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Pathophysiology and management of COPD

Ray Higginson MSc PhD
Chartered Biologist and Senior Lecturer in Critical Care Physiology Faculty of Health, Sport and Science
University of Glamorgan, Wales

Chronic obstructive pulmonary disease is one of the leading causes of death and morbidity in the UK, and a huge burden on the NHS, costing around £800m per year

According to the Department of Health (DH), chronic obstructive pulmonary disease (COPD) affects over three million people in England alone.1 The disease is the fifth biggest killer worldwide, with 250 people worldwide dying of the disease every hour.2 The cost of the disease to the NHS is estimated at around £800m.3

COPD is a broad term used to describe airflow limitation and a progressive and irreversible decline in lung function. Such a decline results in restricted (obstructed) airflow in the lungs.4 Obstructive diseases include bronchitis, in which inflammation causes chronic bronchial secretions and narrowing of the bronchi, and emphysema; a permanent destructive enlargement of the airspaces within the lung.

Lung physiology
Understanding lung physiology is vital to comprehending the complex pathophysiology of COPD. Some of the fundamental lung concepts are listed in Box 1. Although it is possible to discuss COPD without exploring all these in detail, lung compliance and lung resistance are particularly important in the physiological process of COPD.

[[Box 1. Higginson]]

Compliance
Compliance refers to how much effort is required to stretch the lungs and thoracic wall. High compliance means that the lungs and thoracic wall expand easily.5 Low compliance means that the lungs resist expansion. The lungs normally have high compliance and expand easily because elastic fibres in lung tissue are easily stretched and because surfactant reduces surface tension.6

Resistance
Airway resistance is a measure of the opposition to the flow of gases through the airways.7 It is the opposition to the flow of gases caused by friction between the walls of the airway and the gas molecules. An increase in lung resistance obstructs the flow of air through the lungs.

Restrictive and obstructive diseases
Lung diseases are classified into those that impact upon either compliance or resistance. A decrease in lung compliance leads to restrictive lung diseases. An increase in lung resistance leads to obstructive lung diseases.

Restrictive lung diseases
Restrictive lung diseases include conditions producing 'stiff lungs', such as silicosis, pneumoconiosis (a general term for lung disease caused by inhalation of mineral dust) and TB. In addition, restrictive lung diseases include conditions producing paralysis of intercostal muscles, pulmonary oedema and reductions in the production of surfactant.8

Obstructive lung diseases
Obstructive lung disease results from increases in airway resistance and includes conditions such as bronchitis, emphysema and asthma (in emphysema there is an increase in lung compliance due to the destruction of elastic fibres in
alveolar walls).

FEV1 in restrictive and obstructive diseases
The forced expiratory volume in one second (FEV1) is the volume of air exhaled by the lungs during the first second of a forced expiration, after maximal inspiration.9 It is an important tool in lung disease diagnosis and classification.

In normal respiratory health, the forced expiration volume that a person can expire in one second is approximately about 80% of the total forced vital capacity (FVC). In obstructive lung diseases, however, such as bronchitis and emphysema, the forced vital capacity is reduced. In addition, because of the increase in airway resistance patients with an obstructive disease also have a reduced expiratory flow rate. Thus, a patient with an obstructive disease might have a forced vital capacity of only 3.0 l, and in the first second of forced expiration exhale only 1.5 l, giving a FEV1/ FVC ratio of only 50% (1.5 l of FEV1 divided by 3.0 l of FVC, equals 50%). Thus, in obstructive lung diseases the FEV1/ FVC ratio goes down.

In restrictive lung diseases, forced vital capacity is also reduced. However, due to the low compliance in restrictive lung diseases, and the high lung recoil, the FEV1/FVC ratio may be normal or even higher than normal. The distinctive way in which FEV1/FVC ratio is altered in lung diseases enables clinicians to differentiate between restrictive and obstructive diseases.

Obstructive lung diseases: emphysema and bronchitis
Chronic bronchitis
Chronic bronchitis is an inflammatory disease of the mucous membranes of bronchi.10 It is characterised by an increase in the amount mucoid sputum produced for all or part of the year.11,12 The Medical Research Council (MRC) definition of chronic bronchitis is 'chronic cough or mucus reproduction for at least three months in two successive years when other causes have been excluded'.

Chronic inflammatory irritation leads to a defensive increase in mucus production, resulting in increases in numbers of goblet epithelial cells. This leads to mucus gland hyperplasia, in the large airways and increased risk of infection.13,14 As the disease progresses the inflammatory process leads to widespread narrowing in the small airways, increased airway resistance and fibrosis around bronchioles. Ultimately, these factors result in an airway obstruction. As is the case with emphysema, airway narrowing means bronchitis is classified as an obstructive disease.      

Causes and consequences of bronchitis
While respiratory viruses are the most common cause for acute bronchitis, in chronic bronchitis airway epithelial cells release inflammatory mediators in response to long-term noxious, infectious or inflammatory stimuli.7 Factors such as smoking, concomitant lung disease and exposure to some environmental chemicals have also been implicated in causing chronic bronchitis.8

'Pink puffers' and 'blue bloaters'
The terms 'pink puffers' and 'blue bloaters' are still used today within medicine and refer to patients with either emphysema (pink puffers) or chronic bronchitis (blue bloaters). Pink puffers compensate for raised carbon dioxide levels, increasing their respiratory rate. This hyperventilation means that they have less hypoxaemia and (near) normal carbon dioxide levels.11 Blue bloaters are blue because of gross hypoxaemia and are bloated or oedematous because of right-sided heart failure (cor pulmonale).9 Some of the other signs and symptoms of chronic bronchitis are listed in Box 2.

[[Box 2. Higginson]]

Treatment for chronic bronchitis
Because of its obstructive nature, the treatment for chronic bronchitis is similar to that of emphysema, with bronchodilators, steroids and oxygen therapy all being indicated. Long-acting bronchodilators are now recommended if prn short-acting are required regularly and inhaled corticosteroids are recommended not oral except in acute exacerbations. In addition, antibiotics are also indicted for acute exacerbation of the condition when triggered by airway infections.15

Emphysema
Emphysema can be defined as an abnormal, permanent enlargement of air spaces distal to the terminal bronchioles, accompanied by the destruction of alveolar walls and without obvious fibrosis.16 The lungs also lose their natural elasticity. As a result of the overinflation and destruction of the alveolar walls there is a reduction in the lung's surface area, leading to impaired gaseous exchange.16 Emphysema is classified according to the location of lung destruction (see Table 1).

[[Tab 1. Higginson]]

Causes and consequences
Approximately 1-2% of emphysema cases are due to an inherited lack of alpha-1 antitrypsin, a protective protein that protects the lungs by inhibiting neutrophil elastase.17 If alpha-1 antitrypsin is absent then emphysema develops.

Although significant, alpha-1 antitrypsin deficieny is not the leading cause of emphysema. Rather, exposure to noxious stimuli, most often cigarette smoke, is the most common cause for the developmenmt of empysema. Smoking stimulates local inflammatory response in the lungs. The inflammatory activity of cells, such as neutrophils, macrophages and lymphocytes, produces chemicals such as elastase. These inflammtory chemicals then lead to the destruction of the alveoli wall and to to fewer but larger alveoli. The ensuing reduction in the gaseous exchange surface area of the lungs leads to a decreased ability to uptake oxygen and remove carbon dioxide.10 The increase in the blood level of carbon dixoide causes an initial rise in the patient's respiratory rate. However, as the disease progresses prolonged hyperventilation becomes inadequate and the lungs' ability to meet oxygen requirements and remove carbon dioxide fail.

As hypoxaemia progresses the lungs respond by constricting (a phenomenon known as pulmonary hypoxic vasoconstriction). This then leads to pulmonary hypertension and eventually right-sided heart failure. The physiological changes that occur in empyhsema also account for the signs and symptoms of the disease (see Box 3).

[[Box 3. Higginson]]

Treatment 
Although there is no known cure for emphysema, there are a number of treatment options available for patients with the disease. The cessation of smoking is a vital component of treatment. As Caflisch maintains, 'Stopping smoking is the only way to stop the damage to the lungs becoming worse'.18 In addition to smoking cessation, oxygen therapy, pulmonary rehabilitation, bronchodilators and even surgery can be of benefit to patients with emphysema.

Oxygen therapy
An area of continued confusion related to the treatment of emphysema is the use of oxygen. While it is true that oxygen therapy may diminish the only remaining stimulus for respiration in a patient with emphysema - that of anoxia - depriving a hypoxic patient of oxygen is not an appropriate treatment strategy. Indeed, continuous, long-term oxygen use, together with smoking cessation, are the only two strategies proven to have been shown to improve survival time in patients with COPD.19-21 The exact flow-rate and percentage of oxygen are prescribed by the patient's attending physician, based upon the severity of hypoxaemia. Thus, although oxygen therapy in patients with emphysema has its risks, these rarely mean that it is appropriate to withhold it in hypoxaemic patients.

Bronchodilators and corticosteroids
Patients with emphysema (and other obstructive lung diseases) report feeling less breathless after inhalation of beta-adrenergic agonists such as salbutamol and anti-muscarinic drugs like ipratropium. As such, inhaled bronchodilators are a vital treatment strategy in the pharmacological management of COPD.22 A number of authors maintain that corticosteroids can also be given to patients with obstructive lung diseases, with drugs like prednisolone being effective.11,13 However, oral corticosteroids are not recommended by NICE except in acute exacerbations. Short courses of corticosteroids have shown to improve both spirometric and clinical outcomes in acute exacerbations of COPD.23 

Pulmonary rehabilition and surgery
Pulmonary rehabilition aims to reduce  the symptoms and disability associated with obstrutive diseaes such as empysema. Diaphragmatic breathing exercises, muscle stretch gymnastics and walking are the beneficial components parts of pulmonary rehabilitation and have been shown to be beneficial in patients with obstructive diseases.24 In certain circumstances, lung volume reduction surgery (LVRS) can also prove a benefial treatment for empysema, especially if combines with post-surgery rehabilitation. One study found that LVRS, followed by pulmonary rehabilitation, significantly reduces levels of dyspnea during functional activities in patient with emphysema.25

Conclusion
Although pathophysiologically distinct, the diseases discussed above often co-exist. What characterises them all is their obstructive nature. As such, they are grouped under the term COPD, with treating and overcoming the consequences of airway obstruction an important part in managing the disease. 
At present there is no known cure for COPD. Without treatment the disease gradually gets worse, debilitating the lives of people who suffer with it. National guidelines exist to inform best practice when treating patient with the disease and these should also be adhered to. Together with ongoing research, appropriate interventions and drug treatment can minimise
the impact of the disease and improve the lives of COPD
patients.

References
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