Asthma phenotyping, therapy, and prevention: What can we learn from systems biology?

Pediatric Research

Volumn 73, Issue 4-2, 2013, Pages 543-552

  Sittka, Alexandra ^a   Vera, Julio ^b   Lai, Xin ^a,b   Schmeck, Bernd T ^a,c  

^a JUSTUS LIEBIG UNIVERSITY GIESSEN   (Germany)

^b UNIVERSITY OF ROSTOCK   (Germany)

^c PHILIPPS UNIVERSITY MARBURG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ALTRAKINCEPT; ALUMINUM HYDROXIDE; BETA ADRENERGIC RECEPTOR STIMULATING AGENT; CHOLINERGIC RECEPTOR BLOCKING AGENT; CORTICOSTEROID; GAMMA INTERFERON; GLUCOCORTICOID; IMMUNOLOGICAL ADJUVANT; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 13 ANTIBODY; INTERLEUKIN 4; INTERLEUKIN 5; INTERLEUKIN 5 ANTIBODY; MACROLIDE; OVALBUMIN; RECOMBINANT INTERLEUKIN 4; TRANSCRIPTION FACTOR RUNX2; TUMOR NECROSIS FACTOR ALPHA;

ALLERGIC AIRWAY INFLAMMATION; ASTHMA; BIOINFORMATICS; BIOSTATISTICS; CYTOKINE RELEASE; DISEASE EXACERBATION; DRUG TREATMENT FAILURE; EOSINOPHIL; FORCED EXPIRATORY VOLUME; GENOMICS; HUMAN; MATHEMATICAL MODEL; NONHUMAN; PATHOPHYSIOLOGY; PHENOTYPE; PHENOTYPIC VARIATION; PRENATAL PERIOD; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEOMICS; REGULATORY T LYMPHOCYTE; REVIEW; SENSITIZATION; SYSTEMS BIOLOGY; TRANSCRIPTOMICS; WHEEZING;

ANIMALS; ASTHMA; BIOLOGICAL MARKERS; BIOSTATISTICS; COHORT STUDIES; COMPUTATIONAL BIOLOGY; GENOME-WIDE ASSOCIATION STUDY; HUMANS; INFLAMMATION; INTERLEUKIN-13; INTERLEUKIN-5; MICE; MODELS, THEORETICAL; PHENOTYPE; RNA EDITING; SYSTEMS BIOLOGY; TH2 CELLS;

EID: 84877357161     PISSN: 00313998     EISSN: 15300447     Source Type: Journal    
DOI: 10.1038/pr.2013.8     Document Type: Review

References (93)

1. Busse W W, Lemanske RF Jr. Asthma. N Engl J Med 2001;344:350-62.
2. Eder W, Ege MJ, von Mutius E. The asthma epidemic. N Engl J Med 2006;355:2226-35.
3. Haldar P, Pavord ID, Shaw DE, et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med 2008;178:218-24.
4. Barnes PJ. Immunology of asthma and chronic obstructive pulmonary disease. Nat Rev Immunol 2008;8:183-92.
5. Gonem S, Desai D, Siddiqui S, Brightling CC. Evidence for phenotype-driven treatment in asthmatic patients. Curr Opin Allergy Clin Immunol 2011;11:381-5.
6. McGrath K W, Icitovic N, Boushey HA, et al.; Asthma Clinical Research Network of the National Heart, Lung, and Blood Institute. A large subgroup of mild-to-moderate asthma is persistently noneosinophilic. Am J Respir Crit Care Med 2012;185:612-9.
7. Aufray C, Adcock IM, Chung KF, Djukanovic R, Pison C, Sterk PJ. An integrative systems biology approach to understanding pulmonary diseases. Chest 2010;137:1410-6.
8. Strachan DP. Hay fever, hygiene, and household size. BMJ 1989;299:1259-60.
9. Aberg N. Asthma and allergic rhinitis in Swedish conscripts. Clin Exp Allergy 1989;19:59-63.
10. Von Ehrenstein OS, Von Mutius E, Illi S, Baumann L, Böhm O, von Kries R. Reduced risk of hay fever and asthma among children of farmers. Clin Exp Allergy 2000;30:187-93.
11. Riedler J, Braun-Fahrländer C, Eder W, et al.; ALEX Study Team. Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet 2001;358:1129-33.
12. von Mutius E, Vercelli D. Farm living: efects on childhood asthma and allergy. Nat Rev Immunol 2010;10:861-8.
13. Brooks C, Pearce N, Douwes J. The hygiene hypothesis in allergy and asthma: an update. Curr Opin Allergy Clin Immunol 2013;13:70-7.
14. Chen Y, Blaser MJ. Helicobacter pylori colonization is inversely associated with childhood asthma. J Infect Dis 2008;198:553-60.
15. Braun-Fahrländer C, Riedler J, Herz U, et al.; Allergy and Endotoxin Study Team. Environmental exposure to endotoxin and its relation to asthma in school-age children. N Engl J Med 2002;347:869-77.
16. van Strien RT, Engel R, Holst O, et al.; ALEX Study Team. Microbial exposure of rural school children, as assessed by levels of N-acetyl-muramic acid in mattress dust, and its association with respiratory health. J Allergy Clin Immunol 2004;113:860-7.
17. Ege MJ, Mayer M, Normand AC, et al.; GABRIELA Transregio 22 Study Group. Exposure to environmental microorganisms and childhood asthma. N Engl J Med 2011;364:701-9.
18. Genuneit J. Exposure to farming environments in childhood and asthma and wheeze in rural populations: a systematic review with meta-analysis. Pediatr Allergy Immunol 2012;23:509-18.
19. Macy E, Schatz M, Gibbons C, Zeiger R. The prevalence of reversible air-fow obstruction and/or methacholine hyperreactivity in random adult asthma patients identifed by administrative data. J Asthma 2005;42: 213-20.
20. Fuchs O, Genuneit J, Latzin P, et al.; GABRIELA Study Group. Farming environments and childhood atopy, wheeze, lung function, and exhaled nitric oxide. J Allergy Clin Immunol 2012;130:382-8.e6.
21. Omland Ø, Hjort C, Pedersen OF, Miller MR, Sigsgaard T. New-onset asthma and the efect of environment and occupation among farming and nonfarming rural subjects. J Allergy Clin Immunol 2011;128:761-5.
22. von Hertzen L, Hanski I, Haahtela T. Natural immunity. Biodiversity loss and infammatory diseases are two global megatrends that might be related. EMBO Rep 2011;12:1089-93.
23. Hanski I, von Hertzen L, Fyhrquist N, et al. Environmental biodiversity, human microbiota, and allergy are interrelated. Proc Natl Acad Sci USA 2012;109:8334-9.
24. von Mutius E. A fascinating look at the world with a new microscope. J Allergy Clin Immunol 2012;129:1202-3.
25. Lim RH, Kobzik L. Maternal transmission of asthma risk. Am J Reprod Immunol 2009;61:1-10.
26. McKeever TM, Lewis SA, Smith C, Hubbard R. The importance of prenatal exposures on the development of allergic disease: a birth cohort study using the West Midlands General Practice Database. Am J Respir Crit Care Med 2002;166:827-32.
27. Ege MJ, Bieli C, Frei R, et al.; Parsifal Study team. Prenatal farm exposure is related to the expression of receptors of the innate immunity and to atopic sensitization in school-age children. J Allergy Clin Immunol 2006;117:817-23.
28. Douwes J, Cheng S, Travier N, et al. Farm exposure in utero may protect against asthma, hay fever and eczema. Eur Respir J 2008;32:603-11.
29. Mold JE, Michaëlsson J, Burt TD, et al. Maternal alloantigens promote the development of tolerogenic fetal regulatory T cells in utero. Science 2008;322:1562-5.
30. Schaub B, Liu J, Höppler S, et al. Maternal farm exposure modulates neonatal immune mechanisms through regulatory T cells. J Allergy Clin Immunol 2009;123:774-82.e5.
31. Pfeferle PI, Büchele G, Blümer N, et al.; PASTURE Study Group. Cord blood cytokines are modulated by maternal farming activities and consumption of farm dairy products during pregnancy: the PASTURE Study. J Allergy Clin Immunol 2010;125:108-15.e1-3.
32. Macaubas C, de Klerk NH, Holt BJ, et al. Association between antenatal cytokine production and the development of atopy and asthma at age 6 years. Lancet 2003;362:1192-7.
33. Blümer N, Herz U, Wegmann M, Renz H. Prenatal lipopolysaccharide- exposure prevents allergic sensitization and airway infammation, but not airway responsiveness in a murine model of experimental asthma. Clin Exp Allergy 2005;35:397-402.
34. Conrad ML, Ferstl R, Teich R, et al. Maternal TLR signaling is required for prenatal asthma protection by the nonpathogenic microbe Acinetobacter lwofi F78. J Exp Med 2009;206:2869-77.
35. Brand S, Teich R, Dicke T, et al. Epigenetic regulation in murine ofspring as a novel mechanism for transmaternal asthma protection induced by microbes. J Allergy Clin Immunol 2011;128:618-25.e1-7.
36. McCallister J W. Reslizumab and eosinophilic asthma: one step closer to phenotype-directed therapy? Am J Respir Crit Care Med 2011;184:1096-7.
37. Martinez FD, Chinchilli VM, Morgan WJ, et al. Use of beclomethasone dipropionate as rescue treatment for children with mild persistent asthma (TREXA): a randomised, double-blind, placebo-controlled trial. Lancet 2011;377:650-7.
38. Zeiger RS, Mauger D, Bacharier LB, et al.; CARE Network of the National Heart, Lung, and Blood Institute. Daily or intermittent budesonide in preschool children with recurrent wheezing. N Engl J Med 2011;365:1990-2001.
39. Moore WC, Meyers DA, Wenzel SE, et al.; National Heart, Lung, and Blood Institute's Severe Asthma Research Program. Identifcation of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med 2010;181:315-23.
40. Siroux V, Basagaña X, Boudier A, et al. Identifying adult asthma pheno-types using a clustering approach. Eur Respir J 2011;38:310-7.
41. Wenzel SE, Vitari CA, Shende M, Strollo DC, Larkin A, Yousem SA. Asthmatic granulomatosis: a novel disease with asthmatic and granulomatous features. Am J Respir Crit Care Med 2012;186:501-7.
42. Fleming L, Tsartsali L, Wilson N, Regamey N, Bush A. Sputum infam-matory phenotypes are not stable in children with asthma. Torax 2012;67:675-81.
43. Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med 2012;18:716-25.
44. Tantisira KG, Lasky-Su J, Harada M, et al. Genomewide association between GLCCI1 and response to glucocorticoid therapy in asthma. N Engl J Med 2011;365:1173-83.
45. Wechsler ME, Castro M, Lehman E, et al.; NHLBI Asthma Clinical Research Network. Impact of race on asthma treatment failures in the asthma clinical research network. Am J Respir Crit Care Med 2011;184:1247-53.
46. Weatherall M, Wijesinghe M, Perrin K, Harwood M, Beasley R. Meta-analysis of the risk of mortality with salmeterol and the efect of concomitant inhaled corticosteroid therapy. Torax 2010;65:39-43.
47. Bleecker ER, Nelson HS, Kraf M, et al. Beta2-receptor polymorphisms in patients receiving salmeterol with or without futicasone propionate. Am J Respir Crit Care Med 2010;181:676-87.
48. Iwamoto H, Yokoyama A, Shiota N, et al. Tiotropium bromide is efec-tive for severe asthma with noneosinophilic phenotype. Eur Respir J 2008;31:1379-80.
49. Simpson JL, Powell H, Boyle MJ, Scott RJ, Gibson PG. Clarithromycin targets neutrophilic airway infammation in refractory asthma. Am J Respir Crit Care Med 2008;177:148-55.
50. A plea to abandon asthma as a disease concept. Lancet 2006;368:705.
51. Anderson GP. Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease. Lancet 2008;372:1107-19.
52. Busse W W, Morgan WJ, Gergen PJ, et al. Randomized trial of omali-zumab (anti-IgE) for asthma in inner-city children. N Engl J Med 2011;364:1005-15.
53. Leckie MJ, ten Brinke A, Khan J, et al. Efects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 2000;356:2144-8.
54. Haldar P, Brightling CE, Hargadon B, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med 2009;360:973-84.
55. Nair P, Pizzichini MM, Kjarsgaard M, et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med 2009;360:985-93.
56. Castro M, Mathur S, Hargreave F, et al.; Res-5-0010 Study Group. Resli-zumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am J Respir Crit Care Med 2011;184:1125-32.
57. Borish LC, Nelson HS, Lanz MJ, et al. Interleukin-4 receptor in moderate atopic asthma. A phase I/II randomized, placebo-controlled trial. Am J Respir Crit Care Med 1999;160:1816-23.
58. Maes T, Joos GF, Brusselle GG. Targeting interleukin-4 in asthma: lost in translation? Am J Respir Cell Mol Biol 2012;47:261-70.
59. Corren J, Lemanske RF, Hanania NA, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med 2011;365:1088-98.
60. Berry MA, Hargadon B, Shelley M, et al. Evidence of a role of tumor necrosis factor alpha in refractory asthma. N Engl J Med 2006;354:697-708.
61. Holgate ST, Noonan M, Chanez P, et al. Efcacy and safety of etanercept in moderate-to-severe asthma: a randomised, controlled trial. Eur Respir J 2011;37:1352-9.
62. Mestas J, Hughes CC. Of mice and not men: diferences between mouse and human immunology. J Immunol 2004;172:2731-8.
63. Wenzel S, Holgate ST. The mouse trap: It still yields few answers in asthma. Am J Respir Crit Care Med 2006;174:1173-6; discussion 1176-8.
64. Quackenbush J. Computational approaches to analysis of DNA microarray data. Yearb Med Inform 2006;91-103.
65. van 't Veer LJ, Dai H, van de Vijver MJ, et al. Gene expression profling predicts clinical outcome of breast cancer. Nature 2002; 415:530-6.
66. Zou J, Young S, Zhu F, et al. Microarray profle of diferentially expressed genes in a monkey model of allergic asthma. Genome Biol 2002;3:research0020.
67. Park SG, Choi J W, Kim Hj, et al. Genome-wide profling of a ntigen-induced time course expression using murine models for acute and chronic asthma. Int Arch Allergy Immunol 2008;146:44-56.
68. Gray RD, MacGregor G, Noble D, et al. Sputum proteomics in infam-matory and suppurative respiratory diseases. Am J Respir Crit Care Med 2008;178:444-52.
69. Zhao J, Zhu H, Wong CH, Leung KY, Wong WS. Increased lungkine and chitinase levels in allergic airway infammation: a proteomics approach. Proteomics 2005;5:2799-807.
70. Ghosh S, Janocha AJ, Aronica MA, et al. Nitrotyrosine proteome survey in asthma identifes oxidative mechanism of catalase inactivation. J Immunol 2006;176:5587-97.
71. Jardim MJ, Dailey L, Silbajoris R, Diaz-Sanchez D. Distinct microRNA expression in human airway cells of asthmatic donors identifes a novel asthma-associated gene. Am J Respir Cell Mol Biol 2012;47:536-42.
72. O'Neil SE, Sitkauskiene B, Babusyte A, et al. Network analysis of quantitative proteomics on asthmatic bronchi: efects of inhaled glucocorticoid treatment. Respir Res 2011;12:124.
73. Vera J, Wolkenhauer O. A system biology approach to understand functional activity of cell communication systems. Methods Cell Biol 2008;90:399-415.
74. Ashall L, Horton CA, Nelson DE, et al. Pulsatile stimulation determines timing and specifcity of NF-kappaB-dependent transcription. Science 2009;324:242-6.
75. Busse D, de la Rosa M, Hobiger K, et al. Competing feedback loops shape IL-2 signaling between helper and regulatory T lymphocytes in cellular microenvironments. Proc Natl Acad Sci USA 2010;107:3058-63.
76. Hofmann A, Levchenko A, Scott ML, Baltimore D. The IkappaB-NF-kappaB signaling module: temporal control and selective gene activation. Science 2002;298:1241-5.
77. Nelson DE, Ihekwaba AE, Elliott M, et al. Oscillations in NF-kappaB signaling control the dynamics of gene expression. Science 2004;306:704-8.
78. Nikolov S, Vera J, Rath O, Kolch W, Wolkenhauer O. Role of inhibitory proteins as modulators of oscillations in NFB signalling. IET Syst Biol 2009;3:59-76.
79. Hwang S, Son S W, Kim SC, Kim YJ, Jeong H, Lee D. A protein interaction network associated with asthma. J Teor Biol 2008;252:722-31.
80. Höfer T, Nathansen H, Löhning M, Radbruch A, Heinrich R. GATA-3 transcriptional imprinting in T2 lymphocytes: a mathematical model. Proc Natl Acad Sci USA 2002;99:9364-8.
81. van den Ham HJ, de Boer RJ. From the two-dimensional T1 and T2 phenotypes to high-dimensional models for gene regulation. Int Immunol 2008;20:1269-77.
82. Podtschaske M, Benary U, Zwinger S, Höfer T, Radbruch A, Baumgrass R. Digital NFATc2 activation per cell transforms graded T cell receptor activation into an all-or-none IL-2 expression. PLoS ONE 2007;2:e935.
83. Frey U, Brodbeck T, Majumdar A, et al. Risk of severe asthma episodes predicted from fuctuation analysis of airway function. Nature 2005;438:667-70.
84. Tamrin C, Stern G, Strippoli M P, et al. Fluctuation analysis of lung function as a predictor of long-term response to beta2-agonists. Eur Respir J 2009;33:486-93.
85. Frey U. Asthma as a nonlinear complex dynamic system: a novel approach to understand the temporal behaviour of chronic asthma and its response to β-agonists. Eur Respir Rev 2008;17:67-9.
86. Hunter P, Smith N, Fernandez J, Tawhai M. Integration from proteins to organs: the IUPS Physiome Project. Mech Ageing Dev 2005;126:187-92.
87. Lauzon AM, Bates JH, Donovan G, Tawhai M, Sneyd J, Sanderson MJ. A multi-scale approach to airway hyperresponsiveness: from molecule to organ. Front Physiol 2012;3:191.
88. Patel B, Gauvin R, Absar S, et al. Computational and bioengineered lungs as alternatives to whole animal, isolated organ, and cell-based lung models. Am J Physiol Lung Cell Mol Physiol 2012;303:L733-47.
89. Martonen T, Fleming J, Schroeter J, Conway J, Hwang D. In silico modeling of asthma. Adv Drug Deliv Rev 2003;55:829-49.
90. Seeger W, Welte T, Eickelberg O, et al. The German centre for lung research-translational research for the prevention, diagnosis and treatment of respiratory diseases. Pneumologie 2012;66:464-9.
91. Bel EH, Sousa A, Fleming L, et al.; Unbiased Biomarkers for the Prediction of Respiratory Disease Outcome (U-BIOPRED) Consortium, Consensus Generation. Diagnosis and defnition of severe refractory asthma: an international consensus statement from the Innovative Medicine Initiative (IMI). Torax 2011;66:910-7.
92. Maier D, Kalus W, Wolf M, et al. Knowledge management for systems biology a general and visually driven framework applied to translational medicine. BMC Syst Biol 2011;5:38.
93. Politi AZ, Donovan GM, Tawhai MH, et al. A multiscale, spatially distributed model of asthmatic airway hyper-responsiveness. J Teor Biol 2010;266:614-24.