Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis
- Praveen Akuthota, MD
Praveen Akuthota, MD
- Associate Clinical Professor
- University of California, San Diego
- Peter F Weller, MD, MACP
Peter F Weller, MD, MACP
- 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
Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction in response to colonization of the airways with Aspergillus fumigatus that occurs almost exclusively in patients with asthma or cystic fibrosis (CF) [1-4]. In chronic cases, 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 prevalence of allergic bronchopulmonary aspergillosis (ABPA) among patients with persistent asthma is estimated at 1 to 2 percent, although rates up to 28 percent have been reported [1,4,6]. Reported rates are higher in patients seen in asthma clinics and those admitted to the hospital with an asthma exacerbation . Among patients with cystic fibrosis, reported prevalences range from 2 to 9 percent [1,5,7-10].
Rarely, ABPA occurs in patients with bronchiectasis, chronic granulomatous disease, hyperimmunoglobulinemia E, and in lung transplant recipients [4,11-13].
PATHOLOGY AND PATHOGENESIS
Allergic bronchopulmonary aspergillosis (ABPA) is characterized pathologically by mucoid impaction of the bronchi, eosinophilic pneumonia, and bronchocentric granulomatosis in addition to the histologic features of asthma [5,14]. Areas of eosinophilic pneumonia are occasionally found, although not a major feature of the disease . Septated hyphae with acute dichotomous branching may be seen in the mucus-filled bronchial lumen, but fungi do not invade the mucosa. Aspergillus is cultured from the sputum in up to two-thirds of patients with ABPA, but hyphae may not be seen by direct microscopy. (See "Bronchocentric granulomatosis".)
- 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.
- Agarwal R. Burden and distinctive character of allergic bronchopulmonary aspergillosis in India. Mycopathologia 2014; 178:447.
- 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.
- Maturu VN, Agarwal R. Prevalence of Aspergillus sensitization and allergic bronchopulmonary aspergillosis in cystic fibrosis: systematic review and meta-analysis. Clin Exp Allergy 2015; 45:1765.
- Eppinger TM, Greenberger PA, White DA, et al. Sensitization to Aspergillus species in the congenital neutrophil disorders chronic granulomatous disease and hyper-IgE syndrome. J Allergy Clin Immunol 1999; 104:1265.
- Verleden GM, Dupont LJ, Van Raemdonck DE. ABPA: does it really exist after lung transplantation? J Heart Lung Transplant 2009; 28:1239.
- Cerceo E, Kotloff RM, Hadjiliadis D, et al. Central airways obstruction due to Aspergillus fumigatus after lung transplantation. J Heart Lung Transplant 2009; 28:515.
- Riscili BP, Wood KL. Noninvasive pulmonary Aspergillus infections. Clin Chest Med 2009; 30:315.
- Cordier J-F, Cottin V. Eosinophilic pneumonias. In: Interstitial Lung Disease, 5th, Schwarz MI, King TE Jr.. (Eds), People's Medical Publishing House-USA, Shelton, CT 2011. p.833.
- 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.
- 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.
- Schubert MS. Allergic fungal sinusitis: pathophysiology, diagnosis and management. Med Mycol 2009; 47 Suppl 1:S324.
- 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.
- 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.
- 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.
- 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.
- Kaur M, Sudan DS. Allergic Bronchopulmonary Aspergillosis (ABPA)-The High Resolution Computed Tomography (HRCT) Chest Imaging Scenario. J Clin Diagn Res 2014; 8:RC05.
- Mitchell TA, Hamilos DL, Lynch DA, Newell JD. Distribution and severity of bronchiectasis in allergic bronchopulmonary aspergillosis (ABPA). J Asthma 2000; 37:65.
- 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.
- Greenberger PA. When to suspect and work up allergic bronchopulmonary aspergillosis. Ann Allergy Asthma Immunol 2013; 111:1.
- Agarwal R, Khan A, Gupta D, et al. An alternate method of classifying allergic bronchopulmonary aspergillosis based on high-attenuation mucus. PLoS One 2010; 5:e15346.
- 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.
- 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.
- Lake FR, Froudist JH, McAleer R, et al. Allergic bronchopulmonary fungal disease caused by Bipolaris and Curvularia. Aust N Z J Med 1991; 21:871.
- Chowdhary A, Agarwal K, Kathuria S, et al. Allergic bronchopulmonary mycosis due to fungi other than Aspergillus: a global overview. Crit Rev Microbiol 2014; 40:30.
- Pihet M, Carrere J, Cimon B, et al. Occurrence and relevance of filamentous fungi in respiratory secretions of patients with cystic fibrosis--a review. Med Mycol 2009; 47:387.
- Walicka-Serzysko K, Sands D. The clinical presentations of pulmonary aspergillosis in children with cystic fibrosis - preliminary report. Dev Period Med 2015; 19:66.
- Fitzsimons EJ, Aris R, Patterson R. Recurrence of allergic bronchopulmonary aspergillosis in the posttransplant lungs of a cystic fibrosis patient. Chest 1997; 112:281.
- 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.
- 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.
- 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.
- 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.
- Maturu VN, Agarwal R. Acute Invasive Pulmonary Aspergillosis Complicating Allergic Bronchopulmonary Aspergillosis: Case Report and Systematic Review. Mycopathologia 2015; 180:209.
- Shah A, Panjabi C. Contemporaneous occurrence of allergic bronchopulmonary aspergillosis, allergic Aspergillus sinusitis, and aspergilloma. Ann Allergy Asthma Immunol 2006; 96:874.
- Lowes D, Chishimba L, Greaves M, Denning DW. Development of chronic pulmonary aspergillosis in adult asthmatics with ABPA. Respir Med 2015; 109:1509.
- PATHOLOGY AND PATHOGENESIS
- CLINICAL FEATURES
- Signs and symptoms
- Pulmonary function testing
- Diagnostic criteria
- Step-wise evaluation
- Diagnosis of allergic bronchopulmonary mycosis
- Diagnosis of ABPA in cystic fibrosis
- DIFFERENTIAL DIAGNOSIS
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS