Pathogenesis (disease development)
The following factors are important in the pathogenesis of chronic obstructive pulmonary disease (COPD):
- Insufficiency of the ciliated epithelium of the airways; continued damage – e.g., tobacco smoke – results in complete destruction of the epithelium
- Atrophy of the bronchial mucosa
- Abnormally increased mucus production in the bronchi
- Infiltrations mainly of lymphocytes and plasma cells.
- Metaplasia of the squamous epithelium
All these factors together lead to chronic bronchitis, which, if the risk factors persist, may eventually lead to emphysema (irreversible overinflation of the smallest air-filled structures (alveoli, alveoli) of the lungs) due to loss of elasticity of emphysematous lung tissue and cor pulmonale (pressure-loaded right heart due to an increase in pressure in the pulmonary circulation). Note: It is now believed that the pathogenesis of COPD begins earlier than previously thought. Destruction of terminal bronchioles (smallest bronchi) precedes the development of emphysema.
Etiology (Causes)
Biographic causes
- Genetic burden
- Genetic risk depending on gene polymorphisms:
- Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
- Genes: AQP5, FAM13A
- SNP: rs7671167 in the gene FAM13A
- Allele constellation: CT (1.32-fold).
- Allele constellation: TT (1.7-fold)
- SNP: rs3736309 in gene AQP5
- Allele constellation: AG (0.44-fold).
- Allele constellation: GG (0.44-fold)
- Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
- Genetic diseases
- Alpha-1-antitrypsin deficiency (AATD; α1-antitrypsin deficiency; synonyms: Laurell-Eriksson syndrome, protease inhibitor deficiency, AAT deficit): genetic disorder with autosomal recessive inheritance in which too little alpha-1-antitrypsin is produced due to a polymorphism, resulting in the lack of inhibition of elastase, causing the elastin of the pulmonary alveoli to degrade (SNP s. u. Laboratory parameter “alpha-1-antitrypsin deficiency“).
- Genetic risk depending on gene polymorphisms:
- Anatomical variants – dysanapsis (compared to total lung small airways); patients have poorer lung function (FEV1) from a young age than non-smokers who do not later develop COPD (could possibly explain in part why non-smokers can also develop COPD).
- History of bronchial hyperresponsiveness and bronchial asthma.
- Passive smoker as a child (parents smoke).
- Frequent respiratory infections in childhood
- Disorders of lung growth
- Age
Behavioral causes
- Nutrition
- Micronutrient deficiency (vital substances) – see Prevention with micronutrients.
- Consumption of stimulants
- Tobacco (smoking, passive smoking) – The most important risk factor for developing COPD is smoking. Chinese hookah smoking is also associated with a significant increase in COPD risk, although tobacco smoke is filtered by water.However, according to the CanCOLD study (5176 individuals aged 40 years and older; population-based, prospective Canadian Cohort of Obstructive Lung Disease Study (CanCOLD study)), 29% of COPD patients are nonsmokers.
- Overweight (BMI ≥ 25; obesity).
- Android body fat distribution, that is, abdominal/visceral, truncal, central body fat (apple type) – high waist circumference or waist-to-hip ratio (THQ; waist-to-hip ratio (WHR)) is presentWhen measuring waist circumference according to the International Diabetes Federation (IDF, 2005) guideline, the following standard values apply:
- Men < 94 cm
- Women < 80 cm
The German Obesity Society published somewhat more moderate figures for waist circumference in 2006: < 102 cm for men and < 88 cm for women.
Disease-related causes
- Bronchial asthma / “asthma-COPD overlap syndrome”
- Chronic bronchitis (inflammation of the bronchial mucosa).
- Cicatricial emphysema (expansion of lung tissue in the vicinity of shrinking lung districts; e.g., due to inhalation of quartz-containing dusts).
- Subclinical inflammation (engl.”silent inflammation”) – permanent systemic inflammation (inflammation affecting the whole organism), which proceeds without clinical symptoms.
- Hyperexpansion emphysema after partial lung resection (occurs because part of the lung has been removed and the remaining lung fills the remaining space).
Environmental pollution – intoxications (poisonings).
- General air pollution (including NO2, oxon).
- Occupational dusts – quartz-containing dusts, cotton dusts, grain dusts, welding fumes, mineral fibers, irritant gases such as ozone, nitrogen dioxide or chlorine gas.
- Exposure to biogenic heating materials (coal, wood, etc. for at least ten years).
- Wood fire
- Indoor pollution (cooking and heating by burning natural materials).
- Air pollutants: particulate matter, ozone, sulfur dioxide.
- Ship emissions (heavy fuel oil; diesel)
Other causes
- Old-age emphysema
- Childhood hospitalizations for respiratory disease; risk factor for nonsmokers with COPD.