Asthma Update 2015 – Was die zellbiologisch-pneumologische Grundlagenforschung dem Lungenarzt anbieten kann

M. Wegmann; H. Fehrenbach; S. Krauss-Etschmann

doi:10.1055/s-0041-108313

Pneumologie, Inhaltsverzeichnis

Pneumologie 2016; 70(02): 103-109
DOI: 10.1055/s-0041-108313

Serie: Translationale Forschung in der Pneumologie

Asthma Update 2015 – Was die zellbiologisch-pneumologische Grundlagenforschung dem Lungenarzt anbieten kann

Asthma Update 2015 – What Cell Biology in Basic Pulmonary Research Can Offer to the Pneumologist

Autoren

M. Wegmann

Programmbereich Asthma & Allergie, Forschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften, Airway Research Center North (ARCN), Mitglied des Deutschen Zentrums für Lungenforschung (DZL), Borstel
H. Fehrenbach

Programmbereich Asthma & Allergie, Forschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften, Airway Research Center North (ARCN), Mitglied des Deutschen Zentrums für Lungenforschung (DZL), Borstel
S. Krauss-Etschmann

Programmbereich Asthma & Allergie, Forschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften, Airway Research Center North (ARCN), Mitglied des Deutschen Zentrums für Lungenforschung (DZL), Borstel

Verantwortlicher Herausgeber dieser Rubrik: M. Witzenrath, Berlin

Abstract

Zusammenfassung

Asthma bronchiale ist eine der häufigsten chronisch-entzündlichen Erkrankungen weltweit und verursacht vor allem in industrialisierten Ländern erhebliche sozioökonomische Kosten. Asthma wird zunehmend als eine polysymptomatische Krankheit verstanden, die eine ganze Reihe unterscheidbarer Asthmaphänotypen bzw. molekular definierter Asthmaendotypen umfasst. Diese Heterogenität des Asthmas erklärt ihrerseits, warum die Standardmedikation mit inhalativen Steroiden und β-Sympathomimetika nicht in allen Fällen, vor allem nicht während akuter Exazerbationen, eine vollständige Symptomkontrolle ermöglicht. Dementsprechend stehen derzeit Konzepte zur primären Asthmaprävention sowie phänotyp- bzw. endotypspezifische Therapieansätze im Fokus der Asthmaforschung.

Abstract

Bronchial asthma is one of the most common chronic inflammatory diseases world-wide causing an enormous socio-economic burden especially in industrialized countries. Currently, asthma is increasingly considered to be a poly-symptomatic disease comprising a variety of different asthma phenotypes and endotypes. This heterogeneity of asthma explains why the standard treatment with corticosteroids and β-agonists cannot achieve full symptom control in all cases, especially not during acute exacerbations. Therefore, current asthma research focuses on primary prevention of asthma as well as on novel approaches towards a phenotype- and endotype-specific asthma therapy.

Volltext

Referenzen

Literatur
1 http://www.ginasthma.org/
2 Gillissen A, Welte T eds. Weißbuch Lunge 2014 – Die Lunge und ihre Erkrankungen: Zur Lage und Zukunft der Pneumologie in Deutschland. Herne: FRISCHTEXTE Verlag; 2014
3 European Respiratory Society. ERS – Respiratory health and disease in Europe [Internet]. Eur. Lung White B. Available from: http://www.erswhitebook.org/
4 Mallol J, Crane J, von Mutius E et al. The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three: A global synthesis. Allergol Immunopathol (Madr) 2013; 41: 73-85
5 Böcking C, Renz H, Pfefferle PI. Prävalenz und sozioökonomische Bedeutung von Allergien in Deutschland. Bundesgesundheitsblatt 2012; 55: 303-307
6 Lötvall J, Akdis CA, Bacharier LB et al. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol 2011; 127: 355-360
7 Rackemann FM. A working classification of asthma. Am J Med 1947; 3: 601-606
8 Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med 2012; 18: 716-725
9 Nair P, Dasgupta A, Brightling CE et al. How to diagnose and phenotype asthma. Clin Chest Med 2012; 33: 445-457
10 Haldar P, Pavord ID, Shaw DE et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med 2008; 178: 218-224
11 Spycher BD, Silverman M, Kuehni CE. Phenotypes of childhood asthma: are they real?. Clin Exp Allergy 2010; 40: 1130-1141
12 Green RH, Brightling CE, Woltmann G et al. 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
13 Anderson GP. Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease. Lancet 2008; 372: 1107-1119
14 Fahy JV. Type 2 inflammation in asthma – present in most, absent in many. Nat Rev Immunol 2015; 15: 57-65
15 Corren J, Lemanske RF, Hanania NA et al. Lebrikizumab treatment in adults with asthma. N Engl J Med 2011; 365: 1088-1098
16 Saglani S, Bush A. Onset of Structural Airway Changes in Preschool Wheezers A Window and Target for Secondary Asthma Prevention?. Am J RespirCrit Care Med 2015; 192: 121-122
17 Dunn RN, Lehman E, Chinchilli VM et al. Impact of Age and Sex on Response to Asthma Therapy. Am J Respir Crit Care Med 2015; 192: 551-558
18 Cook-Mills JM. Maternal influences over offspring allergic responses. Curr Allergy Asthma Rep 2015; 15: 501
19 Greenough A, Shaheen SO, Shennan A et al. Respiratory outcomes in early childhood following antenatal vitamin C and E supplementation. Thorax 2010; 65: 998-1003
20 Esposito ER, Horn KH, Greene RM et al. An animal model of cigarette smoke-induced in utero growth retardation. Toxicology 2008; 246: 193-202
21 Turcotte-Tremblay AM, Lim R, Laplante DP et al. Prenatal maternal stress predicts childhood asthma in girls: project ice storm. Biomed Res Int 2014; 2014 201717
22 Liu X, Olsen J, Agerbo E et al. Prenatal stress and childhood asthma in the offspring: role of age at onset. Eur J Public Health 2015; [Epub ahead of print]
23 Klingbeil EC, Hew KM, Nygaard UC et al. Polycyclic aromatic hydrocarbons, tobacco smoke, and epigenetic remodeling in asthma. Immunol Res 2014; 58: 369-373
24 Gascon M, Casas M, Morales E et al. Prenatal exposure to bisphenol A and phthalates and childhood respiratory tract infections and allergy. J Allergy Clin Immunol 2015; 135: 370-378
25 Cook DG, Strachan DP, Carey IM. Health effects of passive smoking. 9. Parental smoking and spirometric indices in children. Thorax 1998; 53: 884-893
26 Upton MN, Watt GC, Davey Smith G et al. Permanent effects of maternal smoking on offspringsʼ lung function. Lancet 1998; 352: 453
27 Gilliland FD, Berhane K, Li Y-F et al. Effects of early onset asthma and in utero exposure to maternal smoking on childhood lung function. Am J Respir Crit Care Med 2003; 167: 917-924
28 Upton MN, Smith GD, McConnachie A et al. Maternal and personal cigarette smoking synergize to increase airflow limitation in adults. Am J Respir Crit Care Med 2004; 169: 479-487
29 Milner AD, Rao H, Greenough A. The effects of antenatal smoking on lung function and respiratory symptoms in infants and children. Early Hum Dev 2007; 83: 707-711
30 Duijts L, Jaddoe VW V, van der Valk RJP et al. Fetal exposure to maternal and paternal smoking and the risks of wheezing in preschool children: the Generation R Study. Chest 2012; 141: 876-885
31 Burke H, Leonardi-Bee J, Hashim A et al. Prenatal and passive smoke exposure and incidence of asthma and wheeze: systematic review and meta-analysis. Pediatrics 2012; 129: 735-744
32 den Dekker HT, Sonnenschein-van der Voort AM, de Jongste JC et al. Tobacco smoke exposure, airway resistance and asthma in school-agechildren: The Generation R Study. Chest 2015; [Epub ahead of print]
33 Beyer D, Mitfessel H, Gillissen A. Maternal smoking promotes chronic obstructive lung disease in the offspring as adults. Eur J Med Res 2009; 14 (Suppl. 04) 27-31
34 Svanes C, Sunyer J, Plana E et al. Earlylife origins of chronic obstructive pulmonary disease. Thorax 2010; 65: 14-20
35 Thun M, Peto R, Boreham J et al. Stages of the cigarette epidemic on entering its second century. Tob Control 2012; 21: 96-101
36 The World Health Organization, and the Institute for Global Tobacco Control, Johns Hopkins School of Public Health. “Women and the Tobacco Epidemic: Challenges for the 21st Century”. World Health Organization; 2001: 5-6 Retrieved 2009-01-02
37 Centers for Disease Control and Prevention. Current Cigarette Smoking Among Adults – United States, 2011. Morb Mortal Wkly Rep 2012; 61: 889-894
38 Smedberg J, Lupattelli A, Mårdby A-C et al. Characteristics of women who continue smoking during pregnancy: a cross-sectional study of pregnant women and new mothers in 15 European countries. BMC Pregnancy Childbirth 2014; 14: 213
39 Dietz PM, Homa D, England LJ et al. Estimates of nondisclosure of cigarette smoking among pregnant and nonpregnant women of reproductive age in the United States. Am J Epidemiol 2011; 173: 355-359
40 Tong VT, Dietz PM, Farr SL et al. Estimates of smoking before and during pregnancy, and smoking cessation during pregnancy: comparing two population-based data sources. Public Health Rep 2013; 128: 179-188
41 Centers for Disease Control and Prevention. Preventing Smoking and Exposure to Secondhand Smoke Before, During, and After Pregnancy. Dep Heal Hum Serv USA 2007; 2
42 Li Y-F, Langholz B, Salam MT et al. Maternal and grandmaternal smoking patterns are associated with early childhood asthma. Chest 2005; 127: 1232-1241
43 Magnus MC, Haberg SE, Karlstad O et al. Grandmother’s smoking when pregnant with the mother and asthma in the grandchild: the Norwegian Mother and Child Cohort Study. Thorax 2015; 70: 237-243
44 Haley KJ, Lasky-Su J, Manoli SE et al. RUNX transcription factors: association with pediatric asthma and modulated by maternal smoking. Am J Physiol Lung Cell Mol Physiol 2011; 301: L693-701
45 Blacquière MJ, Hylkema MN, Postma DS et al. Airway inflammation and remodeling in two mouse models of asthma: comparison of males and females. Int Arch Allergy Immunol 2010; 153: 173-181
46 Prins JR, Hylkema MN, Erwich JJ et al. Smoking during pregnancy influences the maternal immune response in mice and humans. Am J Obstet Gynecol 2012; 207: 76.e1-14
47 Leslie FM. Multigenerational epigenetic effects of nicotine on lung function. BMC Med 2013; 11: 27
48 Reddel HK, Taylor DR, Bateman ED et al. American Thoracic Society/European Respiratory Society Task Force on Asthma Control and Exacerbations. An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J RespirCrit Care Med 2009; 180: 59-99
49 Teach SJ, Gergen PJ, Szefler SJ et al. Seasonal risk factors for asthma exacerbations among inner-city children. J Allergy Clin Immunol 2015; 135: 1465-1473
50 Bateman ED, Buhl R, OʼByrne PM et al. Development and validation of a novel risk score for asthma exacerbations: The risk score for exacerbations. J Allergy Clin Immunol 2015; 135: 1457-1464
51 Tillie-Leblond I, Pugin J, Marquette CH et al. Balance between proinflammatory cytokines and their inhibitors in bronchial lavage from patients with status asthmaticus. Am J Respir Crit Care Med 1999; 159: 487-494
52 Norzila MZ, Fakes K, Henry RL et al. Interleukin-8 secretion and neutrophil recruitment accompanies induced sputum eosinophil activation in children with acute asthma. Am J Respir Crit Care Med 2000; 161: 769-774
53 Jackson DJ, Sykes A, Mallia P et al. Asthma exacerbations: origin, effect, and prevention. J Allergy Clin Immunol 2011; 128: 1165-1174
54 Kusel MM, de Klerk NH, Holt PG et al. Role of respiratory viruses in acute upper and lower respiratory tract illness in the first year of life: a birth cohort study. Pediatr Infect Dis J 2006; 25: 680-686
55 Lunding LP, Webering S, Vock C et al. Poly(inosinic-cytidylic) Acid-Triggered Exacerbation of Experimental Asthma Depends on IL-17A Produced by NK Cells. J Immunol 2015; 194: 5615-5625
56 Wenzel SE, Busse WW. National Heart, Lung, and Blood Institute’s Severe Asthma Research Program. Severe asthma: lessons from the Severe Asthma Research Program. J Allergy Clin Immunol 2007; 119: 405-413
57 OʼByrne PM, Inman MD, Parameswaran K. The trials and tribulations of IL-5, eosinophils, and allergic asthma. J Allergy Clin Immunol 2001; 108: 503-508
58 Bel EH, Wenzel SE, Thompson PJ et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med 2014; 371: 1189-1197
59 Ortega HG, Liu MC, Pavord ID et al. MENSA Investigators. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med 2014; 371: 1198-1207
60 Castro M, Zangrilli J, Wechsler ME et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med 2015; 3: 355-366
61 Romeo MJ, Agrawal R, Pomés A et al. A molecular perspective on TH2-promoting cytokine receptors in patients with allergic disease. J Allergy ClinImmunol 2014; 133: 952-960
62 Slager RE, Otulana BA, Hawkins GA et al. IL-4 receptor polymorphisms predict reduction in asthma exacerbations during response to an anti-IL-4 receptor α antagonist. J Allergy ClinImmunol 2012; 130: 516-522
63 Wenzel S, Ford L, Pearlman D et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med 2013; 368: 2455-2466
64 Beck LA, Thaçi D, Hamilton JD et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med 2014; 371: 130-139
65 Sel S, Wegmann M, Dicke T et al. Effective prevention and therapy of experimental allergic asthma using a GATA-3-specific DNAzyme. J Allergy Clin Immunol 2008; 121: 910-916
66 Krug N, Hohlfeld JM, Kirsten AM et al. Allergen-induced asthmatic responses modified by a GATA3-specific DNAzyme. N Engl J Med 2015; 372: 1987-1995
67 Gauvreau GM, OʼByrne PM, Boulet LP et al. Effects of an anti-TSLP antibody on allergen-induced asthmatic responses. N Engl J Med 2014; 370: 2102-2110
68 Gauvreau GM, Boulet LP, Cockcroft DW et al. OX40L blockade and allergen-induced airway responses in subjects with mild asthma. Clin Exp Allergy 2014; 44: 29-37
69 Mizutani N, Nabe T, Yoshino S. Interleukin-33 and alveolar macrophages contribute to the mechanisms underlying the exacerbation of IgE-mediated airway inflammation and remodelling in mice. Immunology 2013; 139: 205-218
70 Ohno T, Morita H, Arae K et al. Interleukin-33 in allergy. Allergy 2012; 67: 1203-1214
71 Erin EM, Leaker BR, Nicholson GC et al. The effects of a monoclonal antibody directed against tumor necrosis factor-alpha in asthma. Am J Respir Crit Care Med 2006; 174: 753-762
72 Morjaria JB, Chauhan AJ, Babu KS et al. The role of a soluble TNFalpha receptor fusion protein (etanercept) in corticosteroid refractory asthma: a double blind, randomised, placebo controlled trial. Thorax 2008; 63: 584-591
73 Wenzel SE, Barnes PJ, Bleecker ER et al. A randomized, double-blind, placebo-controlled study of tumor necrosis factor-alpha blockade in severe persistent asthma. Am J Respir Crit Care Med 2009; 179: 549-558
74 Johnson VJ, Yucesoy B, Luster MI. Prevention of IL-1 signaling attenuates airway hyperresponsiveness and inflammation in a murine model of toluene diisocyanate-induced asthma. J Allergy Clin Immunol 2005; 116: 851-858
75 Li T, Lu WL, Hong HY et al. Pharmacokinetics and anti-asthmatic potential of non-parenterally administered recombinant human interleukin-1 receptor antagonist in animal models. J Pharmacol Sci 2006; 102: 321-330
76 Chu DK, Al-Garawi A, Llop-Guevara A et al. Therapeutic potential of anti-IL-6 therapies for granulocytic airway inflammation in asthma. Allergy Asthma Clin Immunol 2015; 11: 14
77 Finotto S, Eigenbrod T, Karwot R et al. Local blockade of IL-6R signaling induces lung CD4+ T cell apoptosis in a murine model of asthma via regulatory T cells. Int Immunol 2007; 19: 685-693
78 Tan HL, Rosenthal M. IL-17 in lung disease: friend or foe?. Thorax 2013; 68: 788-790
79 Busse WW, Holgate S, Kerwin E et al. Randomized, double-blind, placebo-controlled study of brodalumab, a human anti-IL-17 receptor monoclonal antibody, in moderate to severe asthma. Am J Respir Crit Care Med 2013; 188: 1294-1302
80 Sabroe I, Peck MJ, Van Keulen BJ et al. A small molecule antagonist of chemokine receptors CCR1 and CCR3. Potent inhibition of eosinophil function and CCR3-mediated HIV-1 entry. J Biol Chem 2000; 275: 25985-25992
81 Dent G, Hadjicharalambous C, Yoshikawa T et al. Contribution of eotaxin-1 to eosinophil chemotactic activity of moderate and severe asthmatic sputum. Am J Respir Crit Care Med 2004; 169: 1110-1117
82 Wegmann M, Göggel R, Sel S et al. Effects of a low-molecular-weight CCR-3 antagonist on chronic experimental asthma. Am J Respir Cell Mol Biol 2007; 36: 61-67
83 Wegmann M. Targeting eosinophil biology in asthma therapy. Am J Respir Cell Mol Biol 2011; 45: 667-674
84 Simpson LJ, Patel S, Bhakta NR et al. A microRNA upregulated in asthma airway T cells promotes TH2 cytokine production. Nat Immunol 2014; 15: 1162-1170
85 Marques-Rocha JL, Samblas M, Milagro FI et al. Noncoding RNAs, cytokines, and inflammation-related diseases. FASEB J 2015; pii: fj.14-260323; [Epub ahead of print]