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Heterogeneity in Asthma pp 5–15Cite as

Introduction to Asthma and Phenotyping

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 795))

Abstract

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).

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References

  • Abbas AK, Murphy KM, Sher A (1996) Functional diversity of helper T lymphocytes. Nature 383:787

    Article  PubMed  CAS  Google Scholar 

  • 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, MD

    Google Scholar 

  • 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 162:2341–2351

    Google Scholar 

  • 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 77–113

    Google Scholar 

  • Anderson SD, Daviskas E (2000) The mechanism of exercise-induced asthma is…. J Allergy Clin Immunol 106:453–459

    Article  PubMed  CAS  Google Scholar 

  • 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):299–309

    Article  PubMed  Google Scholar 

  • Berry M, Morgan A, Shaw M et al (2007) Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma. Thorax 62(12):1043–1049

    Article  PubMed  Google Scholar 

  • 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–S30

    Article  PubMed  CAS  Google Scholar 

  • 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 63:784–790

    Article  PubMed  CAS  Google Scholar 

  • 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, Geneva

    Google Scholar 

  • 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 323:1033–1039

    Article  PubMed  CAS  Google Scholar 

  • 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 121:30–37

    Article  PubMed  CAS  Google Scholar 

  • 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 3:147–157

    Article  PubMed  CAS  Google Scholar 

  • Busse WW, Calhoun WF, Sedgwick JD (1993) Mechanism of airway inflammation in asthma. Am Rev Respir Dis 147:S20–S24

    Article  PubMed  CAS  Google Scholar 

  • Calhoun WJ, Sutton LB, Emmett A et al (2003) Asthma variability in patients previously treated with B2 agonists alone. J Allergy Clin Immunol 112:1088–1094

    Article  PubMed  CAS  Google Scholar 

  • 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):247–254

    PubMed  CAS  Google Scholar 

  • Fahy JV, Kim KW, Liu J, Boushey HA (1995) Prominent neutrophilic inflammation in sputum from subjects with asthma exacerbation. J Allergy Clin Immunol 95:843–852

    Article  PubMed  CAS  Google Scholar 

  • 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 155:1828–1834

    Article  PubMed  CAS  Google Scholar 

  • 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):1007–1014

    Article  PubMed  CAS  Google Scholar 

  • Global Strategy for Asthma Management and Prevention Update (2011) Global initiative for asthma. http://www.ginasthma.com

  • 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 57:875–879

    Article  PubMed  CAS  Google Scholar 

  • Hallstrand TS, Curtis JR, Koepsell TD et al (2002) Effectiveness of screening examinations to detect unrecognized exercise-induced bronchoconstriction. J Pediatric 141:343–348

    Article  Google Scholar 

  • 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.e13

    Article  PubMed  CAS  Google Scholar 

  • Horwitz RJ, Busse WW (1995) Inflammation and asthma. Clin Chest Med 16(4):583–602

    PubMed  CAS  Google Scholar 

  • Jarjour NN, Erzurum SC, Bleecker ER et al (2012) Am J Respir Crit Care Med 185(4):356–362

    Article  PubMed  Google Scholar 

  • McFadden ER Jr (1995) Exercise-induced airway obstruction. Clin Chest Med 16(4):671–682

    PubMed  Google Scholar 

  • McFadden ER, Gilbert IA (1999) Exercise-induced asthma as a vascular phenomenon. In: McFadden ER (ed) Exercise-induced asthma. Marcel Dekker, New York, pp 115–135

    Google Scholar 

  • National Heart, Lung, and Blood Institute (2008) Global strategy for asthma management and prevention. NIH Publication, Bethesda, MD

    Google Scholar 

  • 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. 07–4051

    Google Scholar 

  • Pearce N, Pekkanen J, Beasley R (1999) How much asthma is really attributable to atopy? Thorax 54:268–272

    Article  PubMed  CAS  Google Scholar 

  • 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 12:388–395

    Article  PubMed  CAS  Google Scholar 

  • Randolph C (1997) Exercise-induced asthma: update on pathophysiology, clinical diagnosis, and treatment. Curr Probl Pediatr 27(2):53–77

    PubMed  CAS  Google Scholar 

  • 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 132:1871–1875

    Article  PubMed  CAS  Google Scholar 

  • 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):713–719

    Article  PubMed  CAS  Google Scholar 

  • 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):109–115

    Article  PubMed  CAS  Google Scholar 

  • Weiss KB, Gergen PJ, Hodgson TA (1992) An economic evaluation of asthma in the United States. N Engl J Med 326:862–866

    Article  PubMed  CAS  Google Scholar 

  • Wenzel SE (2004) Phenotypes of asthma, useful guides for therapy, distinct biological process, or both? Am J Respir Crit Care Med 170:579–582

    Article  PubMed  Google Scholar 

  • Wenzel SE (2012) Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med 18:716–725

    Article  PubMed  CAS  Google Scholar 

  • 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 156:737–743

    Article  PubMed  CAS  Google Scholar 

  • 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 160:1001–1008

    Article  PubMed  CAS  Google Scholar 

  • Wills-Karp M, Luyimbazi J, Xu X et al (1998) Science 282(5397):2258–2261

    Article  PubMed  CAS  Google Scholar 

  • 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 104:15858–15863

    Article  PubMed  CAS  Google Scholar 

  • 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 180:388–395

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, University of Texas Medical Branch, 4.118 John Sealy Annex, 301 University Blvd, Galveston, TX, 77555-0568, USA

    Regina A. Pillai M.D. & William J. Calhoun M.D.

Authors
  1. Regina A. Pillai M.D.
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  2. William J. Calhoun M.D.
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Correspondence to William J. Calhoun M.D. .

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Editors and Affiliations

  1. Institute for Translational Sciences, University of Texas Medical Branch, Galveston, Texas, USA

    Allan R. Brasier

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Pillai, R.A., Calhoun, W.J. (2014). Introduction to Asthma and Phenotyping. In: Brasier, A. (eds) Heterogeneity in Asthma. Advances in Experimental Medicine and Biology, vol 795. Humana Press, Boston, MA. https://doi.org/10.1007/978-1-4614-8603-9_1

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