Pathogenesis and Cellular Level of Inflammation
The chronic inflammatory process in COPD involves not only the airways but also the pulmonary parenchyma and vasculature. The cellular infiltrate shows an increased number of macrophages, T-lymphocytes, and, most importantly for differential diagnosis, neutrophils.
Neutrophilic inflammation follows a catarrhal or catarrhal-purulent pattern and triggers a cascade of structural changes in the epithelium:
- Goblet cell hyperplasia: the number of mucus-producing cells increases sharply, leading to pronounced hypersecretion.
- Squamous metaplasia: normal ciliated epithelium is replaced, disrupting mucociliary clearance and causing mucus stasis.
Cough with sputum production becomes the first clinical manifestation of these processes. Secretion is actively stimulated by mediators released during neutrophilic inflammation: leukotrienes, interleukins (IL-1$\beta$, IL-6), tumor necrosis factor-alpha (TNF-$\alpha$), as well as various proteinases and neuropeptides.
Destructive Processes and Oxidative Stress
In later stages of the disease, the core pathological process involves the destruction of the extracellular matrix—the connective tissue stroma of the lungs. This process is driven by two biochemical mechanisms:
- Enzymatic imbalance. An imbalance develops between tissue inhibitors and proteolytic enzymes (collagenases and matrix metalloproteinases, including gelatinases). Neutrophils and other inflammatory cells serve as the main source of degradation enzymes.
- Oxidative stress. Neutrophils actively generate reactive oxygen species (ROS), which cause direct destruction of the pulmonary stroma.
A key factor driving the progression of destruction is smoking. Nicotine acts as a potent chemoattractant, continuously recruiting new neutrophils to the bronchi. Furthermore, tobacco pyrolysis products contain their own ROS, vastly amplifying oxidative stress.
Morphological Consequences and Symptoms
The destruction of the elastic framework of the lungs inevitably leads to the development of emphysema. Deprived of stromal support, alveoli increase in size, overinflate, and begin to mechanically compress adjacent pulmonary capillaries and bronchioles.
Such morphological changes trigger severe pathophysiological shifts:
- Airway obstruction worsens.
- Pulmonary blood flow is impaired.
- Pulmonary hypertension develops.
Once respiratory failure is established, the clinical picture changes: dyspnea joins the persistent cough. Functional diagnostics reveal a decrease in vital capacity (VC) and forced expiratory volume (FEV).
Pharmacotherapy Strategy and Principles
The main goals of medical treatment are to prevent disease progression, reduce the frequency of exacerbations, and alleviate symptom severity. Complete smoking cessation is a mandatory prerequisite for the effectiveness of any regimen.
Patient management in COPD differs fundamentally from the treatment of bronchial asthma. First, the intensity of therapy only increases as the condition worsens; a 'step-down' strategy is never applied. Second, due to the absence of an allergic component, leukotriene antagonists and mast cell stabilizers are not used.
Bronchodilators form the primary class of drugs for maintenance therapy. The choice of a specific agent depends on pharmacokinetics and the patient's comorbidities:
- Anticholinergics (muscarinic antagonists) — first-line drugs for elderly patients with cardiovascular comorbidities (hypertension, coronary artery disease, arrhythmias) as they are the safest for the heart.
- $\beta$2-agonists — long-acting agents are preferred (e.g., formoterol).
- Myotropic agents (phosphodiesterase inhibitors) — also recommended in prolonged-release pharmaceutical formulations.