Manifestations and diagnosis of Aspergillus infection │ Clinically essential

Aspergillus (aspergillus) is a fungus widely present in nature, belongs to a subtype of fungi, is a typical filamentous bacteria, belongs to the common condition pathogenic fungus, widely distributed in nature, water, soil, air, moldy food, clothing, etc. are easy to survive in aspergillus. They do not have high requirements for the growth environment, can grow in 6 ~ 55 ° C and relatively low humidity environment, Aspergillus can produce a large number of spores, and can be spread through airborne widespread diffusion.

Aspergillus spores are about 2 to 5 μm in size, in the air can be presented in a suspended state, spores from the respiratory tract into the human body can cause Aspergillosis infection, human respiratory system such as sinuses, pharynx, tracheobronchial and lung is the most susceptible to involvement, can be parasitic in the respiratory system, colonization and then spread to the whole body, can involve bronchial, lungs, gastrointestinal tract, nervous system, bones, skin, mucous membranes, eyes and nose and other multi-organ systems, patients with serious damage to the immune system may cause invasive aspergillosis.

Epidemiology and risk factors

At present, the cases of aspergillosis infection are increasing year by year, according to conservative estimates, there are currently 290,000 cases of chronic pulmonary aspergillosis patients and 4.84 million cases of allergic bronchopulmonary aspergillosis patients in the world, of which about 40,000 cases of chronic pulmonary aspergillosis patients, 490,000 cases of allergic bronchopulmonary aspergillosis patients, 160,000 cases of invasive pulmonary aspergillosis patients.

One of the reasons for the increase in cases year by year is the growth of immunosuppressed populations, such as patients with malignant tumors, or other patients who have received radiotherapy and chemotherapy for a long time and bone marrow hematopoietic stem cell transplantation, there will be agranulocytosis deficiency, and neutrophils, as the main immune cells in the body against Aspergillus, mainly through adhesion to the bacteria, degranulation and release of reactive oxygen species and other non-phagocytic methods to kill filaments or spores, and the lack of granulocytes is the most common risk factor for the occurrence of Aspergillus infection.

Recent studies have found that pulmonary aspergillosis may also increase in people without significant immunodeficiency, such as patients with ICU, invasive mechanical ventilation, and patients with lung diseases or underlying diseases such as pulmonary fibrosis, COPD, bronchiectasis, or respiratory distress syndrome. In addition, serious respiratory viral infections, including influenza virus, respiratory syncytial virus, SARS-CoV-2, etc., can also damage lung epithelial cells, providing an entrance for Aspergillus colonization. Glucocorticoids or other immunomodulatory drugs used during treatment may also exacerbate aspergillosis infection. The use of certain medications, including tyrosine kinase inhibitors and CAR-T therapy, also increases the risk of Aspergillus infection.

Clinical manifestations and diagnosis

Due to the absence of specific manifestations of Aspergillosis infection and the long detection time of pathogenic bacteria, early diagnosis of pulmonary aspergillosis is difficult and easy to misdiagnose.

Allergic bronchopulmonary aspergillosis is more common in children and young people, the symptoms are non-specific, common cough, wheezing, fever, chest pain, etc., typical patients can cough up bronchial tree sputum plugs, sputum plug coughing out bronchospasm symptoms are often significantly improved, most patients are accompanied by other allergic reactions, such as rhinitis, conjunctivitis, allergic dermatitis and increased sensitivity to common lung allergens and pollen.

The clinical symptoms of aspergilloma generally are intermittent and repeated hemoptysis, accompanied by cough, chest pain, and a few fatal large haemoptysis.

Invasive pulmonary aspergillosis is the most common and most harmful type of pulmonary aspergillosis, the clinical manifestations are non-specific and related to the immune status, can be presented as fever, dry cough, hemoptysis, chest pain, etc., may have dyspnea when the lesion is extensive, and may also appear respiratory failure in the early stages.

Chest x-ray presentation includes nodular patches, interstitial exudation, cavities, or pulmonary emboloid changes, and more than 10% of patients have no abnormalities on early chest x-ray. Chest CT should be performed when invasive pulmonary aspergillosis is suspected, which is early manifested by pulmonary nodular changes, surrounded by low-density ground glass shadows, called halo, and the necrosis of the tissue around the terminal disease to form an air-containing cavity, which can be seen typical of air crescent signs.

Galactocerin (GM test) is a unique cell wall polysaccharide component of Aspergillus, when the body is infected with Aspergillus, with the growth of hyphae, galactomannan is released from the tip of the weak hyphae, is the earliest release of antigens, can be detected in serum and alveolar lavage fluid through enzyme-linked immunosorption test, alveolar lavage fluid is more specific than the serum GM test.

(1, 3) β-D dextran (G test) is a major polysaccharide on the cell wall of Aspergillus, which can be detected by chromatographic analysis and is a fungal-specific component in addition to zygocytosis and Cryptococcus.

In addition, whole blood or serum PCR can specifically amplify Aspergillus DNA, diagnose and identify at the same time, not affected by antibiotic treatment, patient population, etc., with high sensitivity and specificity, is a diagnostic technology with good prospects in the early diagnosis of IPA.

Pathological biopsy of lung tissue showing hyphae or spores, although the gold standard for diagnosing pulmonary Aspergillus infection, should not be routinely used because of their invasive procedure.

Combined with diagnostic analysis may help overcome the limitations of any single test, such as a GM test with a sensitivity of 92%; PcR tests were 84%), but sensitivity increased to 99 percent when both tests were used simultaneously, one of which tested positive, and specificity increased to 98 percent when both tests were positive in the same patient.

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