Invasive aspergillosis in COPD

Patients with COPD can, as previously blogged, suffer a range of illnesses caused by the ubiquitous fungus, Aspergillus fumigatus. Of all of these, chronic invasive aspergillosis is the entity I have seen least. Until the last few days.

When I first began to get a handle on aspergillus disease, I thought that invasive aspergillosis was the domain of bone-marrow transplant recipients. It turns out that patients with COPD (particularly emphysema) develop a more indolent form of the disease which looks radiologically pretty similar. However, the prevalence of this condition amongst patients with COPD is unknown. Mortality rates are quoted as between 72 and 95%. And they are not falling, in contrast with mortality rates amongst bone-marrow transplant recipients with invasive aspergillosis..

We should consider this diagnosis in all patients with COPD who have progressive lung infiltrates, or pneumonia which fails to resolve as it should after standard antibiotics.

I have just read a helpful review article in a COPD journal on this topic, and have been reminded that aspergillus spores are tiny - about 2-3microns. When inhaled they end up in the furthest reaches of the respiratory tree - the alveoli. There they can germinate into hyphae which - unless they are mopped up by polymorphonuclear cells - can become invasive.

People with COPD are prone to invasive aspergillosis becuause:
- they are often malnourished;
- they have impaired airway ciliary function;
- consumption of broad spectrum antibiotics may have altered the airway microflora to benefit the fungus;
- aspergillus may be able to grow in a biofilm in these patients, like pseudomonas and haemophilus;
- use of corticosteroids has impaired neutrophil function and altered the distribution of neutrophils.

Diagnosis of invasive aspergillosis can be regarded as either proven, probable or possible. To prove the diagnosis requires demonstration of hyphae in tissue - ie a biopsy, which might carry with it considerable morbidity in these patients. A probable diagnosis can be based on a coalescence of appropriate host, clinical and mycological factors (eg the patient is in an at risk group with the right presentation, the CT scan looks right and the fungus is there - in repeated culture or in a bronchoscopy specimen). It is reasonable to embark on treatment based on a probable - rather than proven - diagnosis (sounding very similar here to the 'clinical conference consensus' vs 'pathology gold standard' diagnostic conversation in fibrosing lung disease).

Voriconazole should probably be the first line treatment of this condition. In Australia, however, Voriconazole is available on the PBS only for patients with invasive aspergillosis who have not tolerated Amphotericin B. These criteria were not drawn up for the COPD patients with this diagnosis who are generally ambulatory, slowly losing weight, progressively breathless but at home. Rather they were established with the sick bone-marrow transplant patient in mind. It makes far more sense to initiate the ambulatory COPD patients on oral Voriconazole than to admit them to hospital for a protracted course of amphotericin B. We are, however, going to have to do a lot more research with these patients even to demonstrate that they are a significant population before that realisation trickles through to the PBS.

Andrew