(Chest. 2003;124:890-892.)
© 2003
American College of Chest Physicians
Mild, Moderate, and Severe Forms of Allergic Bronchopulmonary Aspergillosis*
A Clinical and Serologic Evaluation
Raj Kumar, MD
* From the Department of Respiratory Medicine, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
Correspondence to: Raj Kumar, MD, 44/1, Probyn Rd, Dehli University Campus, Delhi-7, India; e-mail: rajneel44{at}rediffmail.com
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Abstract
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Background: Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity disorder induced by Aspergillus species colonizing the bronchial tree. There are patients with asthma who fulfill the diagnostic criteria of ABPA by serologic evaluation (specific IgE/IgG to Aspergillus fumigatus), bronchography, CT, and or conventional linear tomography.
Objective: To identify different forms of ABPA based on various diagnostic criteria.
Methods: Eighteen patients with asthma fulfilling the criteria of ABPA were evaluated in the present study. Six patients each received a diagnosis of ABPA serologic positive (ABPA-S), ABPA with central bronchiectasis (ABPA-CB), and ABPA with central bronchiectasis and other radiologic features (ABPA-CB-ORF).
Results: The spirometric changes in the ABPA-S group (group 1) were mild, in the ABPA-CB group (group 2) were moderate, and in the ABPA-CB-ORF group (group 3) were severe. Absolute eosinophil count was raised in each group but was maximum (1,233 µL) in severe form of disease (group 3). Specific IgE against A fumigatus was raised in each group, and the maximum was 47.91 IU/mL in ABPA-CB-ORF. CT scan findings of the ABPA-S group were normal without central bronchiectasis. The exacerbation in symptoms was maximum in group 3 compared to other groups.
Conclusion: The present observations suggest that ABPA includes mild (ABPA-S), moderate (ABPA-CB), and severe (ABPA-CB-ORF) forms of disease. It is recommended, therefore, that the disease should be diagnosed early, treated at the mild form of disease (ABPA-S), and prevented from leading to ABPA-CB or ABPA-CB-ORF.
Key Words: allergic bronchopulmonary aspergillosis • enzyme-linked immunosorbent assay • specific IgE/IgG • type III hypersensitivity
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Introduction
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Allergic bronchopulmonary aspergillosis (ABPA) was first reported in England during 1952.1
Since then, a number of cases have been diagnosed and reported from many countries.2
3
The incidence of ABPA in asthmatics varied from 3.7 to 11% in Western countries.3
4
In India, Chetty et al5
reported ABPA in 15% of cases in a group of children with perennial asthma. In a recent study by Kumar and Gaur,6
the prevalence of ABPA in patients with chronic bronchial asthma has been reported as 16% (12% with central bronchiectasis, and 4% only serologic positive). It is very important to make a clinical and serologic evaluation of all patients with ABPA and to ascertain the severity of disease. The present study was planned to identify different forms of ABPA based on various diagnostic criteria.
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Materials and Methods
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ABPA was diagnosed in 18 patients with chronic asthma who were receiving oral short courses of steroids approximately six to eight times per year. The diagnosis of ABPA was made using following criteria: asthma, immediate type cutaneous reactivity to Aspergillus fumigatus, elevated total IgE, specific IgE (enzyme-linked immunosorbent assay) against A fumigatus (IgE-Af), serum precipitating antibodies IgG against A fumigatus (IgG-Af), radiographic pulmonary infiltrates (fixed/transient), and proximal or central bronchiectasis on CT. The patients with all the criteria except central bronchiectasis were labeled as ABPA serologic positive (ABPA-S) [group 1; n = 6]. A second category of patients was labeled as ABPA with central bronchiectasis (ABPA-CB) [group 2; n = 6]. A third category (group 3; n = 6) of patients, who apart from central bronchiectasis had other radiologic features such as pulmonary fibrosis, bleb, bullae, pneumothorax, parenchymal scarring, emphysematous change, multiple cyst, fibrocavitary lesions, aspergilloma, ground-glass appearance, collapse, mediastinal lymph node, pleural effusion and pleural thickening, were labeled as ABPA with central bronchiectasis and other radiologic features (ABPA-CB-ORF).
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Results
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The 18 patients evaluated were nonsmokers and between the ages of 12 years and 54 years. The duration of illness was 4 to 20 years. The clinical details of these patients are summarized in Table 1
. It is evident from the results that the severity of the disease is maximum in group 3 (ABPA-CB-ORF). It is the severe form of ABPA in comparison to ABPA-S (normal CT findings) and ABPA-CB. It has been observed that two patients in group 2 (ABPA-CB) and four patients in group 3 (ABPA-CB-ORF) had earlier received antituberculous drugs due to wrong diagnosis. The clinical and radiologic features suggest ABPA-S as mild, ABPA-CB as moderate, and ABPA-CB-ORF as the severe form. This is further supported by serological data presented in Table 2
. Total IgE was 597 IU/mL, 2,571 IU/mL, and 3,435 IU/mL in ABPA-S, ABPA-CB, and ABPA-CB-ORF groups, respectively. IgE-Af was raised in each group (ABPA-S, 9.88 IU/mL; ABPA-CB, 23.12 IU/mL; and ABPA-CB-ORF, 47.91 IU/mL), but was maximum in ABPA-CB-ORF. Serum precipitins and IgG-Af (enzyme-linked immunosorbent assay) were positive in 50% and 100% in ABPA-S, 66% and 66% in ABPA-CB, and 100% and 66% in ABPA-CB-ORF, respectively. The evaluation of chest CT also showed that ABPA-S is mild, ABPA-CB is moderate, and ABPA-CB-ORF is the severe form of disease. The exacerbation of symptoms was at a minimum in ABPA-S.
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Discussion
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The patients included in the present study were followed up for a 2-year period. It was observed that ABPA-S did not progress to severe form of disease, ie, ABPA-CB or ABPA-CB-ORF. Even ABPA-CB did not progress to ABPA-CB-ORF. This may be due to the early diagnosis of the disease and the regular treatment administered. Patterson et al7
8
reported that early treatment prevents the progress of disease into the severe form. It is evident from the results that ABPA-S lacks demonstrable lung damage and represents a mild clinical form of the disease. The apparent decrease of frequency with which disease exacerbation and pulmonary infiltrates occur in patients with ABPA-S may be due to less intense inflammatory obstructive response and absence of bronchiectasis. Similar observations have been recorded by other workers.9
The pathogenesis of ABPA remains unclear since it has multiple components. Passive transfer of serum containing isotopic antibodies IgE-Af and IgG-Af from patients with ABPA to a monkey resulted in the development of pulmonary lesions when Aspergillus was inhaled.10
IgE-Af and IgG-Af has been demonstrated essential for the development of biopsy lesion consistent with ABPA following A fumigatus aerosol challenge.11
Isotypic antibodies to A fumigatus in the lung likely mediate immunologic injury. Mast cell activation by intersection of IgE and A fumigatus results in mediator release and cytokine production, which contribute to lung damage. Lymphocyte and eosinophil activation may participate in immunologic reaction also. In patients with ABPA and previous infiltrates, bronchiectasis develops and chronic colonization by A fumigatus results in continuing bronchial wall damage. In the case of ABPA-S, there is less intense inflammatory destructive response and hence absence of bronchiectasis. The continuous intense inflammation that results in bronchiectasis or bronchiolitis obliterans as occurs in ABPA-CB has not been identified in ABPA-S. Patients with ABPA-S represent the early stage of the disease or a less aggressive mild form of the disease. In two of the ABPA-S group patients, sputum contained A fumigatus. This shows that spores are able to colonize the bronchial mucosa in this subset of patients, but the absence of bronchiectasis in these patients (ABPA-S) is difficult to understand.
The host response to Aspergilli in the bronchial mucosa may be an important factor in determining why some patients acquire bronchiectasis (ABPA-CB) and others acquire ABPA-S. Robertson and coworkers12
demonstrated that spores of A fumigatus were resistant to phagocytosis by human macrophages in contrast to Pencillium spores that were readily ingested. The Aspergillus spores apparently released a substance that inhibited their ingestion by macrophages. Proteolytic enzymes from Aspergillus spores result in additional bronchial antigenic exposure and consequent immunologic response.13
An exaggerated host response including cytokine release, lymphocyte sensitization, and complement activation is thought to mediate in bronchial wall damage leading to bronchiectasis and later fibrosis of the lung. ABPA is frequently misdiagnosed as pulmonary tuberculosis14
15
and ends up in the severe form of ABPA (ie, ABPA-CB-ORF). This may be due to lack of awareness or requisite diagnostic facilities (especially serologic investigations).
In conclusion, a high index of suspicion of ABPA should be made in all patients with chronic asthma and immediate-type cutaneous reactivity to A fumigatus. It is better to diagnose the disease in the early phase (mild form) of disease (ie, ABPA-S) and start the necessary treatment that may prevent the progression of the disease. ABPA-CB-ORF is clinically and serologically a severe form of ABPA; hence, prevention of this stage should always be attempted by early treatment and longer or life-long follow-up of the patient.
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Acknowledgements
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The author thanks Dr. B. P. Singh, CBT for editorial assistance.
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Footnotes
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Abbreviations: ABPA = allergic bronchopulmonary aspergillosis; ABPA-CB = allergic bronchopulmonary aspergillosis with central bronchiectasis; ABPA-CB-ORF = allergic bronchopulmonary aspergillosis with central bronchiectasis and other radiologic features; ABPA-S = allergic bronchopulmonary aspergillosis serologic positive; IgE-Af = specific IgE against Aspergillus fumigatus; IgG-Af = specific IgG against Aspergillus fumigatus
Received for publication November 27, 2001.
Accepted for publication January 23, 2003.
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References
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- Pepys, J Hypersensitivity disease of the lungs due to fungi and organic dust. Monographs in allergy 1969;Vol 4,41-59 Karger. Basel, Switzerland:
- Henderson, AH, English, MP, Vecht, RJ Pulmonary aspergillosis: a survey of its occurrence in patients with chronic lung disease and a discussion of significance of diagnostic text. Thorax 1968;25,513-553
- Agbayani, BF, Normal, PS, Wukenwerden, W, et al The evidence of allergic aspergillosis in chronic asthma. J Allergy 1967;40,319-326[CrossRef][ISI][Medline]
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Abstract
Introduction
