Clinical utility of asthma biomarkers: From bench to bedside

Biologics: Targets and Therapy

Volumn 7, Issue 1, 2013, Pages 199-210

  Vijverberg, Susanne J H ^a,b   Hilvering, Bart ^b   Raaijmakers, Jan A M ^a   Lammers, Jan Willem J ^b   Maitland van der Zee, Anke Hilse ^a   Koenderman, Leo ^b  

^a UTRECHT UNIVERSITY   (Netherlands)

^b UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

Author keywords

Airway inflammation; Asthma; Biological markers; Metabolomics; Pharmacogenomics

Indexed keywords

BETA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; CHEMOATTRACTANT; CORTICOSTEROID; CYTOKINE; ENDOTHELIAL NITRIC OXIDE SYNTHASE; LEBRIKIZUMAB; LEUKOTRIENE RECEPTOR BLOCKING AGENT; LONG ACTING DRUG; MEPOLIZUMAB; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; OMALIZUMAB; VOLATILE ORGANIC COMPOUND;

ADD ON THERAPY; ADRB2 GENE; ALGORITHM; ALLERGIC ASTHMA; ASTHMA; BLOOD EXAMINATION; BRONCHOSCOPY; BRONCHUS BIOPSY; CHRONIC INFLAMMATION; CHRONIC OBSTRUCTIVE LUNG DISEASE; CLINICAL FEATURE; CLINICAL PRACTICE; DIAGNOSTIC ACCURACY; DIAGNOSTIC VALUE; DISEASE ACTIVITY; DISEASE COURSE; DISEASE EXACERBATION; DISEASE MARKER; DISEASE SEVERITY; EOSINOPHILIA; EXHALATION; GENE; HISTOPATHOLOGY; HUMAN; LUNG FUNCTION TEST; METABOLOMICS; PATHOGENESIS; PATHOPHYSIOLOGY; PHARMACOGENETICS; PHENOTYPE; PREDICTION; REPRODUCIBILITY; RESPIRATORY TRACT INFLAMMATION; REVIEW; SENSITIVITY AND SPECIFICITY; SPUTUM EXAMINATION; SYMPTOM; TRACHEOBRONCHIAL TOILET; TREATMENT RESPONSE;

EID: 84883408101     PISSN: 11775475     EISSN: 11775491     Source Type: Journal    
DOI: 10.2147/BTT.S29976     Document Type: Review

References (115)

1. Global strategy for asthma management and prevention. Global Initiative for Asthma (GINA); 2012. Available from: http://www.ginasthma.org/documents/4. Accessed June 20, 2013.
2. Masoli M, Fabian D, Holt S, Beasley R, Global Initiative for Asthma (GINA) Program. The global burden of asthma: executive summary of the GINA dissemination committee report. Allergy. 2004;59(5):469-478.
3. Busse WW, Lemanske RF. Asthma. N Engl J Med. 2001;344(5): 350-362.
4. Hwang SS, Kim YU, Lee S, etal. Transcription factor YY1 is essential for regulation of the Th2 cytokine locus and for Th2 cell differentiation. Proc Natl Acad Sci U S A. 2013;110(1):276-281.
5. Barnes PJ. The cytokine network in asthma and chronic obstructive pulmonary disease. J Clin Invest. 2008;118(11):3546-3556.
6. Holtzman MJ. Asthma as a chronic disease of the innate and adaptive immune systems responding to viruses and allergens. J Clin Invest. 2012;122(8):2741-2748.
7. Mauad T, Bel EH, Sterk PJ. Asthma therapy and airway remodeling. J Allergy Clin Immunol. 2007;120(5):997-1009.
8. Baena-Cagnani CA, Rossi GA, Canonica GW. Airway remodeling in children: When does it start? Curr Opin Allergy Clin Immunol. 2007;7(2):196-200.
9. Connett GJ. Bronchoalveolar lavage. Paediatr Respir Rev. 2000;1(1): 52-56.
10. Haldar P, Pavord ID, Shaw DE, etal. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med. 2008;178(3): 218-224.
11. Bossley CJ, Fleming L, Gupta A, etal. Pediatric severe asthma is characterized by eosinophilia and remodeling without TH2 cytokines. J Allergy Clin Immunol. 2012;129(4):974-982. e13.
12. Brightling CE, Symon FA, Birring SS, Bradding P, Pavord ID, Wardlaw AJ. TH2 cytokine expression in bronchoalveolar lavage fluid T lymphocytes and bronchial submucosa is a feature of asthma and eosinophilic bronchitis. J Allergy Clin Immunol. 2002;110(6): 899-905.
13. Payne D, McKenzie SA, Stacey S, Misra D, Haxby E, Bush A. Safety and ethics of bronchoscopy and endobronchial biopsy in difficult asthma. Arch Dis Child. 2001;84(5):423-426.
14. Petsky HL, Kynaston JA, Turner C, etal. Tailored interventions based on sputum eosinophils versus clinical symptoms for asthma in children and adults. Cochrane Database Syst Rev. 2007;(2): CD005603.
15. Fahy JV. Eosinophilic and neutrophilic inflammation in asthma: insights from clinical studies. Proc Am Thorac Soc. 2009;6(3):256-259.
16. Macedo P, Hew M, Torrego A, etal. Inflammatory biomarkers in airways of patients with severe asthma compared with non-severe asthma. Clin Exp Allergy. 2009;39(11):1668-1676.
17. Hou C, Zhao H, Li W, etal. Increased heat shock protein 70 levels in induced sputum and plasma correlate with severity of asthma patients. Cell Stress Chaperones. 2011;16(6):663-671.
18. Simpson JL, Scott R, Boyle MJ, Gibson PG. Inflammatory subtypes in asthma: Assessment and identification using induced sputum. Respirology. 2006;11(1):54-61.
19. Pavord ID, Brightling CE, Woltmann G, Wardlaw AJ. Non-eosinophilic corticosteroid unresponsive asthma. Lancet. 1999;353(9171): 2213-2214.
20. Bacci E, Cianchetti S, Bartoli M, etal. Low sputum eosinophils predict the lack of response to beclomethasone in symptomatic asthmatic patients. Chest. 2006;129(3):565-572.
21. Green RH, Brightling CE, McKenna S, etal. Asthma exacerbations and sputum eosinophil counts: A randomised controlled trial. Lancet. 2002;360(9347):1715-1721.
22. Martin RJ, Szefler SJ, King TS, etal. The Predicting Response to Inhaled Corticosteroid Efficacy (PRICE) trial. J Allergy Clin Immunol. 2007;119(1):73-80.
23. Lex C, Jenkins G, Wilson NM, etal. Does sputum eosinophilia predict the response to systemic corticosteroids in children with difficult asthma? Pediatr Pulmonol. 2007;42(3):298-303.
24. Wenzel SE. Eosinophils in asthma-closing the loop or opening the door? N Engl J Med. 2009;360(10):1026-1028.
25. Wang F, He XY, Baines KJ, etal. Different inflammatory phenotypes in adults and children with acute asthma. Eur Respir J. 2011;38(3): 567-574.
26. Fleming L, Wilson N, Regamey N, Bush A. Are inflammatory phenotypes in children with severe asthma stable? Eur Respir J. 2007;30(Suppl 51):483S.
27. Fahy JV, Liu J, Wong H, Boushey HA. Analysis of cellular and biochemical constituents of induced sputum after allergen challenge: a method for studying allergic airway inflammation. J Allergy Clin Immunol. 1994;93(6):1031-1039.
28. Meijer RJ, Postma DS, Kauffman HF, Arends LR, Koëter GH, Kerstjens HA. Accuracy of eosinophils and eosinophil cationic protein to predict steroid improvement in asthma. Clin Exp Allergy. 2002;32(7):1096-1103.
29. Koh GC, Shek LP, Goh DY, Van Bever H, Koh DS. Eosinophil cationic protein: is it useful in asthma? A systematic review. Respir Med. 2007;101(4):696-705.
30. Huerta-Yepez S, Baay-Guzman GJ, Bebenek IG, etal. Hypoxia inducible factor promotes murine allergic airway inflammation and is increased in asthma and rhinitis. Allergy. 2011;66(7):909-918.
31. Kharitonov SA, Yates D, Robbins RA, Logan-Sinclair R, Shinebourne EA, Barnes PJ. Increased nitric oxide in exhaled air of asthmatic patients. Lancet. 1994;343(8890):133-135.
32. Alving K, Weitzberg E, Lundberg JM. Increased amount of nitric oxide in exhaled air of asthmatics. Eur Respir J. 1993;6(9):1368-1370.
33. Dweik RA, Boggs PB, Erzurum SC, etal. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FeNO) for clinical applications. Am J Respir Crit Care Med. 2011;184(5): 602-615.
34. Kharitonov S, Alving K, Barnes PJ. Exhaled and nasal nitric oxide measurements: recommendations. The European Respiratory Society Task Force. Eur Respir J. 1997;10(7):1683-1693.
35. Yates DH. Role of exhaled nitric oxide in asthma. Immunol Cell Biol. 2001;79(2):178-190.
36. Pijnenburg MW, Jongste JC. Exhaled nitric oxide in childhood asthma: a review. Clin Exp Allergy. 2008;38(2):246-259.
37. Payne DN, Adcock IM, Wilson NM, Oates T, Scallan M, Bush A. Relationship between exhaled nitric oxide and mucosal eosinophilic inflammation in children with difficult asthma, after treatment with oral prednisolone. Am J Respir Crit Care Med. 2001;164(8 Pt 1): 1376-1381.
38. Lemière C, Ernst P, Olivenstein R, etal. Airway inflammation assessed by invasive and noninvasive means in severe asthma: eosinophilic and noneosinophilic phenotypes. J Allergy Clin Immunol. 2006;118(5): 1033-1039.
39. 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.
40. Zacharasiewicz A, Wilson N, Lex C, etal. Clinical use of noninvasive measurements of airway inflammation in steroid reduction in children. Am J Respir Crit Care Med. 2005;171(10):1077-1082.
41. Szefler SJ, Phillips BR, Martinez FD, etal. Characterization of within-subject responses to fluticasone and montelukast in childhood asthma. J Allergy Clin Immunol. 2005;115(2):233-242.
42. Knuffman JE, Sorkness CA, Lemanske RF Jr, etal. Phenotypic predictors of long-term response to inhaled corticosteroid and leukotriene modifier therapies in pediatric asthma. J Allergy Clin Immunol. 2009;123(2):411-416.
43. Vijverberg SJ, Koenderman L, Koster ES, van der Ent CK, Raaijmakers JA, Maitland-van der Zee AH. Biomarkers of therapy responsiveness in asthma: Pitfalls and promises. Clin Exp Allergy. 2011;41(5):615-629.
44. Massanari M, Holgate ST, Busse WW, Jimenez P, Kianifard F, Zeldin R. Effect of omalizumab on peripheral blood eosinophilia in allergic asthma. Respir Med. 2010;104(2):188-196.
45. Jansen DF, Rijcken B, Schouten JP, etal. The relationship of skin test positivity, high serum total IgE levels, and peripheral blood eosinophilia to symptomatic and asymptomatic airway hyperresponsiveness. Am J Respir Crit Care Med. 1999;159(3):924-931.
46. Platts-Mills TA. The role of immunoglobulin E in allergy and asthma. Am J Respir Crit Care Med. 2001;164(8 Pt 2):S1-S5.
47. Bhakta NR, Woodruff PG. Human asthma phenotypes: from the clinic, to cytokines, and back again. Immunol Rev. 2011;242(1):220-232.
48. Kato M, Yamada Y, Maruyama K, Hayashi Y. Serum eosinophil cationic protein and 27 Cytokines/Chemokines in acute exacerbation of childhood asthma. Int Arch Allergy Immunol. 2010;152 Suppl 1:62-66.
49. Patil SP, Wisnivesky JP, Busse PJ, Halm EA, Li XM. Detection of immunological biomarkers correlated with asthma control and quality of life measurements in sera from chronic asthmatic patients. Ann Allergy Asthma Immunol. 2011;106(3):205-213.
50. Langereis JD, Schweizer RC, Lammers JW, Koenderman L, Ulfman LH. A unique protein profile of peripheral neutrophils from COPD patients does not reflect cytokine-induced protein profiles of neutrophils in vitro. BMC Pulm Med. 2011;11:44.
51. Kanters D, ten Hove W, Luijk B, etal. Expression of activated FcγRII discriminates between multiple granulocyte-priming phenotypes in peripheral blood of allergic asthmatic subjects. J Allergy Clin Immunol. 2007;120(5):1073-1081.
52. Johansson MW, Kelly EA, Busse WW, Jarjour NN, Mosher DF. Up-regulation and activation of eosinophil integrins in blood and airway after segmental lung antigen challenge. J Immunol. 2008;180(11):7622-7635.
53. Pillay J, Kamp VM, van Hoffen E, etal. A subset of neutrophils in human systemic inflammation inhibits T cell responses through Mac-1. J Clin Invest. 2012;122(1):327-336.
54. Faurschou M, Borregaard N. Neutrophil granules and secretory vesicles in inflammation. Microbes Infect. 2003;5(14):1317-1327.
55. Mengelers HJ, Maikoe T, Brinkman L, Hooibrink B, Lammers JW, Koenderman L. Immunophenotyping of eosinophils recovered from blood and BAL of allergic asthmatics. Am J Respir Crit Care Med. 1994;149(2):345-351.
56. Kelly EA, Koziol-White CJ, Clay KJ, etal. Potential contribution of IL-7 to allergen-induced eosinophilic airway inflammation in asthma. J Immunol. 2009;182(3):1404-1410.
57. Fortunati E, Kazemier KM, Grutters JC, Koenderman L, Van den Bosch VJ. Human neutrophils switch to an activated phenotype after homing to the lung irrespective of inflammatory disease. Clin Exp Immunol. 2009;155(3):559-566.
58. Johansson MW, Barthel SR, Swenson CA, etal. Eosinophil β1 integrin activation state correlates with asthma activity in a blind study of inhaled corticosteroid withdrawal. J Allergy Clin Immunol. 2006;117(6): 1502-1504.
59. Luijk B, Lindemans CA, Kanters D, etal. Gradual increase in priming of human eosinophils during extravasation from peripheral blood to the airways in response to allergen challenge. J Allergy Clin Immunol. 2005;115(5):997-1003.
60. Koenderman L, van der Linden J, Ulfman L, Coffer P. Eosinophils. In: Rogers DF, Donnelly LE, editors. Human Airway Inflammation. Vol 56. Totowa (NJ): Humana Press; 2001:217-226.
61. Jia G, Erickson RW, Choy DF, etal. Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients. J Allergy Clin Immunol. 2012;130(3):647-654. e10.
62. Corren J, Lemanske RF, Hanania NA, etal. Lebrikizumab treatment in adults with asthma. N Engl J Med. 2011;365(12): 1088-1098.
63. Wilson AD, Baietto M. Advances in electronic-nose technologies developed for biomedical applications. Sensors. 2011;11(1): 1105-1176.
64. Dallinga JW, Robroeks CM, van Berkel JJ, etal. Volatile organic compounds in exhaled breath as a diagnostic tool for asthma in children. Clin Exp Allergy. 2010;40(1):68-76.
65. Dragonieri S, Schot R, Mertens BJ, etal. An electronic nose in the discrimination of patients with asthma and controls. J Allergy Clin Immunol. 2007;120(4):856-862.
66. Fens N, Zwinderman AH, van der Schee MP, etal. Exhaled breath profiling enables discrimination of chronic obstructive pulmonary disease and asthma. Am J Respir Crit Care Med. 2009;180(11): 1076-1082.
67. Fens N, de Nijs SB, Peters S, etal. Exhaled air molecular profiling in relation to inflammatory subtype and activity in COPD. Eur Respir J. 2011;38(6):1301-1309.
68. Ibrahim B, Basanta M, Cadden P, etal. Non-invasive phenotyping using exhaled volatile organic compounds in asthma. Thorax. 2011;66(9):804-809.
69. U-BIOPRED [webpage on the Internet]. European Lung Foundation. Available from: http://www.ubiopred.european-lung-foundation.org. Accessed May 2, 2013.
70. Lázár Z, Cervenak L, Orosz M, etal. Adenosine triphosphate concentration of exhaled breath condensate in asthma. Chest. 2010;138(3): 536-542.
71. Loukides S, Bouros D, Papatheodorou G, Panagou P, Siafakas NM. The relationships among hydrogen peroxide in expired breath condensate, airway inflammation, and asthma severity. Chest. 2002;121(2): 338-346.
72. Robroeks CM, Rijkers GT, Jöbsis Q, etal. Increased cytokines, chemokines and soluble adhesion molecules in exhaled breath condensate of asthmatic children. Clin Exp Allergy. 2010;40(1):77-84.
73. Donnelly LE. Exhaled breath condensate: Nitric oxide-related compounds. In: Horvath I, de Jongste JC, editors. European Respiratory Monograph (Exhaled Biomakers). 2010:207-216.
74. Montuschi P. Exhaled breath condensate: 8-isoprostane and eicosanoids. In: Horvath I, de Jongste JC, eds. European respiratory monograph: exhaled biomarkers, Volume 49. Sheffield, UK: European Respiratory Society Journals Ltd. 2010;196-206.
75. Tseliou E, Bessa V, Hillas G, etal. Exhaled nitric oxide and exhaled breath condensate pH in severe refractory asthma. Chest. 2010;138(1): 107-113.
76. Bikov A, Antus B, Losonczy G, Horvath I. Exhaled breath condensate pH. In: Horvath I, de Jongste JC, editors. European Respiratory Monograph (Exhaled Biomarkers). 2010:173-182.
77. Horvath I, Hunt J, Barnes PJ, etal. Exhaled breath condensate: Methodological recommendations and unresolved questions. Eur Respir J. 2005;26(3):523-548.
78. Rabinovitch N. Urinary leukotriene E4 as a biomarker of exposure, susceptibility and risk in asthma. Immunol Allergy Clin North Am. 2012;32(3):433-445.
79. Cai C, Yang J, Hu S, Zhou M, Guo W. Relationship between urinary cysteinyl leukotriene E4 levels and clinical response to antileukotriene treatment in patients with asthma. Lung. 2007;185(2):105-112.
80. Los H, Postmus PE, Boomsma DI. Asthma genetics and intermediate phenotypes: A review from twin studies. Twin Res. 2001;4(2):81-93.
81. Ferreira MA, Matheson MC, Duffy DL, etal. Identification of IL6R and chromosome 11q13.5 as risk loci for asthma. Lancet. 2011;378(9795): 1006-1014.
82. Moffatt MF, Gut IG, Demenais F, etal. A large-scale, consortium-based genomewide association study of asthma. N Engl J Med. 2010;363(13): 1211-1221.
83. Himes BE, Hunninghake GM, Baurley JW, etal. Genome-wide association analysis identifies PDE4D as an asthma-susceptibility gene. Am J Hum Genet. 2009;84(5):581-593.
84. Hobbs K, Negri J, Klinnert M, Rosenwasser L, Borish L. Interleukin-10 and transforming growth factor-beta promoter polymorphisms in allergies and asthma. Am J Respir Crit Care Med. 1998;158(6): 1958-1962.
85. Dijk FN, de Jongste JC, Postma DS, Koppelman GH. Genetics of onset of asthma. Curr Opin Allergy Clin Immunol. 2013;13(2):193-202.
86. Ierodiakonou D, Postma DS, Koppelman GH, etal. TGF-β1 polymorphisms and asthma severity, airway inflammation, and remodeling. J Allergy Clin Immunol. 2013;131(2):582-585.
87. Tantisira KG, Silverman ES, Mariani TJ, etal. FCER2: A pharmacogenetic basis for severe exacerbations in children with asthma. J Allergy Clin Immunol. 2007;120(6):1285-1291.
88. Koster ES, Maitland-van der Zee AH, Tavendale R, etal. FCER2 T2206C variant associated with chronic symptoms and exacerbations in steroid-treated asthmatic children. Allergy. 2011;66(12):1546-1552.
89. Hawkins GA, Lazarus R, Smith RS, etal. The glucocorticoid receptor heterocomplex gene STIP1 is associated with improved lung function in asthmatic subjects treated with inhaled corticosteroids. J Allergy Clin Immunol. 2009;123(6):1376-1383. e7.
90. Tantisira KG, Lasky-Su J, Harada M, etal. Genomewide association between GLCCI1 and response to glucocorticoid therapy in asthma. N Engl J Med. 2011;365(13):1173-1183.
91. Tantisira KG, Hwang ES, Raby BA, etal. TBX21: A functional variant predicts improvement in asthma with the use of inhaled corticosteroids. Proc Natl Acad Sci U S A. 2004;101(52):18099-18104.
92. Li JR, Li JG, Deng GH, etal. A common promoter variant of TBX21 is associated with allele specific binding to yin-yang 1 and reduced gene expression. Scand J Immunol. 2011;73(5):449-458.
93. Telleria JJ, Blanco-Quiros A, Varillas D, etal. ALOX5 promoter genotype and response to montelukast in moderate persistent asthma. Respir Med. 2008;102(6):857-861.
94. Drazen JM, Yandava CN, Dube L, etal. Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Nat Genet. 1999;22(2):168-170.
95. Sampson AP, Siddiqui S, Buchanan D, etal. Variant LTC4synthase allele modifies cysteinyl leukotriene synthesis in eosinophils and predicts clinical response to zafirlukast. Thorax. 2000;55(Suppl 2): S28-S31.
96. Kang MJ, Kwon JW, Kim BJ, etal. Polymorphisms of the PTGDR and LTC4S influence responsiveness to leukotriene receptor antagonists in Korean children with asthma. J Hum Genet. 2011;56(4):284-289.
97. Lipworth BJ, Basu K, Donald HP, etal. Tailored second-line therapy in asthmatic children with the arg(16) genotype. Clin Sci (Lond). 2013;124(8):521-528.
98. Wechsler ME, Kunselman SJ, Chinchilli VM, etal. Effect of [beta]2-adrenergic receptor polymorphism on response to longacting [beta]2 agonist in asthma (LARGE trial): A genotype-stratified, randomised, placebo-controlled, crossover trial. Lancet. 2009;374(9703): 1754-1764.
99. Bleecker ER, Nelson HS, Kraft M, et al. β2-receptor polymorphisms in patients receiving salmeterol with or without fluticasone propionate. Am J Respir Crit Care Med. 2010;181(7):676-687.
100. Bleecker ER, Postma DS, Lawrance RM, Meyers DA, Ambrose HJ, Goldman M. Effect of ADRB2 polymorphisms on response to longacting β2-agonist therapy: A pharmacogenetic analysis of two randomised studies. Lancet. 2007;370(9605):2118-2125.
101. Vijverberg SJH, Koster ES, Koenderman L, etal. Exhaled NO is a poor marker of asthma control in children with a reported use of asthma medication: A pharmacy-based study. Pediatr Allergy Immunol. 2012;23(6):529-536.
102. Mahut B, Trinquart L, Le Bourgeois M, etal. Multicentre trial evaluating alveolar NO fraction as a marker of asthma control and severity. Allergy. 2010;65(5):636-644.
103. Sardón-Prado O, Korta-Murua J, Valverde-Molina J, etal. Association among lung function, exhaled nitric oxide, and the CAN questionnaire to assess asthma control in children. Pediatr Pulmonol. 2010;45(5): 434-439.
104. Ozier A, Girodet P, Bara I, Tunon de Lara J, Marthan R, Berger P. Control maintenance can be predicted by exhaled NO monitoring in asthmatic patients. Respir Med. 2011;105(7):989-996.
105. Perez-de-Llano LA, Carballada F, Castro Anon O, etal. Exhaled nitric oxide predicts control in patients with difficult-to-treat asthma. Eur Resp J. 2010;35(6):1221-1227.
106. Shirai T, Furuhashi K, Suda T, Chida K. Relationship of the asthma control test with pulmonary function and exhaled nitric oxide. Ann Allergy Asthma Immunol. 2008;101(6):608-613.
107. Khalili B, Boggs PB, Shi R, Bahna SL. Discrepancy between clinical asthma control assessment tools and fractional exhaled nitric oxide. Ann Allergy Asthma Immunol. 2008;101(2):124-129.
108. Michils A, Baldassarre S, Van Muylem A. Exhaled nitric oxide and asthma control: a longitudinal study in unselected patients. Eur Respir J. 2008;31(3):539-546.
109. Senna G, Passalacqua G, Schiappoli M, Lombardi C, Wilcock L. Correlation among FEV1, nitric oxide and asthma control test in newly diagnosed asthma. Allergy. 2007;62(2):207-208.
110. Robroeks CM, van de Kant KD, Jöbsis Q, etal. Exhaled nitric oxide and biomarkers in exhaled breath condensate indicate the presence, severity and control of childhood asthma. Clin Exp Allergy. 2007;37(9):1303-1311.
111. Rosias PP, Dompeling E, Dentener MA, etal. Childhood asthma: exhaled markers of airway inflammation, asthma control score, and lung function tests. Pediatr Pulmonol. 2004;38(2):107-114.
112. 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(5):883-892.
113. Franklin PJ, Turner SW, Le Souëf PN, Stick SM. Exhaled nitric oxide and asthma: Complex interactions between atopy, airway responsiveness, and symptoms in a community population of children. Thorax. 2003;58(12):1048-1052.
114. Jones SL, Kittelson J, Cowan JO, etal. The predictive value of exhaled nitric oxide measurements in assessing changes in asthma control. Am J Respir Crit Care Med. 2001;164(5):738-743.
115. Sippel JM, Holden WE, Tilles SA, etal. Exhaled nitric oxide levels correlate with measures of disease control in asthma. J Allergy Clin Immunol. 2000;106(4):645-650.