise-induced bronchoconstriction. J Pediatric 141:343–348CrossRefGoogle Scholar
  23. Hastie AT et al (2010) Analyses of asthma severity phenotypes and inflammatory proteins in subjects stratified by sputum granulocytes. J Allergy Clin Immunol 125:1028–1036.e13PubMedCrossRefGoogle Scholar
  24. Horwitz RJ, Busse WW (1995) Inflammation and asthma. Clin Chest Med 16(4):583–602PubMedGoogle Scholar
  25. Jarjour NN, Erzurum SC, Bleecker ER et al (2012) Am J Respir Crit Care Med 185(4):356–362PubMedCrossRefGoogle Scholar
  26. McFadden ER Jr (1995) Exercise-induced airway obstruction. Clin Chest Med 16(4):671–682PubMedGoogle Scholar
  27. McFadden ER, Gilbert IA (1999) Exercise-induced asthma as a vascular phenomenon. In: McFadden ER (ed) Exercise-induced asthma. Marcel Dekker, New York, pp 115–135Google Scholar
  28. National Heart, Lung, and Blood Institute (2008) Global strategy for asthma management and prevention. NIH Publication, Bethesda, MDGoogle Scholar
  29. National Heart, Lung, and Blood Institute, National Institute of Health (2007) National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the diagnosis and management of asthma. NIH Publication No. 07–4051Google Scholar
  30. Pearce N, Pekkanen J, Beasley R (1999) How much asthma is really attributable to atopy? Thorax 54:268–272PubMedCrossRefGoogle Scholar
  31. Pillai RR, Divekar R, Braiser A et al (2012) Strategies for molecular classification of asthma using bipartite network analysis of cytokine expression. Curr Allergy Asthma Rep 12:388–395PubMedCrossRefGoogle Scholar
  32. Randolph C (1997) Exercise-induced asthma: update on pathophysiology, clinical diagnosis, and treatment. Curr Probl Pediatr 27(2):53–77PubMedGoogle Scholar
  33. Shaw DE, Berry MA, Hargadon B, McKenna S, Shelley MJ, Green RH, Brightling CE, Wardlaw AJ, Pavord ID (2007) Association between neutrophilic airway inflammation and airflow limitation in adults with asthma. Chest 132:1871–1875PubMedCrossRefGoogle Scholar
  34. Sur S, Tb C, Kephart GM et al (1993) Sudden-onset fatal asthma. A distinct entity with few eosinophils and relatively more neutrophils in the airway submucosa. Am Rev Respir Dis 148(3):713–719PubMedCrossRefGoogle Scholar
  35. Walker C, Bode E, Boer L et al (1992) Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in the peripheral blood and bronchoalveolar lavage. Am Rev Respir Dis 146(1):109–115PubMedCrossRefGoogle Scholar
  36. Weiss KB, Gergen PJ, Hodgson TA (1992) An economic evaluation of asthma in the United States. N Engl J Med 326:862–866PubMedCrossRefGoogle Scholar
  37. Wenzel SE (2004) Phenotypes of asthma, useful guides for therapy, distinct biological process, or both? Am J Respir Crit Care Med 170:579–582PubMedCrossRefGoogle Scholar
  38. Wenzel SE (2012) Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med 18:716–725PubMedCrossRefGoogle Scholar
  39. Wenzel SE, Szefler SJ, Leung DY, Sloan SI et al (1997) Bronchoscopic evaluation of severe asthma: persistent inflammation associated with high dose glucocorticoids. Am J Respir Crit Care Med 156:737–743PubMedCrossRefGoogle Scholar
  40. Wenzel SE, Schwartz LB, Langmack EL et al (1999) Evidence that severe asthma can be divided pathophysiologically into town inflammatory subtypes with distinct physiologic and clinical characteristics. Am J Respir Crit Care Med 160:1001–1008PubMedCrossRefGoogle Scholar
  41. Wills-Karp M, Luyimbazi J, Xu X et al (1998) Science 282(5397):2258–2261PubMedCrossRefGoogle Scholar
  42. Woodruff PG, Boushey HA, Dolganov GM et al (2007) Genome wide profiling identifies epithelial cell genes associated with asthma and with treatment response to corticosteroids. Proc Natl Acad Sci USA 104:15858–15863PubMedCrossRefGoogle Scholar
  43. Woodruff PG, Modrek B, Choy DF et al (2009) T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med 180:388–395PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Internal MedicineUniversity of Texas Medical BranchGalvestonUSA

Personalised recommendations