Aspergillosis
Etiology
Aspergillus is a ubiquitous environmental mold that grows in organic matter in the soil. The organism grows as a soil mycelium (filamentous form) and forms aerial hyphal stalks. The conidia (spores) are about 2 to 10 micrometers in diameter. They are formed at the tips of the stalks (conidiophores) by asexual reproduction. Their hydrophobic nature aids in aerosolization.Humans routinely inhale the aerosolized conidia. The conidia are promptly eliminated from the respiratory tract, or may lead to colonization or infection dependent on the underlying local and general immune status of the host.
Approximately 34 of 180 Aspergillus species are known to cause disease in humans. Aspergillus fumigatus is the most common pathogenic species, accounting for 50% to 70% of the aspergillosis syndromes. Increasingly, however, aspergillosis is caused by nonfumigatus species, including A flavus, A terreus, A niger, and A versicolor. A niger is less pathogenic, perhaps due to its large conidia failing to reach the pulmonary alveoli. A terreus, unlike the other species, is resistant to amphotericin B. Because of this, aspergillosis caused by A terreus has a poor prognosis, and occasionally is associated with positive blood cultures. [13] Rarely, the organism gains entry via direct cutaneous inoculation, particularly after trauma.
In aspergilloma, A fumigatus remains the most common species.
Pathophysiology
Invasive aspergillosis (IA)
Upon inhalation of the conidia, the underlying host defenses determine the fate of the organism. Immunocompetent hosts with intact ciliary clearance promptly eliminate the organism from the respiratory tract. The early immune defense is provided by pulmonary macrophages that attempt to phagocytose and destroy the conidia. [15] [16] When conidia survive, germination leads to hyphae (filamentous form), which invades the pulmonary parenchyma. Polymorphonuclear leukocytes phagocytose the swollen conidia and hyphae.
During invasion, interaction occurs between Aspergillus ligands and the pattern recognition receptors, including Toll-like receptors (TLR) and Dectin, on macrophages leading to the production of pro-inflammatory cytokines. Fever is the resultant clinical manifestation.
TLR-4 polymorphisms in humans have been implicated as a risk factor of IA. Angioinvasive hyphae gain entry and locally disseminate via the pulmonary microvasculature and cause thrombus formation and tissue infarction. Infected areas of lung with associated inflammation and pulmonary infarction contribute to clinical symptoms of cough, shortness of breath, and pleuritic chest pain. Lung function may worsen with increased areas of involvement.
Dissemination from the lung via the hematogenous route may commonly occur into the brain and skin, leading to tissue infarction at those sites. Virtually all body sites, including the heart, kidney, liver/spleen, bone, and GI tract, may be affected. Direct invasion from the paranasal sinus cavity into the orbit, sphenoidal sinus, and brain parenchyma may also occur.
Aspergilloma
The intracavitary mass lesion in the lung consists of masses of Aspergillus mycelia, inflammatory cells, fibrin, mucus, and tissue debris. The growth of Aspergillus on the walls of the cavity is facilitated by inadequate drainage. Bleeding is uncommon; however, severe hemoptysis may sometimes occur secondary to erosion of bronchial blood vessels lining the cavity, and mechanical friction of the fungal ball against the blood vessels.
Etiology
Aspergillus is a ubiquitous environmental mold that grows in organic matter in the soil. The organism grows as a soil mycelium (filamentous form) and forms aerial hyphal stalks. The conidia (spores) are about 2 to 10 micrometers in diameter. They are formed at the tips of the stalks (conidiophores) by asexual reproduction. Their hydrophobic nature aids in aerosolization.Humans routinely inhale the aerosolized conidia. The conidia are promptly eliminated from the respiratory tract, or may lead to colonization or infection dependent on the underlying local and general immune status of the host.
Approximately 34 of 180 Aspergillus species are known to cause disease in humans. Aspergillus fumigatus is the most common pathogenic species, accounting for 50% to 70% of the aspergillosis syndromes. Increasingly, however, aspergillosis is caused by nonfumigatus species, including A flavus, A terreus, A niger, and A versicolor. A niger is less pathogenic, perhaps due to its large conidia failing to reach the pulmonary alveoli. A terreus, unlike the other species, is resistant to amphotericin B. Because of this, aspergillosis caused by A terreus has a poor prognosis, and occasionally is associated with positive blood cultures. [13] Rarely, the organism gains entry via direct cutaneous inoculation, particularly after trauma.
In aspergilloma, A fumigatus remains the most common species.
Pathophysiology
Invasive aspergillosis (IA)
Upon inhalation of the conidia, the underlying host defenses determine the fate of the organism. Immunocompetent hosts with intact ciliary clearance promptly eliminate the organism from the respiratory tract. The early immune defense is provided by pulmonary macrophages that attempt to phagocytose and destroy the conidia. [15] [16] When conidia survive, germination leads to hyphae (filamentous form), which invades the pulmonary parenchyma. Polymorphonuclear leukocytes phagocytose the swollen conidia and hyphae.
During invasion, interaction occurs between Aspergillus ligands and the pattern recognition receptors, including Toll-like receptors (TLR) and Dectin, on macrophages leading to the production of pro-inflammatory cytokines. Fever is the resultant clinical manifestation.
TLR-4 polymorphisms in humans have been implicated as a risk factor of IA. Angioinvasive hyphae gain entry and locally disseminate via the pulmonary microvasculature and cause thrombus formation and tissue infarction. Infected areas of lung with associated inflammation and pulmonary infarction contribute to clinical symptoms of cough, shortness of breath, and pleuritic chest pain. Lung function may worsen with increased areas of involvement.
Dissemination from the lung via the hematogenous route may commonly occur into the brain and skin, leading to tissue infarction at those sites. Virtually all body sites, including the heart, kidney, liver/spleen, bone, and GI tract, may be affected. Direct invasion from the paranasal sinus cavity into the orbit, sphenoidal sinus, and brain parenchyma may also occur.
Aspergilloma
The intracavitary mass lesion in the lung consists of masses of Aspergillus mycelia, inflammatory cells, fibrin, mucus, and tissue debris. The growth of Aspergillus on the walls of the cavity is facilitated by inadequate drainage. Bleeding is uncommon; however, severe hemoptysis may sometimes occur secondary to erosion of bronchial blood vessels lining the cavity, and mechanical friction of the fungal ball against the blood vessels.
Comments