Etiology and Diversity of Forms
Interstitial lung diseases encompass over a hundred different nosologies. The primary classification criterion is the cause of the pathological process.
- Identified Etiology: Includes pneumoconioses (reactions to organic and inorganic dust), infections (viruses, bacteria, fungi), exposure to toxins and physical factors (radiation, hyperoxia). Drugs represent a distinct hazard, particularly antineoplastic agents (bleomycin, methotrexate, cyclophosphamide) as well as amiodarone.
- Unidentified Etiology: Accounts for the vast majority of cases. This category includes idiopathic fibrosing alveolitis (IFA), sarcoidosis, Goodpasture syndrome, pulmonary vasculitis, Langerhans cell histiocytosis, and secondary involvement in rheumatic diseases.
Pathogenesis and Pathways of Injury
Regardless of the cause, the key link in pathogenesis is damage to the alveolar septum. Macrophages and polymorphonuclear leukocytes are the first to migrate to the defense of the alveoli. Upon activation, they release reactive oxygen species, proteases, and cytokines, which simultaneously destroy the lung parenchyma and trigger sclerosis.
The sequence of structural destruction depends on the route of the attack:
- Aerogenic pathway: The agent enters via inhaled air. First, the alveolar epithelial lining is destroyed, and then the process extends to the interstitium.
- Hematogenous pathway: Aggression originates from the bloodstream (circulating immune complexes, antibodies). The capillary endothelium suffers first, followed by the extracellular matrix, and lastly the epithelium.
- Immune pathogenesis: Even with the aspiration of minor allergens, if the reaction is mediated by antibodies and T-lymphocytes from the bloodstream, the damage proceeds from the capillaries to the interstitium and epithelium.
The Role of the Basement Membrane in Outcomes
The morphological basis of ILD is fibrosing alveolitis—non-suppurative inflammation of the respiratory divisions. Its outcome critically depends on the integrity of the basement membrane.
- Basement membrane intact: Exudate in the alveoli is reabsorbed, type II pneumocytes proliferate, and the structure is fully restored. In some cases, organization of the exudate with the formation of Masson bodies (carnification) may occur.
- Basement membrane destroyed: Alveolar macrophages stimulate interstitial cells (fibroblasts). These migrate into the alveolar lumen and actively synthesize type I collagen. The result is irreversible fibrosis and scarring.
Clinical and Morphological Picture
The stereotypical progression of ILD is as follows: initial alveolitis is replaced by interstitial fibrosis. The extreme degree of involvement is the "honeycomb lung", in which fibrosis is combined with cystic transformation of the terminal and respiratory bronchioles.
Functionally, this manifests as a restrictive syndrome: lung tissue volume drops, and vital capacity (VC) decreases sharply. Due to the thickening of the alveolar septa, an alveolocapillary barrier block develops. This leads to hypoxia, secondary pulmonary hypertension, right ventricular hypertrophy, and the development of cor pulmonale. Clinically, patients suffer from progressive dyspnea, tachypnea, and cyanosis.
Idiopathic Fibrosing Alveolitis (IFA)
IFA (historically known as Hamman–Rich syndrome) is not a single nosology, but a group of idiopathic interstitial pneumonias. According to the modern ATS/ERS clinical and morphological concept, clinical diagnoses are closely linked to morphological patterns of injury.
| Morphological Variant of IFA | Clinical Form of IFA |
|---|---|
| Usual interstitial pneumonia | Idiopathic pulmonary fibrosis |
| Non-specific interstitial pneumonia | Non-specific interstitial pneumonia |
| Organizing pneumonia | Cryptogenic organizing pneumonia |