Diagnosis, classification, and therapeutic interventions for sinopulmonary Aspergillosis

Abstract

Sinopulmonary aspergillosis represents a diverse collection of allergic, invasive, and chronic sinus and respiratory conditions. These diseases can affect patients with and without immune impairment and in some cases may be life-threatening. Areas covered: We review the diagnosis, classification, and therapeutic options available to treat sinopulmonary aspergillosis and look ahead to emerging diagnostic and therapeutic options that may soon play an important role in clinical practice. Expert commentary: Histopathology and tissue culture remain the gold standard for the diagnosis of invasive sinopulmonary aspergillosis, but several new molecular detection methods have recently emerged, including various PCR-based platforms, MALDI-TOF, and lateral flow assays. We examine these methodologies as well as the barriers associated with the standardization, validation, and implementation. We also explore the pipeline of antifungal agents in development to treat sinopulmonary aspergillosis.

Isolated cerebral aspergillosis in an immunocompetent woman on treatment for bacterial infected necrotizing pancreatitis

“…Aspergillus fungal spores can be inhaled into the upper respiratory tract and survive as a commensal of the paranasal sinuses; it can also colonize the external auditory canal. [ 5 ] Depending on the host's immune status, a variety of diseases can be caused by Aspergillus spp., ranging from allergies and superficial infections to life-threatening invasive mycoses. Inhalation of Aspergillus spp.…”

Pathological Diagnosis of Pulmonary Aspergillosis

“…Allergic bronchopulmonary aspergillosis (ABPA) is an immunological pulmonary disorder caused by hypersensitivity to mainly A. fumigatus and is the most common form of allergic bronchopulmonary mycosis. 14 47 48 The disease develops secondary to fungal colonization of the airways and is almost exclusively seen in patients with impaired mucociliary clearance, i.e., in patients with CF and asthma. 14 26 48 Following inhalation of spores, the conidia germinate in the mucus of the bronchial tree to form hyphae, capable of releasing allergens, virulence factors, and proteases, which elicit further impairment of the mucociliary clearance system, and inhibit the action of fungicidal proteins, complement factors, and phagocytic cells.…”

Pharmacokinetics and Pharmacodynamics of Ibrexafungerp

“…The widespread use of immunosuppressants and immunomodulators in clinical practice has expanded the population of patients with immune impairment who are susceptible to invasive fungal infections [27,28]. For the past two decades, there have only been three major classes of antifungal agents (polyenes, triazoles, and echinocandins) and their use has been diminished by the emergence of drug-resistant fungal species [29][30][31].…”

“…The key finding in this study is that ibrexafungerp is effective in vivo against C. auris even when appropriate therapy is not initiated promptly. This matters because the diagnosis of human fungal pathogens is sometimes delayed owing to limitations in molecular diagnostics [ 27 , 39 ]. Although preclinical comparison studies are limited, this study serves as a proof of principle that ibrexafungerp may be a useful treatment option in clinical practice for an emerging fungal pathogen that is often resistant to existing treatment options, although further studies in humans are needed [ 40 ].…”