Exhaled nitric oxide: A marker of airway inflammation?

Current Opinion in Anaesthesiology

Volumn 9, Issue 6, 1996, Pages 542-548

  Kharitonov, Sergei A ^a   Barnes, Peter J ^a  

^a NATIONAL HEART AND LUNG INSTITUTE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CORTICOSTEROID; NITRIC OXIDE;

ASTHMA; BRONCHIECTASIS; EXPIRED AIR; HUMAN; INHALATIONAL DRUG ADMINISTRATION; MEASUREMENT; PATIENT MONITORING; PRIORITY JOURNAL; RESPIRATORY TRACT INFLAMMATION; REVIEW;

EID: 0029800927     PISSN: 09527907     EISSN: None     Source Type: Journal    
DOI: 10.1097/00001503-199612000-00017     Document Type: Review

References (50)

1. Barnes PJ: Nitric oxide and airway disease. Ann Med 1995, 27:389-393. Concise review focusing on physiology, pathophysiology and pro-inflammatory activity of NO, and the effects of selective iNOS inhibitors. Encompassing review on NO involvement in airway inflammation.
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7. Xue C, Johns RA: Endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N Engl J Med 1995, 333: 1642-1644. Diminished expression of eNOS in pulmonary hypertension has been discussed.
8. Gustafsson LE, Leone AM, Persson M, Wikiund 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.
9. Kharitonov SA, Yates D, Robbins RA, Logan-Sinclair R, Shineboume E, Barnes PJ: Increased nitric oxide in exhaled air of asthmatic patients. Lancet 1994, 343:133-135.
10. Massaro AF, Mehta S, Lilly CM, Kobzik L, Reilly JJ, Drazen JM: Elevated nitric oxide concentrations in isolated lower airway gas of asthmatic subjects. Am J Respir Crit Care Med 1996, 153:1510-1514. Lower airway gas, sampled through the bronchoscope, was found to contain NO in normal individuals, and was significantly higher in patients with asthma.
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12. Kharitonov SA, Wells AU, O'Connor BJ, Hansell DM, Cole PJ, Barnes PJ: Elevated levels of exhaled nitric oxide in bronchiectasis. Am J Respir Crit Care Med 1995,151:1889-1893. Untreated bronchiectasis is associated with an increase in exhaled NO which correlates with disease severity, whereas patients treated with inhaled steroids have levels of exhaled NO within the normal range.
13. Kharitonov S, Chung KF, Evans DJ, O'Connor BJ, Barnes PJ: The elevated level of exhaled nitric oxide in asthmatic patients is mainly derived from the lower respiratory tract. Am J Respir Crit Care Med 1996, 153:1773-1780. The type of exhalation manoeuvre is an important determinant of the exhaled measurement. Tracheal and right middle lobe NO levels were similar to NO values in exhaled air. Nasal NO was considerably greater than in expired air.
14. Kharitonov SA, Yates DH, Chung KF, Barnes PJ: Changes in the dose of inhaled steroid affect exhaled nitric oxide levels in asthmatic patients. Eur Respir J 1996, 9:196-201. NO increases in exhaled air of asthmatic patients when the dose of inhaled steroids is reduced, whereas there was no significant decrease in spirometry or change in peak flow variability. There was also an increase in asthma symptoms at night. Exhaled NO decreased when the dose of inhaled steroids was increased, and this was associated with a reduction in diurnal variability of peak expiratory flow, and in nocturnal symptoms.
15. Kharitonov SA, Yates DH, Barnes PJ: Inhaled budesonide decreases nitric oxide concentration in the exhaled air of asthmatic patients. Am J Resp Crit Care Meet 1996, 153:454-457. It has been shown in a double-blind crossover, placebo-controlled study that inhaled budesonide significantly reduces the level of NO in exhaled air of asthmatic patients over a 3-week period.
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19. Belvisi MG, Ward JK, Mitchell JA, Barnes PJ: Nitric oxide as a neurotransmitter in human airways. Arch Intern Pharm Therapie 1995, 329:97-110. Elaborate review of the nitrergic innervation in inflammatory conditions.
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21. Robbins RA, Barnes PJ, Springall DR, Warren JB, Kwon OJ, Buttery LD, Wilson AJ, Geller DA, Polak JM: Expression of inducible nitric oxide synthase in human bronchial epithelial cells. Biochem Biophys Res Commun 1994, 203:209-218.
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26. Higenbottam TW: Lung disease and pulmonary endothelial nitric oxide. Exper Physiol 1995, 134:855-864. Concise review focusing on eNOS in lung disease. The authors conclude that pulmonary relaxation is mediated by NO and that the impairment of it may be related to the severity of the pre-existing hypoxaemia.
27. Martinez C, Cases E, Vila JM, Aldasoro M, Medina P, Marco V, Lluch S: Influence of endothelial nitric oxide on neurogenic contraction of human pulmonary arteries. Eur Respir J 1995, 8:1328-1332.
28. Barnes PJ, Liew FW: Why does asthma become persistent? Am J Respir Crit Care Med 1996, 153:523-525. Comprehensive mini-review on the mechanisms leading to persistence of asthma. NO may play an important role in perpetuating asthmatic inflammation and may have a deleterious effect in asthmatic airways as it not only increases airway blood flow and therefore plasma exudation, but it may also tip the balance in favour of T helper lymphocyte type 2 cells.
29. Kacmarek RM, Ripple R, Cockrill BA, Bloch KJ, Zapol WM, Johnson DC: Inhaled nitric oxide. A bronchodilator in mild asthmatics with methacholine-induced bronchospasm. Am J Respir Crit Care Med 1996, 153:128-135. Inhalation of NO by patients with mild asthma with methacholine-induced bronchospasm results in a minor but significant relaxation of airway tone.
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31. Yates D, Kharitonov SA, Robbins RA, Thomas PS, Barnes PJ: Effect of a nitric oxide synthase inhibitor and a glucocorticosteroid on exhaled nitric oxide. Am J Respir Crit Care Med 1995,152:892-896. Single inhalation of L-NMMA reduced exhaled NO in normal and asthmatic patients.
32. Yates DH, Kharitonov SA, Thomas PS, Barnes PJ: Endogenous nitric oxide is decreased in asthmatics by an inhibitor of inducible nitric oxide synthase. Am J Respir Crit Care Med 1996, 154:247-250. Single inhalation of L-NAME resulted in reduced exhaled NO in normal and asthmatic patients, whereas a selective iNOS inhibitor, aminoguanidine, reduced NO in asthmatic but not in normal patients. Prednisolone (30 mg for 3 days) has no effect on exhaled NO in normal individuals, but decreases the raised levels of exhaled NO in asthmatic patients.
33. Kharitonov SA, O'Connor BJ, Evans DJ, Barnes PJ: Allergen-induced late asthmatic reactions are associated with elevation of exhaled nitric oxide. Am J Respir Crit Care Med 1995, 151:1894-1899. After inhaled allergen challenge in asthmatic patients there was no change of exhaled NO during the early bronchoconstrictor response, but a progressive increase during the late response. In single responders or during sham challenge there was no change in exhaled NO.
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35. Kharitonov SA, Evans DJ, Barnes PJ, O'Connor BJ: Bronchial provocation challenge with histamine or adenosine 5' monophosphate does not alter exhaled nitric oxide in asthma [Abstract]. Am J Respir Crit Care Med 1995, 151:125.
36. Massaro AF, Gaston B, Kita D, Fanta C, Stamier J, Drazen JM: Expired nitric oxide levels during treatment for acute asthma. Am J Respir Crit Care Med 1995, 152:800-803. Exhaled NO was reduced after 48 h of systemic glucocorticoid therapy in patients with acute asthma, suggesting that expired NO may prove useful as an index of asthma severity and treatment efficacy.
37. Cailes JB, Kharitonov S, Yates D, Barnes P, Du Bois RM: Decreased endogenous nitric oxide in the exhaled air of systemic sclerosis patients [Abstract]. Thorax 1995, 50:452P.
38. Giaid A, Saieh D: Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N Engl J Med 1995, 333:214-221. In the lungs of the control individuals, NOS was expressed at a high level in the vascular endothelium of all types of vessels and in the pulmonary epithelium. In contrast, little or no expression of the enzyme was found in the vascular endothelium of pulmonary arteries in patients with pulmonary hypertension. The intensity of NOS immunoreactivity correlated inversely with the severity of histological changes.
39. Kimberley B, Nejadnik B, Giraud GD, Hoiden WE: Nasal contribution to exhaled nitric oxide at rest and during breath holding in humans. Am J Respir Crit Care Med 1996, 153:829-836. Different techniques to eliminate nasal NO contamination were described.
40. Kharitonov SA, Rajakulasingam K, O'Connor BJ, Durham SR, Barnes PJ: Nasal nitric oxide is increased in patients with asthma and allergic rhinitis and may be modulated by nasal glucocorticosteroids. J Allergy Clin Immunol 1996, (in press). Nasal NO levels were significantly elevated in patients with untreated rhinitis compared with normal individuals or those treated with nasal steroids, whereas exhaled NO was similar to that in normal subjects. In patients with rhinitis and concomitant asthma, nasal NO was also significantly elevated but not when treated with nasal or inhaled steroids.
41. Hill GE, Snider S, Galbraith TA, Forst S, Robbins RA: Glucocorticoid reduction of bronchial epithelial inflammation during cardiopulmonary bypass. Am J Respir Crit Care Med 1995, 152:1791-1795.
42. Yates DH, Kharitonov SA, Scott DM, Worsdell M, Barnes PJ: Short and long acting P2-agonists do not alter exhaled nitric oxide in asthma [Abstract]. Am J Respir Crit Care Med 1995, 151:129
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47. Kharitonov SA, Yates D, Barnes PJ: Increased nitric oxide in exhaled air of normal human subjects with upper respiratory tract infections. Eur Respir J 1995, 8:295-297. Symptomatic upper respiratory tract infections markedly increase exhaled NO and may reflect the induction of iNOS in upper respiratory tract.
48. Barnes PJ, Kharitonov SA: Exhaled nitric oxide: a new lung function test. Thorax 1996, 51:233-237. Review article focusing on NO involvement in upper and lower airway inflammation, technical factors affecting NO measurement detection, effects of treatment on exhaled NO, and other exhaled markers of airway inflammation.
49. Habib MP, Clements NC, Garewal HS: Cigarette smoking and ethane exhalation in humans. Am J Respir Crit Care Med 1995, 151:1368-1372. Cigarette smokers have increased baseline ethane measured by gas chromatography in exhaled breath compared with non-smokers.
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