Invasive pulmonary aspergillosis of the lungs is a lesion of the respiratory organs by mold fungi of the genus Aspergillus, which is characterized by the spread of infection through the epithelial barrier and angioinvasia. The disease proceeds according to the type of severe antibiotic-resistant pneumonia with an increase in temperature to high numbers, cough, hemoptysis and chest pain. The diagnosis is made on the basis of histological examination of biopsy material, bronchoscopy data, CT of the lungs, detection of aspergillus by laboratory methods in sputum and (or) lavage fluid. Treatment includes antifungal drugs, immunomodulators, surgical resection of affected tissues.
ICD 10
B44.0 Invasive pulmonary aspergillosis
Meaning
Invasive pulmonary aspergillosis usually occurs in people with severe immune disorders and proceeds in an acute or chronic form. Over the past 20 years, there has been a steady trend towards an increase in the incidence of this form of mycosis. The number of diagnosed cases increased by approximately 15% during this time period. In terms of the frequency of development, invasive pulmonary aspergillosis ranks first among all aggressive mycotic lung lesions. Up to 40% of patients with primary immunodeficiency, up to 30% of recipients of various organs and tissues, up to 25% of patients with hemoblastosis, about 4% of HIV-infected people become ill. The mortality rate among immunoscompromised patients with this pathology is 50% or higher.
Invasive pulmonary aspergillosis causes
Invasive pulmonary aspergillosis is observed when spores of mold fungi of the genus Aspergillus enter the respiratory system. There are 15 types of aspergillus that can cause disease when certain prerequisites appear. Conditionally pathogenic fungi are ubiquitous saprophytes that live in soil and water. Aspergillus spores, together with dust particles, rise into the air in large quantities. A person becomes infected aerogenically. The majority of infected people do not develop pathology due to the barrier functions of the body. Risk factors for the occurrence of an invasive form of the disease include:
- Violation of the functions of immunocompetent cells. Occurs with a significant decrease in the number of neutrophils and (or) alveolar macrophages or a decrease in their phagocytic activity. Neutropenia is present in a number of hemoblastoses, preparation for organ transplantation and hematopoietic cells, graft-versus-host reactions. Violation of the function of immune cells is noted in chronic granulomatous disease, the progression of AIDS, massive and prolonged therapy with corticosteroids.
- Chronic lung diseases. Invasive pulmonary aspergillosis is often found in patients suffering from chronic pulmonary pathology. Specialists in the field of pulmonology and infectology suggest a local decrease in T-cell immunity in such patients against the background of prolonged use of inhaled corticosteroids. The occurrence of the disease is facilitated by a violation of mucociliary clearance, a change in the architectonics of the bronchopulmonary system, frequent hospitalizations.
- The serious condition of the patient. An invasive variant of the course of respiratory mycosis is increasingly detected in severe patients of intensive care units in the absence of neutropenia and chronic respiratory pathologies. Most often, aspergillosis is diagnosed with liver failure, diabetes mellitus and extensive burns.
Pathogenesis
When inhaling aspergillus spores by a healthy person, most of them are removed from the respiratory tract due to the work of the mucociliary system. The rest are destroyed and absorbed by immune defense cells. Damage to the bronchial mucosa leads to colonization of the airways by micromycetes. Due to the absolute decrease in the number of alveolar macrophages and neutrophils, killing and phagocytosis of micromycetes is not carried out. Fungal spores germinate uncontrollably. Aspergillus hyphae can damage the vascular endothelium, causing arterial and venous thrombosis, pulmonary bleeding. Further spread of infection occurs hematogenically and leads to dissemination of the process.
Classification
Invasive pulmonary aspergillosis includes all forms of mycotic lesions of the respiratory tract with the germination of its epithelium by fungal hyphae. The division into pulmonary invasion and respiratory tract aspergillosis is conditional due to the rapid spread of pathology. An isolated process in the trachea and bronchi is possible only with a chronic course of the disease and a local lesion of the tracheobronchial tree site. The division of mycosis into acute and chronic forms is of therapeutic and diagnostic importance. There are the following variants of invasive pulmonary aspergillosis:
- Acute invasive. It is characterized by nonspecific symptoms of pulmonary inflammation, along the course resembles severe pneumonia or a lung infarction.
- Chronic necrotic. It is a slowly progressing process. Leads to the formation of decay cavities in the pulmonary parenchyma.
Invasive pulmonary aspergillosis symptoms
There are no pathognomonic signs of an acute variant of the course of the disease. The first symptoms of pulmonary aspergillosis are an increase in body temperature and a dry unproductive cough. Fever is accompanied by repeated chills, torrential night sweats. The temperature rises to febrile and hyperthermic values. Its curve is often irregular with morning rises and evening declines to subfebrile or normal figures. In patients receiving corticosteroids, the temperature reaction is less pronounced. The febrile state persists for 7 days or more, despite the ongoing antibacterial therapy.
The cough gradually becomes productive. Gray-green sputum is separated. When the pulmonary vessels germinate with fungal hyphae, an admixture of blood appears in it. Usually there is moderate hemoptysis, rarely – massive pulmonary bleeding. Diffuse damage to the respiratory system and aspergillosis tracheobronchitis are accompanied by shortness of breath of a mixed nature. Sometimes patients are disturbed by rather intense pleural pains, which increase with deep breathing.
Another form of the invasive process – chronic necrotic aspergillosis of the lungs – proceeds sluggishly, sometimes asymptomatically. Within a few months, subfebrility or moderate fever is detected. There is general weakness, increased fatigue, decreased appetite, noticeable weight loss. Patients complain of a constant productive cough. The sputum contains gray-green lumps containing aspergillus. Hemoptysis is often observed.
Complications
Invasive pulmonary aspergillosis of the respiratory tract, spreading hematogenically, causes damage to the central nervous system, abdominal organs, heart, thyroid gland and spleen. The disseminated process can proceed according to the type of mycotic septicemia. Angioinvasia often leads to the development of massive pulmonary hemorrhages and vascular thrombosis, which are the cause of lung and myocardial infarctions. Mortality in complications of pulmonary aspergillosis is 50-90%.
Diagnostics
Timely detection of aspergillus invasion can improve patient survival. Diagnosis of the disease is difficult due to the absence of pathognomonic symptoms and the similarity of the clinical picture with other severe lung diseases. Patients with suspected invasive respiratory aspergillosis are examined by a pulmonologist and an infectious disease specialist. When collecting anamnesis, the presence of risk factors and the body’s response to antibiotic treatment are necessarily taken into account. Physical examination is not informative enough. Such nonspecific signs of damage to the bronchopulmonary system as dry and wet wheezing, pleural friction noise are determined. The final diagnosis is established by:
- Radiography. Invasive pulmonary aspergillosis is detected belatedly on radiographs, therefore, high-resolution computed tomography is recommended. During the first week of the disease, multiple nodes with a characteristic corolla (halo symptom) are detected on CT of the lungs. Later, as a result of necrosis, a crescent-shaped zone of enlightenment appears in the infiltrate (a meniscus symptom).
- Bronchoscopy. During bronchoscopy in patients with aspergillosis tracheobronchitis, changes in the mucous membrane in the form of ulceration or film deposits are noted. Sometimes multiple endobronchial nodules are detected. Histological and cytological examination of nodes are of diagnostic importance.
- Biopsies. Histological examination of lung biopsy material is considered the gold standard for the diagnosis of this form of mycosis. The presence of septa and mycelium branching at an acute angle, as well as the isolation of aspergillus culture from lung tissue are reliable criteria for the disease.
- Laboratory methods. Mold fungi are detected by microscopy of sputum and bronchial flushing waters. Sowing biological fluids on nutrient media gives culture growth within 3-5 days. The aspergill – galactomannan antigen is detected in blood serum by enzyme immunoassay a few days before the appearance of clinical and radiological signs of the disease. In a number of European countries, the galactomannan test is used in patients with hemoblastosis in order to detect invasive fungal growth at the preclinical stage. The disadvantage of the study is frequent false-positive reactions due to low species specificity and absorption of antigen into the blood from food.
Invasive pulmonary aspergillosis treatment
If invasive lung mycosis is suspected, treatment should be started immediately. Broad-spectrum antimycotics are used as etiotropic drugs. This group of drugs includes triazoles, polyenes and echinocandins. It is possible to use a combination of two antifungal drugs belonging to different classes. Immunomodulators are prescribed to correct the functions of the immune system. With severe neutropenia, granulocyte transfusion is performed. Aspergillosis of the lungs with invasive growth is not always subject to surgical treatment. Parenchymal resection is performed at the risk of mycelium germination of fungi of large vessels and pericardium, to reduce the volume of fungal masses before prescribing drugs leading to immunosuppression.
Prognosis and prevention
The prognosis for invasive pulmonary aspergillosis of the respiratory system is always serious. Lethal outcome occurs in 50% of patients with neutropenia. The mortality rate from mycosis among bone marrow recipients reaches 90%. Early (up to 10 days from the onset of the disease), the treatment initiated ensures recovery in approximately 60% of patients. Experimental clinical studies are being conducted with regard to primary prevention, but preventive measures have not yet been sufficiently developed. To prevent the recurrence of the disease in people with risk factors, antimycotics of the polyene or triazole series, immunomodulators are successfully used. In order to prevent hospital infection with aspergillosis, the wards of patients from risk groups are equipped with supply and exhaust ventilation and an air filtration system, and are reliably isolated for the duration of repair work. The amount of aspergillus in the air of such premises should not exceed the established norms.
Literature
- Our 2015 approach to invasive pulmonary aspergillosis. Liss B, Vehreschild JJ, Bangard C, Maintz D, Frank K, Grönke S, Michels G, Hamprecht A, Wisplinghoff H, Markiefka B, Hekmat K, Vehreschild MJ, Cornely OA. Mycoses. 2015 Jun;58(6):375-82. link
- Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Ullmann AJ, Aguado JM, Arikan-Akdagli S, Clin Microbiol Infect. 2018 May;24 Suppl 1:e1-e38. link
- Clinical characteristics, radiologic findings, risk factors and outcomes of serum galactomannan-negative invasive pulmonary aspergillosis. Jung J, Kim MY, Chong YP, Lee SO, Choi SH, Kim YS, Woo JH, Kim SH. J Microbiol Immunol Infect. 2018 Dec;51(6):802-809. link
- Galactomannan testing in bronchoalveolar lavage fluid facilitates the diagnosis of invasive pulmonary aspergillosis in patients with hematologic malignancies and stem cell transplant recipients. Nguyen MH, Leather H, Clancy CJ, Cline C, Jantz MA, Kulkarni V, Wheat LJ, Wingard JR. Biol Blood Marrow Transplant. 2011 Jul;17(7):1043-50. link
- Recent advances in invasive pulmonary aspergillosis. Chai LY, Hsu LY. Curr Opin Pulm Med. 2011 May;17(3):160-6 link