Pulmonary aspergillosis: Clinical presentation, diagnostic tests, management and complications

Department of Medicine, Roswell Park Cancer Institute, School of Medicine and Biomedical Sciences, University of Buffalo, Buffalo, New York 14263, USA.
Current opinion in pulmonary medicine (Impact Factor: 2.76). 05/2010; 16(3):242-50. DOI: 10.1097/MCP.0b013e328337d6de
Source: PubMed


When functioning properly, the immune system recognizes inhaled fungi and controls their growth, while avoiding injurious inflammation and allergy. 'Aspergillosis' represents a spectrum of clinical diseases resulting from impaired or excessive immune responses. Invasive aspergillosis is principally disease of severely immunocompromised patients, whereas allergic forms of aspergillosis result from an excessive inflammatory response to hyphae colonizing the sinopulmonary tract. We will review insights gained in host defense against Aspergillus species and the immunopathogenesis of Aspergillus-related diseases as well as important advances made in fungal diagnostics and antifungal therapy.
Important advances have been made in diagnosis of invasive aspergillosis and in antifungal agents. Voriconazole was superior to amphotericin B deoxycholate as primary therapy for invasive aspergillosis. There is significant interest in combination antifungal therapy for invasive aspergillosis. Fungal genomics offers a powerful opportunity to gain knowledge about fungal virulence factors that can be targets for drug development. In addition, new insights have been gained regarding host defense against Aspergillus species that may be exploited therapeutically.
We have gained substantial knowledge regarding how the immune system recognizes inhaled fungi and calibrates the inflammatory response. There has also been substantial progress in tools to diagnose aspergillosis and in antifungal therapeutics. Future progress will likely involve the development of more refined diagnostic tools, new classes of antifungal agents, and greater knowledge of pathogen and host factors that predispose to aspergillosis.

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    • "This group includes individuals with hematological malignancies, those with genetic immunodeficiencies, patients infected with HIV, and cancer patients treated with chemotherapy [1–6]. This immunodepressed population is currently increasing [7] due to the higher number of organ transplants performed, immunosuppressive and myeloablative therapies for autoimmune and neoplastic diseases, and the HIV pandemic [1,7–9]. The mortality rate resulting from A. fumigatus infections in immunodepressed patients ranges from 40% to 90% [7,9–12]. "
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    ABSTRACT: Aspergillus fumigatus is the causative agent of invasive aspergillosis, leading to infection-related mortality in immunocompromised patients. We previously showed that the conserved and unique-to-fungi veA gene affects different cell processes such as morphological development, gliotoxin biosynthesis and protease activity, suggesting a global regulatory effect on the genome of this medically relevant fungus. In this study, RNA sequencing analysis revealed that veA controls the expression of hundreds of genes in A. fumigatus, including those comprising more than a dozen known secondary metabolite gene clusters. Chemical analysis confirmed that veA controls the synthesis of other secondary metabolites in this organism in addition to gliotoxin. Among the secondary metabolite gene clusters regulated by veA is the elusive but recently identified gene cluster responsible for the biosynthesis of fumagillin, a meroterpenoid known for its anti-angiogenic activity by binding to human methionine aminopeptidase 2. The fumagillin gene cluster contains a veA-dependent regulatory gene, fumR (Afu8g00420), encoding a putative C6 type transcription factor. Deletion of fumR results in silencing of the gene cluster and elimination of fumagillin biosynthesis. We found expression of fumR to also be dependent on laeA, a gene encoding another component of the fungal velvet complex. The results in this study argue that veA is a global regulator of secondary metabolism in A. fumigatus, and that veA may be a conduit via which chemical development is coupled to morphological development and other cellular processes.
    Preview · Article · Oct 2013 · PLoS ONE
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    • "Fungal infections range from superficial to invasive infections. For example, invasive aspergillosis is not only a life-threatening infection in neutropenic patients but also occurs in patients with chronic pulmonary diseases and/or undergoing corticosteroid treatment (Sherif & Segal, 2010; Thornton, 2010). Exposure to mold can cause allergic reactions in fungal-sensitive individuals, who account for about 10% of the total population and 40% of patients with asthma (Burge, 2001; Mendell et al., 2011). "
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    ABSTRACT: Abstract Indoor fungal contamination has been associated with a wide range of adverse health effects, including infectious diseases, toxic effects and allergies. The diversity of fungi contributes to the complex role that they play in indoor environments and human diseases. Molds have a major impact on public health, and can cause different consequences in hospitals, homes and workplaces. This review presents the methods used to assess fungal contamination in these various environments, and discusses advantages and disadvantages for each method in consideration with different health risks. Air, dust and surface sampling strategies are compared, as well as the limits of various methods are used to detect and quantify fungal particles and fungal compounds. In addition to conventional microscopic and culture approaches, more recent chemical, immunoassay and polymerase chain reaction (PCR)-based methods are described. This article also identifies common needs for future multidisciplinary research and development projects in this field, with specific interests on viable fungi and fungal fragment detections. The determination of fungal load and the detection of species in environmental samples greatly depend on the strategy of sampling and analysis. Quantitative PCR was found useful to identify associations between specific fungi and common diseases. The next-generation sequencing methods may afford new perspectives in this area.
    Full-text · Article · Apr 2013 · Critical Reviews in Microbiology
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    • "Invasive pulmonary aspergillosis (IPA) remains a significant cause of morbidity and mortality in immunocompromised patients (Sherif & Segal, 2010). Timely and accurate diagnosis is essential but remains challenging because of non-specific clinical and radiological findings. "
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    ABSTRACT: A case of invasive pulmonary aspergillosis caused by Aspergillus terreus is described. The diagnosis was based on demonstration of branched septate hyphae in a sputum specimen and isolation of the fungus in culture. The diagnosis was further supported by detection of A. terreus-specific DNA, galactomannan (GM) and (1→3)-β-D-glucan (BDG) in consecutive serum specimens. The patient was treated for about 10 weeks with voriconazole. The decreasing levels of GM and BDG in serum samples were accompanied by symptomatic and radiological improvement. The report highlights the value of surrogate markers in the diagnosis and for monitoring the course of invasive aspergillosis during therapy.
    Full-text · Article · Dec 2010 · Journal of Medical Microbiology
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