Chronic Obstructive Pulmonary Disease: Respiratory Infection Depression

Chronic Obstructive Pulmonary Disease (COPD) is a disease characterized by airflow
limitation that is not fully reversible. Airflow limitation is usually progressive and associated
with an inflammatory response in the lungs stimulated by irritants. COPD includes chronic
bronchitis and pulmonary emphysema. Although sometimes included in COPD, asthma is a
reversible disorder and is therefore considered elsewhere.
Chronic bronchitis is chronic inflammation of the lower airways characterized by excessive

secretion of mucus, hypertrophy of mucous glands, and recurring infection, progressing to
narrowing and obstruction of airflow. Emphysema is the enlargement of the air spaces distal to
the terminal bronchioles, with breakdown of alveolar walls and loss of elastic recoil of the lungs.
The two conditions may overlap, resulting in subsequent derangement of airways dynamics (e.g.,
obstruction to airflow). In pulmonary emphysema, lung function progressively deteriorates for
many years before the illness becomes apparent.
The most common cause of COPD is cigarette smoking. Air pollution, occupational exposures,
allergens, and infections may also act as irritants. Alpha1-antitrypsin deficient is an infrequent
cause. Complications include respiratory failure, pneumonia or other overwhelming respiratory
infection, right heart failure (cor pulmonale), arrhythmias, and depression.
Pathophysiology of COPD
COPD is a complex syndrome comprised of airway inflammation, mucociliary dysfunction and
consequent airway structural changes. 1
Airway inflammation
COPD is characterised by chronic inflammation of the airways, lung tissue and pulmonary blood
vessels as a result of exposure to inhaled irritants such as tobacco smoke.
The inhaled irritants cause inflammatory cells such as neutrophils, CD8+ T-lymphocytes, B-
Cells, macrophages and dendritic cells to accumulate. 2 When activated, these cells initiate an
inflammatory cascade triggering the release of inflammatory mediators such as tumour necrosis
factor (TNFα), interferon γ (IFNγ), matrix-metalloproteinases (MMP-6, MMP-9), C-reactive
protein (CRP), Interleukins (IL-1, IL-6, IL-8) and fibrinogen. The inflammatory markers sustain
the inflammatory process and lead to tissue damage as well as a range of systemic effects. The
chronic inflammation is present from the outset of the disease and leads to various structural
changes in the lung which further perpetuate airflow limitation. The chronic inflammatory
cascade for COPD is illustrated in Figure 1.
Figure 1: The chronic inflammatory cascade for COPD. 2
Adapted from Barnes et al. Lancet, 2004;9438(364):985-996.
Available at http://www.sciencedirect.com/science/journal/01406736.
Structural changes
Airway remodelling in COPD is a direct result of the inflammatory response associated with
COPD and leads to narrowing of the airways. Three main factors contribute to this:
peribronchial fibrosis, build up of scar tissue from damage to the airways and over-
multiplication of the epithelial cells lining the airways. 3,4
Emphysema is also associated with loss of lung tissue elasticity, which occurs as a result of
destruction of the structures supporting and feeding the alveoli. This means that the small
airways collapse during exhalation, impeding airflow, trapping air in the lungs and reducing lung
capacity (Figure 2).
Figure 2: Airflow limitation in COPD.
Mucociliary dysfunction
Smoking and inflammation enlarge the mucous glands that line airway walls in the lungs,
causing goblet cell metaplasia and leading to healthy cells being replaced by more mucus-
secreting cells.5 Additionally, inflammation associated with COPD causes damage to the
mucociliary transport which is responsible for clearing mucus from the airways. Both these
factors contribute to excess mucus in the airways which eventually accumulates, blocking them
and worsening airflow (Figure 3).
Figure 3: Mucociliary effects in the COPD airway.
References
1. Agusti. A. COPD, a multicomponent disease: implications for management. Respir Med 2005;99:670-682.
2. Barnes PJ, Hansel TT. Prospect for new drugs for COPD. Lancet, 2004;364:985-996.
3. Chung KF. The role of airway smooth muscle in the pathogenesis of airway remodelling in COPD. Proc Am
Thorac Soc 2005;2:347-354.
4. Laperre TS, Sont JK, van Schadewijk A, et al. Smoking cessation and bronchial epithelial remodelling in
COPD: a cross-sectional study. Respir Res 2007;8:85-93.
5. Danahay H, Jackson AD. Epithelial mucus-hypersecretion and respiratory disease. Curr Drug Targets
Inflamm Allergy 2005;4:651-664.
The airflow limitation that defines chronic obstructive pulmonary disease (COPD) is the result of a
prolonged time constant for lung emptying, caused by increased resistance of the small conducting
airways and increased compliance of the lung as a result of emphysematous destruction. These lesions
are associated with a chronic innate and adaptive inflammatory immune response of the host to a
lifetime exposure to inhaled toxic gases and particles. Processes contributing to obstruction in the small
conducting airways include disruption of the epithelial barrier, interference with mucociliary clearance
apparatus that results in accumulation of inflammatory mucous exudates in the small airway lumen,
infiltration of the airway walls by inflammatory cells, and deposition of connective tissue in the airway
wall. This remodelling and repair thickens the airway walls, reduces lumen calibre, and restricts the
normal increase in calibre produced by lung inflation. Emphysematous lung destruction is associated
with an infiltration of the same type of inflammatory cells found in the airways. The centrilobular
pattern of emphysematous destruction is most closely associated with cigarette smoking, and although
it is initially focused on respiratory bronchioles, separate lesions coalesce to destroy large volumes of
lung tissue. The panacinar pattern of emphysema is characterised by a more even involvement of the
acinus and is associated with α1 antitrypsin deficiency. The technology needed to diagnose and
quantitate the individual small airway and emphysema phenotypes present in people with COPD is being
developed, and should prove helpful in the assessment of therapeutic interventions designed to modify
the progress of either phenotype

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Chronic Obstructive Pulmonary Disease (COPD) is a disease characterized by airflow

Chronic bronchitis is chronic inflammation of the lower airways characterized by excessive

Figure 2: Airflow limitation in COPD.

Figure 3: Mucociliary effects in the COPD airway.

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