• allergic;
  • aspergillosis;
  • asthma;
  • bronchopulmonary


  1. Top of page
  2. Abstract
  3. Aspergillus
  4. Pathophysiology
  5. Pathology of ABPA
  6. Diagnosis of ABPA
  7. Clinical characteristics and stages of ABPA
  8. Biology
  9. Radiology and pulmonary function tests
  10. Treatment
  11. References

Allergic bronchopulmonary aspergillosis (ABPA) occurs in nonimmunocompromised patients and belongs to the hypersensitivity disorders induced by Aspergillus. Genetic factors and activation of bronchial epithelial cells in asthma or cystic fibrosis are responsible for the development of a CD4+Th2 lymphocyte activation and IgE, IgG and IgA-AF antibodies production. The diagnosis of ABPA is based on the presence of a combination of clinical, biological and radiological criteria. The severity of the disease is related to corticosteroid-dependant asthma or/and diffuse bronchiectasis with fibrosis. The treatment is based on oral corticosteroids for 6–8 weeks at acute phase or exacerbation and itraconazole is now recommended and validated at a dose of 200 mg/day for a duration of 16 weeks.

Aspergillus organisms are extremely resilient and ubiquitous in the environment. Although the pathophysiology of the various pulmonary manifestations related to Aspergillus infection remains complex and poorly understood, the severity of these conditions seems to depend mainly on the quantity and virulence of the inhaled Aspergillus inhaled and on the status of the host defence. Clinical, biological, pathological and radiological features differ depending on the type of disease: saprophytic infestation, invasive diseases or allergic diseases such as hypersensitivity pneumonitis, Aspergillus-mediated asthma and allergic bronchopulmonary aspergillosis (ABPA). The ABPA occurs in nonimmunocompromised patients, in the absence of invasive aspergillosis, and is defined as a hypersensitivity disorder induced by an Aspergillus species. The activities of polymorphonuclear leucocytes and alveolar macrophages, cell types involved in host defence against Aspergillus, are not impaired in patients with ABPA. Most patients with ABPA have either asthma or cystic fibrosis. The inhalation of spores from the environment is followed by growth of hyphae in the mucus of the bronchial tree and stimulates an immune response involving Th2 CD4+T-cells and IgE and IgG antibodies. This disease was first reported in 1890 and was later described by Hinson et al. in 1952 (1) in 12 asthmatics with recurrent pulmonary infiltrates, eosinophilia (blood and sputum) and Aspergillus hyphae in their sputum. Precipitating antibodies to Aspergillus were identified by Pepys in 1969 (2).


  1. Top of page
  2. Abstract
  3. Aspergillus
  4. Pathophysiology
  5. Pathology of ABPA
  6. Diagnosis of ABPA
  7. Clinical characteristics and stages of ABPA
  8. Biology
  9. Radiology and pulmonary function tests
  10. Treatment
  11. References

Aspergillus fumigatus is involved in the majority of ABPA cases. However, clinical and radiological features similar to those observed in A. fumigatus ABPA cases are occasionally seen in association with other fungi (such as Stemphylium lanuginosum, Helminthosporium species, Candida species, Curvularia species, Schizophyllum commune, Dreschslera hawaiiensis, Fusarium vasinfectum) and other species of Aspergillus (A. niger, A. flavus, A. nidulans, A. orizae or A. glaucis) (3–5). This review focuses on A. fumigatus, the Aspergillus species that most frequently infects humans. In the mycelium phase, Aspergillus exists in the form of 7–10-μm long, septate, uniform hyphae with dichotomus branching at an angle of 45°. The hyphae can be identified using the PAS and Grocott's stains. Reproduction is characterized by the formation of conidiophores with terminal vesicles producing chains of spores. The spores measure between 2 and 4 μm in diameter, are thermotolerant (grow at temperatures ranging from 15 to 53°C) and are able to grow on Sabouraud dextrose agar slants (6). Conidiophores and spores may be seen together, mainly in structures that are in contact with the atmosphere. Aspergillus is ubiquitous in the environment, existing in water, decaying organic materials, soil spaces, wood chips, mown vegetation, basements/indoor air, walls or ceilings, particularly when these environments contain moisture. Aspergillus-related diseases are most common in individuals working in the farming industry, where it is recognized as an occupational disease. Identification of Aspergillus in cultures derived from the sputum of individuals with ABPA does not necessarily mean that the fungus is implicated in the disease. A relationship between the level of exposure to Aspergillus and the occurrence of ABPA has not been clearly identified, although Radin et al. (7) suggested that high levels of exposure are associated with APBA exacerbations. Inhalation of conidia is followed by airway colonization. In some individuals, proliferation of the fungus in the airway lumen results in chronic bronchial inflammation and an IgE-mediated hypersensitivity response, blood eosinophilia and production of local and blood precipitating antibodies (8–11). Aspergillus spores also bind to activated epithelial cells and basement membrane components. Epithelium activation occurs in individuals with asthma and in those with cystic fibrosis, and may facilitate Aspergillus penetration of the bronchial mucosa. A positive correlation has been identified between impaired pulmonary function and the presence of serum antibodies to A. fumigatus in cystic fibrosis patients.


  1. Top of page
  2. Abstract
  3. Aspergillus
  4. Pathophysiology
  5. Pathology of ABPA
  6. Diagnosis of ABPA
  7. Clinical characteristics and stages of ABPA
  8. Biology
  9. Radiology and pulmonary function tests
  10. Treatment
  11. References

The factors underlying the development of ABPA remain unclear. The roles of genetic factors, mucus quality, preactivation of epithelial cells and the extent to which this activation facilitates the development of Aspergillus spores into hyphae, bronchial penetration of Aspergillus, the immune response and bronchial/bronchiolar inflammation and destruction are not yet fully understood. Indeed, the mechanisms involved in ABPA development are complex (Fig. 1). Pepys suggests that ABPA is a result of types I and III immunologic responses, classified according to Gell and Coombs. However, this classification provides a restricted view of ABPA pathogenesis.


Figure 1. Pathophysiology of ABPA. From Aspergillus adherence and penetration of the bronchial mucosa to the B and T cell response.

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Genetic factors

The CD4+Th2 lymphocytes from ABPA patients are restricted to six MHC class II HLD-R subtypes. Genetic studies suggest that HLA-DR molecules (DR2, DR5, and possibly, DR4 or DR7) are associated with susceptibility to ABPA, whereas HLA-DQ2 molecules are associated with resistance. Thus, a combination of these genetic elements may determine the outcome of ABPA in patients with cystic fibrosis and asthma (12, 13). Marchand et al. (14) found that the frequency of cystic fibrosis transmembrane conductor regulator (CFTR) gene mutations was high in patients with ABPA compared to those with allergic asthma, even though both groups showed normal sweat chloride concentrations. This indicates that CFTR gene mutations are involved in the development of ABPA. In addition, Saxena et al. identified an association between polymorphisms in the collagen region of pulmonary surfactant protein-A2 and a predisposition to ABPA and severity of the disease (15).

The conditions under which A. fumigatus colonizes the respiratory tract in patients developing ABPA is another factor associated with the pathophysiology of the disease. Aspergillus spores are inhaled and penetrate the mucus layer. A combination of factors may lead to greater bronchial adherence of Aspergillus and high levels of Aspergillus antigen absorption in patients developing ABPA: proteolytic enzymes secreted by Aspergillus (16), epithelial cell activation in individuals with asthma or cystic fibrosis and impaired mucus clearance in cystic fibrosis cases (17). Indeed, A. fumigatus activates epithelial cells, resulting in the secretion of increased amounts of IL-6 and IL-8 and up-regulation of epithelial cell detachment (18). This activation process is partly dependent on the Protease Activated Receptor 2 (19). ABPA occurs in only a low percentage of Aspergillus skin test-positive asthmatic individuals (20). Thus, Aspergillus skin test-positive asthmatic individuals must be clearly differentiated from ABPA patients, as sensitivity to Aspergillus is not sufficient to diagnose ABPA. These patients may also be sensitized to other fungal spores (Cladosporium, Alternaria, Stemphyllium, etc.).

Aspergillus antigens strongly activate both T and B cells (12, 21–25). Lymphocyte activation has been shown in humans and animal models. CD4+Th-2 lymphocyte activation is thought to be involved in ABPA. The number of GM-CSF, IL-4 and IL-5 positive cells was higher in ABPA murine models than in controls (26) and IL-10 seemed to be a natural suppressor of pro-inflammatory cytokine production (27). Schuyler (28) demonstrated that interleukins stimulate IgE and IgG synthesis, mast cell proliferation, and eosinophil activation and survival. IL-4 is involved in IgE production and eosinophil activation via the up-regulation of VLA-4 and CCR-3 expression (29–31). Elevated blood sIL-2 receptor concentrations and higher levels of CD23 expression on B-cells were found in ABPA patients than in patients with asthma but no ABPA (32). The increase in CD23 expression is also partly mediated by IL-4 (29). The T-cell response in ABPA patients was associated with B-cell activation and the presence of IgE, IgA and IgG in the blood and bronchial cells. Divergent results have been obtained from studies of blood and bronchoalveolar lavage (BAL) secretion of immunoglobulins directed against A. fumigatus. These inconsistencies may be explained by differences in the detection methods used: some authors have evaluated precipitating antibodies, whereas others have used ELISA or RIA methods. Moreover, the quality of the antigen extracts differed considerably between studies. The use of recombinant antigens should improve detection rates and make the results of these studies more reproducible and reliable. The IgE response is largely, but not exclusively, directed towards A. fumigatus epitopes (9). Total serum IgE production is thus nonspecific and probably enhanced by the local production of large amounts of IL-4. The levels of IgE-Aspergillus-specific antibodies were higher in the BAL than in the blood (33). The same was true of IgA-AF antibody production. In contrast, no differences between BAL and blood secretions have been reported for IgG-A. fumigatus antibodies (33). This suggests that the IgE and IgA antibodies to A. fumigatus are synthesized locally.

Tissue damage (bronchiectasis formation) occurs in ABPA patients as a consequence of the local influx of neutrophils and eosinophils. Sputum eosinophil and neutrophil levels are higher in ABPA patients with bronchiectasis than those without bronchial destruction (34). The extent of the bronchiectasis, detected by high resolution CT-scan, correlates with the eosinophil and neutrophil sputum counts but not with total IgE levels in the serum (34). Recently, Gibson et al. demonstrated that IL-8 gene expression and protein levels in the sputum were higher in ABPA patients than in controls and that that the extent of this alteration correlated with the degree of bronchial neutrophilia and airway obstruction (35). Thus, IL8 may be a key mediator of tissue damage in ABPA.

Pathology of ABPA

  1. Top of page
  2. Abstract
  3. Aspergillus
  4. Pathophysiology
  5. Pathology of ABPA
  6. Diagnosis of ABPA
  7. Clinical characteristics and stages of ABPA
  8. Biology
  9. Radiology and pulmonary function tests
  10. Treatment
  11. References

Pathologic specimens are not necessary for diagnosis. In cases were bronchial samples have been taken, the bronchial tree was dilated and filled with mucus plugs containing macrophages, eosinophils, Charcot–Leyden crystals and sometimes hyphae or hyphal fragments (36, 37). Bronchial walls were infiltrated with inflammatory cells (eosinophils, lymphocytes and plasma cells), and a thickening of the basement membrane and epithelial abrasion were also found (38). The pathology of the peribronchial areas and parenchyma may differ from that described above: bronchocentric granulomatosis with bronchial remodelling and dilation have been described (39). However, bronchocentric granulomatosis is a distinct entity often associated with a pseudo-tumoral radiologic pattern (38), and possibly with other conditions such as tuberculosis, inflammatory diseases of the bowel and rheumatoid arthritis (40–43). The infiltration of the parenchyma with mononuclear cells, eosinophils and lymphocytes leads to inflammation that mimics or is associated with the patterns observed in individuals with other forms of interstitial disease such as granulomatous bronchiolitis, exsudative bronchiolitis or obliterans bronchiolitis (38). Microabcesses with Aspergillus hyphae and granulocytes have been described in the parenchyma, demonstrating that the frontier between invasive and allergic diseases is sometimes poorly delimited.

Diagnosis of ABPA

  1. Top of page
  2. Abstract
  3. Aspergillus
  4. Pathophysiology
  5. Pathology of ABPA
  6. Diagnosis of ABPA
  7. Clinical characteristics and stages of ABPA
  8. Biology
  9. Radiology and pulmonary function tests
  10. Treatment
  11. References

ABPA occurs mainly in asthmatics and patients with cystic fibrosis.

In asthmatic patients, the diagnosis of ABPA is based on the presence of a combination of clinical, biological and radiological criteria. The prevalence of ABPA is difficult to establish. When screening was performed in patients with persistent asthma, the prevalence was between 1 and 2%. (20, 44). The major criteria are listed in Table 1. Eight criteria for ABPA diagnosis were initially identified, but only some of them are essential. The nonessential criteria, for example, pulmonary infiltrates or blood eosinophilia may be only present at the time of exacerbation or during the acute phase of the disease.

Table 1.  Criteria for the diagnosis of ABPA (patients without cystic fibrosis)
Immediate cutaneous reaction to A. fumigatus
Total serum IgE concentration (>1000 ng/ml)
Elevated A. fumigatus-specific serum IgE levels
Precipitating antibodies to A. fumigatus in the serum
Peripheral blood eosinophilia (not essential for diagnosis)
Chest Roentgenographic infiltrates (not essential for diagnosis)
Central bronchiectasis

Bronchiectasis, involving the more central segmental bronchi is a strong diagnosis criterion but is not always present in patients during follow-up and at the time of diagnosis. Greenberger et al. (45) identified two bases for differentiating ABPA patients with and without bronchiectasis: ABPA with central bronchiectasis and seropositive ABPA without bronchiectasis. When a patient with asthma does not have bronchiectasis the following criteria are sufficient for ABPA diagnosis: high total serum IgE levels associated with an immediate cutaneous reaction to Aspergillus, elevated Aspergillus-specific IgE (or IgG) levels and the presence of precipitating Aspergillus antibodies in the serum. In other cases, particularly in the absence of systemic corticosteroids, elevated blood eosinophil counts, marked increases in precipitating Aspergillus antibodies or pulmonary infiltrate allow ABPA diagnosis (46). Several other criteria are also taken into consideration: mucoid impactions have been described in 14–54% of ABPA patients (37, 47) and Aspergillus has been found in the sputum, particularly in the plugs, in some cases (2, 37).

In cystic fibrosis patients, ABPA is a common complication of this disease, occurring in approximately 10% of cases. Diagnosis of ABPA in cystic fibrosis patients is difficult for several reasons. Several of the criteria used for ABPA diagnosis are common manifestations of cystic fibrosis. Cystic fibrosis patients often present exacerbations with bronchial obstruction, pulmonary infiltrate and bronchiectasis (48, 49). In addition, cystic fibrosis patients may have immune responses to Aspergillus (IgE, IgA, IgG antibody production and elevated total serum IgE levels), in the absence of ABPA. The boundary separating these responses from those involved with ABPA is difficult to define (50–52). Recently, the Cystic Fibrosis Foundation has proposed a new set of criteria for ABPA diagnosis in cystic fibrosis patients (53):

  • clinical deterioration (coughing, wheezing, increased sputum production, exercise intolerance and decrease in pulmonary function);
  • immediate hypersensitivity to A. fumigatus (positive skin test or IgE response);
  • total serum IgE concentration >1000 kUI/l;
  • precipitating antibodies to A. fumigatus;
  • abnormal chest roentgenogram (infiltrate, mucus plugs or unexplained changes compared to previous chest X-ray).

These criteria are particularly valuable for diagnosis in cases where the condition of the patient has only slightly improved, or not improved at all, after treatment for bacterial bronchial infection. The recommendation is that cystic fibrosis patients should be screened for ABPA from 6 years of age, once a year or in response to clinical suggestions of ABPA.

The Epidemiologic Register of Cystic Fibrosis reported that ABPA prevalence was 7.8% in 2000 (ranging from 2.1% in Sweden to 13.6% in Belgium). The prevalence of ABPA was low in patients who were less than 6-year old. ABPA was more common in patients in a poorer clinical condition [lower Forced Expiratory Volume in 1 s (FEV1), higher rate of microbial colonization, poor nutritional status]. Most of these patients had a delta f508/delta f508 genotype (54). Due to this strong association between cystic fibrosis and ABPA, it may be useful to perform sudoral tests on patients showing signs of ABPA. In some patients cystic fibrosis was diagnosed as the same time as ABPA (55).

In other conditions, although rare, cases of ABPA have been reported in patients without asthma (56–58). The ABPA has been described in patients with other chronic obstructive pulmonary diseases and in association with allergic fungal sinusitis, bronchocentric granulomatosis, hyper-IgE syndrome (Buckley) and chronic granulomatous disease. In the case of these neutrophil disorders, differentiating between ABPA and an invasive disease related to Aspergillus is sometimes difficult. When ABPA is diagnosed, invasive aspergillosis can be fatal in patients with hyper-IgE syndrome or chronic granulomatous disease as, systemic corticosteroids may accelerate tissue damage and invasive fungal infections.

Clinical characteristics and stages of ABPA

  1. Top of page
  2. Abstract
  3. Aspergillus
  4. Pathophysiology
  5. Pathology of ABPA
  6. Diagnosis of ABPA
  7. Clinical characteristics and stages of ABPA
  8. Biology
  9. Radiology and pulmonary function tests
  10. Treatment
  11. References

The ABPA onset can occur in childhood (59) but is more frequent in young adults. Most patients have other allergic disorders, such as rhinitis, conjunctivitis, atopic dermatitis and sensitization to common pneumallergens and trophallergens. The ABPA onset occurs at the time of, or more frequently after, asthma onset and is usually associated with the transformation of mild asthma into corticosteroid-dependent asthma, with unusual symptoms such as malaise, fever (body temperatures reaching 38.5°C), presence of sputum plugs and purulent sputum, coughing or increased coughing, chest pains and hemoptysis (60). Pulmonary consolidation without bacterial infection has been observed. Physical examination does not give any useful information. In patients with consolidation or fibrosis, crackles may be heard on breathing. In cystic fibrosis patients, exacerbation may be associated with weight loss and a marked increase in productive coughing.

ABPA progresses in five stages (61); listed in Table 2.

Table 2.  Stages of ABPA (according to Patterson et al.)
StagesClinical characteristicsBiologyRadiology
I: acuteFever, cough, chest pain, hemoptysis, sputumElevated total serum IgE +++ levels (±blood eosinophilia)Pulmonary infiltrate(s) (upper/middle lobes)
II: remissionAsymptomatic/stable asthmaNormal or elevated total serum IgE +levelsNo infiltrates (in the absence of systemic corticosteroid therapy for >6 months)
III: exacerbationSymptoms mimicking the acute stage or asymptomaticElevated total serum IgE +++ levels (±blood eosinophilia)Pulmonary infiltrate(s) (upper/middle lobes)
IV: cortico-dependent asthmaPersistent severe asthmaNormal or elevated total serum IgE + levelsWith or without pulmonary infiltrate(s)
V: Fibrosis (end-stage)Cyanosis, severe dyspneaNormal or elevated total serum IgE + levelsCavitary lesions, extensive bronchiectasis, fibrosis

Treatment differs depending on the ABPA stage. Patients with acute exacerbation respond to corticosteroids and early treatment of pulmonary infiltrate with these drugs can prevent bronchial or bronchiolar destruction. Long-term treatment with corticosteroids is not recommended because this treatment does not prevent the emergence of new infiltrates, or progression to fibrosis. Measuring total serum IgE levels is helpful for monitoring the treatment regimen (Table 2). Total serum IgE levels are high during the acute or exacerbation phases of ABPA, levels then decrease slowly over a mean period of 6 weeks. By the end-stage, prognosis and treatment resemble those for cystic fibrosis patient management: of these patients have extensive bronchial destruction and the bronchial tree may be colonized by Staphylococcus aureus and/or Pseudomonas aeruginosa. Response to corticosteroids is limited at this stage. However, progression from stage I to V is not inevitable and progression from stage IV to V is particularly uncommon.

Kumar (62) studied the characteristics of ABPA patients and found that individuals with the disease could be divided into three groups: ABPA with positive serology (ABPA-S), ABPA with central bronchiectasis (ABPA-CB) and ABPA with central bronchiectasis and other radiologic features (ABPA-CB-ORF). Pulmonary function abnormalities were mild in the ABPA-S group, moderate in the ABPA-CB group and severe in the ABPA-CB-ORF group. Absolute eosinophil counts raised in each groups but were highest (1.233/ml) for the ABPA-CB-ORF group. The levels of A. fumigatus-specific IgE followed the same pattern, with a maximum of 47.91 UI/ml for the ABPA-CB-ORF group. Symptom scores were also higher for the ABPA-CB-ORF group than for the other groups. Thus, the ABPA-S group probably contained patients with early stage or a less aggressive form of ABPA. The studies of Greenberger et al. (45) and Greenberger (63) lead them to suggest that early recognition and treatment of ABPA may prevent progression to end-stage ABPA.


  1. Top of page
  2. Abstract
  3. Aspergillus
  4. Pathophysiology
  5. Pathology of ABPA
  6. Diagnosis of ABPA
  7. Clinical characteristics and stages of ABPA
  8. Biology
  9. Radiology and pulmonary function tests
  10. Treatment
  11. References

Nearly all ABPA patients show an immediate cutaneous reaction to skin pricks with an Aspergillus mixture. The dual reaction is rare, about 16–33% of patients. (64, 65). Patients may also have sputum and/or blood eosinophilia, particularly at the time of diagnosis or when exacerbations occur at times when they are not receiving corticosteroids. In these situations, blood eosinophil levels may be unusually high, between 1500 and 3000/mm3 (47). Aspergillus can be detected in the sputum of 50% of ABPA patients (47). The most reliable diagnostic tests are measurements of total serum IgE and serum IgE and IgG AF antibody levels and determination of the presence AF antibody precipitins (results are expressed as the number of precipitation lines). Some Aspergillus antigens (catalase, trypsine and chymotrypsine) are essential for these reactions. These enzyme activities can be detected after gel diffusion and, as these antigens appear to be specific to AF, may be useful for diagnosis (66). Variation of level of specific antibodies are function of treatment, age and stage of ABPA (67–69). Total serum IgE levels are high in ABPA patients, and decrease when they are in remission as a result of corticosteroid treatment. This decrease usually occurs within 2 months after initiation of corticosteroid treatment. Total serum IgE levels sometimes return to within the normal range during the end-stage (67).

Approximately 40 epitopes able to bind the IgE molecule have been identified from A. fumigatus, alongside more than 20 recombinant allergens (named from Asp f 1 to Asp f 22) (63). Studies suggest that some of the recombinant allergens may be useful for discriminating between individuals with ABPA and those with AF-sensitized asthma (70). Kurup et al. have assessed the abilities of recombinant Aspergillus allergens (Asp f 1, f 2, f 3, f 4 and f 6) from the sera of ABPA patients and A. fumigatus sensitive asthmatics to bind to IgE. The number of recombinant allergens able to bind to the IgE antibody was higher in the sera from patients with ABPA than that from the asthmatics. Asp f 2, f 4 and f 6 interacted with IgE in all the ABPA patients tested. Such binding tests could therefore be used in ABPA diagnosis. In contrast, IgE antibody binding to Asp f 1 and f 3 was not specific. Hemmann et al. showed that skin prick tests with rAsp f 4 and rAsp f 6 provoked immediate skin reactions in patients with ABPA but not in controls and therefore allowed discrimination between ABPA and sensitization to A fumigatus (71). Banerjee et al. showed that 70% of patients with ABPA had high levels of serum IgE antibodies to Asp f 16, a 43-kDa protein, whereas patients with positive AF skin test results did not (72). However at the time of the study, recombinant allergens were only available for research purposes and the data obtained needs to be confirmed.

Radiology and pulmonary function tests

  1. Top of page
  2. Abstract
  3. Aspergillus
  4. Pathophysiology
  5. Pathology of ABPA
  6. Diagnosis of ABPA
  7. Clinical characteristics and stages of ABPA
  8. Biology
  9. Radiology and pulmonary function tests
  10. Treatment
  11. References

Radiographic analyses have been carried out on chest X-rays and high resolution CT-scans. Certain abnormalities tend to be transient, such as pulmonary infiltrate, the presence of fluid in the bronchi and lobar or segmental collapse linked to mucous plugs (73). Permanent patterns included bronchiectasis, which was seen most frequently in the upper lobes in the segmental and subsegmental bronchi, and cavities. Bronchiectasis occurs more centrally in ABPA patients than in those with other bronchial diseases. However, this central location is only suggestive of ABPA as bronchiectasis has been reported in the peripheral airways in some cases (74). Analysis using plain film revealed that most patients had upper lobe abnormalities (19/20; 95%), but 9/20 had both upper and lower lobe involvement (75). Descriptions of «glover-finger» opacities are common and correspond to bifurcating opacities caused by the bronchial distribution resulting from mucoid impaction. The collapse of a lobe segment, or entire lobes, has been described and was often associated with clinical exacerbation. Recurrence of mucoid impaction in these segments is not rare and may predispose the patient to bronchial damage.

Pleural effusion or calcification of mucoid impactions are rare but have been reported (76). Pulmonary fibrosis, pneumothorax and cavities occur during end-stage ABPA (74, 75, 77).

High resolution CT scan is more sensitive than chest X-ray for the detection of transient pulmonary infiltrate or bronchectasis. Bronchiectasis patterns are described as cylindrical in most cases, but have also been referred to as cystic or varicous (77). The extent of the bronchectasis is also usually defined (Fig. 2). Several studies have compared abnormalities in ABPA patients with those in Aspergillus-sensitive asthmatics (77–81). One of these studies showed that HRCT scan is more sensitive than radiography for diagnosing bronchiectasis (78). In this study, bronchiectasis was identified in 14/17 ABPA patients (82%), pleural thickening in 14 (82%) and atelectasis in 9 (64%) (78). However, patients with bronchiectasis and asthma do not necessarily have ABPA, although both conditions are present in about 80% of ABPA patients (77).


Figure 2. CT scan showing the diffuse cystic bronchiectasis responsible for lobar retraction of the left upper lobe.

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Respiratory function tests (expiratory flow rates, lung volumes and diffusion capacities) are useful for diagnosis and during follow-up, but alone are not sufficient for monitoring treatment. Obstruction and restriction are both aggravated during acute exacerbations. Reductions in lung volume and diffusion capacity have been observed during exacerbations and in patients with end-stage ABPA (82). The severity of the obstruction in corticosteroid-dependent asthma (stage IV) varies depending on the patient (83–85). Deterioration of lung function also differs between ABPA patients; in some individuals lung function remains stable, whereas in others functional parameters progressively deteriorate in manner that is associated with the pattern of obstruction and restriction (86). Malo et al. compared the results of lung function tests on 20 asthmatic patients with ABPA with those of 20 asthmatics, paired in terms of sex, age and duration of asthma (87). All of the patients with ABPA and 75% of the patients with asthma alone showed significantly reduced FEV1. The FEV1 reversibility was more frequent in patients with asthma alone (50%) than in those with ABPA (31%), and the extent of this reversibility was also statistically greater in patients with asthma compared with those with ABPA (87).


  1. Top of page
  2. Abstract
  3. Aspergillus
  4. Pathophysiology
  5. Pathology of ABPA
  6. Diagnosis of ABPA
  7. Clinical characteristics and stages of ABPA
  8. Biology
  9. Radiology and pulmonary function tests
  10. Treatment
  11. References

The long-term prognosis of ABPA is usually good, with most patients keeping a good respiratory status. Nevertheless, patients with ‘refractory asthma’ or bronchial destruction may have permanent airflow obstructions and/or severe restrictions. Detecting exacerbations is essential for limiting airway destruction, but the long-term use of systemic corticosteroids is not recommended, as there is no proof that this treatment prevents progressive bronchial destruction. In addition, exacerbations have been described in ABPA patients receiving high doses of oral corticosteroids (88), indicating that bronchial inflammation sensitive to corticosteroids is not the only factor involved in ABPA (89, 90). Bronchial colonization by fungal microorganisms represents an additional factor justifying the use of antifungal therapies. The goals of the treatment are:

  • to limit exacerbations (requiring systematic testing for pulmonary infiltrates, which may or may not be associated with clinical symptoms);
  • to eradicate colonization and/or proliferation of A. fumigatus in lumens with bronchiectasis and mucus plugs;
  • to manage cortico-dependent asthma and fibrosis;
  • thus, treatment appears to require two types of molecules: corticosteroids to treat the inflammatory response and antifungal agents to suppress or limit the proliferation of A. fumigatus and limit bronchial inflammation (91).

Oral corticosteroids

Systemic corticosteroids are currently the most effective treatment for the acute phase of ABPA. The recommended dose is 0.5 mg/kg/day for the first 2 weeks, followed by a progressive decrease in dose over the next 6–8 weeks. The treatment is monitored by assessing symptoms (fever, chest pain, hemoptysis, acute wheezing and sputum production), however, monitoring must also include a chest roentgenogram or HRCT scan, as infiltrates do not lead to clinical manifestations in a third of cases (92). Repeated dosages of total IgE serum levels are also recommended every 6–8 weeks during the first year after diagnosis, to determine a base-line value for each patient. Increases in total IgE serum levels of more than 100% above this base-line value indicate that the patient is at high risk of an exacerbation. The lung function tests recommended for asthma patients must also be performed as reductions in lung volume, diffusing capacity or exercise tolerance may be associated with an exacerbation.

Long-term systemic corticosteroid therapy is not recommended and thus assessment of these parameters is necessary for monitoring the treatment. If the patient has no new exacerbation within 6 months, he is judged to be in remission (stage II).

Stage IV patients have severe asthma, which is corticosteroid-dependent. In these cases, the minimal dose required to stabilize the patient must be identified. Treatment preventing corticosteroid-induced osteroporosis must also be proposed if necessary.

The extent of the bronchial destruction in stage V patients makes the prognosis poor. In addition, these patients suffer from recurrent infections (the majority of which involve Pseudomonas) and respiratory insufficiency with limited exercise tolerance. Treatment with corticosteroids is generally proposed, but is poorly efficient. Lee et al. (86) assessed 17 patients with stage V ABPA (fibrotic stage) for a mean observation period of 5 years. Roentgenographic infiltrates reoccurred in only one patient after the initial diagnosis. All patients required long-term prednisone therapy for controlling asthma. The prognosis was poor for patients with FEV1 of less than 0.8 l after the initial corticosteroid treatment.

Antifungal drugs

Several antifungal agents (e.g. amphotericin B, ketoconazole, clitromazole, nystatin and natamycin) have been proposed as treatments for ABPA. However, no significant beneficial effects were observed when these drug treatments were tested and in several cases these agents were responsible for severe adverse effects (93).

In contrast, the new orally administered antifungal agent, Itraconazole, appears to be an effective adjunctive therapy for ABPA. We have conducted a preliminary retrospective clinical study comparing the outcome of a 1-year itraconazole treatment with that of 2-year therapy with the normal treatment of corticosteroids alone. Fourteen patients were included in this study and follow-up lasted for a period of 3 years. The following characteristics were compared: symptom scores, exacerbation frequencies, pulmonary function tests, total and AF-specific serum IgE levels, the amount of corticosteroid required during the first 2 years by the patients treated with these drugs alone and the amount required during the 1-year study period by patients being treated with the itraconazole-corticosteroid combination. The number of exacerbations was lower for the itraconazole-treated group than for the group treated with corticosteroids alone. Corticosteroid daily requirements decreased from 22 to 6.5 mg/day, although the dose required differed substantially between patients (88).

In addition, the results of a 16-week randomized double-blind trial of twice daily treatment with either 200 mg itraconazole or placebo, showed that itraconazole prevented disease progression in corticosteroid-dependent ABPA patients without any toxic effects (94). A positive response was defined as a reduction of at least 50% in corticosteroid dose, a decrease of at least 25% in serum IgE concentration, and one of the following: an improvement of at least 25% in exercise tolerance or pulmonary-function tests or the partial clearance or absence of pulmonary infiltrates. In a second phase of the same trial, consisting of an open-label study, all the patients received 200 mg of itraconazole per day for 16 additional weeks. In the double-blind phase of the trial 46% of the patients in the itraconazole group responded to the treatment, compared with 19% in the placebo group (P = 0.04). About one third (36%) of the patients who did not respond during the double-blind phase responded to treatment in the open-label phase of the trial, and none of the patients who responded in the double-blind phase of the trial had a relapse (94). The mechanisms underlying this treatment remain unclear. However, the results from a separate study suggest that itraconazole has an anti-inflammatory effect in ABPA patients tested (91).

The results from a randomized, double-blind, placebo-controlled trial performed using ABPA patients with stable symptoms (n = 29 and subjects received 400 mg of itraconazole (n = 15) or placebo (n = 14) per day for 16 weeks) demonstrated that itraconazole treatment reduced eosinophilic airway inflammation, systemic immune activation and the number of exacerbations (91). These results indicate that itraconazole could be used as a adjunctive treatment for ABPA.

Meta-analysis of the data available (mainly three prospective, randomized and controlled studies) led to the conclusion that itraconazole modifies the immunologic activation associated with ABPA and improves clinical outcome, at least over a period of 16 weeks (Cochrane Airways Group Asthma Trials Register) (95). Adrenal suppression caused by the inhalation of corticosteroids and itraconazole treatment is a potential concern. On the one hand, treatment with this antifungal agent reduces bronchial inflammation and may prevent bronchial destruction and exacerbation in stable ABPA patients. It also improves the clinical status of corticodependent-ABPA patients. On the other hand, long-term prescription of an antifungal therapy may lead to resistance. The trails validating the use of itraconazole in ABPA patients used a dose of 200 mg/day, administered for a duration of 16 weeks (95).

The impact of long-term exposure to Aspergillus present in the environment is uncertain (47), but direct exposure to high concentrations of this fungus should be avoided. Fiberoptic bronchoscopy may be necessary to remove the mucoid impaction responsible for atelectasis in rare cases where it is refractory to corticosteroid treatment.

In conclusion, ABPA is a common manifestation in chronic allergic asthma and cystic fibrosis patients. Despite the high frequency of the disease among these patients, diagnoses are not generally made until a long time after the initiation of the asthmatic disease. When the clinical, radiological and biological criteria for ABPA appear in combination and the diagnosis is made, a treatment that includes both corticosteroids and the antifungal agent, itraconazole, needs to be administered. However, the treatment regimes for this antifungal therapy have yet to be definitely established.


  1. Top of page
  2. Abstract
  3. Aspergillus
  4. Pathophysiology
  5. Pathology of ABPA
  6. Diagnosis of ABPA
  7. Clinical characteristics and stages of ABPA
  8. Biology
  9. Radiology and pulmonary function tests
  10. Treatment
  11. References
  • 1
    Hinson KF, Moon AJ, Plummer NS. Broncho-pulmonary aspergillosis; a review and a report of eight new cases. Thorax 1952;7: 317333.
  • 2
    Pepys A. Hypersensitivity diseases of the lung due to fungi and organic dusts. In: KargerS, editor. Monographs in allergy. Basel (Switzerland): S. Karger, 1969.
  • 3
    Lake FR, Tribe AE, Mcaleer R, Froudist J, Thompson PJ. Mixed allergic bronchopulmonary fungal disease due to Pseudallescheria boydii and Aspergillus. Thorax 1990;45: 489491.
  • 4
    Crompton G. Fungal disease. Bronchopulmonary aspergillosis. In: BrewisRAL, GibsonGJ, GeddesDM, editors. Respiratory medicine. London: Baillière Tindal, 1990: 10351050.
  • 5
    Greenberger PA. Diagnosis and management of allergic bronchopulmonary aspergillosis. Allergy Proc 1994;15: 335339.
  • 6
    Latge JP. Aspergillus fumigatus and aspergillosis. Clin Microbiol Rev 1999;12: 310350.
  • 7
    Radin RC, Greenberger PA, Patterson R, Ghory A. Mould counts and exacerbations of allergic bronchopulmonary aspergillosis. Clin Allergy 1983;13: 271275.
  • 8
    Greenberger PA. Allergic bronchopulmonary aspergillosis and fungoses. Clin Chest Med 1988;9: 599608.
  • 9
    Patterson R, Rosenberg M, Roberts M. Evidence that Aspergillus fumigatus growing in the airway of man can be a potent stimulus of specific and nonspecific IgE formation. Am J Med 1977;63: 257262.
  • 10
    Patterson R, Roberts M. IgE and IgG antibodies against Aspergillus fumigatus in sera of patients with bronchopulmonary allergic aspergillosis. Int Arch Allergy Appl Immunol 1974;46: 150160.
  • 11
    Leser C, Kauffman HF, Virchow C Sr, Menz G. Specific serum immunopatterns in clinical phases of allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 1992;90: 589599.
  • 12
    Chauhan B, Santiago L, Kirschmann DA et al. The association of HLA-DR alleles and T cell activation with allergic bronchopulmonary aspergillosis. J Immunol 1997;159: 40724076.
  • 13
    Chauhan B, Santiago L, Hutcheson PS et al. Evidence for the involvement of two different MHC class II regions in susceptibility or protection in allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 2000;106: 723729.
  • 14
    Marchand E, Verellen-Dumoulin C, Mairesse M et al. Frequency of cystic fibrosis transmembrane conductance regulator gene mutations and 5T allele in patients with allergic bronchopulmonary aspergillosis. Chest 2001;119: 762767.
  • 15
    Saxena S, Madan T, Shah A, Muralidhar K, Sarma PU. Association of polymorphisms in the collagen region of SP-A2 with increased levels of total IgE antibodies and eosinophilia in patients with allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 2003;111: 10011007.
  • 16
    Fraser RS. Pulmonary aspergillosis: pathologic and pathogenetic features. Pathol Annu 1993;28(Pt 1):231277.
  • 17
    Knutsen A, Bellone CJ, Kauffman HF. Immunopathogenesis of allergic bronchopulmonary aspergillosis in cystic fibrosis. J Cystic Fibrosis 2002;1: 7689.
  • 18
    Tomee JF, Wierenga AT, Hiemstra PS, Kauffman HK. Proteases from Aspergillus fumigatus induce release of proinflammatory cytokines and cell detachment in airway epithelial cell lines. J Infect Dis 1997;176: 300303.
  • 19
    Kauffman HF, Tomee JF, Van de riet MA, Timmerman AJ, Borger P. Protease-dependent activation of epithelial cells by fungal allergens leads to morphologic changes and cytokine production. J Allergy Clin Immunol 2000;105: 11851193.
  • 20
    Greenberger PA, Patterson R. Allergic bronchopulmonary aspergillosis and the evaluation of the patient with asthma. J Allergy Clin Immunol 1988;81: 646650.
  • 21
    Walker CA, Fitzharris P, Longbottom JL, Taylor AJ. Lymphocyte sensitization to Aspergillus fumigatus in allergic bronchopulmonary aspergillosis. Clin Exp Immunol 1989;76: 3440.
  • 22
    Knutsen AP, Slavin RG. In vitro T cell responses in patients with cystic fibrosis and allergic bronchopulmonary aspergillosis. J Lab Clin Med 1989;113: 428435.
  • 23
    Kauffman HF, Koeter GH, Van der Heide S, de Monchy JG, Kloprogge E, de Vries K. Cellular and humoral observations in a patient with allergic bronchopulmonary aspergillosis during a nonasthmatic exacerbation. J Allergy Clin Immunol 1989;83: 829838.
  • 24
    Knutsen AP, Mueller KR, Levine AD, Chouhan B, Hutcheson PS, Slavin RG. Asp f I CD4+ TH2-like T-cell lines in allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 1994;94: 215221.
  • 25
    Slavin RG, Fischer VW, Levine EA, Tsai CC, Winzenburger P. A primate model of allergic bronchopulmonary aspergillosis. Int Arch Allergy Appl Immunol 1978;56: 325333.
  • 26
    Chu HW, Wang JM, Boutet M, Boulet LP, Laviolette M. Immunohistochemical detection of GM-CSF, IL-4 and IL-5 in a murine model of allergic bronchopulmonary aspergillosis. Clin Exp Allergy 1996;26: 461468.
  • 27
    Grunig G, Corry DB, Leach MW, Seymour BW, Kurup VP, Rennick DM. Interleukin-10 is a natural suppressor of cytokine production and inflammation in a murine model of allergic bronchopulmonary aspergillosis. J Exp Med 1997;185: 10891099.
  • 28
    Schuyler M. The Th1/Th2 paradigm in allergic bronchopulmonary aspergillosis. J Lab Clin Med 1998;131: 194196.
  • 29
    Khan S, Mcclellan JS, Knutsen AP. Increased sensitivity to IL-4 in patients with allergic bronchopulmonary aspergillosis. Int Arch Allergy Immunol 2000;123: 319326.
  • 30
    Kurup VP, Murali PS, Guo J et al. Anti-interleukin (IL)-4 and -IL-5 antibodies down-regulate IgE and eosinophilia in mice exposed to Aspergillus antigens. Immunopathologic responses to Aspergillus antigen in interleukin-4 knockout mice. Allergy 1997;52: 12151221.
  • 31
    Kurup VP, Guo J, Murali PS, Choi H, Fink JN. Immunopathologic responses to Aspergillus antigen in interleukin-4 knockout mice. J Lab Clin Med 1997;130: 567575.
  • 32
    Brown JE, Greenberger PA, Yarnold PR. Soluble serum interleukin 2 receptors in patients with asthma and allergic bronchopulmonary aspergillosis. Ann Allergy Asthma Immunol 1995;74: 484488.
  • 33
    Greenberger PA, Smith LJ, Hsu CC, Roberts M, Liotta JL. Analysis of bronchoalveolar lavage in allergic bronchopulmonary aspergillosis: divergent responses of antigen-specific antibodies and total IgE. J Allergy Clin Immunol 1988;82: 164170.
  • 34
    Wark PA, Saltos N, Simpson J, Slater S, Hensley MJ, Gibson PG. Induced sputum eosinophils and neutrophils and bronchiectasis severity in allergic bronchopulmonary aspergillosis. Eur Respir J 2000;16: 10951101.
  • 35
    Gibson PG, Wark PA, Simpson JL et al. Induced sputum IL-8 gene expression, neutrophil influx and MMP-9 in allergic bronchopulmonary aspergillosis. Eur Respir J 2003;21: 582588.
  • 36
    Slavin RG, Bedrossian CW, Hutcheson PS et al. A pathologic study of allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 1988;81: 718725.
  • 37
    Jelihovsky T. The structure of bronchial plugs in mucoid impaction, bronchocentric granulomatosis and asthma. Histopathology 1983;7: 153167.
  • 38
    Fraser R, Müller N, Colman N, Paré P. Fungi and actinomyces. In: FraserRS, ParéPD, editors. Diagnosis of diseases of the chest. Philadelphia: Saunders Company, 1999: 875978.
  • 39
    Hanson G, Flor N, Wells I, Novey H, Galant S. Bronchocentric granulomatosis: a complication of allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 1977;59: 8390.
  • 40
    Koss MN, Robinson RG, Hochholzer L. Bronchocentric granulomatosis. Hum Pathol 1981;12: 632638.
  • 41
    Berendsen HH, Hofstee N, Kapsenberg PD, van Reesema DR, Klein JJ. Bronchocentric granulomatosis associated with seropositive polyarthritis. Thorax 1985;40: 396397.
  • 42
    Katzenstein AL, Liebow AA, Friedman PJ. Bronchocentric granulomatosis, mucoid impaction, and hypersensitivity reactions to fungi. Am Rev Respir Dis 1975;111: 497537.
  • 43
    Hellems SO, Kanner RE, Renzetti AD Jr. Bronchocentric granulomatosis associated with rheumatoid arthritis. Chest 1983;83: 831832.
  • 44
    Schwartz HJ, Greenberger PA. The prevalence of allergic bronchopulmonary aspergillosis in patients with asthma, determined by serologic and radiologic criteria in patients at risk. J Lab Clin Med 1991;117: 138142.
  • 45
    Greenberger PA, Miller TP, Roberts M, Smith LL. Allergic bronchopulmonary aspergillosis in patients with and without evidence of bronchiectasis. Ann Allergy 1993;70: 333338.
  • 46
    Backman KS, Zull D, Patterson R. Diagnostic complexity in a patient with asthma, pulmonary infiltrates, and eosinophilia. Ann Allergy Asthma Immunol 1995;75: 391400.
  • 47
    Mccarthy DS, Pepys J. Allergic broncho-pulmonary aspergillosis. Clinical immunology I. Clinical features. Clin Allergy 1971;1: 261286.
  • 48
    Knutsen A, Slavin RG. Allergic bronchopulmonary mycosis complicating cystic fibrosis. Semin Respir Infect 1992;7: 179192.
  • 49
    Stevens DA, Moss RB, Kurup VP et al. Allergic bronchopulmonary aspergillosis in cystic fibrosis – state of the art: Cystic Fibrosis Foundation Consensus Conference. Clin Infect Dis 2003;37(Suppl. 3):S225S264.
  • 50
    Zeaske R, Bruns WT, Fink JN et al. Immune responses to Aspergillus in cystic fibrosis. J Allergy Clin Immunol 1988;82: 7377.
  • 51
    Silverman M, Hobbs FD, Gordon IR, Carswell F. Cystic fibrosis, atopy, and airways liability. Arch Dis Child 1978;53: 873877.
  • 52
    Nikolaizik WH, Moser M, Crameri R et al. Identification of allergic bronchopulmonary aspergillosis in cystic fibrosis patients by recombinant Aspergillus fumigatus I/a-specific serology. Am J Respir Crit Care Med 1995;152: 634639.
  • 53
    Stevens DA, Moss RB, Kurup VP et al. Allergic bronchopulmonary aspergillosis in cystic fibrosis-state of the art: Cystic Fibrosis Foundation Consensus Conference. Clin Infect Dis 2003;37(Suppl. 3): S225264.
  • 54
    Mastella G, Rainisio M, Harms HK et al. Allergic bronchopulmonary aspergillosis in cystic fibrosis. A European epidemiological study. Epidemiologic Registry of Cystic Fibrosis. Eur Respir J 2000;16: 464471.
  • 55
    Coltey B, Pin I, Ferretti G, Bonadona A, Pison C, Brambilla C. Aspergillose bronchopulmonaire allergique révélatrice d'une mucoviscidose. Rev Mal Respir 2001;18: 549551.
  • 56
    Ricketti AJ, Greenberger PA, Mintzer RA, Patterson R. Allergic bronchopulmonary aspergillosis. Arch Intern Med 1983;143: 15531557.
  • 57
    Berkin KE, Vernon DR, Kerr JW. Lung collapse caused by allergic bronchopulmonary aspergillosis in nonasthmatic patients. Br Med J (Clin Res Ed) 1982;285: 552553.
  • 58
    Glancy JJ, Elder JL, Mcaleer R. Allergic bronchopulmonary fungal disease without clinical asthma. Thorax 1981;36: 345349.
  • 59
    Slavin RG, Laird TS, Cherry JD. Allergic bronchopulmonary aspergillosis in a child. J Pediatr 1970;76: 416421.
  • 60
    Tonnel AB, Gosset P, Wallaert B. Allergic bronchopulmonary aspergillosis. In: MichelFB, BousquetJ, GodardP, editors. Highlights in asthmology. Berlin: Springer-Verlag, 1987: 5865.
  • 61
    Patterson R, Greenberger PA, Radin RC, Roberts M. Allergic bronchopulmonary aspergillosis: staging as an aid to management. Ann Intern Med 1982;96: 286291.
  • 62
    Kumar R. Mild, moderate, and severe forms of allergic bronchopulmonary aspergillosis: a clinical and serologic evaluation. Chest 2003;124: 890892.
  • 63
    Greenberger PA. Allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 2002;110: 685692.
  • 64
    Rosenberg M, Patterson R, Mintzer R, Cooper BJ, Roberts M, Harris KE. Clinical and immunologic criteria for the diagnosis of allergic bronchopulmonary aspergillosis. Ann Intern Med 1977;86: 405414.
  • 65
    Mccarthy DS, Pepys J. Allergic broncho-pulmonary aspergillosis. Clinical immunology. 2. Skin, nasal and bronchial tests. Clin Allergy 1971;1: 415432.
  • 66
    Dessaint JP, Bout D, Fruit J, Capron A. Serum concentration of specific IgE antibody against Aspergillus fumigatus and identification of the fungal allergen. Clin Immunol Immunopathol 1976;5: 314319.
  • 67
    Ricketti AJ, Greenberger PA, Patterson R. Serum IgE as an important aid in management of allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 1984;74: 6871.
  • 68
    Greenberger PA, Liotta JL, Roberts M. The effects of age on isotypic antibody responses to Aspergillus fumigatus: implications regarding in vitro measurements. J Lab Clin Med 1989;114: 278284.
  • 69
    Apter AJ, Greenberger PA, Liotta JL, Roberts M. Fluctuations of serum IgA and its subclasses in allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 1989;84: 367372.
  • 70
    Kurup VP, Banerjee B, Hemmann S, Greenberger PA, Blaser K, Crameri R. Selected recombinant Aspergillus fumigatus allergens bind specifically to IgE in ABPA. Clin Exp Allergy 2000;30: 988993.
  • 71
    Hemmann S, Menz G, Ismail C, Blaser K, Crameri R. Skin test reactivity to 2 recombinant Aspergillus fumigatus allergens in A fumigatus-sensitized asthmatic subjects allows diagnostic separation of allergic bronchopulmonary aspergillosis from fungal sensitization. J Allergy Clin Immunol 1999;104: 601607.
  • 72
    Banerjee B, Kurup VP, Greenberger PA, Johnson BD, Fink JN. Cloning and expression of Aspergillus fumigatus allergen Asp f 16 mediating both humoral and cell-mediated immunity in allergic bronchopulmonary aspergillosis (ABPA). Clin Exp Allergy 2001;31: 761770.
  • 73
    Tillie-Leblond I, Scherpereel A, Iliescu C. Aspergillose broncho-pulmonaire allergique. Rev Fr Allergol Immunol Clin 2002;42: 231240.
  • 74
    Reiff DB, Wells AU, Carr DH et al. CT findings in bronchiectasis: limited value in distinguishing between idiopathic and specific types. AJR Am J Roentgenol 1995;165: 261267.
  • 75
    Mintzer RA, Rogers LF, Kruglik GD, Rosenberg M, Neiman HL, Patterson R. The spectrum of radiologic findings in allergic bronchopulmonary aspergillosis. Radiology 1978;127: 301307.
  • 76
    Murphy D, Lane DJ. Pleural effusion in allergic bronchopulmonary aspergillosis: two case reports. Br J Dis Chest 1981;75: 9195.
  • 77
    Neeld DA, Goodman LR, Gurney JW, Greenberger PA, Fink JN. Computerized tomography in the evaluation of allergic bronchopulmonary aspergillosis. Am Rev Respir Dis 1990;142: 12001205.
  • 78
    Angus RM, Davies ML, Cowan MD, Mcsharry C, Thomson NC. Computed tomographic scanning of the lung in patients with allergic bronchopulmonary aspergillosis and in asthmatic patients with a positive skin test to Aspergillus fumigatus. Thorax 1994;49: 586589.
  • 79
    Ward S, Heyneman L, Lee MJ, Leung AN, Hansell DM, Muller NL. Accuracy of CT in the diagnosis of allergic bronchopulmonary aspergillosis in asthmatic patients. AJR Am J Roentgenol 1999;173: 937942.
  • 80
    Eaton T, Garrett J, Milne D, Frankel A, Wells AU. Allergic bronchopulmonary aspergillosis in the asthma clinic. A prospective evaluation of CT in the diagnostic algorithm. Chest 2000;118: 6672.
  • 81
    Mitchell TA, Hamilos DL, Lynch DA, Newell JD. Distribution and severity of bronchiectasis in allergic bronchopulmonary aspergillosis (ABPA). J Asthma 2000;37: 6572.
  • 82
    Nichols D, Dopico GA, Braun S, Imbeau S, Peters ME, Rankin J. Acute and chronic pulmonary function changes in allergic bronchopulmonary aspergillosis. Am J Med 1979;67: 631637.
  • 83
    Greenberger PA, Patterson R, Ghory A et al. Late sequelae of allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 1980;66: 327335.
  • 84
    Patterson R, Greenberger PA, Lee TM et al. Prolonged evaluation of patients with corticosteroid-dependent asthma stage of allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 1987;80: 663668.
  • 85
    Basich JE, Graves TS, Baz MN et al. Allergic bronchopulmonary aspergillosis in corticosteroid-dependent asthmatics. J Allergy Clin Immunol 1981;68: 98102.
  • 86
    Lee TM, Greenberger PA, Patterson R, Roberts M, Liotta JL. Stage V (fibrotic) allergic bronchopulmonary aspergillosis. A review of 17 cases followed from diagnosis. Arch Intern Med 1987;147: 319323.
  • 87
    Malo JL, Inouye T, Hawkins R, Simon G, Turner-Warwick M, Pepys J. Studies in chronic allergic bronchopulmonary aspergillosis. 4. Comparison with a group of asthmatics. Thorax 1977;32: 275280.
  • 88
    Salez F, Brichet A, Desurmont S, Grosbois JM, Wallaert B, Tonnel AB. Effects of itraconazole therapy in allergic bronchopulmonary aspergillosis. Chest 1999;116: 16651668.
  • 89
    Middleton WG, Paterson IC, Grant IW, Douglas AC. Asthmatic pulmonary eosinophilia: a review of 65 cases. Br J Dis Chest 1977;71: 115122.
  • 90
    Capewell S, Chapman BJ, Alexander F, Greening AP, Crompton GK. Corticosteroid treatment and prognosis in pulmonary eosinophilia. Thorax 1989;44: 925929.
  • 91
    Wark PA, Hensley MJ, Saltos N et al. Anti-inflammatory effect of itraconazole in stable allergic bronchopulmonary aspergillosis: a randomized controlled trial. J Allergy Clin Immunol 2003;111: 952957.
  • 92
    Safirstein BH, D'souza MF, Simon G, Tai EH, Pepys J. Five-year follow-up of allergic bronchopulmonary aspergillosis. Am Rev Respir Dis 1973;108: 450459.
  • 93
    Fournier EC. Trial of ketoconazole in allergic bronchopulmonary aspergillosis. Thorax 1987;42: 831.
  • 94
    Stevens DA, Schwartz HJ, Lee JY et al. A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis. N Engl J Med 2000;342: 756762.
  • 95
    Wark PA, Gibson PG, Wilson AJ. Azoles for allergic bronchopulmonary aspergillosis associated with asthma. Cochrane Database Syst Rev 2003;3: CD001108.