Reviews and Feature Articles
Allergic bronchopulmonary aspergillosis,☆☆

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Abstract

Allergic bronchopulmonary aspergillosis (ABPA) complicates asthma and cystic fibrosis. The survival factors in Aspergillus fumigatus that support saprophytic growth in bronchial mucus are not understood. Prednisone remains the most definitive treatment but need not be administered indefinitely. MHC IIrestricted CD4+ T H2 clones have been derived from patients with ABPA. The total serum IgE concentration is elevated sharply but isnonspecific.IgE serum isotypic antibodies to A fumigatus are useful in diagnosis; this is in contrast to the situation for patients with asthma without ABPA. High-resolution computed tomography of the chest demonstrates multiple areas of bronchiectasis in most patients with ABPA and is a useful radiologic tool. Some asthma control patients might have a few bronchiectatic airways, but not to the extent seen in or of the same character as those in ABPA. This review discusses clinical, radiologic, investigational, pathogenetic, and treatment issues of ABPA. (J Allergy Clin Immunol 2002;110:685-92.)

Section snippets

The diagnosis of ABPA in asthma and cystic fibrosis

For a diagnosis of ABPA in a patient with asthma, there should be a minimum of 5 criteria: (1) asthma, (2) proximal bronchiectasis (dilated bronchi in the inner two thirds of the chest field on a computed tomograph [CT]), (3) immediate cutaneous reactivity to Aspergillus species or Aspergillus fumigatus , (4) a total serum IgE that is elevated (>417 kU/L or 1000 ng/mL), and (5) elevated serum IgE–A fumigatus and/or serum IgG-A fumigatus in comparison with what is seen in sera from skin test–

Defenses against invasive aspergillosis

In ABPA and allergic Aspergillus sinusitis (AAS),31, 32, 33 there is no systemic invasive aspergillosis. The patients are not immunocompromised. There is saprophytic growth of A fumigatus (or other fungi) in bronchial mucus or sinuses. In AAS, there can be expansile effects of the mucoid impactions in closed spaces that thin bones or deviate them outright. It is possible to demonstrate localized bony invasion if adequate surgical debridement and marsupialization have not been performed. For

Characteristics of aspergillus species

Most human disease attributable to the genus Aspergillus is caused by A fumigatus . The spores are remarkably thermotolerant; they grow at temperatures from 15° to 53°C. They can be recovered in outdoor winter air and from warm compost piles. The spores are readily grown on Sabouraud dextrose agar slants. The hyphae are 7 to 10 μm long and septate, and they branch at 45°. Hyphae present in a mucus plug from sputum or sinus debris can be identified through use of a Gomori methenamine silver

Aspergillus -related conditions

Aspergillus species can cause allergic asthma and acute respiratory responses with experimental challenges. In ABPA, bronchoprovocation challenges are not required for the diagnosis and can result in very large reductions in FEV1 . In 1971, McCarthy and Pepys 36 reported declines of as much as 40% to 50% in FEV 1 during the immediate response with reversal by a β- adrenergic agonist.36 Late reactions began within 4 to 10 hours and lasted from 30 to 70 hours; there were declines in FEV1 from 50%

Staging of ABPA

The 5 stages proposed by Patterson et al37 remain useful. These stages are not phases of a disease, and in each case the physician should attempt to determine the stage that is present. The stages are presented in Table III.

. Stages of ABPA

StageDescriptionRadiographic infiltratesTotal serum IgE
IAcuteUpper lobes or middle lobeSharply elevated
IIRemissionNo infiltrate and patient off prednisone for >6 moElevated or normal
IIIExacerbationUpper lobes or middle lobeSharply elevated
IVCorticosteroid-

Radiology

CT with thin (1-2 mm) rather than conventional (10 mm) sections are extremely valuable in the diagnosis of ABPA. Proximal (central) bronchiectasis is defined as being present when there are bronchi that are dilated in comparison with the caliber of an adjacent bronchial artery in the inner two thirds of the lung CT field.40 Bronchiectasis is described as cylindrical when the bronchus does not taper and is 1.5 to >3 times the caliber of diameter of an adjacent artery (Fig 1).

. A 42-year-old woman

Laboratory and investigational findings in ABPA

Antigens from A fumigatus range from 10 to 100 kD in weight, and there are approximately 40 components that bind with IgE antibodies.34, 44, 45 There are 22 recombinant Aspergillus allergens that have been accepted by the Allergen Nomenclature Sub-Committee of the International Union of Immunological Societies.46 Designated Asp f 1 through Asp f 22, they have molecular weights ranging from 11 to 90 kD. The nomenclature designations include recombinant allergens from Aspergillus niger and

Pathogenesis of ABPA

Discussions on pathogenesis are available in greater detail in several additional references. 34, 36, 44, 45, 46, 47, 48, 49, 50, 53, 61, 62, 63 After inhalation of spores of A fumigatus , there is saprophytic growth in the hyphal form. It remains unclear what survival factors there might be in A fumigatus , or what abnormalities there might be in bronchial mucus, that permit its growth in contrast to the clearing seen in all other patients with asthma who do not develop ABPA.

Many of the

Treatment

In the 1960s, attempts were made to treat ABPA with antifungal agents, often by inhalation, and cromolyn.68 When prednisone was compared with cromolyn, it became apparent that the oral corticosteroid provided much better results.68 This was at a time when serial monitoring with total serum IgE concentrations was not done (IgE was not isolated and characterized until 1968). The current recommended approach is presented in Table IV.

. Suggestions for initial treatment of ABPA

1. For new ABPA

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    Supported by the Ernest S. Bazley Grant to Northwestern Memorial Hospital and Northwestern University.

    ☆☆

    Reprint requests: Paul A. Greenberger, MD, Division of Allergy- Immunology, 303 E Chicago Ave, S 207, Chicago, IL 60611 3008.

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