Allergic Bronchopulmonary Aspergillosis
Disease Details
Family Health Simplified
- Description
- Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to the fungus Aspergillus, leading to inflammation and damage in the lungs.
- Type
- Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to the Aspergillus fungus. It is not a genetic disorder and thus does not have a type of genetic transmission. It primarily affects individuals with asthma or cystic fibrosis.
- Signs And Symptoms
- Almost all patients have clinically diagnosed asthma, and present with wheezing (usually episodic in nature), coughing, shortness of breath and exercise intolerance (especially in patients with cystic fibrosis). Moderate and severe cases have symptoms suggestive of bronchiectasis, in particular thick sputum production (often containing brown mucus plugs), as well as symptoms mirroring recurrent infection such as pleuritic chest pain and fever. Patients with asthma and symptoms of ongoing infection, who do not respond to antibiotic treatment, should be suspected of ABPA.
- Prognosis
- Allergic bronchopulmonary aspergillosis (ABPA) is a condition that can be managed effectively with proper treatment. The prognosis for individuals with ABPA largely depends on early diagnosis and adherence to treatment. With appropriate medical management, including corticosteroids and antifungal medications, many patients experience significant improvement and can maintain good lung function. However, if left untreated or if the disease is poorly controlled, ABPA can lead to chronic lung damage and complications such as bronchiectasis, pulmonary fibrosis, or respiratory failure. Regular follow-up with a healthcare provider is essential for monitoring and managing the condition effectively.
- Onset
- Allergic bronchopulmonary aspergillosis (ABPA) typically has a gradual onset, often presenting over weeks to months. It is more common in individuals with asthma or cystic fibrosis. The symptoms may include wheezing, coughing, shortness of breath, and recurrent episodes of bronchitis or pneumonia.
- Prevalence
- The exact prevalence of allergic bronchopulmonary aspergillosis (ABPA) is not well-defined. However, it is estimated to affect approximately 1-2% of people with asthma and 2-15% of those with cystic fibrosis.
- Epidemiology
- There are limited national and international studies into the burden of ABPA, made more difficult by a non-standardized diagnostic criteria. Estimates of between 0.5 and 3.5% have been made for ABPA burden in asthma, and 1–17.7% in CF. Five national cohorts, detecting ABPA prevalence in asthma (based on GINA estimates), were used in a recent meta-analysis to produce an estimate of the global burden of ABPA complicating asthma. From 193 million people with asthma worldwide, ABPA prevalence in asthma is estimated to be between 1.35 and 6.77 million people, using 0.7–3.5% attrition rates. A compromise at 2.5% attrition has also been proposed, placing global burden at around 4.8 million people affected. The Eastern Mediterranean region had the lowest estimated prevalence, with a predicted case burden of 351,000; collectively, the Americas had the highest predicted burden at 1,461,000 cases. These are likely underestimates of total prevalence, given the exclusion of CF patients and children from the study, as well as diagnostic testing being limited in less developed regions.
- Intractability
- Allergic bronchopulmonary aspergillosis (ABPA) is a condition that can be challenging to manage but is not considered intractable. With appropriate treatment, which often includes corticosteroids and antifungal medications, many patients can achieve symptom control and prevent serious complications. However, it requires ongoing management and close monitoring to prevent exacerbations and maintain lung function.
- Disease Severity
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Allergic bronchopulmonary aspergillosis (ABPA) severity can vary among individuals. It ranges from mild to severe:
1. **Mild:** Characterized by occasional wheezing, mild cough, and minimal impact on daily activities. Generally, lung function remains close to normal.
2. **Moderate:** More frequent respiratory symptoms, including persistent cough, wheezing, and shortness of breath. Lung function may show a moderate decline, and there may be episodes of exacerbations requiring medical attention.
3. **Severe:** Persistent symptoms with significant impairment in daily activities. Lung function is often markedly reduced, and there may be complications such as bronchiectasis or fibrosis. Frequent exacerbations and hospitalizations are common at this stage.
Management usually involves corticosteroids to control inflammation and antifungal medications to reduce fungal burden. The severity of the disease necessitates ongoing monitoring and adjustments in treatment. - Healthcare Professionals
- Disease Ontology ID - DOID:13166
- Pathophysiology
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Aspergillus spores are small (2–3 μm in diameter) and can penetrate deep into the respiratory system to the alveolar level. In healthy people, innate and adaptive immune responses are triggered by various immune cells (notably neutrophils, resident alveolar macrophages and dendritic cells) drawn to the site of infection by numerous inflammatory cytokines and neutrophilic attractants (such as CXCR2 receptor ligands). In this situation, mucociliary clearance is initiated and spores are successfully phagocytosed, clearing the infection from the host.In people with predisposing lung diseases—such as persistent asthma or cystic fibrosis (or rarer diseases such as chronic granulomatous disease or Hyper-IgE syndrome)—several factors lead to an increased risk of ABPA. These include immune factors (such as atopy or immunogenic HLA-restricted phenotypes), as well as genetic factors (such as CFTR gene mutations in both asthmatics and cystic fibrosis patients and a ZNF77 mutation resulting in a premature stop codon in asthmatics and ABPA patients). By allowing Aspergillus spores to persist in pulmonary tissues, it permits successful germination which leads to hyphae growing in mucus plugs.
There are hypersensitivity responses, both a type I response (atopic, with formation of immunoglobulin E, or IgE) and a type III hypersensitivity response (with formation of immunoglobulin G, or IgG). The reaction of IgE with Aspergillus antigens results in mast cell degranulation with bronchoconstriction and increased capillary permeability. Immune complexes (a type III reaction) and inflammatory cells are deposited within the mucous membranes of the airways, leading to necrosis (tissue death) and eosinophilic infiltration. Type 2 T helper cells appear to play an important role in ABPA due to an increased sensitivity to interleukin (IL) 4 and IL-5. These cytokines up-regulate mast cell degranulation, exacerbating respiratory decline.Aspergillus also uses a number of factors to continue evading host responses, notably the use of proteolytic enzymes that interrupt IgG antibodies aimed towards it. Another important feature is its ability to interact and integrate with epithelial surfaces, which results in massive pro-inflammatory counter-response by the immune system involving IL-6, IL-8 and MCP-1 (a CCL2 receptor ligand). Proteases released by both the fungus and neutrophils induce further injury to the respiratory epithelium, leading to initiation of repair mechanisms (such as an influx of serum and extracellular matrix (ECM) proteins) at the site of infection. Aspergillus spores and hyphae can interact with ECM proteins, and it is hypothesised that this process facilitates the binding of spores to damaged respiratory sites.As concentrations of Aspergillus proteases increase, the immunological effect switches from pro-inflammatory to inhibitory, and further reduces phagocytic ability to clear Aspergillus. Ultimately, repeated acute episodes lead to wider scale damage of pulmonary structures (parenchyma) and function via irreversible lung remodelling. Left untreated, this manifests as progressive bronchiectasis and pulmonary fibrosis that is often seen in the upper lobes, and can give rise to a similar radiological appearance to that produced by tuberculosis. - Carrier Status
- Allergic bronchopulmonary aspergillosis (ABPA) does not have a carrier status as it is not a genetic disorder. It is an allergic reaction to the fungus Aspergillus, often occurring in individuals with asthma or cystic fibrosis. Genetic factors may influence susceptibility, but one does not "carry" ABPA like a genetic trait.
- Mechanism
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Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to the fungus Aspergillus, typically Aspergillus fumigatus, which colonizes the airways but does not invade lung tissues.
**Mechanism:**
1. **Immune Response**: ABPA occurs primarily in individuals with asthma or cystic fibrosis. In these susceptible individuals, inhaled Aspergillus spores invoke a hypersensitivity reaction.
2. **Immune Activation**: The immune system treats the fungus as a threat, activating a Type I (IgE-mediated) hypersensitivity response and a Type III (immune complex-mediated) hypersensitivity response.
3. **Inflammation**: This leads to inflammation of the bronchial walls, mucus production, bronchiectasis, and airway obstruction.
4. **Cytokine Release**: The immune response also involves the release of various cytokines and chemokines, which perpetuate the inflammatory response and contribute to the clinical manifestations of ABPA.
**Molecular Mechanisms:**
1. **IgE Production**: Upon exposure to Aspergillus antigens, B cells produce IgE antibodies in higher quantities. These IgE antibodies bind to Fc receptors on the surface of mast cells and basophils.
2. **Mast Cell Activation**: Re-exposure to Aspergillus antigens leads to cross-linking of IgE on these cells, causing degranulation and release of histamine and other inflammatory mediators.
3. **T-helper Cells**: Th2 cells are heavily involved, producing interleukins like IL-4, IL-5, and IL-13, which promote IgE production and eosinophil activation.
4. **Eosinophil Activation**: Eosinophils, activated by IL-5, infiltrate the lung tissues and release toxic granules contributing to tissue damage and airway inflammation.
5. **TGF-β and Fibrosis**: Chronic inflammation can lead to cytokine-mediated fibrosis via the action of transforming growth factor-beta (TGF-β), leading to structural changes in the lung.
These processes collectively result in the characteristic clinical and pathological features of ABPA, including bronchial damage, mucus hypersecretion, and fibrosis. - Treatment
- Underlying disease must be controlled to prevent exacerbation and worsening of ABPA, and in most patients this consists of managing their asthma or CF. Any other co-morbidities, such as sinusitis or rhinitis, should also be addressed.Hypersensitivity mechanisms, as described above, contribute to progression of the disease over time and, when left untreated, result in extensive fibrosis of lung tissue. To reduce this, corticosteroid therapy is the mainstay of treatment (for example with prednisone); however, studies involving corticosteroids in ABPA are limited by small cohorts and are often not double-blinded. Despite this, there is evidence that acute-onset ABPA is improved by corticosteroid treatment as it reduces episodes of consolidation. There are challenges involved in long-term therapy with corticosteroids—which can induce severe immune dysfunction when used chronically, as well as metabolic disorders—and approaches have been developed to manage ABPA alongside potential adverse effects from corticosteroids.The most commonly described technique, known as sparing, involves using an antifungal agent to clear spores from airways adjacent to corticosteroid therapy. The antifungal aspect aims to reduce fungal causes of bronchial inflammation, while also minimising the dose of corticosteroid required to reduce the immune system's input to disease progression. The strongest evidence (double-blinded, randomized, placebo-controlled trials) is for itraconazole twice daily for four months, which resulted in significant clinical improvement compared to placebo, and was mirrored in CF patients. Using itraconazole appears to outweigh the risk from long-term and high-dose prednisone. Newer triazole drugs—such as posaconazole or voriconazole—have not yet been studied in-depth through clinical trials in this context.While the benefits of using corticosteroids in the short term are notable, and improve quality of life scores, there are cases of ABPA converting to invasive aspergillosis while undergoing corticosteroid treatment. Furthermore, in concurrent use with itraconazole, there is potential for drug interaction and the induction of Cushing syndrome in rare instances. Metabolic disorders, such as diabetes mellitus and osteoporosis, can also be induced.To mitigate these risks, corticosteroid doses are decreased biweekly assuming no further progression of disease after each reduction. When no exacerbations from the disease are seen within three months after discontinuing corticosteroids, the patient is considered to be in complete remission. The exception to this rule is patients who are diagnosed with advanced ABPA; in this case, removing corticosteroids almost always results in exacerbation and these patients are continued on low-dose corticosteroids (preferably on an alternate-day schedule).Serum IgE can be used to guide treatment, and levels are checked every 6–8 weeks after steroid treatment commences, followed by every 8 weeks for one year. This allows for a determination of baseline IgE levels, though it's important to note that most patients do not entirely reduce IgE levels to baseline. Chest X-ray or CT scans are performed after 1–2 months of treatment to ensure infiltrates are resolving.
- Compassionate Use Treatment
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Compassionate use and off-label or experimental treatments for allergic bronchopulmonary aspergillosis (ABPA) may include:
1. **Biologic Agents:**
- **Omalizumab (Xolair):** An anti-IgE monoclonal antibody primarily used for severe asthma but has shown some efficacy in treating ABPA.
2. **Antifungal Agents:**
- **Itraconazole or Voriconazole:** These antifungal medications may be used off-label to reduce the fungal burden in the lungs.
These treatments are usually considered when standard therapies, such as corticosteroids and traditional antifungals, are inadequate or cause significant side effects. - Lifestyle Recommendations
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For managing allergic bronchopulmonary aspergillosis (ABPA), consider these lifestyle recommendations:
1. **Avoid Mold Exposure**: Reduce exposure to Aspergillus and other molds by keeping living areas dry and well-ventilated. Use dehumidifiers, especially in damp areas like basements.
2. **Follow Medical Treatments**: Adhere strictly to prescribed treatments such as corticosteroids or antifungal medications.
3. **Regular Monitoring**: Attend regular check-ups with your healthcare provider to monitor lung function and adjust treatments as necessary.
4. **Healthy Diet and Hydration**: Maintain a balanced diet to support the immune system and stay hydrated to help keep mucus thin.
5. **Exercise**: Engage in moderate exercise as tolerated to improve overall lung function, but avoid environments that could expose you to mold spores.
6. **Avoid Smoking**: Do not smoke and avoid secondhand smoke since it can exacerbate respiratory symptoms.
7. **Manage Allergies**: Take steps to control other allergies, such as using air purifiers and avoiding known allergens.
8. **Promptly Address Respiratory Infections**: Seek medical attention for respiratory infections to prevent complications.
By following these recommendations, individuals can better manage ABPA and minimize the impact on their daily lives. - Medication
- Allergic bronchopulmonary aspergillosis (ABPA) is typically treated with oral corticosteroids, such as prednisone, to reduce inflammation. Antifungal medications like itraconazole or voriconazole may also be used to decrease the fungal burden. In some cases, biologics such as omalizumab (an anti-IgE monoclonal antibody) are considered for patients who do not respond to standard treatments. Regular monitoring and follow-up are essential to manage the condition effectively.
- Repurposable Drugs
- For Allergic Bronchopulmonary Aspergillosis (ABPA), repurposable drugs include antifungal agents such as itraconazole and corticosteroids like prednisone. These medications can help manage the inflammatory response and fungal load in patients.
- Metabolites
- For allergic bronchopulmonary aspergillosis (ABPA), specific metabolites associated with the disease are not typically a primary focus. Instead, the condition is mainly characterized by an allergic reaction to the fungus Aspergillus, leading to inflammation in the lungs. While individual metabolites are not commonly highlighted in relation to ABPA, this disease involves complex immune responses that might alter various metabolic pathways. Accurate diagnosis and treatment require clinical evaluation and may involve imaging and laboratory tests rather than direct assessment of metabolites.
- Nutraceuticals
- Nutraceuticals do not have a well-documented role in the treatment or management of Allergic Bronchopulmonary Aspergillosis (ABPA). The condition is primarily managed with corticosteroids to reduce inflammation and antifungal treatments to control Aspergillus colonization. Nutritional supplements or alternative therapies are not standard treatments for ABPA and should be considered only with professional medical guidance.
- Peptides
- Allergic bronchopulmonary aspergillosis (ABPA) does not have a defined treatment involving specific peptides or nanotechnology. The management primarily includes corticosteroids to reduce inflammation and antifungal agents like itraconazole to reduce fungal load. Research is ongoing to explore advanced therapeutic options including immunotherapy and novel drug delivery systems, but these are not yet standard treatments.