Exhaled nitric oxide in the assessment of asthma

Current Opinion in Pulmonary Medicine

Volumn 10, Issue 1, 2004, Pages 31-36

  Zeidler, Michelle R ^a,b   Kleerup, Eric C ^a   Tashkin, Donald P ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b Department of Medicine   (United States)

Author keywords

Asthma; Exhaled nitric oxide; Inflammation; Nitric oxide synthetase

Indexed keywords

CORTICOSTEROID; MONTELUKAST; NITRIC OXIDE;

AIRWAY; ASTHMA; CLINICAL TRIAL; CORRELATION ANALYSIS; FORCED EXPIRATORY VOLUME; GENE EXPRESSION; GENETIC ANALYSIS; HUMAN; MORBIDITY; MORTALITY; REVIEW;

EID: 0346963368     PISSN: 10705287     EISSN: None     Source Type: Journal    
DOI: 10.1097/00063198-200401000-00006     Document Type: Review

References (48)

1. Busse WW, Lemanske RF Jr: Asthma. N Engl J Med 2001, 344:350-362.
2. Tashkin DP: The role of small airway inflammation in asthma. Allergy Asthma Proc 2002, 23:233-242.
3. Kharitonov SA, Yates D, Robbins RA, et al.: Increased nitric oxide in exhaled air of asthmatic patients. Lancet 1994, 343:133-135.
4. Kharitonov SA, Donnelly LE, Montuschi P, et al.: Dose-dependent onset and cessation of action of inhaled budesonide on exhaled nitric oxide and symptoms in mild asthma. Thorax 2002, 57:889-896.
5. Furchgott RF, Zawadzki JV: The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980, 288:373-376.
6. Gustafsson LE, Leone AM, Persson MG, et al.: Endogenous nitric oxide is present in the exhaled air of rabbits, guinea pigs and humans. Biochem Biophys Res Commun 1991, 181:852-857.
7. Moncada S, Higgs A: The L-arginine-nitric oxide pathway. N Engl J Med 1993, 329:2002-2012.
8. Robbins RA, Barnes PJ, Springall DR, et al.: Expression of inducible nitric oxide in human lung epithelial cells. Biochem Biophys Res Commun 1994, 203:209-218.
9. Kooy NW, Royall JA, Ye YZ, et al.: Evidence for in vivo peroxynitrite production in human acute lung injury. Am J Respir Crit Care Med 1995, 151:1250-1254.
10. Hart CM: Nitric oxide in adult lung disease. Chest 1999, 115:1407-1417.
11. Jorres RA: Modelling the production of nitric oxide within the human airways. Eur Respir J 2000, 16:555-560.
12. Tsoukias NM, George SC: A two-compartment model of pulmonary nitric oxide exchange dynamics. J Appl Physiol 1998, 85:653-666.
13. Pietropaoli AP, Perillo IB, Torres A, et al.: Simultaneous measurement of nitric oxide production by conducting and alveolar airways of humans. J Appl Physiol 1999, 87:1532-1542.
14. Silkoff PE, Sylvester JT, Zamel N, et al.: Airway nitric oxide diffusion in asthma: Role in pulmonary function and bronchial responsiveness. Am J Respir Crit Care Med 2000, 161:1218-1228.
15. Kharitonov S, Alving K, Barnes PJ: Exhaled and nasal nitric oxide measurements: recommendations. The European Respiratory Society Task Force. Eur Respir J 1997, 10:1683-1693.
16. 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. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med 1999, 160:2104-2117.
17. Baraldi E, de Jongste JC: Measurement of exhaled nitric oxide in children, 2001. Eur Respir J 2002, 20:223-237.
18. Kharitonov SA, Gonio F, Kelly C, et al.: Reproducibility of exhaled nitric oxide measurements in healthy and asthmatic adults and children. Eur Respir J 2003, 21:433-438.
19. Wechsler ME, Grasemann H, Deykin A, et al.: Exhaled nitric oxide in patients with asthma: association with NOS1 genotype. Am J Respir Crit Care Med 2000, 162:2043-2047.
20. Tsang KW, Ip SK, Leung R, et al.: Exhaled nitric oxide: the effects of age, gender and body size. Lung 2001, 179:83-91.
21. Silkoff PE, Wakita S, Chatkin J, et al.: Exhaled nitric oxide after beta2-agonist inhalation and spirometry in asthma. Am J Respir Crit Care Med 1999, 159:940-944.
22. Bruce C, Yates DH, Thomas PS: Caffeine decreases exhaled nitric oxide. Thorax 2002, 57:361-363.
23. Piacentini GL, Bodini A, Peroni DG, et al.: Reduction in exhaled nitric oxide immediately after methacholine challenge in asthmatic children. Thorax 2002, 57:771-773.
24. Yates DH, Kharitonov SA, Barnes, PJ. Effects of short-and long-activity inhaled betaz-agonists on exhaled nitric oxide in asthmatic patients. Eur Respir J 1997, 10:1483-1488.
25. Warke TJ, Fitch PS, Brown V, et al.: Exhaled nitric oxide correlates with airway eosinophils in childhood asthma. Thorax 2002, 57:383-387. Using brochoalveolar lavage in a pediatric population, the authors correlated airways eosinophilia and FE,NO in both steroid-naïve and steroid-treated children with asthma. Positive and negative predictive values of FE,NO predicting airways eosinophilia were reported.
26. van den Toorn LM, Overbeek SE, de Jongste JC, et al.: Airway inflammation is present during clinical remission of atopic asthma. Am J Respir Crit Care Med 2001, 164:2107-2113.
27. Payne DN, Adcock IM, Wilson NM, et al.: 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.
28. Silvestri M, Sabatini F, Sale R, et al.: Correlations between exhaled nitric oxide levels, blood eosinophilia, and airway obstruction reversibility in childhood asthma are detectable only in atopic individuals. Pediatr Pulmonol 2003, 35:358-363. Fraction exhaled nitric oxide levels and blood eosinophils were significantly higher in atopic asthmatic children when compared to nonatopic asthmatic children. A significant correlation between FE,NO and blood eosinophils was only noted in the group of children with atopic asthma.
29. Steerenberg PA, Janssen NA, de Meer G, et al.: Relationship between exhaled NO, respiratory symptoms, lung function, bronchial hyperresponsiveness, and blood eosinophilia in school children. Thorax 2003, 58:242-245.
30. van den Toorn LM, Prins JB, Overbeek SE, et al.: Adolescents in clinical remission of atopic asthma have elevated exhaled nitric oxide levels and bronchial hyperresponsiveness. Am J Respir Crit Care Med 2000, 162:953-957.
31. Spallarossa D, Battistini E, Silvestri M, et al.: Steroid-naive adolescents with mild intermittent allergic asthma have airway hyperresponsiveness and elevated exhaled nitric oxide levels. J Asthma 2003, 40:301-310.
32. de Kluijver J, Evertse CE, Schrumpf JA, et al.: Asymptomatic worsening of airway inflammation during low-dose allergen exposure in asthma: protection by inhaled steroids. Am J Respir Crit Care Med 2002, 166:294-300. This study showed significant airways inflammation in response to a low-dose inhaled allergen that did not decrease FEV, or cause symptoms. FE,NO levels and eosinophil levels were significantly decreased in the subjects using an inhaled corticosteroid before the allergen challenge but not in those subjects using a placebo.
33. Brightling CE, Symon FA, Birring SS, et al.: Comparison of airway immunopathology of eosinophilic bronchitis and asthma. Thorax 2003, 58:528-532.
34. Jatakanon A, Kharitonov S, Lim S, et al.: Effect of differing doses of inhaled budesonide on markers of airway inflammation in patients with mild asthma. Thorax 1999, 54:108-114.
35. Jones SL, Herbison P, Cowan JO, et al.: Exhaled NO and assessment of anti-inflammatory effects of inhaled steroid: dose-response relationship. Eur Respir J 2002, 20:601-608. A dose-response study of beclomethasone between 50 and 500 μg/d using exhaled NO and eosinophil-induced sputum.
36. Currie GP, Lee DK, Haggart K, et al.: Effects of montelukast on surrogate inflammatory markers in corticosteroid-treated patients with asthma. Am J Respir Crit Care Med 2003, 167:1232-1238. The addition of montelukast versus placebo to a fluticasone/salmeterol combination significantly improved AMP PC20, blood eosinophils, and FE,NO in subjects with mild-to-moderate persistent asthma. No invasive studies were performed.
37. Ghiro L, Zanconato S, Rampon O, et al.: Effect of montelukast added to inhaled corticosteroids on fractional exhaled nitric oxide in asthmatic children. Eur Respir J 2002, 20:630-634.
38. Strauch E, Moske O, Thoma S, et al.: A randomized controlled trial on the effect of montelukast on sputum eosinophil cationic protein in children with corticosteroid-dependent asthma. Pediatr Res 2003, 54:198-203.
39. Dupont LJ, Demedts MG, Verleden GM: Prospective evaluation of the validity of exhaled nitric oxide for the diagnosis of asthma. Chest 2003, 1 23:751-756.
40. Deykin A, Massaro AF, Drazen JM, et al.: Exhaled nitric oxide as a diagnostic test for asthma: online versus offline techniques and effect of flow rate. Am J Respir Crit Care Med 2002, 165:1597-1601. This study documented a 70[ref] sensitivity and specificity for the diagnosis of asthma using FE,NO. The flow rate used did not change the sensitivity or specificity of the test.
41. Malmberg LP, Pelkonen AS, Haahtela T, et al.: Exhaled nitric oxide rather than lung function distinguishes preschool children with probable asthma. Thorax 2003, 58:494-499.
42. Martin RJ: Therapeutic significance of distal airway inflammation in asthma. J Allergy Clin Immunol 2002, 109:3447-3460.
43. Saetta M, Di Stefano A, Rosina C, et al.: Quantitative structural analysis of peripheral airways and arteries in sudden fatal asthma. Am Rev Respir Dis 1991, 143:138-143.
44. Carroll N, Elliot J, Morton A, et al.: The structure of large and small airways in nonfatal and fatal asthma. Am Rev Respir Dis 1993, 147:405-410.
45. Kuwano K, Bosken CH, Pare PD, et al.: Small airways dimensions in asthma and in chronic obstructive pulmonary disease. Am Rev Respir Dis 1993, 148:1220-1225.
46. Kraft M, Djukanovic R, Wilson S, et al.: Alveolar tissue inflammation in asthma. Am J Respir Crit Care Med 1996, 154:1505-1510.
47. Lehtimaki L, Kankaanranta H, Saarelainen S, et al.: Extended exhaled NO measurement differentiates between alveolar and bronchial inflammation. Am J Respir Crit Care Med 2001, 163:1557-1561.
48. Lehtimaki L, Kankaanranta H, Saarelainen S, et al.: Increased alveolar nitric oxide concentration in asthmatic patients with nocturnal symptoms. Eur Respir J 2002, 20:841-845. Alveolar FE,NO was elevated in subjects with asthma with nocturnal symptoms but not in subjects with asthma without nocturnal symptoms or in nonasthmatic controls. This correlates with increased alveolar eosinophilic inflammation documented by Kraft et al., although no invasive studies were performed for this trial.