Next Lesson - Pneumonia and Other Lower Respiratory Tract Infections
Core
Chronic Obstructive Pulmonary Disease (COPD) is characterised by airflow obstruction that is not fully reversible, and may involve emphysema and chronic obstructive bronchitis. Chronic bronchitis without demonstrated obstruction does not itself establish COPD. Airflow limitation usually progresses over time. Bronchodilators (drugs that widen the airways) can improve airflow and symptoms, but the obstruction is not fully reversed. An earlier estimate put the number of people in the UK with a diagnosis of COPD at about 1.2 million (source). NICE Clinical Knowledge Summaries (CKS) now report about 1.15 million people with a diagnosis in England, and around 3 million people with COPD across the UK, about 2 million of them undiagnosed.
The primary cause of COPD is smoking, meaning that most patients diagnosed with COPD will have a significant smoking history.
However, it is important to remember that other causes of COPD do exist, including air pollution, occupational exposure to certain chemicals, and inherited conditions such as alpha-1 antitrypsin deficiency (a lack of a protein that protects the lungs from damage).
Emphysema is permanent enlargement of air spaces distal to the terminal bronchioles, with destruction of their walls. Loss of alveolar walls and elastic recoil reduces gas-exchanging surface and promotes small-airway collapse during expiration. Larger emphysematous spaces may join together (coalesce) into bullae (large air-filled spaces), but bullae are not required for the diagnosis and not every enlarged air space is a bulla.
During expiration, when the pressure outside the airway rises, the smaller airways collapse due to the lack of surrounding elastic tissue keeping them patent (open), causing airway obstruction. The loss of elastic tissue in the lungs also causes them to hyperinflate (hold too much air), as the elastic recoil of the lungs has been destroyed.
Image - Lung taken from a cadaver where the patient had emphysema, showing an example of the bullae
Creative commons source by Yale Rosen [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
Chronic bronchitis is a condition that occurs frequently in smokers, in which there is hypersecretion of mucus caused by inflammation of the large airways. There is also ciliary dysfunction, meaning that the normal clearance mechanisms for mucus are not effective. This means that patients with chronic bronchitis have a chronic productive cough, and are more prone to have frequent respiratory tract infections. Chronic bronchitis is clinically defined by productive cough on most days for at least three months in each of two consecutive years, after excluding other causes. It does not, by itself, establish airflow obstruction. Chronic obstructive bronchitis is the syndrome accompanied by spirometric evidence of obstruction. In COPD, airway inflammation and remodelling (structural change in the airway walls) contribute to persistent airflow limitation, which is not fully reversible but may improve with bronchodilators.
Diagram - Components of COPD, with chronic bronchitis on the left and emphysema on the right. It shows the differences between healthy bronchi and air sacs, and those seen in COPD
Public Domain Source by National Heart, Lung, and Blood Institute, NIH [Public domain]
The airway narrowing and destruction of lung tissue predisposes patients with COPD to hypoxia (low oxygen levels in the tissues), particularly during physical activity. This progressive hypoxia causes pulmonary vasoconstriction (to maintain the ventilation/perfusion ratio) and over time, leads to vascular smooth muscle thickening, with subsequent pulmonary hypertension.
A patient with COPD may have features of both emphysema and chronic obstructive bronchitis. COPD airflow limitation is persistent and may progress, but it can partly improve with treatment: bronchodilators can improve airflow and symptoms. Chronic bronchitis without demonstrated obstruction should not automatically be labelled COPD. To summarise, the changes that occur in COPD include:
- Enlargement of the mucus-secreting glands of the central airways leading to increased mucus production and a predisposition to infection in the mucus.
- Replacement of ciliated cells (cells with hair-like projections that sweep mucus out) with goblet cells (mucus-producing cells), and dysfunction of the ciliary cells that remain, leading to a build-up of the already increased amount of mucus.
- Breakdown of elastin, causing destruction of alveolar walls and their structure leading to the formation of large air spaces, reducing the total surface area available for gas exchange.
- Vascular bed changes leading to pulmonary hypertension.
- Loss of elastic recoil.
COPD has a gradual onset and usually presents in older people with a long history of smoking. COPD can also have other causes. A patient with typical COPD symptoms who has never smoked should be investigated for these other causes, such as alpha-1 antitrypsin deficiency. A cough is usually the first symptom of COPD, which begins as a morning cough but becomes constant as the disease progresses. It is usually productive, and the sputum (phlegm) quality and quantity may change with exacerbations and superimposed infections.
Shortness of breath usually occurs on exertion at the start of the disease process but may progress to occurring at rest.
The Medical Research Council (MRC) dyspnoea score is used to grade how severe a patient's breathlessness (dyspnoea) is. It ranges from 1 (not troubled by breathlessness unless exercising strenuously) to 5 (too breathless to leave the house, or gets breathless when dressing or undressing).
The physical signs of COPD include:
- Tachypnoea (fast breathing), as the patient tries to compensate for the hypoxia
- Visible use of accessory muscles (e.g. sternocleidomastoid, a neck muscle, or trapezius) as the patient experiences difficulty moving air in and out of the lungs
- Barrel chest, an increased diameter of the chest due to hyperinflation and incomplete expiration
- Hyper-resonance (a louder, more hollow note) on percussion (tapping) of the chest, due to hyperinflation
- Decreased breath sounds and reduced air entry
- Pursed-lip breathing
- Potential wheeze
Signs of late COPD include:
- Flapping tremor of the hands, caused by hypercapnia (a raised carbon dioxide level in the blood)
- Central cyanosis (a blue tinge to the lips and tongue), due to hypoxia
- Signs of right-sided heart failure, such as distended neck veins and ankle oedema, secondary to pulmonary hypertension
When investigating COPD, spirometry is used. The test is done after the patient has taken a bronchodilator (post-bronchodilator spirometry). It will show an obstructive pattern. The forced expiratory volume in one second (FEV1) is the amount of air a patient can breathe out in the first second. The forced vital capacity (FVC) is the total amount of air they can breathe out. In an obstructive pattern, the FEV1/FVC ratio is less than 0.7 (70%), due to the reduced FEV1. This is the same pattern as seen in patients with asthma, however, in patients with COPD the airflow obstruction is not fully reversible following treatment with bronchodilators. A flow-volume loop (a graph of airflow against the volume of air breathed out) will show the typical obstructive pattern: the breathing-out part of the curve is scooped out (concave).
How well a patient performs on spirometry can be used to grade the severity of their airway obstruction. Grading uses the FEV1 as a percentage of the predicted value, measured after a bronchodilator, when the FEV1/FVC ratio is below 0.7:
- Mild airflow obstruction = FEV1 80% or more of predicted. COPD is only diagnosed at this stage if the patient also has symptoms.
- Moderate airflow obstruction = FEV1 50-79% of predicted.
- Severe airflow obstruction = FEV1 30-49% of predicted.
- Very severe airflow obstruction = FEV1 less than 30% of predicted.
The predicted value for spirometry is based on a patient’s sex, age, height and ethnicity. NICE recommends the Global Lung Function Initiative (GLI) 2012 reference values, but these are not applicable to all ethnic groups.
The most useful piece of imaging to diagnose someone with COPD is a chest x-ray. In COPD, the chest radiograph (x-ray) may show signs of hyperinflation, meaning that the lungs hold too much air. These signs include a flattened diaphragm and an increased antero-posterior diameter (front-to-back width) of the chest. An increased number of ribs may also be seen within the lung fields on a standard chest radiograph.
A chest x-ray may also show signs of complications, such as infiltrates (patchy shadows) consistent with pneumonia, or a pneumothorax (air in the space around the lung, which can make the lung collapse). A chest x-ray is also useful for excluding other diagnoses in patients with a chronic cough, such as lung cancer.
A high-resolution CT scan gives an accurate assessment of the alveolar destruction caused by emphysema. It may help if the diagnosis is uncertain or if surgery is being considered. It is not routinely used to diagnose COPD.
Image - Chest x-ray of a patient with COPD, showing signs like a flattened diaphragm, 8 ribs visible within the lung fields, and the typical ‘barrel chest’ appearance
Creative commons source by Mikael Häggström, M.D [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
Pulse oximetry (a finger probe that measures the oxygen saturation of the blood) and/or arterial blood gas (ABG) analysis (a blood test from an artery that measures oxygen and carbon dioxide levels) can be carried out in acutely unwell patients. They assess for hypoxia, respiratory failure (the lungs cannot keep blood oxygen or carbon dioxide at safe levels) and hypercapnia.
Alpha-1 antitrypsin level may be checked if there is high suspicion of deficiency. NICE gives these reasons: early-onset COPD (for example, a young patient), a minimal smoking history (for example, a non-smoker with COPD symptoms) or a positive family history.
The treatment for COPD is mainly focused on managing symptoms, and is achieved through a mixture of making lifestyle changes and medication. These are the mainstay of treatments, because the disease process of COPD involves destruction of alveolar walls, and scarring of the airways, neither of which can be reversed.
Stopping smoking is the main lifestyle change a patient can make to reduce their symptoms. This is because smoking can irritate the already-inflamed lining of the lungs, and can further contribute to ciliary dysfunction, which increases the risk of exacerbations of COPD.
Patients can also attend pulmonary rehabilitation, a supervised exercise programme which aims to increase the patient’s exercise tolerance, educate them on the disease and give them nutritional advice. This helps to improve symptoms, exercise capacity and quality of life, so patients can live with fewer symptoms for longer.
Stable COPD therapy follows a stepwise plan. These medications aim to reduce the day-to-day symptoms that a patient experiences, and the number of exacerbations (flare-ups).
- Everyone is offered a short-acting bronchodilator (a drug that widens the airways) to use when needed. This is either a short-acting beta-2 agonist (SABA), such as salbutamol, or a short-acting muscarinic antagonist (SAMA), such as ipratropium. Muscarinic antagonists are also called antimuscarinics or anticholinergics: these are different names for one drug group.
- If the patient is still breathless or has exacerbations, despite help to stop smoking, non-drug treatment and vaccinations, a long-acting bronchodilator is added. Patients without asthmatic features are offered a long-acting muscarinic antagonist plus a long-acting beta-2 agonist (LAMA+LABA). Patients with asthmatic features are considered for a long-acting beta-2 agonist plus an inhaled steroid (LABA+ICS, where ICS stands for inhaled corticosteroid). Asthmatic features are signs that the patient may respond to steroids, such as a previous diagnosis of asthma or atopy (a tendency to allergic conditions), a higher blood eosinophil count, or large variation in FEV1 or peak flow over time.
- Triple therapy (LAMA+LABA+ICS) is considered after a clinical review, for patients who have a severe exacerbation (needing hospital admission) or two moderate exacerbations within a year. It can also be used when day-to-day symptoms still reduce quality of life.
Patients with COPD should also be given annual flu vaccines and appropriate pneumococcal vaccination (against infection with Streptococcus pneumoniae) in line with current UK guidance, to help prevent further infections. The RSV vaccine (against respiratory syncytial virus, a common cause of chest infections) is also offered on the NHS to adults aged 75 or over, and to adults aged 65 to 74 who have a long-term lung condition such as COPD. Patients with frequent exacerbations despite optimal inhaled therapy may be considered for prophylactic antibiotics under specialist supervision, to help reduce recurrent infective exacerbations.
Long-term oxygen therapy can improve survival in eligible people with COPD and chronic severe hypoxaemia (low oxygen levels in the blood). NICE advises a minimum of 15 hours per day. Eligibility requires assessment when COPD is stable and optimally treated, with arterial blood gases on two occasions at least three weeks apart. A structured assessment of fire and other safety risks is essential, including smoking by the patient or others in the home. NICE advises not offering long-term oxygen therapy to people who continue to smoke despite cessation support.
The last step in treatment for COPD is surgical intervention, with procedures such as removal of bullae, lung volume reduction and lung transplants. They are used to improve lung dynamics, exercise adherence, and quality of life. However, these surgeries are not often performed, as patients are often not well enough with other co-morbidities to undergo surgery.
An acute exacerbation of COPD is an event characterised by a sustained increase in the patient’s day-to-day symptoms, that is beyond normal variants and acute in onset. These can be infectious or non-infectious, and typically present with acute worsening of shortness of breath, cough and sputum production, with fever sometimes present in infective cases.
Management of an acute COPD exacerbation includes the following treatments. Each has a different aim:
- Monitoring for hypoxia and hypercapnia using pulse oximetry and arterial blood gas analysis, to check that oxygen and carbon dioxide levels are safe.
- Antibiotics when a bacterial infection is likely, particularly to cover Haemophilus influenzae and Streptococcus pneumoniae. Many exacerbations are not caused by bacteria and do not respond to antibiotics. NICE advises weighing the severity of symptoms, especially a change in sputum colour or an increase in its volume or thickness.
- Short-acting bronchodilators to relieve breathlessness. They can be nebulised (given as a mist through a mask) or given by a hand-held inhaler with a spacer (a tube that makes the inhaler easier to use). If the patient has hypercapnia or acidosis (acid in the blood), the nebuliser should be driven by compressed air rather than oxygen, to avoid worsening hypercapnia. Any oxygen that is needed is given at the same time through nasal cannulae (small tubes in the nostrils).
- Oral steroids: prednisolone 30 mg once daily for 5 days, to reduce inflammation in the airways.
- Controlled oxygen therapy with close monitoring, aiming for an oxygen saturation of 88% to 92% until blood gas results are available, while keeping under review for CO2 retention (carbon dioxide building up in the blood). Too much oxygen can make this worse.
- Possible escalation to non-invasive ventilation (NIV, breathing support through a tight-fitting mask, e.g. bi-level positive airway pressure, BiPAP) for persistent hypercapnic respiratory failure (type 2 respiratory failure, with a raised carbon dioxide level) despite optimal medical therapy.
- Intensive treatment unit (ITU) referral for invasive ventilation (a breathing machine, with a tube placed in the windpipe) may be considered if repeated ABG shows no signs of improvement with inpatient management. The decision takes account of the patient's usual function, body mass index (BMI), need for oxygen when stable, other conditions and any earlier ITU stays, and not age or FEV1 alone.
COPD cannot be cured, and the airflow obstruction is not fully reversible. The progressive damage to the lungs predisposes patients to a number of conditions:
- Recurrent infection, possibly progressing to pneumonia (mucus that is hard to clear allows bacteria to grow)
- Pneumothorax (because of abnormal lung tissue and bullae)
- Respiratory failure
- Right-sided heart failure (cor pulmonale), caused by pulmonary hypertension after long-term low oxygen levels
- Secondary polycythaemia (too many red blood cells, made in response to low oxygen levels)
- Lung cancer
- Depression and anxiety
- Muscle wasting
Edited by: Dr. Maddie Swannack
Reviewed by: Dr. Thomas Burnell and Dr. Marcus Judge
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