Allergic bronchopulmonary aspergillosis
Allergic bronchopulmonary aspergillosis | |
---|---|
Other names | ABPA, Hinson-Pepys disease. |
antifungal medications.[2] | |
Medication | Prednisolone and Itraconazole.[2] |
Frequency | 1–15% of cystic fibrosis patients and 2.5% of adults with severe asthma.[3] |
Allergic bronchopulmonary aspergillosis (ABPA) is a condition characterised by an exaggerated response of the immune system (a hypersensitivity response) to the fungus Aspergillus (most commonly Aspergillus fumigatus). It occurs most often in people with asthma or cystic fibrosis.[1] Aspergillus spores are ubiquitous in soil and are commonly found in the sputum of healthy individuals. A. fumigatus is responsible for a spectrum of lung diseases known as aspergilloses.[4]
ABPA causes
The exact criteria for the diagnosis of ABPA are not agreed upon.
Signs and symptoms
Almost all patients have clinically diagnosed asthma,[1] and present with wheezing (usually episodic in nature), coughing, shortness of breath and exercise intolerance (especially in patients with cystic fibrosis).[1][6] 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.[1]
Pathophysiology
Aspergillus
In people with predisposing lung diseases—such as persistent
There are
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.[10][21]
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 (
Diagnosis
The exact criteria for the diagnosis of ABPA are not yet universally agreed upon, though working groups have proposed specific guidelines.[11][23] Minimal criteria include five factors: the presence of asthma and/or cystic fibrosis, a positive skin test to Aspergillus sp., total serum IgE > 416 IU/mL (or kU/L), an increased Aspergillus species–specific IgE and IgG antibodies, and the presence of infiltrates on a chest X-ray.[24][25]
ABPA should be suspected in patients with a predisposing
Blood tests and serology
The first stage involves exposing the skin to Aspergillus fumigatus antigens; an immediate reaction is hallmark of ABPA.[26] The test should be performed first by skin prick testing, and if negative followed with an intradermal injection. The overall sensitivity of the procedure is around 90%, though up to 40% of asthmatic patients without ABPA can still show some sensitivity to Aspergillus antigens (a phenomenon likely linked to a less severe form of ABPA termed severe asthma with fungal sensitization (SAFS)).[11]
Serum blood tests are an important
IgG antibody
Until recently, peripheral eosinophilia (high eosinophil counts) was considered partly indicative of ABPA. More recent studies show that only 40% of people with ABPA present with eosinophilia, and hence a low eosinophil count does not necessarily exclude ABPA; for example patients undergoing steroid therapy have lower eosinophil counts.[11]
Radiological investigation
Consolidation and mucoid impaction are the most commonly described radiological features described in ABPA literature, though much of the evidence for consolidation comes from before the development of computed tomography (CT) scans. Tramline shadowing, finger-in-glove opacities and 'toothpaste shadows' are also prevalent findings.[28]
When using high-resolution CT scans, there can be a better assessment of the distribution and pattern of bronchiectasis within the lungs, and hence this is the tool of choice in the radiological diagnosis of ABPA. Central (confined to medial two-thirds of the medial half of the lung) bronchiectasis that peripherally tapers bronchi is considered a requirement for ABPA pathophysiology, though in up to 43% of cases there is a considerable extension to the periphery of the lung.[1]
Mucoid impaction of the upper and lower airways is a common finding.
CT scans may more rarely reveal mosaic-appearance
Culture
Staging
New criteria by the ABPA Complicated Asthma ISHAM Working Group suggests a 6-stage criteria for the diagnosis of ABPA, though this is yet to be formalised into official guidelines.
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.[30]
The most commonly described technique, known as sparing, involves using an
While the benefits of using corticosteroids in the short term are notable, and improve
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).[30][31]
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.
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,[32][33] and 1–17.7% in CF.[32][34] Five national cohorts, detecting ABPA prevalence in asthma (based on GINA estimates),[35] 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.[33]
References
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