Aspergillosis pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.; Haytham Allaham, M.D. [2]; Serge Korjian M.D.


Aspergillus is primarily transmitted to the human host by inhalation of airborne conidia (usually by dust exposure during building renovation or construction) or contaminated biomedical devices. Aspergillus is not transmitted from one individual to another. The pathogenesis of aspergillosis varies according to the associated clinical syndrome. Allergic bronchopulmonary aspergillosis and allergic Aspergillus rhinosinusitis are thought to be caused by both type I and type III hypersensitivity responses. Aspergilloma, chronic pulmonary aspergillosis, and invasive aspergillosis are directly related to the growth and expansion of the Aspergillus hyphae in the lungs. Lastly, cutaneous aspergillosis may result either from direct access of the Aspergillus through a skin break (primary) or dissemination of the Aspergillus to the skin from a distant infected organ (secondary).


  • Aspergillus is ubiquitous in the environment.
  • Aspergillus can be found in soil, decomposing plant matter, household dust, building materials, plants, food, and water.


  • Transmission of Aspergillus occurs through inhalation of airborne conidia.
  • Hospital-acquired infections may be sporadic or may be associated with dust exposure during building renovation or construction.
  • Occasional outbreaks of cutaneous infection have been traced to contaminated biomedical devices.
  • Aspergillus is not transmitted from one individual to another (no person-to-person transmission).


Following the ingestion of Aspergillus conidia, the mechanism of disease may vary depending on the host immune factors.

  • The following algorithm demonstrates common sequelae of Aspergillus inhalation among different patient groups:

Inhalation of Aspergillus spores
Healthy host
Cavitary lung disease
Chronic lung disease or mildly immunocompromised host
Immunocompromised host
Either asthma, cystic fibrosis, or atopy
No sequelae
Chronic necrotizing aspergillosis
Invasive pulmonary aspergillosis
Allergic bronchopulmonary aspergillosis (ABPA)

Adapted from Kousha M, Tadi R, and Soubani AO. Pulmonary aspergillosis: a clinical review. Euro Respir Rev. 2011;20(121):156-74[1] / Soubani AO, Chandrasekar PH. The clinical spectrum of pulmonary aspergillosis. Chest. 2002;121(6):1988-99.[2]

Allergic Bronchopulmonary Aspergillosis (ABPA)

  • Allergic bronchopulmonary aspergillosis is both a type I (atopic) and type III hypersensitivity immune response.

Type I Hypersensitivity

  • Precipitating antibodies incite a type I acute hypersensitivity reaction that results in the release of immunoglobulin E (IgE) and immunoglobulin G (IgG).
  • Immunoglobulin release induces mast cell degranulation, bronchoconstriction, and increased capillary permeability.

Type III Hypersensitivity

  • Immune complexes and inflammatory cells are deposited within the bronchial mucosa leading to tissue necrosis and eosinophilic infiltrate, a type III reaction.

Pulmonary Tissue Destruction

  • Aspergillus is not usually cleared from the airways despite the immune response.
  • Proteolytic enzymes are released by the immune cells, and toxins are released by the fungi. Together, these result in bronchiectasis, which is most pronounced in the central parts of the airways.
  • The subsequent damage to the bronchial wall causes proximal bronchiectasis. Repeated acute episodes when left untreated can result in progressive pulmonary fibrosis that is often most prominent in the upper zones and can give rise to a similar radiological appearance to that produced by tuberculosis.

Allergic Aspergillus Rhinosinusitis

  • The exact pathogenesis of allergic fungal rhinosinusitis is not fully understood.[3]
  • It is thought that the pathogenesis is similar to the pathogenesis of ABPA, where both type I and type III hypersensitivity responses are involved.[4] However, it is not confirmed whether the reactions are systemic or local in the nose and the paranasal sinuses.[5]
  • Not all patients with allergic fungal rhinosinusitis have other types of allergies, and an alternative mechanism of disease involving T-cell mediated responses to fungi and eosinophilic chemotaxis has been suggested.[3]


  • Aspergillus fumigatus spores are typically inhaled and result in no clinical manifestations among healthy individuals with no prior history of lung disease.
  • Individuals with prior lung diseases (especially lung diseases characterized by cavitary lesions, such as tuberculosis, sarcoidosis, fibrosis, or bronchiectasis), are at risk for developing aspergilloma.[6][7]
  • The fungus settles in a cavity and is able to grow freely. The immune system is unable to penetrate into the cavity.
  • As the fungus multiplies, it forms a ball, which incorporates dead tissue from the surrounding lung, in addition to mucus, inflammatory cells, epithelial cells, and other debris.[8]
  • Aspergillus is also able to produce enzymes that destroy the surrounding lung parenchyma to allow for further expansion of the fungus ball.[6]

Chronic Pulmonary Aspergillosis

Chronic Cavitary Pulmonary Aspergillosis (CCPA)

  • Following spore inhalation, the hyphae expand in multiple cavities and may result in the formation of one or multiple fungus ball(s).[9]

Chronic Fibrosing Pulmonary Aspergillosis (CFPA)

  • Cavitary lesions that form following spore inhalation may progress to result in pulmonary fibrosis.[9]
  • Chronic fibrosing pulmonary aspergillosis (CFPA) may be considered as a complication of chronic cavitary pulmonary aspergillosis (CCPA).[9]
  • Pleural involvement may be present.[9]

Chronic Necrotizing Pulmonary Aspergillosis (CNPA)

  • Subacute (not chronic), progressive aspergillosis that results in tissue necrosis.[9]

Invasive Aspergillosis

  • Invasive Aspergillus infection almost always occurs in patients who are immunosuppressed, with underlying lung disease, on an immunosuppressive drug therapy, or with immunodeficiency.
  • The human defense layers against inhaled spores include a mucous layer, ciliary action in the respiratory tract, and phagocytosis by macrophages and neutrophils.
  • Underlying immunosuppression (eg, HIV disease, chronic granulomatous disease, pharmacologic immunosuppression) results in neutrophil dysfunction or a decrease in the numbers of neutrophils. Accordingly, immunosuppressed individuals are unable to mount an adequate immune response to phagocytose the organism.

Cutaneous Aspergillosis

  • Aspergillus is able to cause skin infection either through skin wounds (primary) or from by dissemination from distant organs that have already been infected to the skin (secondary).
  • Patients with wounds or burns have a compromised skin barrier, as well as a dysfunctional immune defense mechanisms. Both processes allow for the development of cutaneous aspergillosis.
  • Similarly, neonates have an impaired cellular ability to undergo phagocytosis and may also be predisposed to the development of cutaneous aspergillosis.


  1. Kousha M, Tadi R, Soubani AO (2011). "Pulmonary aspergillosis: a clinical review". Eur Respir Rev. 20 (121): 156–74. doi:10.1183/09059180.00001011. PMID 21881144.
  2. Soubani AO, Chandrasekar PH (2002). "The clinical spectrum of pulmonary aspergillosis". Chest. 121 (6): 1988–99. PMID 12065367.
  3. 3.0 3.1 Ponikau JU, Sherris DA, Kern EB, Homburger HA, Frigas E, Gaffey TA; et al. (1999). "The diagnosis and incidence of allergic fungal sinusitis". Mayo Clin Proc. 74 (9): 877–84. doi:10.4065/74.9.877. PMID 10488788.
  4. Safirstein BH (1976). "Allergic bronchopulmonary aspergillosis with obstruction of the upper respiratory tract". Chest. 70 (6): 788–90. PMID 1001063.
  5. Collins M, Nair S, Smith W, Kette F, Gillis D, Wormald PJ (2004). "Role of local immunoglobulin E production in the pathophysiology of noninvasive fungal sinusitis". Laryngoscope. 114 (7): 1242–6. doi:10.1097/00005537-200407000-00019. PMID 15235354.
  6. 6.0 6.1 Kibbler CC, Milkins SR, Bhamra A, Spiteri MA, Noone P, Prentice HG (1988). "Apparent pulmonary mycetoma following invasive aspergillosis in neutropenic patients". Thorax. 43 (2): 108–12. PMC 1020751. PMID 3281310.
  7. Glimp RA, Bayer AS (1983). "Pulmonary aspergilloma. Diagnostic and therapeutic considerations". Arch Intern Med. 143 (2): 303–8. PMID 6824396.
  8. Daly RC, Pairolero PC, Piehler JM, Trastek VF, Payne WS, Bernatz PE (1986). "Pulmonary aspergilloma. Results of surgical treatment". J Thorac Cardiovasc Surg. 92 (6): 981–8. PMID 3097424.
  9. 9.0 9.1 9.2 9.3 9.4 Denning DW, Riniotis K, Dobrashian R, Sambatakou H (2003). "Chronic cavitary and fibrosing pulmonary and pleural aspergillosis: case series, proposed nomenclature change, and review". Clin Infect Dis. 37 Suppl 3: S265–80. doi:10.1086/376526. PMID 12975754.

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