Aspergillosis is a rare infectious and allergic disease caused by Aspergillus, a common environmental mold. Per GARD (GARD:5856) and Orphanet (Orphanet:1163), the condition encompasses several distinct clinical presentations. The four recognized subtypes documented in this packet are: allergic bronchopulmonary aspergillosis (ABPA), in which the fungus triggers an allergic respiratory response without tissue invasion; invasive aspergillosis, a tissue-destructive infection primarily affecting immunocompromised individuals; aspergilloma (fungal ball), a growth developing in pre-existing lung cavities; and neuroaspergillosis, involving the central nervous system. Aspergillus niger infection is additionally documented as a subtype. Prevalence data are not available in this packet. Aspergillosis is not a genetic condition — onset and subtype are determined by host immune status and pre-existing pulmonary anatomy rather than inherited factors.

Clinical presentation varies substantially by aspergillosis subtype. In allergic bronchopulmonary aspergillosis (ABPA), Aspergillus colonization of the airways triggers an allergic immune response producing symptoms resembling asthma — wheezing and coughing — without invasion or destruction of lung tissue. Invasive aspergillosis presents with pulmonary symptoms from direct fungal invasion and tissue destruction; dissemination to the kidneys, brain, and other organs can occur and most commonly affects individuals with compromised immunity (cancer, AIDS, leukemia, post-transplantation, or chemotherapy-related immunosuppression). Aspergilloma develops as a tangled mass of fungal fibers, blood clots, and white blood cells within pre-existing lung cavities from prior diseases such as tuberculosis or lung abscess, causing progressive lung tissue destruction without systemic spread in most cases. Neuroaspergillosis produces central nervous system manifestations. Phenotype-level frequency data are not included in this packet.

Aspergillosis is caused by infection with or allergic response to Aspergillus species — ubiquitous environmental molds found in soil, decaying organic material, and indoor environments. It is not an inherited genetic disorder. Invasive aspergillosis arises in the context of markedly impaired host immunity: cancer, AIDS, leukemia, organ transplantation, chemotherapy, and other causes of reduced white blood cell count are documented risk contexts per the packet definition. ABPA arises from an aberrant allergic immune response to Aspergillus in susceptible individuals. Aspergilloma develops in pre-existing structural lung abnormalities — particularly cavities from prior tuberculosis or lung abscess — where fungal growth is facilitated. No causative genes are documented in this packet, consistent with the acquired, non-heritable etiology.

Diagnostic evaluation in aspergillosis is guided by the clinical presentation, subtype, and host immune context. No formal diagnostic criteria, biomarkers, or testing algorithms are documented in this packet. The research landscape reflects active work in diagnostic prediction: a multicenter study is deriving and validating a fungal pneumonia assessment and likelihood predictor score (NCT07681583, enrolling through 2031). Machine learning-based recurrence prediction models for ABPA are under study (NCT07714863, NCT07611838). The packet does not specify imaging criteria, laboratory thresholds, or microbiologic confirmation requirements.

Three FDA-approved treatments with active market status are documented in this packet for aspergillosis. Itraconazole is available under two brand names: TOLSURA (NDA, approved December 2018) and SPORANOX (NDA, approved September 1992). Prednisolone sodium phosphate (NDA, approved May 1986) holds active market status. No gene therapy treatments are approved. Investigational agents under active clinical evaluation include rezafungin for chronic pulmonary aspergillosis (Phase 2, NCT06794554, Mundipharma Research Limited), interferon-gamma as adjunctive therapy in chronic pulmonary aspergillosis (Phase 2, NCT05653193, Manchester University NHS Foundation Trust), and inhaled liposomal amphotericin B for chronic pulmonary aspergillosis (Phase 1, NCT07530263). Biologic therapy effectiveness is under real-world study for ABPA — tezepelumab (NCT07757841) and benralizumab (NCT07530770) are subjects of ongoing observational studies.

Natural history and long-term prognosis information are not documented in this packet. Clinical course varies by subtype: aspergilloma is characterized by gradual lung tissue destruction without systemic spread in most cases per the packet definition, while invasive aspergillosis outcomes are influenced by host immune status and extent of dissemination. No formal prognosis source data are provided in this packet.

Per ClinicalTrials.gov, 37 active trials are registered. Ongoing studies include a NIAID natural history study of individuals with immune dysfunction predisposing to fungal infections (NCT01386437, ongoing since 2012), a Phase 2 trial of interferon-gamma as adjunctive therapy in chronic pulmonary aspergillosis (NCT05653193, Manchester University NHS Foundation Trust, active through 2026), and a Phase 2 study of rezafungin for chronic pulmonary aspergillosis with limited treatment options (NCT06794554, Mundipharma Research Limited). ABPA-focused studies include real-world effectiveness evaluations of tezepelumab (NCT07757841, Qianfoshan Hospital) and benralizumab (NCT07530770), and multi-omics inflammatory phenotyping for recurrence risk prediction (NCT07611838). A fungal pneumonia assessment score derivation study is enrolling through 2031 (NCT07681583, Azienda Ospedaliero-Universitaria Careggi). Trial interventions span drug therapy, procedural approaches, and other modalities. Published research totals 176 classified publications, with reviews and meta-analyses dominant (72 of 176) and active biomarker and clinical trial publication streams. Patient organization data are not documented in this packet. Authoritative resources include Orphanet (Orphanet:1163) and the NIH GARD database (GARD:5856).