Etiology and variety of forms
Interstitial lung diseases combine more than a hundred different nosologies. The main classification criterion is the cause of the pathological process.
- Established etiology: includes pneumoconioses (reaction to organic and inorganic dust), infections (viruses, bacteria, fungi), exposure to toxins and physical factors (radiation, hyperoxia). Drugs pose a separate threat, especially cytostatics (bleomycin, methotrexate, cyclophosphamide), as well as amiodarone.
- Unestablished etiology: accounts for the overwhelming majority of cases. This includes idiopathic fibrosing alveolitis (IFA), sarcoidosis, Goodpasture's syndrome, pulmonary vasculitis, histiocytosis X, and secondary involvement in rheumatic diseases.
Pathogenesis and pathways of injury
Regardless of the cause, the key link in the 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 pulmonary parenchyma and trigger sclerosis.
The sequence of structural destruction depends on the route of attack:
- Aerogenic route: the agent enters with air. First, the alveolar epithelial lining is destroyed, and then the process spreads to the interstitium.
- Hematogenous route: the aggression comes from the bloodstream (circulation of immune complexes, antibodies). The capillary endothelium suffers first, followed by the extracellular matrix, and lastly the epithelium.
- Immune pathogenesis: even during the aspiration of small allergens, if the reaction is mediated by antibodies and T-lymphocytes from the blood, the damage proceeds from the capillaries to the interstitium and epithelium.
Role of the basement membrane in outcomes
The morphological basis of ILDs is fibrosing alveolitis — non-suppurative inflammation of the respiratory divisions. Its outcome critically depends on the integrity of the basement membrane.
- Basement membrane is intact: exudate in the alveoli resolves, type II pneumocytes proliferate, and the structure is completely restored. In some cases, organization of the exudate with the formation of Masson bodies (carnification) is possible.
- Basement membrane is destroyed: alveolar macrophages stimulate interstitial cells (fibroblasts). They migrate into the alveolar lumen and actively synthesize type I collagen. The result is irreversible fibrosis and scarring.
Clinical and morphological picture
The stereotyped development of ILDs 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: the volume of lung tissue drops, and vital capacity (VC) sharply decreases. Due to the thickening of the alveolar septa, an aerohematic barrier block occurs. 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 Hamman–Rich syndrome) is not a single nosology, but a whole group of idiopathic interstitial pneumonias. According to the modern ATS/ERS clinical and morphological concept, clinical diagnoses are closely linked to morphological variants of involvement.
| Morphological variant of IFA | Clinical form of IFA |
|---|---|
| Usual interstitial pneumonia | Idiopathic pulmonary fibrosis |
| Nonspecific interstitial pneumonia | Nonspecific interstitial pneumonia |
| Organizing pneumonia | Cryptogenic organizing pneumonia |
Briefly: answers to topical questions
What morphological variants of idiopathic interstitial pneumonias are distinguished according to the ATS/ERS classification?
According to the ATS/ERS classification, the following morphological variants of idiopathic interstitial pneumonias are distinguished:
- Usual interstitial pneumonia — corresponds to idiopathic pulmonary fibrosis.
- Nonspecific interstitial pneumonia — corresponds to the clinical form of the same name.
- Organizing pneumonia — corresponds to cryptogenic organizing pneumonia.
- Diffuse alveolar damage — corresponds to acute interstitial pneumonia.
- Respiratory bronchiolitis — corresponds to respiratory bronchiolitis-associated interstitial lung disease.
- Desquamative interstitial pneumonia — corresponds to the clinical form of the same name.
- Lymphocytic interstitial pneumonia — corresponds to the clinical form of the same name.
What stages of morphogenesis does idiopathic fibrosing alveolitis sequentially undergo?
Idiopathic fibrosing alveolitis sequentially undergoes three stages of morphogenesis.
- Alveolitis — the initial stage, characterized by diffuse or granulomatous infiltration.
- Interstitial fibrosis — the stage of disorganization of alveolar structures and the development of pneumofibrosis.
- "Honeycomb lung" — the extreme expression of the process, in which an alveolar-capillary block, panacinar emphysema, bronchiolectasis, and cysts are formed.
For quick memorization of alveolitis outcomes: Intact membrane — Intact alveoli (complete recovery), Damaged membrane — Scar (irreversible fibrosis).
Class and exam questions
What is a "honeycomb lung"?
This is an extreme degree of interstitial fibrosis. Lung tissue is replaced by scars, and terminal and respiratory bronchioles undergo pronounced cystic transformation.
How does the route of entry of the damaging agent affect morphogenesis?
With the aerogenic route, the alveolar epithelium suffers first, followed by the interstitium. With the hematogenous and immune routes, capillary endothelium is primarily damaged, then the matrix, and only lastly the epithelium.
What is the fundamental difference between ILD and COPD?
ILD is a restrictive pathology with decreased lung volume and interstitial fibrosis. COPD is an obstructive disease with impaired bronchial patency and inflammatory infiltration that does not respond to steroid therapy.
What else to study on this topic
- Differential diagnosis of COPD and bronchial asthma
- Features of the cellular composition of bronchoalveolar lavage (BAL) in ILD
- Mechanisms of Masson body formation in lung carnification
- Effect of cytostatics and other drugs on the pulmonary interstitium
- ATS/ERS clinical and morphological concept for idiopathic interstitial pneumonias
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