Seminars in respiratory and critical care medicine
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Semin Respir Crit Care Med · Feb 2024
ReviewChronic Pulmonary Aspergillosis as a Considerable Complication in Post-Tuberculosis Lung Disease.
Post-tuberculosis lung disease (PTLD) has only recently been put in the spotlight as a medical entity. Recent data suggest that up to 50% of tuberculosis (TB) patients are left with PTLD-related impairment after completion of TB treatment. ⋯ Diagnosis of CPA is based on four criteria including a typical radiological pattern, evidence of Aspergillus species, exclusion of alternative diagnosis, and a chronic course of disease. In this manuscript, we provide a narrative review on CPA as a serious complication for patients with PTLD.
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Pulmonary aspergillosis constitutes an increasingly prevalent and potentially fatal complex of mycotic diseases, caused by different species of Aspergillus. The broad spectrum of pathological manifestations associated with pulmonary aspergillosis necessitates a differentiation of commensalism from saprophytic colonization, hypersensitivity reactions, and true invasive infections, which highlights the importance of histopathology as a gold standard in a diagnostic setting. For the past decades, changes in terminology and contradicting contributions from different diagnostic disciplines have made the classification of pulmonary aspergillosis rather confusing. This review offers a categorization of aspergillosis lesions based on what can be histopathologically identified and distinguished, differentiating between acute invasive infection and forms of subacute, chronic, and allergic diseases and coinfections, and summarizes important manifestations of lesions associated with the different forms of pulmonary aspergillosis.
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Semin Respir Crit Care Med · Feb 2024
ReviewAcute Invasive Pulmonary Aspergillosis: Clinical Presentation and Treatment.
Among all clinical manifestations of pulmonary aspergillosis, invasive pulmonary aspergillosis (IPA) is the most acute presentation. IPA is caused by Aspergillus hyphae invading the pulmonary tissue, causing either tracheobronchitis and/or bronchopneumonia. The degree of fungal invasion into the respiratory tissue can be seen as a spectrum, going from colonization to deep tissue penetration with angio-invasion, and largely depends on the host's immune status. ⋯ Adjunctive therapy such as immunomodulatory treatment should also be taken into account. Despite an improving and evolving diagnostic and therapeutic armamentarium, the burden and mortality of IPA still remains high. This review aims to give a comprehensive and didactic overview of the current knowledge and best practices regarding the epidemiology, clinical presentation, diagnosis, and treatment of acute IPA.
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The filamentous fungus Aspergillus causes a wide spectrum of diseases in the human lung, with Aspergillus fumigatus being the most pathogenic and allergenic subspecies. The broad range of clinical syndromes that can develop from the presence of Aspergillus in the respiratory tract is determined by the interaction between host and pathogen. In this review, an oversight of the different clinical entities of pulmonary aspergillosis is given, categorized by their main pathophysiological mechanisms. The underlying immune processes are discussed, and the main clinical, radiological, biochemical, microbiological, and histopathological findings are summarized.
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Semin Respir Crit Care Med · Feb 2024
Antifungal Therapies for Aspergillus spp.: Present and Future.
Currently available and recommended options for the treatment of pulmonary aspergillosis include the triazoles, echinocandins, and amphotericin B products. These therapies have significant limitations. Only the azoles are available orally, but their use is often limited by toxicities, drug-drug interactions, pharmacokinetic variability, and emerging resistance. ⋯ Development of an oral form of amphotericin B that avoids nephrotoxicity and electrolyte disturbances is an exciting development. Finally, olorofim and fosmanogepix, two agents with novel mechanisms of action and oral formulations, hold significant potential to challenge the triazole antifungals place as preferred therapies. However, many questions remain regarding these novel agents, and at the time of this writing, none of these agents have been robustly studied in Phase III studies of aspergillosis, and so their promise remains investigational.