Emerging Fungal Threats in Cystic Fibrosis

Schwarz, C.; Eschenhagen, Patience; Bouchara, Jean Philippe

doi:10.1007/s11046-021-00574-w

Cited by 18 publications

(17 citation statements)

References 111 publications

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“…Besides A . fumigatus , the most frequent isolated fungi from CF airways are the yeast Candida albicans and the mold Scedosporium apiospermum ( Pseudallescheria boydii ) ( 7 , 8 ). Allergic sensitization and allergic bronchopulmonary mycosis (ABPM) caused by C .…”

Section: Resultsmentioning

confidence: 99%

“…In contrast, patients with cystic fibrosis (pwCF) suffer from disease exacerbations due to recurrent and chronic infections of the lung (5,6). A. fumigatus is the most common filamentous fungus found in up to 57% of respiratory secretions from adult pwCF (7,8). A. fumigatus rarely causes invasive or systemic infections in pwCF, but they often develop allergic hypersensitivity against the fungus.…”

Section: Despite This Continuous Challenge Healthy Individuals Rarely...mentioning

confidence: 99%

“…pwCF are typically colonized with multiple fungal microbes. Besides A. fumigatus, the most frequent isolated fungi from CF airways are the yeast Candida albicans and the mold Scedosporium apiospermum (Pseudallescheria boydii) (7,8).…”

Section: A Fumigatus Is a Major Inducer Of Anti-fungal Th2 Responses ...mentioning

confidence: 99%

“…A . fumigatus is the most common filamentous fungus found in up to 57% of respiratory secretions from adult pwCF ( 7 , 8 ). A .…”

Section: Introductionmentioning

confidence: 99%

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Antigen specificity and cross-reactivity drive functionally diverse anti–Aspergillus fumigatus T cell responses in cystic fibrosis

Schwarz¹,

Eschenhagen²,

Schmidt³

et al. 2023

Journal of Clinical Investigation

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Background. The fungus Aspergillus fumigatus causes a variety of clinical phenotypes in patients with cystic fibrosis (pwCF). T-helper (Th) cells orchestrate immune responses against fungi, but the types of A. fumigatus-specific Th-cells in pwCF and their contribution to protective immunity or inflammation remain poorly characterized.Methods. We used antigen-reactive T cell enrichment (ARTE) to investigate fungus-reactive Th cells in peripheral blood of pwCF and healthy controls. Results. We show that clonally expanded, high-avidity A. fumigatus-specific effector Th-cells develop in pwCF, which are absent in healthy donors. Individual patients were characterized by distinct Th1, Th2, or Th17 dominated responses that remained stable over years. These different Th subsets target different A. fumigatus proteins, indicating that differential antigen uptake and presentation directs Th-cell subset development. Patients with allergic bronchopulmonary aspergillosis (ABPA) are characterized by high frequencies of Th2-cells that cross-recognize various filamentous fungi. Conclusion. Our data highlight the development of heterogenous Th responses targeting different protein fractions of a single fungal pathogen and identify the development of multispecies cross-reactive Th2-cells as a potential risk factor for ABPA.

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Section: Resultsmentioning

confidence: 99%

Section: Despite This Continuous Challenge Healthy Individuals Rarely...mentioning

confidence: 99%

Section: A Fumigatus Is a Major Inducer Of Anti-fungal Th2 Responses ...mentioning

confidence: 99%

“…A . fumigatus is the most common filamentous fungus found in up to 57% of respiratory secretions from adult pwCF ( 7 , 8 ). A .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Antigen specificity and cross-reactivity drive functionally diverse anti–Aspergillus fumigatus T cell responses in cystic fibrosis

Schwarz¹,

Eschenhagen²,

Schmidt³

et al. 2023

Journal of Clinical Investigation

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“…In those clinical settings, a combination of two or even three different antifungals might be necessary and is therefore recommended for the initial treatment phase. 11 28 43 44 74 Ideally, the treatment combination used should combine an oral azole (voriconazole, posaconazole, isavuconazole), an intravenous echinocandin, and an inhaled lipidic amphotericin B. In Rasamsonia infections, micafungin would be preferred in combination, and in infections with L. prolificans , terbinafine might be susceptible as well as miltefosine, in combination with an echinocandin and azole.…”

Section: Treatment Of Fungal Pulmonary Infectionsmentioning

confidence: 99%

Clinical Relevance of Fungi in Cystic Fibrosis

Schwarz¹

2023

Semin Respir Crit Care Med

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In cystic fibrosis, a new era has started with the approval and use of highly effective cystic fibrosis transport regulator (CFTR) modulator therapy. As pulmonary function is increasing and exacerbation rate significantly decreases, the current meaning of fungal pulmonary diseases is questioned. During the past couple of decades, several studies have been conducted regarding fungal colonization and infection of the airways in people with cystic fibrosis. Although Aspergillus fumigatus for filamentous fungi and Candida albicans for yeasts remain by far the most common fungal species in patients with cystic fibrosis, the pattern of fungal species associated with cystic fibrosis has considerably diversified recently. Fungi such as Scedosporium apiospermum or Exophiala dermatitidis are recognized as pathogenic in cystic fibrosis and therefore need attention in clinical settings. In this article, current definitions are stated. Important diagnostic steps are described, and their usefulness discussed. Furthermore, clinical treatment strategies and recommendations are named and evaluated. In cystic fibrosis, fungal entities can be divided into different subgroups. Besides colonization, allergic bronchopulmonary aspergillosis, bronchitis, sensitization, pneumonia, and aspergilloma can occur as a fungal disease entity. For allergic bronchopulmonary aspergillosis, bronchitis, pneumonia, and aspergilloma, clear indications for therapy exist but this is not the case for sensitization or colonization. Different pulmonary fungal disease entities in people with cystic fibrosis will continue to occur also in an era of highly effective CFTR modulator therapy. Whether the percentage will decrease or not will be the task of future evaluations in studies and registry analysis. Using the established definition for different categories of fungal diseases is recommended and should be taken into account if patients are deteriorating without responding to antibiotic treatment. Drug–drug interactions, in particular when using azoles, should be recognized and therapies need to be adjusted accordingly.

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Respiratory Mycoses: A Call to Action to Recognize, Educate and Invest

Armstrong‐James

Chotirmall

2021

Mycopathologia

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Emerging Fungal Threats in Cystic Fibrosis

Cited by 18 publications

References 111 publications

Antigen specificity and cross-reactivity drive functionally diverse anti–Aspergillus fumigatus T cell responses in cystic fibrosis

Antigen specificity and cross-reactivity drive functionally diverse anti–Aspergillus fumigatus T cell responses in cystic fibrosis

Clinical Relevance of Fungi in Cystic Fibrosis

Respiratory Mycoses: A Call to Action to Recognize, Educate and Invest

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