An official ATS clinical practice guideline: Interpretation of exhaled nitric oxide levels (FENO) for clinical applications

American Journal of Respiratory and Critical Care Medicine

Volumn 184, Issue 5, 2011, Pages 602-615

  Dweik, Raed A ^a   Boggs, Peter B ^a   Erzurum, Serpil C ^a   Irvin, Charles G ^a   Leigh, Margaret W ^a   Lundberg, Jon O ^a   Olin, Anna Carin ^a   Plummer, Alan L ^a   Taylor, D Robin ^a  

^a NONE

Author keywords

Airway disease; Asthma; Clinical application; Exhaled breath; Inflammation; Nitric oxide

Indexed keywords

ANTIINFECTIVE AGENT; ANTIOXIDANT; ARGININE; BUDESONIDE; CORTICOSTEROID; ENDOTHELIN RECEPTOR ANTAGONIST; METHACHOLINE; NITRIC OXIDE; PHOSPHODIESTERASE V INHIBITOR; PROSTACYCLIN; S NITROSOTHIOL; STEROID;

ASTHMA; CHRONIC OBSTRUCTIVE LUNG DISEASE; CLINICAL PRACTICE; CORTICOSTEROID THERAPY; CYSTIC FIBROSIS; DIAGNOSTIC ACCURACY; DISEASE ASSOCIATION; DRUG MECHANISM; EOSINOPHILIA; EVIDENCE BASED PRACTICE; EXHALED NITRIC OXIDE LEVEL; FORCED EXPIRATORY VOLUME; HUMAN; MEASUREMENT; PATIENT MONITORING; PRACTICE GUIDELINE; PRIORITY JOURNAL; PROVOCATION TEST; PULMONARY HYPERTENSION; RESPIRATORY TRACT EXAMINATION; RESPIRATORY TRACT INFLAMMATION; REVIEW;

ASTHMA; BIOLOGICAL MARKERS; BREATH TESTS; EXHALATION; HUMANS; LUNG; NITRIC OXIDE;

EID: 80052438246     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.9120-11ST     Document Type: Review

References (152)

1. Ignarro LJ, BugaGM,Wood KS, Byrns RE, Chaudhuri G. Endotheliumderived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA 1987;84:9265-9269.
2. Palmer RM, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 1988;333:664-666.
3. Nathan C, Xie QW. Nitric oxide synthases: Roles, tolls, and controls. Cell 1994;78:915-918. (Pubitemid 24292319)
4. Dweik RA, Comhair SA, Gaston B, Thunnissen FB, Farver C, Thomassen MJ, Kavuru M, Hammel J, Abu-Soud HM, Erzurum SC. NO chemical events in the human airway during the immediate and late antigen-induced asthmatic response. Proc Natl Acad Sci USA 2001;98:2622-2627. (Pubitemid 32209532)
5. Guo FH, Comhair SA, Zheng S, Dweik RA, Eissa NT, Thomassen MJ, Calhoun W, Erzurum SC. Molecular mechanisms of increased nitric oxide (NO) in asthma: evidence for transcriptional and post-translational regulation of NO synthesis. J Immunol 2000;164:5970-5980. (Pubitemid 30389845)
6. Ricciardolo FL. Multiple roles of nitric oxide in the airways. Thorax 2003;58:175-182. (Pubitemid 36183008)
7. Khatri SB, Hammel J, Kavuru MS, Erzurum SC, Dweik RA. Temporal association of nitric oxide levels and airflow in asthma after whole lung allergen challenge. J Appl Physiol 2003;95:436-440, discussion 435.
8. Khatri SB, Ozkan M, McCarthy K, Laskowski D, Hammel J, Dweik RA, Erzurum SC. Alterations in exhaled gas profile during allergen-induced asthmatic response. Am J Respir Crit Care Med 2001;164: 1844-1848. (Pubitemid 33152318)
9. Reid DW, Johns DP, Feltis B, Ward C, Walters EH. Exhaled nitric oxide continues to reflect airway hyperresponsiveness and disease activity in inhaled corticosteroid-treated adult asthmatic patients. Respirology 2003;8:479-486. (Pubitemid 38009643)
10. De Sanctis GT, MacLean JA, Hamada K, Mehta S, Scott JA, Jiao A, Yandava CN, Kobzik L, Wolyniec WW, Fabian AJ, et al. Contribution of nitric oxide synthases 1, 2, and 3 to airway hyperresponsiveness and inflammation in a murine model of asthma. J Exp Med 1999;189:1621-1630.
11. Lane C, Knight D, Burgess S, Franklin P, Horak F, Legg J, Moeller A, Stick S. Epithelial inducible nitric oxide synthase activity is the major determinant of nitric oxide concentration in exhaled breath. Thorax 2004;59:757-760. (Pubitemid 39215371)
12. Guo FH, De Raeve HR, Rice TW, Stuehr DJ, Thunnissen FB, Erzurum SC. Continuous nitric oxide synthesis by inducible nitric oxide synthase in normal human airway epithelium in vivo. Proc Natl Acad Sci USA 1995;92:7809-7813.
13. Guo FH, Erzurum SC. Characterization of inducible nitric oxide synthase expression in human airway epithelium. Environ Health Perspect 1998;106:1119-1124. (Pubitemid 28554515)
14. Dweik RA, Erzurum SC. Regulation of nitric oxide (NO) synthases and gas phase NO by oxygen. In: Marczin N, Kharitonov SA, Yacoub MH, Barnes PJ, editors. Disease markers in exhaled breath (lung biology in health and disease). New York: Marcel Dekker, Inc.; 2003. pp. 235-246.
15. Hansel TT, Kharitonov SA, Donnelly LE, Erin EM, Currie MG, Moore WM, Manning PT, Recker DP, Barnes PJ. A selective inhibitor of inducible nitric oxide synthase inhibits exhaled breath nitric oxide in healthy volunteers and asthmatics. FASEB J 2003;17:1298-1300.
16. Guo FH, Uetani K, Haque SJ, Williams BR, Dweik RA, Thunnissen FB, Calhoun W, Erzurum SC. Interferon gamma and interleukin 4 stimulate prolonged expression of inducible nitric oxide synthase in human airway epithelium through synthesis of soluble mediators. J Clin Invest 1997;100:829-838. (Pubitemid 27371701)
17. Gustafsson LE, Leone AM, Persson MG, Wiklund NP, Moncada S. Endogenous nitric oxide is present in the exhaled air of rabbits, guinea pigs and humans. Biochem Biophys Res Commun 1991;181: 852-857.
18. Alving K, Weitzberg E, Lundberg JM. Increased amount of nitric oxide in exhaled air of asthmatics. Eur Respir J 1993;6:1368-1370. (Pubitemid 23329557)
19. Kharitonov SA, Yates D, Robbins RA, Logan-Sinclair R, Shinebourne EA, Barnes PJ. Increased nitric oxide in exhaled air of asthmatic patients. Lancet 1994;343:133-135. (Pubitemid 24028638)
20. Gaston B, Drazen J, Chee CBE, Wohl MEB, Stamler JS. Expired nitric oxide concentrations are elevated in patients with reactive airways disease. Endothelium 1993;1:87-92.
21. Silkoff PE, McClean P, Spino M, Erlich L, Slutsky AS, Zamel N. Dose-response relationship and reproducibility of the fall in exhaled nitric oxide after inhaled beclomethasone dipropionate therapy in asthma patients. Chest 2001;119:1322-1328. (Pubitemid 32686011)
22. Ozkan M, Dweik RA. Nitric oxide and airway reactivity. Clin Pulm Med 2001;8:199-206.
23. Smith AD, Cowan JO, Filsell S, McLachlan C, Monti-Sheehan G, Jackson P, Taylor DR. Diagnosing asthma: comparisons between exhaled nitric oxide measurements and conventional tests. Am J Respir Crit Care Med 2004;169:473-478. (Pubitemid 38187119)
24. 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;101:124-129.
25. Dweik RA. The promise and reality of nitric oxide in the diagnosis and treatment of lung disease. Cleve Clin J Med 2001;68:486, 488, 490, 493.
26. American Thoracic Society. Recommendations for standardized procedures for the on-line and off-line measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide in adults and children-1999. Am J Respir Crit Care Med 1999;160:2104-2117.
27. American Thoracic Society/European Respiratory Society. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med 2005;171:912-930.
28. Grob NM, Dweik RA. Exhaled nitric oxide in asthma. From diagnosis, to monitoring, to screening: are we there yet? Chest 2008; 133:837-839. (Pubitemid 351536854)
29. Guyatt G, Vist G, Falck-Ytter Y, Kunz R, Magrini N, Schunemann H. An emerging consensus on grading recommendations? Evid Based Med 2006;11:2-4. (Pubitemid 43230673)
30. Schunemann HJ, Jaeschke R, Cook DJ, Bria WF, El-Solh AA, Ernst A, Fahy BF, Gould MK, Horan KL, Krishnan JA, et al. An official ATS statement: grading the quality of evidence and strength of recommendations in ATS guidelines and recommendations. Am J Respir Crit Care Med 2006;174:605-614. (Pubitemid 44330555)
31. Cowan DC, Cowan JO, Palmay R, Williamson A, Taylor DR. Effects of steroid therapy on inflammatory cell subtypes in asthma. Thorax 2010;65:384-390.
32. Wenzel SE. Phenotypes in asthma: Useful guides for therapy, distinct biological processes, or both? Am J Respir Crit Care Med 2004;170: 579-580. (Pubitemid 39202195)
33. Moore WC, Bleecker ER, Curran-Everett D, Erzurum SC, Ameredes BT, Bacharier L, Calhoun WJ, Castro M, Chung KF, Clark MP, et al. Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute's Severe Asthma Research Program. J Allergy Clin Immunol 2007;119:405-413. (Pubitemid 46210080)
34. Moore WC, Meyers DA, Wenzel SE, Teague WG, Li H, Li X, D'Agostino R, Jr, Castro M, Curran-Everett D, Fitzpatrick AM, et al.; National Heart. Identification of asthma phenotypes using cluster analysis in the severe asthma research program. Am J Respir Crit Care Med 2010;181:315-323.
35. Dweik RA, Sorkness RL, Wenzel S, Hammel J, Curran-Everett D, Comhair SA, Bleecker E, Busse W, Calhoun WJ, Castro M, et al. Use of exhaled nitric oxide measurement to identify a reactive, at-risk phenotype among patients with asthma. Am J Respir Crit Care Med 2010;181:1033-1041.
36. Mattes J, Storm van's Gravesande K, Reining U, Alving K, Ihorst G, Henschen M, Kuehr K. NO in exhaled air is correlated with markers of eosinophilic airway inflammation in corticosteroid-dependent childhood asthma. Eur Respir J 1999;13:1391-1395. (Pubitemid 29357158)
37. Bousquet J, Chanez P, Lacoste JY, Barneon G, Ghavanian N, Enander I, Venge P, Ahlstedt S, Simony-Lafontaine J, Godard P, et al. Eosinophilic inflammation in asthma. N Engl J Med 1990;323:1033-1039. (Pubitemid 20336962)
38. Green RH, Brightling CE, McKenna S, Hargadon B, Parker D, Bradding P, Wardlaw AJ, Pavord ID. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet 2002;360:1715-1721. (Pubitemid 35447900)
39. 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;35:1175-1179.
40. Warke TJ, Fitch PS, Brown V, Taylor R, Lyons JD, Ennis M, Shields MD. Exhaled nitric oxide correlates with airway eosinophils in childhood asthma. Thorax 2002;57:383-387. (Pubitemid 34494145)
41. Silkoff PE, Lent AM, Busacker AA, Katial RK, Balzar S, Strand M, Wenzel SE. Exhaled nitric oxide identifies the persistent eosinophilic phenotype in severe refractory asthma. J Allergy Clin Immunol 2005; 116:1249-1255. (Pubitemid 41740931)
42. Brown HM. Treatment of chronic asthma with prednisolone; significance of eosinophils in the sputum. Lancet 1958;2:1245-1247.
43. Paoliello-Paschoalato AB, Oliveira SH, Cunha FQ. Interleukin 4 induces the expression of inducible nitric oxide synthase in eosinophils. Cytokine 2005;30:116-124.
44. Barreto M, Villa MP, Monti F, Bohmerova Z, Martella S, Montesano M, Darder MT, Ronchetti R. Additive effect of eosinophilia and atopy on exhaled nitric oxide levels in children with or without a history of respiratory symptoms. Pediatr Allergy Immunol 2005;16:52-58. (Pubitemid 40313964)
45. Strunk RC, Szefler SJ, Phillips BR, Zeiger RS, Chinchilli VM, Larsen G, Hodgdon K, Morgan W, Sorkness CA, Lemanske RF Jr. Relationship of exhaled nitric oxide to clinical and inflammatory markers of persistent asthma in children. J Allergy Clin Immunol 2003;112:883-892. (Pubitemid 37412055)
46. 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: 2107-2113. (Pubitemid 34020253)
47. 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;164:1376-1381. (Pubitemid 33124013)
48. Lim S, Jatakanon A, Meah S, Oates T, Chung KF, Barnes PJ. Relationship between exhaled nitric oxide and mucosal eosinophilic inflammation in mild to moderately severe asthma. Thorax 2000;55: 184-188. (Pubitemid 30245966)
49. Jatakanon A, Lim S, Kharitonov SA, Chung KF, Barnes PJ. Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthma. Thorax 1998; 53:91-95. (Pubitemid 28212132)
50. Jones SL, Kittelson J, Cowan JO, Flannery EM, Hancox RJ, McLachlan CR, Taylor DR. The predictive value of exhaled nitric oxide measurements in assessing changes in asthma control. Am J Respir Crit Care Med 2001;164:738-743. (Pubitemid 32881906)
51. Shaw DE, Berry MA, Thomas M, Green RH, Brightling CE, Wardlaw AJ, Pavord ID. The use of exhaled nitric oxide to guide asthma management: a randomized controlled trial. Am J Respir Crit Care Med 2007;176:231-237. (Pubitemid 47195872)
52. Porsbjerg C, Lund TK, Pedersen L, Backer V. Inflammatory subtypes in asthma are related to airway hyperresponsiveness to mannitol and exhaled NO. J Asthma 2009;46:606-612.
53. Fabbri LM, Romagnoli M, Corbetta L, Casoni G, Busljetic K, Turato G, Ligabue G, Ciaccia A, Saetta M, Papi A. Differences in airway inflammation in patients with fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2003;167:418-424. (Pubitemid 36216426)
54. Brightling CE, Symon FA, Birring SS, Bradding P, Wardlaw AJ, Pavord ID. Comparison of airway immunopathology of eosinophilic bronchitis and asthma. Thorax 2003;58:528-532. (Pubitemid 36714017)
55. Szefler SJ, Martin RJ. Lessons learned from variation in response to therapy in clinical trials. J Allergy Clin Immunol 2010;125:285-292, quiz 293-294.
56. Smith AD, Cowan JO, Brassett KP, Filsell S, McLachlan C, Monti-Sheehan G, Herbison GP, Taylor DR. Exhaled nitric oxide: a predictor of steroid response. Am J Respir Crit Care Med 2005;172:453-459. (Pubitemid 41117391)
57. Szefler SJ, Martin RJ, King TS, Boushey HA, Cherniack RM, Chinchilli VM, Craig TJ, Dolovich M, Drazen JM, Fagan JK, et al. Significant variability in response to inhaled corticosteroids for persistent asthma. J Allergy Clin Immunol 2002;109:410-418. (Pubitemid 34234189)
58. Knuffman JE, Sorkness CA, Lemanske RF Jr, Mauger DT, Boehmer SJ, Martinez FD, Bacharier LB, Strunk RC, Szefler SJ, Zeiger RS, et al. Phenotypic predictors of long-term response to inhaled corticosteroid and leukotriene modifier therapies in pediatric asthma. J Allergy Clin Immunol 2009;123:411-416.
59. Pijnenburg MW, Hofhuis W, Hop WC, De Jongste JC. Exhaled nitric oxide predicts asthma relapse in children with clinical asthma remission. Thorax 2005;60:215-218. (Pubitemid 40380280)
60. Zacharasiewicz A, Wilson N, Lex C, Erin EM, Li AM, Hansel T, Khan M, Bush A. Clinical use of noninvasive measurements of airway inflammation in steroid reduction in children. Am J Respir Crit Care Med 2005;171:1077-1082. (Pubitemid 40663717)
61. Deykin A, Massaro AF, Drazen JM, Israel E. Exhaled nitric oxide as a diagnostic test for asthma: online versus offline techniques and effect of flow rate. Am J Respir Crit CareMed 2002;165:1597-1601. (Pubitemid 34693938)
62. Berkman N, Avital A, Breuer R, Bardach E, Springer C, Godfrey S. Exhaled nitric oxide in the diagnosis of asthma: comparison with bronchial provocation tests. Thorax 2005;60:383-388. (Pubitemid 40685820)
63. Ihre E, Gustafsson LE, Kumlin M, Gyllfors P, Dahlen B. Early rise in exhaled no and mast cell activation in repeated low dose allergen challenge. Eur Respir J 2006;1:1.
64. Meurs H, Maarsingh H, Zaagsma J. Arginase and asthma: novel insights into nitric oxide homeostasis and airway hyperresponsiveness. Trends Pharmacol Sci 2003;24:450-455. (Pubitemid 37088169)
65. Dupont LJ, Rochette F, Demedts MG, Verleden GM. Exhaled nitric oxide correlates with airway hyperresponsiveness in steroid-naive patients with mild asthma. Am J Respir Crit Care Med 1998;157: 894-898.
66. Gronke L, Kanniess F, Holz O, Jorres RA, Magnussen H. The relationship between airway hyper-responsiveness, markers of inflammation and lung function depends on the duration of the asthmatic disease. Clin Exp Allergy 2002;32:57-63. (Pubitemid 34226928)
67. Lapperre TS, Snoeck-Stroband JB, Gosman MM, Stolk J, Sont JK, Jansen DF, Kerstjens HA, Postma DS, Sterk PJ, The GSG. Dissociation of lung function and airway inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004;1:1.
68. Rosi E, Ronchi MC, Grazzini M, Duranti R, Scano G. Sputum analysis, bronchial hyperresponsiveness, and airway function in asthma: results of a factor analysis. J Allergy Clin Immunol 1999;103:232-237. (Pubitemid 29095827)
69. Olin AC, Bake B, Toren K. Fraction of exhaled nitric oxide at 50 mL/s: reference values for adult lifelong never-smokers. Chest 2007;131: 1852-1856. (Pubitemid 46981645)
70. Arora R, Thornblade CE, Dauby PA, Flanagan JW, Bush AC, Hagan LL. Exhaled nitric oxide levels in military recruits with new onset asthma. Allergy Asthma Proc 2006;27:493-498. (Pubitemid 44916015)
71. Deykin A, Massaro AF, Coulston E, Drazen JM, Israel E. Exhaled nitric oxide following repeated spirometry or repeated plethysmography in healthy individuals. Am J Respir Crit Care Med 2000;161: 1237-1240. (Pubitemid 30243835)
72. Dupont LJ, Demedts MG, Verleden GM. Prospective evaluation of the validity of exhaled nitric oxide for the diagnosis of asthma. Chest 2003;123:751-756. (Pubitemid 36315489)
73. Olin AC, Rosengren A, Thelle DS, Lissner L, Bake B, Toren K. Height, age, and atopy are associated with fraction of exhaled nitric oxide in a large adult general population sample. Chest 2006;130: 1319-1325. (Pubitemid 44786722)
74. Borrill Z, Clough D, Truman N, Morris J, Langley S, Singh D. A comparison of exhaled nitric oxide measurements performed using three different analysers. Respir Med 2006;100:1392-1396. (Pubitemid 43964493)
75. Kharitonov SA, Gonio F, Kelly C, Meah S, Barnes PJ. Reproducibility of exhaled nitric oxide measurements in healthy and asthmatic adults and children. Eur Respir J 2003;21:433-438. (Pubitemid 36336201)
76. Buchvald F, Baraldi E, Carraro S, Gaston B, De Jongste J, Pijnenburg MW, Silkoff PE, Bisgaard H. Measurements of exhaled nitric oxide in healthy subjects age 4 to 17 years. J Allergy Clin Immunol 2005; 115:1130-1136. (Pubitemid 40824579)
77. Olivieri M, Talamini G, Corradi M, Perbellini L, Mutti A, Tantucci C, Malerba M. Reference values for exhaled nitric oxide (reveno) study. Respir Res 2006;7:94.
78. Travers J, Marsh S, Aldington S, Williams M, Shirtcliffe P, Pritchard A, Weatherall M, Beasley R. Reference ranges for exhaled nitric oxide derived from a random community survey of adults. Am J Respir Crit Care Med 2007;176:238-242. (Pubitemid 47195873)
79. Dressel H, de la Motte D, Reichert J, Ochmann U, Petru R, Angerer P, Holz O, Nowak D, Jorres RA. Exhaled nitric oxide: independent effects of atopy, smoking, respiratory tract infection, gender and height. Respir Med 2008;102:962-969.
80. Baraldi E, Azzolin NM, Cracco A, Zacchello F. Reference values of exhaled nitric oxide for healthy children 6-15 years old. Pediatr Pulmonol 1999;27:54-58. (Pubitemid 29063802)
81. Kovesi T, Kulka R, Dales R. Exhaled nitric oxide concentration is affected by age, height, and race in healthy 9- to 12-year-old children. Chest 2008;133:169-175.
82. Wong GW, Liu EK, Leung TF, Yung E, Ko FW, Hui DS, Fok TF, Lai CK. High levels and gender difference of exhaled nitric oxide in Chinese schoolchildren. Clin Exp Allergy 2005;35:889-893. (Pubitemid 41032537)
83. Malmberg LP, Petays T, Haahtela T, Laatikainen T, Jousilahti P, Vartiainen E, Makela MJ. Exhaled nitric oxide in healthy nonatopic school-age children: determinants and height-adjusted reference values. Pediatr Pulmonol 2006;41:635-642.
84. Taylor DR, Mandhane P, Greene JM, Hancox RJ, Filsell S, McLachlan CR, Williamson AJ, Cowan JO, Smith AD, Sears MR. Factors affecting exhaled nitric oxide measurements: the effect of sex. Respir Res 2007;8:82.
85. Meijer RJ, Postma DS, Kauffman HF, Arends LR, Koeter GH, Kerstjens HA. Accuracy of eosinophils and eosinophil cationic protein to predict steroid improvement in asthma. Clin Exp Allergy 2002;32:1096-1103. (Pubitemid 34779609)
86. Szefler SJ, Phillips BR, Martinez FD, Chinchilli VM, Lemanske RF, Strunk RC, Zeiger RS, Larsen G, Spahn JD, Bacharier LB, et al. Characterization of within-subject responses to fluticasone and montelukast in childhood asthma. J Allergy Clin Immunol 2005;115:233-242. (Pubitemid 40215084)
87. Pijnenburg MW, Bakker EM, Lever S, Hop WC, De Jongste JC. High fractional concentration of nitric oxide in exhaled air despite steroid treatment in asthmatic children. Clin Exp Allergy 2005;35:920-925. (Pubitemid 41032541)
88. Piacentini GL, Bodini A, Costella S, Vicentini L, Peroni D, Zanolla L, Boner AL. Allergen avoidance is associated with a fall in exhaled nitric oxide in asthmatic children. J Allergy Clin Immunol 1999;104: 1323-1324. (Pubitemid 30004998)
89. Vahlkvist S, Sinding M, Skamstrup K, Bisgaard H. Daily home measurements of exhaled nitric oxide in asthmatic children during natural birch pollen exposure. J Allergy Clin Immunol 2006;117:1272-1276. (Pubitemid 43795757)
90. Pedroletti C, Millinger E, Dahlen B, Soderman P, Zetterstrom O. Clinical effects of purified air administered to the breathing zone in allergic asthma: a double-blind randomized cross-over trial. Respir Med 2009;103:1313-1319.
91. Bodini A, Peroni D, Loiacono A, Costella S, Pigozzi R, Baraldi E, Boner AL, Piacentini GL. Exhaled nitric oxide daily evaluation is effective in monitoring exposure to relevant allergens in asthmatic children. Chest 2007;132:1520-1525. (Pubitemid 350156008)
92. Smith AD, Cowan JO, Taylor DR. Exhaled nitric oxide levels in asthma: personal best versus reference values. J Allergy Clin Immunol 2009;124:714-718.
93. Buchvald F, Eiberg H, Bisgaard H. Heterogeneity of FeNO response to inhaled steroid in asthmatic children. Clin Exp Allergy 2003;33:1735-1740. (Pubitemid 38005396)
94. Gelb AF, Flynn Taylor C, Shinar CM, Gutierrez C, Zamel N. Role of spirometry and exhaled nitric oxide to predict exacerbations in treated asthmatics. Chest 2006;129:1492-1499. (Pubitemid 43894977)
95. Szefler SJ, Mitchell H, Sorkness CA, Gergen PJ, O'Connor GT, Morgan WJ, Kattan M, Pongracic JA, Teach SJ, Bloomberg GR, et al. Management of asthma based on exhaled nitric oxide in addition to guideline-based treatment for inner-city adolescents and young adults: a randomised controlled trial. Lancet 2008;372:1065-1072.
96. Ekroos H, Karjalainen J, Sarna S, Laitinen LA, Sovijarvi AR. Short-term variability of exhaled nitric oxide in young male patients with mild asthma and in healthy subjects. Respir Med 2002;96:895-900. (Pubitemid 35238120)
97. Pijnenburg MW, Floor SE, Hop WC, De Jongste JC. Daily ambulatory exhaled nitric oxide measurements in asthma. Pediatr Allergy Immunol 2006;17:189-193.
98. Massaro AF, Gaston B, Kita D, Fanta C, Stamler JS, Drazen JM. Expired nitric oxide levels during treatment of acute asthma. Am J Respir Crit Care Med 1995;152:800-803.
99. Beck-Ripp J, Griese M, Arenz S, Koring C, Pasqualoni B, Bufler P. Changes of exhaled nitric oxide during steroid treatment of childhood asthma. Eur Respir J 2002;19:1015-1019. (Pubitemid 34649612)
100. Michils A, Baldassarre S, Van Muylem A. Exhaled nitric oxide and asthma control: a longitudinal study in unselected patients. Eur Respir J 2008;31:539-546.
101. de Jongste JC, Carraro S, Hop WC, Baraldi E. Daily telemonitoring of exhaled nitric oxide and symptoms in the treatment of childhood asthma. Am J Respir Crit Care Med 2009;179:93-97.
102. Petsky HL, Cates CJ, Lasserson TJ, Li AM, Turner C, Kynaston JA, Chang AB. A systematic review and meta-analysis: tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils). Thorax
103. Smith AD, Cowan JO, Brassett KP, Herbison GP, Taylor DR. Use of exhaled nitric oxide measurements to guide treatment in chronic asthma. N Engl J Med 2005;352:2163-2173.
104. Gibson PG. Using fractional exhaled nitric oxide to guide asthma therapy: Design and methodological issues for ASthma TReatment ALgorithm studies. Clin Exp Allergy 2009;39:478-490.
105. Perez-de-Llano LA, Carballada F, Castro Anon O, Pizarro M, Golpe R, Baloira A, Vazquez Caruncho M, Boquete M. Exhaled nitric oxide predicts control in patients with difficult-to-treat asthma. Eur Respir J 2010;35:1221-1227.
106. Barnes PJ, Dweik RA, Gelb AF, Gibson PG, George SC, Grasemann H, Pavord ID, Ratjen F, Silkoff PE, Taylor DR, et al. Exhaled nitric oxide in pulmonary diseases: a comprehensive review. Chest 2010; 138:682-692.
107. Pizzichini E, Pizzichini MM, Gibson P, Parameswaran K, Gleich GJ, Berman L, Dolovich J, Hargreave FE. Sputum eosinophilia predicts benefit from prednisone in smokers with chronic obstructive bronchitis. Am J Respir Crit Care Med 1998;158:1511-1517.
108. Brightling CE, Monteiro W, Ward R, Parker D, Morgan MD, Wardlaw AJ, Pavord ID. Sputum eosinophilia and short-term response to prednisolone in chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 2000;356:1480-1485.
109. Zietkowski Z, Kucharewicz I, Bodzenta-Lukaszyk A. The influence of inhaled corticosteroids on exhaled nitric oxide in stable chronic obstructive pulmonary disease. Respir Med 2005;99:816-824. (Pubitemid 40796555)
110. de Laurentiis G, Maniscalco M, Cianciulli F, Stanziola A, Marsico S, Lundberg JO, Weitzberg E, Sofia M. Exhaled nitric oxide monitoring in COPD using a portable analyzer. Pulm Pharmacol Ther 2008;21:689-693.
111. Dummer JF, Epton MJ, Cowan JO, Cook JM, Condliffe R, Landhuis CE, Smith AD, Taylor DR. Predicting corticosteroid response in chronic obstructive pulmonary disease using exhaled nitric oxide. Am J Respir Crit Care Med 2009;180:846-852.
112. Lehtimaki L, Kankaanranta H, Saarelainen S, Annila I, Aine T, Nieminen R, Moilanen E. Bronchial nitric oxide is related to symptom relief during fluticasone treatment in COPD. Eur Respir J 2010;35:72-78.
113. Giaid A, Saleh D. Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N Engl J Med 1995;333:214-221.
114. Ghamra ZW, Dweik RA. Primary pulmonary hypertension: An overview of epidemiology and pathogenesis. Cleve Clin J Med 2003;70:S2-S8.
115. Mayer B, Pfeiffer S, Schrammel A, Koesling D, Schmidt K, Brunner F. A new pathway of nitric oxide/cyclic GMP signaling involving S-nitrosoglutathione. J Biol Chem 1998;273:3264-3270. (Pubitemid 28109738)
116. Kim SF, Huri DA, Snyder SH. Inducible nitric oxide synthase binds, S-nitrosylates, and activates cyclooxygenase-2. Science 2005;310: 1966-1970. (Pubitemid 43005992)
117. Schmidt HH, Hofmann H, Schindler U, Shutenko ZS, Cunningham DD, Feelisch M. No. NO from NO synthase. Proc Natl Acad Sci USA 1996;93:14492-14497.
118. Lim KH, Ancrile BB, Kashatus DF, Counter CM. Tumour maintenance is mediated by eNOS. Nature 2008;452:646-649. (Pubitemid 351483359)
119. Gaston B, Singel D, Doctor A, Stamler JS. S-nitrosothiol signaling in respiratory biology. Am J Respir Crit Care Med 2006;173:1186-1193. (Pubitemid 43848387)
120. Moya MP, Gow AJ, Califf RM, Goldberg RN, Stamler JS. Inhaled ethyl nitrite gas for persistent pulmonary hypertension of the newborn. Lancet 2002;360:141-143. (Pubitemid 34786206)
121. Archer S, Rich S. Primary pulmonary hypertension: A vascular biology and translational research "Work in progress". Circulation 2000;102: 2781-2791.
122. Dweik R. Pulmonary hypertension and the search for the selective pulmonary vasodilator. Lancet 2002;360:886.
123. Kaneko FT, Arroliga AC, Dweik RA, Comhair SA, Laskowski D, Oppedisano R, Thomassen MJ, Erzurum SC. Biochemical reaction products of nitric oxide as quantitative markers of primary pulmonary hypertension. Am J Respir Crit Care Med 1998;158:917-923. (Pubitemid 28449461)
124. Dweik RA. The lung in the balance: Arginine, methylated arginines, and nitric oxide. Am J Physiol Lung Cell Mol Physiol 2007;292:L15-L17. (Pubitemid 46103425)
125. Ozkan M, Dweik RA, Laskowski D, Arroliga AC, Erzurum SC. High levels of nitric oxide in individuals with pulmonary hypertension receiving epoprostenol therapy. Lung 2001;179:233-243. (Pubitemid 34194207)
126. Girgis RE, Champion HC, Diette GB, Johns RA, Permutt S, Sylvester JT. Decreased exhaled nitric oxide in pulmonary arterial hypertension: response to bosentan therapy. Am J Respir Crit Care Med 2005; 172:352-357. (Pubitemid 41026146)
127. Machado RF, Londhe Nerkar MV, Dweik RA, Hammel J, Janocha A, Pyle J, Laskowski D, Jennings C, Arroliga AC, Erzurum SC. Nitric oxide and pulmonary arterial pressures in pulmonary hypertension. Free Radic Biol Med 2004;37:1010-1017. (Pubitemid 39164583)
128. Lundberg JON, Farkas-Szallasi T, Weitzberg E, Rinder J, Lidholm J, Änggård A, Hökfelt T, Lundberg JM, Alving K. High nitric oxide production in human paranasal sinuses. Nat Med 1995;1: 370-373.
129. Lundberg JO, Weitzberg E, Nordvall SL, Kuylenstierna R, Lundberg JM, Alving K. Primarily nasal origin of exhaled nitric oxide and absence in Kartagener's syndrome. Eur Respir J 1994;7:1501-1504. (Pubitemid 24268339)
130. Palm JP, Graf P, Lundberg JO, Alving K. Characterization of exhaled nitric oxide: introducing a new reproducible method for nasal nitric oxide measurements. Eur Respir J 2000;16:236-241. (Pubitemid 30624941)
131. Lundberg JON, Nordvall SL, Weitzberg E, Kollberg H, Alving K. Exhaled NO in pediatric asthma and cystic fibrosis. Arch Dis Child 1996;75:323-326. (Pubitemid 26354604)
132. Balfour-Lynn IM, Laverty A, Dinwiddie R. Reduced upper airway nitric oxide in cystic fibrosis. Arch Dis Child 1996;75:319-322. (Pubitemid 26354603)
133. Arnal JF, Didier A, Rami J, M'Rini C, Charlet JP, Serrano E, Besombes JP. Nasal nitric oxide is increased in allergic rhinitis. Clin Exp Allergy 1997;27:358-362. (Pubitemid 27183357)
134. Kharitonov SA, Rajakulasingam K, O'Connor B, Durham SR, Barnes PJ. Nasal nitric oxide is increased in patients with asthma and allergic rhinitis and may be modulated by nasal glucocorticoids. J Allergy Clin Immunol 1997;99:58-64.
135. Horvath I, Loukides S, Wodehouse T, Csiszer E, Cole PJ, Kharitonov SA, Barnes PJ. Comparison of exhaled and nasal nitric oxide and exhaled carbon monoxide levels in bronchiectatic patients with and without primary ciliary dyskinesia. Thorax 2003;58:68-72. (Pubitemid 36135362)
136. Karadag B, James AJ, Gultekin E, Wilson NM, Bush A. Nasal and lower airway level of nitric oxide in children with primary ciliary dyskinesia. Eur Respir J 1999;13:1402-1405. (Pubitemid 29357160)
137. Wodehouse T, Kharitonov SA, Mackay IS, Barnes PJ, Wilson R, Cole PJ. Nasal nitric oxide measurements for the screening of primary ciliary dyskinesia. Eur Respir J 2003;21:43-47. (Pubitemid 36150299)
138. Bodini A, Rugolotto S, Pradal U, Zanotto G, Peroni D. Nasal nitric oxide for early diagnosis of familial primary ciliary dyskinesia. Arch Dis Child 2008;93:452-453. (Pubitemid 352025813)
139. Stehling F, Roll C, Ratjen F, Grasemann H. Nasal nitric oxide to diagnose primary ciliary dyskinesia in newborns. Arch Dis Child Fetal Neonatal Ed 2006;91:F233. (Pubitemid 43667627)
140. Zheng S, Xu W, Bose S, Banerjee AK, Haque SJ, Erzurum SC. Impaired nitric oxide synthase-2 signaling pathway in cystic fibrosis airway epithelium. Am J Physiol Lung Cell Mol Physiol 2004;287: L374-L381. (Pubitemid 38943920)
141. Kelley TJ, Drumm ML. Inducible nitric oxide synthase expression is reduced in cystic fibrosis murine and human airway epithelial cells. J Clin Invest 1998;102:1200-1207. (Pubitemid 28436280)
142. Meng QH, Springall DR, Bishop AE, Morgan K, Evans TJ, Habib S, Gruenert DC, Gyi KM, Hodson ME, Yacoub MH, et al. Lack of inducible nitric oxide synthase
143. Grasemann H, Kurtz F, Ratjen F. Inhaled L-arginine improves exhaled nitric oxide and pulmonary function in patients with cystic fibrosis. Am J Respir Crit Care Med 2006;174:208-212. (Pubitemid 44015394)
144. Jones KL, Hegab AH, Hillman BC, Simpson KL, Jinkins PA, Grisham MB, Owens MW, Sato E, Robbins RA. Elevation of nitrotyrosine and nitrate concentrations in cystic fibrosis sputum. Pediatr Pulmonol 2000;30:79-85.
145. Snyder AH, McPherson ME, Hunt JF, Johnson M, Stamler JS, Gaston B. Acute effects of aerosolized S-nitrosoglutathione in cystic fibrosis. Am J Respir Crit Care Med 2002;165:922-926. (Pubitemid 34774658)
146. Yoon SS, Coakley R, Lau GW, Lymar SV, Gaston B, Karabulut AC, Hennigan RF, Hwang SH, Buettner G, Schurr MJ, et al. Anaerobic killing of mucoid Pseudomonas aeruginosa by acidified nitrite derivatives under cystic fibrosis airway conditions. J Clin Invest 2006;116:436-446. (Pubitemid 43228361)
147. Gaston B, Ratjen F, Vaughan JW, Malhotra NR, Canady RG, Snyder AH, Hunt JF, Gaertig S, Goldberg JB. Nitrogen redox balance in the cystic fibrosis airway: effects of antipseudomonal therapy. Am J Respir Crit Care Med 2002;165:387-390. (Pubitemid 34118514)
148. Lara A, Khatri SB, Wang Z, Comhair SA, XuW, Dweik RA, Bodine M, Levison BS, Hammel J, Bleecker E, et al. Alterations of the arginine metabolome in asthma. Am J Respir Crit Care Med 2008;178:673-681.
149. Ferrazzoni S, Scarpa MC, Guarnieri G, Corradi M, Mutti A, Maestrelli P. Exhaled nitric oxide and breath condensate ph in asthmatic reactions induced by isocyanates. Chest 2009;136:155-162.
150. Hewitt RS, Smith AD, Cowan JO, Schofield JC, Herbison GP, Taylor DR. Serial exhaled nitric oxide measurements in the assessment of laboratory animal allergy. J Asthma 2008;45:101-107. (Pubitemid 351416960)
151. Reddel HK, Taylor DR, Bateman ED, Boulet LP, Boushey HA, Busse WW, Casale TB, Chanez P, Enright PL, Gibson PG, et al. An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med 2009;180:59-99.
152. Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general US population. Am J Respir Crit Care Med 1999;159:179-187. (Pubitemid 29036522)