4. 4
COPD is used to describe emphysema, chronic
bronchitis or a combination of the two.
Symptomatic patients usually have both
5. The more familiar terms 'chronic bronchitis'
and 'emphysema' are no longer used, but
are now included within the COPD
diagnosis.
COPD is not simply a "smoker's cough" but
an under-diagnosed, life-threatening lung
disease.
6. What is COPD?
Chronic Bronchitis ► Small Airways Diseases
Emphysema ► Parenchymal Destruction
GOLD 2006
8. Chronic obstructive pulmonary disease (COPD)
comprises pathological changes in four
different compartments of the lungs
1) CENTRAL AIRWAYS.
2) PERIPHERAL AIRWAYS.
3) LUNG PARENCHYMA.
4) PULMONARY VASCULATURE.
which are variably present in individuals with
the disease.
8
9. PATHOLOGY
COPD comprises major pathological changes in the
following four different compartments of the lung,
which are variably present in individuals with the
disease:
1. Central airways (cartilaginous airways >2mm of
internal diameter)
2. Peripheral airways (noncartilaginous airways
<2mm internal diameter)
3. Lung parenchyma (respiratory bronchioles, alveoli
and capillaries)
4. Pulmonary vasculature
9
10. The predominant pathologic changes of COPD
are found in the airways, but changes are also
seen in the lung parenchyma and pulmonary
vasculature.
In an individual, the pattern of pathologic
changes depends on the underlying disease
(eg, chronic bronchitis, emphysema), possibly
individual susceptibility, and disease severity .
10
Pathology
11. While radiographic methods do not have
the resolution of histology, high resolution
computed tomography can assess lung
parenchyma , airways , and pulmonary
vasculature
11
12. Central airways
Goblet cell and submucosal gland hyperplasia
occurs .
This results in excessive mucous production or
chronic bronchitis. Cell infiltrates also occur in
bronchial glands.
Airway wall changes include squamous
metaplasia of the airway epithelium, loss of cilia
and ciliary dysfunction, and increased smooth
muscle and connective tissue
12
13. Different inflammatory cells predominate in
different compartments of the central airways.
In the airways wall these are lymphocytes,
predominantly of the CD8+ type, but as the
disease progresses neutrophils also become
prominent .
In the airspaces, in addition to lymphocytes,
neutrophils macrophages can also be identified
13
14. Changes in Large Airways of COPD
Mucus hypersecretion Neutrophils in sputum
Goblet cell
hyperplasia
Mucus gland hyperplasia
Squamous metaplasia of epithelium
No basement membrane thickening
↑ Macrophages
↑ CD8+ lymphocytes
Little increase in
airway smooth muscle
Patients
Source: Peter J. Barnes, MD
15. Peripheral airways
Bronchiolitis is present in the peripheral airways at
an early stage of the disease .
There is pathological extension of goblet cells
and squamous metaplasia in the peripheral
airways .
The inflammatory cells in the airway wall and
airspaces are similar to those in the larger
airways .
As the disease progresses, there is fibrosis and
increased deposition of collagen in the airway
15 walls
16. Changes in Small Airways in COPD Patients
Inflammatory exudate in lumen
Disrupted alveolar attachments
Peribronchial fibrosis
Lymphoid follicle
Thickened wall with inflammatory cells
- macrophages, CD8+ cells, fibroblasts
Source: Peter J. Barnes, MD
17. Small airways –
morfological consequences of smoking
Normal Mucus
Hogg JC. Lancet 2004; 364: 709-721
Inflammation
Remodelling
18. •Proximal airways (trachea, bronchi > 2 mm
i.d .)
Goblet cells, enlarged submucosal glands (both
leading to mucus hypersecretion), squamous
metaplasia of epithelium
•Peripheral airways (bronchioles < 2 mm i.d.)
Airway wall thickening, peribronchial fibrosis,
luminal inflammatory exudate, airway
narrowing (obstructive bronchiolitis)
19. 19
Lung parenchyma (respiratory
bronchioles, alveoli and capillaries)
Alveolar wall destruction, apoptosis of epithelial
and endothelial cells. There are two major types :
1) Centrilobular emphysema: dilatation and
destruction of respiratory bronchioles; most
commonly seen in smokers
2) Panacinar emphysema: destruction of alveolar
sacs as well as respiratory bronchioles; most
commonly seen in alpha-1 antitrypsin
deficiency
20. 20
Lung parenchyma (respiratory
bronchioles, alveoli and capillaries)
Alveolar wall destruction, apoptosis of
epithelial and endothelial cells.
The part of the acinus that is affected by
permanent dilation or destruction determines
the subtype of emphysema.
22. Centriacinar emphysema
The central or proximal parts of the acini, formed by
respiratory bronchioles, are affected, while distal
alveoli are spared.
Both emphysematous and normal airspaces exist
within the same acinus and lobule
The lesions are more common and severe in the
upper lobes, particularly in the apical segments.
Most commonly seen among cigarette smokers.
22 also seen in coal workers pneumonconiosis
24. Panacinar Emphysema
The acini are uniformly enlarged (Involvement of
entire acinus,from the terminal bronchiole to
terminal alveoli)
More common in lower lung zones in contrast to
centriacinar emphysema,
Mostly associated with -1 antitrypsin deficiency
although it can be seen in combination with
proximal emphysema in smokers.
25. Distal Acinar Emphysema
least common form
Predominant involvement of distal part of the acinus -
the proximal portion of the acinus is normal.
Not usually associated with airflow obstruction
Acini adjacent to pleura and interlobular septae most
destroyed - It occurs adjacent to areas of fibrosis,
scarring, or atelectasis
Upper lobes most often involved
27. The characteristic findings are the presence of
multiple, contiguous, enlarged airspaces that
range in diameter from less than 0.5 mm to more
than 2.0 cm, sometimes forming cystlike
structures that with progressive enlargement are
referred to as bullae.
May contribute to spontaneous pneumothoraces
and bullae formation in young , tall, asthenic
male adolescents
27
28. Irregular emphysema
The acinus is irregularly involved,
It is associated with scarring, such as
resulting from healed inflammatory diseases
e.g. tuberculosis and sarcoidosis.
Clinically asymptomatic
28
30. As a result of emphysema there is a significant
loss of alveolar attachments, which contributes
to peripheral airway collapse.
The inflammatory cell profile in the alveolar
walls and the airspaces is similar to that
described in the airways and persists
throughout the course of the disease
30
31. Changes in Lung Parenchyma in COPD
Alveolar wall destruction
Loss of elasticity
Destruction of pulmonary
capillary bed
↑ Inflammatory cells
macrophages, CD8+ lymphocytes
Source: Peter J. Barnes, MD
35. Alveolar Emptying in COPD
In COPD, airflow is limited because small airways are narrowed,
alveoli lose their elasticity, and supportive structures are lost.
36. Pulmonary vasculature
Changes in the pulmonary vasculature include
intimal hyperplasia and
Smoothmuscle hypertrophy/hyperplasia thought
to be due to chronic hypoxic vasoconstriction of
the small pulmonary arteries.
Destruction of alveoli due to emphysema can
lead to loss of the associated areas of the
pulmonary capillary bed
36
37. In advanced stages of the disease, there is
collagen deposition and emphysematous
destruction of the capillary bed .
Eventually, these structural changes lead to
pulmonary hypertension and right ventricular
dysfunction (cor pulmonale)
37
Pulmonary vasculature
38. Changes in Pulmonary Arteries in COPD
Endothelial dysfunction
Intimal hyperplasia
Smooth muscle hyperplasia
Patients
↑ Inflammatory cells
(macrophages, CD8+ lymphocytes)
Source: Peter J. Barnes, MD
39. Pulmonary Hypertension in COPD
Chronic hypoxia
Pulmonary vasoconstriction
Muscularization
Intimal
hyperplasia
Fibrosis
Obliteration
Pulmonary hypertension
Cor pulmonale
Death
Edema
Source: Peter J. Barnes, MD
40.
41. Professor Peter J. Barnes, MD
National Heart and Lung Institute, London UK
42. Professor Peter J. Barnes, MD
National Heart and Lung Institute, London UK
44. COPD IS NOT ASTHMA !
• Different causes
• Different inflammatory cells
• Different inflammatory mediators
• Different inflammatory consequences
• Different response to treatment
46. Tobacco smoking is the main risk factor for
COPD, although other inhaled noxious
particles and gases may contribute.
This causes an inflammatory response in the
lungs, which is exaggerated in some
smokers, and leads to the characteristic
pathological lesions of COPD.
46
47. Pathogenesis of COPD
NOXIOUS AGENT
(tobacco smoke, pollutants, occupational
agent)
Genetic factors
Respiratory infection
Other
COPD
48. COPD: Role of Inflammation
There is a chronic inflammatory process in COPD
But, it differs markedly from that seen in asthma
Different inflammatory cells,
Mediators,
Inflammatory effects,
Responses to treatment
49. I. Airway Inflammation
Chronic Inflammation in COPD occurs in the
airways supporting lung tissues and pulmonary
blood vessels.
Inflammation is present in all stages of COPD
It’s primarily due to chronic exposure to inhaled
irritants, particularly cigarette smoke.
50. The main Inflammatory cells implicated in
COPD are; CD8+ T lymphocytes – Macrophages
– Neutrophils
When activated theses cells release
inflammatory mediators, which enhance and
magnify the inflammatory process and cause
tissue damage
50
I. Airway Inflammation
51. Chronic Inflammation plays a central role
in COPD
Smoke Pollutants
Inflammation
Chronic inflammation
Structural changes
Key inflammatory cells
Neutrophils
CD8+ T-lymphocytes
Macrophages
Systemic
inflammation
Bronchoconstriction,
oedema, mucus,
emphysema
Airflow limitation
Acute
exacerbation
Adapted from Barnes PJ, in Stockley, et al (editors), Chronic Obstructive Pulmonary Disease. Oxford, England: Blackwell Publishing; 2007
56. The major proteinases involved in the pathogenesis of
COPD include those produced by neutrophils
(elastase, cathepsin G and proteinase-3) and
macrophages (cathepsins B, L and S), and various
matrix metalloproteinases (MMP).
Neutrophil elastase not only contributes to
parenchymal destruction but it is also a very potent
inducer of mucous secretion and mucous gland
hyperplasia
56
57. The major antiproteinases involved in the
pathogenesis of COPD include:
α1-antitrypsin, secretory leukoproteinase
inhibitor and tissue inhibitors of MMPs.
57
58. CD8+ T cells can be stimulated by cigarette smoke.
They can contribute to alveolar wall destruction via
the activation of AMs and their subsequent release of
neutrophilic chemotactic factors and tissue
proteases.
Cigarette smoke might also directly activate alveolar
epithelial cells to release further pro-inflammatory
cytokines and TGF-β, which is known to modulate
smooth muscle cell and fibroblast proliferation with
subsequent progression to fibrosis and extracellular
matrix deposition.
58
63. Inflammatory cells involved in COPD.
Cigarette smoke activates macrophages and
epithelial cells to release chemotactic factors that
recruit neutrophils, monocytes and CD8+ T
lymphocytes from the circulation.
They also release factors that activate fibroblasts
leading to small airway obstruction (obstructive
bronchiolitis).
Proteases released from neutrophils and macrophages
may cause mucus hypersecretion and emphysema
63
68. In addition to inflammation, two other processes
an imbalance of proteinases and antiproteinases
in the lungs, and oxidative stress are also
important in the pathogenesis of COPD.
Pathogenesis of COPD.
INFLAMMATION.
PROTEINASE AND ANTIPROTEASE IMBALANCE.
OXIDATIVE STRESS.
68
69. Proteinase and Antiprotease Imbalance
may occur in COPD due to :
1) Increased production (or activity) of
proteinases or
2) Inactivation (or reduced production) of
antiproteinases.
69
74. Cigarette smoke (and possibly other COPD risk
factors), as well as inflammation itself, can
produce oxidative stress that:
1) Primes several inflammatory cells
(macrophages, neutrophils) to release a
combination of proteinases
2) Decreases (or inactivates) several
antiproteinases by oxidation
74
75.
76. Oxidative stress can contribute to COPD by
oxidising a variety of biological molecules (that
can lead to cell dysfunction or death), damaging
the extracellular matrix, inactivating key anti-oxidant
defences (or activating proteinases) or
enhancing gene expression (either by activating
transcription factors (e.g. nuclear factor-κB) or
promoting histone acetylation)
76
Oxidative Stress
78. Professor Peter J. Barnes, MD
National Heart and Lung Institute, London UK
79. REACTIVE OXYGEN SPECIES IN COPD
Mucus secretion
NF-B
IL-8
TNF-
Neutrophil
recruitment
ANTIOXIDANTS
Vitamins C and E
N-acetyl cysteine
Glutathione analogues
Nitrones (spin trap)
O2
-, H2O2
OH., ONOO-Anti-
Isoprostanes Plasma leak Bronchoconstriction
proteases
SLPI 1-AT
Proteolysis
80. COPD: Role of Oxidative Stress
Compounds generating oxidative stress
- superoxide anion,
– O2
- hydrogen peroxide,
– H2O2
– OH• hydroxyl radical,
– ONOO- peroxynitrate
Lead to…
…decreased antiprotease defences
…activation of nuclear factor-(kappa)B
– increased secretion of the cytokines interleukin-8 and
tumor necrosis factor (alpha)
…increased production of isoprostanes
– Oxidative stress marker
…other, direct effects on airway functions
81. COPD - cellular and biochemical mechanisms
Inflammation: alveolar macrophages, neutrophils
production of elastase, cathepsine G, collagenase
oxidative stress in smokers and in COPD patients
Neutrophil and macrophage enzymes and oxidants
destroy components of extracellular matrix (collagen,
elastin, fibronectine, proteoglycans)
Loss of cellular components of lung parenchyma:
- elastase can induce apoptosis
- cells exposed to oxidants may undergo apoptosis or necrosis
82. COPD - cellular and biochemical mechanisms
Destruction of lung
parenchyma
Imbalance
proteases antiproteases system
oxidants antioxidants
Small airways
disorder
85. The different pathogenic mechanisms produce the
pathological changes which, in turn, give rise to the
following physiological abnormalities in COPD:
1) Mucous hypersecretion and cilliary dysfunction
2) Airflow limitation and hyperinflation
3) Gas exchange abnormalities
4) Pulmonary hypertension
5) Systemic effects
85
PATHOPHYSIOLOGY
86. PATHOPHYSIOLOGY
1) Mucous Hypersecretion and Cilliary
Dysfunction
These are typically the first physiological
abnormalities in COPD.
The former Mucous hypersecretion is due to
stimulated secretion from enlarged mucous
glands.
The latter Cilliary dysfunction due to squamous
metaplasia of epithelial cells
86
87. Excess Mucus Production
Mucus is a sticky substance produced by goblet
cells and mucous cells of the submucosal glands.
Overproduction of mucus contributes to airway
narrowing, airway obstruction, productive cough
and shortness of breath that is characteristic of
COPD. It also plays a major role in the frequency
and duration of bacterial lung infections.
87
88. In healthy lungs, goblet cells are more
abundant in the large bronchi, decreasing in
number as they reach the smaller bronchioles.
Submucosal glands are restricted to the larger
airways, yet become increasingly sparse as the
airways narrow, disappearing completely in the
bronchioles.
88
91. Normally, mucus functions in a protective way to help
lubricate the lungs and rid the airways of foreign
debris.
In COPD, mucus production, more-or-less, turns on
itself.
When the lungs are continuously subjected to airway
irritants, goblet cells increase in number and
submucosal glands increase in size .
Consequentially, they become more dense in the
smaller airways, outnumbering the broom-like cilia
cells that help clear mucus out of the lungs .
91
92. When mucus production goes into overdrive and
airway clearance is impaired, mucus begins to
pool in the airways, creating obstruction and a
perfect breeding ground for bacteria to multiply.
As bacteria grow in number, bacterial lung
infection occurs often followed by COPD
exacerbation.
92
93. 2) Airflow Limitation And Hyperinflation
Expiratory (largely irreversible) airflow limitation
is the physiological hallmark of COPD.
The major site of the airflow limitation is in the
smaller conducting airways <2 mm in diameter
and is mainly due to airway remodelling
(fibrosis and narrowing)
93
94. Other factors that also contribute include
1. Loss of elastic recoil (due to destruction of
alveolar walls)
2. Destruction of alveolar support (alveolar
attachments)
3. Accumulation of inflammatory cells, mucous
and plasma exudate in the bronchi
4. Smooth muscle contraction
5. Dynamic hyperinflation during exercise.
The latter is one of the major contributors to
exercise limitation in these patients
94
96. Mechanical Origins of Airflow Limitation
Flow = Pressure
Resistance
In Respiratory Function
Chronic Airflow Limitation
(Flow)
Is Determined By
Loss of Elastic Recoil
(Pressure)
Airway Narrowing
(Resistance)
97. -Chronic Bronchitis predominant
-Airway obstruction is the main problem
Normal
Elastic Recoil
Increased airway resistance
due to thickened wall and
secretions
Elastic Recoil
Chronic Bronchitis
98. -Emphysema Predominant
-This results in a loss of the elastic recoil of the lungs on expiration
-This also results in loss of tethering or support of the most distal
portions of the airway leading to collapse on expiration
Normal
Elastic Recoil
Airway supported
by connective
tissue
Decreased
Elastic Recoil =
Lower Flow
Loss of support = Airway
collapses= Air gets trapped in lung
101. Alveolar Emptying in COPD
In COPD, airflow is limited because small airways are narrowed,
alveoli lose their elasticity, and supportive structures are lost.
102. Air Trapping
Occurs in patients with COPD
Results in an increase in the work of breathing
Places respiratory muscles at a mechanical
disadvantage
Contributes to the sensation of breathlessness (dyspnea)
Normal Hyperinflation
Images courtesy of Denis O’Donnell, Queen’s University, Kingston, Canada
105. COPD Pathophysiology
AIRFLOW OBSTRUCTION
Alveolar Wall Destruction
Air Spaces Enlargement
Alveolar Attachments
Loss
Capillary Network
Reduction
HIGH VA/Q RATIOS
AIRFLOW
OBSTRUCTION
Small Airways
Narrowing-Distortion
Nonhomogeneous
Inspired Air Distribution
Reduced Ventilation
In Dependent Alveoli
LOW VA/Q RATIOS
AIR TRAPPING-LUNG
HYPERINFLATION
Rodríguez-Roisin and MacNee. ERM 1998; 6
AIR TRAPPING
LUNG HYPERINFLATION
106. 3) Gas Exchange Abnormalities
These occur in advanced disease and are
characterised by arterial hypoxaemia with or
without hypercapnia.
An abnormal distribution of ventilation-perfusion
ratios is the main mechanism of abnormal gas
exchange in COPD
An abnormal diffusing capacity of carbon
monoxide per litre of alveolar volume correlates
10 well with the severity of the emphysema
6
107. Gas Exchange Abnormalities
Early in the course of disease, when expiratory
flow is only slightly reduced, mild hypoxemia
may be the only blood gas abnormality.
However, in advanced stages of COPD, 2 distinct
patterns emerge :
1) Patients with the type A pattern : (Pink Puffer)
2) Patients with the type B pattern : (Blue Bloater)
10
7
108. Emphysema (Pink Puffer)
Only mild-to-moderate hypoxemia (partial
pressure of arterial oxygen[PaO2] is usually > 65
mm Hg).
In addition, these patients maintain normal or
even slightly reduced partial pressure of arterial
carbon dioxide (PaCO2).
These patients tend to be thin, to experience
hyperinflation at total lung capacity, and to be
free of signs of right heart failure.
10
8
109. Chronic Bronchitis (Blue Bloater)
Patients with the type B pattern are characterized
by marked hypoxemia and peripheral edema
resulting from right heart failure.
They have frequent respiratory tract infections,
experience chronic carbon dioxide retention
(PaCO2 > 45 mm Hg), and have recurrent
episodes of cor pulmonale.
10
9
110. The 2 clinical types also have very
different consequences for the
cardiovascular system.
In the type B patient, both alveolar hypoxia and
acidosis (secondary to chronic hypercapnia)
stimulate pulmonary arterial vasoconstriction
Hypoxemia stimulates erythrocytosis.
Increased pulmonary vascular resistance, increased
pulmonary blood volume, and possibly increased
blood viscosity from secondary erythrocytosis all
contribute to pulmonary arterial hypertension . 11
0
111. In response to long-term pulmonary hypertension, cor
pulmonale generally develops: The right ventricle
becomes hypertrophic, and increases in cardiac
output are achieved by abnormally high filling
pressure in the right ventricle.
Additional hemodynamic loads may cause the right
ventricle to fail, with the consequent development of
systemic venous hypertension, which is manifested by
jugular venous distention, peripheral edema, passive
11 hepatic congestion, and sometimes ascites.
1
112. The emphysematous lung destruction
characteristic of type A patients leads to a
restricted vascular bed because of the loss of
pulmonary capillaries from the destroyed alveolar
walls.
This condition is reflected in the reduced diffusing
capacity of the lung for carbon monoxide (DLCO)
observed in type A (but not type B) patients
11
2
113. Because PaO2 levels are only mildly depressed in
type A patients, pulmonary vasoconstriction is
minimal and secondary erythrocytosis does not
develop.
As a result, pulmonary hypertension in type A
patients is milder than that in type B patients, and
cor pulmonale develops infrequently, usually
only in the terminal phase of the illness.
11
3
114. Differing degrees of oxygen saturation on
exertion. Differences in gas exchange during
exercise also distinguish the 2 clinical types.
Type A patients develop oxygen desaturation
during exercise, whereas type B patients may
exhibit increases in oxygen saturation during
exercise.
11
4
115. COPD Pathophysiology
AIRFLOW OBSTRUCTION
Alveolar Wall Destruction
Air Spaces Enlargement
Alveolar Attachments
Loss
Capillary Network
Reduction
HIGH VA/Q RATIOS
AIRFLOW
OBSTRUCTION
Small Airways
Narrowing-Distortion
Nonhomogeneous
Inspired Air Distribution
Reduced Ventilation
In Dependent Alveoli
LOW VA/Q RATIOS
AIR TRAPPING-LUNG
HYPERINFLATION
Rodríguez-Roisin and MacNee. ERM 1998; 6
AIR TRAPPING
LUNG HYPERINFLATION
117. Clinical Course of COPD
COPD
Expiratory Flow Limitation
Air Trapping
Hyperinflation
Breathlessness
Inactivity
Deconditioning
Reduced Exercise
Capacity
Poor Health-Related Quality of Life
EXACERBATIONS
Disability Disease progression Death
118. 4) Pulmonary Hypertension
This occurs late in the course of COPD, normally after the
development of severe gas exchange abnormalities.
Factors contributing to pulmonary hypertension in COPD
include vasoconstriction (mostly of hypoxic origin),
endothelial dysfunction, remodelling of pulmonary
arteries and destruction of the pulmonary capillary bed.
This may eventually lead to right ventricular hypertrophy
and dysfunction (cor pulmonale)
11
8
119. Pulmonary Hypertension in COPD
Chronic hypoxia
Pulmonary vasoconstriction
Muscularization
Intimal
hyperplasia
Fibrosis
Obliteration
Pulmonary hypertension
Cor pulmonale
Death
Edema
Source: Peter J. Barnes, MD
120. 5) Systemic Effects
COPD is associated with extrapulmonary
effects, including systemic inflammation and
skeletal muscle wasting.
These systemic effects contribute to limit the
exercise capacity of these patients and to
worsen prognosis, independent of their
pulmonary function
12
0
121. COPD has significant extrapulmonary
(systemic) effects including:
☻Weight loss
☻Nutritional abnormalities
☻Skeletal muscle dysfunction
123. COPD is: More than just a lung disorder
Respiratory system
QuickTime™ an d a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Systemic
inflammation
COPD is:
a multi- component disease
Target organs
with systemic involvement & inflammation
124. Assess COPD Comorbidities
COPD patients are at increased risk for:
☻Cardiovascular diseases
☻Osteoporosis
☻Respiratory infections
☻Anxiety and Depression
☻Diabetes
☻Lung cancer
GOLD revised 2011
125. Systemic Effects of COPD:
Lung Infections
Lung Cancer
Angina
Acute coronary
syndromes
Diabetes
Metabolic syndrome
Systemic
Inflammation
Oxidatitive Stress
Weight loss
Muscle weakness
Osteoporosis
Depression
Peptic ulceration Depression
129. COPD is a multicomponent disease
Inflammation
Airway
obstruction
Structural
changes
Airflow limitation
Muco-ciliary
dysfunction
Cazzola and Dahl, Chest 2004
Inflammation
130. COPD components that contribute to the
symptoms of the disease
Structural
changes
Airflow limitation
Broncho-constriction
Systemic
component
Mucociliary
dysfunction
Symptoms
Airway
inflammation
1. Agusti AGN et al. Respir Med 2005; 99: 670–682.
Disease progression
Death
131. COPD is a multicomponent disease with
inflammation at its core leading to mortality
Declining lung function
Symptoms
Exacerbations
Decreased exercise tolerance
Deteriorating health status
and increasing morbidity
Mortality
Airflow
limitation
Structural
changes
Systemic
component
Mucociliary
dysfunction
Airway
inflammation
Agusti. Respir Med 2005
Agusti et al. Eur Respir J 2003
Bernard et al. Am J Respir Crit Care Med 1998
