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The pharmacological modulation of allergen-induced asthma

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Abstract

Aeroallergens are the most common triggers for the development of asthma. Recent birth cohort studies have identified viral infections occurring against a background of aeroallergen sensitization as a potent risk factor for initiation of asthma. Viral infection enhances immunopathogenic potential of pre-existing inhalant allergy via modulating airway mucosal dendritic cells. By using an allergen inhalation challenge clinical model, studies have shown that the late asthma response (LAR) is associated with more pronounced allergen-induced airway inflammation and airway hyperresponsiveness. The degree of airway eosinophilia, regulated by bone marrow progenitor cells and interleukin-5 level, correlates with the magnitude of the LAR and the increase in hyperresponsiveness. Both myeloid and plasmacytoid dendritic cell subsets have been involved in the pathogenesis of allergen-induced LAR. Myeloid dendritic cells are responsible for the allergen presentation and induction of inflammation and plasmacytoid dendritic cells play a role in the resolution of allergen-induced inflammation. A variety of potential new classes of asthma medication has also been evaluated with the allergen inhalation challenge in mild asthmatic subjects. Examples are TPI ASM8, an inhaled anti-sense oligonucleotide drug product, which attenuated both early and LARs via inhibition of the target gene mRNA of chemokine receptor 3, and the common β chain of interleukin-3, interleukin-5 and granulocyte–macrophage colony-stimulating factor receptor. Anti-human antibody interleukin-13 (IM-638) significantly attenuated both early and late allergen-induced asthma response. Pitrakinra, which targets both interleukin-4 and interleukin-13, substantially diminishes allergen-induced airway responses. Allergen-induced airway responses are a valuable way to evaluate the activity of possible new therapies in asthmatic airways.

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References

  • Allakhverdi Z, Allam M, Renzi PM (2002) Inhibition of antigen-induced eosinophilia and airway hyperresponsiveness by antisense oligonucleotides directed against the common beta chain of IL-3, IL-5, GM-CSF receptors in a rat model of allergic asthma. Am J Respir Crit Care Med 165(7):1015–1021

    PubMed  Google Scholar 

  • Allakhverdi Z, Allam M, Guimond A et al (2006) Multitargeted approach using antisense oligonucleotides for the treatment of asthma. Ann NY Acad Sci 1082:62–73

    Article  PubMed  CAS  Google Scholar 

  • Allam M, Renzi PM (2001) Inhibition of GM-CSF/IL-3/IL-5 signaling by antisense oligodeoxynucleotides targeting the common beta chain of their receptors. Antisense Nucleic Acid Drug Dev 11(5):289–300

    Article  PubMed  CAS  Google Scholar 

  • Bateman ED, Hurd SS, Barnes PJ et al (2008) Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J 31(1):143–178

    Article  PubMed  CAS  Google Scholar 

  • Beyer M, Bartz H, Horner K et al (2004) Sustained increases in numbers of pulmonary dendritic cells after respiratory syncytial virus infection. J Allergy Clin Immunol 113(1):127–133

    Article  PubMed  Google Scholar 

  • Black JL, Panettieri RA Jr, Banerjee A et al (2012) Airway smooth muscle in asthma: just a target for bronchodilation? Clin Chest Med 33(3):543–558

    Article  PubMed  Google Scholar 

  • Blanchard C, Mishra A, Saito-Akei H et al (2005) Inhibition of human interleukin-13-induced respiratory and oesophageal inflammation by anti-human-interleukin-13 antibody (CAT-354). Clin Exp Allergy 35(8):1096–1103

    Article  PubMed  CAS  Google Scholar 

  • Boulet LP, Chapman KR, Cote J et al (1997) Inhibitory effects of an anti-IgE antibody E25 on allergen-induced early asthmatic response. Am J Respir Crit Care Med 155(6):1835–1840

    PubMed  CAS  Google Scholar 

  • Boulet LP, Turcotte H, Laviolette M et al (2000) Airway hyperresponsiveness, inflammation, and subepithelial collagen deposition in recently diagnosed versus long-standing mild asthma. Influence of inhaled corticosteroids. Am J Respir Crit Care Med 162((4 Pt 1)):1308–1313

    PubMed  CAS  Google Scholar 

  • Boulet LP, Gauvreau G, Boulay ME et al (2007) The allergen bronchoprovocation model: an important tool for the investigation of new asthma anti-inflammatory therapies. Allergy 62(10):1101–1110

    Article  PubMed  Google Scholar 

  • Bousquet J, Chanez P, Lacoste JY et al (1990) Eosinophilic inflammation in asthma. N Engl J Med 323(15):1033–1039

    Article  PubMed  CAS  Google Scholar 

  • Boyce JA (2005) Eicosanoid mediators of mast cells: receptors, regulation of synthesis, and pathobiologic implications. Chem Immunol Allergy 87:59–79

    Article  PubMed  CAS  Google Scholar 

  • Bradding P, Holgate ST (1996) The mast cell as a source of cytokines in asthma. Ann NY Acad Sci 796:272–281

    Article  PubMed  CAS  Google Scholar 

  • Braun-Fahrlander C, Riedler J, Herz U et al (2002) Environmental exposure to endotoxin and its relation to asthma in school-age children. N Engl J Med 347(12):869–877

    Article  PubMed  Google Scholar 

  • Bree A, Schlerman FJ, Wadanoli M et al (2007) IL-13 blockade reduces lung inflammation after Ascaris suum challenge in cynomolgus monkeys. J Allergy Clin Immunol 119(5):1251–1257

    Article  PubMed  CAS  Google Scholar 

  • Brewster CE, Howarth PH, Djukanovic R et al (1990) Myofibroblasts and subepithelial fibrosis in bronchial asthma. Am J Respir Cell Mol Biol 3(5):507–511

    PubMed  CAS  Google Scholar 

  • Brown RH, Pearse DB, Pyrgos G et al (2006) The structural basis of airways hyperresponsiveness in asthma. J Appl Physiol 101(1):30–39

    Article  PubMed  Google Scholar 

  • Cartier A, Thomson NC, Frith PA et al (1982) Allergen-induced increase in bronchial responsiveness to histamine: relationship to the late asthmatic response and change in airway caliber. J Allergy Clin Immunol 70(3):170–177

    Article  PubMed  CAS  Google Scholar 

  • Choy DF, Modrek B, Abbas AR et al (2011) Gene expression patterns of Th2 inflammation and intercellular communication in asthmatic airways. J Immunol 186(3):1861–1869

    Article  PubMed  CAS  Google Scholar 

  • Copenhaver CC, Gern JE, Li Z et al (2004) Cytokine response patterns, exposure to viruses, and respiratory infections in the first year of life. Am J Respir Crit Care Med 170(2):175–180

    Article  PubMed  Google Scholar 

  • Corren J, Lemanske RF, Hanania NA et al (2011) Lebrikizumab treatment in adults with asthma. N Engl J Med 365(12):1088–1098

    Article  PubMed  CAS  Google Scholar 

  • Davis BE, Todd DC, Cockcroft DW (2005) Effect of combined montelukast and desloratadine on the early asthmatic response to inhaled allergen. J Allergy Clin Immunol 116(4):768–772

    Article  PubMed  CAS  Google Scholar 

  • Davis BE, Illamperuma C, Gauvreau GM et al (2009) Single-dose desloratadine and montelukast and allergen-induced late airway responses. Eur Respir J 33(6):1302–1308

    Article  PubMed  CAS  Google Scholar 

  • de Heer HJ, Hammad H, Soullie T et al (2004) Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen. J Exp Med 200(1):89–98

    Article  PubMed  Google Scholar 

  • Dorman SC, Sehmi R, Gauvreau GM et al (2004) Kinetics of bone marrow eosinophilopoiesis and associated cytokines after allergen inhalation. Am J Respir Crit Care Med 169(5):565–572

    Article  PubMed  Google Scholar 

  • Dorsch W, Baur X, Emslander HP et al (1980) Pathogenesis and treatment of allergen-induced late bronchial obstruction (author’s transl). Prax Klin Pneumol 34(8):461–468

    PubMed  CAS  Google Scholar 

  • Dua B, Watson RM, Gauvreau GM et al (2010) Myeloid and plasmacytoid dendritic cells in induced sputum after allergen inhalation in subjects with asthma. J Allergy Clin Immunol 126(1):133–139

    Article  PubMed  CAS  Google Scholar 

  • Elbashir SM, Harborth J, Lendeckel W et al (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411(6836):494–498

    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(6):1828–1834

    PubMed  CAS  Google Scholar 

  • Farrell E, O’Connor TM, Duong M et al (2007) Circulating myeloid and plasmacytoid dendritic cells after allergen inhalation in asthmatic subjects. Allergy 62(10):1139–1145

    Article  PubMed  CAS  Google Scholar 

  • Ferrari N, Seguin R, Renzi P (2011) Oligonucleotides: a multi-targeted approach for the treatment of respiratory diseases. Future Med Chem 3(13):1647–1662

    Article  PubMed  CAS  Google Scholar 

  • Fish SC, Donaldson DD, Goldman SJ et al (2005) IgE generation and mast cell effector function in mice deficient in IL-4 and IL-13. J Immunol 174(12):7716–7724

    PubMed  CAS  Google Scholar 

  • Fortin M, Ferrari N, Higgins ME et al (2006) Effects of antisense oligodeoxynucleotides targeting CCR3 on the airway response to antigen in rats. Oligonucleotides 16(3):203–212

    Article  PubMed  CAS  Google Scholar 

  • Foster PS, Webb DC, Yang M et al (2003) Dissociation of T helper type 2 cytokine-dependent airway lesions from signal transducer and activator of transcription 6 signalling in experimental chronic asthma. Clin Exp Allergy 33(5):688–695

    Article  PubMed  CAS  Google Scholar 

  • Gauvreau GM, Doctor J, Watson RM et al (1996) Effects of inhaled budesonide on allergen-induced airway responses and airway inflammation. Am J Respir Crit Care Med 154(5):1267–1271

    PubMed  CAS  Google Scholar 

  • Gauvreau GM, Jordana M, Watson RM et al (1997) Effect of regular inhaled albuterol on allergen-induced late responses and sputum eosinophils in asthmatic subjects. Am J Respir Crit Care Med 156(6):1738–1745

    PubMed  CAS  Google Scholar 

  • Gauvreau GM, Watson RM, O’Byrne PM (1999) Kinetics of allergen-induced airway eosinophilic cytokine production and airway inflammation. Am J Respir Crit Care Med 160(2):640–647

    PubMed  CAS  Google Scholar 

  • Gauvreau GM, Lee JM, Watson RM et al (2000) Increased numbers of both airway basophils and mast cells in sputum after allergen inhalation challenge of atopic asthmatics. Am J Respir Crit Care Med 161(5):1473–1478

    PubMed  CAS  Google Scholar 

  • Gauvreau GM, Boulet LP, Cockcroft DW et al (2008) Antisense therapy against CCR3 and the common beta chain attenuates allergen-induced eosinophilic responses. Am J Respir Crit Care Med 177(9):952–958

    Article  PubMed  CAS  Google Scholar 

  • Gauvreau GM, Boulet LP, Cockcroft DW et al (2011a) 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 

  • Gauvreau GM, Pageau R, Seguin R et al (2011b) Dose-response effects of TPI ASM8 in asthmatics after allergen. Allergy 66(9):1242–1248

    Article  PubMed  CAS  Google Scholar 

  • Gill MA, Palucka AK, Barton T et al (2005) Mobilization of plasmacytoid and myeloid dendritic cells to mucosal sites in children with respiratory syncytial virus and other viral respiratory infections. J Infect Dis 191(7):1105–1115

    Article  PubMed  Google Scholar 

  • Greaves DR, Wang W, Dairaghi DJ et al (1997) CCR6, a CC chemokine receptor that interacts with macrophage inflammatory protein 3alpha and is highly expressed in human dendritic cells. J Exp Med 186(6):837–844

    Article  PubMed  CAS  Google Scholar 

  • Grunig G, Warnock M, Wakil AE et al (1998) Requirement for IL-13 independently of IL-4 in experimental asthma. Science 282(5397):2261–2263

    Article  PubMed  CAS  Google Scholar 

  • Hammad H, Lambrecht BN (2006) Recent progress in the biology of airway dendritic cells and implications for understanding the regulation of asthmatic inflammation. J Allergy Clin Immunol 118(2):331–336

    Article  PubMed  CAS  Google Scholar 

  • Hammad H, de Vries VC, Maldonado-Lopez R et al (2004) Differential capacity of CD8+ alpha or CD8− alpha dendritic cell subsets to prime for eosinophilic airway inflammation in the T-helper type 2-prone milieu of the lung. Clin Exp Allergy 34(12):1834–1840

    Article  PubMed  CAS  Google Scholar 

  • He R, Geha RS (2010) Thymic stromal lymphopoietin. Ann NY Acad Sci 1183:13–24

    Article  PubMed  CAS  Google Scholar 

  • Hebenstreit D, Wirnsberger G, Horejs-Hoeck J et al (2006) Signaling mechanisms, interaction partners, and target genes of STAT6. Cytokine Growth Factor Rev 17(3):173–188

    Article  PubMed  CAS  Google Scholar 

  • Holgate ST (2007) The epithelium takes centre stage in asthma and atopic dermatitis. Trends Immunol 28(6):248–251

    Article  PubMed  CAS  Google Scholar 

  • Holt PG, Sly PD (2012) Viral infections and atopy in asthma pathogenesis: new rationales for asthma prevention and treatment. Nat Med 18(5):726–735

    Article  PubMed  CAS  Google Scholar 

  • Holt PG, Strickland DH (2010) Interactions between innate and adaptive immunity in asthma pathogenesis: new perspectives from studies on acute exacerbations. J Allergy Clin Immunol 125(5):963–972

    Article  PubMed  CAS  Google Scholar 

  • Holt PG, Thomas WR (2005) Sensitization to airborne environmental allergens: unresolved issues. Nat Immunol 6(10):957–960

    Article  PubMed  CAS  Google Scholar 

  • Holt PG, Strickland DH, Wikstrom ME et al (2008) Regulation of immunological homeostasis in the respiratory tract. Nat Rev Immunol 8(2):142–152

    Article  PubMed  CAS  Google Scholar 

  • Holt PG, Rowe J, Kusel M et al (2010) Toward improved prediction of risk for atopy and asthma among preschoolers: a prospective cohort study. J Allergy Clin Immunol 125(3):653–659

    Article  PubMed  Google Scholar 

  • Illi S, von Mutius E, Lau S et al (2001) Early childhood infectious diseases and the development of asthma up to school age: a birth cohort study. BMJ 322(7283):390–395

    Article  PubMed  CAS  Google Scholar 

  • Illi S, von Mutius E, Lau S et al (2006) Perennial allergen sensitisation early in life and chronic asthma in children: a birth cohort study. Lancet 368(9537):763–770

    Article  PubMed  Google Scholar 

  • Jackson DJ, Evans MD, Gangnon RE et al (2012) Evidence for a causal relationship between allergic sensitization and rhinovirus wheezing in early life. Am J Respir Crit Care Med 185(3):281–285

    Article  PubMed  Google Scholar 

  • Jacoby DB, Costello RM, Fryer AD (2001) Eosinophil recruitment to the airway nerves. J Allergy Clin Immunol 107(2):211–218

    Article  PubMed  CAS  Google Scholar 

  • Janson C, Anto J, Burney P et al (2001) The European Community Respiratory Health Survey: what are the main results so far? European Community Respiratory Health Survey II. Eur Respir J 18(3):598–611

    Article  PubMed  CAS  Google Scholar 

  • Jayasena SD (1999) Aptamers: an emerging class of molecules that rival antibodies in diagnostics. Clin Chem 45(9):1628–1650

    PubMed  CAS  Google Scholar 

  • Jeffery P, Zhu J (2002) Mucin-producing elements and inflammatory cells. Novartis Found Symp 248:51–68

    Article  PubMed  CAS  Google Scholar 

  • Kasaian MT, Donaldson DD, Tchistiakova L et al (2007) Efficacy of IL-13 neutralization in a sheep model of experimental asthma. Am J Respir Cell Mol Biol 36(3):368–376

    Article  PubMed  CAS  Google Scholar 

  • Kasaian MT, Tan XY, Jin M et al (2008) Interleukin-13 neutralization by two distinct receptor blocking mechanisms reduces immunoglobulin E responses and lung inflammation in cynomolgus monkeys. J Pharmacol Exp Ther 325(3):882–892

    Article  PubMed  CAS  Google Scholar 

  • Kay AB (2001) Allergy and allergic diseases. Second of two parts. N Engl J Med 344(2):109–113

    Article  PubMed  CAS  Google Scholar 

  • Kelly MM, O’Connor TM, Leigh R et al (2010) Effects of budesonide and formoterol on allergen-induced airway responses, inflammation, and airway remodeling in asthma. J Allergy Clin Immunol 125(2):349–356

    Article  PubMed  CAS  Google Scholar 

  • Kirby JG, Robertson DG, Hargreave FE et al (1986) Asthmatic responses to inhalation of anti-human IgE. Clin Allergy 16(3):191–194

    Article  PubMed  CAS  Google Scholar 

  • Kirkham S, Sheehan JK, Knight D et al (2002) Heterogeneity of airways mucus: variations in the amounts and glycoforms of the major oligomeric mucins MUC5AC and MUC5B. Biochem J 361(Pt 3):537–546

    Article  PubMed  CAS  Google Scholar 

  • Krieg AM, Yi AK, Matson S et al (1995) CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 374(6522):546–549

    Article  PubMed  CAS  Google Scholar 

  • Krieg AM, Matson S, Fisher E (1996) Oligodeoxynucleotide modifications determine the magnitude of B cell stimulation by CpG motifs. Antisense Nucleic Acid Drug Dev 6(2):133–139

    Article  PubMed  CAS  Google Scholar 

  • Kulig M, Bergmann R, Tacke U et al (1998) Long-lasting sensitization to food during the first two years precedes allergic airway disease. The MAS Study Group, Germany. Pediatr Allergy Immunol 9(2):61–67

    Article  PubMed  CAS  Google Scholar 

  • Kusel MM, de Klerk NH, Kebadze T et al (2007) Early-life respiratory viral infections, atopic sensitization, and risk of subsequent development of persistent asthma. J Allergy Clin Immunol 119(5):1105–1110

    Article  PubMed  Google Scholar 

  • Lai H, Rogers DF (2010) New pharmacotherapy for airway mucus hypersecretion in asthma and COPD: targeting intracellular signaling pathways. J Aerosol Med Pulm Drug Deliv 23(4):219–231

    Article  PubMed  CAS  Google Scholar 

  • Lambrecht BN, Hammad H (2009) Biology of lung dendritic cells at the origin of asthma. Immunity 31(3):412–424

    Article  PubMed  CAS  Google Scholar 

  • Lambrecht BN, De Veerman M, Coyle AJ et al (2000a) Myeloid dendritic cells induce Th2 responses to inhaled antigen, leading to eosinophilic airway inflammation. J Clin Invest 106(4):551–559

    Article  PubMed  CAS  Google Scholar 

  • Lambrecht BN, Peleman RA, Bullock GR et al (2000b) Sensitization to inhaled antigen by intratracheal instillation of dendritic cells. Clin Exp Allergy 30(2):214–224

    Article  PubMed  CAS  Google Scholar 

  • Lamkhioued B, Renzi PM, Abi-Younes S et al (1997) Increased expression of eotaxin in bronchoalveolar lavage and airways of asthmatics contributes to the chemotaxis of eosinophils to the site of inflammation. J Immunol 159(9):4593–4601

    PubMed  CAS  Google Scholar 

  • Lamkhioued B, Abdelilah SG, Hamid Q et al (2003) The CCR3 receptor is involved in eosinophil differentiation and is up-regulated by Th2 cytokines in CD34+ progenitor cells. J Immunol 170(1):537–547

    PubMed  CAS  Google Scholar 

  • LaPorte SL, Juo ZS, Vaclavikova J et al (2008) Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system. Cell 132(2):259–272

    Article  PubMed  CAS  Google Scholar 

  • Leigh R, Vethanayagam D, Yoshida M et al (2002) Effects of montelukast and budesonide on airway responses and airway inflammation in asthma. Am J Respir Crit Care Med 166(9):1212–1217

    Article  PubMed  Google Scholar 

  • Li X, Wilson JW (1997) Increased vascularity of the bronchial mucosa in mild asthma. Am J Respir Crit Care Med 156(1):229–233

    PubMed  CAS  Google Scholar 

  • Limb SL, Brown KC, Wood RA et al (2005) Irreversible lung function deficits in young adults with a history of childhood asthma. J Allergy Clin Immunol 116(6):1213–1219

    Article  PubMed  Google Scholar 

  • Lively TN, Kossen K, Balhorn A et al (2008) Effect of chemically modified IL-13 short interfering RNA on development of airway hyperresponsiveness in mice. J Allergy Clin Immunol 121(1):88–94

    Article  PubMed  CAS  Google Scholar 

  • Lowe AJ, Hosking CS, Bennett CM et al (2007) Skin prick test can identify eczematous infants at risk of asthma and allergic rhinitis. Clin Exp Allergy 37(11):1624–1631

    Article  PubMed  CAS  Google Scholar 

  • Ma Y, Hayglass KT, Becker AB et al (2007a) Novel recombinant interleukin-13 peptide-based vaccine reduces airway allergic inflammatory responses in mice. Am J Respir Crit Care Med 176(5):439–445

    Article  PubMed  CAS  Google Scholar 

  • Ma Y, Hayglass KT, Becker AB et al (2007b) Novel cytokine peptide-based vaccines: an interleukin-4 vaccine suppresses airway allergic responses in mice. Allergy 62(6):675–682

    Article  PubMed  CAS  Google Scholar 

  • Mann MJ, Dzau VJ (2000) Therapeutic applications of transcription factor decoy oligonucleotides. J Clin Invest 106(9):1071–1075

    Article  PubMed  CAS  Google Scholar 

  • Martinez FD, Wright AL, Taussig LM et al (1995) Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med 332(3):133–138

    Article  PubMed  CAS  Google Scholar 

  • McKenzie GJ, Fallon PG, Emson CL et al (1999) Simultaneous disruption of interleukin (IL)-4 and IL-13 defines individual roles in T helper cell type 2-mediated responses. J Exp Med 189(10):1565–1572

    Article  PubMed  CAS  Google Scholar 

  • McWilliam AS, Napoli S, Marsh AM et al (1996) Dendritic cells are recruited into the airway epithelium during the inflammatory response to a broad spectrum of stimuli. J Exp Med 184(6):2429–2432

    Article  PubMed  CAS  Google Scholar 

  • McWilliam AS, Marsh AM, Holt PG (1997) Inflammatory infiltration of the upper airway epithelium during Sendai virus infection: involvement of epithelial dendritic cells. J Virol 71(1):226–236

    PubMed  CAS  Google Scholar 

  • Molina C, Brun J, Coulet M et al (1977) Immunopathology of the bronchial mucosa in ‘late onset’ asthma. Clin Allergy 7(2):137–145

    Article  PubMed  CAS  Google Scholar 

  • Nakajima H, Takatsu K (2007) Role of cytokines in allergic airway inflammation. Int Arch Allergy Immunol 142(4):265–273

    Article  PubMed  CAS  Google Scholar 

  • O’Byrne PM, Dolovich J, Hargreave FE (1987) Late asthmatic responses. Am Rev Respir Dis 136(3):740–751

    Article  PubMed  Google Scholar 

  • Oddy WH, de Klerk NH, Sly PD et al (2002) The effects of respiratory infections, atopy, and breastfeeding on childhood asthma. Eur Respir J 19(5):899–905

    Article  PubMed  CAS  Google Scholar 

  • Ordonez CL, Khashayar R, Wong HH et al (2001) Mild and moderate asthma is associated with airway goblet cell hyperplasia and abnormalities in mucin gene expression. Am J Respir Crit Care Med 163(2):517–523

    PubMed  CAS  Google Scholar 

  • Ozier A, Allard B, Bara I et al (2011) The pivotal role of airway smooth muscle in asthma pathophysiology. J Allergy (Cairo) 2011:742710

    Google Scholar 

  • Palmer-Crocker RL, Hughes CC, Pober JS (1996) IL-4 and IL-13 activate the JAK2 tyrosine kinase and Stat6 in cultured human vascular endothelial cells through a common pathway that does not involve the gamma c chain. J Clin Invest 98(3):604–609

    Article  PubMed  CAS  Google Scholar 

  • Peat JK, Salome CM, Woolcock AJ (1990) Longitudinal changes in atopy during a 4-year period: relation to bronchial hyperresponsiveness and respiratory symptoms in a population sample of Australian school children. J Allergy Clin Immunol 85(1 Pt 1):65–74

    Article  PubMed  CAS  Google Scholar 

  • Pepe C, Foley S, Shannon J et al (2005) Differences in airway remodeling between subjects with severe and moderate asthma. J Allergy Clin Immunol 116(3):544–549

    Article  PubMed  Google Scholar 

  • Pepys J, Hargreave FE, Chan M et al (1968) Inhibitory effects of disodium cromoglycate on allergen-inhalation tests. Lancet 2(7560):134–137

    Article  PubMed  CAS  Google Scholar 

  • Perkins C, Wills-Karp M, Finkelman FD (2006) IL-4 induces IL-13-independent allergic airway inflammation. J Allergy Clin Immunol 118(2):410–419

    Article  PubMed  CAS  Google Scholar 

  • Pini L, Hamid Q, Shannon J et al (2007) Differences in proteoglycan deposition in the airways of moderate and severe asthmatics. Eur Respir J 29(1):71–77

    Article  PubMed  CAS  Google Scholar 

  • Power CA, Church DJ, Meyer A et al (1997) Cloning and characterization of a specific receptor for the novel CC chemokine MIP-3α from lung dendritic cells. J Exp Med 186(6):825–835

    Article  PubMed  CAS  Google Scholar 

  • Rhodes HL, Thomas P, Sporik R et al (2002) A birth cohort study of subjects at risk of atopy: twenty-two-year follow-up of wheeze and atopic status. Am J Respir Crit Care Med 165(2):176–180

    PubMed  Google Scholar 

  • Robinson DS (2010) The role of the T cell in asthma. J Allergy Clin Immunol 126(6):1081–1091

    Article  PubMed  CAS  Google Scholar 

  • Rousseau K, Byrne C, Griesinger G et al (2007) Allelic association and recombination hotspots in the mucin gene (MUC) complex on chromosome 11p15.5. Ann Hum Genet 71(Pt 5):561–569

    Article  PubMed  CAS  Google Scholar 

  • Salvato G (2001) Quantitative and morphological analysis of the vascular bed in bronchial biopsy specimens from asthmatic and non-asthmatic subjects. Thorax 56(12):902–906

    Article  PubMed  CAS  Google Scholar 

  • Sehmi R, Wood LJ, Watson R et al (1997) Allergen-induced increases in IL-5 receptor alpha-subunit expression on bone marrow-derived CD34+ cells from asthmatic subjects. A novel marker of progenitor cell commitment towards eosinophilic differentiation. J Clin Invest 100(10):2466–2475

    Article  PubMed  CAS  Google Scholar 

  • Sherrill D, Stein R, Kurzius-Spencer M et al (1999) On early sensitization to allergens and development of respiratory symptoms. Clin Exp Allergy 29(7):905–911

    Article  PubMed  CAS  Google Scholar 

  • Shimura S, Andoh Y, Haraguchi M et al (1996) Continuity of airway goblet cells and intraluminal mucus in the airways of patients with bronchial asthma. Eur Respir J 9(7):1395–1401

    Article  PubMed  CAS  Google Scholar 

  • Sidhu SS, Yuan S, Innes AL et al (2010) Roles of epithelial cell-derived periostin in TGF-beta activation, collagen production, and collagen gel elasticity in asthma. Proc Natl Acad Sci USA 107(32):14170–14175

    Article  PubMed  CAS  Google Scholar 

  • Sly PD, Boner AL, Bjorksten B et al (2008) Early identification of atopy in the prediction of persistent asthma in children. Lancet 372(9643):1100–1106

    Article  PubMed  Google Scholar 

  • Smit JJ, Rudd BD, Lukacs NW (2006) Plasmacytoid dendritic cells inhibit pulmonary immunopathology and promote clearance of respiratory syncytial virus. J Exp Med 203(5):1153–1159

    Article  PubMed  CAS  Google Scholar 

  • Stern DA, Morgan WJ, Wright AL et al (2007) Poor airway function in early infancy and lung function by age 22 years: a non-selective longitudinal cohort study. Lancet 370(9589):758–764

    Article  PubMed  Google Scholar 

  • Takayama G, Arima K, Kanaji T et al (2006) Periostin: a novel component of subepithelial fibrosis of bronchial asthma downstream of IL-4 and IL-13 signals. J Allergy Clin Immunol 118(1):98–104

    Article  PubMed  CAS  Google Scholar 

  • Thai P, Chen Y, Dolganov G et al (2005) Differential regulation of MUC5AC/Muc5ac and hCLCA-1/mGob-5 expression in airway epithelium. Am J Respir Cell Mol Biol 33(6):523–530

    Article  PubMed  CAS  Google Scholar 

  • Turner SW, Heaton T, Rowe J et al (2007) Early-onset atopy is associated with enhanced lymphocyte cytokine responses in 11-year-old children. Clin Exp Allergy 37(3):371–380

    Article  PubMed  CAS  Google Scholar 

  • Twentyman OP, Finnerty JP, Harris A et al (1990) Protection against allergen-induced asthma by salmeterol. Lancet 336(8727):1338–1342

    Article  PubMed  CAS  Google Scholar 

  • Voynow JA, Rubin BK (2009) Mucins, mucus, and sputum. Chest 135(2):505–512

    Article  PubMed  CAS  Google Scholar 

  • Vrugt B, Wilson S, Bron A et al (2000) Bronchial angiogenesis in severe glucocorticoid-dependent asthma. Eur Respir J 15(6):1014–1021

    Article  PubMed  CAS  Google Scholar 

  • Webb DC, McKenzie AN, Koskinen AM et al (2000) Integrated signals between IL-13, IL-4, and IL-5 regulate airways hyperreactivity. J Immunol 165(1):108–113

    PubMed  CAS  Google Scholar 

  • Webb DC, Matthaei KI, Cai Y et al (2004) Polymorphisms in IL-4R alpha correlate with airways hyperreactivity, eosinophilia, and Ym protein expression in allergic IL-13−/− mice. J Immunol 172(2):1092–1098

    PubMed  CAS  Google Scholar 

  • Wenzel S, Wilbraham D, Fuller R et al (2007) Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies. Lancet 370(9596):1422–1431

    Article  PubMed  CAS  Google Scholar 

  • Whittaker L, Niu N, Temann UA et al (2002) Interleukin-13 mediates a fundamental pathway for airway epithelial mucus induced by CD4 T cells and interleukin-9. Am J Respir Cell Mol Biol 27(5):593–602

    PubMed  CAS  Google Scholar 

  • Wills-Karp M (2004) Interleukin-13 in asthma pathogenesis. Immunol Rev 202:175–190

    Article  PubMed  CAS  Google Scholar 

  • Wills-Karp M, Luyimbazi J, Xu X et al (1998) Interleukin-13: central mediator of allergic asthma. Science 282(5397):2258–2261

    Article  PubMed  CAS  Google Scholar 

  • Wong CK, Cheung PF, Ip WK et al (2007) Intracellular signaling mechanisms regulating toll-like receptor-mediated activation of eosinophils. Am J Respir Cell Mol Biol 37(1):85–96

    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(40):15858–15863

    Article  PubMed  CAS  Google Scholar 

  • Wynn TA (2003) IL-13 effector functions. Annu Rev Immunol 21:425–456

    Article  PubMed  CAS  Google Scholar 

  • Yang G, Volk A, Petley T et al (2004) Anti-IL-13 monoclonal antibody inhibits airway hyperresponsiveness, inflammation and airway remodeling. Cytokine 28(6):224–232

    Article  PubMed  CAS  Google Scholar 

  • Yoshida R, Nagira M, Kitaura M et al (1998) Secondary lymphoid-tissue chemokine is a functional ligand for the CC chemokine receptor CCR7. J Biol Chem 273(12):7118–7122

    Article  PubMed  CAS  Google Scholar 

  • Zheng T, Liu W, Oh SY et al (2008) IL-13 receptor α2 selectively inhibits IL-13-induced responses in the murine lung. J Immunol 180(1):522–529

    PubMed  CAS  Google Scholar 

  • Ziegler SF, Artis D (2010) Sensing the outside world: TSLP regulates barrier immunity. Nat Immunol 11(4):289–293

    Article  PubMed  CAS  Google Scholar 

  • Zurawski G, de Vries JE (1994) Interleukin 13, an interleukin 4-like cytokine that acts on monocytes and B cells, but not on T cells. Immunol Today 15(1):19–26

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Firestone Institute of Respiratory Health, St. Joseph’s Healthcare, Department of Medicine, McMaster University, Hamilton, ON, Canada

    L. L. Ma & Paul M. O’Byrne

  2. Rm 3W10, McMaster University Medical Center, 1280 Main Street West, Hamilton, ON, L8S 4K1, Canada

    Paul M. O’Byrne

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  1. L. L. Ma
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  2. Paul M. O’Byrne
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Correspondence to Paul M. O’Byrne.

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Ma, L.L., O’Byrne, P.M. The pharmacological modulation of allergen-induced asthma. Inflammopharmacol 21, 113–124 (2013). https://doi.org/10.1007/s10787-012-0155-3

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  • DOI: https://doi.org/10.1007/s10787-012-0155-3

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