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Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus fumigatus colonizing the airways, seen primarily in patients with Asthma or Cystic fibrosis (CF). It results in eosinophilic inflammation, bronchiectasis, and potentially fibrosis if untreated.

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https://www.youtube.com/watch?v=4TpsTCSnqrk

https://www.youtube.com/watch?v=Vyef4mdMWSo

Pathophysiology

Type I (IgE-mediated) and Type III (immune complex-mediated) hypersensitivity reactions
Airway colonization → immune response → mucus impaction → bronchiectasis and airway damage
May progress to chronic pulmonary fibrosis ("ABPA fibrotica")

![The key events in allergic bronchopulmonary aspergillosis (ABPA) pathogenesis include Aspergillus colonisation followed by skewed type-2 immune responses. Polymorphisms in airway epithelial receptors and innate and adaptive immune pathways prevent elimination of A. fumigatus and promote the development of an aberrant type-2 immune response. Pathogen-associated molecular patterns (PAMPs) from Aspergillus (glucan, galactomannan, galactosaminogalactan, proteases) are recognised by pattern recognition receptors (PRRs), including dectin-1 and toll-like receptors (TLRs), at the lung epithelial cell surface. Fungal proteases can damage the respiratory epithelium and result in release of alarmins (interleukin (IL)-33, IL-25 and thymic stromal lymphopoietin (TSLP)), which in turn stimulate the type 2 innate lymphoid cells (ILC2) and CD4+ type 2 lymphocytes. The dendritic cells also recognise fungal proteins and activate allergen-specific type 2 T-cells (Th2 cells). Eosinophils remain the primary mediators of inflammation in ABPA, with the interaction between eosinophils and A. fumigatus releasing galectin-10 and forming Charcot–Leyden crystals (CLCs). Subsequently, eosinophils undergo cell death forming histone-rich extracellular traps (EETs) and increase the viscosity of mucus plugs, which contribute to ABPA pathogenesis. The skewed type 2 responses lead to secretion of IL-4, IL-5 and IL-13. IL-4 mediates the class switching and production of IgE antibodies, which attach to mast cells and cause mast cell degranulation on allergen exposure. IL-5 is pivotal for eosinophil recruitment, maturation and survival and is central to eosinophilic inflammation. IL-13 from ILC2 and Th2 cells promotes mucus hypersecretion. Finally, immune activation leads to airway inflammation, mucus plugging and bronchiectasis. HAM: high-attenuation mucus. Figure created with Biorender.com.

Jaggi TK, Agarwal R, Tiew PY, et al. Fungal lung disease. European Respiratory Journal. Published online October 3, 2024:2400803. doi:10.1183/13993003.00803-2024](attachment:53be14e8-403b-408c-943b-46f1d12f9d9e:F3.large.jpg)

The key events in allergic bronchopulmonary aspergillosis (ABPA) pathogenesis include Aspergillus colonisation followed by skewed type-2 immune responses. Polymorphisms in airway epithelial receptors and innate and adaptive immune pathways prevent elimination of A. fumigatus and promote the development of an aberrant type-2 immune response. Pathogen-associated molecular patterns (PAMPs) from Aspergillus (glucan, galactomannan, galactosaminogalactan, proteases) are recognised by pattern recognition receptors (PRRs), including dectin-1 and toll-like receptors (TLRs), at the lung epithelial cell surface. Fungal proteases can damage the respiratory epithelium and result in release of alarmins (interleukin (IL)-33, IL-25 and thymic stromal lymphopoietin (TSLP)), which in turn stimulate the type 2 innate lymphoid cells (ILC2) and CD4+ type 2 lymphocytes. The dendritic cells also recognise fungal proteins and activate allergen-specific type 2 T-cells (Th2 cells). Eosinophils remain the primary mediators of inflammation in ABPA, with the interaction between eosinophils and A. fumigatus releasing galectin-10 and forming Charcot–Leyden crystals (CLCs). Subsequently, eosinophils undergo cell death forming histone-rich extracellular traps (EETs) and increase the viscosity of mucus plugs, which contribute to ABPA pathogenesis. The skewed type 2 responses lead to secretion of IL-4, IL-5 and IL-13. IL-4 mediates the class switching and production of IgE antibodies, which attach to mast cells and cause mast cell degranulation on allergen exposure. IL-5 is pivotal for eosinophil recruitment, maturation and survival and is central to eosinophilic inflammation. IL-13 from ILC2 and Th2 cells promotes mucus hypersecretion. Finally, immune activation leads to airway inflammation, mucus plugging and bronchiectasis. HAM: high-attenuation mucus. Figure created with Biorender.com.

Jaggi TK, Agarwal R, Tiew PY, et al. Fungal lung disease. European Respiratory Journal. Published online October 3, 2024:2400803. doi:10.1183/13993003.00803-2024

Epidemiology

Occurs in ~1–2% of asthma patients and ~5–15% of those with cystic fibrosis
Mean age of diagnosis: 20s–40s
Often recurrent or relapsing

Clinical Features

Symptom	Description
Chronic productive cough	May produce brownish mucus plugs
Recurrent asthma exacerbations	Often resistant to standard bronchodilators
Wheezing, dyspnea	Mimics uncontrolled asthma
Low-grade fever, malaise	Mild systemic symptoms
Hemoptysis	Due to bronchiectasis or erosion of inflamed vessels

Greenberger classification:

Acute