- Review
Immunology and Biologics in the Treatment of Allergic Bronchopulmonary Aspergillosis in Cystic Fibrosis
- Esther S. Kim and
- Janice Wang
Allergic bronchopulmonary aspergillosis (ABPA) is mediated by hypersensitivity reactions to Aspergillus fumigatus, which is ubiquitous in the environment. People with Cystic Fibrosis (PwCF) are at an increased risk for developing ABPA, which can lead to frequent pulmonary exacerbations and progressive decline in lung function. In the age of highly effective modulator therapies (HEMT), PwCF have improved clinical outcomes and overall life expectancy, but they continue to suffer from comorbidities such as ABPA, which may be difficult to diagnose and treat. Establishing the diagnosis of ABPA in PwCF requires high clinical suspicion due to similarities in symptoms with the underlying disease. First-line treatment involves corticosteroids and anti-fungals, which have multiple side effects and drug interactions, especially with HEMT. Given this challenge, biologics have gained attention as potential agents directly targeting the Th-2 inflammatory pathway of ABPA with good tolerability and without significant drug interactions with HEMT. In this review, we discuss the diagnostic process and management of ABPA in PwCF, including a brief overview of the current literature on biologic agents.
14 November 2025


![Immune dysregulation in Cystic Fibrosis. A. The periciliary layer of the Cystic Fibrosis airway is dehydrated leading to poor mucociliary clearance as a result of dysfunctional CFTR protein that is normally expressed in airway epithelial cells [47,48]. B. Mucus plugging and biofilm buildup becomes a nidus for inhaled pathogens or allergens such as Aspergillus spp. C. Macrophages with impaired CFTR kill pathogens less efficiently and increase secretion of pro-inflammatory cytokines such as IL-6, IL-4, IL-13, and TNF-α [44,49]. D. CFTR deficient airway epithelial cells lead to increased IL-33 when exposed to allergens, resulting in higher expression of Th2 cell with increased release of IL-5, increased eosinophils, and IL-4 and IL-13, stimulating IgE expression by B cells [50,51]. E. Neutrophils, the predominant type of cell in CF airways, have reduced phagocytosis and can release toxic granule contents (e.g., serine and metalloproteases, oxidants) that can cause tissue damage over time. Neutrophils are known to release neutrophil extracellular traps (NETs), which are DNA fibers that immobilize and kill bacterial and fungal pathogens such as Pseudomonas aeruginosa and Aspergillus fumigatus, respectively. Abundant NET formations may attribute to common colonization of such pathogens in people with CF and reduced lung function; recombinant DNase (e.g., inhaled dornase alfa) improves mucociliary clearance by clearing the NET-DNA meshwork [49,51,52].](/_ipx/b_%23fff&f_webp&q_100&fit_outside&s_470x317/https://mdpi-res.com/jor/jor-05-00019/article_deploy/html/images/jor-05-00019-g001-550.jpg)
