Allergic Bronchopulmonary Aspergillosis (ABPA) in the Era of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulators

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity disease caused by <i>Aspergillus fumigatus</i> (<i>Af</i>), prevalent in persons with cystic fibrosis (CF) or asthma. In ABPA, <i>Af</i> proteases drive a T-helper cell-2 (Th2)-mediated allergic...

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Main Authors: Paulami Chatterjee, Carson Tyler Moss, Sarah Omar, Ekroop Dhillon, Carlos Daniel Hernandez Borges, Alan C. Tang, David A. Stevens, Joe L. Hsu
Format: Article
Language:English
Published: MDPI AG 2024-09-01
Series:Journal of Fungi
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Online Access:https://www.mdpi.com/2309-608X/10/9/656
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author Paulami Chatterjee
Carson Tyler Moss
Sarah Omar
Ekroop Dhillon
Carlos Daniel Hernandez Borges
Alan C. Tang
David A. Stevens
Joe L. Hsu
author_facet Paulami Chatterjee
Carson Tyler Moss
Sarah Omar
Ekroop Dhillon
Carlos Daniel Hernandez Borges
Alan C. Tang
David A. Stevens
Joe L. Hsu
author_sort Paulami Chatterjee
collection DOAJ
description Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity disease caused by <i>Aspergillus fumigatus</i> (<i>Af</i>), prevalent in persons with cystic fibrosis (CF) or asthma. In ABPA, <i>Af</i> proteases drive a T-helper cell-2 (Th2)-mediated allergic immune response leading to inflammation that contributes to permanent lung damage. Corticosteroids and antifungals are the mainstays of therapies for ABPA. However, their long-term use has negative sequelae. The treatment of patients with CF (pwCF) has been revolutionized by the efficacy of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy. Pharmacological improvement in CFTR function with highly effective elexacaftor/tezacaftor/ivacaftor (ETI) provides unprecedented improvements in lung function and other clinical outcomes of pwCF. The mechanism behind the improvement in patient outcomes is a continued topic of investigation as our understanding of the role of CFTR function evolves. As ETI therapy gains traction in CF management, understanding its potential impact on ABPA, especially on the allergic immune response pathways and <i>Af</i> infection becomes increasingly crucial for optimizing patient outcomes. This literature review aims to examine the extent of these findings and expand our understanding of the already published research focusing on the intersection between ABPA therapeutic approaches in CF and the rapid impact of the evolving CFTR modulator landscape. While our literature search yielded limited reports specifically focusing on the role of CFTR modulator therapy on CF-ABPA, findings from epidemiologic and retrospective studies suggest the potential for CFTR modulator therapies to positively influence pulmonary outcomes by addressing the underlying pathophysiology of CF-ABPA, especially by decreasing inflammatory response and <i>Af</i> colonization. Thus, this review highlights the promising scope of CFTR modulator therapy in decreasing the overall prevalence and incidence of CF-ABPA.
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spelling doaj-art-104ba0b62eec4f2d9da2af2b783efc842025-08-20T01:55:34ZengMDPI AGJournal of Fungi2309-608X2024-09-0110965610.3390/jof10090656Allergic Bronchopulmonary Aspergillosis (ABPA) in the Era of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) ModulatorsPaulami Chatterjee0Carson Tyler Moss1Sarah Omar2Ekroop Dhillon3Carlos Daniel Hernandez Borges4Alan C. Tang5David A. Stevens6Joe L. Hsu7Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University School of Medicine, Stanford, CA 94305, USADepartment of Medicine, Stanford University School of Medicine, Stanford, CA 94304, USADivision of Pulmonary, Allergy and Critical Care Medicine, Stanford University School of Medicine, Stanford, CA 94305, USADivision of Pulmonary, Allergy and Critical Care Medicine, Stanford University School of Medicine, Stanford, CA 94305, USADepartment of Internal Medicine, Alta Bates Summit Medical Center, Sutter Health, Oakland, CA 94609, USADepartment of Medicine, Keck School of Medicine, Los Angeles, CA 90089, USADivision of Infectious Diseases and Geographic Medicine, Stanford University Medical School, Stanford, CA 94305, USADivision of Pulmonary, Allergy and Critical Care Medicine, Stanford University School of Medicine, Stanford, CA 94305, USAAllergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity disease caused by <i>Aspergillus fumigatus</i> (<i>Af</i>), prevalent in persons with cystic fibrosis (CF) or asthma. In ABPA, <i>Af</i> proteases drive a T-helper cell-2 (Th2)-mediated allergic immune response leading to inflammation that contributes to permanent lung damage. Corticosteroids and antifungals are the mainstays of therapies for ABPA. However, their long-term use has negative sequelae. The treatment of patients with CF (pwCF) has been revolutionized by the efficacy of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy. Pharmacological improvement in CFTR function with highly effective elexacaftor/tezacaftor/ivacaftor (ETI) provides unprecedented improvements in lung function and other clinical outcomes of pwCF. The mechanism behind the improvement in patient outcomes is a continued topic of investigation as our understanding of the role of CFTR function evolves. As ETI therapy gains traction in CF management, understanding its potential impact on ABPA, especially on the allergic immune response pathways and <i>Af</i> infection becomes increasingly crucial for optimizing patient outcomes. This literature review aims to examine the extent of these findings and expand our understanding of the already published research focusing on the intersection between ABPA therapeutic approaches in CF and the rapid impact of the evolving CFTR modulator landscape. While our literature search yielded limited reports specifically focusing on the role of CFTR modulator therapy on CF-ABPA, findings from epidemiologic and retrospective studies suggest the potential for CFTR modulator therapies to positively influence pulmonary outcomes by addressing the underlying pathophysiology of CF-ABPA, especially by decreasing inflammatory response and <i>Af</i> colonization. Thus, this review highlights the promising scope of CFTR modulator therapy in decreasing the overall prevalence and incidence of CF-ABPA.https://www.mdpi.com/2309-608X/10/9/656allergic bronchopulmonary aspergillosiscystic fibrosis<i>Aspergillus fumigatus</i><i>Aspergillus</i> proteasesallergic inflammationasthma
spellingShingle Paulami Chatterjee
Carson Tyler Moss
Sarah Omar
Ekroop Dhillon
Carlos Daniel Hernandez Borges
Alan C. Tang
David A. Stevens
Joe L. Hsu
Allergic Bronchopulmonary Aspergillosis (ABPA) in the Era of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulators
Journal of Fungi
allergic bronchopulmonary aspergillosis
cystic fibrosis
<i>Aspergillus fumigatus</i>
<i>Aspergillus</i> proteases
allergic inflammation
asthma
title Allergic Bronchopulmonary Aspergillosis (ABPA) in the Era of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulators
title_full Allergic Bronchopulmonary Aspergillosis (ABPA) in the Era of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulators
title_fullStr Allergic Bronchopulmonary Aspergillosis (ABPA) in the Era of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulators
title_full_unstemmed Allergic Bronchopulmonary Aspergillosis (ABPA) in the Era of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulators
title_short Allergic Bronchopulmonary Aspergillosis (ABPA) in the Era of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulators
title_sort allergic bronchopulmonary aspergillosis abpa in the era of cystic fibrosis transmembrane conductance regulator cftr modulators
topic allergic bronchopulmonary aspergillosis
cystic fibrosis
<i>Aspergillus fumigatus</i>
<i>Aspergillus</i> proteases
allergic inflammation
asthma
url https://www.mdpi.com/2309-608X/10/9/656
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