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Aspergilloma

The vast majority of fungal balls in the lungs are due to Aspergillus with rare cases due to Pseudallescheria boydii or Mucorales. This discussion will focus on aspergillomas. The risk of developing an aspergilloma within a cavity of =2cm in diameter is 15-20% Approximately 10% of aspergillomas resolve spontaneously making uncontrolled observations in small numbers of patients difficult to interpret. Distinguishing chronic invasive aspergillosis from genuine aspergillomas is important because the former require systemic antifungal therapy. In the recent report of aspergillomas in AIDS (Addrizzo-Harris et al, 1997), progression of aspergillomas over time was seen with considerable morbidity and some mortality. This probably reflects invasion of cavity walls by Aspergillus rather than simple colonisation of Pneumocystis cavities by Aspergillus.

Several therapeutic strategies have been used in treating aspergillomas. Systemic antifungal therapy with ketoconazole is ineffective. Itraconazole 200mg daily is of marginal symptomatic benefit and little radiological benefit (Campbell et al, 1991). This probably reflects, at least in part, the lack of delivery of drug to the fungus ball and the chronic fibrotic/inflammatory changes in the surrounding lung. In addition, a dose of 400mg daily would have been more appropriate.

Many patients with aspergillomas are corticosteroid-dependent because of other pulmonary or systemic diseases. Steroids in patients with aspergillomas carry a slightly greater risk of the development of chronic invasive aspergillosis. Whether systemic antifungal therapy would prevent this is unclear.

Instillation of nystatin and amphotericin B has been tried with some benefit in some cases (especially with amphotericin B). Early data consisted of single instillations through a metal needle. Recently flexible plastic catheters have been used. Repeated instillations are usually necessary (in one study daily for 15 days (Lee, 1993)). Communication between the cavity and the airways is usual so the instilled agent usually leaks into the airways. Repeated instillations are labour intensive and not very effective for complex and/or bilateral aspergillomas. Recently described is the incorporation of amphotericin B in gelatin or glycerin that solidifies at 37^oC (Giron, et al, 1993; Munk et al, 1993). This type of approach deserves further evaluation. Details of how to make up this preparation is given below.

Surgery is often appropriate for patients with haemoptysis. Surgical removal of aspergillomas is fraught with difficulty because of the very vascular, adherent pleura and because the remaining chest cavity may become infected with Aspergillus (Daly et al, 1986). The table shows the high risks of such an approach in patients with complex aspergillomas. Surgical removal of pleural aspergillomas and thoracoplasty is also prone to many complications and should be avoided if possible (Massard et al, 1992). In addition, many patients have underlying respiratory insufficiency and removal of a lobe of the lung would leave them unacceptably breathless. However, in those patients with major haemoptysis and simple aspergillomas, surgery offers an 84% five year survival compared with a 41% survival with conservative therapy (Jewkes, 1983). More recent series have substantially lower mortality rates, particularly if patients are selected carefully (El-Oakley-R et al, 1997; Chen,et al, 1997).

In patients with haemoptysis who are not fit to undergo surgery , embolisation may be appropriate. In most instances of haemoptysis abnormal and novel vascular connections to the systemic circulation are implicated. Usually this is the bronchial circulation but it may be any of the other arteries supplying the chest, e.g. internal or external mammary arteries etc. Aspergillomas also lead to an extensive network of small vessels. Several abnormal connections may exist in a single patient. The objective of embolisation is to permanently occlude these vessels. Patients with a communication between an intercostal and the anterior spinal artery can only be embolised safely if the catheter is introduced well past the anterior spinal artery. These patients require a skilled interventional radiologist for these difficult procedures.

If surgery is precluded, or the aspergilloma is complex, worsening haemoptysis is an appropriate indication for embolisation. The patient has to be able to lie still for 3-4 hours during the procedure which can be a major limiting factor. Each case has to be assessed on its merits. Depending on the radiologist, approximately 50-70% of embolisation procedures are successful (Remy & Jardin, 1990). However a relapse rate of 50% is typical.

Many patients with aspergillomas are elderly have significant underlying disease, including severe respiratory compromise in addition to the aspergilloma. Thus, many patients die with an aspergilloma rather than of it. However many die directly as a result of complications, e.g. haemoptysis or surgery and in other cases the fibrosis and additional respiratory embarrassment of the aspergilloma contributes to death (Jewkes et al, 1983).

Mortality from aspergilloma in 85 patients # (Jewkes, 1983)  

# outcome over 5 years or until death in 85% of cases studied

* evacuation of aspergilloma and instillation of antifungal agents (44% mortality) in contrast to pulmonary resection (7% mortality).

David W. Denning FRCP FRCPath FIDSA FMedSci
Professor of Medicine and Medical Mycology
Director, National Aspergillosis Centre
Education and Research Centre
University Hospital of South Manchester (Wythenshawe Hospital)
Southmoor Road
Manchester M23 9LT UK