Materiały źródłowe

• #1 Aspergillosis – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/aspergillosis/symptoms-causes/syc-20369619

  Aspergillosis is an infection caused by a type of mold (fungus). […] Depending on the type of aspergillosis, treatment may involve observation, antifungal medications or, in rare cases, surgery. […] If you have a weakened immune system and develop an unexplained fever, shortness of breath or a cough that brings up blood, get immediate medical care. In the case of invasive aspergillosis, prompt treatment is crucial. In some cases, treatment with antifungal medication begins as soon as aspergillosis is suspected, even before testing has confirmed the diagnosis. […] The most serious complication of invasive aspergillosis is the spread of the infection to other parts of your body, especially your brain, heart and kidneys. Invasive aspergillosis spreads rapidly and may be fatal.

• #1 Aspergillosis Symptoms and Diagnosis | American Lung Association

  https://www.lung.org/lung-health-diseases/lung-disease-lookup/aspergillosis/symptoms-diagnosis

  When diagnosing aspergillosis, your doctor will want to consider your risk factors and medical history in conjunction with your symptoms and a physical exam. […] Then, they may suggest lab tests including skin, blood and sputum tests. […] Imaging tests such as a chest X-ray or CT scan can help with diagnosis because your doctor may be able to spot a nodule or fungal mass on your lung, caused by the mold, that would prompt your doctor to do further testing. […] If they are still unsure, a tissue biopsy may be the best way to get a clear diagnosis.

• #1 Diagnosis of invasive aspergillosis – UpToDate

  https://www.uptodate.com/contents/diagnosis-of-invasive-aspergillosis/print

  Diagnosis of invasive aspergillosis […] The diagnosis of invasive aspergillosis will be reviewed here. […] General approach — Culture of Aspergillus spp in combination with the histopathologic demonstration of tissue invasion by hyphae provides definitive evidence of invasive aspergillosis. […] A rational first step to establishing the diagnosis of invasive aspergillosis involves the use of less invasive modalities, such as serum biomarkers (galactomannan, beta-D-glucan, and polymerase chain reaction [PCR] assays), and obtaining sputum and/or bronchoalveolar lavage (BAL) specimens for fungal staining, fungal culture, BAL galactomannan, and/or PCR. […] A positive sputum fungal stain and/or culture should prompt therapy of hosts who are at risk for invasive aspergillosis. In the right clinical context, a positive BAL galactomannan antigen, BAL PCR for aspergillus species, or a positive serum galactomannan antigen can also provide a presumptive diagnosis.

• #1 Aspergillosis Workup: Approach Considerations, Laboratory Studies, Imaging Studies

  https://emedicine.medscape.com/article/296052-workup

  The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology, and the European Respiratory Society (ESCMID-ECMM-ERS) have published recommendations for making the diagnosis based on clinical, radiologic, and microbiologic data. Chest CT and thin-section multidetector CT (MDCT) are recommended to detect pulmonary infiltrates. Pulmonary CT angiography is recommended to identify vessel occlusion or erosion. Specific recommendations include the following: […] Chest computed tomography and bronchoscopy with bronchoalveolar lavage (BAL) are strongly recommended in patients with suspected of having pulmonary invasive aspergillosis (IA). […] For diagnosis, direct microscopy, preferably using optical brighteners, histopathology, and culture are strongly recommended.

• #1 Aspergillosis Workup: Approach Considerations, Laboratory Studies, Imaging Studies

  https://emedicine.medscape.com/article/296052-workup

  Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. […] Polymerase chain reaction (PCR) should be considered in conjunction with other diagnostic tests. […] If invasive pulmonary aspergillosis is suspected, the Infectious Diseases Society of America (IDSA) recommends performing CT scanning of the chest, regardless of chest radiography findings. […] The Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) updated the definition of invasive fungal disease (IFD) in 2021. For the diagnosis of pulmonary aspergillosis, one of the following findings must present on computed tomography: […] Definitive diagnosis of invasive aspergillosis or chronic necrotizing Aspergillus pneumonia depends on the demonstration of the organism in tissue.

• #1 Aspergillosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/296052-overview

  Weekly monitoring of serum levels of galactomannan, a major component of the Aspergillus cell wall, can be used to screen patients who are at high risk for the development of invasive Aspergillus infection. An elevated galactomannan level in BAL fluid may also be helpful for early diagnosis of invasive aspergillosis. […] In early disease, CT scans may demonstrate a characteristic halo sign (ie, an area of ground-glass infiltrate surrounding nodular densities). In later disease, CT scans may show a crescent of air surrounding nodules, indicative of cavitation. […] Because Aspergillus is angioinvasive, infiltrates may be wedge-shaped, pleural-based, and cavitary, which is consistent with pulmonary infarction.

• #1 Aspergillosis Workup: Approach Considerations, Laboratory Studies, Imaging Studies

  https://emedicine.medscape.com/article/296052-workup

  In the appropriate clinical setting of pulmonary infiltrates in a patient who is neutropenic or immunosuppressed, visualization of the characteristic fungi using Gomori methenamine silver stain or Calcofluor or a positive culture result from sputum, needle biopsy, or bronchoalveolar lavage (BAL) fluid should result in the prompt institution of therapy. […] An assay to detect galactomannan, a major component of the Aspergillus cell wall, is available. […] Patients who are at high risk, such as those who have received stem cell transplants or who have prolonged neutropenia, may be screened for the development of invasive Aspergillus infection by monitoring serum galactomannan levels weekly. […] The presence of an elevated galactomannan level in BAL fluid may also be helpful in the diagnosis of pulmonary aspergillosis in patients in whom compatible radiographic changes are present and BAL testing is performed in the suspicious area. […] A study by Luong et al of 150 BAL samples from lung transplant recipients concluded that real-time polymerase chain reaction (PCR) assays could be useful in diagnosis of invasive aspergillosis in high-risk populations.

• #1 Pulmonary aspergillosis: diagnosis and treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9724826/

  Aspergillus species are the most frequent cause of fungal infections of the lungs with a broad spectrum of clinical presentations including invasive pulmonary aspergillosis (IPA) and chronic pulmonary aspergillosis (CPA). […] The diagnosis of pulmonary aspergillosis is complex as it relies on the presence of clinical, radiological and microbiological criteria, which differ according to the type of pulmonary aspergillosis (IPA or CPA) and the type of patient population. […] The available mycological tests for IPA diagnosis include histological examination of biopsy or surgical specimens, culture and nonculture methods, such as fungal biomarkers (galactomannan, 1,3–d-glucan (BDG)) and PCR. […] Because of the paucity of clinical signs and the limited sensitivity and/or specificity of radiology and mycological tests, the diagnosis of IPA is graded according to a scale of probability (possible, probable or proven) of disease.

• #1 Pulmonary aspergillosis: diagnosis and treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9724826/

  The European Organization for Research and Treatment of Cancer and Mycoses Study Group Education and Research Consortium (EORTC-MSGERC) has established definitions for the diagnosis of possible, probable and proven IPA in immunocompromised patients. […] The sensitivity of GM in serum is lower (around 40%) in SOT than in haematologic cancer patients. […] The diagnosis of IPA in this population is difficult because of the lower specificity of radiological findings and lower sensitivity of mycological tests compared to those observed in haematologic cancer patients. […] The EORTC-MSGERC criteria for IPA do not apply in ICU patients who do not have host criteria of immunosuppression in most cases. […] The clinical presentation, diagnostic work-up and performance of diagnostic tests of IPA can vary considerably according to the type of disease and patient population. […] The diagnosis of pulmonary aspergillosis is challenging because of the limited sensitivity and specificity of diagnostic tests and the need to combine these tests for improved diagnostic accuracy.

• #1 Clinical Practice Guideline for the Diagnosis and Management of Aspergillosis: 2016 Update by IDSA

  https://www.idsociety.org/practice-guideline/aspergillosis/

  As research in the area continues, we recommend that clinicians choosing to use PCR assays employ them carefully in the management of individual patients on a case-by-case basis. Clinicians should be aware of the methodologies and performance characteristics of the specific assay used, and interpret results accordingly. When PCR assays are used, results should be considered in conjunction with other diagnostic tests and the clinical context (strong recommendation; moderate-quality evidence). […] Serum and BAL galactomannan (GM) is recommended as an accurate marker for the diagnosis of IA in adult and pediatric patients when used in certain patient subpopulations (hematologic malignancy, HSCT) (strong recommendation; high-quality evidence). […] GM is not recommended for routine blood screening in patients receiving mold-active antifungal therapy or prophylaxis, but can be applied to bronchoscopy specimens from those patients (strong recommendation; high-quality evidence).

• #1 Clinical Practice Guideline for the Diagnosis and Management of Aspergillosis: 2016 Update by IDSA

  https://www.idsociety.org/practice-guideline/aspergillosis/

  GM is not recommended for screening in SOT recipients or patients with chronic granulomatous disease (CGD) (strong recommendation; high-quality evidence). […] Serum assays for (1 3)–D-glucan are recommended for diagnosing IA in high-risk patients (hematologic malignancy, allogeneic HSCT), but are not specific for Aspergillus (strong recommendation; moderate-quality evidence). […] We recommend performing a chest computed tomographic (CT) scan whenever there is a clinical suspicion for IPA regardless of chest radiograph results (strong recommendation; high-quality evidence). […] We recommend performing a bronchoscopy with bronchoalveolar lavage (BAL) in patients with a suspicion of IPA (strong recommendation; moderate-quality evidence). Significant comorbidities such as severe hypoxemia, bleeding, and platelet transfusion-refractory thrombocytopenia may preclude BAL. The yield of BAL is low for peripheral nodular lesions, so percutaneous or endobronchial lung biopsy should be considered. We recommend the use of a standardized BAL procedure and sending the BAL sample for routine culture and cytology as well as non-culture-based methods (eg, GM) (strong recommendation; moderate-quality evidence).

• #1 Diagnosis of Chronic Pulmonary Aspergillosis: Clinical, Radiological or Laboratory?

  https://www.mdpi.com/2309-608X/9/11/1084

  The diagnostic criteria for CPA have been defined by the European Society for Clinical Microbiology and Infectious Diseases (ESCMID), the European Respiratory Society (ERS) and the European Confederation of Medical Mycology (ECMM) and include: (i) a consistent appearance in thoracic imaging (preferably by CT) for ≥3 months, (ii) direct evidence of Aspergillus infection or immunological response to Aspergillus spp., and (iii) exclusion of alternative diagnoses. […] The laboratory abnormalities commonly seen in patients with CPA can vary depending on the individual and the stage of the disease. […] Microbiological and immunological evidence of Aspergillus infection is required for establishing CPA diagnosis, but only in addition to positive thoracic CT findings. […] Serological diagnosis could be helpful in making decisions with CPA diagnosis, as elevated levels of Aspergillus-specific IgG antibodies are found in over 90% of patients with CPA, while Aspergillus precipitins are less sensitive. […] Detecting Aspergillus-specific IgG antibodies presents a key laboratory diagnostic tool in CPA and is the best noninvasive test for obtaining the diagnosis.

• #1 Aspergillosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/296052-overview

  Allergic bronchopulmonary aspergillosis (ABPA) is defined by abnormalities including the following: Asthma, Eosinophilia, A positive skin test result for Aspergillus fumigatus, Serum IgE level 500 IU/dL, Positive test results for Aspergillus precipitins (primarily IgG but also IgA and IgM). […] Chest radiography results in ABPA may vary from fleeting pulmonary infiltrates to mucoid impaction to central bronchiectasis. Computed tomography (CT) is helpful for better defining bronchiectasis, and images may demonstrate that apparent lobulated masses are mucus-filled dilated bronchi. Areas of atelectasis related to bronchial obstruction from mucoid impaction may be present. […] Definitive diagnosis of invasive aspergillosis or CNPA depends on the demonstration of the organism in tissue, as follows: Visualization of the characteristic fungi using Gomori methenamine silver stain or Calcofluor, Positive culture result from sputum, needle biopsy, or bronchoalveolar lavage (BAL) fluid (however, a negative result does not exclude pulmonary aspergillosis).

• #1 Aspergillosis | LDBIO Diagnostics

  https://ldbiodiagnostics.com/en/clinic-applications/mycosis/aspergillosis/

  LDBIO_Contexte-clinique_ASPERGILLOSES_ENAspergillosis are infections due to ubiquitous fungi of the Aspergillus genus. Various pathologies induced depend on several intrinsic characteristics of the fungus itself and on its host, which will condition the virulence of the disease. […] The diversity of aspergillosis forms implies a diversity in the diagnostic tools. For invasive aspergillosis, histopathological observation, imaging, culture, fungal DNA detection using PCR and galactomannan detection via ELISA are the most commonly used techniques (Donnelly et al., 2020). […] The diagnosis of ABPA relies on a set of criteria including clinical data, total and A. fumigatus specific IgE, radiology and specific IgG (Agarwal et al., 2013). Diagnosis is complex because of the overlapping symptoms between ABPA and underlying conditions, most biological markers do not allow by themselves to discriminate between ABPA, fungal sensitization or a disease for another origin (for instance, due to exposure to another fungus such as Alternaria alternata). Alternative markers, such as the immunologic profile analysis by Western Blot (Piarroux et al., 2019a).

• #1 Aspergillosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK482241/

  Culture of the Aspergillus species in the sputum or by bronchoalveolar lavage supports the diagnosis of aspergillosis, but tissue sampling revealing invasive Aspergillus hyphae finalizes the diagnosis. […] Several criteria must be met to diagnose chronic pulmonary aspergillosis. […] Patients with cystic fibrosis or asthma suspected of ABPA should undergo Aspergillus skin testing or IgE against A. fumigatus, chest imaging, a measurement of total IgE level, A. fumigatus specific IgG, serum precipitins, and blood eosinophil count. […] When aspergillosis is suspected, remembering the following pearls is helpful: Send all tissue and fluid for cytology, culture, and histopathology. […] An interprofessional team should include healthcare professionals from various disciplines to assist with care, including infectious diseases clinicians, pulmonologists, otolaryngologists, transplant physicians, pathologists, microbiology laboratory personnel, nurses, pharmacists, and infectious diseases pharmacists.

• #1 Clinical Overview of Aspergillosis | Aspergillosis | CDC

  https://www.cdc.gov/aspergillosis/hcp/clinical-overview/index.html

  Several diagnostic tools are used to diagnose aspergillosis: […] Microscopy: Tissues are observed under the microscope for Aspergillus elements. Definitive identification is difficult to make by this method alone. […] Histopathology: Similar to microscopy, sampled tissues are observed under the microscope for Aspergillus. This method is important for documenting the disease. […] Culture: This method can be done on a variety of sterile specimens to observe Aspergillus, which is typically visible 1 to 3 days after incubation. Culture allows for the microscopic identification down to the species level. […] Galactomannan antigen test: This test detects a polysaccharide that makes up part of the cell wall of Aspergillus. The Platelia assay is approved by the US Food and Drug Administration (FDA) for serum and bronchoalveolar lavage fluid.

• #1 Clinical Overview of Aspergillosis | Aspergillosis | CDC

  https://www.cdc.gov/aspergillosis/hcp/clinical-overview/index.html

  Beta-d-glucan assay: This test also detects a component in the cell wall of Aspergillus species. The Fungitell assay is approved by the FDA for diagnosis of invasive fungal infections. […] Polymerase Chain Reaction (PCR): PCR for detection of Aspergillus species from clinical specimens, including tissue and bronchoalveolar lavage fluid, is offered by some laboratories.

• #1 Laboratory Diagnosis of Invasive Pulmonary Aspergillosis | The AFWG

  https://www.afwgonline.com/resources/articles/laboratory-diagnosis-of-invasive-pulmonary-aspergillosis/

  Galactomannan assay from paired samples of BAL or serum is a nonculture-based diagnostic test. The sensitivity and specificity of galactomannan testing in BAL sample is 77.2% and 77.0%, respectively, with the cut-off level of 0.4; and 85.7% and 76.3%, respectively, with cut-off level of 0.5. For serum galactomannan testing for the diagnosis of chronic pulmonary aspergillosis, the sensitivity and specificity rates are 66.7% and 63.5%, respectively (cut off level 0.7). Aside from the detection of galactomannan from the fungal cell wall, (1-3)–D-glucan is another component that can be examined as well. Even though positive results from these two assays are not definite indications of the fungus, negative results from these tests can provide strong evidence that the sample/specimen does not have non-septate hyphae.

• #1 Pulmonary aspergillosis: infection, diagnosis and treatment – MedCrave online

  https://medcraveonline.com/JBMOA/pulmonary-aspergillosis-infection-diagnosis-and-treatment.html

  Pulmonary Aspergillosis is a group of lung disorder occurs due to the infection of Aspergillus species. […] Diagnosis is mostly done through sputum culture, serological and molecular diagnostic tools. […] Significant progress has been achieved in the categorization, diagnosis, and management of pulmonary Aspergillosis in recent years. […] Noninvasive biomarkers have simplified the suspicion and diagnosis of invasive pulmonary Aspergillosis. […] the diagnosis of Aspergillosis comprises an amalgamation of clinical valuation, laboratory tests, imaging studies and sometimes invasive procedures. […] Histopathological evaluation of lung tissue acquired via thoracoscopic or open-lung biopsy is the gold standard in the diagnosis of invasive pulmonary Aspergillosis. […] Chest computed tomography scans and innovative non-culture-based techniques like antigen detection and polymerase chain reaction may help with early detection of invasive Aspergillosis, although they have limits.

• #1 Aspergillosis – Wikipedia

  https://en.wikipedia.org/wiki/Aspergillosis

  Aspergillosis is caused by Aspergillus, a common mold, which tends to affect people who already have a lung disease such as cystic fibrosis or asthma, or who cannot fight infection themselves. The most common causative species is Aspergillus fumigatus. […] On chest X-ray and CT, pulmonary aspergillosis classically manifests as a halo sign, and later, an air crescent sign. In hematologic patients with invasive aspergillosis, the galactomannan test can make the diagnosis in a noninvasive way. Galactomannan is a component of the fungal wall. False-positive Aspergillus galactomannan tests have been found in patients on intravenous treatment with some antibiotics or fluids containing gluconate or citric acid such as some transfusion platelets, parenteral nutrition, or PlasmaLyte. […] On microscopy, Aspergillus species are reliably demonstrated by silver stains, e.g., Gridley stain or Gomori methenamine-silver. These give the fungal walls a gray-black colour. The hyphae of Aspergillus species range in diameter from 2.5 to 4.5 m. They have septate hyphae, but these are not always apparent, and in such cases they may be mistaken for Zygomycota. Aspergillus hyphae tend to have dichotomous branching that is progressive and primarily at acute angles of around 45.

• #1 Diagnosis – Aspergillosis Patients & Carers Support

  https://aspergillosis.org/diagnosis/

  A chest X-ray allows visualisation of the inside of the lungs and may identify an abnormality such as any lung cavities formed as a result of another underlying disease or infection, or if a fungal ball (aspergilloma) is present. […] A skin test where a small needle is used to scratch the surface of the skin can be used to detect whether a patient has circulating IgE antibodies specific for Aspergillus. This is a more common test if you have asthma or ABPA. A positive result indicates that the patient is sensitised to Aspergillus. […] A sample of sputum, other tissue fluids or tissue biopsies may be sent to the laboratory to be cultured, in order to see if it is possible to grow Aspergillus from the sample. […] A bronchoscopy is a procedure where a flexible tube is passed into the lungs to view the lung and airways the patient is sedated during the procedure. Samples of the lung tissue or fluids can be biopsied through the bronchoscope for examination in the laboratory by culture and molecular tests, if needed.

• #1 Aspergillosis – Wikipedia

  https://en.wikipedia.org/wiki/Aspergillosis

  In those with suspected pulmonary aspergillosis, bronchoalveolar lavage can be done to collect fluid from the airways of the lungs for analysis. This involves exploration of the airway with a bronchoscope, then the introduction of a small amount of fluid into the airway which is then collected for analysis. This analysis can include assessment of cells, galactomannan testing, staining and fungal culture as well as polymerase chain reaction (PCR) assessment. PCR has an 85% sensitivity and 76% specificity for the diagnosis of aspergillosis, sensitivity is increased when the test is combined with galactomannan testing. […] Allergic bronchopulmonary aspergillosis (ABPA) is diagnosed by establishing an immune sensitization to aspergillosis, which can be done by measuring total eosinophils, total immunoglobulin E (IgE) and aspergillus specific IgE and IgG levels. Elevations of these markers, combined with clinical and radiologic findings suggesting infection are used to confirm ABPA.

• #1 Aspergillosis – Infectious Diseases – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/infectious-diseases/fungi/aspergillosis

  Aspergillosis is an opportunistic infection that usually affects the lower respiratory tract and is caused by inhaling spores of the filamentous fungus Aspergillus, commonly present in the environment. […] Diagnosis is based on imaging, histopathology, and specimen staining and culture. […] Diagnosis of Aspergillosis […] Usually fungal culture and histopathology of tissue samples […] Galactomannan antigen test on serum and/or bronchoalveolar lavage fluid […] Culture and histopathology of a tissue sample are usually necessary for confirmation; histopathology helps distinguish invasive infection from colonization. […] Serum Aspergillus galactomannan is specific but often not sufficiently sensitive to identify most cases in their early stages. In invasive pulmonary aspergillosis, the galactomannan test on bronchoalveolar lavage fluid is much more sensitive than that on serum and is often the only diagnostic option for patients with thrombocytopenia, for whom biopsy is contraindicated. […] Culture and histopathology of a tissue sample are usually necessary, but the galactomannan test on bronchoalveolar lavage fluid can help diagnose pulmonary infection.

• #1 Aspergillosis – Diagnosis & treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/aspergillosis/diagnosis-treatment/drc-20369623

  Diagnosing an aspergilloma or invasive aspergillosis can be difficult. Aspergillus is common in all environments but difficult to distinguish from certain other molds under the microscope. The symptoms of aspergillosis are also similar to those of other lung conditions such as tuberculosis. […] Your doctor is likely to use one or more of the following tests to pinpoint the cause of your symptoms: […] Imaging test. A chest X-ray or computerized tomography (CT) scan a type of X-ray that produces more-detailed images than conventional X-rays do can usually reveal a fungal mass (aspergilloma), as well as characteristic signs of invasive aspergillosis and allergic bronchopulmonary aspergillosis. […] Respiratory secretion (sputum) test. In this test, a sample of your sputum is stained with a dye and checked for the presence of aspergillus filaments. The specimen is then placed in a culture that encourages the mold to grow to help confirm the diagnosis.

• #1 Allergic bronchopulmonary aspergillosis – Symptoms, diagnosis and treatment | BMJ Best Practice

  https://bestpractice.bmj.com/topics/en-gb/836

  Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to bronchial colonisation by Aspergillus fumigatus mould, typically affecting patients with an underlying predisposition, specifically asthma or cystic fibrosis. […] Early diagnosis and rapid initiation of treatment can prevent the development of bronchiectasis or pulmonary fibrosis that otherwise occurs in the later stages of the disease. […] ABPA typically presents with a constellation of clinical, laboratory, and radiographic findings, including symptoms of bronchospasm, wheezing, and productive cough; laboratory markers of allergic inflammation such as eosinophilia and elevated IgE levels; evidence of Aspergillus allergy and sensitisation (e.g., formation of Aspergillus-specific IgE and IgG antibodies); as well as characteristic radiographic infiltrates. […] Diagnostic investigations include skin test for Aspergillus fumigatus sensitivity, serum total IgE, FBC with peripheral blood eosinophil count, chest x-ray, high-resolution CT chest, and Aspergillus-specific IgE.

• #1

  https://haematologica.org/article/view/6824

  More recently, the importance of the halo sign as an early sign of IPA was demonstrated in a study in which base-line chest CT scans of 235 patients who participated in a randomized clinical trial were reviewed. […] In these studies, the most reasonable explanation for the improved outcome was that the halo sign represented an earlier stage of IPA, allowing the initiation of antifungal therapy with a lower fungal burden. […] Therefore, attempts to further improve the outcome are needed. In order to do this, clinicians should be able to recognize IPA before the appearance of the halo sign. […] The speed with which the angioinvasive phase evolves also explains the performance of diagnostic tests in neutropenic and non-neutropenic patients. […] The first step is to apply serial serum serology monitoring with galactomannan (3 times/week), and establish aggressive criteria for ordering a chest CT scan.

• #1

  https://haematologica.org/article/view/6824

  As stated above, diagnosing IPA at an earlier stage will result in the initiation of appropriate antifungal therapy when the fungal burden is still low. This may potentially further improve the outcome. […] In summary, the application of serial serum galactomannan and an aggressive strategy of early chest CT scan in neutropenic patients may allow clinicians to diagnose IPA with a low fungal burden, before the appearance of the halo sign, and thus prevent the occurrence of lung infarction.

• #1 Updated guidelines for the diagnosis and management of aspergillosis – Misch – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/11294/9775

  New guidelines for the diagnosis and treatment of infections due to Aspergillus species were published in August of 2016 by the Infectious Diseases Society of America (IDSA), replacing those previously published in 2008. These guidelines incorporate new data published between January 2008 and December 2014. The document provides guidance on non-culture-based diagnosis of Aspergillus infections, discourages the use of combination anti-fungal therapy for primary management, and begins to define the place in therapy for isavuconazole, a new anti-fungal drug of the azole class approved by the U.S. Food and Drug Administration (FDA) in March 2015 to treat aspergillosis and mucormycosis. […] The guidelines address 98 clinical questions that cover the three main presentations of Aspergillus infection, invasive, chronic or saprophytic, and allergic aspergillosis.

• #1 Updated guidelines for the diagnosis and management of aspergillosis – Misch – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/11294/9775

  A central recommendation that remains unchanged from the previous iteration of the guidelines is the pre-eminence of voriconazole as first-line therapy for treatment of all invasive forms of aspergillosis. […] Routine use of combination anti-fungal therapy is not recommended for primary therapy. […] For empiric or pre-emptive anti-fungal therapy (disease site unspecified), liposomal amphotericin B, caspofungin, micafungin, or voriconazole are recommended. […] Modifications to the previous recommendations for management of aspergillosis include the addition of isavuconazole as an alternative to voriconazole for primary treatment of pulmonary aspergillosis. […] For invasive pulmonary aspergillosis (IPA), amphotericin B lipid complex (ABLC), caspofungin, micafungin, posaconazole and itraconazole have been relegated to salvage therapy.

• #1 Updated guidelines for the diagnosis and management of aspergillosis – Misch – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/11294/9775

  For the first time, the guidelines advise reducing mold exposure within the hospital or home environment for the most vulnerable patient groups. […] Three other areas of expanded discussion in the new guidelines include (I) non-culture-based diagnosis of aspergillosis through measurement of fungal cell wall components or amplification of Aspergillus by polymerase chain reaction (PCR) in host tissues; (II) testing for resistance; and (III) the role of combination anti-fungal therapy. […] Methods for the laboratory diagnosis of aspergillosis have evolved considerably beyond culture and now involve detection of fungal cell wall components in human tissues, particularly within blood and bronchoalveolar lavage fluid (BALf), and amplification of fungal DNA by PCR. […] The guidelines recommend restricting the use of either GM or DG as non-culture-based diagnostic tools in patients with hematologic malignancy or HSCT.

• #2

  https://haematologica.org/article/view/6824

  Invasive pulmonary aspergillosis (IPA) is the leading invasive fungal disease in high-risk hematologic patients, including those with acute myeloid leukemia (AML) receiving chemotherapy for induction of remission, and allogeneic hematopoietic cell transplant (HCT) recipients. […] Although the exact reasons for the improvement in the outcome are not clear, it is possible that this is partly due to the fact that IPA has been diagnosed at an earlier disease stage, after the introduction of routine chest computed tomography (CT) scans, and the use of serum biomarkers, such as galactomannan (GMI). […] An important contribution to the management of IPA was made by studies showing the importance of the halo sign as the earliest detectable sign of disease. […] When CT scans were obtained upon clinical suspicion of IPA, the halo sign was detected in 13% of patients, compared with 92% when CT scans were systematically performed.

• #2 Aspergillosis – Symptoms, diagnosis and treatment | BMJ Best Practice

  https://bestpractice.bmj.com/topics/en-gb/425

  Aspergillosis is caused by filamentous fungi of the Aspergillus species, which are found ubiquitously in soil. […] High-resolution computer tomography (CT) scan and serum Aspergillus galactomannan antigen test are useful tests for early diagnosis of IA. […] Early diagnosis and therapy significantly improve prognosis of patients with IA. […] Key diagnostic factors include presence of risk factors, pleuritic chest pain, pleural rub, nasal ulcer, and skin rash. […] 1st investigations to order include CXR, high-resolution chest CT scan, high-resolution sinuses CT scan, high-resolution brain CT scan, MRI sinuses, MRI brain, serum Aspergillus galactomannan (GM) antigen by enzyme immunoassay (EIA), sputum culture, and sputum smear. […] Investigations to consider include BAL Aspergillus galactomannan (GM) antigen, bronchoscopy with bronchoalveolar lavage (BAL) fungal stain, bronchoscopy with BAL fungal culture, polymerase chain reaction, serum (1-3)-beta-D-glucan, serum Aspergillus IgG, tissue biopsy, tissue fungal culture, and tissue fungal stain.

• #2 Pulmonary aspergillosis: diagnosis and treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9724826/

  Aspergillus species are the most frequent cause of fungal infections of the lungs with a broad spectrum of clinical presentations including invasive pulmonary aspergillosis (IPA) and chronic pulmonary aspergillosis (CPA). […] The diagnosis of pulmonary aspergillosis is complex as it relies on the presence of clinical, radiological and microbiological criteria, which differ according to the type of pulmonary aspergillosis (IPA or CPA) and the type of patient population. […] The available mycological tests for IPA diagnosis include histological examination of biopsy or surgical specimens, culture and nonculture methods, such as fungal biomarkers (galactomannan, 1,3–d-glucan (BDG)) and PCR. […] Because of the paucity of clinical signs and the limited sensitivity and/or specificity of radiology and mycological tests, the diagnosis of IPA is graded according to a scale of probability (possible, probable or proven) of disease.

• #2 Aspergillosis – Wikipedia

  https://en.wikipedia.org/wiki/Aspergillosis

  Aspergillosis is caused by Aspergillus, a common mold, which tends to affect people who already have a lung disease such as cystic fibrosis or asthma, or who cannot fight infection themselves. The most common causative species is Aspergillus fumigatus. […] On chest X-ray and CT, pulmonary aspergillosis classically manifests as a halo sign, and later, an air crescent sign. In hematologic patients with invasive aspergillosis, the galactomannan test can make the diagnosis in a noninvasive way. Galactomannan is a component of the fungal wall. False-positive Aspergillus galactomannan tests have been found in patients on intravenous treatment with some antibiotics or fluids containing gluconate or citric acid such as some transfusion platelets, parenteral nutrition, or PlasmaLyte. […] On microscopy, Aspergillus species are reliably demonstrated by silver stains, e.g., Gridley stain or Gomori methenamine-silver. These give the fungal walls a gray-black colour. The hyphae of Aspergillus species range in diameter from 2.5 to 4.5 m. They have septate hyphae, but these are not always apparent, and in such cases they may be mistaken for Zygomycota. Aspergillus hyphae tend to have dichotomous branching that is progressive and primarily at acute angles of around 45.

• #2 Aspergillosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/296052-overview

  Allergic bronchopulmonary aspergillosis (ABPA) is defined by abnormalities including the following: Asthma, Eosinophilia, A positive skin test result for Aspergillus fumigatus, Serum IgE level 500 IU/dL, Positive test results for Aspergillus precipitins (primarily IgG but also IgA and IgM). […] Chest radiography results in ABPA may vary from fleeting pulmonary infiltrates to mucoid impaction to central bronchiectasis. Computed tomography (CT) is helpful for better defining bronchiectasis, and images may demonstrate that apparent lobulated masses are mucus-filled dilated bronchi. Areas of atelectasis related to bronchial obstruction from mucoid impaction may be present. […] Definitive diagnosis of invasive aspergillosis or CNPA depends on the demonstration of the organism in tissue, as follows: Visualization of the characteristic fungi using Gomori methenamine silver stain or Calcofluor, Positive culture result from sputum, needle biopsy, or bronchoalveolar lavage (BAL) fluid (however, a negative result does not exclude pulmonary aspergillosis).

• #2 Clinical Practice Guideline for the Diagnosis and Management of Aspergillosis: 2016 Update by IDSA

  https://www.idsociety.org/practice-guideline/aspergillosis/

  As research in the area continues, we recommend that clinicians choosing to use PCR assays employ them carefully in the management of individual patients on a case-by-case basis. Clinicians should be aware of the methodologies and performance characteristics of the specific assay used, and interpret results accordingly. When PCR assays are used, results should be considered in conjunction with other diagnostic tests and the clinical context (strong recommendation; moderate-quality evidence). […] Serum and BAL galactomannan (GM) is recommended as an accurate marker for the diagnosis of IA in adult and pediatric patients when used in certain patient subpopulations (hematologic malignancy, HSCT) (strong recommendation; high-quality evidence). […] GM is not recommended for routine blood screening in patients receiving mold-active antifungal therapy or prophylaxis, but can be applied to bronchoscopy specimens from those patients (strong recommendation; high-quality evidence).

• #2 Clinical Overview of Aspergillosis | Aspergillosis | CDC

  https://www.cdc.gov/aspergillosis/hcp/clinical-overview/index.html

  Several diagnostic tools are used to diagnose aspergillosis: […] Microscopy: Tissues are observed under the microscope for Aspergillus elements. Definitive identification is difficult to make by this method alone. […] Histopathology: Similar to microscopy, sampled tissues are observed under the microscope for Aspergillus. This method is important for documenting the disease. […] Culture: This method can be done on a variety of sterile specimens to observe Aspergillus, which is typically visible 1 to 3 days after incubation. Culture allows for the microscopic identification down to the species level. […] Galactomannan antigen test: This test detects a polysaccharide that makes up part of the cell wall of Aspergillus. The Platelia assay is approved by the US Food and Drug Administration (FDA) for serum and bronchoalveolar lavage fluid.

• #2 Accuracy of serological tests for diagnosis of chronic pulmonary aspergillosis: A systematic review and meta-analysis | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222738

  Chronic pulmonary aspergillosis (CPA) is a slow and progressive disease that develops in preexisting lung cavities of patients with tuberculosis sequelae, and it is associated with a high mortality rate. […] Serologic tests are indispensable for diagnosis in the absence of positive cultures, and they are considered the best noninvasive tests for diagnosis. […] The Aspergillus IgG antibody test is strongly recommended by the Infectious Diseases Society of America (IDSA). […] In practice, precipitation techniques have already been replaced by Aspergillus enzyme-linked immunosorbent assay (ELISA) IgG antibody detection test. […] Despite its importance, serology for Aspergillus IgG detection using ELISA still cannot reach a definitive conclusion on diagnostic performance in CPA; significant differences in sensitivity, specificity, and coefficient of variation need to be explored in cohorts of well-characterized patients.

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