Skip to main content
PMC home page
Thorax logoLink to Thorax
. 1999 Oct;54(10):947–952. doi: 10.1136/thx.54.10.947

Nasal nitric oxide in man

J Lundberg 1, E Weitzberg 1
PMCID: PMC1745376  PMID: 10491460

Full Text

The Full Text of this article is available as a PDF (1.2 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adisesh L. A., Kharitonov S. A., Yates D. H., Snashell D. C., Newman-Taylor A. J., Barnes P. J. Exhaled and nasal nitric oxide is increased in laboratory animal allergy. Clin Exp Allergy. 1998 Jul;28(7):876–880. doi: 10.1046/j.1365-2222.1998.00332.x. [DOI] [PubMed] [Google Scholar]
  2. Albert J., Schedin U., Lindqvist M., Melcher A., Hjemdahl P., Frostell C. Blockade of endogenous nitric oxide production results in moderate hypertension, reducing sympathetic activity and shortening bleeding time in healthy volunteers. Acta Anaesthesiol Scand. 1997 Oct;41(9):1104–1113. doi: 10.1111/j.1399-6576.1997.tb04852.x. [DOI] [PubMed] [Google Scholar]
  3. Alving K., Weitzberg E., Lundberg J. M. Increased amount of nitric oxide in exhaled air of asthmatics. Eur Respir J. 1993 Oct;6(9):1368–1370. [PubMed] [Google Scholar]
  4. Archer S. Measurement of nitric oxide in biological models. FASEB J. 1993 Feb 1;7(2):349–360. doi: 10.1096/fasebj.7.2.8440411. [DOI] [PubMed] [Google Scholar]
  5. Balfour-Lynn I. M., Laverty A., Dinwiddie R. Reduced upper airway nitric oxide in cystic fibrosis. Arch Dis Child. 1996 Oct;75(4):319–322. doi: 10.1136/adc.75.4.319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Baraldi E., Azzolin N. M., Biban P., Zacchello F. Effect of antibiotic therapy on nasal nitric oxide concentration in children with acute sinusitis. Am J Respir Crit Care Med. 1997 May;155(5):1680–1683. doi: 10.1164/ajrccm.155.5.9154876. [DOI] [PubMed] [Google Scholar]
  7. Beckman J. S., Beckman T. W., Chen J., Marshall P. A., Freeman B. A. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1620–1624. doi: 10.1073/pnas.87.4.1620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Davidson D., Barefield E. S., Kattwinkel J., Dudell G., Damask M., Straube R., Rhines J., Chang C. T. Inhaled nitric oxide for the early treatment of persistent pulmonary hypertension of the term newborn: a randomized, double-masked, placebo-controlled, dose-response, multicenter study. The I-NO/PPHN Study Group. Pediatrics. 1998 Mar;101(3 Pt 1):325–334. doi: 10.1542/peds.101.3.325. [DOI] [PubMed] [Google Scholar]
  9. Dubois A. B., Douglas J. S., Stitt J. T., Mohsenin V. Production and absorption of nitric oxide gas in the nose. J Appl Physiol (1985) 1998 Apr;84(4):1217–1224. doi: 10.1152/jappl.1998.84.4.1217. [DOI] [PubMed] [Google Scholar]
  10. Dötsch J., Demirakça S., Terbrack H. G., Hüls G., Rascher W., Kühl P. G. Airway nitric oxide in asthmatic children and patients with cystic fibrosis. Eur Respir J. 1996 Dec;9(12):2537–2540. doi: 10.1183/09031936.96.09122537. [DOI] [PubMed] [Google Scholar]
  11. Ferguson E. A., Eccles R. Changes in nasal nitric oxide concentration associated with symptoms of common cold and treatment with a topical nasal decongestant. Acta Otolaryngol. 1997 Jul;117(4):614–617. doi: 10.3109/00016489709113447. [DOI] [PubMed] [Google Scholar]
  12. Furukawa K., Harrison D. G., Saleh D., Shennib H., Chagnon F. P., Giaid A. Expression of nitric oxide synthase in the human nasal mucosa. Am J Respir Crit Care Med. 1996 Feb;153(2):847–850. doi: 10.1164/ajrccm.153.2.8564142. [DOI] [PubMed] [Google Scholar]
  13. Geller D. A., Lowenstein C. J., Shapiro R. A., Nussler A. K., Di Silvio M., Wang S. C., Nakayama D. K., Simmons R. L., Snyder S. H., Billiar T. R. Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3491–3495. doi: 10.1073/pnas.90.8.3491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gerlach H., Rossaint R., Pappert D., Falke K. J. Time-course and dose-response of nitric oxide inhalation for systemic oxygenation and pulmonary hypertension in patients with adult respiratory distress syndrome. Eur J Clin Invest. 1993 Aug;23(8):499–502. doi: 10.1111/j.1365-2362.1993.tb00797.x. [DOI] [PubMed] [Google Scholar]
  15. Gerlach H., Rossaint R., Pappert D., Knorr M., Falke K. J. Autoinhalation of nitric oxide after endogenous synthesis in nasopharynx. Lancet. 1994 Feb 26;343(8896):518–519. doi: 10.1016/s0140-6736(94)91465-6. [DOI] [PubMed] [Google Scholar]
  16. Grunewald C., Carlström K., Kumlien G., Ringqvist A., Lundberg J. Exhaled oral and nasal nitric oxide during L-arginine infusion in preeclampsia. Gynecol Obstet Invest. 1998;46(4):232–237. doi: 10.1159/000010040. [DOI] [PubMed] [Google Scholar]
  17. Gustafsson L. E., Leone A. M., Persson M. G., Wiklund N. P., Moncada S. Endogenous nitric oxide is present in the exhaled air of rabbits, guinea pigs and humans. Biochem Biophys Res Commun. 1991 Dec 16;181(2):852–857. doi: 10.1016/0006-291x(91)91268-h. [DOI] [PubMed] [Google Scholar]
  18. Hamid Q., Springall D. R., Riveros-Moreno V., Chanez P., Howarth P., Redington A., Bousquet J., Godard P., Holgate S., Polak J. M. Induction of nitric oxide synthase in asthma. Lancet. 1993 Dec 18;342(8886-8887):1510–1513. doi: 10.1016/s0140-6736(05)80083-2. [DOI] [PubMed] [Google Scholar]
  19. Herulf M., Lundberg J. O., Weitzberg E. Nostril widening improves arterial oxygenation: a role for nasal nitric oxide? Respir Med. 1999 Feb;93(2):134–135. doi: 10.1016/s0954-6111(99)90303-7. [DOI] [PubMed] [Google Scholar]
  20. Imada M., Iwamoto J., Nonaka S., Kobayashi Y., Unno T. Measurement of nitric oxide in human nasal airway. Eur Respir J. 1996 Mar;9(3):556–559. doi: 10.1183/09031936.96.09030556. [DOI] [PubMed] [Google Scholar]
  21. Jain B., Rubinstein I., Robbins R. A., Leise K. L., Sisson J. H. Modulation of airway epithelial cell ciliary beat frequency by nitric oxide. Biochem Biophys Res Commun. 1993 Feb 26;191(1):83–88. doi: 10.1006/bbrc.1993.1187. [DOI] [PubMed] [Google Scholar]
  22. Kharitonov S. A., Rajakulasingam K., O'Connor B., Durham S. R., Barnes P. J. Nasal nitric oxide is increased in patients with asthma and allergic rhinitis and may be modulated by nasal glucocorticoids. J Allergy Clin Immunol. 1997 Jan;99(1 Pt 1):58–64. doi: 10.1016/s0091-6749(97)70301-4. [DOI] [PubMed] [Google Scholar]
  23. Kharitonov S., Alving K., Barnes P. J. Exhaled and nasal nitric oxide measurements: recommendations. The European Respiratory Society Task Force. Eur Respir J. 1997 Jul;10(7):1683–1693. doi: 10.1183/09031936.97.10071683. [DOI] [PubMed] [Google Scholar]
  24. Kimberly B., Nejadnik B., Giraud G. D., Holden W. E. Nasal contribution to exhaled nitric oxide at rest and during breathholding in humans. Am J Respir Crit Care Med. 1996 Feb;153(2):829–836. doi: 10.1164/ajrccm.153.2.8564139. [DOI] [PubMed] [Google Scholar]
  25. Kirsten A. M., Jörres R. A., Kirsten D., Magnussen H. Effect of a nasal challenge with endotoxin-containing swine confinement dust on nasal nitric oxide production. Eur J Med Res. 1997 Aug 28;2(8):335–339. [PubMed] [Google Scholar]
  26. Lee K. H., Tan P. S., Rico P., Delgado E., Kellum J. A., Pinsky M. R. Low levels of nitric oxide as contaminant in hospital compressed air: physiologic significance? Crit Care Med. 1997 Jul;25(7):1143–1146. doi: 10.1097/00003246-199707000-00014. [DOI] [PubMed] [Google Scholar]
  27. Leone A. M., Gustafsson L. E., Francis P. L., Persson M. G., Wiklund N. P., Moncada S. Nitric oxide is present in exhaled breath in humans: direct GC-MS confirmation. Biochem Biophys Res Commun. 1994 Jun 15;201(2):883–887. doi: 10.1006/bbrc.1994.1784. [DOI] [PubMed] [Google Scholar]
  28. Lewandowski K., Busch T., Lohbrunner H., Rensing S., Keske U., Gerlach H., Falke K. J. Low nitric oxide concentrations in exhaled gas and nasal airways of mammals without paranasal sinuses. J Appl Physiol (1985) 1998 Aug;85(2):405–410. doi: 10.1152/jappl.1998.85.2.405. [DOI] [PubMed] [Google Scholar]
  29. Lindberg S., Cervin A., Runer T. Low levels of nasal nitric oxide (NO) correlate to impaired mucociliary function in the upper airways. Acta Otolaryngol. 1997 Sep;117(5):728–734. doi: 10.3109/00016489709113468. [DOI] [PubMed] [Google Scholar]
  30. Lindberg S., Cervin A., Runer T. Nitric oxide (NO) production in the upper airways is decreased in chronic sinusitis. Acta Otolaryngol. 1997 Jan;117(1):113–117. doi: 10.3109/00016489709118001. [DOI] [PubMed] [Google Scholar]
  31. Lorenz R., Born P., Olbert P., Classen M. Factor XIII substitution in ulcerative colitis. Lancet. 1995 Feb 18;345(8947):449–450. doi: 10.1016/s0140-6736(95)90428-x. [DOI] [PubMed] [Google Scholar]
  32. Loukides S., Kharitonov S., Wodehouse T., Cole P. J., Barnes P. J. Effect of arginine on mucociliary function in primary ciliary dyskinesia. Lancet. 1998 Aug 1;352(9125):371–372. doi: 10.1016/S0140-6736(05)60471-0. [DOI] [PubMed] [Google Scholar]
  33. Lundberg J. O. Airborne nitric oxide: inflammatory marker and aerocrine messenger in man. Acta Physiol Scand Suppl. 1996;633:1–27. [PubMed] [Google Scholar]
  34. Lundberg J. O., Ehrén I., Jansson O., Adolfsson J., Lundberg J. M., Weitzberg E., Alving K., Wiklund N. P. Elevated nitric oxide in the urinary bladder in infectious and noninfectious cystitis. Urology. 1996 Nov;48(5):700–702. doi: 10.1016/S0090-4295(96)00423-2. [DOI] [PubMed] [Google Scholar]
  35. Lundberg J. O., Farkas-Szallasi T., Weitzberg E., Rinder J., Lidholm J., Anggåard A., Hökfelt T., Lundberg J. M., Alving K. High nitric oxide production in human paranasal sinuses. Nat Med. 1995 Apr;1(4):370–373. doi: 10.1038/nm0495-370. [DOI] [PubMed] [Google Scholar]
  36. Lundberg J. O., Hellström P. M., Lundberg J. M., Alving K. Greatly increased luminal nitric oxide in ulcerative colitis. Lancet. 1994 Dec 17;344(8938):1673–1674. doi: 10.1016/s0140-6736(94)90460-x. [DOI] [PubMed] [Google Scholar]
  37. Lundberg J. O., Lundberg J. M., Alving K., Weitzberg E. Nitric oxide and inflammation: the answer is blowing in the wind. Nat Med. 1997 Jan;3(1):30–31. doi: 10.1038/nm0197-30. [DOI] [PubMed] [Google Scholar]
  38. Lundberg J. O., Lundberg J. M., Settergren G., Alving K., Weitzberg E. Nitric oxide, produced in the upper airways, may act in an 'aerocrine' fashion to enhance pulmonary oxygen uptake in humans. Acta Physiol Scand. 1995 Dec;155(4):467–468. doi: 10.1111/j.1748-1716.1995.tb09998.x. [DOI] [PubMed] [Google Scholar]
  39. Lundberg J. O., Nordvall S. L., Weitzberg E., Kollberg H., Alving K. Exhaled nitric oxide in paediatric asthma and cystic fibrosis. Arch Dis Child. 1996 Oct;75(4):323–326. doi: 10.1136/adc.75.4.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Lundberg J. O., Rinder J., Weitzberg E., Lundberg J. M., Alving K. Nasally exhaled nitric oxide in humans originates mainly in the paranasal sinuses. Acta Physiol Scand. 1994 Dec;152(4):431–432. doi: 10.1111/j.1748-1716.1994.tb09826.x. [DOI] [PubMed] [Google Scholar]
  41. Lundberg J. O., Rinder J., Weitzberg F., Alving K., Lundberg J. M. Heavy physical exercise decreases nitric oxide levels in the nasal airways in humans. Acta Physiol Scand. 1997 Jan;159(1):51–57. doi: 10.1046/j.1365-201X.1997.68339000.x. [DOI] [PubMed] [Google Scholar]
  42. Lundberg J. O., Settergren G., Gelinder S., Lundberg J. M., Alving K., Weitzberg E. Inhalation of nasally derived nitric oxide modulates pulmonary function in humans. Acta Physiol Scand. 1996 Dec;158(4):343–347. doi: 10.1046/j.1365-201X.1996.557321000.x. [DOI] [PubMed] [Google Scholar]
  43. Lundberg J. O., Weitzberg E., Lundberg J. M., Alving K. Nitric oxide in exhaled air. Eur Respir J. 1996 Dec;9(12):2671–2680. doi: 10.1183/09031936.96.09122671. [DOI] [PubMed] [Google Scholar]
  44. Lundberg J. O., Weitzberg E., Nordvall S. L., Kuylenstierna R., Lundberg J. M., Alving K. Primarily nasal origin of exhaled nitric oxide and absence in Kartagener's syndrome. Eur Respir J. 1994 Aug;7(8):1501–1504. doi: 10.1183/09031936.94.07081501. [DOI] [PubMed] [Google Scholar]
  45. Lundberg J. O., Weitzberg E., Rinder J., Rudehill A., Jansson O., Wiklund N. P., Lundberg J. M., Alving K. Calcium-independent and steroid-resistant nitric oxide synthase activity in human paranasal sinus mucosa. Eur Respir J. 1996 Jul;9(7):1344–1347. doi: 10.1183/09031936.96.09071344. [DOI] [PubMed] [Google Scholar]
  46. Mancinelli R. L., McKay C. P. Effects of nitric oxide and nitrogen dioxide on bacterial growth. Appl Environ Microbiol. 1983 Jul;46(1):198–202. doi: 10.1128/aem.46.1.198-202.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Martin U., Bryden K., Devoy M., Howarth P. Increased levels of exhaled nitric oxide during nasal and oral breathing in subjects with seasonal rhinitis. J Allergy Clin Immunol. 1996 Mar;97(3):768–772. doi: 10.1016/s0091-6749(96)80154-0. [DOI] [PubMed] [Google Scholar]
  48. McCafferty D. M., Mudgett J. S., Swain M. G., Kubes P. Inducible nitric oxide synthase plays a critical role in resolving intestinal inflammation. Gastroenterology. 1997 Mar;112(3):1022–1027. doi: 10.1053/gast.1997.v112.pm9041266. [DOI] [PubMed] [Google Scholar]
  49. Moncada S., Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med. 1993 Dec 30;329(27):2002–2012. doi: 10.1056/NEJM199312303292706. [DOI] [PubMed] [Google Scholar]
  50. Murphy A. W., Platts-Mills T. A., Lobo M., Hayden F. Respiratory nitric oxide levels in experimental human influenza. Chest. 1998 Aug;114(2):452–456. doi: 10.1378/chest.114.2.452. [DOI] [PubMed] [Google Scholar]
  51. Nathan C., Xie Q. W. Nitric oxide synthases: roles, tolls, and controls. Cell. 1994 Sep 23;78(6):915–918. doi: 10.1016/0092-8674(94)90266-6. [DOI] [PubMed] [Google Scholar]
  52. Nijkamp F. P., Folkerts G. Nitric oxide: initiator and modulator. Clin Exp Allergy. 1997 Apr;27(4):347–350. [PubMed] [Google Scholar]
  53. Phillips C. R., Giraud G. D., Holden W. E. Exhaled nitric oxide during exercise: site of release and modulation by ventilation and blood flow. J Appl Physiol (1985) 1996 Jun;80(6):1865–1871. doi: 10.1152/jappl.1996.80.6.1865. [DOI] [PubMed] [Google Scholar]
  54. Pinsky M. R., Genc F., Lee K. H., Delgado E. Contamination of hospital compressed air with nitric oxide: unwitting replacement therapy. Chest. 1997 Jun;111(6):1759–1763. doi: 10.1378/chest.111.6.1759. [DOI] [PubMed] [Google Scholar]
  55. Puybasset L., Rouby J. J., Mourgeon E., Stewart T. E., Cluzel P., Arthaud M., Poète P., Bodin L., Korinek A. M., Viars P. Inhaled nitric oxide in acute respiratory failure: dose-response curves. Intensive Care Med. 1994 May;20(5):319–327. doi: 10.1007/BF01720903. [DOI] [PubMed] [Google Scholar]
  56. Ramis I., Lorente J., Roselló-Catafau J., Quesada P., Gelpí E., Bulbena O. Differential activity of nitric oxide synthase in human nasal mucosa and polyps. Eur Respir J. 1996 Feb;9(2):202–206. doi: 10.1183/09031936.96.09020202. [DOI] [PubMed] [Google Scholar]
  57. Robbins R. A., Millatmal T., Lassi K., Rennard S., Daughton D. Smoking cessation is associated with an increase in exhaled nitric oxide. Chest. 1997 Aug;112(2):313–318. doi: 10.1378/chest.112.2.313. [DOI] [PubMed] [Google Scholar]
  58. Runer T., Cervin A., Lindberg S., Uddman R. Nitric oxide is a regulator of mucociliary activity in the upper respiratory tract. Otolaryngol Head Neck Surg. 1998 Sep;119(3):278–287. doi: 10.1016/S0194-5998(98)70063-4. [DOI] [PubMed] [Google Scholar]
  59. Sanders S. P., Siekierski E. S., Porter J. D., Richards S. M., Proud D. Nitric oxide inhibits rhinovirus-induced cytokine production and viral replication in a human respiratory epithelial cell line. J Virol. 1998 Feb;72(2):934–942. doi: 10.1128/jvi.72.2.934-942.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Sato M., Fukuyama N., Sakai M., Nakazawa H. Increased nitric oxide in nasal lavage fluid and nitrotyrosine formation in nasal mucosa--indices for severe perennial nasal allergy. Clin Exp Allergy. 1998 May;28(5):597–605. doi: 10.1046/j.1365-2222.1998.00270.x. [DOI] [PubMed] [Google Scholar]
  61. Schedin U., Norman M., Gustafsson L. E., Herin P., Frostell C. Endogenous nitric oxide in the upper airways of healthy newborn infants. Pediatr Res. 1996 Jul;40(1):148–151. doi: 10.1203/00006450-199607000-00025. [DOI] [PubMed] [Google Scholar]
  62. Schedin U., Röken B. O., Nyman G., Frostell C., Gustafsson L. E. Endogenous nitric oxide in the airways of different animal species. Acta Anaesthesiol Scand. 1997 Oct;41(9):1133–1141. doi: 10.1111/j.1399-6576.1997.tb04855.x. [DOI] [PubMed] [Google Scholar]
  63. Settergren G., Angdin M., Astudillo R., Gelinder S., Liska J., Lundberg J. O., Weitzberg E. Decreased pulmonary vascular resistance during nasal breathing: modulation by endogenous nitric oxide from the paranasal sinuses. Acta Physiol Scand. 1998 Jul;163(3):235–239. doi: 10.1046/j.1365-201x.1998.00352.x. [DOI] [PubMed] [Google Scholar]
  64. Silkoff P. E., McClean P. A., Slutsky A. S., Furlott H. G., Hoffstein E., Wakita S., Chapman K. R., Szalai J. P., Zamel N. Marked flow-dependence of exhaled nitric oxide using a new technique to exclude nasal nitric oxide. Am J Respir Crit Care Med. 1997 Jan;155(1):260–267. doi: 10.1164/ajrccm.155.1.9001322. [DOI] [PubMed] [Google Scholar]
  65. Watkins D. N., Lewis R. H., Basclain K. A., Fisher P. H., Peroni D. J., Garlepp M. J., Thompson P. J. Expression and localization of the inducible isoform of nitric oxide synthase in nasal polyp epithelium. Clin Exp Allergy. 1998 Feb;28(2):211–219. doi: 10.1046/j.1365-2222.1998.00215.x. [DOI] [PubMed] [Google Scholar]
  66. Xie Q., Nathan C. The high-output nitric oxide pathway: role and regulation. J Leukoc Biol. 1994 Nov;56(5):576–582. doi: 10.1002/jlb.56.5.576. [DOI] [PubMed] [Google Scholar]
  67. Yasuda Y., Itoh T., Miyamura M., Nishino H. Comparison of exhaled nitric oxide and cardiorespiratory indices between nasal and oral breathing during submaximal exercise in humans. Jpn J Physiol. 1997 Oct;47(5):465–470. doi: 10.2170/jjphysiol.47.465. [DOI] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES