Pathogenesis and cellular level of inflammation
The chronic inflammatory process in COPD involves not only the airways but also the pulmonary parenchyma and blood vessels. The cellular infiltrate shows an increased number of macrophages, T-lymphocytes, and, most importantly for differential diagnosis, neutrophils.
Neutrophilic inflammation proceeds in a catarrhal or catarrhal-purulent manner and triggers a cascade of structural changes in the epithelium:
- Goblet cell hyperplasia: the number of mucus-producing cells increases dramatically, leading to pronounced hypersecretion.
- Squamous metaplasia: normal ciliated epithelium is replaced, which disrupts mucociliary clearance and causes mucus stasis.
The first clinical manifestation of these processes is a cough with sputum production. 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 the late stages of the disease, the essence of the pathological process boils down to 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 arises between tissue inhibitors and proteolytic enzymes (collagenases and matrix metalloproteinases, including gelatinases). Neutrophils and other inflammatory cells serve as the primary source of degradation enzymes.
- Oxidative stress. Neutrophils actively produce reactive oxygen species (ROS), which cause direct destruction of the pulmonary stroma.
A key factor in the progression of destruction is smoking. Nicotine acts as a potent chemoattractant, continuously recruiting new neutrophils into the bronchi. In addition, tobacco pyrolysis products contain their own ROS, significantly amplifying oxidative stress.
Morphological consequences and symptoms
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 neighboring pulmonary capillaries and bronchioles.
Such morphological changes cause serious pathophysiological shifts:
- Bronchial obstruction increases.
- Pulmonary blood flow is disrupted.
- Pulmonary hypertension develops.
At the stage of respiratory failure, the clinical picture changes: dyspnea joins the persistent cough. Functional diagnostics register a decrease in vital capacity (VC) and a drop in forced expiratory volume (FEV).
Strategy and principles of pharmacotherapy
The main objectives of medical treatment are to prevent disease progression, reduce the frequency of exacerbations, and lessen symptom severity. A mandatory condition for the effectiveness of any regimen is complete smoking cessation.
The management tactics for COPD patients differ radically from the treatment of bronchial asthma. Firstly, the scope of therapy here only increases as the condition worsens; the "step-down" strategy (reducing treatment volume) is not applied. Secondly, due to the absence of an allergic component, leukotriene antagonists and mast cell stabilizers are not used in the regimens.
Bronchodilators are the main class of drugs for baseline therapy. The choice of a specific agent depends on pharmacokinetics and the patient's comorbidities:
- Anticholinergics are first-line drugs for elderly patients with cardiovascular pathology (hypertension, coronary artery disease, arrhythmias), as they are the safest for the heart.
- $\beta$2-adrenergic agonists — long-acting drugs are preferred (e.g., formoterol).
- Myotropic agents (phosphodiesterase inhibitors) are also recommended for use in sustained-release formulations.
Briefly: answers to topical questions
Which specific drugs belong to anticholinergics for COPD treatment?
Anticholinergics for COPD treatment include the following drugs:
- Ipratropium bromide — a short-acting drug of choice that relieves increased cholinergic influence on bronchial tone.
- Tiotropium bromide — a long-acting drug that selectively blocks M3 and M1 muscarinic receptors.
- Aclidinium bromide — a long-acting anticholinergic drug.
- Glycopyrronium bromide — a long-acting anticholinergic drug.
Which phosphodiesterase inhibitors are prescribed for COPD patients?
COPD patients are prescribed type IV phosphodiesterase inhibitors and myotropic agents — methylxanthines.
- Roflumilast — selectively inhibits phosphodiesterase-4 D-isoform, exhibits bronchodilator and anti-inflammatory effects.
- Cilomilast — a drug from the PDE-4 inhibitor group, a precursor to roflumilast.
- Theophylline — a myotropic antispasmodic, poorly soluble in water.
- Aminophylline — a mixture of 80% theophylline and 20% ethylenediamine; ethylenediamine provides better water solubility.
Which drugs belong to the long-acting beta2-adrenergic agonist group in COPD?
Formoterol is included in the long-acting beta2-adrenergic agonist group for COPD therapy.
- Formoterol — a long-acting drug that is preferred when choosing bronchodilators.
This group of drugs is used as baseline therapy to control symptoms and reduce the risk of future disease exacerbations.
Which pulmonary function (spirometry) indicators decrease in COPD?
In chronic obstructive pulmonary disease, the following pulmonary function indicators decrease:
- VC — vital capacity.
- FEV (specifically, FEV1) — forced expiratory volume.
- Tiffeneau index — the ratio of FEV1 to forced vital capacity (FVC) or VC.
A key spirometric criterion for airflow limitation is a decrease in the post-bronchodilator Tiffeneau index below 0.7 (or less than 70%).
For the differential diagnosis of inflammatory cells on the exam, remember: COPD means Neutrophils (the letter "N" is present in the word "chronic" in Russian, *khronichesky*), while asthma means Eosinophils and Mast cells.
Class and exam questions
Why are mast cell stabilizers and leukotriene antagonists not prescribed for COPD?
This disease lacks an allergic component of inflammation. The key cell of pathogenesis is the neutrophil, not the mast cell or eosinophil, which is why these groups of drugs are ineffective.
Which bronchodilator is safest for an elderly patient with concomitant coronary artery disease and arrhythmia?
First-choice drugs in this situation are anticholinergics. They have the lowest cardiotoxic effect compared to other bronchodilator groups.
What is the role of smoking in the pathogenesis of the disease?
Nicotine acts as a chemoattractant, recruiting neutrophils into the airways. At the same time, tobacco combustion products contain reactive oxygen species that exacerbate oxidative stress and accelerate lung tissue destruction.
Is it possible to reduce drug dosages if the patient feels better?
Generally, no. Unlike bronchial asthma, the "step-down" treatment reduction tactic is not applied in COPD; the volume of therapy can only escalate.
What else to study on this topic
- Biochemical mechanism of action of matrix metalloproteinases and gelatinases
- The role of interleukins (IL-1β, IL-6) and TNF-α in stimulating mucus hypersecretion
- Pathogenesis of pulmonary hypertension in emphysema
- Pharmacokinetics and mechanism of action of long-acting β2-agonists (formoterol)
- Mechanism of action of phosphodiesterase inhibitors (myotropic agents)
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