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. 2002 Mar;57(3):212–216. doi: 10.1136/thorax.57.3.212

Effect of long term treatment with azithromycin on disease parameters in cystic fibrosis: a randomised trial

J Wolter 1, S Seeney 1, S Bell 1, S Bowler 1, P Masel 1, J McCormack 1
PMCID: PMC1746273  PMID: 11867823

Abstract

Background: Relentless chronic pulmonary inflammation is the major contributor to morbidity and mortality in patients with cystic fibrosis (CF). While immunomodulating therapies such as prednisolone and ibuprofen may be beneficial, their use is limited by side effects. Macrolides have immunomodulatory properties and long term use dramatically improves prognosis in diffuse panbronchiolitis, a condition with features in common with the lung disease of CF.

Methods: To determine if azithromycin (AZM) improves clinical parameters and reduces inflammation in patients with CF, a 3 month prospective randomised double blind, placebo controlled study of AZM (250 mg/day) was undertaken in adults with CF. Monthly assessment included lung function, weight, and quality of life (QOL). Blood and sputum collection assessed systemic inflammation and changes in bacterial flora. Respiratory exacerbations were treated according to the policy of the CF Unit.

Results: Sixty patients were recruited (29 men) of mean (SD) age 27.9 (6.5) years and initial forced expiratory volume in 1 second (FEV1) 56.6 (22.3)% predicted. FEV1% and forced vital capacity (FVC)% predicted were maintained in the AZM group while in the placebo group there was a mean (SE) decline of –3.62 (1.78)% (p=0.047) and –5.73 (1.66)% (p=0.001), respectively. Fewer courses of intravenous antibiotics were used in patients on AZM (0.37 v 1.13, p=0.016). Median C reactive protein (CRP) levels declined in the AZM group from 10 to 5.4 mg/ml but remained constant in the placebo group (p<0.001). QOL improved over time in patients on AZM and remained unchanged in those on placebo (p=0.035).

Conclusion: AZM in adults with CF significantly improved QOL, reduced CRP levels and the number of respiratory exacerbations, and reduced the rate of decline in lung function. Long term AZM may have a significant impact on morbidity and mortality in patients with CF. Further studies are required to define frequency of dosing and duration of benefit.

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Selected References

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  1. Abbott J., Dodd M., Bilton D., Webb A. K. Treatment compliance in adults with cystic fibrosis. Thorax. 1994 Feb;49(2):115–120. doi: 10.1136/thx.49.2.115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Abe S., Nakamura H., Inoue S., Takeda H., Saito H., Kato S., Mukaida N., Matsushima K., Tomoike H. Interleukin-8 gene repression by clarithromycin is mediated by the activator protein-1 binding site in human bronchial epithelial cells. Am J Respir Cell Mol Biol. 2000 Jan;22(1):51–60. doi: 10.1165/ajrcmb.22.1.3400. [DOI] [PubMed] [Google Scholar]
  3. Bradley J., Dempster M., Wallace E., Elborn S. The adaptations of a quality of life questionnaire for routine use in clinical practice: the Chronic Respiratory Disease Questionnaire in cystic fibrosis. Qual Life Res. 1999;8(1-2):65–71. doi: 10.1023/a:1026437214170. [DOI] [PubMed] [Google Scholar]
  4. Conway S. P., Pond M. N., Hamnett T., Watson A. Compliance with treatment in adult patients with cystic fibrosis. Thorax. 1996 Jan;51(1):29–33. doi: 10.1136/thx.51.1.29. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Desaki M., Takizawa H., Ohtoshi T., Kasama T., Kobayashi K., Sunazuka T., Omura S., Yamamoto K., Ito K. Erythromycin suppresses nuclear factor-kappaB and activator protein-1 activation in human bronchial epithelial cells. Biochem Biophys Res Commun. 2000 Jan 7;267(1):124–128. doi: 10.1006/bbrc.1999.1917. [DOI] [PubMed] [Google Scholar]
  6. Guyatt G. H., Berman L. B., Townsend M., Pugsley S. O., Chambers L. W. A measure of quality of life for clinical trials in chronic lung disease. Thorax. 1987 Oct;42(10):773–778. doi: 10.1136/thx.42.10.773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Howe R. A., Spencer R. C. Macrolides for the treatment of Pseudomonas aeruginosa infections? J Antimicrob Chemother. 1997 Aug;40(2):153–155. doi: 10.1093/jac/40.2.153. [DOI] [PubMed] [Google Scholar]
  8. Ichikawa Y., Ninomiya H., Koga H., Tanaka M., Kinoshita M., Tokunaga N., Yano T., Oizumi K. Erythromycin reduces neutrophils and neutrophil-derived elastolytic-like activity in the lower respiratory tract of bronchiolitis patients. Am Rev Respir Dis. 1992 Jul;146(1):196–203. doi: 10.1164/ajrccm/146.1.196. [DOI] [PubMed] [Google Scholar]
  9. Jaffé A., Francis J., Rosenthal M., Bush A. Long-term azithromycin may improve lung function in children with cystic fibrosis. Lancet. 1998 Feb 7;351(9100):420–420. doi: 10.1016/S0140-6736(05)78360-4. [DOI] [PubMed] [Google Scholar]
  10. Kawamura-Sato K., Iinuma Y., Hasegawa T., Horii T., Yamashino T., Ohta M. Effect of subinhibitory concentrations of macrolides on expression of flagellin in Pseudomonas aeruginosa and Proteus mirabilis. Antimicrob Agents Chemother. 2000 Oct;44(10):2869–2872. doi: 10.1128/aac.44.10.2869-2872.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Khan A. A., Slifer T. R., Araujo F. G., Remington J. S. Effect of clarithromycin and azithromycin on production of cytokines by human monocytes. Int J Antimicrob Agents. 1999 Feb;11(2):121–132. doi: 10.1016/s0924-8579(98)00091-0. [DOI] [PubMed] [Google Scholar]
  12. Kobayashi H., Takeda H., Sakayori S., Kawakami Y., Otsuka Y., Tamura M., Konishi K., Tanimoto S., Fukakusa M., Shimada K. [Study on azithromycin in treatment of diffuse panbronchiolitis]. Kansenshogaku Zasshi. 1995 Jun;69(6):711–722. doi: 10.11150/kansenshogakuzasshi1970.69.711. [DOI] [PubMed] [Google Scholar]
  13. Molinari G., Guzmán C. A., Pesce A., Schito G. C. Inhibition of Pseudomonas aeruginosa virulence factors by subinhibitory concentrations of azithromycin and other macrolide antibiotics. J Antimicrob Chemother. 1993 May;31(5):681–688. doi: 10.1093/jac/31.5.681. [DOI] [PubMed] [Google Scholar]
  14. Morikawa K., Watabe H., Araake M., Morikawa S. Modulatory effect of antibiotics on cytokine production by human monocytes in vitro. Antimicrob Agents Chemother. 1996 Jun;40(6):1366–1370. doi: 10.1128/aac.40.6.1366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mukae H., Kadota J., Ashitani J., Taniguchi H., Mashimoto H., Kohno S., Matsukura S. Elevated levels of soluble adhesion molecules in serum of patients with diffuse panbronchiolitis. Chest. 1997 Dec;112(6):1615–1621. doi: 10.1378/chest.112.6.1615. [DOI] [PubMed] [Google Scholar]
  16. Oermann C. M., Sockrider M. M., Konstan M. W. The use of anti-inflammatory medications in cystic fibrosis: trends and physician attitudes. Chest. 1999 Apr;115(4):1053–1058. doi: 10.1378/chest.115.4.1053. [DOI] [PubMed] [Google Scholar]
  17. Oldfield E. C., 3rd, Fessel W. J., Dunne M. W., Dickinson G., Wallace M. R., Byrne W., Chung R., Wagner K. F., Paparello S. F., Craig D. B. Once weekly azithromycin therapy for prevention of Mycobacterium avium complex infection in patients with AIDS: a randomized, double-blind, placebo-controlled multicenter trial. Clin Infect Dis. 1998 Mar;26(3):611–619. doi: 10.1086/514566. [DOI] [PubMed] [Google Scholar]
  18. Ramsey B. W., Pepe M. S., Quan J. M., Otto K. L., Montgomery A. B., Williams-Warren J., Vasiljev-K M., Borowitz D., Bowman C. M., Marshall B. C. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group. N Engl J Med. 1999 Jan 7;340(1):23–30. doi: 10.1056/NEJM199901073400104. [DOI] [PubMed] [Google Scholar]
  19. Sugihara E. Effect of macrolide antibiotics on neutrophil function in human peripheral blood. Kansenshogaku Zasshi. 1997 Apr;71(4):329–336. doi: 10.11150/kansenshogakuzasshi1970.71.329. [DOI] [PubMed] [Google Scholar]
  20. Takizawa H., Desaki M., Ohtoshi T., Kawasaki S., Kohyama T., Sato M., Tanaka M., Kasama T., Kobayashi K., Nakajima J. Erythromycin modulates IL-8 expression in normal and inflamed human bronchial epithelial cells. Am J Respir Crit Care Med. 1997 Jul;156(1):266–271. doi: 10.1164/ajrccm.156.1.9612065. [DOI] [PubMed] [Google Scholar]
  21. Villagrasa V., Berto L., Cortijo J., Perpina M., Sanz C., Morcillo E. J. Effects of erythromycin on chemoattractant-activated human polymorphonuclear leukocytes. Gen Pharmacol. 1997 Oct;29(4):605–609. doi: 10.1016/s0306-3623(96)00566-6. [DOI] [PubMed] [Google Scholar]
  22. Wolter J. M., Bowler S. D., Nolan P. J., McCormack J. G. Home intravenous therapy in cystic fibrosis: a prospective randomized trial examining clinical, quality of life and cost aspects. Eur Respir J. 1997 Apr;10(4):896–900. [PubMed] [Google Scholar]

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