Aspergillosis is the name given to a wide variety of diseases caused by infection by fungi of the genus Aspergillus.
Aetiology
A. fumigatus
A. niger
Risk factors:
Immunocompetent state:
Tuberculosis
Chronic Obstructive Pulmonary Disease (COPD)
Immunocompromised state:
Patients with cancer undergoing chemotherapy
Resultant neutropenia
Stem cell transplant recipients
Immunosuppressive therapy
Pathophysiology
Infectious life cycle of A. fumigatus. Aspergillus is ubiquitous in the environment, and asexual reproduction leads to the production of airborne conidia. Inhalation by specific immunosuppressed patient groups results in conidium establishment in the lung, germination, and either PMN-mediated fungal control with significant inflammation (corticosteroid therapy) or uncontrolled hyphal growth with a lack of PMN infiltrates and, in severe cases, dissemination (neutropenia). | Dagenais, T. R. T., & Keller, N. P. (2009). Pathogenesis of Aspergillus fumigatus in Invasive Aspergillosis. Clinical Microbiology Reviews, 22(3), 447–465. https://doi.org/10.1128/CMR.00055-08
Interaction of A. fumigatus with respiratory epithelia. Following inhalation, A. fumigatus encounters airway epithelia (lining trachea, bronchi, and bronchioles), the mucus and fluid lining the upper respiratory tract, and, ultimately, the alveolar space. Fungal products (shown in red) may enhance colonization through tissue injury (cross-haired line) and attachment to epithelial cells or damaged basement membrane. Conidia may also germinate and invade the surrounding lung tissue via the basement membrane or following ingestion by epithelial cells. | Dagenais, T. R. T., & Keller, N. P. (2009). Pathogenesis of Aspergillus fumigatus in Invasive Aspergillosis. Clinical Microbiology Reviews, 22(3), 447–465. https://doi.org/10.1128/CMR.00055-08
A. fumigatus interactions with phagocytes. Alveolar macrophages phagocytose inhaled conidia via PRRs. Conidial swelling (within or outside of the macrophage) releases the protective rodlet layer, exposing β(1,3)-glucan for recognition by dectin-1. Dectin-1-β(1,3)-glucan interactions are primarily responsible for the activation of macrophage proinflammatory responses, including conidial killing. Neutrophils attach to hyphae and degranulate, damaging hyphae by oxidative and nonoxidative mechanisms. Neutrophils may also aggregate conidia and prevent germination. Compromised phagocyte function is the primary risk factor for IA. Fungal products (shown in red) may contribute to fungal pathogenicity in these immunocompromised hosts by evading or modulating host defenses. | Dagenais, T. R. T., & Keller, N. P. (2009). Pathogenesis of Aspergillus fumigatus in Invasive Aspergillosis. Clinical Microbiology Reviews, 22(3), 447–465. https://doi.org/10.1128/CMR.00055-08
Clinical features
Invasive aspergillosis (common):
Chronic pulmonary aspergillosis (CPA)
Aspergilloma
Allergic bronchopulmonary aspergillosis (ABPA)
Sites of involvement:
Lungs
Sinuses
Non- invasive aspergillosis (less common):
Otomycosis
Sinusitis
Aspergilloma
Allergic bronchopulmonary aspergillosis
Clinical spectrum
Interaction of Aspergillus with host. ABPA, allergic bronchopulmonary aspergillosis; IA, invasive aspergillosis | Kosmidis, C., & Denning, D. W. (2015). The clinical spectrum of pulmonary aspergillosis. Thorax, 70(3), 270 LP-277. Retrieved from http://thorax.bmj.com/content/70/3/270.abstract
Pathological features and characteristics of various forms of pulmonary aspergillosis. CGD, chronic granulomatous disease; CPA, chronic pulmonary aspergillosis; GVHD, graft versus host disease; HSCT, haematopoietic stem cell transplant; IPA: invasive pulmonary aspergillosis. | Adapted from Hope et al | Kosmidis, C., & Denning, D. W. (2015). The clinical spectrum of pulmonary aspergillosis. Thorax, 70(3), 270 LP-277. Retrieved from http://thorax.bmj.com/content/70/3/270.abstract
Diagnosis
Primary diagnoses:
Radiology
Histopathology
Demonstration of the invasive hyphae in biopsy samples and culture.
Serology (noninvasive diagnostic test)
Serial estimation of galactomannan in serum samples
X-ray (chest):
Serial chest X-rays of a patient with chronic cavitating pulmonary aspergillosis. (A) January 2001; (B) February 2002; (C) April 2003; (D) July 2003 | Kosmidis, C., & Denning, D. W. (2015). The clinical spectrum of pulmonary aspergillosis. Thorax, 70(3), 270 LP-277. Retrieved from http://thorax.bmj.com/content/70/3/270.abstract
CT-scan:
CT scans from patients with various forms of chronic pulmonary aspergillosis. (A) Simple aspergilloma; (B) Chronic cavitary pulmonary aspergillosis; (C) Chronic fibrosing pulmonary aspergillosis; (D) Aspergillus nodule. | Kosmidis, C., & Denning, D. W. (2015). The clinical spectrum of pulmonary aspergillosis. Thorax, 70(3), 270 LP-277. Retrieved from http://thorax.bmj.com/content/70/3/270.abstract
