Exogenous allergic alveolitis - Causes and pathogenesis

Causes of exogenous allergic alveolitis

The development of exogenous allergic alveolitis is caused by the following etiological factors.

1. Thermophilic and other bacteria and their metabolic products (proteins, glyco- and lipoproteins, polysaccharides, enzymes, endotoxins).
2. Different types of mushrooms.
3. Protein antigens of animal origin (serum proteins and excrement of poultry, cattle, pigs; dust containing particles of animal hair; extract of the posterior lobe of the pituitary gland of cattle - adiurecrina; dust of fish meal; waste products of ticks, etc.);
4. Antigens of plant origin (sawdust of oak, cedar, maple bark, mahogany, moldy straw, cotton and other types of plant dust, coffee bean extracts, etc.);
5. Medicines (antibacterial, antiparasitic, anti-inflammatory, enzyme, radiocontrast and other drugs).

The indicated etiological factors (one or more) are found in certain industries and therefore various etiological forms of exogenous allergic alveolitis are characteristic of certain professions.

Among the numerous etiologic forms of exogenous allergic alveolitis, the most common are “farmers’ lung”, “poultry farmers’ lung” (“bird lovers’ lung”), and drug-induced allergic alveolitis.

Pathogenesis of exogenous allergic alveolitis

In exogenous allergic alveolitis, particles of organic and inorganic dust with antigenic properties and a size of less than 2-3 μm penetrate into the distal airways and alveoli. In response to this, immunological reactions develop with the participation of both humoral and cellular immunity. The main pathogenetic factors of exogenous allergic alveolitis are generally similar to the pathogenesis of idiopathic fibrosing alveolitis. An allergic reaction develops with the formation of specific antibodies and immune complexes that activate the complement system and alveolar macrophages. Under the influence of IL-2 and chemotactic factors secreted by alveolar macrophages, accumulation and specific expansion of neutrophilic leukocytes, eosinophils, mast cells, lymphocytes develops with the secretion of a number of biologically active substances that have a proinflammatory and damaging effect on the alveoli. Sensitized T-helper lymphocytes produce IL-2, under the influence of which cytotoxic T-lymphocytes are formed from resting T-precursor cells and are activated, an inflammatory cell-mediated reaction (delayed-type hypersensitivity reaction) develops. A major role in the development of the inflammatory reaction is played by the secretion of proteolytic enzymes and active oxygen radicals by alveolar macrophages and neutrophilic leukocytes against the background of a decrease in the activity of the antiproteolytic system. Parallel to alveolitis, processes of granuloma formation, fibroblast activation and fibrosis of the pulmonary interstitium occur. Alveolar macrophages play a huge role in this process, producing a factor that induces fibroblast growth and collagen production.

It should be emphasized that atopic IgE-dependent mechanisms (type I allergic reaction) are not characteristic of exogenous allergic alveolitis.

Pathomorphology of exogenous allergic alveolitis

There are acute, subacute and chronic stages (forms) of exogenous allergic alveolitis. The acute stage is characterized by dystrophy and sloughing, desquamation of type I alveolocytes, destruction of the basement membrane, pronounced exudation into the alveolar cavity, infiltration of the alveoli and interalveolar septa by lymphocytes, plasma cells, histiocytes, and edema of the interstitial tissue of the lungs. Damage to the capillary endothelium and their high permeability are also characteristic.

The subacute stage is characterized by less damage to blood vessels, less pronounced exudation, and the formation of epithelioid-cell noncaseating granulomas in the interstitial tissue of the lungs. Granulomas consist of macrophages, epithelioid, lymphoid, and plasma cells. Unlike sarcoidosis, these granulomas are smaller, do not have clear boundaries, are not subject to hyalinosis, and are localized primarily in the interstitium or intraalveolarly. Sarcoidosis is characterized by peribronchial or perivascular localization of granulomas. The subacute form is also characterized by the accumulation of lymphocytes, activated macrophages, and fibroblasts in the interstitial tissue of the lungs.

For the chronic form of exogenous allergic alveolitis, the most significant and essential sign is the proliferation of connective tissue in the interstitium of the lungs (fibrosing alveolitis) and cystic changes in the lung tissue ("honeycomb lung"). At this stage of the process, granulomas disappear. Infiltration of the interstitium with lymphocytes and neutrophilic leukocytes persists. The morphological picture of exogenous allergic alveolitis in the chronic stage is indistinguishable from idiopathic fibrosing alveolitis.

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