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Профилактическая
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Preventive Medicine
and Health
Journal home page:
https://inscience.uz/index.php/preventive-medicine
Chronic Obstructive Pulmonary Disease: pathophysiology
and the role of inflammation
, Davron MUMINOV
Central Asian Medical University,
Tashkent Pediatric Medical Institute
ARTICLE INFO
ABSTRACT
Article history:
Received August 2024
Received in revised form
10 September 2024
Accepted 25 September 2024
Available online
15 October 2024
Chronic Obstructive Pulmonary Disease (COPD) is a
progressive respiratory condition characterized by persistent
airflow limitation and a heightened lung inflammatory response.
Systemic inflammation plays a crucial role in COPD pathogenesis,
influencing disease progression and the development of
comorbidities. This review explores the sequential stages of
inflammation-driven pathological changes in COPD, from early
airway alterations to advanced systemic effects. The disease
process begins with chronic exposure to risk factors such as
smoking, air pollution, and occupational hazards. This leads to
increased mucus secretion and dysfunction of ciliated epithelial
cells, which results in impaired mucociliary clearance and
heightened susceptibility to infections. As inflammation persists,
bronchial obstruction and airway remodeling occur, limiting
airflow. Pulmonary hyperinflation and emphysema further
exacerbate respiratory insufficiency by reducing elastic recoil and
increasing the work of breathing. Future research should
emphasize
precision
medicine
approaches,
biomarker
identification, and novel anti-inflammatory therapies to mitigate
disease progression and enhance patient outcomes.
2181-3663
/©
2024 in Science LLC.
https://doi.org/10.47689/2181-3663-vol3-iss-pp82-88
This is an open-access article under the Attribution 4.0 International
(CC BY 4.0) license (
https://creativecommons.org/licenses/by/4.0/deed.ru
Keywords:
COPD,
systemic inflammation,
oxidative stress,
airway obstruction,
pulmonary hypertension,
inflammatory mediators.
1
Central Asian Medical University. E-mail: farxod.musayev7730@mail.ru
2
MD, PhD, DSc, Tashkent Pediatric Medical Institute. E-mail: dr.muminov1@gmail.com
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Surunkali obstruktiv o‘pka kasalligi: patofiziologiya va
yalligʻlanishning roli
ANNOTATSIYA
Kalit so‘zlar
:
SOOʻK,
tizimli yallig‘lanish,
oksidlanish stressi,
nafas yo‘llarining
obstruktsiyasi,
o‘pka gipertenziyasi,
yallig‘lanish mediatori
.
Surunkali obstruktiv o‘pka kasalligi (SOOʻK) —
bu nafas olish
tizimining yomonlashuvchi kasalligi bo‘lib, doimiy havo oqimining
cheklanishi va o‘pka yallig‘lanishining kuchayishi bilan ajralib
turadi. Tizimli yallig‘lanish SOOʻK patogenezida muhim rol
o‘yn
aydi, kasallikning rivojlanishi va hamroh kasalliklarning paydo
bo‘lishiga ta’sir ko‘rsatadi. Ushbu sharhda SOOʻKda yallig‘lanish
tufayli yuzaga keladigan patologik o‘zgarishlarning ketma
-ket
bosqichlari, dastlabki nafas yo‘llari o‘zgarishlaridan tortib,
r
ivojlangan tizimli ta’sirlargacha o‘rganiladi. Kasallik jarayoni uzoq
muddatli xavf faktorlariga, masalan, chekish, havoning ifloslanishi
va kasbiy xavflarga duchor bo‘lishdan boshlanadi. Bu shilliq
qavatning sekretsiyasining oshishiga va manzarali epiteliya
hujayralarining disfunktsiyasiga olib keladi, natijada mukotsilyar
tozalashning buzilishi va infeksiyalarga nisbatan sezgirlikning
oshishi kuzatiladi. Yallig‘lanish davom etgan sari, bronxial
obstruktsiya va nafas yo‘llarining remodellashtirilishi yuzag
a
keladi, bu esa havo oqimini cheklaydi. O‘pkaning giperinflyatsiyasi
va emfizema nafas olish yetishmovchiligini yanada kuchaytiradi,
elastik tiklanishni kamaytiradi va nafas olish ishini oshiradi.
Kelajakdagi tadqiqotlar aniq tibbiyot yondoshuvlari, biomarkerni
aniqlash va yangi yallig‘lanishga qarshi davolash usullarini ishlab
chiqishga e’tibor qaratishi kerak, bu kasallikning rivojlanishini
sekinlashtirish va bemorlarning natijalarini yaxshilashga yordam
beradi.
Хроническая
обструктивная
болезнь
легких:
патофизиология и роль воспаления
АННОТАЦИЯ
Ключевые слова:
ХОБЛ,
системное воспаление,
оксидативный стресс,
обструкция дыхательных
путей,
легочная гипертензия,
воспалительные
медиаторы
.
Хроническая обструктивная болезнь легких (ХОБЛ) —
прогрессирующее
респираторное
заболевание,
характеризующееся стойким ограничением воздушного
потока и усиленной воспалительной реакцией легких.
Системное воспаление играет ключевую роль в патогенезе
ХОБЛ, влияя на прогрессирование заболевания и развитие
сопутствующих заболеваний. Этот обзор исследует
последовательные этапы воспаления, приводящего к
патологическим изменениям в ХОБЛ, от ранних изменений
в дыхательных путях до поздних системных эффектов.
Процесс
заболевания
начинается
с
хронического
воздействия факторов риска, таких как курение,
загрязнение воздуха и профессиональные опасности. Это
приводит к увеличению секреции слизи и дисфункции
реснитчатых эпителиальных клеток, что нарушает
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мукоцилиарный клиренс и повышает восприимчивость к
инфекциям. По мере продолжения воспаления возникает
бронхиальная
обструкция
и
ремоделирование
дыхательных путей, что ограничивает воздушный поток.
Пульмональная гиперинфляция и эмфизема усугубляют
дыхательную недостаточность, снижая эластичность
легких
и
увеличивая
работу
дыхания.
Будущие
исследования должны сосредоточиться на подходах точной
медицины, идентификации биомаркеров и новых
противовоспалительных
терапиях
для
замедления
прогрессирования заболевания и улучшения результатов
лечения пациентов.
GOLD international research group members have extensively studied the
prevalence of Chronic Obstructive Pulmonary Disease (COPD). The GOLD study covers 18
countries worldwide, aiming to identify risk factors and epidemiology of COPD. Currently,
12 out of 18 countries have completed data collection and analysis, and the results are
published in The Lancet journal. According to this study, the prevalence of moderate-to-
severe COPD (according to the international classification) is 10% (12% among men and
8.5% among women). Compared to previous studies, this figure has increased. The
incidence of COPD rises with smoking and aging (doubling every 10 years). Notably, both
smokers and non-smokers have an equal risk of developing COPD over 10 years [15].
Among patients over 45 years old, COPD ranks fourth among causes of death and continues
to be a leading contributor to mortality, surpassing other diseases [21].
The primary risk factor for COPD development is smoking, accounting for 80-90%
of cases. Mortality rates among smokers due to COPD remain high, with irreversible
obstructive changes in respiratory function and increasing dyspnea. However, COPD also
occurs and progresses among non-smokers [15]. Currently, a key diagnostic criterion for
COPD and chronic non-obstructive bronchitis is long-term and persistent smoking [7, 13].
In recent years, passive smoking has received significant attention [19, 22]. Inflammatory
response plays a central role in COPD pathogenesis. This reaction initially leads to
reversible bronchial obstruction, later becoming irreversible, resulting in airflow
limitation [12]. Inflammation develops throughout the respiratory tract and is influenced
by pollutants in genetically susceptible individuals. Long-term and persistent smoking
primarily affects the oral mucosa, transferring harmful substances through saliva to the
bronchopulmonary system and lymphoid tissue [15]. Occupational exposure to cadmium
and silicon dust has been identified as a significant risk factor for COPD development. High-
risk professions include miners, railway workers, grain, cotton, paper processors, cement
workers, and those in the metal industry. Mining occupations are particularly at risk.
Notably, occupational exposure combined with smoking exacerbates COPD progression
[15]. Genetic predisposition plays a significant role in COPD development, as evidenced by
the fact that not all chronic smokers develop the disease. Currently, alpha-1 antitrypsin
deficiency is the only well-studied genetic pathology leading to emphysema, chronic
obstructive bronchitis, and bronchiectasis.
However, its role in COPD development is less significant compared to smoking. In
the U.S., alpha-1 antitrypsin deficiency is found in less than 1% of COPD patients [15].
Smoking accelerates COPD onset. Dyspnea develops after 40 years of age in smokers,
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whereas in non-smokers, it appears 13-15 years later [15]. The European Respiratory
Society has classified COPD etiological risk factors based on their significance (Table 1)
[15].
Table 1.
Classification of COPD risk factors
Risk Factor
Probability
External Risk Factors
Internal Risk Factors
Established
Smoking; Occupational exposure
(cadmium, silicon)
Alpha-1 antitrypsin deficiency
High
Air pollution (SO2, NO2, O3);
Occupational exposure; Low
socioeconomic status; Childhood
passive smoking
Prematurity; Elevated IgE levels;
Bronchial hyperreactivity; Family
history of COPD
Probable
Adenoviral infection; Vitamin C
deficiency
Genetic predisposition (Blood type
I, IgA deficiency)
It is well known that bronchial hyperreactivity and elevated immunoglobulin E
levels are observed in asthma patients. However, when these factors combine with
smoking, they accelerate COPD progression [15]. Key processes in COPD pathogenesis
include [15] Inflammation, Imbalance between proteases and antiproteases in the lungs,
and Oxidative stress. Chronic inflammation affects the entire respiratory tract, lung
parenchyma, and vasculature, leading to irreversible structural damage over time.
Environmental and genetic factors disrupt enzyme balance and oxidative stress. COPD is
characterized by increased macrophages, neutrophils, and CD8+ T-lymphocytes,
particularly interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-
α), and leukotriene B4
(LTB4), which contribute to lung tissue damage and neutrophilic inflammation [15].
In 1963, Laurell and Eriksson reported that individuals with alpha-1 antitrypsin
deficiency risk developing emphysema due to uncontrolled neutrophil elastase activity.
Today, the connection between alpha-1 antitrypsin deficiency and COPD is well
established. Neutrophils, epithelial cells, and macrophages release various proteases,
which suppress antiprotease activity in the presence of oxidative stress and tobacco
smoke, worsening the protease-antiprotease imbalance in COPD pathogenesis [15].
Markers such as hydrogen peroxide (H2O2) and nitric oxide (NO) are elevated in COPD
patients and smokers' urine, exhaled breath, and epithelial surface fluid. This confirms the
role of oxidative stress in COPD. During disease exacerbations, hydrogen peroxide levels
in exhaled air significantly increase, while nitric oxide levels also rise. F2α
-III, an oxidative
stress biomarker, is elevated in COPD patients' urine and exhaled air, reaching higher
levels during exacerbations [15]. Oxidants degrade proteins, lipids, and nucleic acids,
leading to cellular dysfunction and extracellular matrix destruction. Oxidative stress
exacerbates protease-antiprotease imbalance, further accelerating lung damage.
Additionally, it activates nuclear factor kappa-B (NF-kB), which increases inflammatory
gene expression, including IL-8 and TNF-
α. Oxidative stress can also induce bronchial
obstruction: hydrogen peroxide contracts smooth muscle cells in vitro, while F2α
-III
causes pronounced bronchoconstriction [15]. It is well known that bronchial
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hyperreactivity and elevated immunoglobulin E levels are observed in asthma patients.
However, when these factors combine with smoking, they accelerate COPD progression
[15]. Chronic inflammation affects the entire respiratory tract, lung parenchyma, and
vasculature, leading to irreversible structural damage. Environmental and genetic factors
disrupt enzyme balance and oxidative stress. COPD is characterized by increased
macrophages, neutrophils, and CD8+ T-lymphocytes, particularly interleukin-8 (IL-8),
tumor necrosis factor-alpha (TNF-
α), and leukotriene B4 (LTB4), which contribute to lung
tissue damage and neutrophilic inflammation [15]. In 1963, Laurell and Eriksson reported
that individuals with alpha-1 antitrypsin deficiency risk developing emphysema due to
uncontrolled neutrophil elastase activity. Today, the connection between alpha-1
antitrypsin deficiency and COPD is well established. Neutrophils, epithelial cells, and
macrophages release various proteases, which suppress antiprotease activity in the
presence of oxidative stress and tobacco smoke, worsening the protease-antiprotease
imbalance in COPD pathogenesis [15]. Markers such as hydrogen peroxide (H2O2) and
nitric oxide (NO) are elevated in COPD patients and smokers' urine, exhaled breath, and
epithelial surface fluid. This confirms the role of oxidative stress in COPD. During disease
exacerbations, hydrogen peroxide levels in exhaled air significantly increase, while nitric
oxide levels also rise. F2α
-III, an oxidative stress biomarker, is elevated in COPD patients'
urine and exhaled air, reaching higher levels during exacerbations [15]. Oxidants degrade
proteins, lipids, and nucleic acids, leading to cellular dysfunction and extracellular matrix
destruction. Oxidative stress exacerbates protease-antiprotease imbalance, further
accelerating lung damage. Additionally, it activates nuclear factor kappa-B (NF-kB), which
increases inflammatory gene expression, including IL-8 and TNF-
α. Oxidative stress can
also induce bronchial obstruction: hydrogen peroxide contracts smooth muscle cells in
vitro, while F2α
-III causes pronounced bronchoconstriction [15].
Pathological changes in COPD include
Category
Key Features
Early Airway Alterations
Increased mucus secretion, Dysfunction of
ciliated epithelial cells
Obstruction and Structural Changes
Bronchial obstruction, Airway narrowing
Lung Overinflation and Tissue Damage
Pulmonary
hyperinflation,
Emphysema
development
Gas Exchange Impairment and Vascular Effects Reduced oxygen diffusion, Hypercapnia (CO2
retention)
Pulmonary Hypertension and Systemic
Inflammation
Increased vascular resistance, Cardiovascular
complications
Immune dysregulation in COPD is significant, primarily characterized by increased
neutrophils, macrophages, and CD8+ T-lymphocytes [18]. Key inflammatory mediators
include IL-6, TNF-
α, and IL
-8, which are involved in immune responses and inflammation
[8, 16]. Research shows elevated IL-6, IL-8, and IL-4 levels in COPD patients, while IL-10
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levels decrease. This imbalance indicates that pro-inflammatory cytokines are crucial in
COPD progression [2].
CONCLUSION
A literature review confirms that inflammation is a key driver of COPD pathogenesis.
This chronic inflammatory response initially leads to reversible bronchial obstruction;
however, persistent inflammation causes structural airway remodeling over time,
resulting in irreversible airflow limitation. Various interleukins, including IL-6, IL-8, and
IL-
1β, contribute to these pathological changes by promoting mucus hypersecretion,
epithelial dysfunction, and immune cell infiltration. These processes collectively
exacerbate disease progression, leading to declining lung function and increased
susceptibility to exacerbations.
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