Elsevier

Disease-a-Month

Volume 54, Issue 8, August 2008, Pages 547-564
Disease-a-Month

Allergic Bronchopulmonary Aspergillosis

https://doi.org/10.1016/j.disamonth.2008.05.004Get rights and content

Introduction

Aspergillus species are ubiquitous spore-forming fungi found worldwide in soil and plants. There are nearly 180 species of Aspergillus but the most common ones affecting the humans are Aspergillus fumigatus (AF), Aspergillus flavus, and Aspergillus niger. These three species can cause a variety of clinical manifestations ranging from colonization in allergic bronchopulmonary disease to active infection in locally destructive disease, or in the most severe form as disseminated infection in immunocompromised patients.1 In this article, the allergic bronchopulmonary disease referred to as allergic bronchopulmonary aspergillosis (ABPA) that results in bronchiectasis will be discussed. ABPA was first reported by Hinson and his colleagues and a detailed description of the disease was done by Pepys and coworkers.2, 3, 4 ABPA is a hypersensitivity reaction to Aspergillus mycelia that colonize the bronchi.

ABPA is seen in patients with asthma and cystic fibrosis. The prevalence of ABPA is reported to be 1-2% in asthmatics, 7-14% of steroid-dependent asthmatics, and 2-15% in cystic fibrosis (CF).5, 6, 7, 8 Rarely, in asthmatics, ABPA is seen without central bronchiectasis. In asthmatics, both environmental factors and a genetic predisposition may be present, as there are reports of familial occurrence of ABPA.9, 10 It has been shown that HLA-DR molecules, especially DR2, DR5, and possibly DR4 and DR-7, are associated with susceptibility to ABPA, while HLA-DRQ2 is shown to have resistance to ABPA.11, 12, 13 In CF, the presence of atopy with underlying impaired mucociliary clearance and airway inflammation appear to predispose patients toward developing ABPA.14

Section snippets

Pathogenesis

The airborne spores of Aspergillus are 2 to 3 μm in size and can reach the alveoli when inhaled. The spores germinate in the airways. The exact pathogenesis of ABPA is poorly understood. No correlation between the intensity of spore exposure and rate of sensitization to the fungus via skin testing is shown.15 Response to inhalation of fungal spores in atopic individuals occurs in the two following forms: (1) an asthma-like reaction on transient exposure to high intensity of Aspergillus spores

Clinical Features

In patients with asthma, the clinical features of ABPA range from mild asthma to severe, predominantly central bronchiectasis. ABPA exacerbations are characterized by episodes of fever, pleuritic pain, increase in dyspnea, cough, and sputum production. Patients may cough up brownish mucous plugs and rarely have hemoptysis. On examination, fever, rhonchi, and wheezing during acute an exacerbation may be seen. In some patients with ABPA, symptoms are minimal where radiographic changes of ABPA are

Diagnosis

A diagnosis of ABPA should be considered when treating asthmatics with chest radiograph abnormalities. ABPA accounts for as much as 10% of cases of bronchiectasis, and testing for ABPA is recommended in those presenting with bronchiectasis.23 As discussed above, the presenting symptoms may include recurrent asthma exacerbations, cough, and infiltrates on chest radiograph and may also have systemic features of fever, anorexia, headache, and malaise.3, 19, 20, 21, 24 If clinical suspicion for

Staging of ABPA

The natural history of ABPA is poorly characterized and is difficult to predict. Patterson and coworkers described five stages of ABPA based on clinical presentation and the staging is useful in the management of patients. The staging does not reflect progression of disease.26

Stage I—Acute: Patients are diagnosed with ABPA after meeting the diagnostic criteria outlined above. In the acute stage, the levels of serum IgE and IgG specific to AF are elevated. While peak levels of IgE are noted, IgE

ABPA in Cystic Fibrosis

ABPA is reported to occur in 1 to 15% of patients. Atopy seems to be an important risk factor for ABPA in CF. In cystic fibrosis, ABPA was seen in 22% of atopic patients and only 2% of nonatopic patients.7, 14, 28, 29, 30 Skov and coworkers reported significant elevation of AF-specific antibodies belonging to total IgG and all subclasses in unselected cystic fibrosis patients compared to healthy controls.30 An increased prevalence of ABPA was seen in males (59%), predominantly adolescents, with

Radiographic Abnormalities in ABPA

The pathogenesis of ABPA results in inflammation of airways and excessively thick mucous production leading to obstruction of both small and large airways as well as pulmonary infiltrates. AF resides in bronchial lumen without invading the tissue. This local inflammatory reaction without invasion of surrounding tissues distinguishes ABPA from invasive aspergillosis.

The most common radiographic abnormality in ABPA is dilated bronchi in a central location, otherwise known as central

Management of ABPA

The management of ABPA in asthmatics and cystic fibrosis has three major components in addition to continuing therapy for the underlying asthma and or cystic fibrosis: I. Early diagnosis; II. Institution of therapy to achieve remission; III. Recognition of relapse and prompt treatment.

Practical Approach for Diagnosing ABPA in the Clinic

  • In patients with asthma, suspect ABPA if their symptoms are poorly controlled, when their chest radiograph shows characteristic changes, or when there is a frequent history of bronchitis/pneumonia.

  • In patients with CF, suspect ABPA when new infiltrates appear with wheezing and worsening of clinical course. Annual serum IgE testing is recommended.

  • When ABPA is suspected, check for total IgE levels total as well as IgE specific for Aspergillus species and perform skin testing for Aspergillus

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