Allergic bronchopulmonary aspergillosis (ABPA) is a fungal infection of the lung due to a hypersensitivity reaction to antigens of Aspergillus fumigatus after colonization into the airways. It characteristically presents with bronchospasm, pulmonary infiltrates, eosinophilia, and immunologic evidence of allergy to the antigens of Aspergillus species.
An infection by Aspergillus species causes a broad spectrum of illnesses in humans and depends on the immune status of the host.
Aspergillus species are a common causative organism for fungal infection in immunocompromised individuals.
Allergic bronchopulmonary aspergillosis commonly presents in the third to fifth decade of life. It is also common in children. It usually found in severe asthmatics and patients with cystic fibrosis.
A. fumigatus is the most common organism that causes ABPA, and the fungus requires dead organic matter to survive. The highest incidence of the infection is known to be in the winter season around the world (secondary to fallen leaves).
Genetic association: HLA-DR molecules DR2, DR5, and possibly DR4 or DR7 contribute to susceptibility; whereas, HLA-DQ2 contributes to resistance and a combination of these may determine the outcome of ABPA in CF and asthma.
The pathogenesis of allergic bronchopulmonary aspergillosis remains incompletely understood. A. fumigatus spores that get inhaled in sufficient quantities behave as allergens. Normally a low level of IgG against fungal antigens in the circulation and the low antifungal secretory IgA in bronchoalveolar fluid suggest that healthy individuals can effectively eliminate fungal spores. In contrast, exposure of atopic individuals to fungal spores or mycelial fragments results in the formation of IgE and IgG antibodies.
Th2 cells (Helper T cells) play an essential role in the hypersensitivity reaction caused by the A. fumigatus antigen. It manifests as IgE production, eosinophilia, mast cell degranulation, and bronchiectasis.
A. fumigatus proteases release proinflammatory cytokines, such as IL-8 which causes epithelial cell damage and disruption of protective barriers which triggers the hypersensitivity reaction. It also releases cytokines interleukin (IL)-4, IL-5, and IL-13, which increases blood and airway eosinophils as well as IgE.
Histopathologically, there is chronic bronchial inflammation, eosinophilia (leading to the development of an area of parenchymal scarring), airway remodeling, and bronchiectasis. Bronchi may show impacted mucus plug containing fungal hyphae, fibrin, Charcot-Leyden crystals, Curschmann spirals. The dichotomous branching of hyphae occurs at 45-degree angles.
Allergic bronchopulmonary aspergillosis occurs primarily in patients with asthma or cystic fibrosis.
On physical examination:
There is no individual test that establishes the diagnosis of allergic bronchopulmonary aspergillosis. The diagnosis is based on classic clinical manifestations, radiographic findings, and immunological findings.
Aspergillus skin test:
Radiological manifestations of ABPA:
The following shadows may present radiologically:
Revised radiologic classification of allergic bronchopulmonary aspergillosis based on findings on a high-resolution computed tomography of the chest.
Pulmonary function tests:
Bronchoscopy: Mucoid impaction may be evident, and bronchial brushings may reveal mucus that contains aggregates of eosinophils, fungal hyphae, and eosinophil-derived Charcot–Leyden crystals. The finding of hyphae-filled mucus plugs is considered pathognomonic for ABPA. BAL fluid analysis from patients with ABPA: moderate eosinophilia (especially in steroid-naive patients) and increased levels of Aspergillus-specific IgE and IgA, but not IgG.
Sputum cultures for A. fumigatus: It is not diagnostic, but if it reveals an organism, then it helps in drug susceptibility test.
Following criteria are used for diagnosis and typing of ABPA.
1) Rosenberg-Patterson criteria: It has five major and three minor criteria.
2) Criteria proposed by ISHAM working group :
The main aim of treatment of allergic bronchopulmonary aspergillosis is to control episodes of acute inflammation and to limit progressive lung injury.
Goals of treatment:
• Controlling symptoms • Preventing exacerbations • Preserving normal lung function
Drugs used for the treatment of ABPA:
Corticosteroids: Systemic corticosteroids are the primary therapy for ABPA. A steroid helps to relieve the symptoms and decreases airflow obstruction, decreases serum IgE and reduces peripheral blood eosinophils. Moreover, there is a resolution of pulmonary inflammation, pulmonary infiltrates, and it prevents irreversible lung damage.
Oral antifungal agents: Antifungal agents act by decreasing the fungal load that reduces inflammatory activity and act as steroid-sparing agents. Antifungal therapy may help to decrease exacerbations.
Antibiotics: To prevent or treat an associated secondary bacterial infection.
Omalizumab: An anti-IgE recombinant humanized monoclonal antibody which prevents binding of IgE to Fc-epsilon RI receptor on mast cells and basophils.
Differential Diagnosis of allergic bronchopulmonary aspergillosis:
Itraconazole interferes with the hepatic metabolism of several medications, including cyclosporine, oral hypoglycemics, tacrolimus, terfenadine, cisapride, and midazolam. Impaired absorption is most significant with proton pump inhibitors.
Glucocorticoids side effects: Weight gain, osteopenia, acne, skin atrophy, diabetes mellitus, glaucoma, cataracts, avascular necrosis of bone, infection, hypertension, and growth retardation in children.
Omalizumab side effects: The most common reaction is swelling and redness at the injection site. Anaphylaxis may occur in asthmatics.
New Proposed clinical staging of allergic bronchopulmonary aspergillosis in asthmatic patients:
Stage 0: Asymptomatic
Stage 1: Acute
Stage 2: Response
Stage 3: Exacerbation
Stage 4: Remission
Sustained clinical-radiological improvement and
Stage 5a: Treatment-dependent ABPA
Stage 5b: Glucocorticoid-dependent asthma
Stage 6: Advanced ABPA
EPR-3: third expert panel report; GINA: global initiative against asthma
The natural history, progression, remission, and recurrences of ABPA are not well understood. Patients without central bronchiectasis at the time of diagnosis tend to maintain their lung function despite occasional exacerbations.
With appropriate treatment, long-term control of ABPA is feasible, and durable remissions are common.
Treatment of Stage 1 disease using corticosteroids typically results in decreased sputum production, improved control of bronchospasm, over 35% reduction in total IgE within 8 weeks, clearing of precipitating antibodies, and resolution of radiographic infiltrates. IgE levels typically do not completely normalize, but it decreases by approximately one-half of peak levels seen in the acute stage.
Progression of Stage 5 disease to pulmonary fibrosis may be preventable if patients maintain therapy on low-dose steroids.
Persons with an FEV1 persistently under 0.8 L have a worse prognosis.
Patients with allergic bronchopulmonary aspergillosis have to be more conscious about the worsening of their symptoms. If worsening of respiratory symptoms occurs on treatment or new respiratory symptoms develops on stage 2 and stage 3, then immediately consult a pulmonologist.
Patients with ABPA-CB have a higher chance to get a secondary infection and complications related to bronchiectasis. If fever or hemoptysis occurs, then immediately consult a pulmonologist.
If a patient is receiving long-term oral corticosteroids, all adverse drug effects should be properly understood. Screening should be performed for corticosteroid adverse effects of osteoporosis/osteopenia (by bone density measurement) and cataracts (by eye exams) regularly.
Patients bronchiectasis should receive training on sputum clearance techniques. Recommendations are for influenza and pneumococcal immunizations.
Avoid areas and environmental conditions with high mold counts, such as decomposing organic materials, and moldy indoor environments.
Allergic bronchopulmonary aspergillosis is a fungal infection of the lung secondary to a hypersensitivity reaction to antigens of Aspergillus fumigatus. This disease process is uncommon; however, routine screening is necessary for asthmatic and cystic fibrosis patients. The interprofessional approach of pulmonologists, infectious diseases, primary care physicians, pharmacists, and other healthcare professionals is essential to educate and improve patient outcomes. [Level V] A focused history and physical examination along with appropriate imaging with a high-resolution chest tomography of the chest are critical to establish an early diagnosis and initiate early treatment to prevent the development of bronchiectasis or pulmonary fibrosis. As targeted immunotherapy is evolving, there may be new treatment options in the near future.
The nurse place an important role in monitoring the patient for progression or worsening symptoms that must be reported back to the interdisciplinary team leader. As drug therapy and monitoring is complex in these patients, a pharmacist should evaluate for drug-drug interactions and coordinate drug therapy assisting in monitoring for compliance and side effects and reporting to the clinical team leader if untoward complications arise. The nurse practitioner, physicians assistant must coordinate care and patient and family education together so that they are aware of the need to monitor treatment, follow up regularly, and return for reassessment if unexpected complications occur. This disease is challenging to treat and only through coordinated interdisciplinary care will the best outcomes be achieved. [Level V]
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