Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis

INTRODUCTION — 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 [5].

The pathophysiology, clinical manifestations, and diagnosis of ABPA will be reviewed here. The management of ABPA and general issues related to bronchiectasis are discussed separately. (See "Treatment of allergic bronchopulmonary aspergillosis" and "Clinical manifestations and diagnosis of bronchiectasis in adults" and "Bronchiectasis in adults: Treatment of acute and recurrent exacerbations".)

EPIDEMIOLOGY — 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 [4]. 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 [15]. 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".)

The pathogenesis of ABPA remains incompletely understood [5,14]. 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 [16]. 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 [17,18]. 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 [5]. Aspergillus-responsive T cells generate cytokines interleukin (IL)-4, IL-5, and IL-13, which in turn account for the increases in blood and airway eosinophils 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 [19]. The majority of these clones were CD4+ cells of the Th2 phenotype, which produce IL-4 and IL-5 [19]. 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 [19]. In addition, there is increased sensitivity of B cells, T cells, NK cells, and eosinophils to IL-4 [5]. Single nucleotide polymorphisms in IL-13, IL-4 receptor, and toll like receptor (TLR)-3 have been identified in patients with ABPA in comparison to those with atopic asthma [20].

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 [21]. Heightened Th2 reactivity in these patients correlated with lower mean serum vitamin D levels.

Aspergillus colonization of the asthmatic airway leads to vigorous IgE- and IgG-mediated immune responses superimposed on the asthmatic milieu. In spite of these vigorous responses in ABPA, the fungus is able to colonize the airway and cause recurrent symptoms. Proteolytic enzymes and mycotoxins released by fungi, in concert with Th2-mediated eosinophilic inflammation and IL-8-mediated neutrophilic inflammation [22], may result in airway damage and central bronchiectasis. Eosinophil extracellular traps have been noted in the airway mucous in ABPA patients and may be an additional mediator of ABPA pathobiology [23].

Th17-mediated pathology may have a key role in ABPA and may be further driven by Th17 cell cross-reactivity with Candida-derived antigens [24]. Specifically, Aspergillus-specific Th17 cells can be isolated in the blood during acute exacerbations of ABPA prior to treatment, and these cells demonstrate high cross-reactivity with C. albicans.

CLINICAL FEATURES — Allergic bronchopulmonary aspergillosis (ABPA) occurs primarily in patients with asthma (1 to 5 percent of asthma patients) or cystic fibrosis (CF; 1 to 9 percent of CF patients) [10,25]. (See 'Epidemiology' above.)

Signs and symptoms — The clinical picture of ABPA is dominated by asthma and recurrent exacerbations. In severe cases, episodes of bronchial obstruction, fever, malaise, expectoration of brownish mucus plugs, and, at times, hemoptysis may occur. Wheezing is not always evident, and some patients present with asymptomatic pulmonary consolidation.

A minority of patients with ABPA have concomitant allergic aspergillus rhinosinusitis with symptoms of nasal congestion/obstruction, sinus pressure, and thick, dark-colored nasal discharge [26,27]. Allergic fungal rhinosinusitis is discussed separately. (See "Allergic fungal rhinosinusitis".)

Laboratory — Laboratory abnormalities in ABPA include an elevated total blood eosinophil count (generally >500 cells/microL), elevated total serum IgE (generally >1000 IU/mL), specific IgE to Aspergillus on immunoassay, and specific IgG antibodies or precipitating IgG antibodies (precipitins) to Aspergillus [26,28,29]. However, elevated blood eosinophils and total IgE can be caused by a variety of processes (table 1 and table 2). (See "Overview of in vitro allergy tests" and "Eosinophil biology and causes of eosinophilia", section on 'Major causes of eosinophilia'.)

Expectorated sputum may contain "plugs" with eosinophils, Charcot-Leyden crystals, and may grow Aspergillus in culture [15].

Serum galactomannan is not useful in the identification of ABPA [30].

Imaging — Central bronchiectasis is a frequent feature of ABPA and affects airways in the central one-half to two-thirds of the chest on imaging studies. Evidence of mucus plugging may be present on chest imaging as well.

●Chest radiograph – The chest radiograph may show parenchymal opacities (usually involving the upper lobes), atelectasis due to mucoid impaction, and a number of findings characteristic of bronchiectasis [31] (see "Clinical manifestations and diagnosis of bronchiectasis in adults"). These include:

•"Tram line" shadows due to thickened walls of nondilated bronchi

•"Parallel lines" due to the presence of ectatic bronchi

•"Ring shadows" due to bronchial wall thickening or saccular bronchiectasis

•"Toothpaste shadows" due to mucoid impacted second- to fourth-order bronchi

•"Gloved finger shadows" due to intrabronchial exudates with bronchial wall thickening; these appear as branched tubular radiodensities 2 to 3 cm long and 5 to 8 mm wide that extend from the hilus.

•Perihilar opacities due to mucus plugging may mimic hilar adenopathy.

●High-resolution computed tomography – The high-resolution computed tomography (HRCT) scan of the thorax may show widespread proximal cylindrical bronchiectasis with upper lobe predominance and bronchial wall thickening (image 1). However, central bronchiectasis (affecting medial one-half to two-thirds of the lungs) with normal tapering of distal bronchi has not been a consistently sensitive or specific marker for ABPA in all series [31-36]. In a series of 110 patients with ABPA, 24 (22 percent) had a normal HRCT, while 86 (78 percent) had central bronchiectasis mostly affecting the middle and upper lobes [37]. In a separate series of 15 patients, the sensitivity of central bronchiectasis on chest computed tomography (CT) as a diagnostic feature for ABPA was only 37 percent [32]. (See "High resolution computed tomography of the lungs", section on 'Airways diseases'.)

In addition to bronchiectasis, other findings on HRCT include nodules, mucus plugging, tree-in-bud opacities, high attenuation mucus, atelectasis, peripheral airspace consolidation, or ground-glass attenuation, and possibly mosaic perfusion or air trapping [33,35,37]. High attenuation mucus, defined as mucus that is radiographically denser than skeletal muscle, is seen in 18 to 28 percent of patients with ABPA [37-39]. Using these criteria, in comparison with other forms of eosinophilic lung diseases, radiologists made a correct diagnosis of ABPA in 84 percent of cases [33]. Coordination between clinical and CT findings are advised to optimize the diagnosis of ABPA [33].

Pulmonary function testing — Most patients have airflow obstruction and air trapping with a reduced forced expiratory volume in one second (FEV₁) and increased residual volume; a positive bronchodilator response is found in less than one-half of patients [40].

Individuals with bronchiectasis or fibrosis may exhibit a mixed obstructive and restrictive pattern. A minority of patients has a reduction in diffusing capacity, an abnormality that may be more common in the presence of bronchiectasis [40].

DIAGNOSIS — There is no individual test that establishes the diagnosis of allergic bronchopulmonary aspergillosis (ABPA), nor is there a single set of agreed upon diagnostic criteria [1,5,14,26,41]. The diagnosis is suspected in patients with asthma with recurrent exacerbations; a chest radiograph showing mucus plugging, upper or middle lobe consolidation, or central bronchiectasis; an eosinophil count >500/m³; or a total IgE >417 IU/mL [38]. The diagnosis is based on establishing allergic sensitization to Aspergillus antigens in the proper clinical and radiographic context.

Diagnostic criteria — Although not prospectively validated, we favor the following diagnostic criteria proposed by the International Society for Human and Animal Mycology (ISHAM) working group for ABPA that simplify prior diagnostic schema (table 3) [42]:

●Predisposing conditions (one must be present):

•Asthma

•Cystic fibrosis (CF)

●Obligatory criteria (both must be present):

•Detectable serum IgE levels against Aspergillus fumigatus (>0.35 kU/L) or Aspergillus skin test positivity

•Elevated total serum IgE concentration (typically >1000 IU/mL, but if the patient meets all other criteria, an IgE value <1000 IU/mL may be acceptable, especially if serum Aspergillus fumigatus-specific IgG levels are >27 mg/L)

●Other criteria (at least two must be present):

•Precipitating serum antibodies to A. fumigatus or elevated Aspergillus fumigatus-specific IgG levels (>27 mg/L)

•Radiographic pulmonary opacities consistent with ABPA (see 'Imaging' above)

•Total eosinophil count >500 cells/microL in glucocorticoid-naïve patients (may be historical)

ABPA without asthma or CF is a rare occurrence [43-45]. One series described 11 such patients with ABPA who did not have asthma by history and who had negative bronchodilator responsiveness [43]. Some of these individuals subsequently developed asthma, suggesting that they were diagnosed during a preclinical phase of disease. Three of the 11 patients had hypersensitivity to fungi other than Aspergillus, and differences in the host responses to these pathogens may have accounted for the absence of clinical asthma. In a separate series of 530 patients with ABPA, 37 (7 percent) had ABPA without asthma [45,46]. While these patients were not evaluated for CF, they did have fewer exacerbations and better spirometry than those with ABPA associated with asthma. As examples, COPD and post-tuberculous fibrocavitary disease may predispose to ABPA [42].

Step-wise evaluation — A step-wise evaluation of possible ABPA typically proceeds through the following tests, although the sequence may vary based on the clinical suspicion and results of previous tests:

●Immediate skin test to Aspergillus and/or specific serum IgE – The choice of test to establish the presence of IgE specific to Aspergillus antigens in an asthmatic being evaluated for ABPA will depend partially on the resources available. A negative prick skin test followed by negative intradermal reactivity to Aspergillus virtually excludes ABPA from consideration. Extremely rarely, allergic bronchopulmonary mycosis is diagnosed in a patient with a negative testing for Aspergillus. (See 'Diagnosis of allergic bronchopulmonary mycosis' below.)

The presence of at least a two-fold elevation in specific anti-Aspergillus IgE compared with pooled serum of Aspergillus-sensitized non-ABPA asthmatics has been suggested to distinguish seropositive ABPA from sensitization to Aspergillus in asthmatics without ABPA. However, given that clinical practice does not readily allow for such a comparison with pooled controls, we use the cut-off of 0.35 kU/L suggested by the ISHAM working group [26,42]. Such an approach allows for the use of commercially available semi-quantitative immunoassays in applying these criteria.

●Serum total IgE and peripheral eosinophil count – If the immediate skin test or specific IgE is positive, serum total IgE should be checked if it hasn’t been checked already. Many clinicians obtain the total serum IgE concurrently with Aspergillus-specific IgE, which allows for complete evaluation for the ISHAM obligatory criteria (table 3) [42]. IgE levels, similar to blood eosinophilia, may decrease if the patient is receiving systemic glucocorticoids, but generally do not normalize.

The issue of the appropriate cutoff value of total serum IgE concentration for a diagnosis of ABPA is a source of some confusion. Although there is no single value that has been found to define ABPA, various sources have used 417 IU/mL (1000 ng/mL) and 1000 IU/mL [1,4]. Further complicating matters are criteria from the Cystic Fibrosis Foundation Consensus Conference for establishing a diagnosis of ABPA in CF which use a total IgE cutoff of >500 IU/mL [5]. Until further studies are published, we recommend using the ISHAM value of total IgE >1000 IU/mL, with an allowance for a lower value if all other criteria are met. Total IgE values in ABPA may range as high as 25,000 IU/mL.

Patients with ABPA typically have an elevated total eosinophil count of at least >500/mm³ and often >1000/mm³. While there is no upper limit established for the peripheral eosinophilia observed in ABPA, it is our opinion that clinicians should be particularly attuned to the possibility of alternative diagnoses featuring systemic eosinophilia, such as eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss) and the hypereosinophilic syndromes, at values >2000 /mm³ (table 2).

●Chest imaging – While a chest radiograph can be useful in detecting abnormalities related to ABPA as described above, chest CT has become the modality of choice in evaluating patients suspected of having ABPA, particularly given the need to evaluate for bronchiectasis with a more sensitive test. (See 'Imaging' above.)

●Precipitating Aspergillus antibodies – The detection of Aspergillus serum precipitins continues to have clinical utility in the diagnosis of ABPA [26]. Newer immunoassays can be used to detect or confirm specific IgG antibodies against Aspergillus antigens and may be more sensitive than serum precipitins [26,46-48]. Once documented as positive, precipitating antibodies are not followed or used for monitoring.

Diagnosis of allergic bronchopulmonary mycosis — Rarely, an ABPA-like syndrome will be caused by a fungus other than Aspergillus fumigatus and is termed allergic bronchopulmonary mycosis (ABPM). The list of implicated fungi is long and includes fungi such as Aspergillus species (eg, A. flavus, A. niger, A. oryzae, A. ochraceus), Candida, Helminthosporium, Penicillium, Bipolaris, Scedosporium, and others [4,49-52]. Patients present with clinical features of ABPA (eg, mucus plugging, eosinophilia, elevated serum total IgE), but negative skin tests and serologic studies. The diagnosis is generally suspected after isolation of one of these other agents from sputum cultures or based upon documented exposure (eg, A. oryzae in a soy sauce factory). Support for a diagnosis of ABPM comes from demonstration of positive specific IgE and IgG antibodies to the alternative fungus and/or positive precipitins.

Diagnosis of ABPA in cystic fibrosis — It can be difficult to establish the diagnosis of ABPA in patients with CF due to shared symptoms and often complex radiographic features, including productive cough, wheeze, and bronchiectasis [5,26,53]. We follow the criteria for the diagnosis of ABPA in patients with CF that were formulated by the International Society for Human and Animal Mycology (ISHAM) working group for ABPA, which are similar to previous criteria of the Cystic Fibrosis Foundation Consensus Conference (CFCC) (table 3) [5,26].

Bronchiectasis and recurrent pulmonary infections are typical of CF, but ABPA should be suspected in patients with pulmonary opacities or clinical deterioration that do not respond to one week of antibiotic treatment [5]. (See "Cystic fibrosis: Clinical manifestations of pulmonary disease".)

The CFCC guidelines for screening for ABPA in CF include [5]:

●Maintain a high level of suspicion for ABPA in CF patients >6 years of age, particularly those with clinical deterioration.

●Determine the serum total IgE concentration annually. If the concentration is >500 IU/mL (>1200 ng/mL), evaluate for anti-Aspergillus IgE by determining skin test reactivity or serum immunoassay for IgE to A. fumigatus.

●If the serum IgE is 200 to 500 IU/mL (480 to 1200 ng/mL), repeat the measurement if there is increased clinical suspicion of ABPA and perform further diagnostic tests (eg, skin tests to Aspergillus antigen, in vitro tests for anti-Aspergillus fumigatus IgE, IgG and precipitins, chest radiograph).

Though not in routine use, measurement of basophil activation by assaying levels of the surface marker CD203c by flow cytometry in response to Aspergillus extract stimulation may be useful in the diagnosis of ABPA in patients with cystic fibrosis [54-56].

ABPA must be differentiated from invasive aspergillus infection as patients with CF appear to be at increased risk for this complication due to risk factors such as nutritional deficiency, diabetes mellitus, and chronic/frequent antibiotic therapy [53]. ABPA and other semi-invasive manifestations of Aspergillus infection (eg, bronchial aspergillosis, wound or anastomotic infection) can also occur after lung transplantation for CF [57]. (See "Diagnosis of invasive aspergillosis" and "Fungal infections following lung transplantation" and "Chronic pulmonary aspergillosis: Epidemiology, clinical manifestations and diagnosis", section on 'Diagnosis'.)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of allergic bronchopulmonary aspergillosis (ABPA) largely centers on considering other entities characterized by peripheral eosinophilia and pulmonary abnormalities, including asthma with Aspergillus sensitization, bronchocentric granulomatosis, eosinophilic granulomatosis with polyangiitis, and pulmonary eosinophilia due to drugs or parasitic infection, and chronic pulmonary aspergillosis. (See "Approach to the patient with unexplained eosinophilia" and "Overview of pulmonary eosinophilia".)

●Asthma with fungal sensitization – ABPA is frequently raised as a diagnostic possibility in patients with asthma, particularly if immediate skin test reactivity to Aspergillus is present. Estimates of the frequency of ABPA among asthmatics vary considerably. As examples, a university tertiary care allergy clinic with special interest in ABPA ultimately diagnosed ABPA in 6 percent of asthmatics with immediate reactivity to Aspergillus, but ABPA has been documented in up to 32 percent of patients with asthma and skin test reactivity to Aspergillus in other series [25,58-61].

Many asthmatics have one or more findings of ABPA but do not meet full criteria for the diagnosis. Features of ABPA which are found commonly in asthmatics without ABPA include:

•Positive immediate skin reactivity to A. fumigatus, which is present in 20 to 30 percent of all asthmatics [59,62]. The label "severe asthma with fungal sensitization" has been used to describe such patients, as well as those with skin test reactivity to other fungal antigens. (See "Treatment of allergic bronchopulmonary aspergillosis", section on 'Acute ABPA' and "Treatment of allergic bronchopulmonary aspergillosis", section on 'Treatment'.) .

•Positive serum precipitins to Aspergillus, which occur in 10 percent of asthmatics without ABPA and in 10 percent of nonasthmatic patients with chronic lung disease [63,64].

•Recurrent mucoid impaction and atelectasis, particularly among poorly controlled asthmatics

•Peripheral blood eosinophilia and elevation of serum total IgE

•Bronchiectasis is present on HRCT in 15 to 18 percent of non-ABPA asthmatics with positive immediate skin reactivity to Aspergillus [65-67]. One report compared 17 patients with ABPA to 11 with asthma and a positive skin test to A. fumigatus but not other features of ABPA [67]. Bronchiectasis by CT scan was much more common in the patients with ABPA (42 versus 5 percent of lobes).

ABPA likely lies on the same spectrum of illness as asthma with fungal sensitization, which makes distinguishing these entities from one another challenging, particularly with respect to identifying disease-defining total and specific IgE values.

●Pulmonary eosinophilia — A broad spectrum of diseases other than ABPA can cause pulmonary eosinophilia (table 1). A negative prick skin test and the absence of precipitins to Aspergillus virtually exclude ABPA and should prompt evaluation of other diagnostic possibilities. (See "Overview of pulmonary eosinophilia".)

Diseases to consider in patients with radiographic opacities and eosinophilia in the peripheral blood or bronchoalveolar lavage include the following:

•Acute or chronic eosinophilic pneumonia (see "Idiopathic acute eosinophilic pneumonia", section on 'Diagnosis' and "Chronic eosinophilic pneumonia", section on 'Diagnosis')

•Drug or toxin-induced eosinophilic pneumonia (see "Overview of pulmonary eosinophilia", section on 'Medications and toxins' and "Pulmonary complications of cocaine use", section on 'Acute eosinophilic pneumonia')

•Hypereosinophilic syndromes (see "Hypereosinophilic syndromes: Clinical manifestations, pathophysiology, and diagnosis")

•Tropical eosinophilic pneumonia (see "Tropical pulmonary eosinophilia")

•Loeffler's pneumonia

•Eosinophilic granulomatosis with polyangiitis – Like ABPA, patients with eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss) can present with the combination of asthma, eosinophilia, and radiographic opacities. Features favoring a diagnosis of EGPA include a positive serum antineutrophil cytoplasmic antibody (ANCA), skin lesions, mononeuropathy, or other extrapulmonary manifestation of vasculitis. (See "Clinical features and diagnosis of eosinophilic granulomatosis with polyangiitis (Churg-Strauss)", section on 'Diagnostic criteria'.)

●Bronchiectasis – Patients with bronchiectasis should be evaluated for ABPA unless the patient has clear alternative cause. Although central bronchiectasis is often seen in ABPA, it is a nonspecific finding. As an example, one series of 168 patients found that CT characteristics of bronchiectasis failed to differentiate disease caused by ABPA from that due to hypogammaglobulinemia, ciliary dysfunction, cystic fibrosis (CF), or idiopathic causes [32]. The bronchiectasis was more likely to be widespread and central in ABPA than in other causes, but these findings were not predictive in the individual patient. (See "Clinical manifestations and diagnosis of bronchiectasis in adults".)

●Chronic pulmonary aspergillosis – "Chronic cavitary pulmonary aspergillosis (CCPA)" is characterized by formation and expansion of one or more pulmonary cavities over several months in an immunocompetent patient. Aspergillus precipitins or specific IgG antibodies may be present in the serum; galactomannan is present in the bronchoalveolar lavage fluid in 50 to 90 percent of patients. Aspergillus-specific IgE may also be present, along with a slightly elevated total serum IgE. Aspergillomas may be present. (See "Chronic pulmonary aspergillosis: Epidemiology, clinical manifestations and diagnosis", section on 'Chronic cavitary pulmonary aspergillosis (CCPA)'.)

●Mucoid impaction and bronchocentric granulomatosis – Mucoid impaction and bronchocentric granulomatosis are commonly seen as components of ABPA. However, approximately half the cases of bronchocentric granulomatosis are not associated with ABPA. As bronchocentric granulomatosis is considered a nonspecific response to airway injury, a careful search for an underlying cause (eg, ABPA, mycobacterial and fungal infection, rheumatoid arthritis, granulomatosis with polyangiitis, bronchogenic carcinoma) should be undertaken. (See "Bronchocentric granulomatosis".)

COMPLICATIONS — Complications of allergic bronchopulmonary aspergillosis (ABPA) include acute invasive pulmonary aspergillosis [68], aspergilloma [4,69], chronic pulmonary aspergillosis [70], and the panoply of problems related to bronchiectasis.

Acute invasive pulmonary aspergillosis is a rare complication of ABPA and can occur during itraconazole therapy. At least nine such cases have been reported [68]. Acute invasive pulmonary aspergillosis in this setting can be fulminant, possibly due to the immunosuppressive effect of systemic glucocorticoids. (See "Epidemiology and clinical manifestations of invasive aspergillosis".)

A few case reports have described the development of an aspergilloma in patients with ABPA [4,69].

Central bronchiectasis is a well-known complication of ABPA and can result in recurrent bacterial infections, hemoptysis, and chronic respiratory insufficiency. (See "Clinical manifestations and diagnosis of bronchiectasis in adults".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Aspergillosis".)

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SUMMARY AND RECOMMENDATIONS

●Background – Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction of the airways that occurs when bronchi become colonized by Aspergillus species. ABPA most commonly develops in patients with asthma, but can also develop in patients with cystic fibrosis. Repeated episodes of bronchial obstruction, inflammation, and mucoid impaction can lead to bronchiectasis, fibrosis, and respiratory compromise. (See 'Introduction' above and 'Epidemiology' above.)

●Pathology – ABPA is characterized pathologically by mucoid impaction of the bronchi, eosinophilic pneumonia, and bronchocentric granulomatosis in addition to the histologic features of asthma. Septated hyphae with acute dichotomous branching may be seen in the mucus-filled bronchial lumen, but fungi rarely invade the mucosa. (See 'Pathology and pathogenesis' above.)

●Clinical features – The clinical picture of ABPA is dominated by asthma and recurrent exacerbations. In severe cases, episodes of bronchial obstruction, fever, malaise, expectoration of brownish mucus plugs, and, at times, hemoptysis may occur. Imaging features may include mucus plugging (often with high attenuation mucus) and central bronchiectasis (affects inner one-half to two-thirds of lung). (See 'Clinical features' above.)

●Diagnostic criteria – There is no individual test to establish the diagnosis of ABPA. The diagnosis is usually confirmed by use of a combination of clinical, radiographic, and immunologic criteria. We favor the following diagnostic criteria proposed by the International Society for Human and Animal Mycology (ISHAM) working group that simplify prior diagnostic schema (table 3). (See 'Diagnostic criteria' above.)

●Evaluation – Establishing IgE sensitization to Aspergillus through either skin prick test or measurement of specific serum IgE is a reasonable first step in an asthmatic being evaluated for ABPA. Inability to establish IgE sensitization to Aspergillus virtually excludes ABPA from consideration. If skin testing and/or specific IgE are positive, total serum IgE, precipitins to Aspergillus, and eosinophil count should be assayed. Chest imaging, preferably with a chest CT, should be performed to assess presence and severity of bronchiectasis. (See 'Step-wise evaluation' above.)

●Differential diagnosis – The differential diagnosis of allergic bronchopulmonary aspergillosis (ABPA) largely focuses on entities characterized by peripheral eosinophilia and pulmonary abnormalities, including asthma with Aspergillus sensitization, bronchocentric granulomatosis, eosinophilic granulomatosis with polyangiitis, and pulmonary eosinophilia due to drugs or parasitic infection, and chronic pulmonary aspergillosis (table 1). (See 'Differential diagnosis' above.)

●Complications – Complications of ABPA, while uncommon, include acute invasive pulmonary aspergillosis, aspergilloma, chronic invasive aspergillosis, and problems related to bronchiectasis (eg, recurrent infections, hemoptysis). (See 'Complications' above.)