Therapeutic Advances in Respiratory Disease http://tar.sagepub.com/ Management of allergic bronchopulmonary aspergillosis: a review and update Mahboobeh Mahdavinia and Leslie C. Grammer Ther Adv Respir Dis 2012 6: 173 originally published online 30 April 2012 DOI: 10.1177/1753465812443094 The online version of this article can be found at: http://tar.sagepub.com/content/6/3/173 Published by: http://www.sagepublications.com Additional services and information for Therapeutic Advances in Respiratory Disease can be found at: Email Alerts: http://tar.sagepub.com/cgi/alerts Subscriptions: http://tar.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav Citations: http://tar.sagepub.com/content/6/3/173.refs.html >> Version of Record - May 28, 2012 OnlineFirst Version of Record - Apr 30, 2012 What is This? Downloaded from tar.sagepub.com at NORTHWESTERN UNIV LIBRARY on January 3, 2014 TAR631753465812443094LC Grammer and M MahdaviniaTherapeutic Advances in Respiratory Disease 4430942012 Therapeutic Advances in Respiratory Disease Review Ther Adv Respir Dis Management of allergic bronchopulmonary (2012) 6(3) 173 –187 DOI: 10.1177/ aspergillosis: a review and update 1753465812443094 © The Author(s), 2012. Reprints and permissions: Mahboobeh Mahdavinia and Leslie C. Grammer http://www.sagepub.co.uk/ journalsPermissions.nav Abstract: Since the first description of allergic bronchopulmonary aspergillosis (ABPA) in the 1950s there have been numerous studies that have shed light on the characteristics and immunopathogenesis of this disease. The increased knowledge and awareness have resulted in earlier diagnosis and treatment of patients with this condition. This article aims to provide a summary and updates on ABPA by reviewing the results of recent studies on this disease with a focus on articles published within the last 5 years. A systematic search of PubMed/Medline with keywords of ABPA or allergic bronchopulmonary aspergillosis was performed. All selected articles were reviewed with a focus on findings of articles published from December 2006 to December 2011. The relevant findings are summarized in this paper. Keywords: ABPA, aspergillosis, cystic fibrosis, mold, asthma, bronchiectasis Introduction bronchioles result in mucus impaction and Correspondence to: Leslie C. Grammer, MD, Allergic bronchopulmonary aspergillosis (ABPA) inflammatory cell infiltration in bronchial wall PhD is a hypersensitivity lung disease that occurs and peribronchial tissues, that can progress to Northwestern University, 676 N St Claire Suite 1400, almost exclusively in patients with asthma and organizing pneumonia, bronchiectasis and Chicago, IL 60611, USA cystic fibrosis (CF) in the setting of bronchial bronchocentric noncaseating granulomatosis grammer@northwestern. colonization by Aspergillus fumigatus, which is a [Greenberger, 2002; Knutsen et al. 2012]. edu Mahboobeh Mahdavinia, ubiquitous saprophytic mold species that can MD, PhD cause a variety of pathologies in its host [Geiser ABPA is generally more common among severe Northwestern University, et al. 2007]. As depicted in Figure 1, there are five asthmatic patients who are steroid dependent. Chicago, IL 60611, USA major pulmonary diseases caused by A. fumigatus: While the prevalence of ABPA was reported to ABPA, hypersensitivity pneumonitis, aspergilloma, be as low as 1–2% in asthmatic patients in outpa- chronic necrotizing Aspergillus pneumonia, and tient clinics [Donnelly et al. 1991; Novey, 1975], invasive aspergillosis [Soubani and Chandrasekar, this rate was reported as 7–14% among steroid- 2002; Zmeili and Soubani, 2007]. ABPA mani- dependent asthma patients who were referred to fests as recurrent pulmonary infiltrates, bronchi- specialty clinics [Basich et al. 1981], and was ectasis and productive cough with mucus plugs in even higher (39%) in patients who have been asthmatic and CF patients [Greenberger and admitted to the ICU with severe asthma attacks Patterson, 1988; Rosenberg et al. 1977]. There [Agarwal et al. 2010b]. The prevalence of ABPA are differences in characteristics, prevalence, in CF ranges from 6% to 10% [de Almeida et al. diagnostic criteria and treatment of ABPA in 2006; Chotirmall et al. 2008]. Untreated disease asthmatics versus CF patients. for prolonged periods of time can result in irre- versible pulmonary damage. Therefore early The pathogenesis of ABPA is complex and involves detection and treatment of ABPA is critical in cascades of immunologic reactions including preventing serious lung damage such as bronchi- Aspergillus-specific IgE-mediated (type I) hyper- ectasis [Greenberger, 2003]. sensitivity, IgG-mediated immune complex (type III) hypersensitivity, and abnormal cell-mediated Since the first description of ABPA in the 1950s immune responses [Knutsen, 2003, 2011]. In [Hinson et al. 1952], there have been numerous genetically susceptible individuals, these hyper- studies that have shed light on the characteristics sensitivity responses in the bronchi and and immunopathogenesis of this disease. The http://tar.sagepub.com 173 Downloaded from tar.sagepub.com at NORTHWESTERN UNIV LIBRARY on January 3, 2014 Therapeutic Advances in Respiratory Disease 6 (3) Figure 1. In human hosts with a normal immune system and normal lung architecture, the inhalation of Aspergillus spores results in no disease. If the host is immunocompromised, has abnormal lung architecture or develops hypersensitivity responses to Aspergillus, the following five pulmonary diseases may result: invasive aspergillosis; chronic necrotizing aspergillosis; aspergilloma; hypersensitivity pneumonitis; allergic bronchopulmonary aspergillosis (ABPA) in asthma; or cystic fibrosis (CF). Atopic asthma and severe asthma with fungal sensitization (SAFS) are associated with IgE against Aspergillus. increased knowledge and awareness have resulted (HRCT) of the chest is the imaging modality of in earlier diagnosis and treatment of patients with choice for the diagnosis of ABPA. There are this condition. This article aims to provide a sum- patients with ABPA who fulfill diagnostic criteria mary and updates on ABPA by reviewing the but do not have the CT chest finding consistent results of recent studies on this disease with focus with proximal or central bronchiectasis; this on articles published within the last 5 years. A sys- group of patients is labeled as serological ABPA tematic search of PubMed/Medline with key- (ABPA-S). In contrast, ABPA-CB refers to patients words of ABPA or allergic bronchopulmonary with central bronchiectasis [Greenberger et al. aspergillosis was performed. All selected articles 1993]. were reviewed with focus on findings of articles published from December 2006 to December More recently another phenotype of severe 2011. The relevant findings are summarized in asthma has been defined. These asthma patients this paper. have positive skin prick test to Aspergillus but their antibody levels to A. fumigatus is below the thresh- old for diagnosis of ABPA and thus do not fulfill Diagnostic criteria the minimal criteria; this group of patients are The diagnosis of ABPA in asthma is based on classified as severe asthma with fungal sensitiza- clinical features and immunologic sensitivity to A. tion (SAFS) [Agarwal et al. 2011; Denning et al. fumigatus. The Rosenberg–Patterson criteria was 2006]. It should be noted that patients with ABPA described in 1977 for diagnosis of this disease might not fulfill serologic criteria except when [Rosenberg et al. 1977]. According to the authors, they are in acute or exacerbation stages of the the presence of six of the seven major criteria disease. Therefore, it is recommended to repeat made the diagnosis likely, and the presence of all the serologic tests in this group of patients during seven made it certain. recurrent exacerbation. The criteria were further modified to the minimal There is controversy on the threshold for total IgE essential criteria as detailed in Table 1 [Greenberger, level used for diagnosis with some centers using 2003; Schwartz and Greenberger, 1991] which 1000 ng/ml (equivalent to 417 IU/ml) [Greenberger, is currently widely used. High-resolution CT 2003] and others using 1000 IU/ mL [Agarwal 174 http://tar.sagepub.com Downloaded from tar.sagepub.com at NORTHWESTERN UNIV LIBRARY on January 3, 2014 LC Grammer and M Mahdavinia Table 1. The minimal essential criteria for allergic bronchopulmonary aspergillosis (ABPA) diagnosis. Minimal essential criteria for ABPA-central bronchiectasis (ABPA-CB) 1. Asthma 2. Immediate cutaneous reactivity on skin-prick testing (1000 protein nitrogen units/ml of A. fumigatus); 3. Elevated total serum IgE (more than 417 kU/l) 4. Elevated serum IgE and IgG to A. fumigatus ( IgG and/or IgE above twice the pooled serum samples from patients with asthma) 5. Proximal (central) bronchiectasis on radiograph (inner two-thirds of lung on computed tomography scan) Other criteria (not minimal essential criteria) Chest roentgenographic infiltrates Serum precipitating antibodies to A. fumigatus Minimal essential criteria for the diagnosis of ABPA-seropositive (ABPA-S) 1. Asthma 2. Immediate cutaneous reactivity on skin-prick testing (1000 protein nitrogen units/ml of A. fumigatus); 3. Elevated total serum IgE (more than 417 kU/l) 4. Elevated serum IgE and IgG to A. fumigatus (IgG and/or IgE above twice the pooled serum samples from patients with asthma) Other criteria (not minimal essential criteria) Chest roentgenographic