Blood eosinophils as a marker of likely corticosteroid response in children with preschool wheeze: Time for an eosinophil guided clinical trial?

Clinical and Experimental Allergy

Volumn 45, Issue 9, 2015, Pages 1384-1395

  Gaillard, E A ^a   McNamara, P S ^b   Murray, C S ^c   Pavord, I D ^d   Shields, M D ^e  

^a UNIVERSITY OF LEICESTER   (United Kingdom)

^b UNIVERSITY OF LIVERPOOL   (United Kingdom)

^c MANCHESTER UNIVERSITY NHS FOUNDATION TRUST   (United Kingdom)

^d UNIVERSITY OF OXFORD   (United Kingdom)

^e QUEEN'S UNIVERSITY BELFAST   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CORTICOSTEROID; EOSINOPHIL CATIONIC PROTEIN; EOSINOPHIL PEROXIDASE; EOSINOPHIL PROTEIN X; INTERLEUKIN 13; INTERLEUKIN 4; INTERLEUKIN 5; LEUKOTRIENE RECEPTOR BLOCKING AGENT; MAJOR BASIC PROTEIN; MEPOLIZUMAB; BIOLOGICAL MARKER;

ALLERGIC ASTHMA; ASTHMA; BRONCHOSCOPY; CORTICOSTEROID THERAPY; CYTOKINE RELEASE; DISEASE SEVERITY; DRUG RESPONSE; EOSINOPHIL; EOSINOPHIL COUNT; EPIDEMIC; FORCED EXPIRATORY VOLUME; GROWTH RATE; HUMAN; PHENOTYPE; PRIORITY JOURNAL; REVIEW; TREATMENT RESPONSE; WHEEZING; ABNORMAL RESPIRATORY SOUND; ADULT; BLOOD; CLINICAL TRIAL (TOPIC); FEMALE; IMMUNOLOGY; INFANT; MALE; METABOLISM; PRESCHOOL CHILD;

ADRENAL CORTEX HORMONES; ADULT; BIOMARKERS; CHILD, PRESCHOOL; CLINICAL TRIALS AS TOPIC; EOSINOPHILS; FEMALE; HUMANS; INFANT; MALE; RESPIRATORY SOUNDS;

EID: 84939640508     PISSN: 09547894     EISSN: 13652222     Source Type: Journal    
DOI: 10.1111/cea.12535     Document Type: Review

References (132)

1. Lai CK, Beasley R, Crane J, Foliaki S, Shah J, Weiland S. Global variation in the prevalence and severity of asthma symptoms: phase three of the International Study of Asthma and Allergies in Childhood [ISAAC]. Thorax 2009; 64:476-83.
2. Spycher BD, Silverman M, Brooke AM, Minder CE, Kuehni CE. Distinguishing phenotypes of childhood wheeze and cough using latent class analysis. Eur Respir J 2008; 31:974-81.
3. Henderson J, Granell R, Heron J et al. Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airway responsiveness in mid-childhood. Thorax 2008; 63:974-80.
4. Ducharme FM, Tse SM, Chauhan B. Diagnosis, management, and prognosis of preschool wheeze. Lancet 2014; 383:1593-604.
5. Garner R, Kohen D. Changes in the prevalence of asthma among Canadian children. Health Rep 2008; 19:45-50.
6. Staley KG, Herzallah R, Pandya H, Humphreys E, Gaillard EA. A novel evaluation of the impact of severe allergic asthma in children: the family perspective. Eur Respir J 2010; 36(Suppl.): http://www.ers-education.org/home/browse-all-content.aspx?idParent=85423
7. Costa LD, Costa PS, Camargos PA. Exacerbation of asthma and airway infection: is the virus the villain? J Pediatr [Rio J] 2014; 90:542-55.
8. Rakes GP, Arruda E, Ingram JM et al. Rhinovirus and respiratory syncytial virus in wheezing children requiring emergency care. IgE and eosinophil analyses. Am J Respir Crit Care Med 1999; 159:785-90.
9. Jartti T, Kuusipalo H, Vuorinen T et al. Allergic sensitization is associated with rhinovirus-, but not other virus-, induced wheezing in children. Pediatr Allergy Immunol 2010; 21:1008-14.
10. Caliskan M, Bochkov YA, Kreiner-Moller E et al. Rhinovirus wheezing illness and genetic risk of childhood-onset asthma. N Engl J Med 2013; 368:1398-407.
11. Jackson DJ, Gangnon RE, Evans MD et al. Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children. Am J Respir Crit Care Med 2008; 178:667-72.
12. Midulla F, Nicolai A, Ferrara M et al. Recurrent wheezing 36 months after bronchiolitis is associated with rhinovirus infections and blood eosinophilia. Acta Paediatr 2014; 103:1094-9.
13. Brand PL, Caudri D, Eber E et al. Classification and pharmacological treatment of preschool wheezing: changes since 2008. Eur Respir J 2014; 43:1172-7.
14. Bush A, Grigg J, Saglani S. Managing wheeze in preschool children. BMJ 2014; 348:g15.
15. Schultz A, Devadason SG, Savenije OE, Sly PD, Le Souef PN, Brand PL. The transient value of classifying preschool wheeze into episodic viral wheeze and multiple trigger wheeze. Acta Paediatr 2010; 99:56-60.
16. Garcia-Marcos L, Martinez FD. Multitrigger versus episodic wheeze in toddlers: new phenotypes or severity markers? J Allergy Clin Immunol 2010; 126:489-90.
17. Castro-Rodriguez JA, Holberg CJ, Wright AL, Martinez FD. A clinical index to define risk of asthma in young children with recurrent wheezing. Am J Respir Crit Care Med 2000; 162:1403-6.
18. Pescatore AM, Dogaru CM, Duembgen L et al. A simple asthma prediction tool for preschool children with wheeze or cough. J Allergy Clin Immunol 2014; 133:111-8.
19. Guilbert TW, Mauger DT, Lemanske RF Jr. Childhood asthma-predictive phenotype. J Allergy Clin Immunol Pract 2014; 2:664-70.
20. Castro-Rodriguez JA, Rodrigo GJ. Efficacy of inhaled corticosteroids in infants and preschoolers with recurrent wheezing and asthma: a systematic review with meta-analysis. Pediatrics 2009; 123:e519-25.
21. Wilson N, Sloper K, Silverman M. Effect of continuous treatment with topical corticosteroid on episodic viral wheeze in preschool children. Arch Dis Child 1995; 72:317-20.
22. https://www.brit-thoracic.org.uk/document-library/clinical-information/asthma/btssign-asthma-guideline-2014/.
23. Panickar J, Lakhanpaul M, Lambert PC et al. Oral prednisolone for preschool children with acute virus-induced wheezing. N Engl J Med 2009; 360:329-38.
24. Beigelman A, King TS, Mauger D et al. Do oral corticosteroids reduce the severity of acute lower respiratory tract illnesses in preschool children with recurrent wheezing? J Allergy Clin Immunol 2013; 131:1518-25.
25. Vuillermin PJ, Robertson CF, Carlin JB, Brennan SL, Biscan MI, South M. Parent initiated prednisolone for acute asthma in children of school age: randomised controlled crossover trial. BMJ 2010; 340:c843.
26. Brand PL, Luz G-GM, Morison A, Vermeulen JH, Weber HC. Ciclesonide in wheezy preschool children with a positive asthma predictive index or atopy. Respir Med 2011; 105:1588-95.
27. Murray CS, Woodcock A, Langley SJ, Morris J, Custovic A. IFWIN study team. Secondary prevention of asthma by the use of Inhaled Fluticasone propionate in Wheezy INfants (IFWIN): double-blind, randomised, controlled study. Lancet 2006; 368:754-62.
28. Guilbert TW, Morgan WJ, Zeiger RS et al. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med 2006; 354:1985-97.
29. Guilbert TW, Morgan WJ, Krawiec M et al. The Prevention of Early Asthma in Kids study: design, rationale and methods for the Childhood Asthma Research and Education network. Control Clin Trials 2004; 25:286-310.
30. Kupczyk M, Haque S, Middelveld RJ, Dahlen B, Dahlen SE. BIOAIR Investigators. Phenotypic predictors of response to oral glucocorticosteroids in severe asthma. Respir Med 2013; 107:1521-30.
31. Ulrik CS. Peripheral eosinophil counts as a marker of disease activity in intrinsic and extrinsic asthma. Clin Exp Allergy 1995; 25:820-7.
32. Grol MH, Postma DS, Vonk JM et al. Risk factors from childhood to adulthood for bronchial responsiveness at age 32-42 yr. Am J Respir Crit Care Med 1999; 160:150-6.
33. Wills-Karp M. Immunologic basis of antigen-induced airway hyperresponsiveness. Annu Rev Immunol 1999; 17:255-81.
34. Foster PS, Hogan SP, Ramsay AJ, Matthaei KI, Young IG. Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model. J Exp Med 1996; 183:195-201.
35. O'Byrne PM, Inman MD, Parameswaran K. The trials and tribulations of IL-5, eosinophils, and allergic asthma. J Allergy Clin Immunol 2001; 108:503-8.
36. Collins PD, Marleau S, Griffiths-Johnson DA, Jose PJ, Williams TJ. Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo. J Exp Med 1995; 182:1169-74.
37. Sur S, Gleich GJ, Offord KP et al. Allergen challenge in asthma: association of eosinophils and lymphocytes with interleukin-5. Allergy 1995; 50:891-8.
38. Sur S, Gleich GJ, Swanson MC, Bartemes KR, Broide DH. Eosinophilic inflammation is associated with elevation of interleukin-5 in the airways of patients with spontaneous symptomatic asthma. J Allergy Clin Immunol 1995; 96:661-8.
39. Foster PS, Hogan SP, Yang M et al. Interleukin-5 and eosinophils as therapeutic targets for asthma. Trends Mol Med 2002; 8:162-7.
40. Ulrik CS, Frederiksen J. Mortality and markers of risk of asthma death among 1075 outpatients with asthma. Chest 1995; 108:10-5.
41. Cookson WO, Craddock CF, Benson MK, Durham SR. Falls in peripheral eosinophil counts parallel the late asthmatic response. Am Rev Respir Dis 1989; 139:458-62.
42. Horn BR, Robin ED, Theodore J, Van Kessel A. Total eosinophil counts in the management of bronchial asthma. N Engl J Med 1975; 292:1152-5.
43. Ferguson AC, Vaughan R, Brown H, Curtis C. Evaluation of serum eosinophilic cationic protein as a marker of disease activity in chronic asthma. J Allergy Clin Immunol 1995; 95:23-8.
44. Gibson PG, Dolovich J, Girgis-Gabardo A et al. The inflammatory response in asthma exacerbation: changes in circulating eosinophils, basophils and their progenitors. Clin Exp Allergy 1990; 20:661-8.
45. Nadif R, Siroux V, Oryszczyn MP et al. Heterogeneity of asthma according to blood inflammatory patterns. Thorax 2009; 64:374-80.
46. Taylor KJ, Luksza AR. Peripheral blood eosinophil counts and bronchial responsiveness. Thorax 1987; 42:452-6.
47. Koh YI, Choi S. Blood eosinophil counts for the prediction of the severity of exercise-induced bronchospasm in asthma. Respir Med 2002; 96:120-5.
48. Malinovschi A, Fonseca JA, Jacinto T, Alving K, Janson C. Exhaled nitric oxide levels and blood eosinophil counts independently associate with wheeze and asthma events in National Health and Nutrition Examination Survey subjects. J Allergy Clin Immunol 2013; 132:821-7.
49. Tran TN, Khatry DB, Ke X, Ward CK, Gossage D. High blood eosinophil count is associated with more frequent asthma attacks in asthma patients. Ann Allergy Asthma Immunol 2014; 113:19-24.
50. Oommen A, McNally T, Grigg J. Eosinophil activation and preschool viral wheeze. Thorax 2003; 58:876-9.
51. Just J, Nicoloyanis N, Chauvin M, Pribil C, Grimfeld A, Duru G. Lack of eosinophilia can predict remission in wheezy infants? Clin Exp Allergy 2008; 38:767-73.
52. Hyvarinen MK, Kotaniemi-Syrjanen A, Reijonen TM, Piippo-Savolainen E, Korppi M. Eosinophil activity in infants hospitalized for wheezing and risk of persistent childhood asthma. Pediatr Allergy Immunol 2010; 21:96-103.
53. Kotaniemi-Syrjanen A, Reijonen TM, Korhonen K, Korppi M. Wheezing requiring hospitalization in early childhood: predictive factors for asthma in a six-year follow-up. Pediatr Allergy Immunol 2002; 13:418-25.
54. Karakoc F, Remes ST, Martinez FD, Wright AL. The association between persistent eosinophilia and asthma in childhood is independent of atopic status. Clin Exp Allergy 2002; 32:51-6.
55. Cranendonk E, van Gennip AH, Abeling NG, Behrendt H, Hart AA. Reference values for automated cytochemical differential count of leukocytes in children 0-16 years old: comparison with manually obtained counts from Wright-stained smears. J Clin Chem Clin Biochem 1985; 23:663-7.
56. Bradding P, Feather IH, Wilson S et al. Immunolocalization of cytokines in the nasal mucosa of normal and perennial rhinitic subjects. The mast cell as a source of IL-4, IL-5, and IL-6 in human allergic mucosal inflammation. J Immunol 1993; 151:3853-65.
57. Schauer U, Trube M, Jager R, Gieler U, Rieger CH. Blood eosinophils, eosinophil-derived proteins, and leukotriene C4 generation in relation to bronchial hyperreactivity in children with atopic dermatitis. Allergy 1995; 50:126-32.
58. Sugai T, Sakiyama Y, Matumoto S. Eosinophil cationic protein in peripheral blood of pediatric patients with allergic diseases. Clin Exp Allergy 1992; 22:275-81.
59. Tupker F, Blok F, Irving S, Bush A, Fleming L, Saglani S. Non-invasive markers of airway eosinophilic inflammation in pre-school children. Eur Respir J 2014; 44(Suppl. 58):P4201.
60. Brightling CE. Eosinophils, bronchitis and asthma: pathogenesis of cough and airflow obstruction. Pulm Pharmacol Ther 2011; 24:324-7.
61. Wardlaw AJ, Dunnette S, Gleich GJ, Collins JV, Kay AB. Eosinophils and mast cells in bronchoalveolar lavage in subjects with mild asthma. Relationship to bronchial hyperreactivity. Am Rev Respir Dis 1988; 137:62-9.
62. Djukanovic R, Wilson JW, Britten KM et al. Quantitation of mast cells and eosinophils in the bronchial mucosa of symptomatic atopic asthmatics and healthy control subjects using immunohistochemistry. Am Rev Respir Dis 1990; 142:863-71.
63. Pizzichini E, Pizzichini MM, Kidney JC et al. Induced sputum, bronchoalveolar lavage and blood from mild asthmatics: inflammatory cells, lymphocyte subsets and soluble markers compared. Eur Respir J 1998; 11:828-34.
64. Fleming L, Tsartsali L, Wilson N, Regamey N, Bush A. Sputum inflammatory phenotypes are not stable in children with asthma. Thorax 2012; 67:675-81.
65. Gibson PG, Simpson JL, Chalmers AC et al. Airway eosinophilia is associated with wheeze but is uncommon in children with persistent cough and frequent chest colds. Am J Respir Crit Care Med 2001; 164:977-81.
66. Twaddell SH, Gibson PG, Carty K, Woolley KL, Henry RL. Assessment of airway inflammation in children with acute asthma using induced sputum. Eur Respir J 1996; 9:2104-8.
67. Norzila MZ, Fakes K, Henry RL, Simpson J, Gibson PG. Interleukin-8 secretion and neutrophil recruitment accompanies induced sputum eosinophil activation in children with acute asthma. Am J Respir Crit Care Med 2000; 161:769-74.
68. Green RH, Brightling CE, McKenna S et al. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet 2002; 360:1715-21.
69. Chlumsky J, Striz I, Terl M, Vondracek J. Strategy aimed at reduction of sputum eosinophils decreases exacerbation rate in patients with asthma. J Int Med Res 2006; 34:129-39.
70. Jayaram L, Pizzichini MM, Cook RJ et al. Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations. Eur Respir J 2006; 27:483-94.
71. Shields MD, Brown V, Stevenson EC et al. Serum eosinophilic cationic protein and blood eosinophil counts for the prediction of the presence of airways inflammation in children with wheezing. Clin Exp Allergy 1999; 29:1382-9.
72. Baraldo S, Turato G, Bazzan E et al. Noneosinophilic asthma in children: relation with airway remodelling. Eur Respir J 2011; 38:575-83.
73. Barbato A, Turato G, Baraldo S et al. Airway inflammation in childhood asthma. Am J Respir Crit Care Med 2003; 168:798-803.
74. Saglani S, Malmstrom K, Pelkonen AS et al. Airway remodeling and inflammation in symptomatic infants with reversible airflow obstruction. Am J Respir Crit Care Med 2005; 171:722-7.
75. 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.
76. Krawiec ME, Westcott JY, Chu HW et al. Persistent wheezing in very young children is associated with lower respiratory inflammation. Am J Respir Crit Care Med 2001; 163:1338-43.
77. Marguet C, Jouen-Boedes F, Dean TP, Warner JO. Bronchoalveolar cell profiles in children with asthma, infantile wheeze, chronic cough, or cystic fibrosis. Am J Respir Crit Care Med 1999; 159:1533-40.
78. Gibson PG. Asthma phenotypes in childhood. Paediatr Respir Rev 2011; 12:151.
79. Zar HJ, Tannenbaum E, Apolles P, Roux P, Hanslo D, Hussey G. Sputum induction for the diagnosis of pulmonary tuberculosis in infants and young children in an urban setting in South Africa. Arch Dis Child 2000; 82:305-8.
80. Gaillard EA, Grigg J, Tellabati A, McNally T, Whittaker A, Beardsmore CS. Isolation of cells from the lower airways in infants with wheeze by sputum induction. Eur Respir J 2013; 41:483-5.
81. Gleich GJ, Adolphson CR. The eosinophilic leukocyte: structure and function. Adv Immunol 1986; 39:177-253.
82. Gleich GJ, Frigas E, Loegering DA, Wassom DL, Steinmuller D. Cytotoxic properties of the eosinophil major basic protein. J Immunol 1979; 123:2925-7.
83. Frigas E, Loegering DA, Gleich GJ. Cytotoxic effects of the guinea pig eosinophil major basic protein on tracheal epithelium. Lab Invest 1980; 42:35-43.
84. Flavahan NA, Slifman NR, Gleich GJ, Vanhoutte PM. Human eosinophil major basic protein causes hyperreactivity of respiratory smooth muscle. Role of the epithelium. Am Rev Respir Dis 1988; 138:685-8.
85. Gleich GJ, Flavahan NA, Fujisawa T, Vanhoutte PM. The eosinophil as a mediator of damage to respiratory epithelium: a model for bronchial hyperreactivity. J Allergy Clin Immunol 1988; 81:776-81.
86. Venge P. Eosinophil activity in bronchial asthma. Allergy Proc 1994; 15:139-41.
87. Venge P, Bystrom J, Carlson M et al. Eosinophil cationic protein [ECP]: molecular and biological properties and the use of ECP as a marker of eosinophil activation in disease. Clin Exp Allergy 1999; 29:1172-86.
88. Zimmerman B, Lanner A, Enander I, Zimmerman RS, Peterson CG, Ahlstedt S. Total blood eosinophils, serum eosinophil cationic protein and eosinophil protein X in childhood asthma: relation to disease status and therapy. Clin Exp Allergy 1993; 23:564-70.
89. Juntunen-Backman K, Jarvinen P, Sorva R. Serum eosinophil cationic protein during treatment of asthma in children. J Allergy Clin Immunol 1993; 92:34-8.
90. Villa JR, Garcia G, Rueda S, Nogales A. Serum eosinophilic cationic protein may predict clinical course of wheezing in young children. Arch Dis Child 1998; 78:448-52.
91. Koh YY, Kang H, Kim CK. Ratio of serum eosinophil cationic protein/blood eosinophil counts in children with asthma: comparison between acute exacerbation and clinical remission. Allergy Asthma Proc 2003; 24:269-74.
92. Koller DY, Wojnarowski C, Herkner KR et al. High levels of eosinophil cationic protein in wheezing infants predict the development of asthma. J Allergy Clin Immunol 1997; 99:752-6.
93. Koh YY, Kang H, Nah KM, Kim CK. Absence of association of peripheral blood eosinophilia or increased eosinophil cationic protein with bronchial hyperresponsiveness during asthma remission. Ann Allergy Asthma Immunol 2003; 91:297-302.
94. Rao R, Frederick JM, Enander I, Gregson RK, Warner JA, Warner JO. Airway function correlates with circulating eosinophil, but not mast cell, markers of inflammation in childhood asthma. Clin Exp Allergy 1996; 26:789-93.
95. Joseph-Bowen J, de Klerk N, Holt PG, Sly PD. Relationship of asthma, atopy, and bronchial responsiveness to serum eosinophil cationic proteins in early childhood. J Allergy Clin Immunol 2004; 114:1040-5.
96. Reichenbach J, Jarisch A, Khan S, Homberg M, Bez C, Zielen S. Serum ECP levels and methacholine challenge in infants with recurrent wheezing. Ann Allergy Asthma Immunol 2002; 89:498-502.
97. Holgate ST. Biomarkers of asthma. Lancet 1998; 351:1300-1.
98. Lane C, Knight D, Burgess S et al. Epithelial inducible nitric oxide synthase activity is the major determinant of nitric oxide concentration in exhaled breath. Thorax 2004; 59:757-60.
99. Berry MA, Shaw DE, Green RH, Brightling CE, Wardlaw AJ, Pavord ID. The use of exhaled nitric oxide concentration to identify eosinophilic airway inflammation: an observational study in adults with asthma. Clin Exp Allergy 2005; 35:1175-9.
100. Nair P, Kjarsgaard M, Armstrong S, Efthimiadis A, O'Byrne PM, Hargreave FE. Nitric oxide in exhaled breath is poorly correlated to sputum eosinophils in patients with prednisone-dependent asthma. J Allergy Clin Immunol 2010; 126:404-6.
101. Strunk RC, Szefler SJ, Phillips BR et al. Relationship of exhaled nitric oxide to clinical and inflammatory markers of persistent asthma in children. J Allergy Clin Immunol 2003; 112:883-92.
102. van den Toorn LM, Overbeek SE, de Jongste JC, Leman K, Hoogsteden HC, Prins JB. Airway inflammation is present during clinical remission of atopic asthma. Am J Respir Crit Care Med 2001; 164:2107-13.
103. Dweik RA, Boggs PB, Erzurum SC et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med 2011; 184:602-15.
104. Petsky HL, Cates CJ, Li A, Kynaston JA, Turner C, Chang AB. Tailored interventions based on exhaled nitric oxide versus clinical symptoms for asthma in children and adults. Cochrane Database Syst Rev 2009; (4):CD006340.
105. Pizzichini E, Pizzichini MM, Efthimiadis A, Dolovich J, Hargreave FE. Measuring airway inflammation in asthma: eosinophils and eosinophilic cationic protein in induced sputum compared with peripheral blood. J Allergy Clin Immunol 1997; 99:539-44.
106. Wagener AH, de Nijs SB, Lutter R et al. External validation of blood eosinophils, FENO and serum periostin as surrogates for sputum eosinophils in asthma. Thorax 2015; 70:115-20.
107. Schleich FN, Manise M, Sele J, Henket M, Seidel L, Louis R. Distribution of sputum cellular phenotype in a large asthma cohort: predicting factors for eosinophilic vs neutrophilic inflammation. BMC Pulm Med 2013; 13:11.
108. Claman DM, Boushey HA, Liu J, Wong H, Fahy JV. Analysis of induced sputum to examine the effects of prednisone on airway inflammation in asthmatic subjects. J Allergy Clin Immunol 1994; 94:861-9.
109. Baigelman W, Chodosh S, Pizzuto D, Cupples LA. Sputum and blood eosinophils during corticosteroid treatment of acute exacerbations of asthma. Am J Med 1983; 75:929-36.
110. Griffin E, Hakansson L, Formgren H, Jorgensen K, Peterson C, Venge P. Blood eosinophil number and activity in relation to lung function in patients with asthma and with eosinophilia. J Allergy Clin Immunol 1991; 87:548-57.
111. Pizzichini MM, Pizzichini E, Clelland L et al. Sputum in severe exacerbations of asthma: kinetics of inflammatory indices after prednisone treatment. Am J Respir Crit Care Med 1997; 155:1501-8.
112. Lonnkvist K, Anderson M, Hedlin G, Svartengren M. Exhaled NO and eosinophil markers in blood, nasal lavage and sputum in children with asthma after withdrawal of budesonide. Pediatr Allergy Immunol 2004; 15:351-8.
113. Petsky HL, Cates CJ, Lasserson TJ et al. A systematic review and meta-analysis: tailoring asthma treatment on eosinophilic markers [exhaled nitric oxide or sputum eosinophils]. Thorax 2012; 67:199-208.
114. Little SA, Chalmers GW, MacLeod KJ, McSharry C, Thomson NC. Non-invasive markers of airway inflammation as predictors of oral steroid responsiveness in asthma. Thorax 2000; 55:232-4.
115. Di Franco A, Bacci E, Bartoli ML et al. Inhaled fluticasone propionate is effective as well as oral prednisone in reducing sputum eosinophilia during exacerbations of asthma which do not require hospitalization. Pulm Pharmacol Ther 2006; 19:353-60.
116. Duddridge M, Ward C, Hendrick DJ, Walters EH. Changes in bronchoalveolar lavage inflammatory cells in asthmatic patients treated with high dose inhaled beclomethasone dipropionate. Eur Respir J 1993; 6:489-97.
117. Deykin A, Lazarus SC, Fahy JV et al. Sputum eosinophil counts predict asthma control after discontinuation of inhaled corticosteroids. J Allergy Clin Immunol 2005; 115:720-7.
118. Cowan DC, Cowan JO, Palmay R, Williamson A, Taylor DR. Effects of steroid therapy on inflammatory cell subtypes in asthma. Thorax 2010; 65:384-90.
119. 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.
120. Berry M, Morgan A, Shaw DE et al. Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma. Thorax 2007; 62:1043-9.
121. Bacci E, Cianchetti S, Bartoli M et al. Low sputum eosinophils predict the lack of response to beclomethasone in symptomatic asthmatic patients. Chest 2006; 129:565-72.
122. Zacharasiewicz A, Wilson N, Lex C et al. Clinical use of noninvasive measurements of airway inflammation in steroid reduction in children. Am J Respir Crit Care Med 2005; 171:1077-82.
123. Fleming L, Wilson N, Regamey N, Bush A. Use of sputum eosinophil counts to guide management in children with severe asthma. Thorax 2012; 67:193-8.
124. Strunk RC, Bacharier LB, Phillips BR et al. Azithromycin or montelukast as inhaled corticosteroid-sparing agents in moderate-to-severe childhood asthma study. J Allergy Clin Immunol 2008; 122:1138-44.
125. Prehn A, Seger RA, Torresani T, Molinari L, Sennhauser FH. Evaluation of a clinical algorithm involving serum eosinophil cationic protein for guiding the anti-inflammatory treatment of bronchial asthma in childhood. Pediatr Allergy Immunol 2000; 11:87-94.
126. Wolthers O, Heuck C. Impact of Age and Administration Regimens on the Suppressive Effect of Inhaled Glucocorticoids on Eosinophil Markers in Children with Asthma. Pediatr Asthma Allergy Immunol 2004; 17:45-51.
127. Aldridge RE, Hancox RJ, Cowant JO, Frampton CM, Town GI, Taylor DR. Eosinophils and eosinophilic cationic protein in induced sputum and blood: effects of budesonide and terbutaline treatment. Ann Allergy Asthma Immunol 2002; 89:492-7.
128. Leckie MJ, ten Brinke A, Khan J et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 2000; 356:2144-8.
129. Haldar P, Brightling CE, Hargadon B et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med 2009; 360:973-84.
130. Nair P, Pizzichini MM, Kjarsgaard M et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med 2009; 360:985-93.
131. Ortega HG, Liu MC, Pavord ID et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med 2014; 371:1198-207.
132. Pavord ID, Korn S, Howarth P et al. Mepolizumab for severe eosinophilic asthma [DREAM]: a multicentre, double-blind, placebo-controlled trial. Lancet 2012; 380:651-9.