Chronic Obstructive Pulmonary Disease (COPD) exacerbations are ac common complications of patients diagnosed with COPD. It is defined as an acute event characterized by increased intensity of cough, sputum production, and dyspnea, which requires a change in treatment measurements. Common causes of COPD exacerbations include viral infections and air pollutants.
The diagnosis of COPD exacerbation is usually clinical, with adjunct studies to assess respiratory and cardiac function, along with microbiological studies when indicated. Treatment consists of bronchodilator therapy, oxygen therapy, and antibiotic treatment.
Introduction to COPD Exacerbation
Chronic obstructive pulmonary disease (COPD) is one of the most common respiratory diseases, with high mortality rates and prevalence all over the world. It is characterized by airway abnormalities and irreversible airflow limitation. It usually presents as acute exacerbation in the emergency department with complaints like dyspnea, cough, chest pain, increased sputum production, and purulence. The acute episodes are usually due to infection of the airways by bacteria and viruses or an irritant, causing aggravation of the patient’s signs and symptoms.
Chronic obstructive pulmonary disease (COPD) is third on the list of diseases with the highest mortality rates worldwide, as the World Health Organization (WHO) describes. This is the only leading cause of death that is still increasing in numbers in contrast to cardiovascular diseases. (1)
According to a study conducted in the United States, COPD is associated with 15.4 million outpatient department (OPD) visits, 1.5 million emergency department (E.D.) presentations, and 726,000 hospitalizations. (2) During 2012–2018, an estimated 5.8 million U.S. working adults aged ≥18 years had COPD, and 40% of them never smoked (3). According to statistics provided by Global Burden of Disease, developing countries are the most affected by COPD, as 63% of deaths due to COPD occur in low-income and middle-income countries (4).
Definition of COPD Exacerbation
According to World Health Organization (WHO), U.S. National Heart Lung and Blood Institute and Global Initiative for Chronic Obstructive Lung Disease (GOLD), the definition of an acute exacerbation of COPD is given as an acute event in the natural course of the disease which is characterized by a change in the pattern and increase in the intensity of patient’s cough, sputum production and baseline dyspnea that is beyond normal day-to-day variations and may need a change in regular medication in a patient who is a known case of COPD. (5)
Epidemiology of COPD Exacerbation:
As described earlier, COPD is a very common disease with high mortality. Acute exacerbations of the disease also have high incidence rates and are the main cause of emergency visits and hospital admissions during the course of the disease. A patient with COPD is estimated to experience almost 1 to 4 episodes of acute exacerbations in a year, and 1 in 6 of these exacerbations has the tendency and severity to demand hospitalization of the patient. (6)
Patients with acute exacerbations with respiratory failure make up 11% to 26% of emergency patients with associated respiratory failure and need immediate and proper management (7). A higher tendency of respiratory failure is seen in patients admitted in high dependency units (HDU) or intensive care units (ICU) (7).
COPD also exhibits a difference in incidence and prevalence between males and females. Differences in clinical features and presenting complaints are also recognizable. Males are more affected by COPD due to increased smoking rates. However, females are more susceptible to tobacco exposure, as proved in previous studies, and may develop the symptoms of the disease at a lower level of tobacco smoke exposure as compared to men. (8)
The same study in patients of COPD has proved that, after similar exposure to tobacco smoke, females exhibit the disease’s characteristic symptoms earlier than male patients, and their pulmonary functions decline more sharply, especially FEV1 (forced expiratory volume in one second). They are also suspected of having a more severe disease course. (8)
Etiology of COPD Exacerbation:
The most common risk factor and cause of COPD seen to date is exposure to tobacco smoke. It can be either active or passive smoking. Other causes of COPD, which also play an important role in acute exacerbations, are as follows: (9)
- Air pollution due to industrial and automobile exhausts is a real concern, especially in urban areas.
- Respiratory infections, as recurrent respiratory tract infections, can accelerate the decline of pulmonary functions, especially FEV1; adenovirus infections may alter the inflammatory response of lung tissue making it more susceptible to damage; HIV infection is also associated with the development of emphysema.
- Occupations such as coal mining or construction work can also expose people to occupational pollution, including silica and coal dust.
- Low birth weight is associated with a reduced ability to attain maximal lung function in adult life.
- Lung development (recurrent childhood infections, smoking by the mother during pregnancy, or passive smoking in childhood can result in reduced lung development and a lower maximally attained lung function in adult life).
- Cannabis smoking.
- Genetic factors such as alpha-one antitrypsin deficiency; other COPD-associated genes are likely to be identified (17).
Pathophysiology of COPD Exacerbation:
- Chronic obstructive pulmonary disease (COPD) is an inflammatory disease. Factors such as respiratory tract infections, increased exposure to irritants in the environment, and altered immunity are known to worsen the symptoms of the disease. COPD affects the respiratory airway, lung tissue, and vasculature in the respiratory system. Emphysema and chronic bronchitis are the two variants of COPD. Chronic bronchitis is the inflammation of the respiratory passage, especially the bronchi, while emphysema involves the destruction of the alveolar air sacs resulting in an obstructive disease.
- The inflammatory response is usually caused by an irritant (for example, smoking or allergens), leading to the recruitment of neutrophils and macrophages to the affected area and the release of inflammatory mediators. The production of excess proteases and oxidative stress cause the destruction of alveolar air sacs. This destruction leads to loss of elastin, and as a result, elastic recoil of the lung decreases. The collapse of airways ensues and produces the symptom of breathlessness. (10)
- The obstruction of the airway caused by the inflammatory process leads to a decreased forced expiratory volume (FEV1), further leading to impaired gaseous exchange and limited airflow. Increased air is trapped within the respiratory tree due to airway collapse, leading to lung hyperinflation, as seen in imaging studies. As the disease progresses, there is an elevation in CO2 levels, and pulmonary hypertension may occur. (11)
- Acute COPD exacerbations usually occur when exposure to a trigger stimulus, such as smoke, allergens, bacterial or viral infections, and environmental irritants. These factors induce inflammatory factors to be released. These include Neutrophil proteinase, tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), and the chemoattractants leukotriene B4 (LTB4), interleukin 8 (CXCL8), and growth-related oncogene α (GROα) (11), which lead to constriction of the airways, which can also lead to alveolar collapse as well as excessive mucus production through mucus gland hyperplasia. Although other cells and proteinases have been involved in the distal lung, the neutrophil remains the central cell implicated in many of the features and effects of exacerbations in the more proximal airways. (12)
History and Clinical Features:
A complete history is essential in acute exacerbations of COPD presenting to the emergency department with complaints of dyspnea. History of tobacco use, family history, history of similar symptoms, aggravating and relieving factors, medical and surgical history, occupational history, and any medication usage should be considered and co-related with the presenting complaints. This gives an insight into the patient’s disease and helps in diagnosis and further management plan. (13)
The signs and symptoms of acute exacerbation of COPD include cough, dyspnea, sputum production, cyanosis, wheezing, and pursed lip breathing. On Clinical examination, patients usually have a barrel-shaped chest, paradoxical inspiratory indrawing of costal margins (Hoover’s sign), and decreased air entry is noted on auscultation. COPD patients tend to lean forward as this helps relieve their dyspnea, which is called the tripod position. They also tend to use accessory muscles of respiration, which is noticeable in the form of elevation of clavicles and by gently pressing fingertips over scalene and sternocleidomastoid muscles.
Clinical features may vary from patient to patient and depending on the severity. Most patients are adults, and acute exacerbations are common in winter. Different scoring criteria have been developed to assess the severity of the disease. These include CAT, EXACT, CCQ, and mMRC dyspnea scales.
|Grades of mMRC Dyspnea Scale||Symptoms of Dyspnea|
|Grade 0||Breathlessness only noticed in strenuous exercise|
|Grade 1||Shortness of Breath noticed while walking on an inclined plane|
|Grade 2||Walks at a slower pace as compared to individuals of the same age and stops for breath while walking at their own pace|
|Grade 3||Shortness of Breath was reported after walking 100 yards or a few minutes|
|Grade 4||Breathless while dressing or undressing|
Patients are also advised to keep a record of previous exacerbations and medication for clinicians to have a quick assessment of disease chronicity and severity. (14)
All other diseases which can present with dyspnea and cough should be considered and ruled out with proper evidence before starting the treatment. These diseases include:
- Interstitial lung diseases.
- Asthma-COPD overlap syndrome
- Bronchiolitis obliterans
- Pulmonary embolism
- Heart failure
- Cystic fibrosis
- Acute exacerbations of COPD are usually diagnosed clinically and by relating it to previous history. Investigations may also prove helpful in diagnosis but are mainly done to check the severity of the disease, and appropriate management is done according to it. The investigations done in acute exacerbations of COPD are as follows:
- Pulse oximetry is an initial test and should be performed on all patients along with other vitals. The oxygen saturation in normal persons is greater than 94%. But in COPD patients, an oxygen level of 88% to 92% may be normal and preferred as hypoxia (low oxygen level) is the main stimulant of breathing in COPD patients in contrast to normal persons in which hypercapnia (high CO2 level) is the one stimulating the normal breathing pattern. (15)
- Chest Radiography should be done to rule out other pulmonary diseases. COPD findings on chest X-ray include hyperinflation of the chest. Pulmonary infiltrates may also be present in acute exacerbations of COPD due to superinfection.
- In cases of acute exacerbations, arterial blood gases should also be measured, as COPD is one of the most common causes of respiratory acidosis and should be managed accordingly.
- ECG is usually done in cases when the patient presents with dyspnea and associated chest pain to investigate the possibility of myocardial infarction.
- Some authors also recommend eosinophilic counts as exacerbations are more common in patients with eosinophilia, and they respond more to systemic steroid therapy. (16)
- Whole blood count and other basic biochemical tests such as random blood sugar, serum urea, and electrolyte concentrations can also be done.
- Blood culture, sputum culture, or throat swab culture are not done in routine cases but can be done in case of purulent sputum or if the patent is not responding to empirical antibiotic therapy.
- Spirometry is not recommended in cases of acute exacerbations but is done at the time of diagnosis of COPD to check the prognosis. FEV1 (forced expiratory volume in one second) is the most important parameter in determining the obstructive nature of the disease and the prognosis of COPD. (16, 17)
Treatment of COPD Exacerbation:
Acute exacerbation of COPD is an emergency condition and demands immediate management. The initial management consists of assessing the medical history and severity of symptoms, administration of oxygen therapy, inhaled bronchodilators, systemic corticosteroids (oral or intravenous), and appropriate antibiotics if needed. Non-invasive ventilation and invasive ventilation approaches can also be used depending on the situation. (16, 18, 19) Let us discuss these options in detail separately.
Both short-acting beta-agonists (SABA) and long-acting beta-agonists (LABA) are used in the management of COPD. In case of acute exacerbations, inhaled beta-agonists are usually used to cause bronchodilation and relieve the symptoms. Inhaled beta-agonists are preferred over systemic ones due to their localized effects and less harmful effects on heart and hypertension. SABA and LABA are used according to the severity of COPD and the rate of COPD exacerbations. SABAs are useful in acute exacerbations, while LABAs are mostly given as maintenance therapy upon discharge from the hospital.
Anticholinergics or antimuscarinics are used as bronchodilators along with beta-agonists. Inhaled short-acting antimuscarinics (SAMA) are also used as initial treatment along with inhaled SABA in COPD exacerbations. Long-acting antimuscarinics (LAMA) are also used as maintenance therapy. Global Initiative for Chronic Obstructive Lung Disease (GOLD) in 2017 recommended the usage of LAMA as an initial therapy. In some cases, a combination of LABA and LAMA can also be given for better response. (19)
For a long time, steroids have been used for both emergency cases and maintenance therapy. They are both inhaled and systemic. They are thought to improve lung function, shorten hospitalization, and fasten recovery. Although, it is suggested not to lengthen the course of therapy with steroids. It is recommended not to use systemic corticosteroids for more than five days.
Moreover, oral therapy should be encouraged rather than intravenous corticosteroids, even in hospitalized patients. It prevents the patients from hyperglycemia and fungal infections while reducing the cost to the hospital. Recent evidence indicates that the progression of COPD, which is expressed as the change in lung function over time, is not only modified by inhaled corticosteroid-containing regimes, but it can also have a significant impact in delaying deteriorating health status in symptomatic patients. (20)
Antibiotics are also suggested in cases of acute exacerbations by ERS/ATS guidelines. (27) An increase in respiratory symptoms, purulent sputum, and associated fever suggest a bacterial infection for which antibiotics should be used. The duration of antibiotic therapy can be 5-7 days and only given when there is an indication of bacterial infection. Procalcitonin levels can be used to differentiate between acute infection and chronic colonization by bacteria. An elevated procalcitonin level probably indicates an acute infection, and antibiotics should be given in this case.
It is considered a first-line intervention along with medical treatment in COPD exacerbations. It helps to decrease mortality and also prevents invasive procedures. In acute respiratory failure, non-invasive ventilation is the standard approach and should be done before mechanical ventilation. (19, 22)
Improving the lifestyle can also improve the prognosis of COPD and decrease the number of exacerbations. Exercise, smoking cessation, maintaining low body fat, and avoiding allergens and irritants can prevent acute exacerbations with overall improvement in pulmonary functions. Moreover, it also prevents other comorbidities such as coronary heart disease (CHD), diabetes, and hypertension. That is why lifestyle changes are very important for the overall outcome of the disease.
Complications of COPD Exacerbation:
The complications which can develop in COPD are as follows:
- Acute on chronic respiratory failure.
- Pulmonary hypertension.
- Weight loss.
- Bacterial infections.
- Cor pulmonale.
- Corticosteroids side effects.
Prognosis of COPD Exacerbation:
Various factors contribute to the prognosis of COPD. This includes comorbidities (such as cardiovascular disease, obesity, diabetes, pulmonary hypertension, and malignancy), the lifestyle of the patient, exposure to environmental pollutants, smoking, and age. Smoking cessation, avoidance of allergens and irritants, and a healthy lifestyle is associated with a good prognosis. While comorbidities and old age point towards a bad prognosis.
The criteria used to check the prognosis of COPD is the BODE index. The components of this criteria are as follows:
- Body-mass index, calculated as the mass in kilograms divided by height in meters squared.
- Obstruction to airflow, described in terms of FEV1 as forced expiratory volume in one second calculated by spirometry.
- Dyspnea assessed by mMRC scale.
- Exercise capacity of the patient checked by comparing a 6-minute walk distance with a normal person.
The point score for the BODE index is calculated on a scale of 1-10. The total score is calculated and correlated with 4-year survival. (23)
The author does not report any conflict of interest.
This information is for educational purposes and is not intended to treat disease or supplant professional medical judgment. Physicians should follow local policy regarding the diagnosis and management of medical conditions.
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