Correspondence
Invasive Pulmonary Aspergillosis Associated with High-Dose Inhaled Fluticasone
N Engl J Med 2000; 343:586August 24, 2000
- Article
To the Editor:
A 44-year-old man with moderately severe asthma was first seen in the infectious-disease clinic in November 1999 because of a recent diagnosis of pulmonary aspergillosis. The patient had noted an increase in his asthma symptoms during the summer of 1999. A chest x-ray film obtained at that time had revealed bilateral cavitary lesions. An open-lung biopsy in September 1999 had revealed chronic necrotizing aspergillosis.
The patient had no known history of immunosuppression. His medications included fluticasone (delivered in two puffs of 220 μg four times a day [total daily dose, 1760 μg]) and zafirlukast (20 mg per day). The patient was initially treated with oral itraconazole for invasive pulmonary aspergillosis. Repeated imaging showed progression of disease. Hemoptysis developed. Treatment was switched to an investigational antifungal medication. During the course of therapy, hypertension developed and the patient's abdominal girth increased. The results of a cosyntropin (Cortrosyn) stimulation test were consistent with the presence of adrenal insufficiency. The dose of inhaled corticosteroids was gradually tapered. Recent computed tomographic scans of the thorax demonstrate improvement, the patient's cough has decreased, and he has had no further episodes of hemoptysis.
High-dose systemic corticosteroids are a risk factor for invasive aspergillosis. We believe that this is the first reported case of invasive pulmonary aspergillosis associated with an inhaled corticosteroid. A Medline search produced one reported case of laryngeal aspergillosis associated with inhaled fluticasone.1
Fluticasone is the most potent inhaled corticosteroid available in the United States. It was made available because it has greater topical potency, a higher degree of retention in tissue, and a longer half-life than the other inhaled corticosteroids. Inhaled corticosteroids have been linked to adverse effects traditionally associated with systemic corticosteroids, including adrenal suppression and effects on linear growth and bone metabolism.2 There have been numerous reports of adrenal insufficiency associated with the use of inhaled corticosteroids. A meta-analysis of studies of adrenal suppression among patients who used inhaled corticosteroids demonstrated that fluticasone was nearly twice as likely to cause adrenal suppression as beclomethasone, triamcinolone, or budesonide at equivalent dosages. The effects were more obvious at daily doses of more than 0.8 mg.3
Our findings add to a growing body of evidence that in certain patients, inhaled corticosteroids can exert clinically significant systemic effects. Patients who are taking high doses may be at risk for secondary immunosuppression and opportunistic infection. Practitioners should be aware of these risks when they prescribe these medications, particularly the more potent formulations.
3 ReferencesBrett A. Leav, M.D.
Barry Fanburg, M.D.
Susan Hadley, M.D.
New England Medical Center, Boston, MA 021111
Fairfax AJ ,David V ,Douce G . Laryngeal aspergillosis following high dose inhaled fluticasone therapy for asthma. Thorax 1999;54:860-861
CrossRef | Web of Science | Medline2
Wilson AM ,Blumsohn A ,Jung RT ,Lipworth BJ . Asthma and Cushing's syndrome. Chest 2000;117:593-594
CrossRef | Web of Science | Medline3
Lipworth BJ . Systemic adverse effects of inhaled corticosteroid therapy: a systematic review and meta-analysis. Arch Intern Med 1999;159:941-955
CrossRef | Web of Science | Medline
- Citing Articles (18)
Citing Articles
1
H. Xu, L. Li, W.-J. Huang, L.-X. Wang, W.-F. Li, W.-F. Yuan. (2011) Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: a case control study from China. Clinical Microbiology and Infectionno-no
CrossRef2
Néstor Soler, Arturo Huerta, Antoni Torres. (2011) The Importance of Aspergillus species Infection in Chronic Obstructive Pulmonary Disease Exacerbations. Clinical Pulmonary Medicine 18:4, 161-168
CrossRef3
David A. Stevens, George L. Melikian. (2011) Aspergillosis in the ‘Nonimmunocompromised’ Host. Immunological Investigations 40:7-8, 751-766
CrossRef4
Benjamin Thonar, Mark Yoder, Constance Cleaves. (2010) Not Your Typical Chronic Obstructive Pulmonary Disease Exacerbation: Aspergillus Tracheobronchitis in a Nonclassical Immunocompromised Host. Southern Medical Journal 103:4, 361-365
CrossRef5
Chin-Chung Shu, Huey-Dong Wu, Ming-Chih Yu, Jann-Tay Wang, Chih-Hsin Lee, Hao-Chien Wang, Jann-Yuan Wang, Li-Na Lee, Chong-Jen Yu, Pan-Chyr Yang. (2010) Use of High-Dose Inhaled Corticosteroids is Associated With Pulmonary Tuberculosis in Patients With Chronic Obstructive Pulmonary Disease. Medicine 89:1, 53-61
CrossRef6
Russell E. Lewis, Dimitrios P. Kontoyiannis. (2009) Invasive aspergillosis in glucocorticoid-treated patients. Medical Mycology 47:s1, S271-S281
CrossRef7
Maurizio Cutolo, Bruno Seriolo, Carmen Pizzorni, Maria Elena Secchi, Stefano Soldano, Sabrina Paolino, Paola Montagna, Alberto Sulli. (2008) Use of glucocorticoids and risk of infections. Autoimmunity Reviews 8:2, 153-155
CrossRef8
W. Meersseman, K. Lagrou, J. Maertens, E. V. Wijngaerden. (2007) Invasive Aspergillosis in the Intensive Care Unit. Clinical Infectious Diseases 45:2, 205-216
CrossRef9
Giovanni A. Rossi, Franklin Cerasoli, Mario Cazzola. (2007) Safety of inhaled corticosteroids: Room for improvement. Pulmonary Pharmacology & Therapeutics 20:1, 23-35
CrossRef10
2006. Corticosteroids—glucocorticoids, inhaled. , 958-977.
CrossRef11
Carlos Agustí, Ana Rañó, Ivet Aldabó, Antoni Torres. (2006) Fungal pneumonia, chronic respiratory diseases and glucocorticoids. Medical Mycology 44:s1, 207-211
CrossRef12
Marcel Bonay, Catherine Bancal, Bruno Crestani. (2005) The risk/benefit of inhaled corticosteroids in chronic obstructive pulmonary disease. Expert Opinion on Drug Safety 4:2, 251-271
CrossRef13
M. Cornet, H. Mallat, D. Somme, E. Guerot, G. Kac, J. L. Mainardi, P. Fornes, L. Gutmann, V. Lavarde. (2003) Fulminant invasive pulmonary aspergillosis in immunocompetent patients-a two-case report. Clinical Microbiology and Infection 9:12, 1224-1227
CrossRef14
Michail S Lionakis, Dimitrios P Kontoyiannis. (2003) Glucocorticoids and invasive fungal infections. The Lancet 362:9398, 1828-1838
CrossRef15
R. L. Bratton, P. W. Brazis, W. C. Hellinger, R. E. Wharen, D. F. Broderick. (2002) Aspergillosis Related to Long-Term Nasal Corticosteroid Use. Mayo Clinic Proceedings 77:12, 1353-1357
CrossRef16
Elvis Peter, Faris Bakri, Donna M. Ball, Richard T. Cheney, Brahm H. Segal. (2002) Invasive Pulmonary Filamentous Fungal Infection in a Patient Receiving Inhaled Corticosteroid Therapy. Clinical Infectious Diseases 35:5, e54-e56
CrossRef17
Melanie W. Pound, Richard H. Drew, John R. Perfect. (2002) Recent advances in the epidemiology, prevention, diagnosis, and treatment of fungal pneumonia. Current Opinion in Infectious Diseases 15:2, 183-194
CrossRef18
&NA;. (2000) Fluticasone propionate. Reactions Weekly &NA;:817, 7
CrossRef
