Experimental and Clinical Studies on Invasive Pulmonary Aspergillosis: pathophysiology, diagnosis and management

Abstract

Aspergillus is a saprofytic fungus that grows in humid environments on decaying organic matter. Its ability to adapt to a wide variability of conditions accounts for its worldwide distribution. Invasive aspergillosis (IA) is a disease characterised by invasion of normal tissue by Aspergillus organisms, resulting in significant tissue damage and necrosis. Most commonly, IA develops in patients with impaired host defence. Factors that predispose patients to develop IA include prolonged granulocytopenia, the development of graft-versus-host disease, immunosuppressive therapy, the use of adrenal corticosteroids, and the prolonged reduction of host defences associated with diseases such as chronic granulomatous disease. The most common route of infection is the inhalation of fungal spores, and therefore the majority of IA patients (± 90%) develop an invasive pulmonary aspergillosis (IPA). Other manifestations of the disease include IA of the paranasal sinuses, skin, wounds and eyes. There are several factors that make IPA a challenging fungal infection to manage: • IPA is currently a major direct or contributory cause of death in severely immunocompromised patients such as haemato-oncological patients receiving chemotherapy, and its incidence has shown a significant increase in the past few decades. • IPA is difficult to diagnose, especially in the early stages of the disease. • The treatment of IPA is suboptimal, with reported response rates below 55% in leukaemia- and bone marrow transplant patients.