Reviews and Feature ArticlesAllergic bronchopulmonary aspergillosis☆,☆☆
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.
Stage Description Radiographic infiltrates Total serum IgE I Acute Upper lobes or middle lobe Sharply elevated II Remission No infiltrate and patient off prednisone for >6 mo Elevated or normal III Exacerbation Upper lobes or middle lobe Sharply elevated IV Corticosteroid-
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).
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.
1. For new ABPA
References (73)
- et al.
Allergic bronchopulmonary aspergillosis in a child
J Pediatr
(1970) - et al.
Allergic bronchopulmonary aspergillosis and the evaluation of the patient with asthma
J Allergy Clin Immunol
(1988) - et al.
Prevalence of allergic bronchopulmonary aspergillosis and atopy in adult patients with cystic fibrosis
Chest
(1996) - et al.
Allergic bronchopulmonary aspergillosis in cystic fibrosis: reported prevalence, regional distribution, and patient characteristics
Chest
(1999) - et al.
Immune responses to Aspergillus in cystic fibrosis
J Allergy Clin Immunol
(1988) - et al.
Allergic bronchopulmonary aspergillosis in cystic fibrosis
J Allergy Clin Immunol
(1984) - et al.
Allergic bronchopulmonary aspergillosis in patients with cystic fibrosis
Chest
(1994) - et al.
Allergic bronchopulmonary aspergillosis in cystic fibrosis: role of atopy and response to itraconazole
Chest
(1999) - et al.
Allergic Aspergillus sinusitis with concurrent allergic bronchopulmonary Aspergillus : report of a case
J Allergy Clin Immunol
(1988) - et al.
Sensitization to Aspergillus species in the congenital neutrophil disorders chronic granulomatous disease and hyper- IgE syndrome
J Allergy Clin Immunol
(1999)
Prolonged evaluation of patients with corticosteroid-dependent asthma stage of allergic bronchopulmonary aspergillosis
J Allergy Clin Immunol
Serum IgE as an important aid in management of allergic bronchopulmonary aspergillosis
J Allergy Clin Immunol
Allergic bronchopulmonary aspergillosis in the asthma clinic: a prospective evaluation of CT in the diagnostic algorithm
Chest
T cell proliferation and cytokine secretion to T cell epitopes of Asp f 2 in ABPA patients
Clin Immunol
IgE downregulation and cytokine induction by Aspergillus antigens in human allergic bronchopulmonary aspergillosis
J Lab Clin Med
Evidence for the involvement of two different MHC class II regions in susceptibility or protection in allergic bronchopulmonary aspergillosis
J Allergy Clin Immunol
Fluctuations of serum IgA and its subclasses in allergic bronchopulmonary aspergillosis
J Allergy Clin Immunol
Evidence that Aspergillus fumigatus growing in the airway of man can be a potent stimulus of specific and nonspecific IgE formation
Am J Med
Analysis of bronchoalveolar lavage in allergic bronchopulmonary aspergillosis: divergent responses of antigen specific antibodies and total IgE
J Allergy Clin Immunol
Frequency of cystic fibrosis transmembrane conductance regulator gene mutations and 5T allele in patients with allergic bronchopulmonary aspergillosis
Chest
Allergic bronchopulmonary aspergillosis
Chest
Immunologic significance of a collagen- derived culture filtrate containing proteolytic activity in Aspergillus- related diseases
J Allergy Clin Immunol
The Th1/Th2 paradigm in allergic bronchopulmonary aspergillosis
J Lab Clin Med
Antifungals in the treatment of allergic bronchopulmonary aspergillosis
Ann Allergy Asthma Immunol
Effects of itraconazole therapy in allergic bronchopulmonary aspergillosis
Chest
Hypersensitivity disease of the lung
Univ Michigan Med Center J
Bronchopulmonary aspergillosis: a review and report of eight new cases
Thorax
The prevalence of allergic bronchopulmonary aspergillosis in patients with asthma, determined by serologic and radiologic criteria in patients at risk
J Lab Clin Med
Specific IgG subclass antibody pattern to Aspergillus fumigatus in patients with cystic fibrosis with allergic bronchopulmonary aspergillosis (ABPA)
Thorax
Cystic fibrosis in adolescents and asthma
Q J Med
Aspergillosis and atopy in cystic fibrosis
Am Rev Respir Dis
Allergic bronchopulmonary aspergillosis in cystic fibrosis: a secretory immune response to a colonizing organism
Ann Allergy
Increase in allergic bronchopulmonary aspergillosis in CF patients in San Diego
Pediatr Pulmonol
A prospective study of Aspergillus fumigatus (Af) allergy and/or Af bronchopulmonary infection in children with cystic fibrosis
Pediatr Pulmonol
Rise in total IgE as an indicator of allergic bronchopulmonary aspergillosis in cystic fibrosis
Thorax
Cystic Fibrosis Foundation
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Supported by the Ernest S. Bazley Grant to Northwestern Memorial Hospital and Northwestern University.
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Reprint requests: Paul A. Greenberger, MD, Division of Allergy- Immunology, 303 E Chicago Ave, S 207, Chicago, IL 60611 3008.