Allergic bronchopulmonary aspergillosis
- Praveen Akuthota, MD
Praveen Akuthota, MD
- Assistant Professor of Medicine
- Harvard Medical School
- 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 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, Critical Care, and Sleep Medicine
- Section Editor — Asthma
- Professor of Medicine
- National Heart and Lung Institute, Imperial College, London
Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction, often in patients with asthma or cystic fibrosis (CF), that occurs when bronchi become colonized by Aspergillus species [1-4]. Repeated episodes of bronchial obstruction, inflammation, and mucoid impaction can lead to bronchiectasis, fibrosis, and respiratory compromise .
The pathophysiology, diagnosis, and treatment of ABPA will be reviewed here. General issues related to bronchiectasis are discussed separately. (See "Clinical manifestations and diagnosis of bronchiectasis in adults" and "Treatment of bronchiectasis in adults".)
The pathogenesis of allergic bronchopulmonary aspergillosis (ABPA) remains incompletely understood [5,6]. There is no relation between the intensity of exposure to airborne Aspergillus spores and rates of sensitization to the fungus as measured by skin testing . Although all spores that are inhaled in sufficient quantities can behave as allergens, the normally low level of IgG against fungal antigens in the circulation and the low antifungal secretory IgA in bronchoalveolar fluid suggest that healthy individuals are able to effectively eliminate fungal spores [8,9]. In contrast, exposure of atopic individuals to fungal spores or mycelial fragments results in the formation of IgE and IgG antibodies.
T cells also play an important role in ABPA. There are increases in Th2 CD4+ cell responses to Aspergillus antigens both in the bronchoalveolar lymphoid tissue and systemically . Aspergillus-responsive T cells generate cytokines interleukin (IL)-4, IL-5, and IL-13, which in turn account for the increases in eosinophilia and IgE in ABPA. In one study, T cell clones specific to the Asp f 1 antigen of A. fumigatus were established from the peripheral blood of three patients with ABPA . The majority of these clones were CD4+ cells of the Th2 phenotype, which produce IL-4 and IL-5 . The response to the Asp f 1 antigen was HLA restricted, being mediated exclusively by either HLA-DR2 or HLA-DR5 and was restricted to specific T cell receptor V-beta chains . In addition, there is increased sensitivity of B cells, T cells, NK cells, and eosinophils to IL-4 .
In another study, the costimulatory molecule OX40 ligand was crucial for driving Th2 responses to A. fumigatus in the CD4+ cells of patients with cystic fibrosis (CF) and ABPA . Heightened Th2 reactivity in these patients correlated with lower mean serum vitamin D levels.
- 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.
- Riscili BP, Wood KL. Noninvasive pulmonary Aspergillus infections. Clin Chest Med 2009; 30:315.
- Beaumont F, Kauffman HF, de Monchy JG, et al. Volumetric aerobiological survey of conidial fungi in the North-East Netherlands. II. Comparison of aerobiological data and skin tests with mould extracts in an asthmatic population. Allergy 1985; 40:181.
- Greenberger PA, Smith LJ, Hsu CC, et al. Analysis of bronchoalveolar lavage in allergic bronchopulmonary aspergillosis: divergent responses of antigen-specific antibodies and total IgE. J Allergy Clin Immunol 1988; 82:164.
- Kauffman HF, Tomee JF, van der Werf TS, et al. Review of fungus-induced asthmatic reactions. Am J Respir Crit Care Med 1995; 151:2109.
- Chauhan B, Knutsen Ap, Hutcheson PS, et al. T cell subsets, epitope mapping, and HLA-restriction in patients with allergic bronchopulmonary aspergillosis. J Clin Invest 1996; 97:2324.
- Kreindler JL, Steele C, Nguyen N, et al. Vitamin D3 attenuates Th2 responses to Aspergillus fumigatus mounted by CD4+ T cells from cystic fibrosis patients with allergic bronchopulmonary aspergillosis. J Clin Invest 2010; 120:3242.
- Gibson PG, Wark PA, Simpson JL, et al. Induced sputum IL-8 gene expression, neutrophil influx and MMP-9 in allergic bronchopulmonary aspergillosis. Eur Respir J 2003; 21:582.
- Agarwal R, Aggarwal AN, Gupta D, Jindal SK. Aspergillus hypersensitivity and allergic bronchopulmonary aspergillosis in patients with bronchial asthma: systematic review and meta-analysis. Int J Tuberc Lung Dis 2009; 13:936.
- Patterson R, Greenberger PA, Radin RC, Roberts M. Allergic bronchopulmonary aspergillosis: staging as an aid to management. Ann Intern Med 1982; 96:286.
- Buckingham SJ, Hansell DM. Aspergillus in the lung: diverse and coincident forms. Eur Radiol 2003; 13:1786.
- Reiff DB, Wells AU, Carr DH, et al. CT findings in bronchiectasis: limited value in distinguishing between idiopathic and specific types. AJR Am J Roentgenol 1995; 165:261.
- Johkoh T, Müller NL, Akira M, et al. Eosinophilic lung diseases: diagnostic accuracy of thin-section CT in 111 patients. Radiology 2000; 216:773.
- Neeld DA, Goodman LR, Gurney JW, et al. Computerized tomography in the evaluation of allergic bronchopulmonary aspergillosis. Am Rev Respir Dis 1990; 142:1200.
- Paganin F, Trussard V, Seneterre E, et al. Chest radiography and high resolution computed tomography of the lungs in asthma. Am Rev Respir Dis 1992; 146:1084.
- Ward S, Heyneman L, Lee MJ, et al. Accuracy of CT in the diagnosis of allergic bronchopulmonary aspergillosis in asthmatic patients. AJR Am J Roentgenol 1999; 173:937.
- Agarwal R, Gupta D, Aggarwal AN, et al. Clinical significance of hyperattenuating mucoid impaction in allergic bronchopulmonary aspergillosis: an analysis of 155 patients. Chest 2007; 132:1183.
- Malo JL, Longbottom J, Mitchell J, et al. Studies in chronic allergic bronchopulmonary aspergillosis. 3. Immunological findings. Thorax 1977; 32:269.
- Greenberger PA, Patterson R. Diagnosis and management of allergic bronchopulmonary aspergillosis. Ann Allergy 1986; 56:444.
- Vlahakis NE, Aksamit TR. Diagnosis and treatment of allergic bronchopulmonary aspergillosis. Mayo Clin Proc 2001; 76:930.
- Angus RM, Davies ML, Cowan MD, et al. Computed tomographic scanning of the lung in patients with allergic bronchopulmonary aspergillosis and in asthmatic patients with a positive skin test to Aspergillus fumigatus. Thorax 1994; 49:586.
- Glancy JJ, Elder JL, McAleer R. Allergic bronchopulmonary fungal disease without clinical asthma. Thorax 1981; 36:345.
- Berkin KE, Vernon DR, Kerr JW. Lung collapse caused by allergic bronchopulmonary aspergillosis in non-asthmatic patients. Br Med J (Clin Res Ed) 1982; 285:552.
- Greenberger PA, Patterson R. Allergic bronchopulmonary aspergillosis and the evaluation of the patient with asthma. J Allergy Clin Immunol 1988; 81:646.
- Schwartz HJ, Citron KM, Chester EH, et al. A comparison of the prevalence of sensitization to Aspergillus antigens among asthmatics in Cleveland and London. J Allergy Clin Immunol 1978; 62:9.
- Schwartz HJ, Greenberger PA. The prevalence of allergic bronchopulmonary aspergillosis in patients with asthma, determined by serologic and radiologic criteria in patients at risk. J Lab Clin Med 1991; 117:138.
- Basich JE, Graves TS, Baz MN, et al. Allergic bronchopulmonary aspergillosis in corticosteroid-dependent asthmatics. J Allergy Clin Immunol 1981; 68:98.
- Eaton T, Garrett J, Milne D, et al. Allergic bronchopulmonary aspergillosis in the asthma clinic. A prospective evaluation of CT in the diagnostic algorithm. Chest 2000; 118:66.
- Denning DW, O'Driscoll BR, Powell G, et al. Randomized controlled trial of oral antifungal treatment for severe asthma with fungal sensitization: The Fungal Asthma Sensitization Trial (FAST) study. Am J Respir Crit Care Med 2009; 179:11.
- Bahous J, Malo JL, Paquin R, et al. Allergic bronchopulmonary aspergillosis and sensitization to Aspergillus fumigatus in chronic bronchiectasis in adults. Clin Allergy 1985; 15:571.
- Faux JA, Shale DJ, Lane DJ. Precipitins and specific IgG antibody to Aspergillus fumigatus in a chest unit population. Thorax 1992; 47:48.
- Simmonds EJ, Littlewood JM, Evans EG. Cystic fibrosis and allergic bronchopulmonary aspergillosis. Arch Dis Child 1990; 65:507.
- Hiller EJ. Aspergillosis. J R Soc Med 1992; 85 Suppl 19:33.
- Laufer P, Fink JN, Bruns WT, et al. Allergic bronchopulmonary aspergillosis in cystic fibrosis. J Allergy Clin Immunol 1984; 73:44.
- Knutsen AP, Hutcheson PS, Mueller KR, Slavin RG. Serum immunoglobulins E and G anti-Aspergillus fumigatus antibody in patients with cystic fibrosis who have allergic bronchopulmonary aspergillosis. J Lab Clin Med 1990; 116:724.
- Becker JW, Burke W, McDonald G, et al. Prevalence of allergic bronchopulmonary aspergillosis and atopy in adult patients with cystic fibrosis. Chest 1996; 109:1536.
- Nepomuceno IB, Esrig S, Moss RB. Allergic bronchopulmonary aspergillosis in cystic fibrosis: role of atopy and response to itraconazole. Chest 1999; 115:364.
- Geller DE, Kaplowitz H, Light MJ, Colin AA. Allergic bronchopulmonary aspergillosis in cystic fibrosis: reported prevalence, regional distribution, and patient characteristics. Scientific Advisory Group, Investigators, and Coordinators of the Epidemiologic Study of Cystic Fibrosis. Chest 1999; 116:639.
- Fitzsimons EJ, Aris R, Patterson R. Recurrence of allergic bronchopulmonary aspergillosis in the posttransplant lungs of a cystic fibrosis patient. Chest 1997; 112:281.
- CAMPBELL MJ, CLAYTON YM. BRONCHOPULMONARY ASPERGILLOSIS. A CORRELATION OF THE CLINICAL AND LABORATORY FINDINGS IN 272 PATIENTS INVESTIGATED FOR BRONCHOPULMONARY ASPERGILLOSIS. Am Rev Respir Dis 1964; 89:186.
- McCarthy DS, Pepys J. Allergic broncho-pulmonary aspergillosis. Clinical immunology. 2. Skin, nasal and bronchial tests. Clin Allergy 1971; 1:415.
- Rosenberg M, Patterson R, Mintzer R, et al. Clinical and immunologic criteria for the diagnosis of allergic bronchopulmonary aspergillosis. Ann Intern Med 1977; 86:405.
- Chapman BJ, Capewell S, Gibson R, et al. Pulmonary eosinophilia with and without allergic bronchopulmonary aspergillosis. Thorax 1989; 44:919.
- Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2008; 46:327.
- 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.
- 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.
- Marchant JL, Warner JO, Bush A. Rise in total IgE as an indicator of allergic bronchopulmonary aspergillosis in cystic fibrosis. Thorax 1994; 49:1002.
- 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, Gibson PG, Wilson AJ. Azoles for allergic bronchopulmonary aspergillosis associated with asthma. Cochrane Database Syst Rev 2004; :CD001108.
- 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.
- Laoudi Y, Paolini JB, Grimfed A, Just J. Nebulised corticosteroid and amphotericin B: an alternative treatment for ABPA? Eur Respir J 2008; 31:908.
- Knutsen AP, Bush RK, Demain JG, et al. Fungi and allergic lower respiratory tract diseases. J Allergy Clin Immunol 2012; 129:280.
- 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.
- Tillie-Leblond I, Germaud P, Leroyer C, et al. Allergic bronchopulmonary aspergillosis and omalizumab. Allergy 2011; 66:1254.
- CLINICAL FEATURES
- Staging system
- Radiographic features
- - High-resolution computed tomography
- Pulmonary function testing
- ABPA versus conventional asthma
- ABPA in cystic fibrosis
- ABPA and pulmonary eosinophilia
- ABPA and bronchiectasis
- Antifungal agents
- - Approach to antifungal therapy
- Duration of therapy
- Other interventions
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS