Bülent Taner KARADAĞ, Goncagül HAKLAR, Zeynep Seda UYAN, Fazilet KARAKOÇ, Elif DAĞLI, Sedat OKTEM, Refika ERSU, Göksenin ÜNLÜGÜZEL ÜSTÜN, Erkan ÇAKIR

Effect of inhaled steroids on clinical and inflammatoryparameters in children with cystic fibrosis

Background/aim: The effectiveness of inhaled corticosteroids (ICSs) in cystic fibrosis (CF) is controversial. The aim of this study was to investigate the effect of an ICS on bronchial hyperreactivity (BHR), oxidative status, and clinical and inflammatory parameters in CF patients. Materials and methods: CF patients were randomized to receive either 2 mg/day nebulized budesonide or 0.9% normal saline as placebo for 8 weeks. Results: Twenty-nine CF patients (mean age: 10.5 ± 2.9 years) were enrolled in the study. There was no statistically significant difference between the two groups at the end of 8 weeks in terms of symptoms, pulmonary function, BHR, oxidative burst, hs-CRP, or ESR. Although there was a significant decrease in malondialdehyde levels in both groups, there was no difference between the two groups. Percentage of neutrophils in the sputum of patients decreased in the budesonide group (P = 0.006). Although sputum IL-8 levels significantly increased in both groups, there was no statistically significant difference between the two groups. Conclusion: Although there was a significant decrease in the percentage of neutrophils in sputum with budesonide, 8 weeks of 2 mg/ day nebulized budesonide was not effective in terms of BHR, oxidative status, or clinical and other inflammatory parameters in children with CF.

PDF

___

1. Konstan MW, Berger M. Current understanding of the inflammatory process in cystic fibrosis: onset and etiology. Pediatr Pulmonol 1997; 24: 137-142.
2. Chmiel JF, Konstan MW. Inflammation and anti-inflammatory therapies for cystic fibrosis. Clin Chest Med 2007; 28: 331-346.
3. Kennedy MJ. Inflammation and cystic fibrosis pulmonary disease. Pharmacotherapy 2001; 21: 593-603.
4. Rosenstein BJ, Eigen H. Risks of alternate day prednisone in patients with cystic fibrosis. Pediatrics 1991; 87: 245-246.
5. Kontsan MW, Byard PJ, Hoppel CL, Davis PB. Effects of high dose ibuprofen in patients with cystic fibrosis. N Engl J Med 1995; 332: 848-854.
6. Jaffe A, Francis J, Rosenthal M, Bush A. Long-term azithromycin may improve lung function in children with cystic fibrosis. Lancet 1998; 351: 420.
7. Nikolaizik WH, Schoni MH. Pilot study to assess the effect of inhaled corticosteroids on lung function in patients with cystic fibrosis. J Pediatr 1996; 128: 271-274.
8. van Haren EH, Lammers JW, Festen J, Heijerman HG, Groot CA, van Herwaarden CL. The effects of the inhaled corticosteroid budesonide on lung function and bronchial hyperresponsiveness in adult patients with cystic fibrosis. Respir Med 1995; 89: 209-214.
9. Wojtczak HA, Kerby GS, Wagener JS, Copenhaver SC, Gotlin RW, Riches DW, Accurso FJ. Beclomethasone diproprionate reduced airway inflammation without adrenal suppression in young children with cystic fibrosis: a pilot study. Pediatr Pulmonol 2001; 32: 293-302.
10. Balfour-Lynn IM, Klein NJ, Dinwiddie R. Randomised controlled trial of inhaled corticosteroids (fluticasone proprionate) in cystic fibrosis. Arch Dis Child 1997; 77: 124- 130.
11. Prescott WA, Johnson CE. Antiinflammatory therapies for cystic fibrosis: past, present and future. Pharmacotherapy 2005; 25: 555-573.
12. Balfour-Lynn IM, Welch K. Inhaled corticosteroids for cystic fibrosis (review). Cochrane Database Syst Rev 2014; 10: CD001915. doi: 10.1002/14651858.CD001915.
13. Allen DB, Bielory L, Derendorf H, Dluhy R, Colice GL, Szelfer SJ. Inhaled corticosteroids: past lessons and future issues. J Allergy Clin Immunol 2003; 112: S1-40.
14. Shwachman H, Kulczycki LL. Long-term study of one hundred five patients with cystic fibrosis; studies made over a five- to fourteen-year period. AMA J Dis Child 1958; 96: 6-15.
15. Brasfield D, Hicks G, Soong S, Tiller RE. The chest roentgenogram in cystic fibrosis: a new scoring system. Pediatrics 1979; 63: 24-29.
16. Helbich TH, Heinz-Peer G, Eichler I, Wunderbaldinger P, Götz M, Wojnarowski C, Brasch RC, Herold CJ. Cystic fibrosis: CT assessment of lung involvement in children and adults. Radiology 1999; 213: 537-544.
17. Guran T, Ersu R, Karadag B, Karakoc F, Demirel GY, Hekim N, Dagli E. Withdrawal of inhaled steroids in children with noncystic fibrosis bronchiectasis. J Clin Pharm Ther 2008; 33: 603- 611.
18. Wong HH, Fahy JV. Safety of one method of sputum induction in asthmatic subjects. Am J Respir Crit Care Med 1997; 156: 299-303.
19. American Thoracic Society. Standardization of spirometry, 1994 update. Am J Respir Crit Care Med 1995; 152: 1107-1136.
20. Knudson RJ, Lebowitz MD, Holberg GJ, Burrows B. Changes in the normal maximal expiratory flow-volume curve with growth and aging. Am Rev Respir Dis 1983; 127: 725-734.
21. Crapo RO, Casaburi R, Coates AL, Enright PL, Hankinson JL, Irvin CG, MacIntyre NR, McKay RT, Wanger JS, Anderson SD et al. Guidelines for metacholine and exercise challenge testing - 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 2000; 161: 309-329.
22. Hargreave FE, Ryan G, Thomson NC, OByrne PM, Latimer K, Juniper EF, Dolovich J. Bronchial responsiveness to histamine or metacholine in asthma: measurement and clinical significance. J Allergy Clin Immunol 1981; 68: 347-355.
23. Konstan MW, VanDevanter DR, Rasouliyan L, Pasta DJ, Yegin A, Morgan WJ, Wagener JS, for the Scientific Advisory Group and Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis. Trends in the use of routine therapies in cystic fibrosis. Pediatr Pulmonol 2010; 45: 1167-1172.
24. Balfour-Lynn IM, Elborn JS. CF asthma: what is it and what do we do about it? Thorax 2002; 57: 742-748.
25. Balfour-Lynn IM, Welch K. Inhaled corticosteroids for cystic fibrosis. Cochrane Database Syst Rev 2009 Jan 21; 1: CD001915. doi: 10.1002/14651858.CD001915.
26. Elizur A, Cannon C, Ferkol TW. Airway inflammation in cystic fibrosis. Chest 2008; 133: 489-495.
27. Ren CL, Pasta DJ, Rasouliyan L, Wagener JS, Konstan MW, Morgan WJ: Scientific Advisory Group and the Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis. Relationship between inhaled corticosteroid therapy and rate of lung function decline in children with cystic fibrosis. J Pediatr 2008; 153: 746-751.
28. De Boeck K, Vermeulen F, Wanyama S, Thoms M, on behalf of the members of the Belgian CF Registry. Inhaled corticosteroids and lower lung function decline in young children with cystic fibrosis. Eur Respir J 2011; 37: 1091-1095.
29. Elborn JS. Cystic fibrosis. Lancet 2016; 388: 2519-2531.
30. Montgomery ST, Mall MA, Kicic A, Stick SM on behalf of AREST CF. Hypoxia and sterile inflammation in cystic fibrosis airways: mechanisms and potential therapies. Eur Respir J 2017; 49. pii: 1600903.
31. Sawicki G, Haver K. Asthma in children younger than 12 years: epidemiology and pathophysiology. UpToDate 2016.
32. Sanchez I, Powell RE, Pasterkamp H. Wheezing and airflow obstruction during methacholine challenge in children with cystic fibrosis and in normal children. Am Rev Respir Dis 1993; 147: 705-709.
33. Bisgaard H, Pedersen SS, Nielsen KG, Skov M, Laursen EM, Kronborg G, Reimert CM, Høiby N, Koch C. Controlled trial of inhaled budesonide in patients with cystic fibrosis and chronic bronchopulmonary Pseudomonas aeruginosa infection. Am J Respir Crit Care Med 1997; 156: 1190-1196.
34. Brand PL. Bronchodilators in cystic fibrosis. J R Soc Med 2000; 93: 37-39.
35. Dauletbaev N, Viel K, Behr J, Loitsch S, Buhl R, Wagner TO, Bargon J. Effects of short-term inhaled fluticasone on oxidative burst of sputum cells in cystic fibrosis patients. Eur Respir J 1999; 14: 1150-1155.
36. Leech M, Hutchinson P, Holdsworth SR, Morand EF. Endogenous glucocorticoids modulate neutrophil migration and synovial P-selectin but not neutrophil phagocytic or oxidative function in experimental arthritis. Clin Exp Immunol 1998; 112: 383-388.
37. Llewellyn-Jones CG, Hill SL, Stockley RA. Effect of fluticasone propionate on neutrophil chemotaxis, superoxide generation, and extracellular proteolytic activity in vitro. Thorax 1994; 49: 207-212.
38. Gould NS, Gauthier S, Kariya CT, Min E, Huang J, Brian DJ. Hypertonic saline increases lung epithelial lining fluid glutathione and thiocyanate: two protective CFTR-dependent thiols against oxidative injury. Respir Res 2010; 11: 119-129.
39. Osika E, Cavaillon JM, Chadelat K, Boule M, Fitting C, Tournier G, Clement A. Distinct sputum cytokine profiles in cystic fibrosis and other chronic inflammatory airway disease. Eur Respir J 1999; 14: 339-346.
40. Salva PS, Doyle NA, Graham L, Eigen H, Doerschuk CM. TNF-α, soluble ICAM-1 and neutrophils in sputum of cystic fibrosis patients. Pediatr Pulmonol 1996; 21: 11-19.
41. Shanks KK, Guang W, Kim KC, Lillehoj EP. Interleukin-8 production by human airway epithelial cells in response to Pseudomonas aeruginosa clinical isolates expressing type a or type b flagellins. Clin Vaccine Immunol 2010; 17: 1196-1202.
42. Balfour-Lynn IM, Lees B, Hall P, Phillips G, Khan M, Flather M, Elborn JS, on behalf of the CF WISE Investigators. Multicenter randomized controlled trial of withdrawal of inhaled corticosteroids in cystic fibrosis. Am J Respir Crit Care Med 2006; 173: 1356-1362.
43. Patel H, Platt R, Lozano JM, Wang EEL. Glucocorticoids for acute viral bronchiolitis in infants and young children. Cochrane Database of Systematic Reviews 2004, Issue 3. [DOI: 10.1002/14651858].
44. Zhang X, Moilanen E, Kankaanranta H. Beclomethasone, budesonide and fluticasone propionate inhibit human neutrophil apoptosis. Eur J Pharmacol 2001; 431: 365-371.
45. Balfour-Lynn IM, Welch K. Inhaled corticosteroids for cystic fibrosis (review). Cochrane Database Syst Rev 2016; 10: CD001915. doi: 10.1002/14651858.CD001915.