Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterised by obstruction of airflow that cannot be fully reversed with inhaler medications, called bronchodilators. The most common symptoms of COPD are breathlessness and persistent cough with sputum production. As the condition worsens, even daily activities such as walking up a short flight of stairs or the exertion of washing or dressing become difficult.
The importance of COPD as a global health problem cannot be overstated. According to the latest World Health Organisation (WHO) statistics (2005), approximately 210 million people suffer from COPD worldwide, and 5% of all deaths globally are estimated to be due to this disease. This corresponds to more than 3 million deaths annually, of which 90% are thought to occur in low and middle-income countries. A recent projection published by the WHO Global Burden of Disease Project indicates that COPD will be the 3rd leading cause of death globally by the year 2030.
Cigarette smoking is the major risk factor for COPD, and much of the increase in COPD is associated with projected increases in tobacco use, especially in the developing world. However, recent studies have suggested that a quarter to almost a half of all cases of COPD occur in non-smokers. Other risk factors for the development of COPD include such diverse influences as environmental tobacco smoke exposure (passive smoking), smoke from coal and wood fires, exposure to dust, fumes and vapours, childhood illness, and previous tuberculosis.
Whatever the cause, it seems that chronic inhalation of noxious particles and gases stimulates inflammation in the lung. Unlike the acute inflammation of infection or trauma, this inflammation smoulders on chronically for decades, resulting in progressive damage to the tissue that supports airway structures and the gas exchange surface of the lung. Depending on which part of the lung is predominantly affected can determine whether patients develop either chronic bronchitis or emphysema, two diseases that are now recognised as sub-types of COPD.
Chronic bronchitis occurs when the inflammatory process affects mainly the large airway walls, leading to mucus over-production and inflammatory swelling of the inner layers of the airways, with subsequent obstruction to airflow. Emphysema, on the other hand, is when the damage involves the delicate gas exchange part of the lungs, the tiny sacs called alveoli. Destruction of these structures leads to large non-functional spaces in the lungs known as bullae, which have a limited capacity to take up oxygen, with subsequent severe exercise impairment in affected individuals. The two different subtypes can also co-exist in the same individual.
The cells involved in the inflammatory response are the normal white cells (neutrophils and macrophages), which should protect the body during infective challenges. The normal defence mechanism of the body, which is aimed primarily at mopping up the invasive substances, attacks normal lung tissue to the detriment of the respiratory system. The toxic substances released by these activated cells, usually produced in response to an infection and designed to destroy bacteria, are unleashed on the lung’s own tissue. Destruction of the fine elastic fibres that support lung tissue leads to an inability to empty the lungs normally, with air-trapping. Thickening of the bronchial walls, formation of scar tissue and eventual destruction of the minute alveoli, which are responsible for oxygen uptake, impairs airflow and the uptake of life-sustaining oxygen and removal of carbon dioxide. The inflammatory response will periodically flare up during attacks of influenza and bronchitis, during which period patients may become acutely ill and very short of breath.
A characteristic of the inflammatory response of COPD is that it is not responsive to long-term medication with drugs such as corticosteroids, which are used successfully for prevention of asthma. When the inflammatory response has, over a period of years, caused extensive damage to the small airways and alveoli, patients will present with respiratory failure due to lack of oxygenation, or right heart failure (See Symptoms and diagnosis of COPD).
The disease is not confined to the lungs; it has systemic (whole body) effects that result in, for example, weight and appetite loss, and particularly a decrease of muscle mass in the limbs of severely ill patients. This leads to a vicious circle, as weakened patients who are extremely short of breath tend to withdraw, become completely inactive and frequently die in isolation
Who gets it?
As it takes many years for the inflammation in the lungs to have an effect, COPD is primarily a disease of the elderly. It affects adults over 45 years of age, and rates as one of the major causes of death world-wide. The World Health Organisation rates COPD as the fourth most common cause of death throughout the world. An alarming rise in the prevalence of this condition, particularly among women, indicates that mortality and morbidity (illness) due to COPD may be much higher by 2030, and it is estimated that it will become the 3rd most important cause of death worldwide.
Patients with this condition experience a prolonged decline of exercise capacity and in the final years of their life are severely short of breath, often unable to lead a normal life, and needing to access healthcare services regularly. This incurs great personal and national expense. The financial burden of COPD, particularly in developing countries, will parallel the ongoing abuse of factors that cause the disease, such as smoking.
Reversing this trend will take time: the effects of successful public education programmes will only be noticed after several decades, given that the negative effects of smoking only become apparent 30-40 years after its onset.
Susceptibility genes (e.g. alpha-1 antitrypsin deficiency)
Poor lung growth and development (especially in neonatal life)
Low socio-economic status
Indoor air pollution from heating and cooking with coal and wood in poorly ventilated dwellings
Outdoor air pollution
Occupational dusts and chemicals
The role of tobacco smoke as a causative agent for COPD has been proven beyond all doubt. It appears that starting smoking at a young age, the "total pack years" (the number of cigarettes smoked per year multiplied by the number of years of smoking) and the person's current smoking status all contribute to the final state of respiratory impairment due to COPD.
In spite of this, only an estimated 20% of smokers develop the disease. However, this figure does not take into consideration the combined effect of several other risk factors that commonly occur in individuals in underprivileged communities, with a subsequent greater likelihood of developing the disease.
Evidence has been found that secondary cigarette smoke can cause COPD in non-smoking bystanders. This has serious health and legal implications, as smokers could jeopardise the health of the non-smoking population.
In a number of occupations, including mining and industry, dust and exposure to welding gases and fumes have been associated with the development of COPD. Enforcement of protective measures in the workplace, including wearing masks and monitoring levels of dust and toxic fumes, have minimised and in some cases abolished the danger of industrial exposure.
Low socio-economic status is a risk factor for the development of COPD due to the high prevalence of other risk factors, including secondary cigarette smoke exposure, particularly in childhood, and tuberculosis, which tends to occur in deprived communities. There is some evidence that tuberculosis (TB), particularly recurrent episodes of the disease, leads to the development of COPD in patients in developing countries.
Additional risk factors in disadvantaged communities include the indoor burning of biomass fuels and a tendency to recurrent chest infections, which in their own right cause further damage to the bronchial walls and contribute to the onset of COPD. In these communities, children of parents who smoke are at a proven disadvantage, as recurrent chest infections and impaired lung growth predispose these unfortunate individuals to early development of COPD.
The fact that many industrial workers and miners smoke and contract tuberculosis serves as one example of how combinations of risk factors contribute through a final common pathway of airway inflammation to create an accumulative burden for causing COPD.
It should be evident that as long as these risk factors prevail in communities, the disease prevalence will continue its upward spiral and continue to be a major burden on national and personal health budgets.
There is also growing evidence that HIV infection, either alone or together with other opportunistic infections and tuberculosis, may be an independent risk factor for the development of COPD. Whether this is due to repeated respiratory infections, the effect of the virus on the lung tissue itself, or simply the result of decreased immunity is unknown, and is currently under investigation. This interaction obviously has enormous public health implications for a country like South Africa, with its high rate of both HIV and TB.
Differentiating COPD from asthma
Young asthmatics who smoke or who are exposed to noxious agents in the workplace tend to have an early onset of COPD. A common mistake, however, is to label wheezy COPD patients as asthmatics. Asthma is a disease that tends to have its onset in the teens or early adulthood, is usually associated with allergic symptoms like hay fever and is caused by readily definable antigens that induce attacks of airway obstruction. (For the sake of specific treatment, the attending physician has to make a decision of where asthma ends and COPD starts). Treatment and prognosis for asthma is completely different to that for COPD, with a favourable response to treatment in asthmatics and less so in COPD patients.
Symptoms and diagnosis
In spite the well-known risk factors, the majority of COPD patients (up to 70%) remain undiagnosed. In the early phases, patients may have respiratory symptoms, like cough with sputum production, but may have no exercise impairment or may not be physically active enough for their shortness of breath to become evident. It is only by a regular measurement of lung functions in patients at risk, that the disease will be unmasked in its early stages.
COPD should be considered in any patient who has a chronic cough, sputum production, shortness of breath and/or history of exposure to risk factors. The cornerstone of the diagnosis of COPD is the measurement of lung function by spirometry. Spirometry is a test in which patients are asked to exhale a full in-breath (in other words, to breathe fully in and then fully out) as fast as they can. Measurements include the amount of air blown out in one second, called the forced expiratory volume in one second (FEV1), the total amount of air blown out in the entire forced exhalation, called the forced vital capacity (FVC), and ratio between the two, called the FEV1/FVC ratio. Normal lungs can almost completely empty in one second, but when airflow obstruction is present, the time taken to empty the lungs is lengthened and so the volume of air exhaled in one second decreases. When this ratio is less than 70%, airflow obstruction is said to be present. To determine the severity of the obstruction, the FEV1 as a percentage of the normal predicted value for a person of the same age, gender, height and ethnicity is examined.
The importance of early diagnosis is that preventative measures, including avoidance of risk factors, can be instituted. This will have major long-term benefits for affected individuals.
Symptoms are frequently precipitated by a respiratory infection, usually during the wintertime when influenza and colds are endemic. These patients commonly complain of a change in their baseline level of shortness of breath, together with a productive cough and a change in their sputum colour.
Smokers usually have a much longer recovery time than non-smokers and experience more severe symptoms during acute exacerbations of COPD.
In patients with severe respiratory impairment, these attacks may lead to respiratory failure. Oxygenation becomes so limited that a blue tongue and lips indicate severe impairment of oxygen uptake. Acute exacerbations may also be accompanied by evidence of failure of the right ventricle to pump adequately due to increased pressure in the vascular bed of the lungs, which is characterised by swollen ankles and legs, an enlarged liver and elevated neck veins. Symptoms of respiratory and right heart failure usually justify admission to hospital. Active treatment of these conditions can reverse the heart or lung failure, while identification of factors that cause exacerbation e.g. respiratory infections; fluid overload or lung clots should be remedied, thereby preventing further acute incidents.
Staging of COPD
A staging system for COPD severity has been established by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). This staging system defines disease severity according to airflow limitation. It can be used as a guide for the management of patients with stable COPD.
Treatment and monitoring
Once the diagnosis has been confirmed and the stage of the disease determined, the focus turns to:
patient education to help him/her understand the disease
modification of risk factors - with smoking cessation of the utmost importance to slow the progression of the disease
medications like inhaled bronchodilators, oral and inhaled corticosteroids, antibiotics and others.
These pharmacological and non-pharmacological therapies should be added in a step-wise fashion as outlined below to control symptoms, prevent exacerbations and improve quality of life.
Treatment of Stable COPD
1) Smoking cessation
All of us, whether we smoke or not, or whether we have COPD or not, will experience a decline in our lung function over time. This is a function of ageing, and results from the loss of elasticity within the lung. This is a normal process, and can be compared to the development of wrinkles in the skin, also a function of the loss of elastic tissue. However, this loss of lung function is rarely symptomatic as it never deteriorates to the threshold at which shortness of breath is experienced. In patients with COPD, inflammation within the lung leads to accelerated loss of lung function, with more rapid deterioration to the point of respiratory disability.
So while no curative treatment for COPD exists, cessation of smoking is the only significant therapeutic intervention that can retard the accelerated decline in lung function experienced by smokers with COPD. Patients must be informed that secondary cigarette smoke, as well as exposure to noxious fumes, gases and dust at work, needs to be addressed to preserve respiratory function.
Any extra treatment of COPD will depend on the severity of the patient’s COPD. COPD can be classified as mild, moderate, severe or very severe. This classification is based on staging systems for COPD, using the value of FEV1 ("forced expiratory volume in one second") as a percentage of the normal value for an individual of the same age, height, gender and ethnicity. The degree of airflow (FEV1) reduction has implications for the prognosis and relates with the mortality and morbidity.
Patients with COPD have vulnerable lungs with reduced respiratory reserve and need to be protected from preventable respiratory infections. These individuals should be vaccinated against the predominant viral strains every year – in particular seasonal and pandemic influenza serotypes, where available. All patients with chronic respiratory disease should also receive a pneumococcal vaccination every 5 - 10 years with the 23-polyvalent vaccine to protect against Streptococcus pneumonia.
These include inhaled anticholinergics and beta-agonists, both of which are available in short or long-acting preparations, and oral theophylline.
The use of short-acting bronchodilator therapy (medications to dilate the bronchial airways), on an as-needed basis during episodes of wheezing is very effective. Inhaled bronchodilators in combination have been shown to have the most benefit on lung function, and usually include an anticholinergic like iprapropium bromide and a beta2-antagonist like salbutamol
In patients in whom short-acting bronchodilaotrs alone or in combination are insufficient to control symptoms, or in patients with more advanced disease, long-acting inhaled bronchodilators can be added. Both long-acting anticholinergic drugs (like tiotropium) or long-acting beta-2-agonists (called LABAs, like salmeterol or formoterol) can be used. Tiotropium has been conclusively shown in the recent large UPLIFT trial to improve airflow, hyperinflation, exercise tolerance, exacerbation frequency, and health-related quality of life with a convenient once-daily dosing, A combination of both classes of drugs is the most effective strategy, and provides an additive effect on lung function throughout a 24-hour period.
The benefits of oral theophylline are modest, and this therapy is least preferred because of its potential toxicity and interactions with other medications.
4) Inhaled corticosteroids
For patients who continue to have symptoms or have advanced disease (GOLD Stage III), or those who continue to have repeated exacerbations despite an optimal long-acting bronchodilator regimen, it is recommended that inhaled corticosteroids (ICS) are added. If the existing regimen contains a long-acting beta-2-agonist (called LABA, like salmeterol), the ICS can be added alone; if the regimen does not already contain a LABA, the combination of ICS and a LABA can be added.
Many patients with severe COPD will therefore qualify for long-acting anticholinergics, long-acting beta-agonists, and inhaled corticosteroids – so-called “triple-inhaler therapy”.
5) Other treatments
Long-term antibiotic prophylaxis
Chronic antibiotic therapy is without benefit in most patients with COPD, except in those who have a chronic bronchial infection called bronchiectasis.
Thick, tenacious secretions can be a major problem in COPD – however, there is little evidence that thinning these secretions with mucolytics confers any clinical benefit. Thus the use of agents like n-acetylcysteine is not recommended.
More than 30% of patients with COPD have protein-calorie malnutrition, and loss of weight is an important symptom in late-stage COPD. Low body-mass index is associated with increased mortality impaired respiratory muscle function and diminished immune competence. High calorie diets and appetite stimulants have been used in an effort to combat malnutrition, but there is no evidence that these treatments confer a long-term benefit.
Rehabilitation is an important component of treatment of patients with severe COPD. The aim is to improve the fitness of exercising muscle to better cope with the low oxygen tension in the blood: this involves strengthening the arm and leg muscles as well as the muscles of respiration, and enables patients to cope with moderate exercise and to carry on with their daily routine in spite of considerable loss of lung function and low blood oxygen concentrations. This state of “fitness” is only achieved after an intensive rehabilitation programme, which has to be conducted under supervision of doctors and physiotherapists.
Long-term oxygen therapy
All patients with severe COPD feel better on oxygen, however this therapy has only been shown to decrease mortality in the sub-set of patients with chronically low blood oxygen concentrations. However, the provision of home oxygen is expensive, and it is imperative that patients who are prescribed this therapy have stopped smoking. Oxygen devices that operate through home power sources generate enough oxygen to support patients for an essential 16 hours per day.
Lung volume reduction surgery
Surgery known as lung volume reduction surgery (LVRS) has been shown to be of benefit in a small subset of carefully selected patients who have predominantly upper lobe emphysema, low exercise capacity and no other serious co-morbid disease. The surgery works by excising parts of the lung with the extensive thin-walled cysts called bullae, allowing the adjacent non-involved lung to inflate better, resulting in less gas-trapping.
6) Future directions in COPD treatment
Several novel treatments are being investigated for COPD which target inflammatory pathways. Roflumilast is a highly-specific, oral, second-generation PDE-4 inhibitor being investigated for patients with COPD. Its treatment benefits are, however, small compared to standard bronchodilators.
Treatment of exacerbations
Acute exacerbations are characterised by acute worsening of the symptoms of COPD, including:
increased shortness of breath
increased sputum production
change in sputum colour (often becoming yellow or green).
The mainstays of therapy include
Oxygen therapy to correct the hypoxia
Bronchodilators to improve airflow to and from the lungs. A combination of nebulised or inhaled anticholinergic and beta-adrenergic agonists (fast-acting) are often used as first-line therapy.
Antibiotics such as penicillins, quinolones or tetracyclines for 7 - 14 days to reduce the infection and phlegm production.
Oral or injected corticosteroids for 5 - 10 days to reduce inflammation in the airways. Inhaled corticosteroids have not been proven effective in treating COPD exacerbations.
Non-invasive ventilation, if available, in the case of respiratory failure
Mechanical ventilation in ICU if unresponsive to above measures. The decision to intubate and ventilate is dependant on multiple factors, including the relative reversibility of the precipitating insult, the patient’s baseline level of functioning and quality of life, and the wishes of the patient and their family.
The battle for prevention of COPD will be won or lost depending on the education those health authorities, doctors and the media provide to the public about COPD. Preventing smoking at school level is a much more cost-effective method of combating the disease than trying to convert smokers or treating symptoms when they occur.
The management and treatment of patients with COPD has frequently been met with a very nihilistic attitude by health providers. The argument that it is a self-induced, progressive disease, to which treatment does not make a difference, needs to be replaced with a new and more enthusiastic approach to the problem.
Much has changed during recent years in terms of understanding and preventing the disease, and its rational treatment, which may alleviate the suffering of a large number of patients. Clearly, education of health authorities, health workers and the public will contribute to a decreasing prevalence of this much neglected condition.
Written by Prof J.R. Joubert, MSc, MBChB (Stell), FCP (SA), MMed (Int. Med), MD (Stell)
Reviewed by Dr Greg Calligaro, physician at the Lung Unit, Groote Schuur Hospital and University of Cape Town, August 2010