Chronic obstructive pulmonary disease (COPD) is a disease state characterised by a progressive limitation of airflow in the lungs which, unlike asthma, is not fully reversible by medication.360 the characteristic symptoms of COPD are chronic and progressive dyspnoea, cough and sputum production. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) definition for COPD is:
“COPD is a preventable and treatable disease with some significant extrapulmonary effects that may contribute to the severity in individual patients. Its pulmonary component is characterised by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases.”360
It is important to note that the terms ‘chronic bronchitis’ and ‘emphysema’ are no longer included in the formal definition of COPD, although they are still used clinically.360 Emphysema is a pathologic term used to describe destruction of the alveolar-capillary membrane, and chronic bronchitis is a clinical term used to describe the presence of cough or sputum production for at least a three-month duration during two consecutive years.361
The chronic airflow limitation characteristic of COPD is caused by a mixture of small airway disease (obstructive bronchiolitis) and parenchymal destruction (emphysema), the relative contributions of which varies between patients (Figure 26).360
Figure 26. Mechanisms of underlying airflow limitation in COPD360 !
Small airway disease
Airway inflammation Airway remodelling Parenchymal destruction Airway inflammation Airway remodelling INFLAMMATION AIRFLOW LIMITATION
Prolonged exposure to toxic gases or particles causes chronic inflammation, which results in structural changes and narrowing of the small airways (Figure 27).362 Destruction of the lung parenchyma, also by inflammatory processes, leads to the loss of alveolar attachments to the small airways and decreased lung elastic recoil.363-365 These changes result in a prolonged time constant for lung emptying and decreases expiratory airflow.366
Figure 27. Illustrative representation of the pathophysiological changes in COPD367
Airflow limitation, measured by reduced FEV1, progresses slowly over several decades, so that most patients with symptomatic COPD are in late middle age or are elderly.368
Table 49. Spirometric classification of COPD severity369
COPD classification Post-bronchodilator FEV1
Stage I: mild FEV1/FVC* ratio < 0.70, FEV1 ! 80% predicted
Stage II: moderate FEV1/FVC ratio < 0.70, 50% " FEV1 < 80% predicted
Stage III: severe FEV1/FVC ratio < 0.70, 30% "FEV1 < 50% predicted
Stage IV: very severe FEV1/FVC ratio < 0.70, FEV1 < 30% predicted or < 50% predicted plus chronic respiratory failure†
*FVC = Forced vital capacity. †Respiratory failure: arterial partial pressure of oxygen < 60 mm Hg with or without arterial partial pressure of CO2 > 50 mm Hg while breathing air at sea level.
The natural course of COPD is complicated by the development of extra-pulmonary effects, including systemic inflammation, weight loss, skeletal muscle dysfunction, cardiovascular disease, anxiety, depression and osteoporosis (Table 50).370 The high burden of COPD resulting from respiratory symptoms is further contributed to by these systemic effects, leading to a pronounced deterioration of health status, a diminished QOL and increased mortality.371 While the relationships between the pulmonary and extra-pulmonary effects of COPD are not fully understood, local and systemic inflammation, oxidative stress and disturbances in neuro-hormonal states are some of the likely mechanisms.372 The involvement of common susceptible genes or risk factors is also possible.
Table 50. Systemic effects of COPD370
Type of effects Examples of effects
Oxidative stress373,374
Activated inflammatory cells375,376 Systemic inflammation
Increased plasma levels of cytokines and acute phase proteins377,378
Increased resting energy expenditure379 Abnormal body composition380 Nutritional abnormalities and weight loss
Abnormal amino acid metabolism381 Loss of muscle mass
Abnormal muscle structure/function382,383 Skeletal muscle dysfunction
Exercise limitation384
Cardiovascular effects (e.g. ischemic heart disease)385 Nervous system effects (e.g. anxiety and depression)386 Other potential systemic effects
COPD is a heterogeneous disease process that varies greatly from person to person with respect to lung pathology, natural history of disease and systemic effects and co- morbidities.388,389 The risk for COPD is related to an interaction between genetic factors and many different environmental exposures.390 It appears that an enhanced or abnormal inflammatory response to inhaled particles or gases, beyond the normal protective inflammatory response in the lungs, is a characteristic feature of COPD and has the potential to produce lung injury.391 Cigarette smoking is by far the most commonly encountered risk factor for COPD.390 The population-attributable risk of smoking (current smoking and ex-smoking) for COPD is reportedly up to 78%.392 This population-attributable risk identifies that at least 22% of COPD still needs to be explained by other genetic and environmental risk factors. However, due to complex relationships between the known risk factors for COPD, individuals with similar smoking and exposure histories can vary a great deal in their predisposition to the disease, severity of their disease and response to intervention. Most of the evidence concerning risk factors for COPD (Table 51) comes from cross-sectional epidemiological studies that identify associations rather than cause-and-effect relationships.
Table 51. Risk factors for COPD
Type of risk factor Examples
Tobacco smoke393-395
Occupational dusts (organic and inorganic)396
Indoor air pollution from heating and cooking with biomass397,398 Exposure to particles
Outdoor air pollution398,399
Genetic Hereditary deficiency of the serine protease inhibitor alpha-1 antitrypsin400-403
Low birth weight404,405 Lung growth and development
Reduced maximal attained lung function406
Infections Exposure to respiratory infections in childhood405,407 Ageing Age over 40 years393,394
Prevalence of COPD higher in males393,408 Gender
Females may be more susceptible to the effects of tobacco smoke409-411 Socioeconomic status Low socioeconomic status and/or factors relating to low socioeconomic