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Aspergillus is a ubiquitous filamentous fungus that causes a spectrum of diseases ranging from allergic syndromes to life-threatening invasive infections. Although hundreds of species exist, fewer than 40 cause human disease, most commonly Aspergillus fumigatus, followed by Aspergillus terreus, Aspergillus flavus, and Aspergillus niger. This course outlines the transmission of this pathogen that follows inhalation of airborne conidia, which are typically cleared by intact host defenses, particularly neutrophils and macrophages, and high-risk factors for invasive disease, including immunocompromised individuals, such as those with prolonged neutropenia, malignancy, transplantation, severe viral pneumonia, or critical illness, who have historically high mortality rates. Clinical manifestations of aspergillosis, which include invasive pulmonary aspergillosis, chronic pulmonary aspergillosis, allergic bronchopulmonary aspergillosis, rhinosinusitis, and disseminated infection, are also discussed. This activity reviews the diverse clinical presentations, host risk factors, radiographic and laboratory findings, and evidence-based antifungal therapy of Aspergillus infections, which often must be initiated empirically. Participants will also gain an understanding of invasive syndromes predominantly affecting complex ICU and immunocompromised populations, antifungal selection and monitoring considerations, and guideline-based management strategies. This activity for healthcare professionals is designed to enhance the learner's competence in identifying aspergillosis, performing the recommended evaluation and risk stratification, preventing complications, and implementing an appropriate interprofessional approach when managing this condition, ultimately enhancing patient safety and clinical outcomes. Objectives: Identify patient-specific risk factors that increase susceptibility to aspergillosis. Interpret diagnostic findings that support the timely diagnosis of Aspergillus infections. Implement guideline-directed management strategies for invasive pulmonary aspergillosis. Collaborate with interprofessional team members to improve care coordination and outcomes for individuals with Aspergillus infection. Access free multiple choice questions on this topic.

Aspergillus is a ubiquitous, filamentous fungus that primarily causes infection in immunocompromised hosts and individuals with underlying pulmonary disease.[1][2] However, Aspergillus is increasingly recognized as a cause of infection in critically ill individuals in the intensive care unit (ICU), including those with severe influenza and coronavirus disease 2019 (COVID-19).[3] In the environment, Aspergillus species obtain nutrients from dead material and reproduce asexually via conidia.[1][4] Fewer than 40 species of Aspergillus are capable of causing human disease, with A fumigatus, followed by A flavus, A terreus, and A niger, the most implicated species.[5][CDC. Aspergillosis Basics. April 24, 2024] Although caused by the same genus of fungi, aspergillosis should be considered a spectrum of processes that vary widely depending on the host's immune status. Thus, the implications of infection can range from life-threatening, as seen in invasive pulmonary aspergillosis and invasive rhinosinusitis in severely immunocompromised individuals, to nonurgent in the case of small aspergillomas in the immunocompetent host, where monitoring with serial imaging is appropriate in most cases.[6][7] Please see StatPearls' companion resource, "Aspergilloma," for further information on this condition. Allergic bronchopulmonary syndrome (ABPA) and chronic pulmonary aspergillosis (CPA) fall somewhere along this spectrum. Please see StatPearls' companion resources, "Aspergilloma" and "Allergic Bronchopulmonary Aspergillosis" for further information on these conditions.

Although caused by the same genus of fungi, aspergillosis should be considered a spectrum of processes that vary widely depending on the host's immune status. Thus, the implications of infection can range from life-threatening, as seen in invasive pulmonary aspergillosis and invasive rhinosinusitis in severely immunocompromised individuals, to nonurgent in the case of small aspergillomas in the immunocompetent host, where monitoring with serial imaging is appropriate in most cases.[6][7] Please see StatPearls' companion resource, "Aspergilloma," for further information on this condition. Allergic bronchopulmonary syndrome (ABPA) and chronic pulmonary aspergillosis (CPA) fall somewhere along this spectrum. Please see StatPearls' companion resources, "Aspergilloma" and "Allergic Bronchopulmonary Aspergillosis" for further information on these conditions. Individuals inhale an estimated few hundred to several thousand Aspergillus conidia daily.[8] Most people do not develop aspergillosis because a robust immune response effectively clears inhaled conidia.[6][9] Host defenses, including physical barriers, innate immunity, and soluble factors, destroy conidia before germination can occur. Neutrophils play a central role in controlling Aspergillus species, which explains the heightened risk in immunocompromised individuals, particularly those with prolonged neutropenia.[9] Historically, invasive aspergillosis carried mortality rates up to 80%, and recent analyses estimate a global crude mortality of 85%.[10][11][10] Lower mortality has been observed in specific populations, eg, a 58% all-cause mortality rate among hematopoietic stem cell transplant recipients in the United States.[12]

Hundreds of Aspergillus species exist, but fewer than 40 have been associated with human disease.[CDC. Aspergillosis Basics. April 24, 2024] Aspergillus fumigatus is the most common species implicated across all forms of aspergillosis.[13][14][15] Historically, A fumigatus was thought to account for approximately 90% of invasive infections; however, recent studies indicate a lower proportion, with prevalence varying by geographic and clinical settings.[16][17][16] In a study of organ transplant recipients across 23 United States centers, A fumigatus caused 60% of infections, while A flavus, A niger, and A terreus accounted for smaller percentages. Multiple species contributed to 12% of infections.[18] Conversely, among ICU patients with invasive mold infections in India, A flavus caused 47% of cases, followed by A fumigatus at 39%, A terreus at 6%, and A niger at 4%.[19] The route of infection and the manifestation of disease depend on the specific clinical syndrome. Pulmonary Pulmonary aspergillosis is contracted via inhalation of Aspergillus conidia.[6] Aspergillus is ubiquitous in the environment, with concentrations ranging from 1 to 100 conidia/m³, depending on whether the location is indoors or outdoors, and higher in certain areas, eg, areas with soil disruption.[20] In invasive pulmonary and bronchial aspergillosis, the underlying cause is an inadequate immune response, which allows fungal growth and invasion.[1] CPA arises from colonization in structurally abnormal lungs, such as cavities remaining after prior tuberculosis; approximately one-third of individuals treated for pulmonary TB retain residual cavities, contributing to CPA prevalence in TB-endemic regions.[21] ABPA and severe asthma with fungal sensitization result from hypersensitivity reactions, with A fumigatus acting as the primary allergen.[1] Rhinosinusitis

Pulmonary aspergillosis is contracted via inhalation of Aspergillus conidia.[6] Aspergillus is ubiquitous in the environment, with concentrations ranging from 1 to 100 conidia/m³, depending on whether the location is indoors or outdoors, and higher in certain areas, eg, areas with soil disruption.[20] In invasive pulmonary and bronchial aspergillosis, the underlying cause is an inadequate immune response, which allows fungal growth and invasion.[1] CPA arises from colonization in structurally abnormal lungs, such as cavities remaining after prior tuberculosis; approximately one-third of individuals treated for pulmonary TB retain residual cavities, contributing to CPA prevalence in TB-endemic regions.[21] ABPA and severe asthma with fungal sensitization result from hypersensitivity reactions, with A fumigatus acting as the primary allergen.[1] Rhinosinusitis Rhinosinusitis is contracted by inhalation of conidia through the nasal route and predominantly occurs in severely immunocompromised hosts. Poorly controlled diabetes mellitus is a significant risk factor.[9] Although A fumigatus is generally thought to be the most common cause of fungal sinusitis caused by Aspergillus species, A flavus is a common cause in certain geographic settings, including the Middle East, Africa, and Southeast Asia.[22] In addition, chronic granulomatous invasive rhinosinusitis occurs in immunocompetent patients, with A flavus the most predominant causative species.[7] Cerebral Aspergillus species reach the central nervous system (CNS) and brain either hematogenously, in the case of disseminated infection, or via direct extension from contiguous areas, eg, the mastoid, middle ear, or paranasal sinuses.[23] Endophthalmitis Cataract surgery can serve as an entry point for Aspergillus species, leading to fungal endophthalmitis.[24] Keratitis caused by Aspergillus species is often associated with contact lenses or other substances that damage the corneal epithelium, which increases the risk of infection.[25][26] Osteomyelitis Aspergillus enters the bone via disseminated infection in severely immunocompromised hosts or by direct inoculation, eg, intravenous drug use or surgical site infection.[27][28] Cutaneous and Soft Tissue

Cataract surgery can serve as an entry point for Aspergillus species, leading to fungal endophthalmitis.[24] Keratitis caused by Aspergillus species is often associated with contact lenses or other substances that damage the corneal epithelium, which increases the risk of infection.[25][26] Osteomyelitis Aspergillus enters the bone via disseminated infection in severely immunocompromised hosts or by direct inoculation, eg, intravenous drug use or surgical site infection.[27][28] Cutaneous and Soft Tissue Aspergillus can enter the skin via venous catheters, chronic inflammatory skin conditions, or trauma.[29] Burns provide ample portals of entry.[30] Aspergillus is among the most common invasive fungal infections due to combat-related trauma, eg, complex blast injuries.[31] Aspergillus species have been increasingly recognized as a cause of onychomycosis, with nail trauma, immunodeficiency, and exposure of the nails to the soil as gateways to procuring this infection.[32] Disseminated and Other Sites Disseminated infections often originate from one of the sites described above in the immunocompromised host, but dissemination from the pulmonary route is common.[33] Growing hyphae gain access to the bloodstream by invading the endothelium of blood vessels.[33] Endocarditis due to Aspergillus is a rare event, most often occurring in the setting of cardiac surgery, in persons with prosthetic heart valves, or in severely immunosuppressed individuals.[34] Rarely, gastrointestinal aspergillosis can develop due to ingestion of fungal conidia.[35] Profound immunosuppression and the presence of underlying mucositis are thought to contribute as entry points.[35]

Pulmonary Invasive aspergillosis mostly impacts the immunocompromised population, eg, people living with advanced stages of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), those with hematologic malignancies, prolonged neutropenia, long-term corticosteroid use, those on immunosuppression, and recipients of hematopoietic or solid organ transplants.[36][37][38][39] Incidence after a hematopoietic stem-cell transplant ranges from 0.5% after an autologous stem-cell transplant to up to 3.9% after a transplant from an unrelated donor.[40] Invasive aspergillosis can also be seen in critically ill intensive care patients with an underlying pulmonary condition, eg, chronic obstructive pulmonary disease (COPD) or asthma.[39] Invasive aspergillosis has affected those with severe influenza (termed influenza-associated pulmonary aspergillosis or IAPA) and, more recently, severe COVID-19 infection (termed COVID-19-associated pulmonary aspergillosis or CAPA).[41][42] The incidence of invasive aspergillosis in hospitalized patients rose by 44% between 2004 and 2013, and increased in 2020 and 2021 due to the COVID-19 pandemic.[43][44] The rise in incidence is, in part, due to improved diagnostics and increased frequency of transplantation procedures.[45] Rarely, invasive pulmonary aspergillosis can occur following trauma, including traumatic combat-related injury, severe burns, or near-drowning.[31][46][47][46][48] Those working in construction, farming, and wastewater treatment plants may be at increased risk of Aspergillus infection due to chronic exposure in their work environments.[49] Smoking marijuana contaminated with the fungus may also place an individual at risk for infection.[50] Nosocomial Aspergillus infections have been reported from hospital showers and healthcare facilities undergoing construction.[51] Worldwide, approximately 2 million cases of invasive aspergillosis are estimated to occur annually.[11]

The incidence of invasive aspergillosis in hospitalized patients rose by 44% between 2004 and 2013, and increased in 2020 and 2021 due to the COVID-19 pandemic.[43][44] The rise in incidence is, in part, due to improved diagnostics and increased frequency of transplantation procedures.[45] Rarely, invasive pulmonary aspergillosis can occur following trauma, including traumatic combat-related injury, severe burns, or near-drowning.[31][46][47][46][48] Those working in construction, farming, and wastewater treatment plants may be at increased risk of Aspergillus infection due to chronic exposure in their work environments.[49] Smoking marijuana contaminated with the fungus may also place an individual at risk for infection.[50] Nosocomial Aspergillus infections have been reported from hospital showers and healthcare facilities undergoing construction.[51] Worldwide, approximately 2 million cases of invasive aspergillosis are estimated to occur annually.[11] Persons with underlying lung diseases, eg, COPD, TB, asthma, lung cancer, and sarcoidosis, are at risk for developing CPA.[6] All persons with CPA have a history of structural lung disease, eg, residual cavities, scarring, or bullae. The most significant risk factor for CPA is prior treatment for pulmonary TB. In one systematic review, among all individuals with TB, the prevalence of CPA was approximately 9% during treatment and 13% following treatment. In those with persistent respiratory symptoms, the prevalence of CPA was approximately 20% during treatment and almost 50% following treatment.[52] The annual incidence of CPA is estimated to be 1.8 million.[11] ABPA is almost exclusively found in persons with asthma and cystic fibrosis.[53] Among those with asthma, an estimated 2% to 3% of individuals have ABPA.[54] In those with cystic fibrosis, the estimated prevalence of ABPA is approximately 9%.[55] Rhinosinusitis Other forms of aspergillosis are less common. Approximately 12 million cases of fungal rhinosinutitis are estimated worldwide,[56] with Aspergillus species a common causative pathogen. The most common risk factors are immunosuppression and poorly controlled diabetes mellitus.[57] Cerebral

ABPA is almost exclusively found in persons with asthma and cystic fibrosis.[53] Among those with asthma, an estimated 2% to 3% of individuals have ABPA.[54] In those with cystic fibrosis, the estimated prevalence of ABPA is approximately 9%.[55] Rhinosinusitis Other forms of aspergillosis are less common. Approximately 12 million cases of fungal rhinosinutitis are estimated worldwide,[56] with Aspergillus species a common causative pathogen. The most common risk factors are immunosuppression and poorly controlled diabetes mellitus.[57] Cerebral Among patients with proven invasive aspergillosis, approximately 5% demonstrate CNS involvement.[58] An autopsy study reported CNS involvement in 21% of individuals with disseminated aspergillosis.[59] Immunosuppression represents the principal risk factor, particularly prolonged neutropenia associated with hematologic malignancies and hematopoietic stem cell transplantation.[60][61] Endophthalmitis Fungal endophthalmitis is rare. Risk factors for endophthalmitis include exogenous sources, eg, intraocular surgery, penetrating foreign bodies, or contaminated intraocular foreign bodies. Endogenous endopthalmitis develops due to hematogenous spread from another source in the body, eg, the lungs. Exogenous endophthalmitis accounts for an estimated 80% of cases. Aspergillus and Fusarium species account for the majority of cases.[62] Osteomyelitis Osteomyelitis due to Aspergillus species is rare. In a literature review conducted between 1936 and 2013, 310 cases were identified.[63] Risk factors included chronic granulomatous disease, hematological malignancy, transplantation, and diabetes mellitus. Infections involved the spine (49%), skull, bones (18%), ribs (9%), long bones (9%), sternum (5%), and chest wall (4%). A fumigatus was the most common species, followed by A flavus and A nidulans.[63] In another literature review from 2003 to 2021, 63 cases were noted. Most involved the ribs, followed by the sternum, and the tibia.[27] Cutaneous and Soft Tissue

Osteomyelitis due to Aspergillus species is rare. In a literature review conducted between 1936 and 2013, 310 cases were identified.[63] Risk factors included chronic granulomatous disease, hematological malignancy, transplantation, and diabetes mellitus. Infections involved the spine (49%), skull, bones (18%), ribs (9%), long bones (9%), sternum (5%), and chest wall (4%). A fumigatus was the most common species, followed by A flavus and A nidulans.[63] In another literature review from 2003 to 2021, 63 cases were noted. Most involved the ribs, followed by the sternum, and the tibia.[27] Cutaneous and Soft Tissue The incidence of invasive fungal infections following admission to burn centers ranges from approximately 1% to 15%, with Aspergillus species among the most commonly isolated pathogens.[64][65] In a study using a large United States dataset, infection with Aspergillus species was associated with a higher mortality rate than with any other fungal pathogen.[66] In a retrospective study of United States military personnel injured during combat in Afghanistan, 13% developed an invasive fungal infection, with risk factors including dismounted blast injury, traumatic amputation, and receipt of large blood volume transfusion. Mucorales, Aspergillus species, and Fusarium species are the most commonly isolated pathogens.[67] Disseminated and Other Sites Dissemination most commonly occurs hematogenously from a primary infection in the lungs. Fungal endocarditis is generally rare. Candida species account for approximately 52% of fungal endocarditis cases, while Aspergillus species is the most common cause of non-Candida fungal endocarditis, accounting for approximately 24% of cases. Risk factors include prosthetic heart valves, structural heart disease, implantable cardiac devices, injection drug use, and immunosuppression.[68]

An intact immune system typically can clear inhaled Aspergillus conidia through multiple layers of defense, including: Physical barriers (eg, mucus and cilia) Innate immunity of macrophages and neutropils Reactive oxygen species Neutrophil extracellular traps (NETS) Soluble factors (eg, surfactants and complement) Dendritic cells' participation in an adaptive immune response In an immunocompetent person, Aspergillus conidia are inhaled and taken up by phagocytes in the lungs.[1] Neutrophils, pulmonary macrophages, and pulmonary epithelial cells play a crucial immunologic role. The conidia germinate into hyphae at body temperature. Phagocytes are attracted to proteins from the fungal cell wall, eg, beta-1,3-glucan, which activate major immune effector pathways and recruit alveolar macrophages.[1] Neutrophils are attracted via released cytokines and kill the invasive hyphae via the release of nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reactive oxygen species.[9][69] If any of these mechanisms are impaired in an immunocompromised patient, the infection may propagate.[70] Aspergillus is notable for angioinvasion, with thrombosis of blood vessels causing tissue necrosis and allowing spread to distant sites.[6] Patients with structural lung disease and viral pneumonitis are at risk of developing aspergillosis due to the following pathogenesis: Impaired mucociliary clearance Pulmonary epithelial damage Poorly vascularized regions of the lung Loss of alveolar immune responses [71] Critically ill patients receiving intensive care are at risk of infection due to critical illness-associated immune dysregulation. Moreover, patients receiving prolonged mechanical ventilation experience disruption of pulmonary defense mechanisms.[71] In the case of ABPA, Aspergillus conidia do not trigger the typical immune response and instead activate TH2 CD4 T-cells.[6]

Submitting appropriate specimens for analysis is paramount for accurate and timely diagnosis.[72] Tissue, aspirates, and fluids (eg, bronchoalveolar lavage) obtained from the affected organs or area of concern are ideal specimens. Additionally, although fungal features are readily apparent in formalin-fixed tissue, clinicians must consider that formalin fixation sterilizes the biopsy. Therefore, sending tissue for culture in a sterile tube or container along with a formalin-fixed specimen speeds diagnosis and the receipt of crucial information. Aspergillus may be seen in hematoxylin-eosin-stained tissue specimens. (see Image. Invasive Pulmonary Aspergilosis) Additional stains used in the examination of Aspergillus species include periodic acid-Schiff and Gomori's methenamine silver stain (GMS). Fluorescent dyes, eg, calicoflor white, are often employed. Septate hyphae that exhibit dichotomous (acute angle) branching are observed.[72] Several species of Aspergillus have characteristic features. A fumigatus is notable for having a uniseriate conidiophore with phialides sporulating from the upper two-thirds of the vesicle (see Image. Aspergillus Fumigatus).[73] A niger is notable for having larger conidia.[73] Tissue pathology from individuals with invasive fungal sinusitis reveals pale and necrotic mucosa, as infarction occurs due to angioinvasion. Evaluation of vessel walls reveals occlusion and evidence of invading fungal hyphae.[7]

A thorough history and physical exam should be performed on every individual suspected of having an Aspergillus infection. Care should be taken to understand potential individual risk factors for invasive disease and to focus on eliciting all history related to immunosuppression, including any chemotherapy, prolonged corticosteroid use, and immunosuppressants. Attention should be paid to any history of malignancy with a detailed treatment history, including a history of ibrutinib, fludarabine, venetoclax use, or history of CAR-T therapy.[9] Transplant history should be noted, with careful review of the posttransplant course, including the history of graft-versus-host disease and the duration of any neutropenia. A history of lung disease and any environmental exposures, eg, construction work, gardening, or work in wastewater treatment, should be carefully noted. When obtaining clinical history, clinicians should also inquire about recent pulmonary infections, eg, COVID-19 or influenza. Furthermore, clinicians should perform an in-depth investigation of current and past medical conditions to assess the potential for an immunocompromised state, including taking a detailed sexual history and carefully obtaining information about frequent infections that could raise concern for immunodeficiency, eg, chronic granulomatous disease. Invasive Pulmonary Aspergillosis Individuals with invasive aspergillosis are often critically ill or immunocompromised. The most common initial symptoms of pulmonary infection include fever, worsening dyspnea, increased sputum production, hemoptysis, and pleuritic chest pain. Fever may not manifest in the severely immunocompromised; therefore, fever can be absent despite progressive infection.[6] Invasive aspergillosis is rapidly progressive, and symptoms often manifest only once the disease is advanced. Rales, rhonchi, dullness to percussion, and bloody sputum or endotracheal tube secretions may be present. The importance of early administration of antifungal therapy in the treatment of invasive pulmonary aspergillosis cannot be overemphasized, and establishing a timely, definite diagnosis is almost always a challenge. Thus, a presumptive diagnosis based on a combination of risk factors, nonspecific symptoms and signs, radiographic findings, and surrogate markers of infection is necessary. Invasive Fungal Rhinosinusitis

Invasive aspergillosis is rapidly progressive, and symptoms often manifest only once the disease is advanced. Rales, rhonchi, dullness to percussion, and bloody sputum or endotracheal tube secretions may be present. The importance of early administration of antifungal therapy in the treatment of invasive pulmonary aspergillosis cannot be overemphasized, and establishing a timely, definite diagnosis is almost always a challenge. Thus, a presumptive diagnosis based on a combination of risk factors, nonspecific symptoms and signs, radiographic findings, and surrogate markers of infection is necessary. Invasive Fungal Rhinosinusitis Invasive fungal sinusitis often presents with vague symptoms, but facial pain, retro-orbital pain, exophthalmos, visual impairment, nasal congestion, and fever can be noted.[74] On physical exam, sinus tenderness, nasal discharge, pallor or necrosis of the oral or nasal mucosa or conjunctiva, new mobility or hypesthesia of teeth, proptosis, or cranial nerve abnormalities may be present.[75] Chronic Pulmonary Aspergillosis CPA most commonly presents with a cough.[6] Due to lung vascularity, hemoptysis occurs in approximately 50% of cases from encroachment on the involved vessels. Hemoptysis may be the first presenting symptom. Systemic symptoms, including fever, night sweats, and weight loss, are commonly seen in the disease’s cavitary, fibrosing, and necrotizing forms. These symptoms are similar to those of pulmonary TB, so it can be difficult to differentiate these entities clinically. The physical examination in CPA depends on the extent of the infection and underlying pulmonary disease. ABPA ABPA presents with recurrent asthma exacerbations, with the most prominent finding being dyspnea and wheezing, along with copious sputum production often containing brown mucus plugs.[53] Wheezing is often noted.[6] Aspergilloma Individuals with a single aspergilloma are frequently asymptomatic and present with an incidental finding on radiographic imaging. People with small aspergillomas or nodules are often asymptomatic and have normal physical examinations.[6] The most common symptom, if it occurs, is cough or hemoptysis.

The presence of Aspergillus in a sputum sample in and of itself does not establish the presence of infection unless other signs, symptoms, and host risk factors are present. Evaluation should proceed based on the suspected clinical syndrome. Invasive Pulmonary Aspergillosis Patients with suspected invasive pulmonary aspergillosis should undergo diagnostic testing, including chest computed tomography (CT), to evaluate the presence or extent of the disease and to guide further efforts, eg, bronchoscopy.[76] Noninvasive testing may include obtaining respiratory specimens for staining, histopathology, fungal culture, molecular testing, and biomarker analysis. The presence of narrow (3 to 6 microns wide), septated hyphae with dichotomous, acute-angle branching is consistent with Aspergillus species. However, other molds, including Scedosporium and Fusarium, can have a similar appearance. Fungal culture Aspergillus grows on fungal culture within 1 to 3 days of incubation. Both microscopy and culture are relatively insensitive. Culture of Aspergillus species from sputum or bronchoalveolar lavage supports the diagnosis of aspergillosis in patients with risk factors and characteristic radiographs. Tissue sampling from a sterile site revealing Aspergillus hyphae confirms the diagnosis.[76] Consensus definitions for invasive aspergillosis have been developed by the European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSG).[77]

Aspergillus grows on fungal culture within 1 to 3 days of incubation. Both microscopy and culture are relatively insensitive. Culture of Aspergillus species from sputum or bronchoalveolar lavage supports the diagnosis of aspergillosis in patients with risk factors and characteristic radiographs. Tissue sampling from a sterile site revealing Aspergillus hyphae confirms the diagnosis.[76] Consensus definitions for invasive aspergillosis have been developed by the European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSG).[77] The timely diagnosis of invasive aspergillosis is always challenging. Obtaining appropriate tissue specimens is often difficult, particularly in critically ill patients who may not tolerate the procedure. In the absence of contraindications, patients should undergo bronchoscopy if noninvasive testing is inconclusive and suspicion for invasive aspergillosis is high. Bronchoscopy permits inspection of the airways, collection of tissue for fungal culture, PCR, cytopathology, and collection of deep lower respiratory tract fungal cultures and galactomannan samples.[76] Individuals suspected of having invasive aspergillosis should be managed by infectious disease clinicians, pulmonologists, critical care physicians, and, if indicated, transplant physicians. Patients within the first 3 months of a lung transplant are at increased risk of invasive fungal infection at the site of the anastomosis.[76] This risk is the highest during the first 3 to 4 weeks posttransplantation.[78] Anastomotic infections may be identified upon routine screening bronchoscopy and generally require debridement at the anastomotic site.[76] Serum biomarkers Serum biomarkers, eg, the galactomannan enzyme immunoassay, are helpful in select populations. Serum biomarkers have the best-studied utility in patients with hematologic malignancy and hematopoietic stem cell transplant recipients, with an approximate 70% sensitivity.[76] Sensitivity decreases in other patient populations, with values as low as 20% reported in patients receiving solid-organ transplants.[76]

Serum biomarkers, eg, the galactomannan enzyme immunoassay, are helpful in select populations. Serum biomarkers have the best-studied utility in patients with hematologic malignancy and hematopoietic stem cell transplant recipients, with an approximate 70% sensitivity.[76] Sensitivity decreases in other patient populations, with values as low as 20% reported in patients receiving solid-organ transplants.[76] Galactomannan test sensitivity is also decreased in patients with IAPA and CAPA.[79] For this reason, serum galactomannan is recommended as a biomarker in patients with hematologic malignancy and hematopoietic stem cell transplant recipients not receiving mold prophylaxis.[76][80] At an optical density of 0.5, galactomannan has a sensitivity of 97.4% for detecting likely invasive aspergillosis.[81] Galactomannan can also be measured in bronchoalveolar lavage samples, with a sensitivity of 93.2% at an optical density of 0.5.[82] Causes of false-positive galactomannan enzyme immunoassay include receipt of recent blood transfusion, presence of certain crystalloids used in collecting bronchoalveolar lavage samples, administration of piperacillin-tazobactam and amoxicillin-clavulanate, total parenteral nutrition, and ingestion of food items containing plant-based galactomannans, including ice-popsicles.[76][83][80] Cross-reactivity with Fusarium, Histoplasma, Blastomyces, and Talaromyces species is also present.[76][80] The 1,3-beta-D-glucan (BDG) tests are very sensitive but are nonspecific, as BDG is a component of the cell wall of a variety of fungi.[76] Several causes of false-positive tests have been identified, including the use of membrane filters during blood processing, the administration of beta-lactam and beta-asparaginase drugs, the administration of albumin, and contamination of blood collection tubes with glucan. Molecular studies

The 1,3-beta-D-glucan (BDG) tests are very sensitive but are nonspecific, as BDG is a component of the cell wall of a variety of fungi.[76] Several causes of false-positive tests have been identified, including the use of membrane filters during blood processing, the administration of beta-lactam and beta-asparaginase drugs, the administration of albumin, and contamination of blood collection tubes with glucan. Molecular studies Notably, blood cultures are very rarely positive for Aspergillus species, even with disseminated disease.[84] Polymerase chain reaction (PCR) is increasingly available for Aspergillus detection in whole blood, serum, and plasma.[85] PCR has a higher sensitivity in bronchoalveolar lavage fluid than in blood. In a meta-analysis, the sensitivity and specificity of PCR for invasive aspergillosis were 84% and 76%, respectively. The sensitivity was 65%, and the specificity was 95% with 2 positive PCR results.[86] However, PCR has historically lacked standardization across assays, and sensitivity decreases for individuals on mold-active prophylaxis.[87] Molecular diagnostic tests have enabled the identification of Aspergillus species.[88] Diagnostic imaging Chest CT scans may demonstrate characteristic findings of invasive pulmonary aspergillosis. The characteristic halo sign consists of a central nodule surrounded by ground-glass changes (see Image. Halo Sign). The nodule consists of invasive Aspergillus, and the ground-glass opacities are due to surrounding thrombosis and hemorrhage, best seen with contrast CT. Although the halo sign is the most characteristic finding of invasive aspergillosis, nodules without surrounding ground-glass changes are more commonly seen. The air crescent sign may be seen later in the course of invasive aspergillosis, after neutropenia resolves. It consists of a crescent of air around a macronodule.[89] Pleural effusions due to invasive aspergillosis are exceedingly rare and result from necrosis of lung tissue adjacent to the pleura.[90] Empyema due to A niger can be associated with very dark pleural fluid and has been rarely reported.[91] Invasive Fungal Rhinosinusitis

Chest CT scans may demonstrate characteristic findings of invasive pulmonary aspergillosis. The characteristic halo sign consists of a central nodule surrounded by ground-glass changes (see Image. Halo Sign). The nodule consists of invasive Aspergillus, and the ground-glass opacities are due to surrounding thrombosis and hemorrhage, best seen with contrast CT. Although the halo sign is the most characteristic finding of invasive aspergillosis, nodules without surrounding ground-glass changes are more commonly seen. The air crescent sign may be seen later in the course of invasive aspergillosis, after neutropenia resolves. It consists of a crescent of air around a macronodule.[89] Pleural effusions due to invasive aspergillosis are exceedingly rare and result from necrosis of lung tissue adjacent to the pleura.[90] Empyema due to A niger can be associated with very dark pleural fluid and has been rarely reported.[91] Invasive Fungal Rhinosinusitis Suspicion of invasive fungal rhinosinusitis should prompt emergent evaluation by an otolaryngologist to perform nasal endoscopy with tissue collected for histopathology and culture, or to proceed with other surgical intervention. Patients should be managed by infectious disease clinicians, otolaryngologists, and, if indicated, transplant physicians. Adjunctive imaging, eg, CT of the maxillofacial sinuses and magnetic resonance imaging (MRI) of the brain, helps identify bone abnormalities and characterize the extent of sinus disease. However, clinicians should note that CT can underestimate the extent of the infection, and MRI may better characterize disease progression.[92] Chronic Pulmonary Aspergillosis The European Society for Clinical Microbiology and Infectious Diseases (ESCMID), in collaboration with the European Respiratory Society (ERS) and the Infectious Diseases Society of America (IDSA), has published comprehensive guidelines for the diagnosis and management of CPA.[93][76] Several criteria must be met to establish a diagnosis, including at least 3 months of compatible pulmonary symptoms, systemic symptoms, or progressive characteristic radiologic findings, in association with confirmatory microbiology or serology.[76]

The European Society for Clinical Microbiology and Infectious Diseases (ESCMID), in collaboration with the European Respiratory Society (ERS) and the Infectious Diseases Society of America (IDSA), has published comprehensive guidelines for the diagnosis and management of CPA.[93][76] Several criteria must be met to establish a diagnosis, including at least 3 months of compatible pulmonary symptoms, systemic symptoms, or progressive characteristic radiologic findings, in association with confirmatory microbiology or serology.[76] Furthermore, this must be accompanied by a compatible underlying pulmonary condition in the setting of immunocompetency.[76] A positive serum Aspergillus IgG can also help diagnose chronic aspergillosis.[76][94] A tissue biopsy of an aspergilloma may help confirm the diagnosis and exclude alternative conditions that may cause lung masses.[2][95] Chest CT scans often reveal 1 or more thin- or thick-walled cavities with intracavitary material. In chronic necrotizing aspergillosis, consolidation can be seen, which generally starts in the upper lobes with bronchiectasis and evolves into cavitation.[96] Pleural thickening can be noted adjacent to lung cavities, which is concerning for locally invasive diseases.[89] Please see StatPearls' companion resource, "Aspergilloma," for further information on this condition. ABPA No single test establishes the diagnosis of ABPA, which is based on classic clinical manifestations, characteristic radiographs, and immunological findings (see Image. Allergic Bronchopulmonary Aspergillosis). Patients with cystic fibrosis or asthma suspected of ABPA should undergo Aspergillus skin testing or measurement of Aspergillus-specific IgE. Additional testing should include total serum IgE levels, Aspergillus-specific IgG or serum precipitins, peripheral eosinophil count, and chest radiographs.

No single test establishes the diagnosis of ABPA, which is based on classic clinical manifestations, characteristic radiographs, and immunological findings (see Image. Allergic Bronchopulmonary Aspergillosis). Patients with cystic fibrosis or asthma suspected of ABPA should undergo Aspergillus skin testing or measurement of Aspergillus-specific IgE. Additional testing should include total serum IgE levels, Aspergillus-specific IgG or serum precipitins, peripheral eosinophil count, and chest radiographs. A diagnosis is established in patients who have a positive Aspergillus skin test or serum IgE, in addition to at least 2 of the following: total serum IgE greater than 1000 IU/mL, elevated Aspergillus IgG or precipitins, eosinophilia, and characteristic radiologic findings (see Images. Chronic Obstructive Pulmonary Disease and Allergic Bronchopulmonary Aspergillosis and COPD and ABPA X-Ray).[6] A chest CT scan can reveal dilation of the central airways with mucoid impaction (see Image. COPD and ABPA CT Scan).[89][96] Additionally, "toothpaste shadows" can transiently be seen, caused by mucus plugging.[6] Please see StatPearls' companion resource, "Allergic Bronchopulmonary Aspergillosis," for further information. Aspergilloma The ESCMID, ERS, and IDSA have published comprehensive guidelines for the diagnosis and management of aspergilloma.[93][76] Aspergilloma is often suspected based on findings from chest x-rays or CT scans in patients being evaluated for symptoms related to underlying pulmonary diseases. For example, aspergillomas may be suspected in individuals with preexisting TB lung cavities, bronchiectasis, tumors, or chronic lung abscesses based on radiographic evidence. Alternatively, hemoptysis resulting from an aspergilloma may also prompt further evaluation. Aspergillomas can be seen on chest radiographs and CT of the chest as well-defined masses within preexisting cavities (see Image. Aspergilloma Mass).[89] A tissue biopsy of an aspergilloma may help confirm the diagnosis and exclude alternative conditions that may cause lung masses.[2][95] Please see StatPearls' companion resource, "Aspergilloma," for further information on this condition.

Invasive Pulmonary Aspergillosis Treatment for suspected invasive aspergillosis should be promptly initiated while investigations are ongoing, given the rapidly progressive nature of the infection. When selecting an antifungal, clinicians must consider the local resistance profiles of Aspergillus species, the history of antimold prophylaxis used, the Aspergillus species involved (if known), and the patient's comorbidities, immune status, organ dysfunction, and potential for QT prolongation.[76] Clinicians should note that A terreus and A alliaceus are intrinsically resistant to amphotericin B, and A calidoustus is intrinsically resistant to azoles.[80] In most instances, for individuals with presumptive and established invasive aspergillosis, either voriconazole or isavuconazole is recommended.[76][79] Voriconazole troughs should be monitored 4 to 7 days into therapy and after dosage changes or modifications in other medications that could affect therapeutic levels.[76] Isavuconazole is noninferior to voriconazole, has a more predictable pharmacokinetic profile, and has fewer adverse effects.[79] Additionally, clinicians should counsel patients regarding the adverse effects of voriconazole, including photosensitivity. In the transplant population, an association between prolonged voriconazole use and increased risk of cutaneous squamous carcinoma has been noted.[97] In the absence of transplantation, this risk associated with voriconazole has not been definitively established.[98] Alternative therapies for invasive aspergillosis include posaconazole, itraconazole, and liposomal amphotericin B (L-AmB).[76] Please see StatPearls' companion resource, "Antifungal Agents," for further information.

Additionally, clinicians should counsel patients regarding the adverse effects of voriconazole, including photosensitivity. In the transplant population, an association between prolonged voriconazole use and increased risk of cutaneous squamous carcinoma has been noted.[97] In the absence of transplantation, this risk associated with voriconazole has not been definitively established.[98] Alternative therapies for invasive aspergillosis include posaconazole, itraconazole, and liposomal amphotericin B (L-AmB).[76] Please see StatPearls' companion resource, "Antifungal Agents," for further information. For patients receiving mold prophylaxis with voriconazole, treatment with L-AmB is recommended until susceptibility testing is available.[76] Echinocandin monotherapy is not recommended due to its fungistatic activity against Aspergillus. The role of combination therapy of echinocandins plus either azoles or amphotericin B has not been firmly established; some experts recommend this approach as salvage therapy for individuals with severe disease or those at high risk for poor outcomes.[76][80][79] Immunosuppression should be reduced to its furthest extent possible.[76] Therapy should continue for at least 6 to 12 weeks, but may need to be continued longer based on the extent of the disease and the degree of immunosuppression.[99][100] When treating invasive pulmonary aspergillosis, a repeat CT scan of the chest is recommended after 2 weeks of therapy to monitor for improvement. This interval may need to be shorter if nodules or other signs of invasive disease are noted sufficiently proximal to major blood vessels. In these cases, surgery may also be considered to avoid pulmonary hemorrhage. Invasive Fungal Rhinosinusitis

For patients receiving mold prophylaxis with voriconazole, treatment with L-AmB is recommended until susceptibility testing is available.[76] Echinocandin monotherapy is not recommended due to its fungistatic activity against Aspergillus. The role of combination therapy of echinocandins plus either azoles or amphotericin B has not been firmly established; some experts recommend this approach as salvage therapy for individuals with severe disease or those at high risk for poor outcomes.[76][80][79] Immunosuppression should be reduced to its furthest extent possible.[76] Therapy should continue for at least 6 to 12 weeks, but may need to be continued longer based on the extent of the disease and the degree of immunosuppression.[99][100] When treating invasive pulmonary aspergillosis, a repeat CT scan of the chest is recommended after 2 weeks of therapy to monitor for improvement. This interval may need to be shorter if nodules or other signs of invasive disease are noted sufficiently proximal to major blood vessels. In these cases, surgery may also be considered to avoid pulmonary hemorrhage. Invasive Fungal Rhinosinusitis The treatment of invasive fungal rhinosinusitis involves a combination of surgical removal of necrotic tissue to obtain specimens for diagnostic evaluation and antifungal therapy. As with other forms of invasive aspergillosis, reducing immunosuppression when possible is recommended. Empiric treatment with L-AmB is recommended before species identification as it covers common causes of fungal rhinosinusitis, including Mucorales. Once the causative pathogen has been determined, targeted treatment is the same as for invasive pulmonary aspergillosis. Since fungal rhinosinusitis often involves extensive tissue damage and deep fungal invasion of the skull, treatment is typically extended to 3 to 6 months. Maintaining strict glycemic control is important in patients with diabetes mellitus. Chronic Pulmonary Aspergillosis

The treatment of invasive fungal rhinosinusitis involves a combination of surgical removal of necrotic tissue to obtain specimens for diagnostic evaluation and antifungal therapy. As with other forms of invasive aspergillosis, reducing immunosuppression when possible is recommended. Empiric treatment with L-AmB is recommended before species identification as it covers common causes of fungal rhinosinusitis, including Mucorales. Once the causative pathogen has been determined, targeted treatment is the same as for invasive pulmonary aspergillosis. Since fungal rhinosinusitis often involves extensive tissue damage and deep fungal invasion of the skull, treatment is typically extended to 3 to 6 months. Maintaining strict glycemic control is important in patients with diabetes mellitus. Chronic Pulmonary Aspergillosis In general, the primary goal of aspergillosis treatment is to alleviate symptoms and achieve clinical and radiologic stability to prevent disease progression and minimize or prevent hemoptysis. Please see StatPearls' companion resource, "Aspergilloma," for more detailed management information. While clinical improvement is the primary aim, achieving clinical stability is often the accepted outcome. Treatment is typically initiated with either voriconazole or itraconazole. Evidence suggests better clinical outcomes with voriconazole compared to itraconazole.[101] A minimum of 6 months of therapy for all patients is recommended, though lifelong therapy may be necessary for patients with chronic progressive disease. In the case of azole resistance, micafungin, caspofungin, or L-AmB should be considered. Tranexamic acid may be effective in the management of mild to moderate hemoptysis, but bronchial artery embolization and surgical resection should be considered for severe cases. Treatment response is measured by evaluating symptoms, performing pulmonary function testing, and following serum Aspergillus IgG levels.[76] Repeat radiologic imaging, recommended after 6 months of therapy, may show the decreased size of aspergillomas and cavitary lesions. ABPA

A minimum of 6 months of therapy for all patients is recommended, though lifelong therapy may be necessary for patients with chronic progressive disease. In the case of azole resistance, micafungin, caspofungin, or L-AmB should be considered. Tranexamic acid may be effective in the management of mild to moderate hemoptysis, but bronchial artery embolization and surgical resection should be considered for severe cases. Treatment response is measured by evaluating symptoms, performing pulmonary function testing, and following serum Aspergillus IgG levels.[76] Repeat radiologic imaging, recommended after 6 months of therapy, may show the decreased size of aspergillomas and cavitary lesions. ABPA In brief, the main goals of treatment for ABPA are to control symptoms, prevent exacerbations, and preserve lung function. Please see StatPearls' companion resource, "Allergic Bronchopulmonary Aspergillosis," for more detailed management information. For acute ABPA exacerbations with opacities on lung imaging and elevated total serum IgE levels, systemic glucocorticoids are the primary treatment. Both the IDSA and ISHAM recommend antifungal therapy, preferentially with itraconazole or voriconazole, in cases where individuals are not responsive to glucocorticoids.[76][102] Biologic agents, eg, anti-interleukin (IL)-5 (eg, mepolizumab, benralizumab), anti-IgE (eg, omalizumab), or anti-IL-4 receptor alpha subunit antibodies (eg, dupilumab) can be used in persons with recurrent exacerbations or in those unable to taper off oral glucocorticoids.[76] Aspergilloma In persons without hemoptysis and minimal to no symptoms, treatment of Aspergilloma is typically unnecessary. Please see StatPearls' companion resource, "Aspergilloma," for more detailed information on management. Approximately 7% to 10% of aspergillomas resolve without treatment.[103] An episode of minor hemoptysis predicts subsequent massive hemoptysis in approximately 30% of patients.[104] If symptoms like hemoptysis develop, resection is advised unless contraindicated. In those without spontaneous resolution, annual imaging is typically performed to monitor for stability.

In persons without hemoptysis and minimal to no symptoms, treatment of Aspergilloma is typically unnecessary. Please see StatPearls' companion resource, "Aspergilloma," for more detailed information on management. Approximately 7% to 10% of aspergillomas resolve without treatment.[103] An episode of minor hemoptysis predicts subsequent massive hemoptysis in approximately 30% of patients.[104] If symptoms like hemoptysis develop, resection is advised unless contraindicated. In those without spontaneous resolution, annual imaging is typically performed to monitor for stability. For those with severe hemoptysis, surgery or bronchial artery embolization is indicated.[76] Surgery is most effective in patients with a single lesion and not diffuse disease. Therapeutic embolization can control hemoptysis but is not curative.[105] For individuals undergoing surgery, preoperative antifungal therapy is typically not indicated unless there is a risk of surgical spillage. Postoperatively, antifungals are typically unnecessary unless spillage of fungal contents into the pleural space occurred or an incomplete aspergilloma resection was performed. In this case, 3 months of antifungal treatment is typically appropriate, and follow-up CT imaging 6 to 12 months after surgery is recommended. In high-risk surgical candidates and those reluctant to undergo surgery, prolonged courses of triazoles are recommended.

Differential diagnoses for invasive aspergillosis include: Asthma Atypical mycobacterial infection Bacterial pneumonia Bacterial sinusitis with abscess Blastomycosis Bronchiectasis Cavitary lung cancer Cavitary polyangiitis with granulomatosis Coccidioidomycosis Cystic fibrosis Eosinophilia Eosinophilic pneumonia Histoplasmosis Hypersensitivity pneumonitis Interstitial lung disease Nocardiosis Pulmonary sarcoidosis Tuberculosis Differential diagnoses for CPA include: Pulmonary tuberculosis Nontuberculous mycobacteria Histoplasmosis Coccidioidomycosis Actinomycosis Neoplasm Differential diagnoses for an aspergilloma include: Primary lung malignancy Metastatic disease Hydatid cyst Lung abscess Differential diagnoses for ABPA include: Corticosteroid-dependent asthma without ABPA Severe asthma with fungal sensitivity (SAFS) Cystic fibrosis Bronchiectasis Chronic necrotizing aspergillosis Chronic eosinophilic pneumonia Chronic obstructive pulmonary disease (COPD) Churg–Strauss syndrome Bronchocentric granulomatosis Acute eosinophilic pneumonia (including drug-induced pneumonitis) Pulmonary tuberculosis Parasitic infections Hypersensitivity pneumonitis

A landmark trial in 2002 reported decreased mortality in patients with invasive pulmonary aspergillosis treated with voriconazole (survival rate at 12 weeks: 70.8%) compared with amphotericin B deoxycholate (survival rate: 57.9%).[106] A higher remission rate in the voriconazole group was also observed.[106] As of January 2026, the following ongoing clinical trials were investigating the optimal treatment of aspergillosis infections: Invasive Aspergillosis NCT05101187 is a phase 3, multicenter, blinded, randomized study evaluating olorofim versus liposomal amphotericin B followed by standard of care in persons with proven or probable invasive aspergillosis. NCT05238116 is a phase 3, double-blind, multicenter, randomized study assessing the safety and efficacy of nebulized PC945 (opelconazole) versus placebo in combination with other antifungal therapy for the treatment of refractory invasive pulmonary aspergillosis. CPA NCT06794554 is a phase 2, open-label, multicenter, single-arm study evaluating the safety and effectiveness of rezafungin for the treatment of CPA in persons with limited treatment options. NCT05653193 is a phase 2, single-center, randomized feasibility study evaluating oral triazoles plus subcutaneous interferon gamma versus oral triazoles only for the treatment of CPA. NCT03656081 is a phase 3, single-center, randomized study evaluating oral itraconazole plus nebulized liposomal amphotericin B versus oral itraconazole plus nebulized placebo for the treatment of CPA. ABPA NCT06174922 is a phase 3, single-center, randomized study evaluating oral itraconazole plus prednisolone versus prednisolone only versus itraconazole only for the treatment of ABPA.

Invasive Pulmonary Aspergillosis Historically, invasive aspergillosis was associated with mortality rates as high as 80%.[10] A recent analysis estimates a crude mortality rate of 85% globally.[11] Lower mortality rates have also been observed, including an all-cause mortality rate of 58% in a cohort of hematopoietic stem cell transplant recipients in the United States.[12] Poor outcomes are associated with severe immunosuppression, critical illness, older age, underlying malignancy, disseminated disease, receipt of corticosteroids, delayed diagnosis, and antifungal resistance, among others.[107][108] Invasive Fungal Rhinosinusitis In a 2013 systematic review, the mortality rate was approximately 50% for acute invasive fungal sinusitis.[109] Poor outcomes are associated with severe immunosuppression, extensive disease involving the skull base, orbit, or brain, delayed diagnosis, poorly-controlled diabetes mellitus, and tobacco use.[109][110] Chronic Pulmonary Aspergillosis The prognosis following treatment for CPA varies. In one study, approximately 50% of individuals experienced significant clinical improvement, 30% worsened clinically, and approximately 20% had stable disease after treatment.[111] Predictors of poor clinical response include underlying lung disease (including lung cancer and emphysema), older age, male sex, lower body mass index, hypoalbuminemia, the presence of an aspergilloma, and systemic corticosteroid use.[112][113] ABPA The prognosis of allergic bronchopulmonary aspergillosis is favorable in patients with mild alterations in pulmonary function.[53] However, many patients may require steroids for a prolonged period of time if the diagnosis is delayed.[53] Delays in diagnosis may lead to steroid resistance and the development of lung fibrosis.[114] Poor outcomes have been linked to a younger age of ABPA onset, allergic sensitization, airway fungal burden, high attenuation mucus in the airway, longer durations of asthma, and poor pulmonary function.[115][116]] Aspergilloma

The prognosis of allergic bronchopulmonary aspergillosis is favorable in patients with mild alterations in pulmonary function.[53] However, many patients may require steroids for a prolonged period of time if the diagnosis is delayed.[53] Delays in diagnosis may lead to steroid resistance and the development of lung fibrosis.[114] Poor outcomes have been linked to a younger age of ABPA onset, allergic sensitization, airway fungal burden, high attenuation mucus in the airway, longer durations of asthma, and poor pulmonary function.[115][116]] Aspergilloma Spontaneous resolution occurs in approximately 10% of cases of simple aspergilloma. Outcomes for simple aspergilloma after treatment, particularly following surgery, are generally excellent. The 5-year survival rate following surgery is generally between 85% and 95%, and most individuals experience resolution of their symptoms.[117][118] In one study, the 10-year survival rate was 88% for individuals with complex aspergilloma.[118] Between 5% and 7% can experience recurrence, typically due to incomplete resection of the aspergilloma, retention of cavities or other parenchymal lung abnormalities, and continued immunosuppression.[117]

The following complications are associated with various forms of aspergillosis: Invasive pulmonary aspergillosis Lung damage (eg, fibrosis, pulmonary infarction, respiratory failure, hemoptysis, tracheobronchitis) Disseminated disease Renal failure Liver failiure Treatment-related complications Multi-organ damage Death Invasive fungal rhinosinusitis Vision loss Periostitis/osteomyelitis Disseminated disease Cerebral infarction or stroke Cavernous sinus thrombosis Mycotic aneurysm Hemoptysis Treatment-related complications Death Chronic pulmonary aspergillosis Hemoptysis Aspergilloma formation Progressive fibrosis and lung destruction Chronic cavities Respiratory failure Disseminated disease Treatment-related complications Death ABPA Recurrent asthma exacerbations and steroid dependence Aspergilloma Invasive aspergillosis Chronic pulmonary aspergillosis Cavitation Local emphysema Chronic or recurrent lobar atelectasis Honeycomb fibrosis Complications related to bronchiectasis, eg, hemoptysis, recurrent pulmonary infection Treatment-related complications Aspergilloma Hemoptysis Adverse effects of antifungal agents Intraoperative and postoperative complications

Consultations that are typically requested for patients with aspergillosis include: An infectious disease consultation is imperative for invasive aspergillosis and can be helpful for other forms of aspergillosis to guide antifungal therapy. Pulmonology evaluation is highly recommended for patients with pulmonary forms of aspergillosis. Otolaryngology evaluation is imperative when invasive fungal rhinosinusitis is suspected. Those with allergic aspergillosis benefit from the management by an allergist A thoracic surgeon should be consulted to evaluate patients with CPA or aspergilloma who do not respond as expected to antifungal therapies or have hemoptysis. An interventional radiologist is often required for embolization therapy in patients with CPA, aspergilloma, and acute hemoptysis.

Aspergillosis is an opportunistic infection that requires targeted prevention strategies in immunocompromised patients. Hospitalized individuals at high risk for invasive aspergillosis require placement in private rooms equipped with HEPA filtration to reduce environmental fungal exposure.[76] Additionally, high-risk patients also require counseling to avoid activities associated with elevated fungal burdens, including gardening, exposure to construction sites, and occupations such as wastewater treatment.[76] In selected populations, antifungal prophylaxis reduces the incidence of invasive fungal infections. Prophylactic therapy warrants consideration in patients experiencing prolonged neutropenia due to chemotherapy, recipients of allogeneic hematopoietic stem cell transplants, individuals with severe or prolonged graft-versus-host disease, lung transplant recipients during the first 3 to 4 months posttransplantation, and other solid organ transplant recipients.[76] Lung transplant recipients who develop Aspergillus airway colonization within the first 6 months after transplantation or who receive intensified immunosuppression for rejection within the preceding 3 months require preemptive antifungal therapy.[76]

The following factors should be kept in mind when managing aspergillosis: Infection can range from life-threatening, as in invasive pulmonary aspergillosis and invasive rhinosinusitis, to nonurgent in cases of CPA, ABPA, and aspergilloma. Risk factors for invasive aspergillosis include immune dysfunction, most notably prolonged neutropenia, bone marrow, and solid organ transplants Lung transplant recipients are at high risk, particularly within the first 3-months posttransplant Additional risk factors include: Prolonged corticosteroid use Biologic immunosuppressants Critically ill patients receiving intensive care Severe influenza pneumonitis Severe Covid-19 pneumonitis The major risk factor for CPA and aspergilloma is underlying structural lung disease ABPA is almost exclusively found in persons with asthma and cystic fibrosis A fumigatis, A flavus, A niger, and A tereus, in that order, are the most common species causing infection Inhalation of aerosolized conidia is the most common form of transmission Direct inoculation of tissues from trauma is possible Disseminated infection from a primary site of infection is possible Fungemia occurs and is responsible for dissemination; however, the presence of positive blood cultures is exceedingly rare Pulmonary aspergillosis has been increasingly identified in patients with pneumonitis due to influenza and COVID-19 Aspergillus organisms appear as dichotomous (acute angle) branching septate hyphae Scedosporium and Fusarium have a similar appearance The presence of Aspergillus in sputum and bronchoalveolar lavage fluid, in and of itself, is not diagnostic of infection Histology of biopsied tissue demonstrating the presence of Aspergillus invading tissue is diagnostic of invasive aspergillosis Elevated serum galactomannan is a biomarker of invasive disease Sensitivity is approximately 70% in patients with hematologic malignancies and those who have received bone marrow transplants Sensitivity is decreased in other settings solid organ transplantation Critically ill patients receiving intensive care Severe influenza pneumonitis Severe Covid-19 pneumonitis Other mold infections can cause elevated galactomannan levels False positive galactomannan tests can be due to beta-lactams, foods rich in plant polysaccharides, enteral nutrition, mucositis, and crystalloid solutions, and lab contamination Chest CT scans are valuable in the diagnosis and evaluation of invasive pulmonary aspergillosis

Other mold infections can cause elevated galactomannan levels False positive galactomannan tests can be due to beta-lactams, foods rich in plant polysaccharides, enteral nutrition, mucositis, and crystalloid solutions, and lab contamination Chest CT scans are valuable in the diagnosis and evaluation of invasive pulmonary aspergillosis Parenchymal nodules are common Nodules surrounded by ground-glass opacities (halo sign) are characteristic Chest CT scans are valuable in the diagnosis and evaluation of acute fungal rhinosinusitis, CPA, ABPA, and aspergilloma. Patients with suspected invasive aspergillosis must receive antifungal therapy immediately while undergoing diagnostic evaluation. Voriconazole or isavuconazole are the drugs of choice Posaconazole, itraconazole, or liposomal amphotericin B (LAm-B) are acceptable alternatives Echinocandin monotherapy is not recommended Combination therapy with an azole or LAm-B plus an echinocandin can be considered for salvage therapy Patients with suspected rhinocerebral aspergillosis must receive antifungal therapy immediately and require emergency debridement A combination of clinical, radiologic, microbiologic, and immunologic evidence is required to establish a diagnosis of CPA. A combination of clinical, radiologic, and immunologic evidence is required to establish a diagnosis of CPA and ABPA Aspergilloma is most often diagnosed incidentally on chest radiographs. Pulmonary cavities due to TB are a significant risk factor for the development of an aspergilloma. Aspergilloma is often asymptomatic, unless it causes hemoptysis Hemoptysis can be mild or life-threatening Invasive aspergillosis is associated with a mortality rate of approximately 60% to 85%

Aspergillosis encompasses a spectrum of disease ranging from allergic and chronic pulmonary conditions to rapidly progressive invasive infections. Prognosis remains favorable in immunocompetent individuals but becomes guarded in transplant recipients and other immunocompromised patients, particularly those with prolonged neutropenia or critical illness. Early recognition and prompt initiation of targeted antifungal therapy are essential when invasive aspergillosis is suspected. Evidence-based guidelines support integrated diagnostic strategies, including advanced imaging, galactomannan assays, microbiologic evaluation, and bronchoscopy when appropriate, to expedite diagnosis and improve survival. Optimal outcomes require a coordinated interprofessional approach. Infectious disease clinicians, pulmonologists, otolaryngologists, transplant physicians, pathologists, microbiology laboratory personnel, nurses, and pharmacists each contribute specialized expertise. Physicians and advanced practitioners must rapidly assess risk factors, initiate empiric antifungal therapy, and align care with guideline-directed pathways. Microbiology teams ensure timely processing of cultures and biomarkers, while pharmacists optimize antifungal selection, dosing, therapeutic drug monitoring, and drug interaction management.[120] Nurses monitor clinical status, reinforce infection prevention strategies, and support patient education. Clear communication among consultants, adherence to standardized protocols, and coordinated follow-up enhance patient safety, reduce delays in care, and strengthen overall team performance.