Pulmonary aspergillosis is a significant global health concern, although still too often neglected and underdiagnosed. It affects people who are immunocompromised, those with underlying lung disease, or even previously healthy individuals. In the human lung, the ubiquitous fungus Aspergillus causes a wide spectrum of disease that cannot be untangled from the host's immune state. In this issue of Seminars of Respiratory and Critical Care Medicine, we aim to elucidate the spectrum of pulmonary aspergillosis in all its facets. In the first chapter, the authors unravel how Aspergillus can take up residence in the lung and how the interaction between host and pathogen determines the development of distinct and overlapping clinical syndromes, providing a complete overview of the disease spectrum from an immunological point of view.[1] We are all breathing in many fungal spores every day, but usually, these do not cause illness. In patients with structural airway damage, asymptomatic colonization, or inappropriate type 2 immune responses may occur, and when the host environment looks welcoming, such as in the presence of preexistent cavities, an aspergilloma may start to grow in a saprophytic way. When the host immune response falls short, chronic cavitary pulmonary aspergillosis may develop, and in the severely immunocompromised, invasive aspergillosis might install.

In clinical practice, one of the main challenges remains the diagnosis of pulmonary aspergillosis—for instance, to assess the relevance of Aspergillus spp. cultured from a respiratory specimen, or to interpret nonspecific findings on chest computed tomography in high-risk patients. Four subsequent chapters of this issue are, therefore, dedicated to the diagnostic toolbox available for pulmonary aspergillosis, among which many tools are part of the established diagnostic criteria for the different disease entities. First, the existing microbiological diagnostic modalities and their future prospects are being discussed.[2] Second, the increasing problem of antifungal resistance in Aspergillus spp. is reviewed, including the mechanisms of resistance and their therapeutic implications, emphasizing the urgency of surveillance and research in this area.[3] Third, Jensen and Becker provide a comprehensive and richly illustrated overview of histopathological diagnosis as a gold standard in differentiating between fungal contamination, commensalism, and disease states—from angioinvasive infection to hypersensitivity pneumonitis.[4] Fourth, Laurent et al. highlight the radiological features that aid in the diagnosis and classification of pulmonary aspergillosis, and touch upon promising new imaging strategies such as magnetic resonance and artificial intelligence.[5]

Before diving deeper into the different clinical entities of pulmonary aspergillosis, the current therapeutic antifungal landscape is explored, offering a glimpse of the promising antifungal pipeline.[6] Many of these novel therapies hold significant potential to treat different forms of pulmonary aspergillosis—also beyond the classical risk groups and presentations. Toxicity, drug–drug interactions, and resistance development warrant an expansion of our antifungal treatment arsenal—not only in acute but also in chronic pulmonary aspergillosis (CPA), where oral formulations are the preferred treatment. One of the challenges for the mycological community is, therefore, to ensure capacity building to set up randomized trials in these neglected populations. In addition, further research is needed to explore therapies directed at the host immune response against Aspergillus infection.

In the second half of this series, we are zooming in on clinical presentation and management of the main disease entities within the pulmonary aspergillosis spectrum. Although acute invasive pulmonary aspergillosis (IPA) is traditionally considered in classical risk groups such as prolonged and severe neutropenia, the authors outline the importance of looking beyond the EORTC/MSGERC host factors, such as critical illness, chronic obstructive pulmonary disease, liver disease, and the increasingly recognized phenomenon of virus-associated IPA.[7] In contrast, CPA remains one of the most neglected forms of Aspergillus disease, both in terms of diagnostic and therapeutic options. Consequently, the authors define outstanding questions and formulate research opportunities for CPA.[8] In the next chapter, authors from the Chronic Pulmonary Aspergillosis Network (CPAnet) advocate for more awareness and screening for CPA in people with post-tuberculosis lung disease.[9] At the other end of the spectrum, Agarwal et al. guide us through the clinical, diagnostic and therapeutic aspects of allergic bronchopulmonary aspergillosis, an overzealous hypersensitivity reaction to Aspergillus antigens leading to severe bronchial inflammation and airway destruction.[10] In the final chapter, Schwarz et al. uncover the unique challenges of Aspergillus spp. infection and disease in people living with cystic fibrosis, providing a window into the complexities and particularities of this specific population.[11]

The contributions in this issue cover a wide array of topics, carefully elaborated by internationally recognized clinicians and scientists, each shedding light on a different aspect of pulmonary aspergillosis. We would like to extend our heartfelt gratitude to all the authors who have contributed their expertise, insights, and time to make this issue a treasure trove of evidence, clinical wisdom, and innovative insights into the management of pulmonary aspergillosis. It is our hope that this series will not only serve as a reference for current practice but also inspire new avenues of research and collaboration in the quest to better understand, diagnose, and treat this complex spectrum of disease.

Article published online:
29 January 2024

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