Epithelial function and dysfunction in asthma

Clinical and Experimental Allergy

Volumn 44, Issue 11, 2014, Pages 1299-1313

  Loxham, M ^a   Davies, D E ^a   Blume, C ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

BETA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; CHEMOKINE; CORTICOSTEROID; CYTOKINE; GROWTH FACTOR; ICOSANOID; OMALIZUMAB; REACTIVE OXYGEN METABOLITE; AUTACOID; SIGNAL PEPTIDE;

AIRWAY REMODELING; ASTHMA; CELLULAR STRESS RESPONSE; DISEASE CLASSIFICATION; DISEASE PREDISPOSITION; EPITHELIUM CELL; FORCED EXPIRATORY VOLUME; GENETIC ASSOCIATION; GENETIC SUSCEPTIBILITY; HUMAN; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; RESPIRATORY EPITHELIUM; RESPIRATORY TRACT INFLAMMATION; REVIEW; TISSUE STRUCTURE; ANIMAL; GENETIC PREDISPOSITION; IMMUNOLOGY; LIPID METABOLISM; METABOLISM; PATHOLOGY; PHYSIOLOGICAL STRESS; RESPIRATORY TRACT MUCOSA;

AIRWAY REMODELING; ANIMALS; ASTHMA; CYTOKINES; GENETIC PREDISPOSITION TO DISEASE; HUMANS; INFLAMMATION MEDIATORS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; LIPID METABOLISM; RESPIRATORY MUCOSA; STRESS, PHYSIOLOGICAL;

EID: 84912032596     PISSN: 09547894     EISSN: 13652222     Source Type: Journal    
DOI: 10.1111/cea.12309     Document Type: Review

References (228)

1. Salter HH. On asthma: its pathology and treatment. Philadelphia: Blanchard and Lea, 1860.
2. Lemanske RF, Busse WW. Asthma: clinical expression and molecular mechanisms. J Allergy Clin Immunol 2010; 125:S95-102.
3. To T, Stanojevic S, Moores G et al. Global asthma prevalence in adults: findings from the cross-sectional world health survey. BMC Public Health 2012;12:204.
4. Asthma UK. Asthma facts and FAQs, 2013.
5. National Health Service UK. What is asthma? 2013.
6. Holgate S, Bisgaard H, Bjermer L et al. The Brussels Declaration: the need for change in asthma management. Eur Respir J 2008;32: 1433-42.
7. British Thoracic Society Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma. Thorax 2008;63: iv1-121.
8. Yawn BP. Factors accounting for asthma variability: achieving optimal symptom control for individual patients. Prim Care Respir J 2008; 17:138-47.
9. Taylor DR, Bateman ED, Boulet LP et al. A new perspective on concepts of asthma severity and control. Eur Respir J 2008; 32:545-54.
10. Agache IO. From phenotypes to endotypes to asthma treatment. Curr Opin Allergy Clin Immunol 2013; 13:249-56.
11. Wenzel SE. Asthma: defining of the persistent adult phenotypes. Lancet 2006; 368:804-13.
12. Lotvall 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: 355-60.
13. Moore WC, Meyers DA, Wenzel SE et al. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med 2010; 181:315-23.
14. Haldar P, Pavord ID, Shaw DE et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med 2008;178: 218-24.
15. Green RH, Brightling CE, Woltmann G, Parker D, Wardlaw AJ, Pavord ID. Analysis of induced sputum in adults with asthma: identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticosteroids. Thorax 2002; 57:875-9.
16. Pavord ID, Brightling CE, Woltmann G, Wardlaw AJ. Non-eosinophilic corticosteroid unresponsive asthma. Lancet 1999; 353:2213-4.
17. Holgate ST, Arshad HS, Roberts GC, Howarth PH, Thurner P, Davies DE. A new look at the pathogenesis of asthma. Clin Sci 2010; 118:439-50.
18. Sporik R, Holgate ST, Plattsmills TAE, Cogswell JJ. Exposure to house dust mite allergen (Der p 1) and the development of asthma in childhood - a prospective study. N Engl J Med 1990;323: 502-7.
19. Hammad H, Chieppa M, Perros F, Willart MA, Germain RN, Lambrecht BN. House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells. Nat Med 2009;15: 410-6.
20. Black PN, Udy AA, Brodie SM. Sensitivity to fungal allergens is a risk factor for life-threatening asthma. Allergy 2000; 55:501-4.
21. O'Driscoll BR, Hopkinson LC, Denning DW. Mold sensitization is common amongst patients with severe asthma requiring multiple hospital admissions. BMC Pulm Med 2005; 5:4.
22. Denning DW, O'Driscoll BR, Hogaboam CM, Bowyer P, Niven RM. The link between fungi and severe asthma: a summary of the evidence. Eur Respir J 2006; 27:615-26.
23. Darrow LA, Hess J, Rogers CA, Tolbert PE, Klein M, Sarnat SE. Ambient pollen concentrations and emergency department visits for asthma and wheeze. J Allergy Clin Immunol 2012; 130:630-8.
24. Dales RE, Cakmak S, Judek S et al. Influence of outdoor aeroallergens on hospitalization for asthma in Canada. J Allergy Clin Immunol 2004; 113:303-6.
25. Miller EK, Edwards KM, Weinberg GA et al. A novel group of rhinoviruses is associated with asthma hospitalizations. J Allergy Clin Immunol 2009; 123:98-104.
26. Papadopoulos NG, Xepapadaki P, Mallia P et al. Mechanisms of virus-induced asthma exacerbations: state-of-the-art. A GA(2)LEN and InterAirways document. Allergy 2007; 62:457-70.
27. Johnston NW, Johnston SL, Duncan JM et al. The September epidemic of asthma exacerbations in children: a search for etiology. J Allergy Clin Immunol 2005; 115:132-8.
28. Althuis MD, Sexton M, Prybylski D. Cigarette smoking and asthma symptom severity among adult asthmatics. J Asthma 1999; 36:257-64.
29. Li N, Hao MQ, Phalen RF, Hinds WC, Nel AE. Particulate air pollutants and asthma - a paradigm for the role of oxidative stress in PM-induced adverse health effects. Clin Immunol 2003; 109:250-65.
30. Dykewicz MS. Occupational asthma: current concepts in pathogenesis, diagnosis, and management. J Allergy Clin Immunol 2009; 123:519-28.
31. Anderson SD, Daviskas E. The mechanism of exercise-induced asthma is... J Allergy Clin Immunol 2000; 106:453-9.
32. Stevenson DD, Szczeklik A. Clinical and pathologic perspectives on aspirin sensitivity and asthma. J Allergy Clin Immunol 2006; 118:773-86.
33. Farah CS, Salome CM. Asthma and obesity: a known association but unknown mechanism. Respirology 2012; 17:412-21.
34. Sutherland ER, Goleva E, King TS et al. Cluster analysis of obesity and asthma phenotypes. PLoS ONE 2012; 7:e36631.
35. Fenger RV, Gonzalez-Quintela A, Vidal C et al. Exploring the obesity-asthma link: do all types of adiposity increase the risk of asthma? Clin Exp Allergy 2012; 42:1237-45.
36. Loerbroks A, Gadinger MC, Bosch JA, Sturmer T, Amelang M. Work-related stress, inability to relax after work and risk of adult asthma: a population-based cohort study. Allergy 2010; 65:1298-305.
37. Ober C, Cox NJ, Abney M et al. Genome-wide search for asthma susceptibility loci in a founder population. Hum Mol Genet 1998; 7:1393-8.
38. Harada M, Hirota T, Jodo AI et al. Thymic Stromal lymphopoietin gene promoter polymorphisms are associated with susceptibility to bronchial asthma. Am J Respir Cell Mol Biol 2011; 44:787-93.
39. He JQ, Hallstrand TS, Knight D et al. A thymic stromal lymphopoietin gene variant is associated with asthma and airway hyperresponsiveness. J Allergy Clin Immunol 2009; 124:222-9.
40. Gudbjartsson DF, Bjornsdottir US, Halapi E et al. Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction. Nat Genet 2009; 41:342-7.
41. Moffatt MF, Gut IG, Demenais F et al. A large-scale, consortium-based genomewide association study of asthma. N Engl J Med 2010; 363:1211-21.
42. Reijmerink NE, Postma DS, Bruinenberg M et al. Association of IL1RL1, IL18R1, and IL18RAP gene cluster polymorphisms with asthma and atopy. J Allergy Clin Immunol 2008; 122:651-4.
43. Van Eerdewegh P, Little RD, Dupuis J et al. Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness. Nature 2002; 418:426-30.
44. Puxeddu I, Pang YY, Harvey A et al. The soluble form of a disintegrin and metalloprotease 33 promotes angiogenesis: implications for airway remodeling in asthma. J Allergy Clin Immunol 2008; 121:1400-6.
45. Koppelman GH, Meyers DA, Howard TD et al. Identification of PCDH1 as a novel susceptibility gene for bronchial hyperresponsiveness. Am J Respir Crit Care Med 2009; 180:929-35.
46. Bonnelykke K, Sleiman P, Nielsen K et al. A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations. Nat Genet 2014; 46:51-5.
47. Palmer CNA, Irvine AD, Terron-Kwiatkowski A et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 2006; 38:441-6.
48. Weidinger S, O'Sullivan M, Illig T et al. Filaggrin mutations, atopic eczema, hay fever, and asthma in children. J Allergy Clin Immunol 2008; 121:1203-9.
49. McLean WHI, Palmer CNA, Henderson J, Kabesch M, Weidinger S, Irvine AD. Filaggrin variants confer susceptibility to asthma. J Allergy Clin Immunol 2008; 121:1294-5.
50. Moffatt MF, Kabesch M, Liang LM et al. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature 2007; 448:470-3.
51. Cantero-Recasens G, Fandos C, Rubio-Moscardo F, Valverde MA, Vicente R. The asthma-associated ORMDL3 gene product regulates endoplasmic reticulum-mediated calcium signaling and cellular stress. Hum Mol Genet 2010; 19:111-21.
52. Carreras-Sureda A, Cantero-Recasens G, Rubio-Moscardo F et al. ORMDL3 modulates store-operated calcium entry and lymphocyte activation. Hum Mol Genet 2013; 22:519-30.
53. Wu H, Romieu I, Sienra-Monge JJ, Li H, del Rio-Navarro BE, London SJ. Genetic variation in ORM1-like 3 (ORMDL3) and gasdermin-like (GSDML) and childhood asthma. Allergy 2009; 64:629-35.
54. Nieminen MM, Kaprio J, Koskenvuo M. A population-based study of bronchial-asthma in adult twin pairs. Chest 1991; 100:70-5.
55. Skadhauge LR, Christensen K, Kyvik KO, Sigsgaard T. Genetic and environmental influence on asthma: a population based study of 11, 688 Danish twin pairs. Eur Respir J 1999; 13:8-14.
56. von Mutius E. Gene-environment interactions in asthma. J Allergy Clin Immunol 2009; 123:3-11.
57. Ober C, Vercelli D. Gene-environment interactions in human disease: nuisance or opportunity? Trends Genet 2011; 27:107-15.
58. Holgate ST. The airway epithelium is central to the pathogenesis of asthma. Allergol Int 2008; 57:1-10.
59. Lambrecht BN, Hammad H. The airway epithelium in asthma. Nat Med 2012; 18:684-92.
60. Holgate ST. The sentinel role of the airway epithelium in asthma pathogenesis. Immunol Rev 2011; 242:205-19.
61. Knight DA, Holgate ST. The airway epithelium: structural and functional properties in health and disease. Respirology 2003; 8:432-46.
62. Kirch J, Guenther M, Doshi N et al. Mucociliary clearance of micro- and nanoparticles is independent of size, shape and charge-an ex vivo and in silico approach. J Control Release 2012; 159:128-34.
63. Antunes MB, Cohen NA. Mucociliary clearance - a critical upper airway host defense mechanism and methods of assessment. Curr Opin Allergy Clin Immunol 2007; 7:5-10.
64. Rogers DF. The airway goblet cell. Int J Biochem Cell B 2003; 35:1-6.
65. Reynolds SD, Malkinson AM. Clara cell: progenitor for the bronchiolar epithelium. Int J Biochem Cell B 2010; 42:1-4.
66. Rock JR, Onaitis MW, Rawlins EL et al. Basal cells as stem cells of the mouse trachea and human airway epithelium. Proc Natl Acad Sci USA 2009; 106:12771-5.
67. Hong KU, Reynolds SD, Watkins S, Fuchs E, Stripp BR. Basal cells are a multipotent progenitor capable of renewing the bronchial epithelium. Am J Pathol 2004; 164:577-88.
68. Cozens AL, Yezzi MJ, Kunzelmann K et al. CFTR expression and chloride secretion in polarized immortal human bronchial epithelial cells. Am J Respir Cell Mol Biol 1994; 10:38-47.
69. Boublil L, Assemat E, Borot MC et al. Development of a repeated exposure protocol of human bronchial epithelium in vitro to study the long-term effects of atmospheric particles. Toxicol In Vitro 2013; 27:533-42.
70. Bruewer M, Luegering A, Kucharzik T et al. Proinflammatory cytokines disrupt epithelial barrier function by apoptosis-independent mechanisms. J Immunol 2003; 171:6164-72.
71. Sawada N, Murata M, Kikuchi K et al. Tight junctions and human diseases. Med Electron Microsc 2003; 36:147-56.
72. Furuse M, Hirase T, Itoh M, Nagafuchi A, Yonemura S, Tsukita S. Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol 1993; 123:1777-88.
73. Morita K, Furuse M, Fujimoto K, Tsukita S. Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands. Proc Natl Acad Sci USA 1999; 96:511-6.
74. Krause G, Winkler L, Mueller SL, Haseloff RF, Piontek J, Blasig IE. Structure and function of claudins. Biochim Biophys Acta 2008; 1778:631-45.
75. Fanning AS, Anderson JM. Zonula occludens-1 and-2 are cytosolic scaffolds that regulate the assembly of cellular junctions. Ann N Y Acad Sci 2009; 1165:113-20.
76. Fanning AS, Jameson BJ, Jesaitis LA, Anderson JM. The tight junction protein ZO-1 establishes a link between the transmembrane protein occludin and the actin cytoskeleton. J Biol Chem 1998; 273:29745-53.
77. Fanning AS, Van Itallie CM, Anderson JM. Zonula occludens-1 and-2 regulate apical cell structure and the zonula adherens cytoskeleton in polarized epithelia. Mol Biol Cell 2012; 23:577-90.
78. Steed E, Balda MS, Matter K. Dynamics and functions of tight junctions. Trends Cell Biol 2010; 20:142-9.
79. Van Itallie CM, Anderson JM. Claudins and epithelial paracellular transport. Annu Rev Physiol 2006; 68:403-29.
80. Van Itallie CM, Fanning AS, Anderson JM. Reversal of charge selectivity in cation or anion-selective epithelial lines by expression of different claudins. Am J Physiol-Renal 2003; 285:F1078-84.
81. Furuse M, Furuse K, Sasaki H, Tsukita S. Conversion of zonulae occludentes from tight to leaky strand type by introducing claudin-2 into Madin-Darby canine kidney I cells. J Cell Biol 2001; 153:263-72.
82. Amasheh S, Meiri N, Gitter AH et al. Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells. J Cell Sci 2002; 115:4969-76.
83. Van Itallie C, Rahner C, Anderson JM. Regulated expression of claudin-4 decreases paracellular conductance through a selective decrease in sodium permeability. J Clin Invest 2001; 107:1319-27.
84. Knust E, Bossinger O. Composition and formation of intercellular junctions in epithelial cells. Science 2002; 298:1955-9.
85. Baum B, Georgiou M. Dynamics of adherens junctions in epithelial establishment, maintenance, and remodeling. J Cell Biol 2011; 192:907-17.
86. Green KJ, Jones JC. Desmosomes and hemidesmosomes: structure and function of molecular components. FASEB J 1996; 10:871-81.
87. Barczyk M, Carracedo S, Gullberg D. Integrins. Cell Tissue Res 2010; 339:269-80.
88. Xiao C, Puddicombe SM, Field S et al. Defective epithelial barrier function in asthma. J Allergy Clin Immunol 2011; 128:549-56.
89. Hardyman MA, Wilkinson E, Martin E et al. TNF-alpha-mediated bronchial barrier disruption and regulation by src-family kinase activation. J Allergy Clin Immunol 2013; 132:665-75.e8.
90. Nicholas B, Skipp P, Mould R et al. Shotgun proteomic analysis of human-induced sputum. Proteomics 2006; 6:4390-401.
91. Williams OW, Sharafkhaneh A, Kim V, Dickey BF, Evans CM. Airway mucus - from production to secretion. Am J Respir Cell Mol Biol 2006; 34:527-36.
92. Cone RA. Barrier properties of mucus. Adv Drug Deliver Rev 2009; 61:75-85.
93. Lai SK, Wang YY, Hanes J. Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv Drug Deliver Rev 2009; 61:158-71.
94. Jachak A, Lai SK, Hida K et al. Transport of metal oxide nanoparticles and single-walled carbon nanotubes in human mucus. Nanotoxicology 2012; 6:614-22.
95. Thornton DJ, Rousseau K, McGuckin MA. Structure and function of the polymeric mucins in airways mucus. Annu Rev Physiol 2008; 70:459-86.
96. Evans CM, Kim K, Tuvim MJ, Dickey BF. Mucus hypersecretion in asthma: causes and effects. Curr Opin Pulm Med 2009; 15:4-11.
97. Kirkham S, Sheehan JK, Knight D, Richardson PS, Thornton DJ. Heterogeneity of airways mucus: variations in the amounts and glycoforms of the major oligomeric mucins MUC5AC and MUC5B. Biochem J 2002; 361:537-46.
98. Voynow JA, Gendler SJ, Rose MC. Regulation of mucin genes in chronic inflammatory airway diseases. Am J Respir Cell Mol Biol 2006; 34:661-5.
99. Rose MC, Voynow JA. Respiratory tract mucin genes and mucin glycoproteins in health and disease. Physiol Rev 2006; 86:245-78.
100. Kuperman DA, Huang XZ, Koth LL et al. Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma. Nat Med 2002; 8:885-9.
101. Park KS, Korfhagen TR, Bruno MD et al. SPDEF regulates goblet cell hyperplasia in the airway epithelium. J Clin Invest 2007; 117:978-88.
102. Chen G, Korfhagen TR, Xu Y et al. SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production. J Clin Invest 2009; 119:2914-24.
103. Song KS, Lee WJ, Chung KC et al. Interleukin-1 beta and tumor necrosis factor-alpha induce MUC5AC overexpression through a mechanism involving ERK/p38 mitogen-activated protein kinases-MSK1-CREB activation in human airway epithelial cells. J Biol Chem 2003; 278:23243-50.
104. Fujisawa T, Velichko S, Thai P, Hung LY, Huang F, Wu R. Regulation of airway MUC5AC expression by IL-1 beta and IL-17A; the NF-kappa B Paradigm. J Immunol 2009; 183:6236-43.
105. Shao MXG, Nakanaga T, Nadel JA. Cigarette smoke induces MUC5AC mucin overproduction via tumor necrosis factor-alpha-converting enzyme in human airway epithelial (NCI-H292) cells. Am J Physiol Lung Cell Mol Physiol 2004; 287:L420-7.
106. Takeyama K, Jung B, Shim JJ et al. Activation of epidermal growth factor receptors is responsible for mucin synthesis induced by cigarette smoke. Am J Physiol Lung Cell Mol Physiol 2001; 280:L165-72.
107. Parker D, Prince A. Innate immunity in the respiratory epithelium. Am J Respir Cell Mol Biol 2011; 45:189-201.
108. Rahman I, Biswas SK, Kode A. Oxidant and antioxidant balance in the airways and airway diseases. Eur J Pharmacol 2006; 533:222-39.
109. Kelly FJ. Oxidative stress: its role in air pollution and adverse health effects. Occup Environ Med 2003; 60:612-6.
110. Schwandner R, Dziarski R, Wesche H, Rothe M, Kirschning CJ. Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by toll-like receptor 2. J Biol Chem 1999; 274:17406-9.
111. Yoshimura A, Lien E, Ingalls RR, Tuomanen E, Dziarski R, Golenbock D. Cutting edge: recognition of gram-positive bacterial cell wall components by the innate immune system occurs via toll-like receptor 2. J Immunol 1999; 163:1-5.
112. Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. Recognition of double-stranded RNA and activation of NF-kappa B by Toll-like receptor 3. Nature 2001; 413:732-8.
113. Hoshino K, Takeuchi O, Kawai T et al. Cutting edge: toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J Immunol 1999; 162:3749-52.
114. Diebold SS, Kaisho T, Hemmi H, Akira S, Sousa CRE. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 2004; 303:1529-31.
115. Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol 2004; 4:499-511.
116. Yoneyama M, Kikuchi M, Natsukawa T et al. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol 2004; 5:730-7.
117. Adams MN, Ramachandran R, Yau MK et al. Structure, function and pathophysiology of protease activated receptors. Pharmacol Therapeut 2011; 130:248-82.
118. Cambi A, Koopman M, Figdor CG. How C-type lectins detect pathogens. Cell Microbiol 2005; 7:481-8.
119. Uehara A, Fujimoto Y, Fukase K, Takada H. Various human epithelial cells express functional Toll-like receptors, NOD1 and NOD2 to produce anti-microbial peptides, but not proinflammatory cytokines. Mol Immunol 2007; 44:3100-11.
120. Bianchi ME. DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukocyte Biol 2007; 81:1-5.
121. Kono H, Rock KL. How dying cells alert the immune system to danger. Nat Rev Immunol 2008; 8:279-89.
122. Willart MAM, Lambrecht BN. The danger within: endogenous danger signals, atopy and asthma. Clin Exp Allergy 2009; 39:12-9.
123. Liew FY, Pitman NI, McInnes IB. Disease-associated functions of IL-33: the new kid in the IL-1 family. Nat Rev Immunol 2010; 10:103-10.
124. Kouzaki H, Iijima K, Kobayashi T, O'Grady SM, Kita H. The danger signal, extracellular ATP, is a sensor for an airborne allergen and triggers IL-33 release and innate Th2-type responses. J Immunol 2011; 186:4375-87.
125. Idzko M, Hammad H, van Nimwegen M et al. Extracellular ATP triggers and maintains asthmatic airway inflammation by activating dendritic cells. Nat Med 2007; 13:913-9.
126. Aikawa T, Shimura S, Sasaki H, Ebina M, Takishima T. Marked goblet cell hyperplasia with mucus accumulation in the airways of patients who died of severe acute asthma attack. Chest 1992; 101:916-21.
127. Kuyper LM, Pare PD, Hogg JC et al. Characterization of airway plugging in fatal asthma. Am J Med 2003; 115:6-11.
128. Shimura S, Andoh Y, Haraguchi M, Shirato K. Continuity of airway goblet cells and intraluminal mucus in the airways of patients with bronchial asthma. Eur Respir J 1996; 9:1395-401.
129. Pohunek P, Warner JO, Turzikova J, Kudrmann J, Roche WR. Markers of eosinophilic inflammation and tissue re-modelling in children before clinically diagnosed bronchial asthma. Pediatr Allergy Immunol 2005; 16:43-51.
130. Saglani S, Payne DN, Zhu J et al. Early detection of airway wall remodeling and eosinophilic inflammation in preschool wheezers. Am J Respir Crit Care Med 2007; 176:858-64.
131. Fedorov IA, Wilson SJ, Davies DE, Holgate ST. Epithelial stress and structural remodelling in childhood asthma. Thorax 2005; 60:389-94.
132. Baraldo S, Turato G, Bazzan E et al. Noneosinophilic asthma in children: relation with airway remodelling. Eur Respir J 2011; 38:575-83.
133. Proud D, Leigh R. Epithelial cells and airway diseases. Immunol Rev 2011; 242:186-204.
134. Grainge CL, Lau LCK, Ward JA et al. Effect of bronchoconstriction on airway remodeling in asthma. N Engl J Med 2011; 364:2006-15.
135. Bucchieri F, Puddicombe SM, Lordan JL et al. Asthmatic bronchial epithelium is more susceptible to oxidant-induced apoptosis. Am J Respir Cell Mol Biol 2002; 27:179-85.
136. Leino MS, Loxham M, Blume C et al. Barrier disrupting effects of alternaria alternata extract on bronchial epithelium from asthmatic donors. PLoS ONE 2013; 8:e71278.
137. Hackett TL, Singhera GK, Shaheen F et al. Intrinsic phenotypic differences of asthmatic epithelium and its inflammatory responses to respiratory syncytial virus and air pollution. Am J Respir Cell Mol Biol 2011; 45:1090-100.
138. Wark PA, Johnston SL, Bucchieri F et al. Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus. J Exp Med 2005; 201:937-47.
139. Roth HM, Wadsworth SJ, Kahn M, Knight DA. The airway epithelium in asthma: developmental issues that scar the airways for life? Pulm Pharmacol Ther 2012; 25:420-6.
140. Davies DE. The role of the epithelium in airway remodeling in asthma. Proc Am Thorac Soc 2009; 6:678-82.
141. Wilson JW, Li X. The measurement of reticular basement membrane and submucosal collagen in the asthmatic airway. Clin Exp Allergy 1997; 27:363-71.
142. Araujo BB, Dolhnikoff M, Silva LFF et al. Extracellular matrix components and regulators in the airway smooth muscle in asthma. Eur Respir J 2008; 32:61-9.
143. Faux SP, Tai T, Thorne D, Xu Y, Breheny D, Gaca M. The role of oxidative stress in the biological responses of lung epithelial cells to cigarette smoke. Biomarkers 2009; 14(Suppl 1):90-6.
144. Li N, Xia T, Nel AE. The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles. Free Radic Biol Med 2008; 44:1689-99.
145. Nakayama Wong LS, Aung HH, Lame MW, Wegesser TC, Wilson DW. Fine particulate matter from urban ambient and wildfire sources from California's San Joaquin Valley initiate differential inflammatory, oxidative stress, and xenobiotic responses in human bronchial epithelial cells. Toxicol In Vitro 2011; 25:1895-905.
146. Jaspers I, Ciencewicki JM, Zhang W et al. Diesel exhaust enhances influenza virus infections in respiratory epithelial cells. Toxicol Sci 2005; 85:990-1002.
147. Hosakote YM, Liu T, Castro SM, Garofalo RP, Casola A. Respiratory syncytial virus induces oxidative stress by modulating antioxidant enzymes. Am J Respir Cell Mol Biol 2009; 41:348-57.
148. Papi A, Contoli M, Gasparini P et al. Role of xanthine oxidase activation and reduced glutathione depletion in rhinovirus induction of inflammation in respiratory epithelial cells. J Biol Chem 2008; 283:28595-606.
149. Fitzpatrick AM, Jones DP, Brown LA. Glutathione redox control of asthma: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal 2012; 17:375-408.
150. Piacentini S, Polimanti R, Simonelli I et al. Glutathione S-transferase polymorphisms, asthma susceptibility and confounding variables: a meta-analysis. Mol Biol Rep 2013; 40:3299-313.
151. Wu W, Peden DB, McConnell R, Fruin S, Diaz-Sanchez D. Glutathione-S-transferase M1 regulation of diesel exhaust particle-induced pro-inflammatory mediator expression in normal human bronchial epithelial cells. Part Fibre Toxicol 2012; 9:31.
152. Li N, Nel AE. Role of the Nrf2-mediated signaling pathway as a negative regulator of inflammation: implications for the impact of particulate pollutants on asthma. Antioxid Redox Signal 2006; 8:88-98.
153. Mercado N, Thimmulappa R, Thomas CM et al. Decreased histone deacetylase 2 impairs Nrf2 activation by oxidative stress. Biochem Biophys Res Commun 2011; 406:292-8.
154. Ito K, Hanazawa T, Tomita K, Barnes PJ, Adcock IM. Oxidative stress reduces histone deacetylase 2 activity and enhances IL-8 gene expression: role of tyrosine nitration. Biochem Biophys Res Commun 2004; 315:240-5.
155. Walter P, Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science 2011; 334:1081-6.
156. Garg AD, Kaczmarek A, Krysko O, Vandenabeele P, Krysko DV, Agostinis P. ER stress-induced inflammation: does it aid or impede disease progression? Trends Mol Med 2012; 18:589-98.
157. Tanjore H, Lawson WE, Blackwell TS. Endoplasmic reticulum stress as a pro-fibrotic stimulus. Biochim Biophys Acta 2013; 1832:940-7.
158. Wei J, Rahman S, Ayaub EA, Dickhout JG, Ask K. Protein misfolding and endoplasmic reticulum stress in chronic lung disease. Chest 2013; 143:1098-105.
159. Miller M, Tam AB, Cho JY et al. ORMDL3 is an inducible lung epithelial gene regulating metalloproteases, chemokines, OAS, and ATF6. Proc Natl Acad Sci USA 2012; 109:16648-53.
160. Schmidt LM, Belvisi MG, Bode KA et al. Bronchial epithelial cell-derived prostaglandin E2 dampens the reactivity of dendritic cells. J Immunol 2011; 186:2095-105.
161. Safholm J, Dahlen SE, Delin I et al. PGE2 maintains the tone of the guinea pig trachea through a balance between activation of contractile EP1 receptors and relaxant EP2 receptors. Br J Pharmacol 2013; 168:794-806.
162. Garrison G, Huang SK, Okunishi K et al. Reversal of myofibroblast differentiation by prostaglandin E2. Am J Respir Cell Mol Biol 2013; 48:550-8.
163. Sastre B, del Pozo V. Role of PGE2 in asthma and nonasthmatic eosinophilic bronchitis. Mediators Inflamm 2012; 2012:645383.
164. Romano M. Lipoxin and aspirin-triggered lipoxins. ScientificWorldJournal 2010; 10:1048-64.
165. Levy BD. Resolvin D1 and resolvin E1 promote the resolution of allergic airway inflammation via shared and distinct molecular counter-regulatory pathways. Front Immunol 2012; 3:390.
166. Planaguma A, Levy BD. Uncontrolled airway inflammation in lung disease represents a defect in counter-regulatory signaling. Future Lipidol 2008; 3:697-704.
167. Hallstrand TS, Lai Y, Henderson WR Jr, Altemeier WA, Gelb MH. Epithelial regulation of eicosanoid production in asthma. Pulm Pharmacol Ther 2012; 25:432-7.
168. Hallstrand TS, Henderson WR. An update on the role of leukotrienes in asthma. Curr Opin Allergy Clin Immunol 2010; 10:60-6.
169. Hallstrand TS, Wurfel MM, Lai Y et al. Transglutaminase 2, a novel regulator of eicosanoid production in asthma revealed by genome-wide expression profiling of distinct asthma phenotypes. PLoS ONE 2010; 5:e8583.
170. Lai Y, Oslund RC, Bollinger JG et al. Eosinophil cysteinyl leukotriene synthesis mediated by exogenous secreted phospholipase A2 group X. J Biol Chem 2010; 285:41491-500.
171. Bartemes KR, Kita H. Dynamic role of epithelium-derived cytokines in asthma. Clin Immunol 2012; 143:222-35.
172. Ingram JL, Kraft M. IL-13 in asthma and allergic disease: asthma phenotypes and targeted therapies. J Allergy Clin Immunol 2012; 130:829-42; quiz 43-4.
173. Maes T, Joos GF, Brusselle GG. Targeting interleukin-4 in asthma: lost in translation? Am J Respir Cell Mol Biol 2012; 47:261-70.
174. Swindle EJ, Collins JE, Davies DE. Breakdown in epithelial barrier function in patients with asthma: identification of novel therapeutic approaches. J Allergy Clin Immunol 2009; 124:23-34.
175. Blume C, Swindle EJ, Dennison P et al. Barrier responses of human bronchial epithelial cells to grass pollen exposure. Eur Respir J 2013; 42:87-97.
176. Coleman JM, Naik C, Holguin F et al. Epithelial eotaxin-2 and eotaxin-3 expression: relation to asthma severity, luminal eosinophilia and age at onset. Thorax 2012; 67:1061-6.
177. Uller L, Leino M, Bedke N et al. Double-stranded RNA induces disproportionate expression of thymic stromal lymphopoietin versus interferon-beta in bronchial epithelial cells from donors with asthma. Thorax 2010; 65:626-32.
178. Freishtat RJ, Watson AM, Benton AS et al. Asthmatic airway epithelium is intrinsically inflammatory and mitotically dyssynchronous. Am J Respir Cell Mol Biol 2011; 44:863-9.
179. Yang IV, Schwartz DA. Epigenetic mechanisms and the development of asthma. J Allergy Clin Immunol 2012; 130:1243-55.
180. Zijlstra GJ, Ten Hacken NH, Hoffmann RF, van Oosterhout AJ, Heijink IH. Interleukin-17A induces glucocorticoid insensitivity in human bronchial epithelial cells. Eur Respir J 2012; 39:439-45.
181. Li LB, Leung DY, Martin RJ, Goleva E. Inhibition of histone deacetylase 2 expression by elevated glucocorticoid receptor beta in steroid-resistant asthma. Am J Respir Crit Care Med 2010; 182:877-83.
182. Butler CA, McQuaid S, Taggart CC et al. Glucocorticoid receptor beta and histone deacetylase 1 and 2 expression in the airways of severe asthma. Thorax 2012; 67:392-8.
183. Baraldo S, Contoli M, Bazzan E et al. Deficient antiviral immune responses in childhood: distinct roles of atopy and asthma. J Allergy Clin Immunol 2012; 130:1307-14.
184. Contoli M, Message SD, Laza-Stanca V et al. Role of deficient type III interferon-lambda production in asthma exacerbations. Nat Med 2006; 12:1023-6.
185. Bochkov YA, Hanson KM, Keles S, Brockman-Schneider RA, Jarjour NN, Gern JE. Rhinovirus-induced modulation of gene expression in bronchial epithelial cells from subjects with asthma. Mucosal Immunol 2010; 3:69-80.
186. Lopez-Souza N, Favoreto S, Wong H et al. In vitro susceptibility to rhinovirus infection is greater for bronchial than for nasal airway epithelial cells in human subjects. J Allergy Clin Immunol 2009; 123:1384-90.
187. Schoggins JW, Rice CM. Interferon-stimulated genes and their antiviral effector functions. Curr Opin Virol 2011; 1:519-25.
188. Corne JM, Marshall C, Smith S et al. Frequency, severity, and duration of rhinovirus infections in asthmatic and non-asthmatic individuals: a longitudinal cohort study. Lancet 2002; 359:831-4.
189. Holtzman MJ. Asthma as a chronic disease of the innate and adaptive immune systems responding to viruses and allergens. J Clin Invest 2012; 122:2741-8.
190. Gavala ML, Bertics PJ, Gern JE. Rhinoviruses, allergic inflammation, and asthma. Immunol Rev 2011; 242:69-90.
191. Halwani R, Al-Muhsen S, Al-Jahdali H, Hamid Q. Role of transforming growth factor-beta in airway remodeling in asthma. Am J Respir Cell Mol Biol 2011; 44:127-33.
192. Tatler AL, Jenkins G. TGF-beta activation and lung fibrosis. Proc Am Thorac Soc 2012; 9:130-6.
193. Lopez-Guisa JM, Powers C, File D, Cochrane E, Jimenez N, Debley JS. Airway epithelial cells from asthmatic children differentially express proremodeling factors. J Allergy Clin Immunol 2012; 129:990-7.e6.
194. Boxall C, Holgate ST, Davies DE. The contribution of transforming growth factor-beta and epidermal growth factor signalling to airway remodelling in chronic asthma. Eur Respir J 2006; 27:208-29.
195. Doerner AM, Zuraw BL. TGF-beta1 induced epithelial to mesenchymal transition (EMT) in human bronchial epithelial cells is enhanced by IL-1beta but not abrogated by corticosteroids. Respir Res 2009; 10:100.
196. Bedke N, Sammut D, Green B et al. Transforming growth factor-beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response. PLoS ONE 2012; 7:e44580.
197. Skevaki CL, Psarras S, Volonaki E et al. Rhinovirus-induced basic fibroblast growth factor release mediates airway remodeling features. Clin Transl Allergy 2012; 2:14.
198. Leigh R, Oyelusi W, Wiehler S et al. Human rhinovirus infection enhances airway epithelial cell production of growth factors involved in airway remodeling. J Allergy Clin Immunol 2008; 121:1238-45.
199. Meyer N, Akdis CA. Vascular endothelial growth factor as a key inducer of angiogenesis in the asthmatic airways. Curr Allergy Asthma Rep 2013; 13:1-9.
200. Burgel PR, Nadel JA. Epidermal growth factor receptor-mediated innate immune responses and their roles in airway diseases. Eur Respir J 2008; 32:1068-81.
201. Royce SG, Cheng V, Samuel CS, Tang ML. The regulation of fibrosis in airway remodeling in asthma. Mol Cell Endocrinol 2012; 351:167-75.
202. Loffek S, Schilling O, Franzke CW. Series "matrix metalloproteinases in lung health and disease": biological role of matrix metalloproteinases: a critical balance. Eur Respir J 2011; 38:191-208.
203. Tacon CE, Wiehler S, Holden NS, Newton R, Proud D, Leigh R. Human rhinovirus infection up-regulates MMP-9 production in airway epithelial cells via NF-{kappa}B. Am J Respir Cell Mol Biol 2010; 43:201-9.
204. Sidhu SS, Yuan S, Innes AL et al. Roles of epithelial cell-derived periostin in TGF-beta activation, collagen production, and collagen gel elasticity in asthma. Proc Natl Acad Sci USA 2010; 107:14170-5.
205. Waldeck B. β-adrenoceptor agonists and asthma - 100 years of development. Eur J Pharmacol 2002; 445:1-12.
206. Barnes PJ. Efficacy of inhaled corticosteroids in asthma. J Allergy Clin Immunol 1998; 102:531-8.
207. Bousquet J, Cabrera P, Berkman N et al. The effect of treatment with omalizumab, an anti-IgE antibody, on asthma exacerbations and emergency medical visits in patients with severe persistent asthma. Allergy 2005; 60:302-8.
208. Walker S, Monteil M, Phelan K, Lasserson TJ, Walters EH. Anti-IgE for chronic asthma in adults and children. Cochrane Database Syst Rev 2006: (2):CD003559.
209. Holgate ST. Trials and tribulations in identifying new biologic treatments for asthma. Trends Immunol 2012; 33:238-46.
210. Bates JHT, Rincon M, Irvin CG. Animal models of asthma. Am J Physiol Lung Cell Mol Physiol 2009; 297:L401-10.
211. Zosky GR, Sly PD. Animal models of asthma. Clin Exp Allergy 2007; 37:973-88.
212. Blume C, Davies DE. In vitro and ex vivo models of human asthma. Eur J Pharm Biopharm 2013; 84:394-400.
213. Allan K, Devereux G. Diet and asthma: nutrition implications from prevention to treatment. J Am Diet Assoc 2011; 111:258-68.
214. He X, Wang L, Szklarz G, Bi Y, Ma Q. Resveratrol inhibits paraquat-induced oxidative stress and fibrogenic response by activating the nuclear factor erythroid 2-related factor 2 pathway. J Pharmacol Exp Ther 2012; 342:81-90.
215. Zhang HQ, Shih A, Rinna A, Forman HJ. Exacerbation of tobacco smoke mediated apoptosis by resveratrol: an unexpected consequence of its antioxidant action. Int J Biochem Cell B 2011; 43:1059-64.
216. Kode A, Rajendrasozhan S, Caito S, Yang SR, Megson IL, Rahman I. Resveratrol induces glutathione synthesis by activation of Nrf2 and protects against cigarette smoke-mediated oxidative stress in human lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 2008; 294:L478-88.
217. Hofmann B, Steinhilber D. 5-Lipoxygenase inhibitors: a review of recent patents (2010-2012). Expert Opin Ther Pat 2013; 23:895-909.
218. Malhotra S, Deshmukh SS, Dastidar SG. COX inhibitors for airway inflammation. Expert Opin Ther Targets 2012; 16:195-207.
219. Benyahia C, Gomez I, Kanyinda L et al. PGE(2) receptor (EP(4)) agonists: potent dilators of human bronchi and future asthma therapy? Pulm Pharmacol Ther 2012; 25:115-8.
220. Hisada T, Ishizuka T, Aoki H, Mori M. Resolvin E1 as a novel agent for the treatment of asthma. Expert Opin Ther Targets 2009; 13:513-22.
221. Lee CH. Resolvins as new fascinating drug candidates for inflammatory diseases. Arch Pharmacal Res 2012; 35:3-7.
222. Grumbach Y, Quynh NV, Chiron R, Urbach V. LXA4 stimulates ZO-1 expression and transepithelial electrical resistance in human airway epithelial (16HBE14o-) cells. Am J Physiol Lung Cell Mol Physiol 2009; 296:L101-8.
223. Corren J, Lemanske RF, Hanania NA et al. Lebrikizumab treatment in adults with asthma. N Engl J Med 2011; 365:1088-98.
224. 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 alpha antagonist. J Allergy Clin Immunol 2012; 130:516-22.e4.
225. Wenzel S, Ford L, Pearlman D et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med 2013; 368:2455-66.
226. Liu Y, Zhang S, Li DW, Jiang SJ. Efficacy of anti-interleukin-5 therapy with mepolizumab in patients with asthma: a meta-analysis of randomized placebo-controlled trials. PLoS ONE 2013; 8:e59872.
227. LaFemina MJ, Rokkam D, Chandrasena A et al. Keratinocyte growth factor enhances barrier function without altering claudin expression in primary alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol 2010; 299:L724-34.
228. Cakebread JA, Xu Y, Grainge C et al. Exogenous IFN-beta has antiviral and anti-inflammatory properties in primary bronchial epithelial cells from asthmatic subjects exposed to rhinovirus. J Allergy Clin Immunol 2011; 127:1148-54.e9.