Asthma is a chronic disabling respiratory disease that can be triggered by a variety of factors, including allergens, respiratory infections, psychological factors, occupational agents, exercise, atmospheric pollutants, and drugs. The asthma syndrome has been treated for decades according to a “one-fits-all” treatment strategy based on bronchodilators and steroids. With the availability of new forms of treatment targeting the different pathomechanisms of the asthma syndrome, such as anti-immunoglobulin E and cytokine-targeting therapies, the interest in biomarkers that can dis criminate different forms of asthma according to their pathomechanisms has increased. This review attempts to provide an overview of protein biomarkers in asthma and how they might be used to discriminate different forms of asthma that may respond positively to sophisticated new targeted therapies.

Keywords:
Allergy, Biomarkers, Asthma, Molecular allergology
1.
Kim HY, DeKruyff RH, Umetsu DT: The many paths to asthma: phenotype shaped by innate and adaptive immunity. Nat Immunol 2010; 11: 577–584.
2.
Xu D, Wang Y, Chen Z, Li S, Cheng Y, Zhang L, Zhao L: Prevalence and risk factors for asthma among children aged 0–14 years in Hangzhou: a cross-sectional survey. Respir Res 2016; 17: 122.
3.
See KC, Phua J, Lim TK: Trigger factors in asthma and chronic obstructive pulmonary disease: a single-centre cross-sectional survey. Singapore Med J 2016; 57: 561–565.
4.
Bousquet J, Clark TJ, Hurd S, Khaltaev N, Lenfant C, O’byrne P, Sheffer A: GINA guidelines on asthma and beyond. Allergy 2007; 62: 102–112.
5.
Incorvaia C, Riario-Sforza GG, Ridolo E: IgE depletion in severe asthma: what we have and what could be added in the near future. EBioMedicine 2017; 17: 16–17.
6.
Lupinek C, Derfler K, Lee S, Prikoszovich T, Movadat O, Wollmann E, Cornelius C, Weber M, Fröschl R, Selb R, Blatt K, Smiljkovic D, Schoder V, Cervenka R, Plaichner T, Stegfellner G, Huber H, Henning R, Kozik-Jaromin J, Perkmann T, Niederberger V, Petkov V, Valent P, Gauly A, Leinenbach HP, Uhlenbusch-Koerwer I, Valenta R: Extracorporeal IgE immunoadsorption in allergic asthma: safety and efficacy. EBioMedicine 2017; 17: 119–133.
7.
Bagnasco D, Ferrando M, Varricchi G, Passalacqua G, Canonica GW: A critical evaluation of anti-IL-13 and anti-IL-4 strategies in severe asthma. Int Arch Allergy Immunol 2016; 170: 122–131.
8.
Varricchi G, Senna G, Loffredo S, Bagnasco D, Ferrando M, Canonica GW: Reslizumab and eosinophilic asthma: one step closer to precision medicine? Front Immunol 2017; 8: 242.
9.
Heck S, Nguyen J, Le DD, Bals R, Dinh QT: Pharmacological therapy of bronchial asthma: the role of biologicals. Int Arch Allergy Immunol 2015; 168: 241–252.
10.
Wenzel SE: Emergence of biomolecular pathways to define novel asthma phenotypes: type-2 immunity and beyond. Am J Respir Cell Mol Biol 2016; 55: 1–4.
11.
Terl M, Sedlák V, Cap P, Dvořáková R, Kašák V, Kočí T, Novotna B, Seberova E, Panzner P, Zindr V: Asthma management: a new phenotype-based approach using presence of eo-sinophilia and allergy. Allergy 2017; 72: 1279–1287.
12.
Edlmayr J, Niespodziana K, Linhart B, Focke-Tejkl M, Westritschnig K, Scheiblhofer S, Stoecklinger A, Kneidinger M, Valent P, Campana R, Thalhamer J, Popow-Kraupp T, Valenta R: A combination vaccine for allergy and rhinovirus infections based on rhinovirus-derived surface protein VP1 and a nonallergenic peptide of the major timothy grass pollen allergen Phl p 1. J Immunol 2009; 182: 6298–6306.
13.
Edlmayr J, Niespodziana K, Popow-Kraupp T, Krzyzanek V, Focke-Tejkl M, Blaas D, Grote M, Valenta R: Antibodies induced with recombinant VP1 from human rhinovirus exhibit cross-neutralisation. Eur Respir J 2011; 37: 44–52.
14.
Traub S, Nikonova A, Carruthers A, Dunmore R, Vousden KA, Gogsadze L, Hao W, Zhu Q, Bernard K, Zhu J, Dymond M, McLean GR, Walton RP, Glanville N, Humbles A, Khaitov M, Wells T, Kolbeck R, Leishman AJ, Sleeman MA, Bartlett NW, Johnston SL: An anti-human ICAM-1 antibody inhibits rhinovirus-induced exacerbations of lung inflammation. PLoS Pathog 2013; 9:e1003520.
15.
Lee S, Nguyen MT, Currier MG, Jenkins JB, Strobert EA, Kajon AE, Madan-Lala R, Bochkov YA, Gern JE, Roy K, Lu X, Erdman DD, Spearman P, Moore ML: A polyvalent inactivated rhinovirus vaccine is broadly immunogenic in rhesus macaques. Nat Commun 2016; 7: 12838.
16.
Fathl E, Mesbah-Namin SA, Farahzadi R: Biomarkers in medicine: an overview. Br J Med Res 2014; 4: 1701–1718.
17.
Hansel TT, Tunstall T, Trujillo-Torralbo MB, Shamji B, Del-Rosario A, Dhariwal J, Kirk PDW, Stumpf MPH, Koopmann J, Telcian A, Aniscenko J, Gogsadze L, Bakhsoliani E, Stanciu L, Bartlett N, Edwards M, Walton R, Mallia P, Hunt TM, Hunt TL, Hunt DG, Westwick J, Edwards M, Kon OM, Jackson DJ, Johnston SL: A comprehensive evaluation of nasal and bronchial cytokines and chemokines following experimental rhinovirus infection in allergic asthma: increased interferons (IFN-γ and IFN-λ) and type 2 inflammation (IL-5 and IL-13). EBioMedicine 2017; 19: 128–138.
18.
Pruski P, MacIntyre DA, Lewis HV, Inglese P, Correia GD, Hansel TT, Bennett PR, Holmes E, Takats Z: Medical swab analysis using desorption electrospray ionization mass spectrometry: a noninvasive approach for mucosal diagnostics. Anal Chem 2017; 89: 1540–1550.
19.
Murphy TM, Wong CCY, Arseneault L, Burrage J, Macdonald R, Hannon E, Fisher HL, Ambler A, Moffitt TE, Caspi A, Mill J: Methylomic markers of persistent childhood asthma: a longitudinal study of asthma-discordant monozygotic twins. Clin Epigenetics 2015;7:130.
20.
Antus B: Oxidative stress markers in sputum. Oxid Med Cell Longev 2016;2016: 2930434.
21.
Kuang Z, Wilson JJ, Luo S, Zhu SW, Huang R-P: Deciphering asthma biomarkers with protein profiling technology. Int J Inflam 2015;2015:630637.
22.
Novikov VV, Egorova NI, Kurnikov GY, Evsegneeva IV, Baryshnikov AY, Karaulov AV: Serum levels of soluble HLA and IL-2R molecules in patients with urogenital chlamydia infection. Adv Exp Med Biol 2007; 601: 285–289.
23.
Lebedev MJ, Krizhanova MA, Vilkov SA, Sholkina MN, Vyasmina ES, Baryshnikov AJ, Novikov VV: Peripheral blood lymphocytes immunophenotype and serum concentration of soluble HLA class I in burn patients. Burns 2003; 29: 123–128.
24.
Lebedev MJ, Egorova NI, Sholkina MN, Vilkov SA, Baryshnikov AJ, Novikov VV: Serum levels of different forms of soluble CD38 antigen in burned patients. Burns 2004; 30: 552–556.
25.
Valenta R, Lidholm J, Niederberger V, Hayek B, Kraft D, Grönlund H: The recombinant allergen-based concept of component-resolved diagnostics and immunotherapy (CRD and CRIT). Clin Exp Allergy 1999; 29: 896–904.
26.
Hiller R, Laffer S, Harwanegg C, Huber M, Schmidt WM, Twardosz A, Barletta B, Becker WM, Blaser K, Breiteneder H, Chapman M, Crameri R, Duchêne M, Ferreira F, Fiebig H, Hoffmann-Sommergruber K, King TP, Kleber-Janke T, Kurup VP, Lehrer SB, Lidholm J, Müller U, Pini C, Reese G, Schei-ner O, Scheynius A, Shen HD, Spitzauer S, Suck R, Swoboda I, Thomas W, Tinghino R, Van Hage-Hamsten M, Virtanen T, Kraft D, Müller MW, Valenta R: Microarrayed allergen molecules: diagnostic gatekeepers for allergy treatment. FASEB J 2002; 16: 414–416.
27.
Lupinek C, Wollmann E, Baar A, Banerjee S, Breiteneder H, Broecker BM, Bublin M, Curin M, Flicker S, Garmatiuk T, Hochwallner H, Mittermann I, Pahr S, Resch Y, Roux KH, Srinivasan B, Stentzel S, Vrtala S, Willison LN, Wickman M, Lødrup-Carlsen KC, Antó JM, Bousquet J, Bachert C, Ebner D, Schlederer T, Harwanegg C, Valenta R: Advances in allergen-microarray technology for diagnosis and monitoring of allergy: the MeDALL allergen-chip. Methods 2014; 66: 106–119.
28.
Curin M, Garib V, Valenta R: Single recombinant and purified major allergens and peptides: how they are made and how they change allergy diagnosis and treatment. Ann Allergy Asthma Immunol 2017; 119: 201–209.
29.
van Hage M, Hamsten C, Valenta R: ImmunoCAP assays: pros and cons in allergology. J Allergy Clin Immunol 2017;140:974–977.
30.
Niespodziana K, Napora K, Cabauatan C, Focke-Tejkl M, Keller W, Niederberger V, Tsolia M, Christodoulou I, Papadopoulos NG, Valenta R: Misdirected antibody responses against an N-terminal epitope on human rhinovirus VP1 as explanation for recurrent RV infections. FASEB J 2012; 26: 1001–1008.
31.
Niespodziana K, Cabauatan CR, Jackson DJ, Gallerano D, Trujillo-Torralbo B, Del Rosario A, Mallia P, Valenta R, Johnston SL: Rhino-virus-induced VP1-specific antibodies are group-specific and associated with severity of respiratory symptoms. EBioMedicine 2014; 2: 64–70.
32.
Stenberg-Hammar K, Niespodziana K, Söderhäll C, James A, Cabauatan CR, Konradsen JR, Melén E, van Hage M, Valenta R, Hedlin G: Rhinovirus-specific antibody responses in preschool children with acute wheeze reflect severity of respiratory symptoms. Allergy 2016; 71: 1728–1735.
33.
Valenta R: Mucosal lining fluid biomarkers in asthma: basis for rational use of new targeted therapies? EBioMedicine 2017; 19: 12–13.
34.
Incorvaia C, Fuiano N, Canonica W: Seeking allergy when it hides: which are the best fitting tests? World Allergy Organ J 2013; 6: 11.
35.
Wu W, Bleecker E, Moore W, Busse WW, Castro M, Chung KF, Calhoun WJ, Erzurum S, Gaston B, Israel E, Curran-Everett D, Wenzel SE: Unsupervised phenotyping of Severe Asthma Research Program participants using expanded lung data. J Allergy Clin Immunol 2014; 133: 1280–1288.
36.
Lötvall J, Akdis CA, Bacharier LB, Bjermer L, Casale TB, Custovic A, Lemanske RF Jr, Wardlaw AJ, Wenzel SE, Greenberger PA: Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol 2011; 127: 355–360.
37.
Perlikos F, Hillas G, Loukides S: Phenotyping and endotyping asthma based on biomarkers. Curr Top Med Chem 2016; 16: 1582–1586.
38.
Kim M-A, Shin YS, Pham LD, Park H-S: Adult asthma biomarkers. Curr Opin Allergy Clin Immunol 2014; 14: 49–54.
39.
Muraro A, Lemanske RF Jr, Hellings PW, Akdis CA, Bieber T, Casale TB, Jutel M, Ong PY, Poulsen LK, Schmid-Grendelmeier P, Simon HU, Seys SF, Agache I: Precision medicine in patients with allergic diseases: airway diseases and atopic dermatitis – PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology. J Allergy Clin Immunol 2016; 137: 1347–1358.
40.
Liang Z, Liu L, Zhao H, Xia Y, Zhang W, Ye Y, Jiang M, Cai S: A systemic inflammatory endotype of asthma with more severe disease identified by unbiased clustering of the serum cytokine profile. Medicine (Baltimore) 2016; 95:e3774.
41.
Raedler D, Ballenberger N, Klucker E, Böck A, Otto R, Prazeres Da Costa O, Holst O, Illig T, Buch T, Von Mutius E, Schaub B: Identification of novel immune phenotypes for allergic and nonallergic childhood asthma. J Allergy Clin Immunol 2015; 135: 81–91.
42.
Westerhof GA, Korevaar DA, Amelink M, De Nijs SB, De Groot JC, Wang J, Weersink EJ, Ten Brinke A, Bossuyt PM, Bel EH: Biomarkers to identify sputum eosinophilia in different adult asthma phenotypes. Eur Respir J 2015; 46: 688–696.
43.
Wagener AH, De Nijs SB, Lutter R, Sousa AR, Weersink EJM, Bel EH, Sterk PJ: External validation of blood eosinophils, FeNO and serum periostin as surrogates for sputum eosinophils in asthma. Thorax 2015; 70: 115–120.
44.
Kasaian MT, Marquette K, Fish S, DeClercq C, Agostinelli R, Cook TA, Brennan A, Lee J, Fitz L, Brooks J, Vugmeyster Y, Williams CMM, Lofquist A, Tchistiakova L: An IL-4/IL-13 dual antagonist reduces lung inflammation, airway hyperresponsiveness, and IgE production in mice. Am J Respir Cell Mol Biol 2013; 49: 37–46.
45.
Izuhara K, Nunomura S, Nanri Y, Ogawa M, Ono J, Mitamura Y, Yoshihara T: Periostin in inflammation and allergy. Cell Mol Life Sci 2017; 74: 4293–4303.
46.
Shamji MH, Kappen JH, Akdis M, Jensen-Jarolim E, Knol EF, Kleine-Tebbe J, Bohle B, Chaker AM, Till SJ, Valenta R, Poulsen LK, Calderon MA, Demoly P, Pfaar O, Jacobsen L, Durham SR, Schmidt-Weber CB: Biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunctivitis and allergic asthma: an EAACI position paper. Allergy 2017; 72: 1156–1173.
47.
Woodruff PG, Modrek B, Choy DF, Jia G, Abbas AR, Ellwanger A, Koth LL, Arron JR, Fahy JV: T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med 2009; 180: 388–395.
48.
Matsunaga K, Ichikawa T, Yanagisawa S, Akamatsu K, Koarai A, Hirano T, Sugiura H, Minakata Y, Ichinose M: Clinical application of exhaled breath condensate analysis in asthma: prediction of FEV1 improvement by steroid therapy. Respiration 2009; 78: 393–398.
49.
Sinz H, Renz H, Skevaki C: Cellular and noncellular bloodborne biomarkers in asthma. Ann Allergy Asthma Immunol 2017; 118: 672–679.
50.
Flood-Page P, Menzies-Gow A, Phipps S, Ying S, Wangoo A, Ludwig MS, Barnes N, Robinson D, Kay AB: Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics. J Clin Invest 2003; 112: 1029–1036.
51.
Grünig G, Corry DB, Reibman J, Wills-Karp M: Interleukin 13 and the evolution of asthma therapy. Am J Clin Exp Immunol 2012; 1: 20–27.
52.
Cheng D, Xue Z, Yi L, Shi H, Zhang K, Huo X, Bonser LR, Zhao J, Xu Y, Erle DJ, Zhen G: Epithelial interleukin-25 is a key mediator in Th2-high, corticosteroid-responsive asthma. Am J Respir Crit Care Med 2014; 190: 639–648.
53.
Yao X, Sun Y, Wang W, Sun Y: Interleukin (IL)-25: pleiotropic roles in asthma. Respirology 2016; 21: 638–647.
54.
Drake LY, Kita H: IL-33: biological properties, functions, and roles in airway disease. Immunol Rev 2017; 278: 173–184.
55.
Dinarello CA: Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 2011; 17: 3720–3732.
56.
Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK: IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 2005; 23: 479–490.
57.
Iikura M, Suto H, Kajiwara N, Oboki K, Ohno T, Okayama Y, et al: IL-33 can promote survival, adhesion and cytokine production in human mast cells. Lab Invest 2007; 87: 971–978.
58.
Guo L, Wei G, Zhu J, Liao W, Leonard WJ, Zhao K, Paul W: IL-1 family members and STAT activators induce cytokine production by Th2, Th17, and Th1 cells. Proc Natl Acad Sci USA 2009; 106: 13463–13468.
59.
Carriere V, Roussel L, Ortega N, Lacorre DA, Americh L, Aguilar L, Bouche G, Girard JP: IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated nuclear factor in vivo. Proc Natl Acad Sci USA 2007; 104: 282–287.
60.
Farahani R, Sherkat R, Hakemi MG, Eskandari N, Yazdani R: Cytokines (interleukin-9, IL-17, IL-22, IL-25 and IL-33) and asthma. Adv Biomed Res 2014; 3: 127.
61.
Kearley J, Erjefalt JS, Andersson C, Benjamin E, Jones CP, Robichaud A, Pegorier S, Brewah Y, Burwell TJ, Bjermer L, Kiener PA, Kolbeck R, Lloyd CM, Coyle AJ, Humbles AA: IL-9 governs allergen-induced mast cell numbers in the lung and chronic remodeling of the airways. Am J Respir Crit Care Med 2011; 183: 865–875.
62.
Jia L, Wang Y, Li J, Li S, Zhang Y, Shen J, Tan W, Wu C: Detection of IL-9 producing T cells in the PBMCs of allergic asthmatic patients. BMC Immunol 2017; 18: 38.
63.
Hirose K, Iwata A, Tamachi T, Nakajima H: Allergic airway inflammation: key players beyond the Th2 cell pathway. Immunol Rev 2017; 278: 145–161.
64.
Aoi N, Masuda T, Murakami D, Yajima T, Mizubuchi H, Yamada H, Kawauchi H, Yoshikai Y: IL-15 prevents allergic rhinitis through reactivation of antigen-specific CD8+ cells. J Allergy Clin Immunol 2006; 117: 1359–1366.
65.
Lombard C, André F, Paul J, Wanty C, Vosters O, Bernard P, Pilette C, Dupont P, Sokal EM, Smets F: Clinical parameters vs. cytokine profiles as predictive markers of IgE-mediated allergy in young children. PLoS One 2015; 10:e0132753.
66.
Wu J, Wang G, Hao J, Gong W: The correlation between IL-20 and the Th2 immune response in human asthma. Asian Pac J Allergy Immunol 2014; 32: 316–320.
67.
Raedler D, Schaub B: Immune mechanisms and development of childhood asthma. Lancet Respir Med 2014; 2: 647–656.
68.
Raundhal M, Morse C, Khare A, Oriss TB, Milosevic J, Trudeau J, Huff R, Pilewski J, Holguin F, Kolls J, Wenzel S, Ray P, Ray A: High IFN-γ and low SLPI mark severe asthma in mice and humans. J Clin Invest 2015; 125: 3037–3050.
69.
Schoenborn JR, Wilson CB: Regulation of interferon-gamma during innate and adaptive immune responses. Adv Immunol 2007; 96: 41–101.
70.
Artis D, Spits H: The biology of innate lymphoid cells. Nature 2015; 517: 293–301.
71.
Pope SM, Zimmermann N, Stringer KF, Karow ML, Rothenberg ME: The eotaxin chemokines and CCR3 are fundamental regulators of allergen-induced pulmonary eosinophilia. J Immunol 2005; 175: 5341–5350.
72.
Wu D, Zhou J, Bi H, Li L, Gao W, Huang M, Adcock IM, Barnes PJ, Yao X: CCL11 as a potential diagnostic marker for asthma? J Asthma 2014; 51: 847–854.
73.
Bhardwaj N, Ghaffari G: Biomarkers for eosinophilic esophagitis: a review. Ann Allergy Asthma Immunol 2012; 109: 155–159.
74.
Leung TF, Wong CK, Chan IH, Ip WK, Lam CW, Wong GW: Plasma concentration of thymus and activation-regulated chemokine is elevated in childhood asthma. J Allergy Clin Immunol 2002; 110: 404–409.
75.
Oyamada H, Kamada Y, Saito N, Tsuda A, Urayama O, Yamada H, Hirasawa H, Yamaguchi K, Ueki S, Chihara J: RANTES production from mononuclear cells in response to the specific allergen in asthma patients. Allergol Int 2006; 55: 253–259.
76.
Machura E, Szczepanska M, Mazur B, Chrobak E, Ziora K, Ziora D, Kasperska-Zajac A: Selected CC and CXC chemokines in children with atopic asthma. Postepy Dermatol Alergol 2016; 33: 96–101.
77.
Zietkowski Z, Tomasiak MM, Skiepko R, Bodzenta-Lukaszyk: A RANTES in exhaled breath condensate of stable and unstable asthma patients. Respir Med 2008; 102: 198–202.
78.
Kalayci O, Sonna LA, Woodruff PG, Camargo CA Jr, Luster AD, Lilly CM: Monocyte chemotactic protein-4 (MCP-4; CCL-13): a biomarker of asthma. J Asthma 2004; 41: 27–33.
79.
Al-Shami A, Spolski R, Kelly J, Keane-Myers A, Leonard WJ: A role for TSLP in the development of inflammation in an asthma model. J Exp Med 2005; 202: 829–839.
80.
Ito T, Wang Y-H, Duramad O, Hori T, Delespesse GJ, Watanabe N, Qin FX-F, Yao Z, Cao W, Liu Y-J: TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand. J Exp Med 2005; 202: 1213–1223.
81.
Nguyen KD, Vanichsarn C, Nadeau KC: TSLP directly impairs pulmonary Treg function: association with aberrant tolerogenic immunity in asthmatic airway. Allergy Asthma Clin Immunol 2010; 6: 4.
82.
Ragusa F, Fallahi P: IP-10 in occupational asthma: review of the literature and case-control study. Clin Ter 2017; 168:e151–e157.
83.
Suzuki K, Kato M, Matsuda S, Nukaga M, Enseki M, Tabata H, Hirai K, Yamada Y, Maruyama K, Hayashi Y, Mochizuki H: IP-10 is elevated in virus-induced acute exacerbations in childhood asthma. Tokai J Exp Clin Med 2016; 41: 210–217.
84.
Izuhara K, Conway SJ, Moore BB, Matsumoto H, Holweg CTJ, Matthews JG, Arron JR: Roles of periostin in respiratory disorders. Am J Respir Crit Care Med 2016; 193: 949–956.
85.
Kou K, Okawa T, Yamaguchi Y, Ono J, Inoue Y, Kohno M, Matsukura S, Kambara T, Ohta S, Izuhara K, Aihara M: Periostin levels correlate with disease severity and chronicity in patients with atopic dermatitis. Br J Dermatol 2014; 171: 283–291.
86.
James AJ, Reinius LE, Verhoek M, Gomes A, Kupczyk M, Hammar U, Ono J, Ohta S, Izuhara K, Bel E, Kere J, Söderhäll C, Dahlén B, Boot RG, Dahlén S-E, Gaga M, Siafakas NM, Papi A, Fabbri LM, Joos G, Brusselle G, Rabe KF, Kanniess F, Hiemstra P, Johnston SL, Chanez P, Vachier I, Gjomarkaj M, Sterk PJ, Howarth PH, Nizankowska-Mogilnicka E, Middelveld R, Holgate ST, Wilson S: Increased YKL-40 and chitotriosidase in asthma and chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2016; 193: 131–142.
87.
Mogensen I, Alving K, Bjerg A, Borres MP, Hedlin G, Sommar J, Dahlén SE, Janson C, Malinovschi A: Simultaneously elevated exhaled nitric oxide and serum-eosinophil cationic protein relate to recent asthma events in asthmatics in a cross-sectional population-based study. Clin Exp Allergy 2016; 46: 1540–1548.
88.
Klaassen EMM, Thönissen BEJT, van Eys G, Dompeling E, Jöbsis Q: A systematic review of CD14 and toll-like receptors in relation to asthma in Caucasian children. Allergy Asthma Clin Immunol 2013; 9: 10.
89.
Wüthrich B, KÄgi MK, Joller-Jemelka H: Soluble CD14 but not interleukin-6 is a new marker for clinical activity in atopic dermatitis. Arch Dermatol Res 1992; 284: 339–342.
90.
Martin AC, Laing IA, Khoo S-K, Zhang G, Rueter K, Teoh L, Taheri S, Hayden CM, Geelhoed GC, Goldblatt J, LeSouëf PN: Acute asthma in children: relationships among CD14 and CC16 genotypes, plasma levels, and severity. Am J Respir Crit Care Med 2006; 173: 617–622.
91.
Virchow JC Jr, Julius P, Matthys H, Kroegel C, Luttmann W: CD14 expression and soluble CD14 after segmental allergen provocation in atopic asthma. Eur Respir J 1998; 11: 317–323.
92.
Su K-W, Tu Y-L, Chiu C-Y, Huang Y-L, Liao S-L, Chen L-C, Yao T-C, Ou L-S, Lee W-I, Huang J-L, Yeh K-W: Cord blood soluble CD14 predicts wheeze and prolonged cough in young children: the PATCH study. Int Arch Allergy Immunol 2016; 169: 189–197.
93.
Curigliano G, Criscitiello C, Gelao L, Goldhirsch A: Molecular pathways: human leukocyte antigen G (HLA-G). Clin Cancer Res 2013; 19: 5564–5571.
94.
Rizzo R, Andersen AS, Lassen MR, Sørensen HC, Bergholt T, Larsen MH, Melchiorri L, Stignani M, Baricordi OR, Hviid TV: Soluble human leukocyte antigen-G isoforms in maternal plasma in early and late pregnancy. Am J Reprod Immunol 2009; 62: 320–338.
95.
Montilla D, Pérez M, Borges L, Bianchi G, Cova JA: Soluble human leukocyte antigen-G in the bronchoalveolar lavage of lung cancer patients. Arch Bronconeumol 2016; 52: 420–424.
96.
Alsahebfosoul F, Zavaran Hosseini A, Salehi R, Etemadifar M, Esmaeil N, Jamshidian A: Evaluation of soluble human leukocyte antigen-G (sHLA-G) isoforms and regulatory T cells in relapsing-remitting multiple sclerosis. Iran J Allergy Asthma Immunol 2015; 14: 298–305.
97.
White SR, Loisel DA, McConville JF, Stern R, Tu Y, Marroquin BA, Noth I, Ober C: Levels of soluble HLA-G are increased in asthmatic airways. Eur Respir J 2010; 35: 925–927.
98.
Zheng X-Q, Li C-C, Xu D-P, Lin A, Bao W-G, Yang G-S, Yan W-H: Analysis of the plasma soluble human leukocyte antigen-G and interleukin-10 levels in childhood atopic asthma. Hum Immunol 2010; 71: 982–987.
99.
Reisinger J, Triendl A, Küchler E, Bohle B, Krauth MT, Rauter I, Valent P, Koenig F, Valenta R, Niederberger V: IFN-gamma-enhanced allergen penetration across respiratory epithelium augments allergic inflammation. J Allergy Clin Immunol 2005,115: 973–981.
100.
Patil SP, Wisnivesky JP, Busse PJ, Halm EA, Li X-M: Detection of immunological biomarkers correlated with asthma control and quality of life measurements in sera from chronic asthmatic patients. Ann Allergy Asthma Immunol 2011; 106: 205–213.
101.
Ichikawa T, Matsunaga K, Minakata Y, Yanagisawa S, Ueshima K, Akamatsu K, Hirano T, Nakanishi M, Sugiura H, Yamagata T: Possible impact of salivary influence on cytokine analysis in exhaled breath condensate. Anal Chem Insights 2007; 1: 85–92.
102.
Hastie AT, Moore WC, Meyers DA, Vestal PL, Li H, Peters SP, Bleecker ER: Analyses of asthma severity phenotypes and inflammatory proteins in subjects stratified by sputum granulocytes. J Allergy Clin Immunol 2010; 125: 1028–1036.
103.
Zissler UM, Esser-von Bieren J, Jakwerth CA, Chaker AM, Schmidt-Weber CB: Current and future biomarkers in allergic asthma. Allergy 2016; 71: 475–494.
104.
Simpson A, Lazic N, Belgrave D, Johnson P, Bishop C, Mills C, Custovic A: Patterns of IgE responses to multiple allergen components and clinical symptoms at age 11 years. J Allergy Clin Immunol 2015; 136: 1224–1231.
105.
Global Initiative for Asthma: 2017 GINA report: global strategy for asthma management and prevention. http://ginasthma.org.
106.
Sears MR, Greene JM, Willan AR, Wiecek EM, Taylor DR, Flannery EM, Cowan JO, Herbison GP, Silva PA, Poulton R: A longitudinal, population-based, cohort study of childhood asthma followed to adulthood. N Engl J Med 2003; 349: 1414–1422.
107.
Sheehan WJ, Phipatanakul W: Indoor allergen exposure and asthma outcomes. Curr Opin Pediatr 2016; 28: 772–777.
108.
Wickman M, Lupinek C, Andersson N, Belgrave D, Asarnoj A, Benet M, Pinart M, Wieser S, Garcia-Aymerich J, Baar A, Pershagen G, Simpson A, Kull I, Bergström A, Melén E, Hamsten C, Antó JM, Bousquet J, Custovic A, Valenta R, van Hage M: Detection of IgE reactivity to a handful of allergen molecules in early childhood predicts respiratory allergy in adolescence. EBioMedicine 2017; 26: 91–99.
109.
Kabesch M: Early origins of asthma (and allergy). Mol Cell Pediatr 2016; 3: 31.
110.
Perečinský S, Varga M, Petrovičová J, Ragač O, Perečinská K, Jančová A, Murínová L, Bačinský T, Legáth L: Different clinical effect of several types of airborne allergens on the severity of bronchial hyperreactivity. Wien Klin Wochenschr 2017; 129: 674–679.
111.
Asarnoj A, Hamsten C, Wadén K, Lupinek C, Andersson N, Kull I, Curin M, Anto J, Bousquet J, Valenta R, Wickman M, van Hage M: Sensitization to cat and dog allergen molecules in childhood and prediction of symptoms of cat and dog allergy in adolescence: a BAMSE/MeDALL study. J Allergy Clin Immunol 2016; 137: 813–821.
112.
Salo P, Arbes S, Sever M, Jaramillo R, Cohn R, London S, Zeldin D: Exposure to Alternaria alternata in US homes is associated with asthma symptoms. J Allergy Clin Immunol 2006; 118: 892–898.
113.
Do DC, Zhao Y, Gao P: Cockroach allergen exposure and risk of asthma. Allergy 2016; 71: 463–474.
114.
Soto-Quiros M, Avila L, Platts-Mills TA, Hunt JF, Erdman DD, Carper H, Murphy DD, Odio S, James HR, Patrie JT, Hunt W, O’Rourke AK, Davis MD, Steinke JW, Lu X, Kennedy J, Heymann PW: High titers of IgE antibody to dust mite allergen and risk for wheezing among asthmatic children infected with rhinovirus. J Allergy Clin Immunol 2012; 129: 1499–1505.
115.
Resch Y, Michel S, Kabesch M, Lupinek C, Valenta R, Vrtala S: Different IgE recognition of mite allergen components in asthmatic and nonasthmatic children. J Allergy Clin Immunol 2015; 136: 1083–1091.
116.
Posa D, Perna S, Resch Y, Lupinek C, Panetta V, Hofmaier S, Rohrbach A, Hatzler L, Grabenhenrich L, Tsilochristou O, Chen KW, Bauer CP, Hoffman U, Forster J, Zepp F, Schuster A, Wahn U, Keil T, Lau S, Vrtala S, Valenta R, Matricardi PM: Evolution and predictive value of IgE responses toward a comprehensive panel of house dust mite allergensduring the first 2 decades of life. J Allergy Clin Immunol 2017; 139: 541–549 .
117.
Weghofer M, Grote M, Resch Y, Casset A, Kneidinger M, Kopec J, Thomas WR, Fernández-Caldas E, Kabesch M, Ferrara R, Mari A, Purohit A, Pauli G, Horak F, Keller W, Valent P, Valenta R, Vrtala S: Identification of Der p 23, a peritrophin-like protein, as a new major Dermatophagoides pteronyssinus allergen associated with the peritrophic matrix of mite fecal pellets. J Immunol 2013; 190: 3059–3067.
118.
Banerjee S, Weber M, Blatt K, Swoboda I, Focke-Tejkl M, Valent P, Valenta R, Vrtala S: Conversion of Der p 23, a new major house dust mite allergen, into a hypoallergenic vaccine. J Immunol 2014; 192: 4867–4875.
119.
Shek LP, Chong AR, Soh SE, Cheong N, Teo AS, Yi FC, Giam YC, Chua KY, Van Bever HP: Specific profiles of house dust mite sensitization in children with asthma and in children with eczema. Pediatr Allergy Immunol 2010; 21:e718–e722.
120.
Santos da Silva E, Asam C, Lackner P, Hofer H, Wallner M, Silva Pinheiro C, Alcântara-Neves NM, Ferreira F: Allergens of Blomia tropicalis: an overview of recombinant molecules. Int Arch Allergy Immunol 2017; 172: 203–214.
121.
Lee MF, Song PP, Hwang GY, Lin SJ, Chen YH: Sensitization to Per a 2 of the American cockroach correlates with more clinical severity among airway allergic patients in Taiwan. Ann Allergy Asthma Immunol 2012; 108: 243–248.
122.
Pomés A, Arruda LK: Investigating cockroach allergens: aiming to improve diagnosis and treatment of cockroach allergic patients. Methods 2014; 66: 75–85.
123.
Phipatanakul W, Litonjua AA, Platts-Mills TA, Naccara LM, Celedón JC, Abdulkerim H, Hoffman EB, Gold DR: Sensitization to mouse allergen and asthma and asthma morbidity among women in Boston. J Allergy Clin Immunol 2007; 120: 954–956.
124.
Bush RK, Prochnau JJ: Alternaria-induced asthma. J Allergy Clin Immunol 2004; 113: 227–234.
125.
Kurup VP, Banerjee B, Murali PS, Greenberger PA, Krishnan M, Hari V, Fink JN: Immunodominant peptide epitopes of allergen, Asp f 1 from the fungus Aspergillus fumigatus. Peptides 1998; 19: 1469–1477.
126.
Arruda LK, Ferriani VP, Vailes LD, Pomés A, Chapman MD: Cockroach allergens: environmental distribution and relationship to disease. Curr Allergy Asthma Rep 2001; 1: 466–473.
127.
Rosenstreich DL, Eggleston P, Kattan M, et al: The role of cockroach allergy and exposure to cockroach allergen in causing morbidity among inner-city children with asthma. New Engl J Med 1997; 336: 1356–1363.
128.
Barbosa MC, Santos AB, Ferriani VP, Pomés A, Chapman MD, Arruda LK: Efficacy of recombinant allergens for diagnosis of cockroach allergy in patients with asthma and/or rhinitis. Int Arch Allergy Immunol 2013; 161: 213–219.
129.
Jeal H, Jones M: Allergy to rodents: an update. Clin Exp Allergy 2010; 40: 1593–1601.
130.
Permaul P, Sheehan WJ, Baxi SN, Gaffin JM, Fu C, Petty CR, Gold DR, Phipatanakul W: Predictors of indoor exposure to mouse allergen in inner-city elementary schools. Ann Allergy Asthma Immunol 2013; 111: 299–301.
131.
Gergen PJ, Mitchell HE, Calatroni A, Sever ML, Cohn RD, Salo PM, Thorne PS, Zeldin DC: Sensitization and exposure to pets: the effect on asthma morbidity in the US population. J Allergy Clin Immunol Pract 2018; 6: 101–107.
132.
Chen CH, Chao HJ, Chan CC, Chen BY, Guo YL: Current asthma in schoolchildren is related to fungal spores in classrooms. Chest 2014; 146: 123–134.
133.
Sharpe RA, Bearman N, Thornton CR, Husk K, Osborne NJ: Indoor fungal diversity and asthma: a meta-analysis and systematic review of risk factors. J Allergy Clin Immunol 2015; 135: 110–122.
134.
Black PN, Udy AA, Brodie SM: Sensitivity to fungal allergens is a risk factor for life-threatening asthma. Allergy 2000; 55: 501–504.
135.
Rick EM, Woolnough K, Pashley CH, Wardlaw AJ: Allergic fungal airway disease. J Investig Allergol Clin Immunol 2016; 26: 344–354.
136.
Twaroch TE, Curin M, Valenta R, Swoboda I: Mold allergens in respiratory allergy: from structure to therapy. Allergy Asthma Immunol Res 2015; 7: 205–220.
137.
Banerjee B, Greenberger PA, Fink JN, Kurup VP: Immunological characterization of Asp f 2, a major allergen from Aspergillus fumigatus associated with allergic bronchopulmonary aspergillosis. Infect Immun 1998; 66: 5175–5182.
138.
Pollock J, Shi L, Gimbel RW: Outdoor environment and pediatric asthma: an update on the evidence from North America. Can Respir J 2017; 2017: 8921917.
139.
Pallasaho P, Ronmark E, Haahtela T, Sovijarvi AR, Lundback B: Degree and clinical relevance of sensitization to common allergens among adults: a population study in Helsinki, Finland. Clin Exp Allergy 2006; 36: 503–509.
140.
Garib V, Wollmann E, Djambekova G, Lemell P, Kmenta M, Berger U, Zieglmayer P, Valenta R: Possible effect of landscape design on IgE recognition profiles of two generations revealed with micro-arrayed allergens. Allergy 2017; 72: 1579–1582.
141.
D’Amato G, Ruffilli A, Sacerdoti G, Bonini S: Parietaria pollinosis: a review. Allergy 1992; 47: 443–449.
142.
Quiralte J, Llanes E, Barral P, Arias de Saavedra JM, Saenz de San Pedro B, Villalba M, Florido JF, Rodriguez R, Lahoz C, Cardaba B: Ole e 2 and Ole e 10: new clinical aspects and genetic restrictions in olive pollen allergy. Allergy 2005; 60: 360–365.
143.
Gadermaier G, Hauser M, Ferreira F: Allergens of weed pollen: an overview on recombinant and natural molecules. Methods 2014; 66: 55–66.
144.
Gangl K, Niederberger V, Valenta R: Multiple grass mixes as opposed to single grasses for allergen immunotherapy in allergic rhinitis. Clin Exp Allergy 2013; 43: 1202–1216.
145.
Mothes N, Horak F, Valenta R: Transition from a botanical to a molecular classification in tree pollen allergy: implications for diagnosis and therapy. Int Arch Allergy Immunol 2004; 135: 357–373.
146.
Hatzler L, Panetta V, Illi S, Hofmaier S, Rohrbach A, Hakimeh D, Bauer CP, Hoffman U, Forster J, Zepp F, Schuster A, Stock P, Wahn U, Keil T, Lau S, Matricardi PM: Parental hay fever reinforces IgE to pollen as pre-clinical biomarker of hay fever in childhood. Pediatr Allergy Immunol 2014; 25: 366–373.
147.
Westritschnig K, Horak F, Swoboda I, Balic N, Spitzauer S, Kundi M, Fiebig H, Suck R, Cromwell O, Valenta R: Different allergenic activity of grass pollen allergens revealed by skin testing Eur J Clin Invest 2008; 38: 260–267.
148.
Suphioglu C, Singh MB, Taylor P, Bellomo R, Holmes P, Puy R, Knox RB: Mechanism of grass-pollen-induced asthma. Lancet 1992; 339: 569–572.
149.
Taylor PE, Flagan RC, Valenta R, Glovsky MM: Release of allergens as respirable aerosols: a link between grass pollen and asthma. J Allergy Clin Immunol 2002; 109: 51–56.
150.
Göbl C, Focke-Tejkl M, Najafi N, Schrank E, Madl T, Kosol S, Madritsch C, Dorofeeva Y, Flicker S, Thalhamer J, Valenta R, Zangger K, Tjandra N: Flexible IgE epitope-containing domains of Phl p 5 cause high allergenic activity. J Allergy Clin Immunol 2017; 140: 1187–1191.
151.
Domínguez-Ortega J, López-Matas MÁ, Alonso MD, Feliú A, Ruiz-Hornillos J, González E, Moya R, Carnés J: Prevalence of allergic sensitization to conifer pollen in a high cypress exposure area. Allergy Rhinol (Providence) 2016; 7: 200–206.
152.
Quiralte J, Palacios L, Rodríguez R, Cárdaba B, Arias de Saavedra JM, Villalba M, Florido JF, Lahoz C: Modelling diseases: the allergens of Olea europaea pollen. J Investig Allergol Clin Immunol 2007; 1: 24–30.
153.
Zieglmayer P, Focke-Tejkl M, Schmutz R, Lemell P, Zieglmayer R, Weber M, Kiss R, Blatt K, Valent P, Stolz F, Huber H, Neubauer A, Knoll A, Horak F, Henning R, Valenta R: Mechanisms, safety and efficacy of a B cell epitope-based vaccine for immunotherapy of grass pollen allergy. EBioMedicine 2016; 11: 43–57.
154.
Valenta R, Campana R, Niederberger V: Recombinant allergy vaccines based on allergen-derived B cell epitopes. Immunol Lett 2017; 189: 19–26.
155.
Niederberger V, Neubauer A, Gevaert P, Zidarn M, Worm M, Aberer W, Malling HJ, Pfaar O, Klimek L, Pfützner W, Ring J, Darsow U, Novak N, Gerth van Wijk R, Eckl-Dorna J, Focke-Tejkl M, Weber M, Müller HH, Klinger J, Stolz F, Breit N, Henning R, Valenta R: Safety and efficacy of immunotherapy with the recombinant B-cell epi-tope-based grass pollen vaccine BM32. J Allergy Clin Immunol 2018;pii: S0091-6749(17)31884-5.
156.
Skrindo I, Lupinek C, Valenta R, Hovland V, Pahr S, Baar A, Carlsen KH, Mowinckel P, Wickman M, Melen E, Bousquet J, Anto JM, Lødrup Carlsen KC: The use of the MeDALL-chip to assess IgE sensitization: a new diagnostic tool for allergic disease? Pediatr Allergy Immunol 2015; 26: 239–246.
157.
Westman M, Lupinek C, Bousquet J, Andersson N, Pahr S, Baar A, Bergström A, Holmström M, Stjärne P, Lødrup Carlsen KC, Carlsen KH, Antó JM, Valenta R, van Hage M, Wickman M; Mechanisms for the Development of Allergies Consortium: Early childhood IgE reactivity to pathogenesis-related class 10 proteins predicts allergic rhinitis in adolescence. J Allergy Clin Immunol 2015; 135: 1199–1206.
158.
Westman M, Asarnoj A, Hamsten C, Wickman M, van Hage M: Windows of opportunity for tolerance induction for allergy by studying the evolution of allergic sensitization in birth cohorts. Semin Immunol 2017; 30: 61–66.
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2018
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