Allergic Bronchopulmonary Aspergillosis - An Intricate Disease

Introduction

Allergic bronchopulmonary aspergillosis (ABPA) is an infrequent lung disease. It occurs due to a severe allergic reaction after exposure to Aspergillus fumigatus (a fungus). Although many people are exposed to the fungus, an allergic reaction is rare in people with normal immunity. However, the immune system gives an exaggerated response (hypersensitivity) to the fungus in some individuals. As a result, it can injure the airways and lead to permanent lung damage. The fungus mainly inhabits the air passages of asthma and cystic fibrosis patients. Therefore, early diagnosis and prompt management are critical to prevent disease progression and complications.

What Is the Pathophysiology of Allergic Bronchopulmonary Aspergillosis?

The disease mechanism of ABPA needs elaboration. A. fumigatus spores act as allergens on inhalation. Healthy individuals can effectively eliminate fungal spores. On the other hand, in individuals with atopy (an immune system condition that makes one susceptible to allergic diseases), fungal spores result in the formation of antibodies (immune proteins). The hypersensitivity reaction caused by the antigen leads to IgE antibody release (an immune protein increased in allergy), increased eosinophil production, mast cell degranulation (eosinophils and mast cells increase in allergy), and bronchiectasis (lung damage). Further, the release of inflammatory mediators causes epithelial cell damage and disruption of protective barriers in the lung.

How Does Allergic Bronchopulmonary Aspergillosis Present in Patients?

ABPA patients have a history of recurrent wheezing (high-pitched whistling noise). Also, patients may have a cough, shortness of breath, chest pain, and blood-stained sputum. Other non-specific complaints are loss of appetite, tiredness, body ache and muscle pain, low-grade fever, and weight loss. However, ABPA occurs primarily in patients with asthma or cystic fibrosis.

1. ABPA With Asthma: Asthma is characterized by airway narrowing and difficulty breathing in patients. ABPA can occur in less than one percent of poorly controlled asthma patients. An asthmatic patient with ABPA has difficulty controlling asthma despite appropriate treatment.

2. ABPA With Cystic Fibrosis: Cystic fibrosis (CF) is an inherited life-threatening lung and digestive system condition. ABPA can be seen in about 15 percent of CF patients. ABPA is considered when a CF patient has worsening symptoms and is not responding to the respective therapy.

How Is Allergic Bronchopulmonary Aspergillosis Evaluated?

No individual test can diagnose ABPA. Therefore, the investigations required to arrive at the correct diagnosis are:

1. Blood Test: A blood test can indicate an allergic reaction. It includes evaluating IgE levels. Asthmatic patients have higher than normal IgE levels. However, ABPA patients have higher levels of IgE than those with asthma. Furthermore, estimating IgE levels can monitor the control of ABPA.

2. Sputum Culture: A sputum culture can check fungal growth in the airways. However, it is not reliable as many people have A. fumigatus in airway secretions. Also, a person can still have ABPA even if the sputum culture is negative.

3. Imaging: Chest X-rays do not help diagnose ABPA. It is because a chest X-ray has only 50 percent sensitivity for ABPA diagnosis. However, a computed tomography (CT) scan gives a more detailed view and can detect bronchiectasis. A high-resolution chest CT (chest HRCT) is the preferred imaging procedure for ABPA.

4. Aspergillus Skin Test: Aspergillus skin test (AST) for IgE antibodies to A. fumigatus can be done if a person is allergic to the fungus. The individual does not have ABPA if the skin tests are negative for A. fumigatus.

5. Pulmonary (Lung) Function Tests: Spirometry (lung function testing) can detect the severity of the disease and check treatment response.

What Is the Management of Allergic Bronchopulmonary Aspergillosis?

The four objectives of treatment for ABPA are to control symp­toms of asthma or CF, treat respiratory aggravations of ABPA, reduce lung inflammation, and reduce disease progression. A delay in treatment for ABPA can lead to complications such as lung fibrosis, chronic bronchiectasis, severe asthma, and impaired lung function.

1. Corticosteroids: Corticosteroids are the mainstay for ABPA treatment. Currently, oral glucocorticoids (Prednisolone) are the most effective drugs for the same. Despite its efficacy, the optimal dose of Prednisolone is unclear. The treatment strategy is the use of Prednisolone daily for 14 days. It is followed by alternate-day treatment, dose tapering, and discontinuation after three months. The clinical response to corticosteroid treatment must be monitored for one to two months.

2. Antifungal Therapy: Itraconazole and Voriconazole are the antifungal agents against ABPA. However, they are used in those who are unable to taper oral Prednisolone or with an ABPA exacerbation. Further, the antifungal agents are used only for 16 weeks with benefits due to a lack of data. Itraconazole and Voriconazole function by decreasing the fungal load. They also control the antigenic stimulus and decrease inflammation. Itraconazole also impairs the metabolism of Prednisolone, thus raising plasma levels in corticosteroid-dependent ABPA patients. Voriconazole has better gastrointestinal (stomach and intestines) tolerance and dose availability. Recently, Posaconazole (a newer antifungal agent) has also been tried for ABPA treatment in CF patients.

3. Omalizumab: Omalizumab is an artificially created antibody (monoclonal antibody) aimed against IgE. Studies suggest that Omalizumab can be used in the treatment of ABPA in asthma patients. However, Omalizumab in ABPA patients with CF requires more clinical trials.

4. Supportive Measures: ABPA-related bronchiectasis patients should be prescribed nebulization for mucus clearance. Patients must avoid areas and environmental conditions with high fungal concentrations. It is especially true for decomposing organic matter and moist indoor environments. Also, antibiotic therapy is given to prevent or treat secondary bacterial infections.

Treatment of early disease with corticosteroids results in decreased sputum production, reduced bronchospasm (tightening of lung muscles), and lung infiltrate (accumulation of abnormal substances) resolution. Furthermore, it also reduces about 35 percent IgE levels within two months. With proper treatment, long-term control and a good prognosis for ABPA is possible.

The treatment for ABPA in patients with CF is similar to the routine regimens despite a lack of research. Also, all asthmatic and CF patients must be routinely screened for ABPA using A. fumigatus-specific IgE levels.

Conclusion

Studies on ABPA conclude that it is an underdiagnosed condition. ABPA underdiagnosis may be due to a lack of agreement regarding diagnosis and treatment. Studies report about five million cases of ABPA, and India accounts for approximately 1.4 million cases. Moreover, ABPA among asthmatic patients may be as high as 13 percent. Thus, clinicians must suspect ABPA while treating a patient with bronchial asthma. It is because early diagnosis and treatment can delay bronchiectasis onset. Hence, all patients with bronchial asthma must be screened for ABPA.