Allergic bronchopulmonary aspergillosis begins with the inhalation of Aspergillus conidia (spores). In a genetically susceptible (HLA-DR restriction) asthmatic patient or one with cystic fibrosis, the spores develop into hyphal forms as the bronchi become colonized. A local inflammatory reaction develops. Antigens of the hyphae react with IgE, IgG, and IgA antibodies as the response escalates to damage of the bronchial wall and infiltration with eosinophils. Antigen-specific CD₄ Th2-like T lymphocytes produce increased levels of interleukin (IL)-4 and IL-5. The bronchial wall is infiltrated with mononuclear cells and eosinophils. Mucus and exudate, along with segments of the fungus, may fill the bronchi. The lung parenchyma may become involved with granulomatous reactions. Vasculitis is an uncommon finding with this type of pulmonary aspergillosis, and the lack of an acute neutrophil response is compatible with a delayed hypersensitivity response.

The pathogenesis of invasive aspergillosis differs considerably from that of allergic aspergillosis. Although pulmonary aspergillosis is found occasionally in presumably otherwise normal individuals, the usual host for any invasive form of the disease is one whose immune system has been compromised. Normally, inhaled Aspergillus conidia that reach the paranasal sinuses and lung are ingested and digested by polymorphonuclear leukocytes or alveolar macrophages. If this arm of the defense mechanism is impaired, as it is in patients with chronic granulomatous disease (in whom oxidative intracellular killing is impaired) and in patients with other phagocytic defects or quantitative deficits, the organism may colonize and develop hyphal and invasive forms. With this type of host-parasite relationship, the outcome often is hemorrhagic infarction and necrosis.

The pathologic pattern appears to be related, to some extent, to the severity of immunocompromise. A fibrosing granulomatous reaction or chronic, nonspecific inflammatory response may be found in an otherwise healthy patient. A severely compromised host exhibits massive hyphal invasion of blood vessels and no granulation tissue. In some patients, the
infection may localize with formation of a cavity—the aspergilloma. The cavity is occupied partially by a ball of Aspergillus hyphae. Rarely, a chronic, necrotizing, granulomatous pneumonia is seen around a central zone of infarct-like necrosis of parenchyma resulting from angioinvasive aspergilli. These lesions tend to be found in the upper lobes. Paranasal sinuses infected with this fungus may exhibit a spectrum of tissue responses similar to the pattern described for the lung, or the site may be colonized only, with hypertrophy of the sinus mucosa.