A randomized controlled trial of inhaled l-Arginine in patients with cystic fibrosis

Journal of Cystic Fibrosis

Volumn 12, Issue 5, 2013, Pages 468-474

  Grasemann, H ^a,b   Tullis, E ^c   Ratjen, F ^a,b  

^a HOSPITAL FOR SICK CHILDREN   (Canada)

^b HOSPITAL FOR SICK CHILDREN RESEARCH INSTITUTE   (Canada)

^c ST MICHAEL'S HOSPITAL   (Canada)

Author keywords

Airway inflammation; Clinical trial; L Arginine; Nitric oxide; Polyamines

Indexed keywords

ARGINASE; ARGININE; BIOLOGICAL MARKER; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; ORNITHINE; PLACEBO; POLYAMINE; SODIUM CHLORIDE;

ARTICLE; CLINICAL ARTICLE; COLD LIKE SYMPTOMS; CONTROLLED STUDY; COUGH HEADACHE; COUGHING; CYSTIC FIBROSIS; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERANCE; ENZYME ACTIVITY; EPISTAXIS; FEVER; FORCED EXPIRATORY VOLUME; HEADACHE; HEART RATE; HOARSENESS; HUMAN; OCULAR PRURITUS; RANDOMIZED CONTROLLED TRIAL; RASH; SIDE EFFECT; SPUTUM; STOMACH PAIN; TREATMENT DURATION; URTICARIA; WHEEZING;

AIRWAY INFLAMMATION; CLINICAL TRIAL; L-ARGININE; NITRIC OXIDE; POLYAMINES;

ADMINISTRATION, INHALATION; ADOLESCENT; ADULT; ARGININE; CROSS-OVER STUDIES; CYSTIC FIBROSIS; DOUBLE-BLIND METHOD; FEMALE; HUMANS; MALE; MIDDLE AGED; NITRIC OXIDE; RESPIRATORY FUNCTION TESTS; YOUNG ADULT;

EID: 84882882270     PISSN: 15691993     EISSN: 18735010     Source Type: Journal    
DOI: 10.1016/j.jcf.2012.12.008     Document Type: Article

References (23)

1. Grasemann H., Schwiertz R., Grasemann C., Vester U., Racke K., Ratjen F. Decreased systemic bioavailability of l-arginine in patients with cystic fibrosis. Respir Res 2006, 7:87.
2. Grasemann H., Schwiertz R., Matthiesen S., Racke K., Ratjen F. Increased arginase activity in cystic fibrosis airways. Am J Respir Crit Care Med 2005, 172(12):1523-1528.
3. Grasemann H., Al-Saleh S., Scott J.A., Shehnaz D., Mehl A., Amin R., et al. Asymmetric dimethylarginine contributes to airway nitric oxide deficiency in patients with cystic fibrosis. Am J Respir Crit Care Med 2011, 183(10):1363-1368.
4. Bueb J.L., Da Silva A., Mousli M., Landry Y. Natural polyamines stimulate G-proteins. Biochem J 1992, 282(Pt 2):545-550.
5. Chen H., Macleod C., Deng B., Mason L., Kasaian M., Goldman S., et al. CAT-2 amplifies the agonist-evoked force of airway smooth muscle by enhancing spermine-mediated phosphatidylinositol-(4)-phosphate-5-kinase-gamma activity. Am J Physiol Lung Cell Mol Physiol 2007, 293(4):L883-L891.
6. Grasemann H., Michler E., Wallot M., Ratjen F. Decreased concentration of exhaled nitric oxide (NO) in patients with cystic fibrosis. Pediatr Pulmonol 1997, 24(3):173-177.
7. Ho L.P., Innes J.A., Greening A.P. Exhaled nitric oxide is not elevated in the inflammatory airways diseases of cystic fibrosis and bronchiectasis. Eur Respir J 1998, 12(6):1290-1294.
8. Keen C., Gustafsson P., Lindblad A., Wennergren G., Olin A.C. Low levels of exhaled nitric oxide are associated with impaired lung function in cystic fibrosis. Pediatr Pulmonol 2010, 45(3):241-248.
9. Jaffe A., Slade G., Rae J., Laverty A. Exhaled nitric oxide increases following admission for intravenous antibiotics in children with cystic fibrosis. J Cyst Fibros 2003, 2(3):143-147.
10. Gaston B., Ratjen F., Vaughan J.W., Malhotra N.R., Canady R.G., Snyder A.H., et al. Nitrogen redox balance in the cystic fibrosis airway: effects of antipseudomonal therapy. Am J Respir Crit Care Med 2002, 165(3):387-390.
11. 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(2):208-212.
12. Wang X., Dockery D.W., Wypij D., Fay M.E., Ferris B.G. Pulmonary function between 6 and 18years of age. Pediatr Pulmonol 1993, 15(2):75-88.
13. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide. Am J Respir Crit Care Med 2005, 171(8):912-930.
14. Byun J.A., Lee S.H., Jung B.H., Choi M.H., Moon M.H., Chung B.C. Analysis of polyamines as carbamoyl derivatives in urine and serum by liquid chromatography-tandem mass spectrometry. Biomed Chromatogr 2008, 22(1):73-80.
15. Bieth J., Spiess B., Wermuth C.G. The synthesis and analytical use of a highly sensitive and convenient substrate of elastase. Biochem Med 1974, 11(4):350-357.
16. Grasemann H., Gartig S.S., Wiesemann H.G., Teschler H., Konietzko N., Ratjen F. Effect of l-arginine infusion on airway NO in cystic fibrosis and primary ciliary dyskinesia syndrome. Eur Respir J 1999, 13(1):114-118.
17. Grasemann H., Grasemann C., Kurtz F., Tietze-Schillings G., Vester U., Ratjen F. Oral l-arginine supplementation in cystic fibrosis patients: a placebo-controlled study. Eur Respir J 2005, 25(1):62-68.
18. Grasemann H., Ioannidis I., Tomkiewicz R.P., de Groot H., Rubin B.K., Ratjen F. Nitric oxide metabolites in cystic fibrosis lung disease. Arch Dis Child 1998, 78(1):49-53.
19. Dietzsch H.J., Gottschalk B., Heyne K., Leupoid W., Wunderlich P. Cystic fibrosis: comparison of two mucolytic drugs for inhalation treatment (acetylcysteine and arginine hydrochloride). Pediatrics 1975, 55(1):96-100.
20. Yoon S.S., Coakley R., Lau G.W., Lymar S.V., Gaston B., Karabulut A.C., et al. Anaerobic killing of mucoid Pseudomonas aeruginosa by acidified nitrite derivatives under cystic fibrosis airway conditions. J Clin Invest 2006, 116(2):436-446.
21. http://www.clinicaltrials.gov/ct2/show/NCT00570349.
22. Maarsingh H., Zuidhof A.B., Bos I.S., van Duin M., Boucher J.L., Zaagsma J., et al. Arginase inhibition protects against allergen-induced airway obstruction, hyperresponsiveness, and inflammation. Am J Respir Crit Care Med 2008, 178(6):565-573.
23. Ricciardolo F.L., Zaagsma J., Meurs H. The therapeutic potential of drugs targeting the arginase pathway in asthma. Expert Opin Investig Drugs 2005, 14(10):1221-1231.