Aspergillus fumigatus - Respiratory infections

Aspergillus fumigatus

Definition

There are essentially three patterns of lung disease caused by Aspergillus infection: Allergic bronchopulmonary aspergillosis (ABPA), aspergilloma and invasive aspergillosis.

Aetiology

It is a filamentous fungus, the spores (5 µm in diameter) are ubiquitously present in the atmosphere. It rarely causes disease. The pattern of disease that arises depends on the degree of tissue invasiveness, the dose inhaled and the level of the host’s defence.

Allergic bronchopulmonary aspergillosis (ABPA)

Pathophysiology

This results from Types I and III hypersensitivity reactions to persistent airway infection with the organism in susceptible (atopic) individuals.

·        i Initially it causes bronchospasm which commonly presents as asthma.

·    Recurrent episodes of eosinophilic pneumonia occur due to obstruction of the lumen, with the expectoration of firm sputum plugs containing the fungal mycelium.

·    Chronic infection and inflammation leads to irreversible dilatation of the bronchi (classically proximal bronchiectasis).

·    If left untreated progressive pulmonary fibrosis may develop, usually in the upper zones.

Clinical features

ABPA presents as worsening of asthma symptoms with episodic wheeze and cough productive of mucus plugs. There may be intermittent fever and malaise. A large mucus plug may obstruct a bronchus causing lung collapse.

Investigation

The peripheral blood eosinophil count is raised, and sputum may show eosinophilia and mycelia. Eosinophilic pneumonia causes transient lung shadows on chest X-ray. Precipitating antibodies are present in serum. Hypersensitivity is usually confirmed by skin-prick testing. Lung function testing confirms reversible obstruction in all cases, and may show reduced lung volumes in cases where there is chronic fibrosis.

Management

Generally it is not possible to eradicate the fungus. Itraconazole has been shown to modify the immunologic activation and improves clinical outcome, at least over the period of 16 weeks. Oral corticosteroids are used to suppress inflammation until clinically and radiographically returned to normal. Maintenance steroid therapy may be required subsequently. The asthmatic component is treated as per asthma guidelines.

Aspergilloma

This results from Aspergillus growing within an area of previously damaged lung such as an old tuberculous cavity (sometimes called a mycetoma). These are usually asymptomatic but occasionally may cause massive haemoptysis and require resection. Antifungal treatment is rarely effective.

Investigation

Seen on X-ray as a round lesion with an air ‘halo’ above it. The fungal mycelium may be seen in sputum and the chronic antigenic stimulation gives rise to serum precipitating antibody.

Invasive aspergillosis

In immunosuppressed individuals with a low granulocyte count, the organism may proliferate causing a severe pneumonia, causing necrosis and infarction of the lung. The organisms are present as masses of hyphae invading lung tissue and often involving vessel walls. Invasive aspergillosis presents as a pneumonia or septicaemia in the immunocompromised. Systemic invasive aspergillosis may manifest as meningitis, cerebral abscess or lesions in bone or liver.

Investigation

Invasive aspergillosis can only by diagnosed by lung biopsy.

Management

Invasive aspergillosis is treated with intravenous amphotericin B (often requiring liposomal preparations due to renal toxicity), often combined with flucytosine. Itraconazole and voriconazole have been used more recently but current studies comparing efficacy with amphotericin B have yet to prove definitive.