Mechanisms of Chronic Lung Diseases
In pathology, three main mechanisms lead to severe chronic processes in the respiratory system:
- Bronchogenic mechanism. Based on impaired pulmonary drainage and bronchial patency. Obstructive diseases develop along this pathway: chronic bronchitis, bronchiectasis, and chronic obstructive pulmonary emphysema.
- Pneumoniogenic mechanism. Closely linked to preceding bronchopneumonia, lobar pneumonia, and their complications (e.g., acute abscess or carnification). The outcome is chronic abscess or chronic pneumonia. A distinguishing feature is a prominent restrictive component.
- Pneumonitogenic mechanism. The pathological process localizes in the interstitium of the respiratory zones of the lungs. It is characterized by chronic inflammation and fibrosis, typical of interstitial lung diseases.
Regardless of the mechanism, the terminal outcome of these processes is universal: pneumosclerosis (pneumocirrhosis), secondary pulmonary hypertension, right ventricular hypertrophy (forming cor pulmonale), and cardiopulmonary failure. Additionally, it creates a background for lung cancer development.
Etiology and Molecular Pathogenesis
Chronic bronchitis is triggered by exogenous and endogenous factors (ethnic traits, genetic predisposition). The most crucial factor is cigarette smoking (active and passive).
Pathogenesis of tobacco smoke exposure includes:
- Suppression of bronchial epithelial cilia activity, leading to impaired mucociliary clearance.
- Inhibitory effects on alveolar macrophages, disrupting local pulmonary defense mechanisms.
- Direct damage to the surface epithelium followed by squamous cell metaplasia.
- Secondary compensatory reaction — hyperplasia of mucus-producing cells.
Other factors include atmospheric pollutants (sulfur dioxide and nitrogen oxide emissions in urban areas) and occupational hazards (exposure to organic and mineral dusts, toxic gases).
At the molecular level, these triggers stimulate nerve endings via acetylcholine, upregulate mucociliary clearance and mucin genes, cause mucus hypersecretion, and release transforming growth factor-beta (TGF-beta).
Pathomorphological Changes
The morphological picture consists of two parallel processes: epithelial changes and stromal inflammation. The most prominent changes are recorded in the small bronchi.
Macroscopically: Bronchial walls are thickened, surrounded by layers of connective tissue, and deformed. With prolonged progression, bronchiectasis—saccular or cylindrical dilations of the bronchial lumens—develops.
Microscopically: The process manifests as chronic mucous or purulent catarrhal inflammation.
- Epithelial and glandular changes: Begin with injury and desquamation (shedding). This is followed by hyperplasia of bronchial glands and goblet cells. Metaplasia develops: mucous (increase in goblet cell number) and squamous (replacement of ciliated epithelium by stratified squamous epithelium). Dysplasia—disruption of cellular structure and differentiation—capsulates the cascade as a precancerous process.
- Stromal changes: Characterized by marked inflammatory infiltration. Infiltration cells release inflammatory and damaging mediators: proteases (tissue-destroying), reactive oxygen species, tumor necrosis factor (TNF), and interleukin-8 (IL-8). An antiprotease imbalance occurs. Granulation tissue proliferates in the wall (sometimes forming inflammatory mucosal polyps), while the muscle layer undergoes sclerosis and atrophy. Driven by cytokines and growth factors, fibrosis progresses.
Morphometry and Complications
To objectively assess mucous gland hyperplasia (one of the primary signs of the disease), the Reid index is used. This is the ratio of the thickness of the submucosal glands to the thickness of the entire bronchial wall.
- Normally, the index is 0.44 ± 0.09.
- In pathology, it increases to 0.52 ± 0.08.
Note: at the level of small bronchi, evaluating goblet cell hyperplasia holds greater diagnostic value.
Complications: The disease course may be complicated by secondary infection leading to bronchopneumonia. Impaired bronchial patency leads to foci of atelectasis and obstructive pulmonary emphysema. Ultimately, pneumofibrosis develops.