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The Role and Immunobiology of Eosinophils in the Respiratory System: a Comprehensive Review

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Abstract

The eosinophil is a fully delineated granulocyte that disseminates throughout the bloodstream to end-organs after complete maturation in the bone marrow. While the presence of eosinophils is not uncommon even in healthy individuals, these granulocytes play a central role in inflammation and allergic processes. Normally appearing in smaller numbers, higher levels of eosinophils in the peripheral blood or certain tissues typically signal a pathologic process. Eosinophils confer a beneficial effect on the host by enhancing immunity against molds and viruses. However, tissue-specific elevation of eosinophils, particularly in the respiratory system, can cause a variety of short-term symptoms and may lead to long-term sequelae. Eosinophils often play a role in more commonly encountered disease processes, such as asthma and allergic responses in the upper respiratory tract. They are also integral in the pathology of less common diseases including eosinophilic pneumonia, allergic bronchopulmonary aspergillosis, hypersensitivity pneumonitis, and drug reaction with eosinophilia and systemic symptoms. They can be seen in neoplastic disorders or occupational exposures as well. The involvement of eosinophils in pulmonary disease processes can affect the method of diagnosis and the selection of treatment modalities. By analyzing the complex interaction between the eosinophil and its environment, which includes signaling molecules and tissues, different therapies have been discovered and created in order to target disease processes at a cellular level. Innovative treatments such as mepolizumab and benralizumab will be discussed. The purpose of this article is to further explore the topic of eosinophilic presence, activity, and pathology in the respiratory tract, as well as discuss current and future treatment options through a detailed literature review.

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References

  1. Wardlaw AJ, Brightling C, Green R, Woltmann G, Pavord I (2000) Eosinophils in asthma and other allergic diseases. Br Med Bull 56:985–1003

    Article  CAS  PubMed  Google Scholar 

  2. Scott KA, Wardlaw AJ (2006) Eosinophilic airway disorders. Semin Respir Crit Care Med 27:128–133

    Article  PubMed  Google Scholar 

  3. Adkinson NF, Bochner BS, Busse WW et al (2009) Middleton’s allergy: principles and practice, 7th edn. Mosby/Elsevier, Philadelphia

  4. Adkinson NF, Bochner BS, Burks AW et al (2014) Middleton’s allergy: principles and practice, 8th edn. Elsevier/Saunders, Philadelphia

  5. Stone KD, Prussin C, Metcalfe DD (2010) IgE, mast cells, basophils, and eosinophils. J Allergy Clin Immunol 125:S73–S80

    Article  PubMed  PubMed Central  Google Scholar 

  6. Percopo CM, Dyer KD, Ochkur SI et al (2014) Activated mouse eosinophils protect against lethal respiratory virus infection. Blood 123:743–752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lilly LM, Scopel M, Nelson MP, Burg AR, Dunaway CW, Steele C (2014) Eosinophil deficiency compromises lung defense against Aspergillus fumigatus. Infect Immun 82:1315–1325

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Wechsler ME (2007) Pulmonary eosinophilic syndromes. Immunol Allergy Clin N Am 27:477–492

    Article  Google Scholar 

  9. Cottin V, Cordier JF (2012) Eosinophilic lung diseases. Immunol Allergy Clin N Am 32:557–586

    Article  Google Scholar 

  10. Jeong YJ, Kim KI, Seo IJ et al (2007) Eosinophilic lung diseases: a clinical, radiologic, and pathologic overview. Radiographics Rev Publ Radiol Soc North Am Inc 27:617–637, discussion 637-619

    Google Scholar 

  11. Ying S, Meng Q, Zeibecoglou K et al (1999) Eosinophil chemotactic chemokines (eotaxin, eotaxin-2, RANTES, monocyte chemoattractant protein-3 (MCP-3), and MCP-4), and C-C chemokine receptor 3 expression in bronchial biopsies from atopic and nonatopic (Intrinsic) asthmatics. J Immunol 163:6321–6329

    CAS  PubMed  Google Scholar 

  12. Peterson MW, Monick M, Hunninghake GW (1987) Prognostic role of eosinophils in pulmonary fibrosis. Chest 92:51–56

    Article  CAS  PubMed  Google Scholar 

  13. Henderson WR, Chi EY, Klebanoff SJ (1980) Eosinophil peroxidase-induced mast cell secretion. J Exp Med 152:265–279

    Article  CAS  PubMed  Google Scholar 

  14. Dechatelet LR, Migler RA, Shirley PS, Bass DA, McCall CE (1978) Enzymes of oxidative metabolism in the human eosinophil. Proceedings of the Society for Experimental Biology and Medicine. Soc Exp Biol Med 158:537–541

    Article  CAS  Google Scholar 

  15. Rudd RM, Haslam PL, Turner-Warwick M (1981) Cryptogenic fibrosing alveolitis. Relationships of pulmonary physiology and bronchoalveolar lavage to response to treatment and prognosis. Am Rev Respir Dis 124:1–8

    CAS  PubMed  Google Scholar 

  16. Frigas E, Loegering DA, Gleich GJ (1980) Cytotoxic effects of the guinea pig eosinophil major basic protein on tracheal epithelium. Lab Investig J Tech Methods Pathol 42:35–43

    CAS  Google Scholar 

  17. Davis WB, Fells GA, Sun XH, Gadek JE, Venet A, Crystal RG (1984) Eosinophil-mediated injury to lung parenchymal cells and interstitial matrix. A possible role for eosinophils in chronic inflammatory disorders of the lower respiratory tract. J Clin Investig 74:269–278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Weller PF (2014) Approach to the patient with unexplained eosinophilia

    Google Scholar 

  19. Daimon T, Johkoh T, Sumikawa H et al (2008) Acute eosinophilic pneumonia: thin-section CT findings in 29 patients. Eur J Radiol 65:462–467

    Article  PubMed  Google Scholar 

  20. Sohn JW (2013) Acute eosinophilic pneumonia. Tuberc Respir Dis 74:51–55

    Article  Google Scholar 

  21. Rom WN, Weiden M, Garcia R et al (2002) Acute eosinophilic pneumonia in a New York City firefighter exposed to World Trade Center dust. Am J Respir Crit Care Med 166:797–800

    Article  PubMed  Google Scholar 

  22. Philit F, Etienne-Mastroianni B, Parrot A, Guerin C, Robert D, Cordier JF (2002) Idiopathic acute eosinophilic pneumonia: a study of 22 patients. Am J Respir Crit Care Med 166:1235–1239

    Article  PubMed  Google Scholar 

  23. Rose DM, Hrncir DE (2013) Primary eosinophilic lung diseases. Allergy Asthma Proc Off J Reg State Allergy Soc 34:19–25

    Article  CAS  Google Scholar 

  24. Janz DR, O’Neal HR Jr, Ely EW (2009) Acute eosinophilic pneumonia: a case report and review of the literature. Crit Care Med 37:1470–1474

    Article  PubMed  Google Scholar 

  25. Cottin V, Cordier JF (2005) Eosinophilic pneumonias. Allergy 60:841–857

    Article  CAS  PubMed  Google Scholar 

  26. Carrington CB, Addington WW, Goff AM et al (1969) Chronic eosinophilic pneumonia. N Engl J Med 280:787–798

    Article  CAS  PubMed  Google Scholar 

  27. Ge Y, Han X, Liu X (2013) Chronic eosinophilic pneumonia: a case report and review of the literature. Open J Internal Med 3:121–125

    Article  Google Scholar 

  28. Akuthota P, Weller PF (2012) Eosinophilic pneumonias. Clin Microbiol Rev 25:649–660

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Okubo Y, Horie S, Hachiya T et al (1998) Predominant implication of IL-5 in acute eosinophilic pneumonia: comparison with chronic eosinophilic pneumonia. Int Arch Allergy Immunol 116:76–80

    Article  CAS  PubMed  Google Scholar 

  30. Jhun BW, Kim SJ, Kim K, Lee JE, Hong DJ (2014) Clinical implications of correlation between peripheral eosinophil count and serum levels of IL-5 and tryptase in acute eosinophilic pneumonia. Respir Med

  31. Obayashi Y, Yamadori I, Fujita J, Yoshinouchi T, Ueda N, Takahara J (1997) The role of neutrophils in the pathogenesis of idiopathic pulmonary fibrosis. Chest 112:1338–1343

    Article  CAS  PubMed  Google Scholar 

  32. Prasad R, Gupta N, Singh A, Gupta P (2015) Diagnosis of idiopathic pulmonary fibrosis: current issues. Intractable Rare Diseases Res 4:65–69

    Article  Google Scholar 

  33. Iwai K, Mori T, Yamada N, Yamaguchi M, Hosoda Y (1994) Idiopathic pulmonary fibrosis. Epidemiologic approaches to occupational exposure. Am J Respir Crit Care Med 150:670–675

    Article  CAS  PubMed  Google Scholar 

  34. Raghu G, Weycker D, Edelsberg J, Bradford WZ, Oster G (2006) Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 174:810–816

    Article  PubMed  Google Scholar 

  35. Kroegel C, Foerster M, Grahmann PR, Braun R (1998) Eosinophil priming and migration in idiopathic pulmonary fibrosis. Eur Respir J 11:999–1001

    Article  CAS  PubMed  Google Scholar 

  36. Gioffredi A, Maritati F, Oliva E, Buzio C (2014) Eosinophilic granulomatosis with polyangiitis: an overview. Front Immunol 5:549

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Klion A (2009) Hypereosinophilic syndrome: current approach to diagnosis and treatment. Annu Rev Med 60:293–306

    Article  CAS  PubMed  Google Scholar 

  38. Ogbogu PU, Bochner BS, Butterfield JH et al (2009), Hypereosinophilic syndromes: a multicenter, retrospective analysis of clinical characteristics and response to therapy. J Allergy Clin Immunol. 124, 1319-1325

  39. Fernandez Perez ER, Olson AL, Frankel SK (2011) Eosinophilic lung diseases. Med Clin North Am 95:1163–1187

    Article  PubMed  Google Scholar 

  40. Mullarkey MF, Hill JS, Webb DR (1980) Allergic and nonallergic rhinitis: their characterization with attention to the meaning of nasal eosinophilia. J Allergy Clin Immunol 65:122–126

    Article  CAS  PubMed  Google Scholar 

  41. Bachert C (2004) Persistent rhinitis—allergic or nonallergic? Allergy 59(Suppl 76):11–15, discussion 15

    Article  PubMed  Google Scholar 

  42. Moneret-Vautrin DA, Hsieh V, Wayoff M, Guyot JL, Mouton C, Maria Y (1990) Nonallergic rhinitis with eosinophilia syndrome a precursor of the triad: nasal polyposis, intrinsic asthma, and intolerance to aspirin. Annals of allergy 64:513–518

    CAS  PubMed  Google Scholar 

  43. Leone C, Teodoro C, Pelucchi A et al (1997) Bronchial responsiveness and airway inflammation in patients with nonallergic rhinitis with eosinophilia syndrome. J Allergy Clin Immunol 100:775–780

    Article  CAS  PubMed  Google Scholar 

  44. Ellis AK, Keith PK (2006) Nonallergic rhinitis with eosinophilia syndrome. Current Allergy Asthma Rep 6:215–220

    Article  Google Scholar 

  45. Fang CH, Mady LJ, Mirani NM, Baredes S, Eloy JA (2014) Sinonasal eosinophilic angiocentric fibrosis: a systematic review. Int Forum Allergy Rhinology 4:745–752

    Article  Google Scholar 

  46. Nguyen DB, Alex JC, Calhoun B (2004) Eosinophilic angiocentric fibrosis in a patient with nasal obstruction. Ear Nose Throat J 83:183–184, 186

    PubMed  Google Scholar 

  47. Onder S, Sungur A (2004) Eosinophilic angiocentric fibrosis: an unusual entity of the sinonasal tract. Arch Pathol Lab Med 128:90–91

    PubMed  Google Scholar 

  48. Jain R, Robblee JV, O’Sullivan-Mejia E et al (2008) Sinonasal eosinophilic angiocentric fibrosis: a report of four cases and review of literature. Head Neck Pathol 2:309–315

    Article  PubMed  PubMed Central  Google Scholar 

  49. Lotvall J, Akdis CA, Bacharier LB et al (2011) Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol 127:355–360

    Article  PubMed  Google Scholar 

  50. Lemanske RF Jr, Busse WW (2010) Asthma: clinical expression and molecular mechanisms. J Allergy Clin Immunol 125:S95–S102

    Article  PubMed  PubMed Central  Google Scholar 

  51. National Asthma E, Prevention P (2007) Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Summary Report 2007. J Allergy Clin Immunol 120:S94–S138

    Article  Google Scholar 

  52. Keglowich L, Roth M, Philippova M et al (2013) Bronchial Smooth muscle cells of asthmatics promote angiogenesis through elevated secretion of CXC-Chemokines (ENA-78, GRO-alpha, and IL-8). PLoS One 8, e81494

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Agache I, Akdis C, Jutel M, Virchow JC (2012) Untangling asthma phenotypes and endotypes. Allergy 67:835–846

    Article  CAS  PubMed  Google Scholar 

  54. Miranda C, Busacker A, Balzar S, Trudeau J, Wenzel SE (2004) Distinguishing severe asthma phenotypes: role of age at onset and eosinophilic inflammation. J Allergy Clin Immunol 113:101–108

    Article  PubMed  Google Scholar 

  55. Haldar P, Pavord ID, Shaw DE et al (2008) Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med 178:218–224

    Article  PubMed  PubMed Central  Google Scholar 

  56. Green RH, Brightling CE, McKenna S et al (2002) Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet 360:1715–1721

    Article  PubMed  Google Scholar 

  57. Al-Samri MT, Benedetti A, Prefontaine D et al (2010) Variability of sputum inflammatory cells in asthmatic patients receiving corticosteroid therapy: A prospective study using multiple samples. J Allergy Clin Immunol 125(1161–1163), e1164

    Google Scholar 

  58. Wang F, He XY, Baines KJ et al (2011) Different inflammatory phenotypes in adults and children with acute asthma. Eur Respir J 38:567–574

    Article  CAS  PubMed  Google Scholar 

  59. Walford HH, Doherty TA (2014) Diagnosis and management of eosinophilic asthma: a US perspective. J Asthma Allergy 7:53–65

    PubMed  PubMed Central  Google Scholar 

  60. Yoo Y (2013) Phenotypes and endotypes of severe asthma in children. Korean J Pediatr 56:191–195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Campo P, Rodriguez F, Sanchez-Garcia S et al (2013) Phenotypes and endotypes of uncontrolled severe asthma: new treatments. J Investig Allergol Clin Immunol 23:76–88, quiz 71 p follow 88

    CAS  PubMed  Google Scholar 

  62. Xie M, Wenzel SE (2013) A global perspective in asthma: from phenotype to endotype. Chin Med J 126:166–174

    PubMed  Google Scholar 

  63. Wenzel S (2012) Severe asthma: from characteristics to phenotypes to endotypes. Clin Exp Allergy J Br Soc Allergy Clin Immunol 42:650–658

    Article  CAS  Google Scholar 

  64. Hamelmann E, Gelfand EW (2001) IL-5-induced airway eosinophilia—the key to asthma? Immunol Rev 179:182–191

    Article  CAS  PubMed  Google Scholar 

  65. Pace E, Ferraro M, Siena L et al (2008) Cigarette smoke increases Toll-like receptor 4 and modifies lipopolysaccharide-mediated responses in airway epithelial cells. Immunology 124:401–411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Monick MM, Yarovinsky TO, Powers LS et al (2003) Respiratory syncytial virus up-regulates TLR4 and sensitizes airway epithelial cells to endotoxin. J Biol Chem 278:53035–53044

    Article  CAS  PubMed  Google Scholar 

  67. Galowitz S, Chang C (2014) Immunobiology of Critical Pediatric Asthma. Clin Rev Allergy Immunol

  68. Muzio M, Polentarutti N, Bosisio D, Manoj Kumar PP, Mantovani A (2000) Toll-like receptor family and signalling pathway. Biochem Soc Trans 28:563–566

    Article  CAS  PubMed  Google Scholar 

  69. Dabbagh K, Dahl ME, Stepick-Biek P, Lewis DB (2002) Toll-like receptor 4 is required for optimal development of Th2 immune responses: role of dendritic cells. J Immunol 168:4524–4530

    Article  CAS  PubMed  Google Scholar 

  70. Saenz SA, Siracusa MC, Perrigoue JG et al (2010) IL25 elicits a multipotent progenitor cell population that promotes T(H)2 cytokine responses. Nature 464:1362–1366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Neill DR, Wong SH, Bellosi A et al (2010) Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature 464:1367–1370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Fort MM, Cheung J, Yen D et al (2001) IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo. Immunity 15:985–995

    Article  CAS  PubMed  Google Scholar 

  73. Schneider E, Petit-Bertron AF, Bricard R et al (2009) IL-33 activates unprimed murine basophils directly in vitro and induces their in vivo expansion indirectly by promoting hematopoietic growth factor production. J Immunol 183:3591–3597

    Article  CAS  PubMed  Google Scholar 

  74. Zhou B, Comeau MR, De Smedt T et al (2005) Thymic stromal lymphopoietin as a key initiator of allergic airway inflammation in mice. Nat Immunol 6:1047–1053

    Article  CAS  PubMed  Google Scholar 

  75. Fang C, Siew LQ, Corrigan CJ, Ying S (2010) The role of thymic stromal lymphopoietin in allergic inflammation and chronic obstructive pulmonary disease. Arch Immunol Ther Exp 58:81–90

    Article  CAS  Google Scholar 

  76. Trivedi SG, Lloyd CM (2007) Eosinophils in the pathogenesis of allergic airways disease. Cell Mol Life Sci CMLS 64:1269–1289

    Article  CAS  PubMed  Google Scholar 

  77. Jeffery PK (2000) Comparison of the structural and inflammatory features of COPD and asthma. Giles F Filley Lect Chest 117:251S–260S

    CAS  Google Scholar 

  78. Qiu Y, Zhu J, Bandi V, Guntupalli KK, Jeffery PK (2007) Bronchial mucosal inflammation and upregulation of CXC chemoattractants and receptors in severe exacerbations of asthma. Thorax 62:475–482

    Article  PubMed  PubMed Central  Google Scholar 

  79. Fahy JV, Kim KW, Liu J, Boushey HA (1995) Prominent neutrophilic inflammation in sputum from subjects with asthma exacerbation. J Allergy Clin Immunol 95:843–852

    Article  CAS  PubMed  Google Scholar 

  80. Sur S, Crotty TB, Kephart GM et al (1993) Sudden-onset fatal asthma. A distinct entity with few eosinophils and relatively more neutrophils in the airway submucosa? Am Rev Respir Dis 148:713–719

    Article  CAS  PubMed  Google Scholar 

  81. Qiu Y, Zhu J, Bandi V et al (2003) Biopsy neutrophilia, neutrophil chemokine and receptor gene expression in severe exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 168:968–975

    Article  PubMed  Google Scholar 

  82. Imaizumi T, Albertine KH, Jicha DL, McIntyre TM, Prescott SM, Zimmerman GA (1997) Human endothelial cells synthesize ENA-78: relationship to IL-8 and to signaling of PMN adhesion. Am J Respir Cell Mol Biol 17:181–192

    Article  CAS  PubMed  Google Scholar 

  83. Wuyts A, Proost P, Lenaerts JP, Ben-Baruch A, Van Damme J, Wang JM (1998) Differential usage of the CXC chemokine receptors 1 and 2 by interleukin-8, granulocyte chemotactic protein-2 and epithelial-cell-derived neutrophil attractant-78. Eur J Biochem FEBS 255:67–73

    Article  CAS  Google Scholar 

  84. Moore WC, Meyers DA, Wenzel SE et al (2010) Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med 181:315–323

    Article  PubMed  PubMed Central  Google Scholar 

  85. Fitzpatrick AM, Teague WG, Meyers DA et al (2011) Heterogeneity of severe asthma in childhood: confirmation by cluster analysis of children in the national institutes of health/national heart, lung, and blood institute severe asthma research program. J Allergy Clin Immunol 127:382–389, e381-313

    Article  PubMed  PubMed Central  Google Scholar 

  86. Jarjour NN, Erzurum SC, Bleecker ER et al (2012) Severe asthma: lessons learned from the national heart, lung, and blood institute severe asthma research program. Am J Respir Crit Care Med 185:356–362

    Article  PubMed  PubMed Central  Google Scholar 

  87. Bossley CJ, Fleming L, Gupta A et al (2012) Pediatric severe asthma is characterized by eosinophilia and remodeling without T(H)2 cytokines. J Allergy Clin Immunol 129:974–982, e913

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Silkoff PE, Lent AM, Busacker AA et al (2005) Exhaled nitric oxide identifies the persistent eosinophilic phenotype in severe refractory asthma. J Allergy Clin Immunol 116:1249–1255

    Article  CAS  PubMed  Google Scholar 

  89. Saglani S, Lloyd CM (2014) Eosinophils in the pathogenesis of paediatric severe asthma. Curr Opin Allergy Clin Immunol 14:143–148

    Article  CAS  PubMed  Google Scholar 

  90. Lemiere C, Ernst P, Olivenstein R et al (2006) Airway inflammation assessed by invasive and noninvasive means in severe asthma: eosinophilic and noneosinophilic phenotypes. J Allergy Clin Immunol 118:1033–1039

    Article  PubMed  Google Scholar 

  91. Saglani S, Malmstrom K, Pelkonen AS et al (2005) Airway remodeling and inflammation in symptomatic infants with reversible airflow obstruction. Am J Respir Crit Care Med 171:722–727

    Article  PubMed  Google Scholar 

  92. Marguet C, Bocquel N, Benichou J et al (2008) Neutrophil but not eosinophil inflammation is related to the severity of a first acute epidemic bronchiolitis in young infants. Pediatr Allergy Immunol Off Publ Eur Soc Pediatr Allergy Immunol 19:157–165

    Article  Google Scholar 

  93. de Blic J, Tillie-Leblond I, Tonnel AB, Jaubert F, Scheinmann P, Gosset P (2004) Difficult asthma in children: an analysis of airway inflammation. J Allergy Clin Immunol 113:94–100

    Article  PubMed  Google Scholar 

  94. Arshad SH, Raza A, Lau L et al (2014) Pathophysiological characterization of asthma transitions across adolescence. Respir Res 15:153

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  96. Stern DA, Morgan WJ, Halonen M, Wright AL, Martinez FD (2008) Wheezing and bronchial hyper-responsiveness in early childhood as predictors of newly diagnosed asthma in early adulthood: a longitudinal birth-cohort study. Lancet 372:1058–1064

    Article  PubMed  PubMed Central  Google Scholar 

  97. Gibson PG, Simpson JL, Saltos N (2001) Heterogeneity of airway inflammation in persistent asthma : evidence of neutrophilic inflammation and increased sputum interleukin-8. Chest 119:1329–1336

    Article  CAS  PubMed  Google Scholar 

  98. Gibson PG (2009) Inflammatory phenotypes in adult asthma: clinical applications. Clin Respir J 3:198–206

    Article  PubMed  Google Scholar 

  99. Jenkins HA, Cherniack R, Szefler SJ, Covar R, Gelfand EW, Spahn JD (2003) A comparison of the clinical characteristics of children and adults with severe asthma. Chest 124:1318–1324

    Article  PubMed  Google Scholar 

  100. Nizankowska E, Soja J, Pinis G et al (1995) Treatment of steroid-dependent bronchial asthma with cyclosporin. Eur Respir J 8:1091–1099

    Article  CAS  PubMed  Google Scholar 

  101. Presta LG, Lahr SJ, Shields RL et al (1993) Humanization of an antibody directed against IgE. J Immunol 151:2623–2632

    CAS  PubMed  Google Scholar 

  102. Schulman ES (2001) Development of a monoclonal anti-immunoglobulin E antibody (omalizumab) for the treatment of allergic respiratory disorders. Am J Respir Crit Care Med 164:S6–S11

    Article  CAS  PubMed  Google Scholar 

  103. Erin EM, Leaker BR, Nicholson GC et al (2006) The effects of a monoclonal antibody directed against tumor necrosis factor-alpha in asthma. Am J Respir Crit Care Med 174:753–762

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  105. Simpson JL, Powell H, Boyle MJ, Scott RJ, Gibson PG (2008) Clarithromycin targets neutrophilic airway inflammation in refractory asthma. Am J Respir Crit Care Med 177:148–155

    Article  CAS  PubMed  Google Scholar 

  106. Ortega HG, Liu MC, Pavord ID et al (2014) Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med 371:1198–1207

    Article  PubMed  CAS  Google Scholar 

  107. Bel EH, Wenzel SE, Thompson PJ et al (2014) Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med 371:1189–1197

    Article  PubMed  CAS  Google Scholar 

  108. Laviolette M, Gossage DL, Gauvreau G et al (2013) Effects of benralizumab on airway eosinophils in asthmatic patients with sputum eosinophilia. J Allergy Clin Immunol 132(1086–1096), e1085

    Google Scholar 

  109. Castro M, Wenzel SE, Bleecker ER et al. (2014) Benralizumab, an anti-interleukin 5 receptor alpha monoclonal antibody, versus placebo for uncontrolled eosinophilic asthma: a phase 2b randomised dose-ranging study. Lancet Respir Med

  110. Fitzpatrick AM, Gaston BM, Erzurum SC, Teague WG, National Institutes of Health/National Heart and P. Blood Institute Severe Asthma Research (2006) Features of severe asthma in school-age children: atopy and increased exhaled nitric oxide. J Allergy Clin Immunol 118:1218–1225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Covar RA, Spahn JD, Martin RJ et al (2004) Safety and application of induced sputum analysis in childhood asthma. J Allergy Clin Immunol 114:575–582

    Article  PubMed  Google Scholar 

  112. Wedes SH, Wu W, Comhair SA et al (2011) Urinary bromotyrosine measures asthma control and predicts asthma exacerbations in children. J Pediatr 159(248–255), e241

    Google Scholar 

  113. Selman M (2004) Hypersensitivity pneumonitis: a multifaceted deceiving disorder. Clin Chest Med 25(531–547):vi

    Google Scholar 

  114. Lacasse Y, Cormier Y (2006) Hypersensitivity pneumonitis. Orphanet J Rare Dis 1:25

    Article  PubMed  PubMed Central  Google Scholar 

  115. Monkare S, Ikonen M, Haahtela T (1985) Radiologic findings in farmer’s lung. Prognosis Correlation Lung Funct Chest 87:460–466

    CAS  Google Scholar 

  116. Cormier Y, Belanger J, LeBlanc P, Laviolette M (1986) Bronchoalveolar lavage in farmers’ lung disease: diagnostic and physiological significance. Br J Ind Med 43:401–405

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Lacasse Y, Selman M, Costabel U et al (2003) Clinical diagnosis of hypersensitivity pneumonitis. Am J Respir Crit Care Med 168:952–958

    Article  PubMed  Google Scholar 

  118. Monkare S (1983) Influence of corticosteroid treatment on the course of farmer’s lung. Eur J Respir Dis 64:283–293

    CAS  PubMed  Google Scholar 

  119. Bochenek G, Nizankowska-Mogilnicka E (2013) Aspirin-exacerbated respiratory disease: clinical disease and diagnosis. Immunol Allergy Clin N Am 33:147–161

    Article  Google Scholar 

  120. Burnett T, Katial R, Alam R (2013) Mechanisms of aspirin desensitization. Immunol Allergy Clin N Am 33:223–236

    Article  Google Scholar 

  121. Choi JH, Kim MA, Park HS (2014) An update on the pathogenesis of the upper airways in aspirin-exacerbated respiratory disease. Curr Opin Allergy Clin Immunol 14:1–6

    Article  CAS  PubMed  Google Scholar 

  122. Saltzstein SL, Ackerman LV (1959) Lymphadenopathy induced by anticonvulsant drugs and mimicking clinically pathologically malignant lymphomas. Cancer 12:164–182

    Article  CAS  PubMed  Google Scholar 

  123. Camous X, Calbo S, Picard D, Musette P (2012) Drug Reaction with eosinophilia and systemic symptoms: an update on pathogenesis. Curr Opin Immunol 24:730–735

    Article  CAS  PubMed  Google Scholar 

  124. Bocquet H, Bagot M, Roujeau JC (1996) Drug-induced pseudolymphoma and drug hypersensitivity syndrome (Drug Rash with Eosinophilia and Systemic Symptoms: DRESS). Semin Cutaneous Med Surg 15:250–257

    Article  CAS  Google Scholar 

  125. Tetart F, Picard D, Janela B, Joly P, Musette P (2013) Prolonged Evolution of Drug Reaction With Eosinophilia and Systemic Symptoms: Clinical, Virologic, and Biological Features. JAMA Dermatol

  126. Peyriere H, Dereure O, Breton H et al (2006) Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: does a DRESS syndrome really exist? Br J Dermatology 155:422–428

    Article  CAS  Google Scholar 

  127. Favrolt N, Bonniaud P, Collet E et al (2007) Severe drug rash with eosinophilia and systemic symptoms after treatment with minocycline. Rev Mal Respir 24:892–895

    Article  CAS  PubMed  Google Scholar 

  128. Husain Z, Reddy BY, Schwartz RA (2013) DRESS syndrome: Part I. Clinical perspectives. J Am Acad Dermatol 68:693, e691-614; quiz 706-698

    Article  PubMed  CAS  Google Scholar 

  129. Kano Y, Shiohara T (2009) The variable clinical picture of drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms in relation to the eliciting drug. Immunol Allergy Clin N Am 29:481–501

    Article  Google Scholar 

  130. Tohyama M, Hashimoto K, Yasukawa M et al (2007) Association of human herpesvirus 6 reactivation with the flaring and severity of drug-induced hypersensitivity syndrome. Br J Dermatol 157:934–940

    Article  CAS  PubMed  Google Scholar 

  131. Heiner DC, Sears JW, Kniker WT (1962) Multiple precipitins to cow’s milk in chronic respiratory disease. A syndrome including poor growth, gastrointestinal symptoms, evidence of allergy, iron deficiency anemia, and pulmonary hemosiderosis. Am J Dis Child 103:634–654

    Article  CAS  PubMed  Google Scholar 

  132. Moissidis I, Chaidaroon D, Vichyanond P, Bahna SL (2005) Milk-induced pulmonary disease in infants (Heiner syndrome). Pediatric Allergy Immunol Off Publ Eur Soc Pediatr Allergy Immunol 16:545–552

    Article  Google Scholar 

  133. Tan J, Bernstein JA (2014) Occupational asthma: an overview. Curr Allergy Asthma Rep 14:431

    Article  PubMed  CAS  Google Scholar 

  134. Lummus ZL, Wisnewski AV, Bernstein DI (2011) Pathogenesis and disease mechanisms of occupational asthma. Immunol Allergy Clin N Am 31(699–716):vi

    Google Scholar 

  135. Malo JL, Vandenplas O (2011) Definitions and classification of work-related asthma. Immunol Allergy Clin N Am 31:645–662, v

    Article  Google Scholar 

  136. Enriquez A, Fernandez C, Jimenez A, Seoane E, Alcorta AR, Rodriguez J (2011) Occupational asthma induced by Mucor species contaminating esparto fibers. J Investig Allergol Clin Immunol 21:251–252

    CAS  PubMed  Google Scholar 

  137. Agarwal R, Chakrabarti A, Shah A et al (2013) Allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria. Clin Exp Allergy J Br Soc Allergy Clin Immunol 43:850–873

    Article  CAS  Google Scholar 

  138. Gibson PG (2006) Allergic bronchopulmonary aspergillosis. Semin Respir Crit Care Med 27:185–191

    Article  PubMed  Google Scholar 

  139. Wark PA, Hensley MJ, Saltos N et al (2003) Anti-inflammatory effect of itraconazole in stable allergic bronchopulmonary aspergillosis: a randomized controlled trial. J Allergy Clin Immunol 111:952–957

    Article  CAS  PubMed  Google Scholar 

  140. Moss RB (2012) The use of biological agents for the treatment of fungal asthma and allergic bronchopulmonary aspergillosis. Ann N Y Acad Sci 1272:49–57

    Article  CAS  PubMed  Google Scholar 

  141. Zirbes JM, Milla CE (2008) Steroid-sparing effect of omalizumab for allergic bronchopulmonary aspergillosis and cystic fibrosis. Pediatr Pulmonol 43:607–610

    Article  PubMed  Google Scholar 

  142. Gupta D (2011) Allergic Bronchopulmonary Aspergillosis (ABPA): Relevance of Absolute Eosinophil Count (AEC) in Peripheral Blood. Chest 140

  143. Denning DW, O’Driscoll BR, Hogaboam CM, Bowyer P, Niven RM (2006) The link between fungi and severe asthma: a summary of the evidence. Eur Respir J 27:615–626

    Article  CAS  PubMed  Google Scholar 

  144. Denning DW, O’Driscoll BR, Powell G et al (2009) Randomized controlled trial of oral antifungal treatment for severe asthma with fungal sensitization: The Fungal Asthma Sensitization Trial (FAST) study. Am J Respir Crit Care Med 179:11–18

    Article  CAS  PubMed  Google Scholar 

  145. Klion AD, Nutman TB (2004) The role of eosinophils in host defense against helminth parasites. J Allergy Clin Immunol 113:30–37

    Article  CAS  PubMed  Google Scholar 

  146. Craig JM, Scott AL (2014) Helminths in the lungs. Parasite Immunol 36:463–474

    Article  CAS  PubMed  Google Scholar 

  147. Keiser PB, Nutman TB (2004) Strongyloides stercoralis in the Immunocompromised Population. Clin Microbiol Rev 17:208–217

    Article  PubMed  PubMed Central  Google Scholar 

  148. Shin MH, Lee YA, Min DY (2009) Eosinophil-mediated tissue inflammatory responses in helminth infection. Korean J Parasitol 47(Suppl):S125–S131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Pandit R, Scholnik A, Wulfekuhler L, Dimitrov N (2007) Non-small-cell lung cancer associated with excessive eosinophilia and secretion of interleukin-5 as a paraneoplastic syndrome. Am J Hematol 82:234–237

    Article  CAS  PubMed  Google Scholar 

  150. Slungaard A, Ascensao J, Zanjani E, Jacob HS (1983) Pulmonary carcinoma with eosinophilia. Demonstration of a tumor-derived eosinophilopoietic factor. N Engl J Med 309:778–781

    Article  CAS  PubMed  Google Scholar 

  151. Wilson F, Tefferi A (2005) Acute lymphocytic leukemia with eosinophilia: two case reports and a literature review. Leukemia & Lymphoma 46:1045–1050

    Article  Google Scholar 

  152. Furuta K, Taki M, Murase H, Nakagawa A, Nishiyama H, Nohgawa M (2011) [A case of eosinophilic pneumonia which occurred after bone marrow transplantation for acute myeloid leukemia]. Journal of the. Jpn Respir Soc 49:20–24

  153. Trojan A, Meier R, Licht A, Taverna C (2002) Eosinophilic pneumonia after administration of fludarabine for the treatment of non-Hodgkin’s lymphoma. Ann Hematol 81:535–537

    Article  CAS  PubMed  Google Scholar 

  154. Verstraeten AS, De Weerdt A, van Den Eynden G, Van Marck E, Snoeckx A, Jorens PG (2011) Excessive eosinophilia as paraneoplastic syndrome in a patient with non-small-cell lung carcinoma: a case report and review of the literature. Acta Clin Belg 66:293–297

    CAS  PubMed  Google Scholar 

  155. Stevens DA, Moss RB, Kurup VP et al (2003) Allergic bronchopulmonary aspergillosis in cystic fibrosis--state of the art: cystic fibrosis foundation consensus conference. Clin Infect Dis Off Publ Infect Dis Soc Am 37(Suppl 3):S225–S264

    Article  Google Scholar 

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Authors and Affiliations

  1. Thomas Jefferson University, Philadelphia, PA, USA

    Stephanie S. Eng & Magee L. DeFelice

  2. Division of Allergy and Immunology, Nemours/AI duPont Hospital for Children, Wilmington, DE, USA

    Stephanie S. Eng & Magee L. DeFelice

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  1. Stephanie S. Eng
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Drs. Eng and DeFelice have disclosed no financial relationships relevant to this article. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product or device.

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Eng, S.S., DeFelice, M.L. The Role and Immunobiology of Eosinophils in the Respiratory System: a Comprehensive Review. Clinic Rev Allerg Immunol 50, 140–158 (2016). https://doi.org/10.1007/s12016-015-8526-3

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