Safety of inhaled corticosteroids: Room for improvement

Pulmonary Pharmacology and Therapeutics

Volumn 20, Issue 1, 2007, Pages 23-35

  Rossi, Giovanni A ^a   Cerasoli, Franklin ^b   Cazzola, Mario ^c  

^a G GASLINI INSTITUTE   (Italy)

^b ALTANA Pharma US   (United States)

^c Department of Respiratory Medicine   (Italy)

Author keywords

Adrenal suppression; Growth velocity; HPA axis; Inhaled corticosteroids; Skin thinning

Indexed keywords

BECLOMETASONE DIPROPIONATE; BUDESONIDE; CICLESONIDE; CORTICOSTEROID; FLUNISOLIDE; FLUTICASONE PROPIONATE; INFLUENZA VACCINE; MOMETASONE FUROATE; NEDOCROMIL; TRIAMCINOLONE;

ADRENAL CORTEX INSUFFICIENCY; ANTIINFLAMMATORY ACTIVITY; ARTICLE; ASPERGILLOSIS; ASTHMA; BONE DENSITY; CATARACT; CHRONIC OBSTRUCTIVE LUNG DISEASE; CLINICAL TRIAL; CORTICOSTEROID THERAPY; DRUG ABSORPTION; DRUG MEGADOSE; DRUG SAFETY; FRACTURE; GLAUCOMA; GROWTH RETARDATION; HIGH RISK PATIENT; HOARSENESS; HUMAN; HYPOTHALAMUS HYPOPHYSIS ADRENAL SYSTEM; LUNG ASPERGILLOSIS; LUNG INFECTION; MYCOSIS; OSTEOPOROSIS; PARTICLE SIZE; PATIENT COMPLIANCE; PHARYNGITIS; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; SKIN BRUISING; SKIN MANIFESTATION; SKIN THINNING; SKINFOLD THICKNESS; THRUSH;

ADMINISTRATION, INHALATION; ADRENAL CORTEX HORMONES; ANTI-ALLERGIC AGENTS; ASTHMA; HUMANS; MODELS, BIOLOGICAL; PREGNENEDIONES; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE; RISK ASSESSMENT;

EID: 33750450043     PISSN: 10945539     EISSN: 15229629     Source Type: Journal    
DOI: 10.1016/j.pupt.2005.10.008     Document Type: Article

References (146)

1. National Institutes of Health. Global initiative for asthma: global strategy for asthma management and prevention (2004). http://www.ginasthma.com/workshop_revised.pdf Available at:
2. Umland S.P., Schleimer R.P., and Johnston S.L. Review of the molecular and cellular mechanisms of action of glucocorticoids for use in asthma. Pulm Pharmacol Ther 15 (2002) 35-50
3. Pelaia G., Vatrella A., Cuda G., Maselli R., and Marsico S.A. Molecular mechanisms of corticosteroid actions in chronic inflammatory airway diseases. Life Sci 72 (2003) 1549-1561
4. Cazzola M., and Dahl R. Inhaled combination therapy with long-acting beta 2-agonists and corticosteroids in stable COPD. Chest 126 (2004) 220-237
5. de Melo M.N., Ernst P., and Suissa S. Inhaled corticosteroids and the risk of a first exacerbation in COPD patients. Eur Respir J 23 (2004) 692-697
6. Alsaeedi A., Sin D.D., and McAlister F.A. The effects of inhaled corticosteroids in chronic obstructive pulmonary disease: a systematic review of randomized placebo-controlled trials. Am J Med 113 (2002) 59-65
7. Cazzola M., Matera M.G., and Pauwels R. Corticosteroids in COPD. In: Celli B.R. (Ed). Pharmacotherapy in chronic obstructive pulmonary disease (2004), Marcel Dekker, New York 265-298
8. Colice G.L. Comparing inhaled corticosteroids. Respir Care 45 (2000) 846-853
9. Edsbacker S. Pharmacological factors that influence the choice of inhaled corticosteroids. Drugs 58 Suppl. 4 (1999) 7-16 [discussion 51-52]
10. Singh J.M., Palda V.A., Stanbrook M.B., and Chapman K.R. Corticosteroid therapy for patients with acute exacerbations of chronic obstructive pulmonary disease: a systematic review. Arch Intern Med 162 (2002) 2527-2536
11. Thorsson L., Dahlstrom K., Edsbacker S., Kallén A., Paulson J., and Wiren J.E. Pharmacokinetics and systemic effects of inhaled fluticasone propionate in healthy subjects. Br J Clin Pharmacol 43 (1997) 155-161
12. Rohatagi S., Appajosyula S., Derendorf H., Szefler S., Nave R., Zech K., et al. Risk-benefit value of inhaled glucocorticoids: a pharmacokinetic/pharmacodynamic perspective. J Clin Pharmacol 44 (2004) 37-47
13. Pedersen S., and O'Byrne P. A comparison of the efficacy and safety of inhaled corticosteroids in asthma. Allergy 52 Suppl. 39 (1997) 1-34
14. Masoli M., Holt S., Weatherall M., and Beasley R. Dose-response relationship of inhaled budesonide in adult asthma: a meta-analysis. Eur Respir J 23 (2004) 552-558
15. Kelly H.W., and Nelson H.S. Potential adverse effects of the inhaled corticosteroids. J Allergy Clin Immunol 112 (2003) 469-478
16. Cave A., Arlett P., and Lee E. Inhaled and nasal corticosteroids: factors affecting the risks of systemic adverse effects. Pharmacol Ther 83 (1999) 153-179
17. Hanania N.A., Chapman K.R., and Kesten S. Adverse effects of inhaled corticosteroids. Am J Med 98 (1995) 196-208
18. Salvatoni A., Piantanida E., Nosetti L., and Nespoli L. Inhaled corticosteroids in childhood asthma: long-term effects on growth and adrenocortical function. Paediatr Drugs 5 (2003) 351-361
19. Leone F.T., Fish J.E., Szefler S.J., and West S.L. Systematic review of the evidence regarding potential complications of inhaled corticosteroid use in asthma: collaboration of American College of Chest Physicians, American Academy of Allergy, Asthma, and Immunology, and American College of Allergy, Asthma, and Immunology. Chest 124 (2003) 2329-2340
20. Lipworth B.J. Systemic adverse effects of inhaled corticosteroid therapy: a systematic review and meta-analysis. Arch Intern Med 159 (1999) 941-955
21. van Grunsven P.M., van Schayck C.P., Derenne J.P., Kerstjens H.A.M., Renkema T.E.J., Postma D.S., et al. Long term effects of inhaled corticosteroids in chronic obstructive pulmonary disease: a meta-analysis. Thorax 54 (1999) 7-14
22. Suris J.C., Parera N., and Puig C. Chronic illness and emotional distress in adolescence. J Adolesc Health 19 (1996) 153-156
23. Howenstine M.S., and Eigen H. Medical care of the adolescent with asthma. Adolesc Med 11 (2000) 501-519
24. Okelo S.O., Wu A.W., Krishnan J.A., Rand C.S., Skinner E.A., and Diette G.B. Emotional quality-of-life and outcomes in adolescents with asthma. J Pediatr 145 (2004) 523-529
25. Boulet L.-P. Perception of the role and potential side effects of inhaled corticosteroids among asthmatic patients. Chest 113 (1998) 587-592
26. Meibohm B., Hochhaus G., Rohatagi S., Mollmann H., Barth J., Wagner M., et al. Dependency of cortisol suppression on the administration time of inhaled corticosteroids [published correction appears in J Clin Pharmacol 1997; 37: 1000]. J Clin Pharmacol 37 (1997) 704-710
27. Barnes N.C. Safety of high-dose inhaled corticosteroids. Respir Med 87 Suppl. A (1993) 27-31
28. Todd G.R., Acerini C.L., Ross-Russell R., Zahra S., Warner J.T., and McCance D. Survey of adrenal crisis associated with inhaled corticosteroids in the United Kingdom. Arch Dis Child 87 (2002) 457-461
29. Thomas M., Leather D., and Price D. Unlicensed use of high-dose inhaled corticosteroids in the UK occurs principally with fluticasone-an observational study of 26359 patients. Eur Respir J 24 (2004) 501s [Abstract P3137]
30. Wolthers O.D., Hansen M., Juul A., Nielsen H.K., and Pedersen S. Knemometry, urine cortisol excretion, and measures of the insulin-like growth factor axis and collagen turnover in children treated with inhaled glucocorticosteroids. Pediatr Res 41 (1997) 44-50
31. Kannisto S., Korppi M., Remes K., and Voutilainen R. Adrenal suppression, evaluated by a low dose adrenocorticotropin test, and growth in asthmatic children treated with inhaled steroids. J Clin Endocrinol Metab 85 (2000) 652-657
32. Barnes N.C., Hallett C., and Harris T.A. Clinical experience with fluticasone propionate in asthma: a meta-analysis of efficacy and systemic activity compared with budesonide and beclomethasone dipropionate at half the microgram dose or less. Respir Med 92 (1998) 95-104
33. Mahachoklertwattana P., Sudkronrayudh K., Direkwattanachai C., Choubtum L., and Okascharoen C. Decreased cortisol response to insulin induced hypoglycaemia in asthmatics treated with inhaled fluticasone propionate. Arch Dis Child 89 (2004) 1055-1058
34. Sim D., Griffiths A., Armstrong D., Clarke C., Rodda C., and Freezer N. Adrenal suppression from high-dose inhaled fluticasone propionate in children with asthma. Eur Respir J 21 (2003) 633-636
35. Martin R.J., Szefler S.J., Chinchilli V.M., Kraft M., Dolovich M., Boushey M.A., et al. Systemic effect comparisons of six inhaled corticosteroid preparations. Am J Respir Crit Care Med 165 (2002) 1377-1383
36. Samaras K., Pett S., Gowers A., McMurchie M., and Cooper D.A. Iatrogenic Cushing's syndrome with osteoporosis and secondary adrenal failure in human immunodeficiency virus-infected patients receiving inhaled corticosteroids and ritonavir-boosted protease inhibitors: six cases. J Clin Endocrinol Metab 90 (2005) 4394-4398
37. Kennedy M.J., Carpenter J.M., Lozano R.A., and Castile R.G. Impaired recovery of hypothalamic-pituitary-adrenal axis function and hypoglycemic seizures after high-dose inhaled corticosteroid therapy in a toddler. Ann Allergy Asthma Immunol 88 (2002) 523-526
38. Allen D.B. Inhaled corticosteroid therapy for asthma in preschool children: growth issues. Pediatrics 109 (2002) 373-380
39. National Institutes of Health. National Heart, Lung and Blood Institute: Expert panel report: guidelines for the diagnosis and management of asthma: update on selected topics 2002. NIH Publication No. 02-5074, June 2003.
40. Agertoft L., and Pedersen S. Short-term knemometry and urine cortisol excretion in children treated with fluticasone propionate and budesonide: a dose response study. Eur Respir J 10 (1997) 1507-1512
41. Anhoj J., Bisgaard A.M., and Bisgaard H. Systemic activity of inhaled steroids in 1- to 3-year-old children with asthma. Pediatrics 109 (2002) E40
42. Visser M.J., van Aalderen W.M., Elliott B.M., Odink R.J., and Brand P.L. Short-term growth in asthmatic children using fluticasone propionate. Chest 113 (1998) 584-586
43. Bisgaard H., Allen D., Milanowski J., Kalev I., Willits L., and Davies P. Twelve-month safety and efficacy of inhaled fluticasone propionate in children aged 1-3 years with recurrent wheezing. Pediatrics 113 (2004) E87-E94
44. The Childhood Asthma Management Program Research Group. Long-term effects of budesonide or nedocromil in children with asthma. N Engl J Med 343 (2000) 1054-1063
45. Silverstein M.D., Yunginger J.W., Reed C.E., Petterson T., Zimmerman D., Li J.T., et al. Attained adult height after childhood asthma: effect of glucocorticoid therapy. J Allergy Clin Immunol 99 (1997) 466-474
46. Agertoft L., and Pedersen S. Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. N Engl J Med 343 (2000) 1064-1069
47. Purucker M., and Malozowski S. Inhaled corticosteroids and growth velocity in children with asthma. J Pediatr 135 (1999) 264-266
48. Malozowski S., Purucker M., and Worobec A. Cushing's syndrome induced by betamethasone nose drops. Children taking intranasal corticosteroids should be monitored for growth retardation. Br Med J 318 (1999) 1355
49. Purucker M., and Malozowski S. Asthma, corticosteroids, and growth. N Engl J Med 344 (2001) 607 [author reply 607-8]
50. Drazen J.M., Silverman E.K., and Lee T.H. Heterogeneity of therapeutic responses in asthma. Br Med Bull 56 (2000) 1054-1070
51. Pelaia G., Vatrella A., Gallelli L., Cazzola M., Maselli R., and Marsico S.A. Potential genetic influences on the response to asthma treatment. Pulm Pharmacol Ther 17 (2004) 253-261
52. van Staa T.P., Leufkens H.G., and Cooper C. The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int 13 (2002) 777-787
53. Weinstein R.S., Jilka R.L., Parfitt A.M., and Manolagas S.C. Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest 102 (1998) 274-282
54. Manolagas S.C. Corticosteroids and fractures: a close encounter of the third cell kind. J Bone Miner Res 15 (2000) 1001-1005
55. Randell T.L., Donaghue K.C., Ambler G.R., Cowell C.T., Fitzgerald D.A., and van Asperen P.P. Safety of the newer inhaled corticosteroids in childhood asthma. Paediatr Drugs 5 (2003) 481-504
56. Allen H.D.W., Thong I.G., Clifton-Bligh P., Holmes S., Nery L., and Wilson K.B. Effects of high-dose inhaled corticosteroids on bone metabolism in prepubertal children with asthma. Pediatr Pulmonol 29 (2000) 188-193
57. Lukert B.P., and Raisz L.G. Glucocorticoid-induced osteoporosis: pathogenesis and management. Ann Intern Med 112 (1990) 352-364
58. Hopp R.J., Degan J.A., Phelan J., Lappe J., and Gallagher G.C. Cross-sectional study of bone density in asthmatic children. Pediatr Pulmonol 20 (1995) 189-192
59. Gregson R.K., Rao R., Murrills A.J., Taylor P.A., and Warner J.O. Effect of inhaled corticosteroids on bone mineral density in childhood asthma: comparison of fluticasone propionate with beclomethasone dipropionate. Osteoporos Int 8 (1998) 418-422
60. Schlienger R.G., Jick S.S., and Meier C.R. Inhaled corticosteroids and the risk of fractures in children and adolescents. Pediatrics 114 (2004) 469-473
61. Allen D.B. Systemic effects of inhaled corticosteroids in children. Curr Opin Pediatr 16 (2004) 440-444
62. Marystone J.F., Barrett-Connor E.L., and Morton D.J. Inhaled and oral corticosteroids: their effects on bone mineral density in older adults. Am J Public Health 85 (1995) 1693-1695
63. Herrala J., Puolijoki H., Impivaara O., Liippo K., Tala E., and Nieminen M.M. Bone mineral density in asthmatic women on high-dose inhaled beclomethasone dipropionate. Bone 15 (1994) 621-623
64. Packe G.E., Douglas J.G., McDonald A.F., Robins S.P., and Reid D.M. Bone density in asthmatic patients taking high dose inhaled beclomethasone dipropionate and intermittent systemic corticosteroids. Thorax 47 (1992) 414-417
65. Wong C.A., Walsh L.J., Smith C.J.P., Wisniewski A.F., Lewis S.A., Hubbard R., et al. Inhaled corticosteroid use and bone-mineral density in patients with asthma. Lancet 355 (2000) 1399-1403
66. Scanlon P.D., Connett J.E., Wise R.A., Tashkin D.P., Madhok T., Skeans M., et al. Loss of bone density with inhaled triamcinolone in Lung Health Study II. Am J Respir Crit Care Med 170 (2004) 1302-1309
67. Melton III L.J., Patel A., Achenbach S.J., Oberg A.L., and Yunginger J.W. Long-term fracture risk following adult-onset asthma: a population-based study. Osteoporos Int 15 (2004) 311-316
68. Simons F.E., Persaud M.P., Gillespie C.A., Cheang M., and Shuckett E.P. Absence of posterior subcapsular cataracts in young patients treated with inhaled glucocorticoids. Lancet 342 (1993) 776-778
69. Toogood J.H., Markov A.E., Baskerville J., and Dyson C. Association of ocular cataracts with inhaled and oral steroid therapy during long-term treatment of asthma. J Allergy Clin Immunol 91 (1993) 571-579
70. Cumming R.G., Mitchell P., and Leeder S.R. Use of inhaled corticosteroids and the risk of cataracts. N Engl J Med 337 (1997) 8-14
71. Smeeth L., Boulis M., Hubbard R., and Fletcher A.E. A population based case-control study of cataract and inhaled corticosteroids. Br J Ophthalmol 87 (2003) 1247-1251
72. Samiy N., Walton D.S., and Dreyer E.B. Inhaled steroids: effect on intraocular pressure in patients without glaucoma. Can J Ophthalmol 31 (1996) 120-123
73. Garbe E., LeLorier J., Boivin J.F., and Suissa S. Inhaled and nasal glucocorticoids and the risks of ocular hypertension or open-angle glaucoma. J Am Med Assoc 277 (1997) 722-727
74. Capewell S., Reynolds S., Shuttleworth D., Edwards C., and Finlay A.Y. Purpura and dermal thinning associated with high dose inhaled corticosteroids. Br Med J 300 (1990) 1548-1551
75. Mak V.H., Melchor R., and Spiro S.G. Easy bruising as a side-effect of inhaled corticosteroids. Eur Respir J 5 (1992) 1068-1074
76. Roy A., Leblanc C., Paquette L., Ghezzo H., Cote J., Cartier A., et al. Skin bruising in asthmatic subjects treated with high doses of inhaled steroids: frequency and association with adrenal function. Eur Respir J 9 (1996) 226-231
77. Autio P., Karjalainen J., Risteli L., Risteli J., Kiistala U., and Oikarinen A. Effects of an inhaled steroid (budesonide) on skin collagen synthesis of asthma patients in vivo. Am J Respir Crit Care Med 153 (1996) 1172-1175
78. Pauwels R.A., Lofdahl C.G., Laitinen L.A., Schouten J.P., Postma D.S., Pride N.B., et al. Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. European Respiratory Society Study on Chronic Obstructive Pulmonary Disease. N Engl J Med 340 (1999) 1948-1953
79. Tashkin D.P., Murray H.E., Skeans M., and Murray R.P. Skin manifestations of inhaled corticosteroids in COPD patients: results from Lung Health Study II. Chest 126 (2004) 1123-1133
80. Fairfax A.J., David V., and Douce G. Laryngeal aspergillosis following high dose inhaled fluticasone therapy for asthma. Thorax 54 (1999) 860-861
81. Leav B.A., Fanburg B., and Hadley S. Invasive pulmonary aspergillosis associated with high-dose inhaled fluticasone. N Engl J Med 343 (2000) 586
82. Peter E., Bakri F., Ball D.M., Cheney R.T., and Segal B.H. Invasive pulmonary filamentous fungal infection in a patient receiving inhaled corticosteroid therapy. Clin Infect Dis 35 (2002) e54-e56
83. Welch M.J. Inhaled steroids and severe viral infections. J Asthma 31 (1994) 43-50
84. Bahceciler N.N., Nuhoglu Y., Nursoy M.A., Kodalli N., Barlan I.B., and Basaran M.M. Inhaled corticosteroid therapy is safe in tuberculin-positive asthmatic children. Pediatr Infect Dis J 19 (2000) 215-218
85. Masten B., McWilliams B., Lipscomb M., Archibeque T., Qualls C., Kelly H.W., et al. Immune response to hepatitis B vaccine in asthmatic children. Pediatr Pulmonol 36 (2003) 522-528
86. Verstraeten T., Jumaan A.O., Mullooly J.P., Seward J.F., Izurieta H.S., DeStefano F., et al. A retrospective cohort study of the association of varicella vaccine failure with asthma, steroid use, age at vaccination, and measles-mumps-rubella vaccination. Pediatrics 112 (2003) e98-e103
87. Hanania N.A., Sockrider M., Castro M., Holbrook J.T., Tonascia J., Wise R., et al. Immune response to influenza vaccination in children and adults with asthma: effect of corticosteroid therapy. J Allergy Clin Immunol 113 (2004) 717-724
88. Crim C., Pierre L.N., and Daley-Yates P.T. A review of the pharmacology and pharmacokinetics of inhaled fluticasone propionate and mometasone furoate. Clin Ther 23 (2001) 1339-1354
89. Derendorf H. Pharmacokinetic and pharmacodynamic properties of inhaled corticosteroids in relation to efficacy and safety. Respir Med 91 Suppl. A (1997) 22-28
90. Derendorf H., Hochhaus G., Meibohm B., Mollmann H., and Barth J. Pharmacokinetics and pharmacodynamics of inhaled corticosteroids. J Allergy Clin Immunol 101 Suppl. (1998) S440-S446
91. Affrime M.B., Cuss F., Padhi D., Wirth M., Pai S., Clement R.P., et al. Bioavailability and metabolism of mometasone furoate following administration by metered-dose and dry-powder inhalers in healthy human volunteers. J Clin Pharmacol 40 (2000) 1227-1236
92. Sharpe M., and Jarvis B. Inhaled mometasone furoate: a review of its use in adults and adolescents with persistent asthma. Drugs 61 (2001) 1325-1350
93. 14C] ciclesonide after oral and intravenous administration to healthy subjects. Clin Pharmacokinet 43 (2004) 479-486
94. Valotis A., Neukam K., Elert O., and Hogger P. Human receptor kinetics, tissue binding affinity, and stability of mometasone furoate. J Pharm Sci 93 (2004) 1337-1350
95. Rohatagi S., Arya V., Zech K., Nave R., Hochhaus G., Jensen B.K., et al. Population pharmacokinetics and pharmacodynamics of ciclesonide. J Clin Pharmacol 43 (2003) 365-378
96. Rohatagi S., Derendorf H., Zech K., Nave R., and Banerji D. PK/PD of inhaled corticosteroids: the risk/benefit of inhaled ciclesonide. J Allergy Clin Immunol 111 Suppl. (2003) S218 [Abstract 598]
97. Stoeck M., Riedel R., Hochhaus G., Häfner D., Masso J.M., Schmidt B., et al. In vitro and in vivo anti-inflammatory activity of the new glucocorticoid ciclesonide. J Pharmacol Exp Ther 309 (2004) 249-258
98. Leach C.L., Davidson P.J., and Boudreau R.J. Improved airway targeting with the CFC-free HFA-beclomethasone metered-dose inhaler compared with CFC-beclomethasone. Eur Respir J 12 (1998) 1346-1353
99. Leach C.L., Davidson P.J., Hasselquist B.E., and Boudreau R.J. Lung deposition of hydrofluoroalkane-134a beclomethasone is greater than that of chlorofluorocarbon fluticasone and chlorofluorocarbon beclomethasone: a cross-over study in healthy volunteers. Chest 122 (2002) 510-516
100. Thorsson L., Edsbacker S., and Conradson T.B. Lung deposition of budesonide from Turbuhaler is twice that from a pressurized metered-dose inhaler P-MDI. Eur Respir J 7 (1994) 1839-1844
101. Pickering H., Pitcairn G.R., Hirst P.H., Bacon R.E., Newman S.P., Affrime M.B., et al. Regional lung deposition of a technetium 99m-labeled formulation of mometasone furoate administered by hydrofluoroalkane 227 metered-dose inhaler. Clin Ther 22 (2000) 1483-1493
102. 99mTc-labelled ciclesonide administered via HFA-MDI to patients with asthma. Respir Med, 2005, in press, doi:10.1016/j.rmed.2005.09.027.
103. Allen D.B., Bielory L., Derendorf H., Dluhy R., Colice G.L., and Szefler S.J. Inhaled corticosteroids: past lessons and future issues. J Allergy Clin Immunol 112 Suppl. (2003) S1-S40
104. Kelly H.W. Comparative potency and clinical efficacy of inhaled corticosteroids. Respir Care Clin North Am 5 (1999) 537-553
105. Foe K., Cutler D.J., Brown K.F., and Seale J.P. Metabolism kinetics of beclomethasone propionate esters in human lung homogenates. Pharm Res 17 (2000) 1007-1012
106. Colice GL, Derendorf H, Shapiro GG. Inhaled corticosteroids: is there an ideal therapy? [Medscape from WebMD Web site] Released February 20, 2004.
107. Pritchard J.N. The influence of lung deposition on clinical response. J Aerosol Med 14 Suppl. 1 (2001) S19-S26
108. Mollmann H., Wagner M., Meibohm B., Hochhaus G., Barth J., Stockmann R., et al. Pharmacokinetic and pharmacodynamic evaluation of fluticasone propionate after inhaled administration. Eur J Clin Pharmacol 53 (1998) 459-467
109. Balter M.S., Adams S.G., and Chapman K.R. Inhaled beclomethasone dipropionate improves acoustic measures of voice in patients with asthma. Chest 120 (2001) 1829-1834
110. Borgstrom L. The pharmacokinetics of inhaled hydrofluoroalkane formulations. J Allergy Clin Immunol 104 Suppl. (1999) S246-S249
111. Lotvall J. Inhalation therapy of the future-how will it change the way we treat asthma?. J Aerosol Med 14 Suppl. 1 (2001) S45-S50
112. Derendorf H., Hochhaus G., Rohatagi S., Mollmann H., Barth J., Sourgens H., et al. Pharmacokinetics of triamcinolone acetonide after intravenous, oral, and inhaled administration. J Clin Pharmacol 35 (1995) 302-305
113. Brogden R.N., and McTavish D. Budesonide. An updated review of its pharmacological properties, and therapeutic efficacy in asthma and rhinitis [published correction appears in Drugs 1992; 44: 1012 and Drugs 1993; 45: 1301]. Drugs 44 (1992) 375-407
114. Chaplin M.D., Rooks II W., Swenson E.W., Cooper W.C., Nerenberg C., and Chu N.I. Flunisolide metabolism and dynamics of a metabolite. Clin Pharmacol Ther 27 (1980) 402-413
115. Lipworth B.J., and Jackson C.M. Safety of inhaled and intranasal corticosteroids: lessons for the new millennium. Drug Saf 23 (2000) 11-33
116. Sabatini F., Silvestri M., Scarso L., Brazzola G., and Rossi G.A. The antiinflammatory activity of budesonide on human airway epithelial cells is lasting after removal of the drug from cultures. J Asthma 39 (2002) 11-20
117. Edsbacker S., and Brattsand R. Budesonide fatty-acid esterification: a novel mechanism prolonging binding to airway tissue. Review of available data. Ann Allergy Asthma Immunol 88 (2002) 609-616
118. Pahuja S.L., and Hochberg R.B. A comparison of the fatty acid esters of estradiol and corticosterone synthesized by tissues of the rat. J Biol Chem 264 (1989) 3216-3222
119. Hochberg R.B., Pahuja S.L., Zielinski J.E., and Larner J.M. Steroidal fatty acid esters. J Steroid Biochem Mol Biol 40 (1991) 577-585
120. Wieslander E., Delander E.L., Jarkelid L., Hjertberg E., Tunek A., and Brattsand R. Pharmacologic importance of the reversible fatty acid conjugation of budesonide studied in a rat cell line In vitro. Am J Respir Cell Mol Biol 19 (1998) 477-484
121. Tunek A., Sjodin K., and Hallstrom G. Reversible formation of fatty acid esters of budesonide, an antiasthma glucocorticoid, in human lung and liver microsomes. Drug Metab Dispos 25 (1997) 1311-1317
122. Miller-Larsson A., Mattsson H., Hjertberg E., Dahlbäck M., Tunek A., and Brattsand R. Reversible fatty acid conjugation of budesonide. Novel mechanism for prolonged retention of topically applied steroid in airway tissue. Drug Metab Dispos 26 (1998) 623-630
123. Nave R., Meyer W., Fuhst R., and Zech K. Formation of fatty acid conjugates of ciclesonide active metabolite in the rat lung after 4-week inhalation of ciclesonide. Pulm Pharmacol Ther 18 (2005) 390-396
124. Ryrfeldt A., Andersson P., Edsbacker S., Tonnesson M., Davies D., and Pauwels R. Pharmacokinetics and metabolism of budesonide, a selective glucocorticoid. Eur J Respir Dis Suppl 122 (1982) 86-95
125. 14C-ciclesonide after oral and intravenous administration in healthy subjects. Eur Respir J 20 Suppl. 38 (2002) 109s [Abstract P745]
126. Gupta R., Jindal D.P., and Kumar G. Corticosteroids: the mainstay in asthma therapy. Bioorg Med Chem 12 (2004) 6331-6342
127. Holliday S.M., Faulds D., and Sorkin E.M. Inhaled fluticasone propionate. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in asthma. Drugs 47 (1994) 318-331
128. Dietzel K, Engelstätter R, Keller A. Ciclesonide: an on-site-activated steroid. In: Hansel TT, Barnes PJ, editors. New drugs for asthma, allergy and COPD. Basel, Switzerland: Karger. Progress in Respiratory Research 2001; 31: 91-93.
129. Humbert M. Ciclesonide: a novel inhaled corticosteroid. Expert Opin Invest Drugs 13 (2004) 1349-1360
130. Serpero L., Petecchia L., Silvestri M., and Sabatini F. In vitro modulation of the cytokine-induced human bronchial epithelial cell (HBEC) functions by ciclesonide (CIC). Eur Respir J 24 Suppl. 48 (2004) 346S [Abstract P2173]
131. Silvestri M, Serpero L, Petecchia L, Sabatini F, Cerasoli F, Rossi GA. Cytokine-activated bronchial epithelial cell pro-inflammatory functions are effectively downregulated in vitro by ciclesonide. Pulm Pharmacol Ther, 2005, in press, doi:10.1016/j.pupt.2005.05.006.
132. Rohatagi S., Luo Y., Shen L., et al. Protein binding and its potential for eliciting minimal systemic side effects with a novel inhaled corticosteroid, ciclesonide. Am J Ther 12 (2005) 201-209
133. Nave R., Zech K., and Bethke T.D. Lower oropharyngeal deposition of inhaled ciclesonide via hydrofluoroalkane metered-dose inhaler compared with budesonide via chlorofluorocarbon metered-dose inhaler in healthy subjects. Eur J Clin Pharmacol 61 (2005) 203-208
134. Dent G. Ciclesonide (Byk Gulden). Curr Opin Invest Drugs 3 (2002) 78-83
135. Reynolds N.A., and Scott L.J. Ciclesonide. Drugs 64 (2004) 511-519
136. Chapman K.R., Patel P., and D'Urzo A.D. Maintenance of asthma control by once-daily inhaled ciclesonide in adults with persistent asthma. Allergy 60 (2005) 330-337
137. Hansel T., Engelstätter R., Benezet O., Kafé H., Ponitz H.H., Cheung D., et al. Once daily ciclesonide (80 or 320 μg) is equally effective as budesonide 200 μg given twice daily: a 12-week study in asthma patients [abstract]. Eur Respir J 22 Suppl. 45 (2003) 410s
138. Derom E., Van De Velde V., Marissens S., Engelstatter R., Vincken W., and Pauwels R. Effects of inhaled ciclesonide and fluticasone propionate on cortisol secretion and airway responsiveness to adenosine 5′ monophosphate in asthmatic patients. Pulm Pharmacol Ther 18 (2005) 328-336
139. Chapman K.R., Patel P., Boulet L.P., D'Urzo A.D., Alexander M., Mehra S., et al. Efficacy and long-term safety of ciclesonide in asthmatic patients as demonstrated in a 52 week long study. Eur Respir J 20 Suppl. 38 (2002) 373s-374s [Abstract 2328]
140. Lipworth B.J., Kaliner M.A., LaForce C.F., Baker J.W., Kaiser H.B., Amin D., et al. Effect of ciclesonide and fluticasone on hypothalamic-pituitary-adrenal axis function in adults with mild-to-moderate persistent asthma. Ann Allergy Asthma Immunol 94 (2005) 465-472
141. Buhl R., Vinkler I., Magyar P., Rybacki C., Middle M.V., Escher A., et al. Once daily ciclesonide is as effective as fluticasone propionate given twice daily in treating patients with asthma. Am J Respir Crit Care Med 169 Suppl. (2004) [Abstract A91]
142. Postma D.S., Sevette C., Martinat Y., Schlösser N., Aumann J., and Kafé H. Treatment of asthma by the inhaled corticosteroid ciclesonide given either in the morning or evening. Eur Respir J 17 (2001) 1083-1088
143. Shapiro G., Bensch G., Lanier R., Sher L., Lloyd M., Kundu S., et al. Once-daily treatment with ciclesonide is effective and well-tolerated in children with persistent asthma [abstract]. J Allergy Clin Immunol 115 (2005) S6
144. Agertoft L., and Pedersen S. Short-term lower-leg growth rate and urine cortisol excretion in children treated with ciclesonide. J Allergy Clin Immunol 115 (2005) 940-945
145. Bernstein J.A., Noonan M.J., Rim C., Fish J., Kundu S., Williams J., et al. Ciclesonide has minimal oropharyngeal side effects in the treatment of patients with moderate-to-severe asthma. J Allergy Clin Immunol 113 Suppl. (2004) S113 [Abstract 349]
146. Engelstätter R., Banerji D., Steinijans V.W., and Wurst W. Low incidence of oropharyngeal adverse events in asthma patients treated with ciclesonide: results from a pooled analysis [abstract]. Am J Respir Crit Care Med 169 Suppl. (2004)