Treatment of allergic bronchopulmonary aspergillosis
- Praveen Akuthota, MD
Praveen Akuthota, MD
- Clinical Instructor of Medicine
- University of California, San Diego
- Peter F Weller, MD, FACP
Peter F Weller, MD, FACP
- Editor-in-Chief — Infectious Diseases
- Section Editor — Tropical Medicine
- William Bosworth Castle Professor of Medicine
- Harvard Medical School
- Professor of Immunology and Infectious Diseases
- Harvard T. H. Chan School of Public Health
- Section Editors
- Carol A Kauffman, MD
Carol A Kauffman, MD
- Section Editor — Fungal Infections
- Professor of Internal Medicine
- University of Michigan Medical School
- Veterans Affairs Ann Arbor Healthcare System
- Peter J Barnes, DM, DSc, FRCP, FRS
Peter J Barnes, DM, DSc, FRCP, FRS
- Editor-in-Chief — Pulmonary and Critical Care Medicine
- Section Editor — Asthma
- Professor of Medicine
- National Heart and Lung Institute, Imperial College, London
- Deputy Editors
- Helen Hollingsworth, MD
Helen Hollingsworth, MD
- Deputy Editor — Pulmonary, Critical Care, and Sleep Medicine
- Associate Professor of Medicine
- Boston University School of Medicine
- Anna R Thorner, MD
Anna R Thorner, MD
- Deputy Editor — Infectious Diseases
- Assistant Professor of Medicine, Part-time
- Harvard Medical School
Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction that occurs in response to colonization of the airways with Aspergillus fumigatus and almost exclusively in patients with asthma or cystic fibrosis (CF) [1-4]. In some cases, repeated episodes of bronchial obstruction, inflammation, and mucoid impaction can lead to bronchiectasis, fibrosis, and respiratory compromise .
The treatment and prognosis of ABPA will be reviewed here. The clinical manifestations and diagnosis of ABPA and general issues related to the management of asthma and bronchiectasis are discussed separately. (See "Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis" and "An overview of asthma management" and "Treatment of bronchiectasis in adults" and "Management of bronchiectasis in children without cystic fibrosis".)
Treatment of allergic bronchopulmonary aspergillosis (ABPA) aims to control episodes of acute inflammation and to limit progressive lung injury. The roles of systemic glucocorticoids and antifungal agents vary with the disease activity. Antifungal therapy may help to decrease exacerbations. Inhaled glucocorticoids may help control symptoms of asthma but do not have documented efficacy in preventing acute episodes of ABPA.
Acute ABPA — For acute ABPA manifest by radiographic opacities (usually upper or middle lobes) and an elevated total serum IgE (generally >1000 IU/mL), systemic glucocorticoids are the mainstay of treatment [6-9]. In addition, the 2016 Infectious Diseases Society of America (IDSA) guidelines on the treatment of aspergillosis recommend that therapy of acute or recurrent ABPA should consist of a combination of glucocorticoids and itraconazole . Voriconazole is a reasonable alternative to itraconazole because it is better tolerated in some patients and is well absorbed.
Systemic glucocorticoids — Systemic glucocorticoids are considered the mainstay of treatment of acute ABPA based on the results of case series; no clinical trials have been performed. As an example, a case series of 84 patients found no patients who failed to respond to a course of prednisone with clearing of radiographic opacities, a decline of >50 percent in total IgE, and a return of blood eosinophil counts to normal . In a separate series, 126 patients with a new diagnosis of ABPA all responded to a course of oral glucocorticoids with development of remission (decline in IgE levels >35 percent and clearance of chest radiographic lesions) by six weeks .
- Greenberger PA. Allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 2002; 110:685.
- Zander DS. Allergic bronchopulmonary aspergillosis: an overview. Arch Pathol Lab Med 2005; 129:924.
- Tillie-Leblond I, Tonnel AB. Allergic bronchopulmonary aspergillosis. Allergy 2005; 60:1004.
- Agarwal R. Allergic bronchopulmonary aspergillosis. Chest 2009; 135:805.
- Stevens DA, Moss RB, Kurup VP, et al. Allergic bronchopulmonary aspergillosis in cystic fibrosis--state of the art: Cystic Fibrosis Foundation Consensus Conference. Clin Infect Dis 2003; 37 Suppl 3:S225.
- Greenberger PA, Patterson R. Allergic bronchopulmonary aspergillosis and the evaluation of the patient with asthma. J Allergy Clin Immunol 1988; 81:646.
- McCarthy DS, Pepys J. Allergic broncho-pulmonary aspergillosis. Clinical immunology. 2. Skin, nasal and bronchial tests. Clin Allergy 1971; 1:415.
- Breslin AB, Jenkins CR. Experience with allergic bronchopulmonary aspergillosis: some unusual features. Clin Allergy 1984; 14:21.
- Golbert TM, Patterson R. Pulmonary allergic aspergillosis. Ann Intern Med 1970; 72:395.
- Patterson TF, Thompson GR 3rd, Denning DW, et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis 2016; 63:e1.
- Patterson R, Greenberger PA, Halwig JM, et al. Allergic bronchopulmonary aspergillosis. Natural history and classification of early disease by serologic and roentgenographic studies. Arch Intern Med 1986; 146:916.
- Agarwal R, Gupta D, Aggarwal AN, et al. Allergic bronchopulmonary aspergillosis: lessons from 126 patients attending a chest clinic in north India. Chest 2006; 130:442.
- Natarajan S, Subramanian P. Allergic bronchopulmonary aspergillosis: A clinical review of 24 patients: Are we right in frequent serologic monitoring? Ann Thorac Med 2014; 9:216.
- Wark PA, Gibson PG, Wilson AJ. Azoles for allergic bronchopulmonary aspergillosis associated with asthma. Cochrane Database Syst Rev 2004; :CD001108.
- Agarwal R, Chakrabarti A, Shah A, et al. Allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria. Clin Exp Allergy 2013; 43:850.
- Knutsen AP, Bush RK, Demain JG, et al. Fungi and allergic lower respiratory tract diseases. J Allergy Clin Immunol 2012; 129:280.
- Stevens DA, Schwartz HJ, Lee JY, et al. A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis. N Engl J Med 2000; 342:756.
- Wark PA, Hensley MJ, Saltos N, et al. Anti-inflammatory effect of itraconazole in stable allergic bronchopulmonary aspergillosis: a randomized controlled trial. J Allergy Clin Immunol 2003; 111:952.
- Pasqualotto AC, Powell G, Niven R, Denning DW. The effects of antifungal therapy on severe asthma with fungal sensitization and allergic bronchopulmonary aspergillosis. Respirology 2009; 14:1121.
- Salez F, Brichet A, Desurmont S, et al. Effects of itraconazole therapy in allergic bronchopulmonary aspergillosis. Chest 1999; 116:1665.
- Lebrun-Vignes B, Archer VC, Diquet B, et al. Effect of itraconazole on the pharmacokinetics of prednisolone and methylprednisolone and cortisol secretion in healthy subjects. Br J Clin Pharmacol 2001; 51:443.
- Varis T, Kaukonen KM, Kivistö KT, Neuvonen PJ. Plasma concentrations and effects of oral methylprednisolone are considerably increased by itraconazole. Clin Pharmacol Ther 1998; 64:363.
- Bolland MJ, Bagg W, Thomas MG, et al. Cushing's syndrome due to interaction between inhaled corticosteroids and itraconazole. Ann Pharmacother 2004; 38:46.
- Woods DR, Arun CS, Corris PA, Perros P. Cushing's syndrome without excess cortisol. BMJ 2006; 332:469.
- Parmar JS, Howell T, Kelly J, Bilton D. Profound adrenal suppression secondary to treatment with low dose inhaled steroids and itraconazole in allergic bronchopulmonary aspergillosis in cystic fibrosis. Thorax 2002; 57:749.
- Skov M, Main KM, Sillesen IB, et al. Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide. Eur Respir J 2002; 20:127.
- Wong J, Black P. Acute adrenal insufficiency associated with high dose inhaled steroids. BMJ 1992; 304:1415.
- Erwin GE, Fitzgerald JE. Case report: allergic bronchopulmonary aspergillosis and allergic fungal sinusitis successfully treated with voriconazole. J Asthma 2007; 44:891.
- Glackin L, Leen G, Elnazir B, Greally P. Voriconazole in the treatment of allergic bronchopulmonary aspergillosis in cystic fibrosis. Ir Med J 2009; 102:29.
- Chishimba L, Niven RM, Cooley J, Denning DW. Voriconazole and posaconazole improve asthma severity in allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization. J Asthma 2012; 49:423.
- Ricketti AJ, Greenberger PA, Patterson R. Serum IgE as an important aid in management of allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 1984; 74:68.
- Agarwal R, Gupta D, Aggarwal AN, et al. Clinical significance of decline in serum IgE levels in allergic bronchopulmonary aspergillosis. Respir Med 2010; 104:204.
- Denning DW, Van Wye JE, Lewiston NJ, Stevens DA. Adjunctive therapy of allergic bronchopulmonary aspergillosis with itraconazole. Chest 1991; 100:813.
- Marchant JL, Warner JO, Bush A. Rise in total IgE as an indicator of allergic bronchopulmonary aspergillosis in cystic fibrosis. Thorax 1994; 49:1002.
- Voskamp AL, Gillman A, Symons K, et al. Clinical efficacy and immunologic effects of omalizumab in allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol Pract 2015; 3:192.
- Tillie-Leblond I, Germaud P, Leroyer C, et al. Allergic bronchopulmonary aspergillosis and omalizumab. Allergy 2011; 66:1254.
- Tanou K, Zintzaras E, Kaditis AG. Omalizumab therapy for allergic bronchopulmonary aspergillosis in children with cystic fibrosis: a synthesis of published evidence. Pediatr Pulmonol 2014; 49:503.
- Lee TM, Greenberger PA, Patterson R, et al. Stage V (fibrotic) allergic bronchopulmonary aspergillosis. A review of 17 cases followed from diagnosis. Arch Intern Med 1987; 147:319.
- Poole CJ, Wong M. Allergic bronchopulmonary aspergillosis in garden waste (compost) collectors--occupational implications. Occup Med (Lond) 2013; 63:517.
- Allmers H, Huber H, Baur X. Two year follow-up of a garbage collector with allergic bronchopulmonary aspergillosis (ABPA). Am J Ind Med 2000; 37:438.
- Akiyama K, Takizawa H, Suzuki M, et al. Allergic bronchopulmonary aspergillosis due to Aspergillus oryzae. Chest 1987; 91:285.
- Mehta SK, Sandhu RS. Immunological significance of Aspergillus fumigatus in cane-sugar mills. Arch Environ Health 1983; 38:41.
- Laoudi Y, Paolini JB, Grimfed A, Just J. Nebulised corticosteroid and amphotericin B: an alternative treatment for ABPA? Eur Respir J 2008; 31:908.
- Moss RB. Allergic bronchopulmonary aspergillosis and Aspergillus infection in cystic fibrosis. Curr Opin Pulm Med 2010; 16:598.
- Elphick HE, Southern KW. Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. Cochrane Database Syst Rev 2012; :CD002204.
- Nepomuceno IB, Esrig S, Moss RB. Allergic bronchopulmonary aspergillosis in cystic fibrosis: role of atopy and response to itraconazole. Chest 1999; 115:364.
- Vlahakis NE, Aksamit TR. Diagnosis and treatment of allergic bronchopulmonary aspergillosis. Mayo Clin Proc 2001; 76:930.
- Agarwal R, Garg M, Aggarwal AN, et al. Serologic allergic bronchopulmonary aspergillosis (ABPA-S): long-term outcomes. Respir Med 2012; 106:942.