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Aspergilose broncopulmonar alergica revisão do chest 2009
1.
Allergic Bronchopulmonary Aspergillosis
Ritesh Agarwal Chest 2009;135;805-826 DOI 10.1378/chest.08-2586 The online version of this article, along with updated information and services can be found online on the World Wide Web at: http://chestjournal.chestpubs.org/content/135/3/805.full.html Chest is the official journal of the American College of Chest Physicians. It has been published monthly since 1935. Copyright2009by the American College of Chest Physicians, 3300 Dundee Road, Northbrook, IL 60062. All rights reserved. No part of this article or PDF may be reproduced or distributed without the prior written permission of the copyright holder. (http://chestjournal.chestpubs.org/site/misc/reprints.xhtml) ISSN:0012-3692 Downloaded from chestjournal.chestpubs.org by guest on April 23, 2012 © 2009 American College of Chest Physicians
2.
CHEST
Global Medicine Allergic Bronchopulmonary Aspergillosis* Ritesh Agarwal, MD, DM, FCCP Allergic bronchopulmonary aspergillosis (ABPA) is an immunologic pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus. Clinically, a patient presents with chronic asthma, recurrent pulmonary infiltrates, and bronchiectasis. The population prevalence of ABPA is not clearly known, but the prevalence in asthma clinics is reported to be around 13%. The disorder needs to be detected before bronchiectasis has developed because the occurrence of bronchiec- tasis is associated with poorer outcomes. Because many patients with ABPA may be minimally symptomatic or asymptomatic, a high index of suspicion for ABPA should be maintained while managing any patient with bronchial asthma whatever the severity or the level of control. This underscores the need for routine screening of all patients with asthma with an Aspergillus skin test. Finally, there is a need to update and revise the criteria for the diagnosis of ABPA. This review summarizes the advances in the diagnosis and management of ABPA using a systematic search methodology. (CHEST 2009; 135:805– 826) Key words: allergic bronchopulmonary aspergillosis; Aspergillus; bronchial asthma; cystic fibrosis; prevalence Abbreviations: AAS ϭ allergic Aspergillus sinusitis; ABPA ϭ allergic bronchopulmonary aspergillosis; ABPA-CB ϭ allergic bronchopulmonary aspergillosus with central bronchiectasis; ABPA-CB-ORF ϭ allergic bronchopulmonary aspergillosus with central bronchiectasis and other radiological findings; ABPA-S ϭ seropositive allergic bronchopulmonary aspergillosus; AH ϭ Aspergillus hypersensitivity; CF ϭ cystic fibrosis; HRCT ϭ high-resolution CT; IL ϭ interleukin A spergillus is aand 22% ofmold representing be- tween 0.1% ubiquitous the total air spores migatus clinically manifesting as chronic asthma, recur- rent pulmonary infiltrates, and bronchiectasis.5–13 The sampled.1 There are approximately 250 species of condition has immunologic features of immediate hy- Aspergillus, but only a few are human pathogens.2,3 persensitivity (type I), antigen-antibody complexes Depending on the host immunity and the organism (type III), and eosinophil-rich inflammatory cell virulence, the respiratory diseases caused by As- responses (type IVb), based on the revised Gell and pergillus are classified as saprophytic (aspergilloma), Coombs classification of immunologic hypersensitiv- allergic (allergic Aspergillus sinusitis, allergic bron- ity.14,15 The disorder was first described by Hinson et chopulmonary aspergillosis [ABPA], and hypersensitiv- al16 in 1952 in the United Kingdom. Occasionally, ity pneumonias) and invasive (airway invasive aspergil- patients can develop a syndrome similar to ABPA, losis, chronic necrotizing pulmonary aspergillosis, and but it is caused by fungi other than A fumigatus and invasive aspergillosis).4 ABPA is an allergic pulmonary is called allergic bronchopulmonary mycosis.17 The disorder caused by hypersensitivity to Aspergillus fu- prevalence of ABPA is believed to be about 1 to 2% in patients with asthma and 2 to 15% in patients with *From the Department of Pulmonary Medicine, Postgraduate cystic fibrosis (CF).13 The condition remains underdi- Institute of Medical Education and Research, Chandigarh, India. agnosed in many countries with reports of mean diag- The author has no conflicts of interest to disclose. Manuscript submitted November 4, 2008; revision accepted nostic latency of even 10 years between the occurrence November 20, 2008. of symptoms and the diagnosis.18 In the past two Reproduction of this article is prohibited without written permission decades, there has been an increase in the number from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml). of cases of ABPA due to the heightened physician Correspondence to: Ritesh Agarwal, MD, DM, FCCP, Assistant awareness and the widespread availability of sero- Professor, Department of Pulmonary Medicine, Postgraduate logic assays.19 –23 This review provides a summary of Institute of Medical Education and Research, Sector-12, Chandi- garh 160012, India; e-mail: riteshpgi@gmail.com the advances in the field of ABPA. For the purpose of DOI: 10.1378/chest.08-2586 this review, a systematic search of PubMed and Em- www.chestjournal.org CHEST / 135 / 3 / MARCH, 2009 805 Downloaded from chestjournal.chestpubs.org by guest on April 23, 2012 © 2009 American College of Chest Physicians
3.
Table 1—Studies Describing
the Prevalence of AH and/or ABPA in Patients with Bronchial Asthma Over the Last Two Decades* Type of Skin Criteria Used for Prevalence of AH Prevalence of ABPA Study/Year Type of Study Test Type of Antigen Diagnosis of ABPA in Asthma (n/N) in Asthma (n/N) Attapattu31/1991 Prospective Intradermal Commercial (Bencard Major (A/R/T/E/P) 58/134 8/134 Allergie; Munich, Minor (C) Germany) Eaton et al33/2000 Prospective Prick Commercial (Hollister- Major (A/R/T/E/P/ 47/255 9/35 Stier Laboratories) I/C/S) Kumar and Gaur34/ Prospective Intradermal Locally prepared Major (A/R/T/E/P/ 47/200 32/200 2000 I/C/S) Minor (C/S/B) Al-Mobeireek et al20/ Prospective Prick Commercial (Soluprick; 12/53 2001 ALK Laboratories; Wallingford, CT) Maurya et al35/2005 Prospective Intradermal Locally prepared Major (A/R/T/E/P/ 30/105 8/105 I/C/S) Minor (C/S) Agarwal et al23/2007 Prospective Intradermal Commercial (Hollister- Major (A/R/T/E/P/ 291/755 155/755 Stier Laboratories) I/C/S) Minor (S/B) Prasad et al36/2008 Prospective Intradermal Not available Major (A/R/T/E/P/ 74/244 18/244 I/C/S) Minor (C/S/B) * Criteria for ABPA: Major (A ϭ asthma, R ϭ radiologic opacities, T ϭ immediate positive skin test, E ϭ eosinophilia, P ϭ precipitins to A fumigatus, I ϭ IgE elevated, C ϭ central bronchiectasis, S ϭ specific IgG/IgE to A fumigatus); Minor (C ϭ sputum cultures of A fumigatus, S ϭ type III skin test positivity, B ϭ brownish black mucus plugs). Base was performed for relevant studies published from high in patients attending asthma clinics. Table 1 1952 to 2008. A total of 250 articles were reviewed for the summarizes the prevalence of ABPA in patients with purpose of this article. asthma reported in various studies20,23,31–36 over the last two decades. The prevalence of ABPA in pa- Epidemiology of ABPA tients admitted with acute severe asthma is even higher. In a recent study of 57 patients with acute Aspergillus hypersensitivity (AH) is defined by the severe asthma admitted in the respiratory ICUs, we presence of an immediate-type cutaneous hypersen- demonstrated the prevalence of AH and ABPA to be sitivity to A fumigatus antigens, and it is the first step around 51% and 39%, respectively.37 The occurrence in the development of ABPA.24 Only a minority of of AH and ABPA was significantly higher in patients patients with AH develop the complete clinical with acute asthma compared to the outpatient bron- picture of ABPA.25 The population prevalence of chial asthma (around 39% and 21%, respectively).23 ABPA in asthma, generally referred to as 1 to 2%,5,13,26,27 is based on the inference of only three Pathogenesis of ABPA studies (one peer-reviewed and two non–peer-re- viewed studies).28,29 In the only peer-reviewed The susceptibility of asthmatic patients to develop study,28 14 patients with allergic bronchopulmonary ABPA is not fully understood (Fig 1). Some authors mycosis were identified from a total of 1,390 new have reported that exposure to large concentrations referrals in a catchment area population of half a of spores of A fumigatus may cause ABPA.16,38 – 41 million, estimating a period prevalence of just above Environmental factors are not considered the main 1%. The other two non–peer-reviewed question- pathogenetic factors because not all asthmatics de- naire-based studies suggested a maximum preva- velop ABPA despite being exposed to the same lence of ABPA of 1% in the United States.29 In a environment. In a genetically predisposed individu- recent metaanalysis,30 we demonstrated a prevalence al42–54 (Table 2), inhaled conidia of A fumigatus of AH and ABPA in asthma of 28% and 12.9%, persist and germinate into hyphae with release of respectively. The limitation noted in this review was antigens that compromise the mucociliary clearance, that all the studies were performed in specialized stimulate and breach the airway epithelial barrier, clinics and may not be representative of the general and activate the innate immunity of the lung.55–58 population. Thus the exact population prevalence of This leads to inflammatory cell influx and a resultant ABPA remains speculative but is likely to be fairly early- and late-phase inflammatory reaction.59,60 The 806 Global Medicine Downloaded from chestjournal.chestpubs.org by guest on April 23, 2012 © 2009 American College of Chest Physicians
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Figure 1. A
line diagram depicting the pathogenesis of allergic bronchopulmonary aspergillosis. Th ϭ T-helper. antigens are also processed presented to T-cells with Charcot-Leyden crystals, and inflammatory cells. activation of Th2 CD4ϩ T-cell responses.42,61–63 The Th2 Scanty hyphae can often be demonstrated in the cytokines (interleukin [IL]-4, IL-5, and IL-13) lead to total bronchiectatic cavities. The bronchial wall in ABPA and A fumigatus-specific IgE synthesis, mast cell degran- is usually infiltrated by inflammatory cells, primarily ulation, and promotion of a strong eosinophilic response. the eosinophils.65 The peribronchial parenchyma This causes the characteristic pathology of ABPA. shows an inflammatory response with conspicuous eosinophilia. Occasionally, fungal growth in the lung Pathology of ABPA parenchyma can occur in some patients with ABPA.66 The pathology of ABPA varies from patient to Patients can also demonstrate a pattern similar to that patient, and in different areas of the lung in the same of bronchiolitis obliterans with organizing pneumo- patient (Fig 2).64,65 Histologic examination reveals nia.67 Bronchocentric granulomatosis, the presence of the presence of mucus, fibrin, Curschmann spirals, noncaseating granulomas containing eosinophils and www.chestjournal.org CHEST / 135 / 3 / MARCH, 2009 807 Downloaded from chestjournal.chestpubs.org by guest on April 23, 2012 © 2009 American College of Chest Physicians
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Table 2—Genetic Factors
Involved in the Pathogenesis is seen in 31 to 69% of patients.21,23,34 The symptoms of ABPA* of hemoptysis, expectoration of brownish black mu- HLA associations: presence of HLA DR-2 and absence of cus plugs, and history of pulmonary opacities in an HLA-DQ2 sequences42,44,45 asthmatic patient suggests ABPA. Patients can oc- IL-10 promoter polymorphisms49 casionally be asymptomatic, and the disorder is Polymorphism at position 1,082 produces higher levels of IL-10 diagnosed on routine screening of asthmatic pa- if 1082G allele is present and lower levels of IL-10 if the tients.22,23,33 Physical examination can be normal or 1082A allele is present may reveal polyphonic wheeze. Clubbing is rare, In patients with CF there is a relationship between the 1082GG genotype with both Aspergillus colonization and ABPA seen in only 16% of patients. On auscultation, coarse Surfactant protein A gene polymorphisms48,53 crackles can be heard in 15% of patients.23 Physical A significantly higher frequency of the AGA allele (A1660G) of examination can also detect complications such as SP-A2 found in patients with ABPA vs control subjects. pulmonary hypertension and/or respiratory failure.76 Coexistence of A1660G polymorphism with SP-A2 G1649C During exacerbations of ABPA, localized findings of (Ala91Pro) found with 10-fold higher odds in patients with ABPA. Patients with ABPA with GCT and AGG alleles consolidation and atelectasis can occur that needs to showed significantly higher levels of total IgE and percentage be differentiated from other conditions. eosinophilia vs patients with ABPA with CCT and AGA alleles48 Laboratory Findings The T allele at T1492C and G allele at G1649C of SP-A2 observed at higher frequencies in ABPA patients than in Aspergillus Skin Test: The Aspergillus skin test is controls. Also there is a higher frequency of the TT genotype performed using an A fumigatus antigen, either at position1492 of SP-A2 than controls53 commercial (eg, Aspergillin; Hollister-Stier Labora- There were no polymorphisms found in SP-A1 gene53 tories; Spokane, WA) or locally prepared. The test is CFTR gene mutation:43,46,47 increased frequency of CFTR read every 15 min for 1 h, and then after 6 to 8 h. mutations in patients with ABPA vs skin-prick test positive or negative patients with bronchial asthma The reactions are classified as type I if a wheal and IL-15 polymorphisms:52 higher frequency of IL-15 ϩ 13689*A erythema developed within 1 min, reaches a maxi- allele and A/A genotype mum after 10 to 20 min, and resolves within 1 to 2 h. TNF-␣ polymorphisms:52 lower frequency of the TNF-␣ 308 * A/A A type III reaction is read after 6 h, and any amount genotype of subcutaneous edema is considered a positive Mannose-binding lectins:53 the intronic single nucleotide result. An immediate cutaneous hypersensitivity to A polymorphism G1011A of mannose-binding lection seen with increased frequency in patients with ABPA fumigatus antigens is a characteristic finding of IL-4 receptor polymorphisms:51 single nucleotide polymorphism of ABPA and represents the presence A fumigatus- the extracellular IL-4R␣ ile75val observed in 80% of ABPA specific IgE antibodies, whereas a type III skin patients reaction probably represents the immune complex IL-13 polymorphisms:50 the arg110gln polymorphism found with hypersensitivity reaction, although its exact signifi- increased frequency in ABPA and the combination of IL-4R␣ cance remains unclear. The test can be performed ile75val/IL-13 arg110gln polymorphism found with an even higher frequency using either a skin-prick test or intradermal injection Toll-like receptor gene polymorphisms:54 susceptibility to ABPA with the latter being more sensitive.30,77,78 A skin- was associated with allele C on T1237C (TLR9) prick test should be performed for Aspergillus skin *HLA ϭ human leukocyte antigen; TNF ϭ tumor necrosis factor; testing, and if the results are negative should be CFTR ϭ CF transmembrane conductance regulator. confirmed by an intradermal test.30 There is no difference on the outcome of the test and the type of antigen (locally prepared or commercial) used for performance of the test.30 multinucleated giant cells centered on the airway, are also seen.68,69 Rarely, invasive aspergillosis complicat- Total Serum IgE Levels: The total IgE level is the ing the course of ABPA has also been described.70 –74 most useful test for diagnosis and follow-up of ABPA. A normal serum IgE level excludes ABPA as the cause of the patient’s current symptoms. The only situation Clinical Features where IgE levels can be normal in active ABPA is when There is no gender predilection and majority of the the patient is already on glucocorticoid therapy for any cases present in the third to fourth decade. A family reason and investigation for IgE levels has been con- history of ABPA may be elicited occasionally.75 Table 3 ducted. After treatment with glucocorticoids, the se- summarizes the clinical features of ABPA encoun- rum IgE levels decline, and a 35 to 50% decrease is tered in three large series from our institute.19,21,23 taken as a criteria for remission.79 The serum IgE Most present with low-grade fever, wheezing, bron- determination is also used for follow-up, and a doubling chial hyperreactivity, hemoptysis, or productive of the patient’s baseline IgE levels indicates relapse of cough. Expectoration of brownish black mucus plugs ABPA.80,81 808 Global Medicine Downloaded from chestjournal.chestpubs.org by guest on April 23, 2012 © 2009 American College of Chest Physicians
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Figure 2. Histopathologic
findings in a patient with allergic bronchopulmonary aspergillosis. Top left, A: photomicrograph showing bronchial lumen containing allergic mucin (hematoxylin-eosin, original ϫ100). Top right, B: high-magnification photomicrograph of allergic mucin having variegated appearance, necrotic eosino- phils, Charcot-Leyden crystals (thin arrow), and an occasional septate fungal hyphae indicated by a thick arrow (hematoxylin-eosin, original ϫ200). Bottom left, C: photomicrograph showing eosinophilic pneumonia. There is filling of the alveolar spaces by eosinophils admixed with variable number of macrophages (hematoxylin-eosin, original ϫ200). Bottom right, D: photomicrograph showing bronchocentric granulomatosis. There is partial replacement of bronchial epithelium by palisading histiocytes (hematoxylin-eosin, original ϫ100). Serum IgE and IgG Antibodies Specific to A cutoff value of IgG/IgE more than twice the pooled fumigatus: An elevated level of A fumigatus-specific serum samples from patients with AH can greatly antibodies measured by fluorescent enzyme immuno- help in the differentiation of ABPA from other assay is considered the hallmark of ABPA.22 A conditions.82 Table 3—Clinical Features Encountered in Three Large Case Series of ABPA Published From the Author’s Institute* Clinical Features Behera et al19/1994 Chakrabarti et al21/2002 Agarwal et al23/2007 Patients, No. 35 89 155 Male/female gender, No. 14/21 53/35 79/76 Mean age, yr 34.3 36.4 33.4 Mean duration of asthma, yr 11.1 12.1 8.9 History of asthma 94% 90% 100% Expectoration of sputum plugs Not available 69% 46.5% Mean eosinophil count, per L 1,264 AEC Ͼ 500/L, % 12/28 (43%) 100% 76.1% Fleeting shadows 77% 74% 40% History of intake of antituberculous drugs 34% 29% 44.5% Skin test against Aspergillus Type I 51% 85% 100% Type III 25.7% 16.9% 83.2% Mean IgE levels Not done Not done 6,434 Elevated IgE levels, % 100% Aspergillus-specific IgE/IgG Not done Not done 100% Serum precipitins against Aspergillus 77% 71.9% 86.5% Central bronchiectasis 71% 69% 76.1% *AEC ϭ absolute blood eosinophil count. www.chestjournal.org CHEST / 135 / 3 / MARCH, 2009 809 Downloaded from chestjournal.chestpubs.org by guest on April 23, 2012 © 2009 American College of Chest Physicians
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Radiologic Investigations: A
wide spectrum of have associated peripheral bronchiectasis.22,96 Mini- radiographic appearances can occur in ABPA (Table mal bronchiectasis can also be seen in asthma,97,98 4). The chest radiographic findings of ABPA include but the findings of bronchiectasis affecting three or transient or fixed pulmonary opacities (Fig 3), tram- more lobes, centrilobular nodules, and mucoid im- line shadows, finger-in-glove opacities, and tooth- paction are highly suggestive of ABPA.99 The un- paste shadows.83– 87 Findings noted on high-resolution common radiologic manifestations of ABPA include CT (HRCT) include central bronchiectasis, mucoid miliary nodular opacities,100 perihilar opacities impaction, mosaic attenuation, presence of centri- simulating hilar lymphadenopathy,84,101,102 pleural lobular nodules, and tree-in-bud opacities (Fig effusions,103–105 and pulmonary masses.106 –111 4).88,89 High-attenuation mucoid impaction (mucus visually denser than the paraspinal muscle) is a Serum Precipitins Against A fumigatus: The pre- pathognomonic finding encountered in patients with cipitating IgG antibodies are elicited from crude ABPA.23,90 –95 Central bronchiectasis with peripheral extracts of A fumigatus and can be demonstrated tapering of bronchi on HRCT is believed to be a sine using the double gel diffusion technique.112,113 They qua non for the diagnosis of ABPA. Bronchiectasis can also be present in other pulmonary disorders and may not be present in all patients with ABPA, may be thus represent supportive not diagnostic evidence for present in patients with CF without ABPA, and ABPA.112–114 almost 40% of the bronchiectatic segments can also Peripheral Eosinophilia: A blood absolute eosino- phil count Ͼ 1,000 cells/L is also a major criterion for the diagnosis of ABPA. However, 53% of patients Table 4 —Radiologic Findings Encountered in Patients With ABPA in our series22 had an absolute eosinophil count Ͻ 1,000 cells/L, and thus a low eosinophil count 1. Chest radiographic findings does not exclude the diagnosis of ABPA. Transient changes Common Sputum Cultures for A fumigatus: Culture of A Patchy areas of consolidation Radiologic infiltrates: toothpaste and gloved finger shadows fumigatus in the sputum is supportive but not diag- due to mucoid impaction in dilated bronchi nostic of ABPA. The fungus can also be grown in Collapse: lobar or segmental patients with other pulmonary diseases due to the Uncommon ubiquitous nature of the fungi. We rarely perform Bronchial wall thickening: tramline shadows sputum cultures for the diagnosis of ABPA. Air-fluid levels from dilated central bronchi filled with fluid Perihilar infiltrates simulating adenopathy Massive consolidation: unilateral or bilateral Pulmonary Function Tests: These tests help cate- Small nodules gorize the severity of the lung disease but have no Pleural effusions diagnostic value in ABPA and need not constitute Permanent changes the basis for screening.22 The usual finding is an Common obstructive defect of varying severity.115–117 Parallel-line shadows representing bronchial widening Ring-shadows 1–2 cm in diameter representing dilated bronchi en face Role of Specific Aspergillus Antigens: Patients with Pulmonary fibrosis: fibrotic scarred upper lobes with ABPA are evaluated with crude extracts from As- cavitation pergillus, which lack reproducibility and consistency, Uncommon and they frequently cross-react with other anti- Pleural thickening gens.118 The advances in molecular techniques have Mycetoma formation Linear scars enabled detection and cloning of specific Aspergillus 2. HRCT findings antigens. The recombinant allergens Asp f1, Asp f2, Common Asp f3, Asp f4, and Asp f6 have been evaluated for Central bronchiectasis their diagnostic performance in serologic studies in Mucus plugging with bronchoceles asthmatic patients119 –122 and in patients with Consolidation Centrilobular nodules with tree-in-bud opacities CF121,123–125 Preliminary data suggest a promising Bronchial wall thickening role of these antigens in the diagnosis of ABPA. Areas of atelectasis Further studies are required before they can be Mosaic perfusion with air trapping on expiration implemented in routine clinical practice. Uncommon High-attenuation mucus (finding most helpful in differential diagnosis) Diagnosis and Diagnostic Criteria Pleural involvement The Rosenberg-Patterson criteria6,9 are most often Randomly scattered nodular opacities used for the diagnosis (Table 5). There are also a set 810 Global Medicine Downloaded from chestjournal.chestpubs.org by guest on April 23, 2012 © 2009 American College of Chest Physicians
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Figure 3. Chest
radiograph showing transient pulmonary opacities in the right lower lobe (left) in a patient with allergic bronchopulmonary aspergillosis that have spontaneously disappeared (right). of minimal diagnostic criteria for ABPA (Table ABPA.97–99 There are no cutoffs for total IgE levels 5).32,33 These criteria continue to be challenged and with many using 1,000 IU/mL,8,9,22,23,82,128 –130 and modified because there is lack of evidence on the others using 1,000 ng/mL (equivalent to 417 IU/ number of criteria that should be present to make mL).5,27,33,34 The total IgE levels may also be ele- the diagnosis. The differentiation of patients with vated in patients with AH without ABPA. As the ABPA from patients with AH can also be problem- understanding of ABPA has evolved, it is clear that atic. Serum precipitins to A fumigatus is present in patients with AH may present with less than the full 69 to 90% of patients with ABPA23,112,116,126,127 but complement of diagnostic criteria.131 Thus, a cutoff also in 9% of asthmatics.112 Central bronchiectasis value of 1,000 ng/mL IgE will probably lead to an can be seen in patients with asthma without overdiagnosis of ABPA.131 The use of A fumigatus- Figure 4. HRCT images of different patients with allergic bronchopulmonary aspergillosis. Top right: bilateral central bronchiectasis with centrilobular nodules and tree-in-bud opacities in the left lung. Top left: bilateral central bronchiectasis with many mucus-filled bronchi. Bottom, left and right: images from the same patient show high-attenuation mucoid impaction. Bottom right: the mucoid impaction in the right lung is visually denser than the paraspinal skeletal muscle. www.chestjournal.org CHEST / 135 / 3 / MARCH, 2009 811 Downloaded from chestjournal.chestpubs.org by guest on April 23, 2012 © 2009 American College of Chest Physicians
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Table 5—Criteria Used
for the Diagnosis of ABPA systemic corticosteroids are essential to prevent irre- 6,9 versible damage.137 The natural course of ABPA can Rosenberg-Patterson criteria Major criteria (mnemonic ARTEPICS) be best understood if we recognize the two impor- A ϭ Asthma tant classification schemes (Tables 6 and 7) of ABPA: R ϭ Roentgenographic fleeting pulmonary opacities (1) classification of ABPA into five stages as de- T ϭ Skin test positive for Aspergillus (type I reaction, scribed by Patterson et al8, and (2) classification of immediate cutaneous hyperreactivity) E ϭ Eosinophilia ABPA into ABPA-S (seropositive ABPA) and ABPA-CB P ϭ Precipitating antibodies (IgG) in serum (ABPA with central bronchiectasis) described by I ϭ IgE in serum elevated (Ͼ 1,000 IU/mL) Greenberger et al.12 C ϭ Central bronchiectasis S ϭ Serums A fumigatus-specific IgG and IgE (more than twice the value of pooled serum samples from patients with Staging of ABPA: ABPA has been classified into asthma who have Aspergillus hypersensitivity) five stages, but a patient does not necessarily Minor criteria Presence of Aspergillus in sputum progress from one stage to the other sequentially Expectoration of brownish black mucus plugs (Table 6). Patients in stage I or III (depending on Delayed skin reaction to Aspergillus antigen (type III whether or not the disorder has been previously reaction) diagnosed) are generally symptomatic with radio- The presence of six of eight major criteria makes the diagnosis almost certain; the disease is further classified as ABPA-S or graphic infiltrates, raised IgE levels, and elevated A ABPA-CB on the absence or presence of central fumigatus-specific IgG/IgE.23 With glucocorticoid bronchiectasis, respectively therapy, there is clearing of radiographic opacities Minimal diagnostic criteria for ABPA32 with a 35 to 50% decline in IgE levels by 6 weeks Minimal ABPA-CB Asthma that defines remission or stage II. The aim of Immediate cutaneous hyperreactivity to Aspergillus antigens glucocorticoid therapy is not normalization of total Central bronchiectasis IgE levels because the immunologic process goes in Elevated IgE remission with just 35 to 50% decline in IgE levels, Raised A fumigatus-specific IgG and IgE Minimal ABPA-S and in many patients the IgE levels do not come to Asthma down to normal values. The test needs to be often Immediate cutaneous hyperreactivity to Aspergillus antigens repeated during therapy to determine the lowest Transient pulmonary infiltrates on chest radiograph level for an individual patient that serves as the Elevated IgE Raised A fumigatus-specific IgG and IgE baseline for that particular patient. Treatment is continued for 6 to 9 months, and if there are no exacerbations over the next 3 months after stopping specific IgE and IgG levels can help in confirming therapy, we label it as “complete remission.” Patients the diagnosis of ABPA because values of IgG/IgE in complete remission are followed up by serial IgE more than twice the pooled serum samples from levels every 6 months for the first year and then patients with asthma are raised only in ABPA.113,132 annually. Even in patients with complete remission, We currently use a cutoff value of 1,000 IU/mL for the IgE levels decline to normal in only a minority of the diagnosis of ABPA.22,23 While investigating a patients,128,133 and the aim of glucocorticoid therapy patient with asthma, we first perform an Aspergillus is not achievement of normal IgE levels.79 A com- skin test. Once it is positive, the total serum IgE plete remission does not imply a permanent remis- levels are done.131 If the value is Ͼ 1,000 IU/mL, we sion because exacerbations can occur several years perform the other tests (Fig 5). If the value is after remission.135 Almost 25 to 50% of the patients between 500 and 1,000 IU/mL, the next step is analysis have relapse/exacerbation of the disease, defined by of A fumigatus-specific IgE and IgG antibodies. If the doubling of the baseline IgE levels (stage III).8,9,22 levels are raised, the patient is followed up every 6 weeks Patients in stage IV require oral glucocorticoids for with total IgE levels. If the absolute value rises Ͼ 1,000 control of asthma (glucocorticoid-dependent asthma) IU/mL or there is a rising trend with clinical deterioration, or ABPA (glucocorticoid-dependent ABPA).10,22 Pa- the treatment is started. If the value is between 500 and tients in stage V are those with widespread bronchi- 1,000 IU/mL and IgE and IgG specific to A fumigatus are ectasis and varying degrees of pulmonary dysfunc- not raised, the patient is followed up with a yearly total tion. We define patients in stage V if they have IgE levels (Fig 5). hypercapnic respiratory failure (Pao2 Ͻ 60 mm Hg and Paco2 Ն 45 mm Hg) and/or cor pulmonale. Natural History Even in stage V ABPA, the disease can be clinically The natural history of ABPA is not well character- as well as immunologically active requiring long- ized.9,128,133–136 An early diagnosis and initiation of term glucocorticoid therapy.136,138 812 Global Medicine Downloaded from chestjournal.chestpubs.org by guest on April 23, 2012 © 2009 American College of Chest Physicians
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Figure 5. Algorithm
followed in the diagnostic workup for allergic bronchopulmonary aspergillosis in the author’s chest clinic. Radiologic Classification of ABPA: ABPA is clas- and ABPA-CB-ORF (other radiologic findings) sified as ABPA-S or ABPA-CB, respectively, de- (Table 7). Patients with ABPA-S probably repre- pending on the absence or presence of bronchiec- sent the earliest stage of the disorder. It is be- tasis or as ABPA-S (mild), ABPA-CB (moderate), lieved that patients with ABPA-S have a milder www.chestjournal.org CHEST / 135 / 3 / MARCH, 2009 813 Downloaded from chestjournal.chestpubs.org by guest on April 23, 2012 © 2009 American College of Chest Physicians
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Table 6 —Stages
of ABPA8,22 Stage Description Clinical Picture Radiologic Findings Immunologic Features I Acute phase Usually symptomatic, Normal or presence of IgE Ͼ 1,000 IU/mL, raised fever, weight loss, radiologic opacities specific IgG/IgE and wheeze precipitins to A fumigatus II Remission Asymptomatic Generally normal or significant Usually 35–50% decline in IgE resolution of radiologic levels by 6 wk to 3 mo; we opacities from the acute give additional label of phase “complete remission” if the patient did not have any additional ABPA exacerbations over the next 3 mo after stopping steroid therapy III Exacerbation Symptomatic as in acute Transient or fixed pulmonary Doubling of IgE levels from phase opacities baseline IV Glucocorticoid-dependent Symptomatic Transient or fixed pulmonary Two groups can be identified: ABPA opacities one in whom IgE levels do not rise but require steroids for asthma control (glucocorticoid- dependent asthma); the other in whom steroids are required to continually suppress the disease activity (glucocorticoid- dependent ABPA) V End-stage (fibrotic) Symptomatic, findings of Evidence of bronchiectasis, Serum IgE levels and specific ABPA fixed airway pulmonary fibrosis, immunoglobulins do not obstruction, severe pulmonary hypertension become normal in most pulmonary patients, and even these dysfunction, type II patients can have frequent respiratory failure, cor exacerbations pulmonale clinical course and less severe immunologic find- creases the probability of a smoother course of this ings when compared to ABPA-CB based on the relapsing-remitting disorder. inference of three studies (total of 124 pa- tients).12,139,140 In the largest of these three studies Management (76 patients), only the A fumigatus-specific IgG levels were higher in patients with ABPA-CB The management of ABPA includes two important compared to ABPA-S. Other immunologic param- aspects: institution of glucocorticoids to control the eters were not significantly different between the immunologic activity and close monitoring for detec- two groups.12 In our study of 126 patients, the tion of relapses. Another possible target is the use of clinical, spirometric, and immunologic findings antifungal agents to attenuate the fungal burden were not significantly different when classifying secondary to the fungal colonization in the airways. ABPA into ABPA-S and ABPA-CB or as ABPA-S, ABPA-CB, and ABPA-CB-ORF.22 Systemic Glucocorticoid Therapy: Oral corticoste- However, the course of patients with ABPA-S is roids are the treatment of choice for ABPA. They not likely to be less severe when compared to those with only suppress the immune hyperfunction but are also ABPA-CB. In a multivariate analysis of 155 patients antiinflammatory. There are no data to guide the with ABPA, we demonstrated that the severity of dose and duration of glucocorticoids, and different bronchiectasis and presence of hyperattenuating regimens of glucocorticoids have been used (Table mucoid impaction on HRCT-predicted relapses of 8). The use of lower doses of glucocorticoids was ABPA and the severity of bronchiectasis was an associated with frequent relapses or corticosteroid independent predictor of failure to achieve long- dependence (45%).9 We use a higher dosage of term remission.23 Thus it may not be important to glucocorticoids for a longer duration and observed stage the severity of ABPA based on the presence higher remission rates and a lower prevalence of or absence of CB, but it remains prudent to glucocorticoid-dependent ABPA (13.5%).22 This diagnose and treat ABPA early to prevent the raises the possibility of a higher dose and prolonged development of bronchiectasis because it in- duration of corticosteroid therapy being associated 814 Global Medicine Downloaded from chestjournal.chestpubs.org by guest on April 23, 2012 © 2009 American College of Chest Physicians
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Table 7—Radiologic Classification
of ABPA* Table 8 —Treatment Protocols for the Management of ABPA Classification Features Oral glucocorticoids Greenberger et al 12 Regime 15 classification Prednisolone, 0.5 mg/kg/d, for 1–2 wk, then on alternate days ABPA-S All the diagnostic features of ABPA for 6–8 wk. Then taper by 5–10 mg every 2 wk and but no evidence of central discontinue bronchiectasis on HRCT. Repeat the total serum IgE concentration and chest Patients with ABPA-S may be radiograph in 6 to 8 wk classified as Patterson stages I to Regime 222,113 IV. These patients may have Prednisolone, 0.75 mg/kg, for 6 wk, 0.5 mg/kg for 6 wk, then recurrent exacerbations and may tapered by 5 mg every 6 wk to continue for a total duration also be classified as stage III of at least 6 to 12 mo. The total IgE levels are repeated (ABPA-CB) All findings of ABPA including CB every 6 to 8 wk for 1 yr to determine the baseline IgE on HRCT. Patients with ABPA- concentrations CB may belong to any of the Follow-up and monitoring Patterson stages The patients are followed up with a medical history and Kumar140 classification physical examination, chest radiograph, and measurement of ABPA-S ABPA without CB total IgE levels every 6 wk to demonstrate decline in IgE ABPA-CB ABPA with CB levels and clearing of the chest radiograph ABPA-CB-ORF ABPA with CB other radiologic A 35% decline in IgE level signifies satisfactory response to features such as pulmonary therapy. Doubling of the baseline IgE value can signify a fibrosis, bleb, bullae, silent ABPA exacerbation pneumothorax, parenchymal If the patient cannot be tapered off prednisolone, the disease scarring, emphysematous change, has evolved into stage IV. Management should be multiple cyst, fibrocavitary attempted with alternate-day prednisone with the least lesions, aspergilloma, ground- possible dose glass appearance, collapse, Monitor for adverse effects (eg, hypertension, secondary mediastinal lymph node, pleural diabetes) effusion, and pleural thickening Prophylaxis for osteoporosis: oral calcium and bisphosphonates *Both the classification schemes believe that patients without CB and Oral itraconazole ORF have serologically milder disease, but it has been shown that Dose: 200 mg bid for 16 wk then once a day for 16 wk there is no difference in clinical, spirometric, and serological Indication: First relapse of ABPA or glucocorticoid-dependent severity between patients with and without bronchiectasis (see text ABPA for details). Follow-up and monitoring Monitor for adverse effects (eg, nausea, vomiting, diarrhea, and elevated liver enzymes) with better outcomes. However, there are no direct Monitor for drug–drug interactions comparisons between the two regimens, and the Monitor clinical response based on clinical course, selection is a matter of personal preference. The radiography, and total IgE levels clinical effectiveness of steroid therapy is reflected by marked decreases in the patient’s total serum IgE levels (there seems to be no correlation between serum levels of A fumigatus-specific IgE levels and agent, itraconazole.130,141,148 –160 Only two random- disease activity141) along with symptom and radio- ized controlled studies (84 patients) have evaluated graphic improvements. The goal of therapy is not to the role of itraconazole in ABPA.130,156 Pooled anal- attempt normalization of IgE levels but to decrease ysis showed that itraconazole could significantly de- the IgE levels by 35 to 50%, which leads to clinical crease the IgE levels by Ն 25% when compared to and radiographic improvement. One should also placebo but did not cause significant improvement in establish a stable serum level of total IgE to serve as lung function.161 A major limitation was that neither a guide to future detection of relapse. of the studies reported long-term outcomes in ABPA. Thus longer term trials are required before a Inhaled Corticosteroids: Although small case stud- firm recommendation can be made for the use of ies suggest some benefit of inhaled corticosteroids in itraconazole in ABPA. We currently use itraconazole the management of ABPA,142–145 a double-blind mul- only after the first relapse of ABPA despite glucocor- ticenter placebo-controlled trial in 32 patients sug- ticoid therapy or in patients with glucocorticoid- gested no superiority over placebo.146 We use inhaled dependent ABPA (Table 8). In the limited numbers corticosteroids only for the control of asthma once the of patients in whom we have used the drug, there oral prednisolone dose is reduced to Ͻ 10 mg/day. was no observable advantage.22 Itraconazole not only has numerous adverse effects,162 but it also inhibits Oral Itraconazole: Ketoconazole has been tried in the metabolism of methylprednisolone (but not the past147 and has been replaced by the less toxic prednisolone) with resultant increased frequency of www.chestjournal.org CHEST / 135 / 3 / MARCH, 2009 815 Downloaded from chestjournal.chestpubs.org by guest on April 23, 2012 © 2009 American College of Chest Physicians
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Table 9 —Studies
Describing Prevalence of AH and/or ABPA in Patients With CF Study Year Nature of Study Patients, No. AH in CF ABPA* in CF Diagnosis of AH† 184 Mearns et al 1967 Prospective 86 28/86 Skin test Allan et al185 1975 Prospective 30 11/30 Skin test Silverman et al186 1978 Prospective 48 17 Skin test Nelson et al187 1979 Prospective 46 18/46 5/46 Skin test Laufer et al177 1984 Prospective 100 53/100 10/100 Skin test Feanny et al188 1988 Prospective 117 18/117 12/117 Skin test Schonheyder et al189 1988 Prospective 200 10/200 Zeaske et al190 1988 Prospective 75 44/75 10/75 Skin test Knutsen et al176 1990 Prospective 73 18/73 9/73 Skin test Nicolai et al179 1990 Prospective 148 58/148 Serology Simmonds et al191 1990 Prospective 137 8/137 Hutcheson et al192 1991 Prospective 79 24/79 Skin test el-Dahr et al193 1994 Prospective 147 30/147 22/147 Serology Marchant et al194 1994 Retrospective 160 16/160 Skin test Mroueh and Spock178 1994 Retrospective 236 38/87 15/236 Skin test Becker et al181 1996 Prospective 53 15/51 1/53 Skin test Hutcheson et al195 1996 Prospective 118 47/112 6/118 Skin test Geller et al182 1999 Prospective 14,210 281/14,210 Nepomuceno et al153 1999 Retrospective 172 16/172 Cimon et al196 2000 Prospective 128 5/128 Mastella et al174 2000 Prospective 12,447 967/12,447 Taccetti et al197 2000 Prospective 3,089 191/3,089 Ritz et al180 2005 Prospective 160 20/160 11/160 Serology Skov et al183 2005 Retrospective 277 13/277 Almeida et al198 2006 Prospective 32 11/32 2/32 Skin test Kraemer et al173 2006 Prospective 122 16/122 Chotirmall et al199 2008 Prospective 50 6/50 Rapaka and Kolls200 2008 Retrospective 440 31/440 * ABPA: Studies have used different inclusion criteria for diagnosing ABPA. See text for further details. † AH: Defined as immediate cutaneous hypersensitivity to Aspergillus antigen or a positive specific IgE in serum against A fumigatus (radioallergosorbent test class Ն 2) and/or increased specific IgE in serum against rAsp f1 Ͼ 9.6 EU/mL, with normal values for rAsp f4 (Ͻ 8.4 EU/mL) and rAsp f6 (Ͻ 7.2 EU/mL) steroid side effects including adrenal insufficiency.163 clude recurrent asthma exacerbations and, if Adrenal suppression has also been reported with the untreated, the development of bronchiectasis with concomitant use of itraconazole and inhaled budes- subsequent pulmonary hypertension and respiratory onide.164,165 failure. In fact, this is the reason why routine screen- ing is recommended in bronchial asthma to prevent Other Therapies: There is a single patient case the complications just described. report of ABPA treated with inhaled amphotericin and budesonide.166 Similarly, there is another case ABPA in Special Situations record on the use of omalizumab for the manage- ABPA Complicating CF: The association of ABPA ment of ABPA.167 One author has also used pulse and CF was first reported in 1965.172 The occur- doses of IV methylprednisolone for the treatment of rence of ABPA in CF is associated with deterioration severe ABPA.168 Recently, voriconazole has also of lung function, higher rates of microbial coloniza- been tried in the treatment of ABPA.169 –171 tion, pneumothorax, massive hemoptysis, and poorer nutritional status.153,173,174 A key element in the Differential Diagnosis and Complications immunopathogenesis may be exposure to high levels The disorder needs to be differentiated from the of Aspergillus allergens due to abnormal mucus following conditions: Aspergillus hypersensitive properties.175 The recognition of ABPA in CF can be bronchial asthma, pulmonary tuberculosis in en- difficult because ABPA shares many clinical charac- demic areas, community-acquired pneumonia (espe- teristics with poorly controlled CF lung disease. cially acute presentations), and other inflammatory Presence of wheezing, pulmonary infiltrates, bron- pulmonary disorders such as eosinophilic pneumo- chiectasis, and mucus plugging are common mani- nia, bronchocentric granulomatosis, and Churg- festations of CF-related pulmonary disease without Strauss syndrome. The complications of ABPA in- ABPA. The prevalence of AH in patients with CF 816 Global Medicine Downloaded from chestjournal.chestpubs.org by guest on April 23, 2012 © 2009 American College of Chest Physicians
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has been reported
between 29% and 53%,176 –180 and prevalence of ABPA of 7.8% (95% confidence inter- the prevalence of ABPA as 1 to 15%. Atopy seems to val, 5.8 to 10) using a random effects model [Figs 6 be an important risk factor for ABPA in CF, with and 7]. There was no uniformity in the diagnostic ABPA observed in 22% of atopic patients but only criteria between different studies with varying crite- 2% of nonatopic patients.153,181–183 ria used for diagnosis of AH and ABPA. This fact has To determine the prevalence of AH/ABPA in CF, also been previously reported in a questionnaire- a systematic search was performed. The search based study, which revealed a considerable variabil- yielded 28 studies (16 studies [1,391 patients] de- ity in the criteria used for the diagnosis of ABPA in scribing the prevalence of AH in CF and 23 CF.201 Therefore, prospective reporting of cases with studies [32,589 patients] describing the prevalence uniform criteria would be the only way to reliably of ABPA in CF) that have described the preva- identify the true prevalence of ABPA in CF. lence of AH and/or ABPA in patients with CF Although a high proportion of CF patients develop (Table 9).153,173,174,176 –200 A proportion metaanalysis of sensitization to A fumigatus, many demonstrate a these studies suggested the prevalence of AH in CF spontaneous decline in many immunologic parame- of 34% (95% confidence interval, 27 to 41) and the ters, including IgE levels.192 The diagnosis of ABPA Figure 6. Proportion metaanalysis showing the prevalence of Aspergillus hypersensitivity in patients with cystic fibrosis (random effects model). www.chestjournal.org CHEST / 135 / 3 / MARCH, 2009 817 Downloaded from chestjournal.chestpubs.org by guest on April 23, 2012 © 2009 American College of Chest Physicians
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Figure 7. Proportion
metaanalysis showing the prevalence of allergic bronchopulmonary aspergillosis in patients with CF (random effects model). in CF should not be based solely on serology and data are available to formulate conclusive treatment skin test results, and prolonged testing might be recommendations for ABPA in CF. The treatment required to make a definite diagnosis (Table 10). The issues are further complicated because pulmonary treatment of ABPA in CF is not very different from exacerbations in a patient with ABPA and CF could that of ABPA in bronchial asthma, except minimal be related to ABPA or pulmonary infection, and 818 Global Medicine Downloaded from chestjournal.chestpubs.org by guest on April 23, 2012 © 2009 American College of Chest Physicians
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Table 10 —Consensus
Conference Proposed Diagnostic lung diseases like idiopathic bronchiectasis,209 and Screening Criteria for ABPA in CF202 post-tubercular bronchiectasis,210 bronchiectasis Classic diagnostic criteria secondary to Kartagener syndrome,211 COPD,212 1. Acute or subacute clinical deterioration (cough, wheeze, and and in patients with chronic granulomatous dis- other pulmonary symptoms) not explained by another etiology ease and hyper IgE syndrome.213 However, these 2. Serum total IgE levels Ͼ 1,000 IU/mL are case reports or small case studies, and larger 3. Immediate cutaneous reactivity to Aspergillus or presence of observations are required to definitely establish an serum IgE antibody to A fumigatus 4. Precipitating antibodies to A fumigatus or serum IgG antibody association. to A fumigatus 5. New or recent abnormalities on chest radiograph or chest CT Coexistence of ABPA and Aspergilloma: The sero- scan that have not cleared with antibiotics and standard logic findings of ABPA have also been reported in physiotherapy patients with aspergilloma214 –224 and chronic necro- Minimal diagnostic criteria 1. Acute or subacute clinical deterioration (cough, wheeze, and tizing pulmonary aspergillosis.225 This ABPA-like other pulmonary symptoms) not explained by another etiology syndrome probably represents a true hypersensitivity 2. Total serum IgE levels Ͼ 500 IU/mL. If total IgE level is 200– reaction consequent to the colonization of Aspergil- 500 IU/mL, repeat testing in 1–3 mo is recommended lus in long-standing pulmonary cavities and the 3. Immediate cutaneous reactivity to Aspergillus or presence of continuous release of Aspergillus antigens that leads serum IgE antibody to A fumigatus 4. One of the following: (1) precipitins to A fumigatus or to immunologic activation.214,215 Most patients show demonstration of IgG antibody to A fumigatus; or (2) new or a brisk response to glucocorticoids.214 –217,224 recent abnormalities on chest radiography (on chest radiography or chest CT scan that have not cleared with antibiotics and Allergic Bronchopulmonary Mycosis: Allergic standard physiotherapy) bronchopulmonary mycosis is the occurrence of an Screening for ABPA in CF 1. Maintain a high level of suspicion for ABPA in patients with CF ABPA-like syndrome due to non-A fumigatus fungal 2. Determine the total serum IgE levels annually. If the total organisms. A variety of fungal agents (Table 11) have serum IgE levels is Ͼ 500 IU/mL, perform A fumigatus skin test been reported to cause this syndrome, but the fre- or use an IgE antibody to A fumigatus. If results are positive, quency is far less when compared to ABPA.218,226 –240 consider diagnosis on the basis of minimal criteria 3. If the total serum IgE levels is 200–500 IU/mL, repeat the measurement if there is increased suspicion for ABPA and perform ABPA and Allergic Aspergillus Sinusitis: Allergic further diagnostic tests (immediate skin test reactivity to A Aspergillus sinusitis (AAS) is a clinical entity in which fumigatus, IgE antibody to A fumigatus, A fumigatus precipitins, or mucoid impaction akin to that of ABPA occurs in the serum IgG antibody to A fumigatus, and chest radiography) paranasal sinuses.241 The pathogenesis is also similar to ABPA and represents an allergic hypersensitivity hence continuous assessment may be required over response to the presence of fungi within the sinus months with repeat performance of all the serologic cavity.242 The patient is often asymptomatic or can investigations for ABPA before a decision to treat an manifest with symptoms of nasal obstruction, rhinor- individual case is made.202 ABPA Without Bronchial Asthma: ABPA may Table 11—Fungi Implicated in the Causation of occasionally develop in an individual without preex- Allergic Bronchopulmonary Mycosis isting asthma. We have performed a systematic MEDLINE search for the occurrence of ABPA Fungi Study/Year without bronchial asthma.100 In total they included A niger Sharma et al218/1985 36 cases reported across the globe; two cases dem- Helminthosporium spp Dolan et al226/1970 onstrated bronchodilator reversibility,203 and one Penicillium spp Sahn and Lakshminarayan227/1973 Aspergillus ochraceus Novey and Wells228/1978 showed airway hyperresponsiveness to methacholine Stemphylium spp Benatar et al229/1980 challenge.204 Most of the cases demonstrated hy- Aspergillus terreus Laham et al230/1981 persensitivity to A fumigatus, but three cases Drechslera spp McAleer et al231/1981 showed hypersensitivity to Helminthosporium,203 Torulopsis spp Patterson et al232/1982 and one case each to Aspergillus niger.205,206 Be- Mucor-like spp Patterson et al232/1982 Candida spp Akiyama et al234/1984 cause of the absence of bronchial asthma, these Pseudallescheria spp Lake et al235/1990 cases are often mistaken initially for other pulmo- Bipolaris spp Lake et al236/1991 nary disorders like bronchogenic carcinoma206 –208 Curvularia spp Lake et al236/1991 or pulmonary tuberculosis.100 Schizophyllum spp Kamei et al237/1994 Fusarium spp Backman et al238/1995 ABPA Complicating Other Conditions: Occasion- Cladosporium spp Moreno-Ancillo et al239/1996 Saccharomyces spp Ogawa et al240/2004 ally ABPA has been reported to complicate other www.chestjournal.org CHEST / 135 / 3 / MARCH, 2009 819 Downloaded from chestjournal.chestpubs.org by guest on April 23, 2012 © 2009 American College of Chest Physicians
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rhea, headache, and
epistaxis. Occasionally, the 5 Greenberger PA. Allergic bronchopulmonary aspergillo- allergic fungal sinusitis may extend into adjacent sis. J Allergy Clin Immunol 2002; 110:685– 692 6 Rosenberg M, Patterson R, Mintzer R, et al. Clinical and spaces such as the orbit and manifest as propto- immunologic criteria for the diagnosis of allergic broncho- sis.243 Although in many patients with ABPA, pulmonary aspergillosis. Ann Intern Med 1977; 86:405– 414 sinusitis can often be radiologically demonstrated, 7 Greenberger PA, Patterson R, Ghory A, et al. Late sequelae it may not be possible to confirm the diagnosis of of allergic bronchopulmonary aspergillosis. J Allergy Clin AAS because many patients decline to undergo the Immunol 1980; 66:327–335 8 Patterson R, Greenberger PA, Radin RC, et al. Allergic diagnostic procedures required to establish the bronchopulmonary aspergillosis: staging as an aid to man- diagnosis. We currently label the patients with agement. Ann Intern Med 1982; 96:286 –291 ABPA as having concomitant AAS if there is 9 Patterson R, Greenberger PA, Halwig JM, et al. Allergic combination of hyperattenuating mucus and/or bronchopulmonary aspergillosis: natural history and classifi- bony erosion on a paranasal CT scan. Treatment is cation of early disease by serologic and roentgenographic studies. Arch Intern Med 1986; 146:916 –918 initiated for ABPA with patients receiving addi- 10 Patterson R, Greenberger PA, Lee TM, et al. Prolonged tional intranasal glucocorticoids. If the symptoms evaluation of patients with corticosteroid-dependent asthma persist or are troublesome, surgical management stage of allergic bronchopulmonary aspergillosis. J Allergy may be required for the management of AAS. Clin Immunol 1987; 80:663– 668 11 Greenberger PA, Patterson R. Allergic bronchopulmonary aspergillosis and the evaluation of the patient with asthma. J Allergy Clin Immunol 1988; 81:646 – 650 Conclusions 12 Greenberger PA, Miller TP, Roberts M, et al. Allergic bronchopulmonary aspergillosis in patients with and without A high index of suspicion for ABPA should be evidence of bronchiectasis. Ann Allergy 1993; 70:333–338 maintained while managing any patient with bron- 13 Greenberger PA. Clinical aspects of allergic bronchopulmo- chial asthma whatever the severity or the level of nary aspergillosis. Front Biosci 2003; 8:S119 –S127 14 Rajan TV. The Gell-Coombs classification of hypersensitivity control. Host immunologic responses are central to reactions: a re-interpretation. Trends Immunol 2003; 24:376 – the pathogenesis, and they are the primary determi- 379 nants of the clinical, biologic, pathologic, and radio- 15 Geha RS, Sampson HA, Askenase PW, et al. Allergy and logic features of this disorder. ABPA may precede hypersensitivity. In: Janeway CA, Travers P, Walport M, et al. the clinical recognition of the disorder for many eds. Immunobiology. New York, NY: Garland, 2001; 517–556 16 Hinson KFW, Moon AJ, Plummer NS. Broncho-pulmonary years or even decades, and it is often misdiagnosed as aspergillosis; a review and a report of eight new cases. a variety of pulmonary diseases. Because a patient Thorax 1952; 7:317–333 with ABPA can be minimally symptomatic or asymp- 17 Muscat I, Oxborrow S, Siddorn J. Allergic bronchopulmo- tomatic, all patients with bronchial asthma should be nary mycosis. Lancet 1988; 1:1341 routinely screened with an Aspergillus skin test. In 18 Kirsten D, Nowak D, Rabe KF, et al. [Diagnosis of bron- chopulmonary aspergillosis is often made too late]. Med Klin patients with Aspergillus hypersensitivity, further (Munich) 1993; 88:353–356 immunologic studies are warranted to diagnose 19 Behera D, Guleria R, Jindal SK, et al. Allergic bronchopul- ABPA before the development of bronchiectasis monary aspergillosis: a retrospective study of 35 cases. because bronchiectasis is a poor prognostic marker Indian J Chest Dis Allied Sci 1994; 36:173–179 in the natural history of this disease. 20 Al-Mobeireek AF, El-Rab M, Al-Hedaithy SS, et al. Allergic bronchopulmonary mycosis in patients with asthma: period ACKNOWLEDGMENT: The author wishes to thank Dr. Aman- prevalence at a university hospital in Saudi Arabia. Respir jit Bal, Assistant Professor, Department of Histopathology, Med 2001; 95:341–347 PGIMER, Chandigarh for providing the histopathology photo- 21 Chakrabarti A, Sethi S, Raman DS, et al. Eight-year study of graphs. allergic bronchopulmonary aspergillosis in an Indian teach- ing hospital. Mycoses 2002; 45:295–299 22 Agarwal R, Gupta D, Aggarwal AN, et al. Allergic broncho- pulmonary aspergillosis: lessons from 126 patients attending References a chest clinic in North India. Chest 2006; 130:442– 448 1 Bardana EJ Jr. The clinical spectrum of aspergillosis—part 23 Agarwal R, Gupta D, Aggarwal AN, et al. Clinical signifi- 1: epidemiology, pathogenicity, infection in animals and cance of hyperattenuating mucoid impaction in allergic immunology of Aspergillus. Crit Rev Clin Lab Sci 1981; bronchopulmonary aspergillosis: an analysis of 155 patients. 13:21– 83 Chest 2007; 132:1183–1190 2 Geiser DM, Klich MA, Frisvad JC, et al. The current status 24 Agarwal R, Chakrabarti A. Epidemiology of allergic bron- of species recognition and identification in Aspergillus. Stud chopulmonary aspergillosis. In: Pasqualotto A, ed. As- Mycol 2007; 59:1–10 pergillosis: from diagnosis to prevention. New York, NY: 3 Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of Springer, 2009 (in press) aspergillosis: clinical practice guidelines of the infectious 25 Bateman ED. A new look at the natural history of Aspergil- diseases society of America. Clin Infect Dis 2008; 46:327– lus hypersensitivity in asthmatics. Respir Med 1994; 88:325– 360 327 4 Soubani AO, Chandrasekar PH. The clinical spectrum of 26 Malde B, Greenberger PA. Allergic bronchopulmonary as- pulmonary aspergillosis. Chest 2002; 121:1988 –1999 pergillosis. Allergy Asthma Proc 2004; 25:S38 –S39 820 Global Medicine Downloaded from chestjournal.chestpubs.org by guest on April 23, 2012 © 2009 American College of Chest Physicians
18.
27 Tillie-Leblond I,
Tonnel AB. Allergic bronchopulmonary gene mutations and 5T allele in patients with allergic broncho- aspergillosis. Allergy 2005; 60:1004 –1013 pulmonary aspergillosis. Chest 2001; 119:762–767 28 Donnelly SC, McLaughlin H, Bredin CP. Period prevalence 47 Eaton TE, Weiner Miller P, Garrett JE, et al. Cystic fibrosis of allergic bronchopulmonary mycosis in a regional hospital transmembrane conductance regulator gene mutations: do outpatient population in Ireland 1985– 88. Ir J Med Sci they play a role in the aetiology of allergic bronchopulmo- 1991; 160:288 –290 nary aspergillosis? Clin Exp Allergy 2002; 32:756 –761 29 Novey HS. Epidemiology of allergic bronchopulmonary 48 Saxena S, Madan T, Shah A, et al. Association of polymor- aspergillosis. Immunol Allergy Clin North Am 1998; 18:641– phisms in the collagen region of SP-A2 with increased levels 653 of total IgE antibodies and eosinophilia in patients with 30 Agarwal R, Aggarwal AN, Gupta D, et al. Prevalence of allergic bronchopulmonary aspergillosis. J Allergy Clin Im- Aspergillus hypersensitivity and allergic bronchopulmonary munol 2003; 111:1001–1007 aspergillosis in patients with bronchial asthma: a systematic 49 Brouard J, Knauer N, Boelle PY, et al. Influence of inter- review and meta-analysis. Int J Tuberc Lung Dis 2009 (in leukin-10 on Aspergillus fumigatus infection in patients with press) cystic fibrosis. J Infect Dis 2005; 191:1988 –1991 31 Attapattu MC. Allergic bronchopulmonary aspergillosis 50 Knutsen AP. Genetic and respiratory tract risk factors for among asthmatics. Ceylon Med J 1991; 36:45–51 aspergillosis: ABPA and asthma with fungal sensitization. 32 Schwartz HJ, Greenberger PA. The prevalence of allergic Med Mycol 2006; 44(suppl 1):61–70 bronchopulmonary aspergillosis in patients with asthma, 51 Knutsen AP, Kariuki B, Consolino JD, et al. IL-4 alpha chain determined by serologic and radiologic criteria in patients at receptor (IL-4R␣) polymorphisms in allergic bronchopul- risk. J Lab Clin Med 1991; 117:138 –142 monary aspergillosis. Clin Mol Allergy 2006; 4:3 33 Eaton T, Garrett J, Milne D, et al. Allergic bronchopulmo- 52 Sambatakou H, Pravica V, Hutchinson IV, et al. Cytokine nary aspergillosis in the asthma clinic: a prospective evalu- profiling of pulmonary aspergillosis. Int J Immunogenet ation of CT in the diagnostic algorithm. Chest 2000; 118: 2006; 33:297–302 66 –72 53 Vaid M, Kaur S, Sambatakou H, et al. Distinct alleles of 34 Kumar R, Gaur SN. Prevalence of allergic bronchopulmo- mannose-binding lectin (MBL) and surfactant proteins A nary aspergillosis in patients with bronchial asthma. Asian (SP-A) in patients with chronic cavitary pulmonary aspergil- Pac J Allergy Immunol 2000; 18:181–185 losis and allergic bronchopulmonary aspergillosis. Clin 35 Maurya V, Gugnani HC, Sarma PU, et al. Sensitization to Chem Lab Med 2007; 45:183–186 Aspergillus antigens and occurrence of allergic bronchopul- 54 Carvalho A, Pasqualotto AC, Pitzurra L, et al. Polymor- monary aspergillosis in patients with asthma. Chest 2005; phisms in toll-like receptor genes and susceptibility to 127:1252–1259 pulmonary aspergillosis. J Infect Dis 2008; 197:618 – 621 36 Prasad R, Garg R, Sanjay, et al. A study on prevalence of 55 Tomee JF, Wierenga AT, Hiemstra PS, et al. Proteases from allergic bronchopulmonary aspergillosis in patients of bron- Aspergillus fumigatus induce release of proinflammatory chial asthma. Internet J Pulmonary Med 2008; 9 cytokines and cell detachment in airway epithelial cell lines. 37 Agarwal R, Nath A, Aggarwal AN, et al. Aspergillus hyper- J Infect Dis 1997; 176:300 –303 sensitivity and allergic bronchopulmonary aspergillosis in 56 Tomee JF, Kauffman HF, Klimp AH, et al. Immunologic patients with acute severe asthma in a respiratory ICU in significance of a collagen-derived culture filtrate containing North India. Mycoses 2009 (in press) proteolytic activity in Aspergillus-related diseases. J Allergy 38 Henderson AH. Allergic aspergillosis: review of 32 cases. Clin Immunol 1994; 93:768 –778 Thorax 1968; 23:513–523 57 Hogaboam CM, Blease K, Schuh JM. Cytokines and che- 39 Kramer MN, Kurup VP, Fink JN. Allergic bronchopulmo- mokines in allergic bronchopulmonary aspergillosis (ABPA) nary aspergillosis from a contaminated dump site. Am Rev and experimental Aspergillus-induced allergic airway or Respir Dis 1989; 140:1086 –1088 asthmatic disease. Front Biosci 2003; 8:e147– e156 40 Kagen SL, Kurup VP, Sohnle PG, et al. Marijuana smoking 58 Kauffman HF. Immunopathogenesis of allergic bronchopul- and fungal sensitization. J Allergy Clin Immunol 1983; monary aspergillosis and airway remodeling. Front Biosci 71:389 –393 2003; 8:e190 – e196 41 Allmers H, Huber H, Baur X. Two year follow-up of a 59 Kauffman HK, Tomee JFC. Inflammatory cells and airway garbage collector with allergic bronchopulmonary aspergil- defense against Aspergillus fumigatus. Immunol Allergy Clin losis (ABPA). Am J Ind Med 2000; 37:438 – 442 North Am 1998; 18:619 – 640 42 Chauhan B, Knutsen A, Hutcheson PS, et al. T cell subsets, 60 Kauffman HF, Tomee JF, van de Riet MA, et al. Protease- epitope mapping, and HLA-restriction in patients with dependent activation of epithelial cells by fungal allergens allergic bronchopulmonary aspergillosis. J Clin Invest 1996; leads to morphologic changes and cytokine production. 97:2324 –2331 J Allergy Clin Immunol 2000; 105:1185–1193 43 Miller PW, Hamosh A, Macek M Jr, et al. Cystic fibrosis 61 Chauhan B, Santiago L, Kirschmann DA, et al. The transmembrane conductance regulator (CFTR) gene muta- association of HLA-DR alleles and T cell activation with tions in allergic bronchopulmonary aspergillosis. Am J Hum allergic bronchopulmonary aspergillosis. J Immunol 1997; Genet 1996; 59:45–51 159:4072– 4076 44 Aron Y, Bienvenu T, Hubert D, et al. HLA-DR polymor- 62 Schuyler M. The Th1/Th2 paradigm in allergic bronchopul- phism in allergic bronchopulmonary aspergillosis. J Allergy monary aspergillosis. J Lab Clin Med 1998; 131:194 –196 Clin Immunol 1999; 104:891– 892 63 Knutsen AP, Bellone C, Kauffman H. Immunopathogenesis 45 Chauhan B, Santiago L, Hutcheson PS, et al. Evidence for of allergic bronchopulmonary aspergillosis in cystic fibrosis. the involvement of two different MHC class II regions in J Cyst Fibros 2002; 1:76 – 89 susceptibility or protection in allergic bronchopulmonary 64 Slavin RG, Bedrossian CW, Hutcheson PS, et al. A aspergillosis. J Allergy Clin Immunol 2000; 106:723–729 pathologic study of allergic bronchopulmonary aspergil- 46 Marchand E, Verellen-Dumoulin C, Mairesse M, et al. Fre- losis. J Allergy Clin Immunol 1988; 81:718 –725 quency of cystic fibrosis transmembrane conductance regulator 65 Chan-Yeung M, Chase WH, Trapp W, et al. Allergic bron- www.chestjournal.org CHEST / 135 / 3 / MARCH, 2009 821 Downloaded from chestjournal.chestpubs.org by guest on April 23, 2012 © 2009 American College of Chest Physicians
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