Allergic bronchopulmonary aspergillosis

December 31, 2014

Synonyms

Overview

Allergic bronchopulmonary aspergillosis is a condition characterised by an exaggerated response of the immune system (ahypersensitivity response) to the fungus Aspergillus (most commonly Aspergillus fumigatus). It occurs most often in patients with asthma or cystic fibrosis. 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.

ABPA causes airway inflammation, leading to bronchiectasis—a condition marked by abnormal dilation of the airways. Left untreated, the immune system and fungal spores can damage sensitive lung tissues and lead to scarring.
The exact criteria for the diagnosis of ABPA are not agreed upon. Chest X-rays and CT scans, raised blood levels of IgE and eosinophils, immunological tests for Aspergillus together with sputum staining and sputum cultures can be useful. Treatment consists of corticosteroids andantifungal medications.

Symptoms

Wheezing (usually episodic in nature)
Bronchial hyperreactivity
Hemoptysis
Productive cough
Low-grade fever
Malaise
Weight loss
Shortness of breath
Asthma or cystic fibrosis
Pleuritic chest pain
Bronchiectasis; sputum production (often containing brown mucus plugs)
Abnormality of eosinophils

Causes

ABPA develops when the patient breathes air containing Aspergillus spores. These spores are found worldwide, especially around riverbanks, marshes, bogs, forests, and wherever there is wet or decaying vegetation. They are also found on wet paint, construction materials, and in air conditioning systems.

Prevention

ABPA is difficult to prevent because Aspergillus is a common fungus; it can be found in the saliva and sputum of most healthy individuals. Patients with ABPA can protect themselves somewhat by avoiding haystacks, compost piles, bogs, marshes, and other locations with wet or rotting vegetation; by avoiding construction sites or newly painted surfaces; and by having their air conditioners cleaned regularly. Some patients may be helped by air filtration systems for their bedrooms or offices.

Diagnosis

The exact criteria for the diagnosis of ABPA are not yet universally agreed upon, though working groups have proposed specific guidelines.

ABPA should be suspected in patients with a predisposing lung disease—most commonly asthma or cystic fibrosis—presenting with symptoms of recurrent infection such as fever, but who do not respond to conventional antibiotic therapy. Poorly-controlled asthma is a common finding, with a case series only finding 19% of ABPA patients with well-controlled asthma. Wheezing and hemoptysis (coughing up blood) are common features, and mucus plugging is seen in 31–69% of patients.

Blood tests and serology:
The first stage involves exposing the skin to Aspergillus fumigatus antigens; an immediate reaction is hallmark of ABPA. The test should be performed first by skin prick testing, and if negative followed with an intradermal injection. 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)).

Serum blood tests are an important marker of disease severity, and are also useful for the primary diagnosis of ABPA. When serum IgE is normal (and patients are not being treated by glucocorticoid medications), ABPA is excluded as the cause of symptoms. A raised IgE increases suspicion, though there is no universally accepted cut-off value. Values can be stated in international units (IU/mL) or ng/mL, where 1 IU is equal to 2.4 ng/mL. Since studies began documenting IgE levels in ABPA during the 1970s, various cut-offs between 833–1000 IU/mL have been employed to both exclude ABPA and to warrant further serological testing. Current consensus is that a cut-off of 1000 IU/mL should be employed, as lower values are encountered in SAFS and asthmatic sensitization.

IgG antibody precipitin testing from serum is useful, as positive results are found in between 69–90% of patients, though also in 10% of asthmatics with and without SAFS. Therefore, it must be used in conjunction with other tests. Various forms exist, including enzyme-linked immunosorbent assay (ELISA) and fluorescent enzyme immunoassay (FEIA). Both are more sensitive than conventional counterimmunoelectrophoresis. IgG may not be entirely specific for ABPA, as high levels are also found in chronic pulmonary aspergillosis (CPA) alongside more severe radiological findings.

Until recently, peripheral eosinophilia (high eosinophil counts) was considered partly indicative of ABPA. More recent studies show that only 40% of ABPA sufferers present with eosinophilia, and hence a low eosinophil count does not necessary exclude ABPA; for example patients undergoing steroid therapy have lower eosinophil counts.

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.

When utilising high resolution CT scans, there can be 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 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 considerable extension to the periphery of the lung.

Mucoid impaction of the upper and lower airways is a common finding. Plugs are hypodense but appear on CT with high attenuation in up to 20% of patients. Where present it is a strong diagnostic factor of ABPA and distinguishes symptoms from other causes of bronchiectasis.[8]

CT scans may more rarely reveal mosaic-appearance attenuation, centrilobular nodules, tree-in-bud opacities and pleuropulmonary fibrosis (a finding consistent with CPA, a disease with ABPA as a known precursor). Rarely other manifestations can be seen on CT scans, including military nodular opacities, perihilar opacities (that mimic hilar lymphadenopathy), pleural effusions and pulmonary masses. Cavitation and aspergilloma are rarer findings, not exceeding 20% of patients, and likely represent a shift from ABPA to CPA if accompanied by pleural thickening or fibrocavitary disease.

Culture:
Culturing fungi from sputum is a supportive test in the diagnosis of ABPA, but is not 100% specific for ABPA as A. fumigatus is ubiquitous and commonly isolated from lung expectorant in other diseases. Nevertheless, between 40–60% of patients do have positive cultures depending on the number of samples taken.

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. This would replace the current gold standard staging protocol devised by Patterson and colleagues. Stage 0 would represent an asymptomatic form of ABPA, with controlled asthma but still fulfilling the fundamental diagnostic requirements of a positive skin test with elevated total IgE (>1000 IU/mL). Stage 6 is an advanced ABPA, with the presence of type II respiratory failure or pulmonary heart disease, with radiological evidence of severe fibrosis consistent with ABPA on a high-resolution CT scan. It must be diagnosed after excluding the other, reversible causes of acute respiratory failure.

Prognosis

Most patients with ABPA respond well to corticosteroid treatment. Others have a chronic course with gradual improvement over time. The best indicator of a good prognosis is a long-term fall in the patient's IgE level. Patients with lung complications from ABPA may develop severe airway obstruction.

Treatment

ABPA is usually treated with prednisone (Meticorten) or other corticosteroids taken by mouth, and with bronchodilators. Antifungal drugs are not used to treat ABPA because it is caused by an allergic reaction to Aspergillus rather than by direct infection of tissue.