Table of Contents
- Definition of COPD
- Causes and Risk Factors of COPD
- Epidemiology of COPD
- Etiology of COPD
- Classification of COPD
- Pathogenesis of COPD
- Pathophysiology of COPD
- Signs and Symptoms of COPD
- Differential Diagnosis of COPD
- Acute Exacerbation of COPD
- Therapy of COPD
- Prevention of COPD
- Learn more about COPD
- Review Questions
Definition of COPD
The term COPD refers to a chronic obstructive pulmonary disease and thus summarizes chronic respiratory diseases, where an airflow limitation occurs. A distinction must be done between the definition of the WHO and the Global Initiative For Chronic Obstructive Lung Disease (GOLD).
The WHO defines a chronic bronchitis as the daily occurrence of productive cough over the period of three months in two consecutive years.
According to the Global Initiative For Chronic Obstructive Lung Disease COPD is a preventable and treatable disease of the airways, which is accompanied by a restriction of the respiratory flow. The disease is progressive and associated with a chronic inflammatory reaction of the lung to noxious particles or gases.
Causes and Risk Factors of COPD
Almost 3 million people are having COPD in the United Kingdom. Roughly 900,000 patients among them are having diagnosed COPD while about 2 million people are having undiagnosed COPD. 90 % of the COPD patients are smokers. People above the age 50 are most affected. Heavy smokers can develop COPD after the age of 35.
The major cause of COPD is smoking, either active or passive. Other causes include long-term inhalation of chemical fumes, dust, and air pollutants. Genetical alpha 1 antitrypsin deficiency can also damage the lungs and lead to COPD. Smoking is a risk factor in these people as well.
Almost all preterm babies need long-term oxygen therapy as their lungs are still underdeveloped. This can lead to lung injury (neonatal chronic lung disease) increasing the risk for COPD later in adult age. Chronic bronchitis is defined on the basis of the history as chronic productive cough for at least 3 months in two consecutive years. Emphysema is defined by loss of alveoli.
Epidemiology of COPD
The prevalence of COPD in the United States of America is among the over 45-year-olds about 5 %, but due to the unreported cases a much higher number can be estimated. In the seventh decade of life, the prevalence is the highest. Worldwide, COPD is the third leading cause among men and women. Men and women are equally affected.
Etiology of COPD
Exogenous and endogenous factors can be recognized as the causes of COPD. The exogenous factors include especially smoking, which is responsible for COPD in approximately 90 % of all cases. However, air pollution by ozone or fine dust, miners are often affected, is a trigger of COPD.
The progression of COPD is supported by recurrent bronchopulmonary infections. In addition, a disturbed lung maturation in embryogenesis is known as a cause of later COPD. Important endogenous factors are α1-antitrypsin deficiency, and IgA- deficiency which may contribute to the development of COPD as well – especially in younger age.
Classification of COPD
The COPD can be divided into different levels of severity. After the Global Initiative For Chronic Obstructive Lung Disease (GOLD), the following grades can be distinguished:
|GOLD I (easy)||FEV1 ≥ 80 %, FEV1/VC < 70 %|
|GOLD II (medium)||FEV1 50 – 79 %, FEV1/VC < 70 %|
|GOLD III (severe)||FEV1 30 – 49 %, FEV1/VC < 70 %|
|GOLD IV (very severe)||FEV1 < 30 %, FEV1/VC < 70 %|
Spirometry is done after every two years of initial diagnosis. The patient is also evaluated for other associated conditions like anemia, cancer, anxiety/depression, ischemic heart disease, congestive heart failure, metabolic syndrome, peripheral muscle dysfunction, osteopenia, osteoporosis etc.
The Medical Research Council (MRC) has proposed a dyspnea scale:
- Grade 1: No breathlessness except with strenuous exercise
- Grade 2: Breathlessness when walking up a slight hill or hurrying on the level
- Grade 3: Patient walks relatively slower than normal people on the level because of shortness of breath or has to catch for breath while walking at own pace on the level
- Grade 4: Patient stops to catch breath after roughly 100 yards (90 m) walk or after a few minutes on the level
- Grade 5: Patient is not able to leave his house due to breathlessness or breathless during dressing or undressing.
Pathogenesis of COPD
Airway limitation is the main feature of this disease. Initial stages of COPD are without any significant symptom. People take a mild cough and shortness of breath on exertion as a normal part of aging. COPD can take years to complicate and produce significant symptoms; however, complications lead to permanent damage to the lungs. Although the damage caused by COPD cannot be undone, it is still possible to prevent further damage and manage the patients.
COPD includes chronic bronchitis and emphysema. Chronic bronchitis is the inflammation of the airways in response to smoking or any other pollutant, leading to narrowing and increased mucous deposition in the airway. Narrowed or blocked airways disturb effective respiration, making the patient symptomatic. Emphysema is the breakdown of the air sacs (alveoli) and alveolar membranes. Alveoli lose their strength and the air entering the lungs is decreased, leading to cough and dyspnea.
Rarely, inherited deficiency of alpha 1 antitrypsin can lead to COPD. Emphysema occurs in these patients after the age of 30. Deficiency of the alpha 1 antitrypsin protein in the blood leads to the destruction of lung tissue by the WBCs.
Pathophysiology of COPD
After years of damage caused by inhaled toxicants such as cigarette smoke, there is a hypertrophy and hyperplasia of goblet cells in the mucosa of the bronchi. This results in an increased production of mucus whose removal can no longer be guaranteed by the ciliated epithelium. The lumen of the bronchi is constricted and therefore promotes a lasting inflammatory reaction.
This inflammation leads to a remodeling process, so the obstruction is both functionally and structurally permanent. Another consequence of chronic inflammation is a non-physiological ratio between proteases and protease inhibitors, so that there is a destruction of connective tissue and thus leading to destroying the supporting structures of the lung and developing of a pulmonary emphysema.
The elasticity of the lung decreases, the residual volume increases. The affected patients have to increase their work of breathing. The obstruction of the respiratory tract causes a distribution of interference, which leads in the hypoxic areas to pulmonary vasoconstriction according to the Euler-Liljestrand mechanism. If the total cross section of all pulmonary vessels continues to decrease, it results into a pulmonary hypertension or even in a pulmonary heart disease.
Additionally it comes to a non-specific bronchial hyper-responsiveness. In forced expiration, for example during physical exertion, a bronchial collapse occurs that results in hyperinflation of the lung. This creates a massive performance limitation of patients.
Signs and Symptoms of COPD
COPD produces symptoms, disability and impaired quality of life which may respond to pharmacological and other therapies that have limited impact on the airflow obstruction. Symptoms of COPD include:
- Shortness of breath or breathlessness on exertion or at rest (in late stages)
- Chest tightness on exertion or at rest (in late stages)
- Chronic Cough with sputum, a feature of chronic bronchitis
- Wheezing, particularly on expiration
- Other symptoms like weight loss, ankle swelling, low appetite.
Signs seen on examination
COPD patients can have the following signs depending upon the severity of the disease:
Barrel-shaped chest due to hyperinflation and labored breathing using accessory muscles of respiration
- Cyanosis of the lips and/or nail beds due to impaired lung function
- Wheeze with breathing, particularly with expiration
- Distant breath sound sounds on auscultation of the chest
- Scattered rhonchi on auscultation of the chest
- Hyper-resonance of the lungs on percussion
- Pulmonary hypertension can develop and produce signs of cor pulmonale like ankle swelling, orthopnea, chest tightness, raised JVP, etc.
Asthma and COPD have a different pathogenesis. Asthma is triggered by allergens in the environment and airway inflammation is done by CD4+ T cells, lymphocytes, eosinophil, and ILs-4. However, the symptoms of asthma are completely reversible, while COPD develops in response to noxious agents. Airway inflammation in COPD is done by CD8+ T-lymphocytes and CD68+ macrophages/PMNS but airway obstruction is permanent and irreversible.
The typical presentation of COPD is a chronic cough with whitish or purulent liquid to tough expectoration and dyspnoea. Frequently COPD precedes a simple chronic bronchitis, coughing and expectoration that are reversible. Two types can be distinguished on their clinical picture:
- Pink buffer: emphysemic COPD type with strong dyspnoea and late pulmonary heart disease
- Blue bloater: bronchial COPD type with low dyspnoea, cyanosis and pronounced oedema
History– and physical examination
History is essential for existing risk factors, particularly asking about smoking behaviour and already known respiratory diseases such as asthma or allergies. You can determine the severity of the disease from the history by asking about the degree of distress with daily activities.
In the physical examination, evidence of COPD (for example cyanosis or barrel chest) can already be found in the inspection. In palpation a reduced vocal fremitus, in percussion a hyper-resonant sound can be heard due to the hyperinfiltration of the lungs.
In auscultation a prolonged expiratory phase can be heard, which is accompanied by whistling and also by wheezing and humming. Reduced breathing sound can be heard in the hyperinfiltrated lung. Fine rales can also be heard accompanying a pneumonia infection.
Pulmonary functions tests
A patient presenting with shortness of breath, cough with sputum and chest tightness should be thoroughly evaluated and tests for COPD should be performed.
Initially, clinical history and physical examination should be done. Baseline investigations should be sent to the laboratory and ECG with chest x-ray is advised to rule out other causes like lung cancers, cardiac diseases. Pulmonary function tests are performed using spirometer.
Spirometry is the most important test to diagnose obstructive and restrictive lung diseases. FEV1 and FVC are calculated using spirometry. FEV1 is the forced expiratory volume of the air in one sec while FVC is the forced vital capacity. FEV1 measures the rate at which air moves out of the lungs. Arterial blood gasses are done to measure the content of oxygen, carbon dioxide, and H+ ions. Oxygen saturation is also monitored regularly for COPD patients.
An alpha 1 antitrypsin test is done rarely to rule out the inherited cause of COPD. CT scan plain or HRCT chest is done to see the detailed picture of the lungs.
After inhalation of salbutamol only a slight reversibility of less than 200 ml/ or less than 15 % appears in the bronchospasmolysis test. A reduced transfer coefficient (DLCO/VA9 sheds light on an existing emphysema, or about the degree of its scale. A decreased MEF25-75 shows an obstruction of the small airways.In smokers, the CO content in the exhaled air may be determined, which increases to the consumption of cigarettes (> 50 ppm). In addition, the HbCO in blood gas analysis is increased in smokers. The arterial blood gas analysis also gives information about whether it is a respiratory partially influence (pCO2 decreased) or a generalized respiratory insufficiency (pO2 decreased and pCO2 increased).
Type of respiratory failure:
- Pco2 increased → if patient is hypercapnic only: type 1 respiratory failure
- Po2 decreased and pco2 decreased → if patient is hypoxic and hypercapnic: it´s type 2 respiratory failure.
Arterial blood gases and oximetry may demonstrate resting exertional hypoxemia. Arterial blood gases provide additional information about alveolar ventilation and acid-base status by measuring artial Pco2 and pH.
In addition, certain patterns can be identified in spirometry, which are typical of COPD. Typical in the flow-volume graph an emphysema bend and in the resistance loop the image of a golf club are shown.
In the laboratory diagnosis, it is necessary to investigate the α1-antitrypsin deficiency, especially in younger patients who do not smoke. Complete blood count may show elevated hematocrit level which suggests the presence of chronic hypoxemia.
In case of recurrent severe exacerbations or treatment failure, a sputum culture should be asked. For the diagnosis, morning expectoration must be collected, the obtaining of endobronchial secretion, for example as part of a bronchoscopy, is even better. Potential pathogens are frequently Haemophilus influenza, pneumococcal or Moraxella catarrhalis and different virus types.
Characteristic radiographic findings:
- Hyperinflation with → 1- flattened hemidiaphragms 2- increased anteroposterior chest diameter.
- Parenchymal destruction produces : attenuated peripheral vascular markings.
- Pulmonary hypertension produces : proximal pulmonary artery dilation .
- Cardiac size may be increased, suggesting right heart volume overload.
- Cystic or bullous changes.
In chest X-ray, small opacities may suggest inflammatory infiltrates or restricted ventilation. Changes due to emphysema or pulmonary heart disease can be detected, and other diseases such as lung cancer or pneumonia are excluded. Since the chronic bronchitis is a diagnosis of exclusion, an X-ray image is always needed before a diagnosis is made!
In addition, a bronchoscopy is a possibility, especially with regard to various differential diagnoses that result in symptoms such as haemoptysis and dyspnoea. Therefore, a biopsy for histological examination can be taken.
There is no single diagnostic test for COPD to reach a diagnosis. Physician relies on clinical judgment based on a combination of history, physical examination and confirmation of the presence of airflow obstruction using spirometry. COPD is characterized by airflow obstruction that is not fully reversible. Airflow obstruction is defined as a reduced FEV1/FVC ratio such that FEV1/FVC is less than 0.7. If FEV1 is ≥ 80 % predicted normal. A diagnosis of COPD should only be made in the presence of respiratory symptoms, for example, breathlessness or cough.
Differential Diagnosis of COPD
A differential diagnosis of COPD is bronchial asthma. This manifest itself, unlike COPD, mostly in childhood or adolescence, and is accompanied by paroxysmal dyspnoea, allergies and a good response to corticosteroids and is completely reversible in the bronchiospasmolysis test.
Other lung diseases must be excluded. To exclude bronchiectasis a greater amount of sputum is necessary as well as a HR-CT. A tracheal or larynx stenosis may be differentiated by laryngoscopy or bronchoscopy. An otolaryngologist may establish a sinubronchial syndrome with chronic sinusitis from COPD.
To exclude a left ventricular failure that occurs especially with nocturnal cough and cardiac asthma, cardiac diagnostics are necessary. The cystic fibrosis can be diagnosed through a sweat test. Important is the demarcation of a bronchial carcinoma. Therefore, X-rays and CT scans or a biopsy by bronchoscopy is necessary. In addition, a pulmonary embolism and the gastroesophageal reflux disease should be excluded.
- Cardiovascular or pulmonary vascular disease
- Severe deconditioning
- Interstitial lung disease
- Neuromuscular disease
Acute Exacerbation of COPD
A sudden attack of shortness of breath, wheezing and cyanosis with signs of respiratory distress in a patient with diagnosed COPD is called acute exacerbation of COPD. Infections caused by bacteria or viruses, or body response to environmental pollutants can be the triggers of an acute attack. Management includes systemic and inhaled corticosteroids with oxygen therapy and regular monitoring with antibiotic cover if required.
Therapy of COPD
The treatment of COPD is divided into a medical and a conservative approach. The basis of the conservative therapy is the absolute nicotine abstention and the elimination of other inhaled noxious agents. Patient training and breathing exercises combined with a training to improve cardiopulmonary capacity are also necessary.
Vaccination against pneumococcal and influenza viruses are indicated for the prevention of infections. Furthermore, prophylaxis of osteoporosis with calcium and vitamin D3 is useful as is promotes osteoporosis with a glucocorticoid therapy. Existing infection sources have to be eliminated and comorbidities need to be treated consistently.
Drug therapy is structured according to a graduated scheme.
- The first group of patients with GOLD 1 to 2, 0 to 1 exacerbations per year and a few symptoms can be treated with a short-acting antichlinergic or short-acting β2-sympathomimetic each if needed. Alternative or supplement to this stage is a therapy with theophylline.
- The second group of patients with GOLD 1 to 2, from 0 to 1 exacerbations per year but with stronger symptoms is treated with a long-acting anticholinergic, or a long acting β2-sympathomemimic. Alternative of supplement to this stage is a therapy with short-acting anticholinergics and/or short-acting β2-sympathomimetic and theophylline.
- The third group of patients with GOLD 3 to 4, two or more exacerbations per years and few symptoms is treated with an inhaled glucocorticosteroids and a long-acting anticholinergic, or a long-acting β2-sympathomimetic. Alternative or supplement to this stage is a therapy with short-acting anticholinergics and/or short-acting β2-sympathomometic and theophylline.
- The fourth group of patients with OLD 3 to 4, two or more exacerbations per years and stronger symptoms gets inhaled glucocorticosteroids and a long-effective β2-sympathomemitetic and/or a long-effective anticholinergic. Alternative or supplement to this stage is a therapy with short-acting anticholinergics and/or short-acting β2-sympathomimetic and theophylline and carbocisteine.
Therapy of acute recurrent exacerbations
In this case, a hospitalization is often sought, especially if strong dyspnoea and/or tachypnoea or a higher age of the patients occur. When infection-related exacerbations, antibiotic therapy is indicated based on antibiotic susceptibility of the suspected pathogens as well as the patient’s clinical condition Patients with mild exacerbations can be treated in outpatient with aminopenicillin (alternatively doxycycline, macrolides).
Patients with moderate to severe exacerbations need hospital admission and treatment with aminopenicillin with beta-lactamase inhibitor or parenteral cephalosporin of the 2nd or 3rd group(alternatively pneumococcal fluoroquinolones). In patients with suspected P. aeruginosa infections or in patients in intensive care, pseudomonas effective carbapenems, cephalosporin or fluoroquinoles should be used.
The bronchodilator therapy may be temporarily intensified and combined with intravenous glucocorticoids. There are also aerosol treatments, an apparatus inhalation therapy with 0.9 % NaCl, β2-sympathomimetics such as salbutamol, and an oxygen treatment, so that the pO2 is maintained above 60 mmHg
Acute recurrent exacerbations is a complication of COPD, which requires an adjustment of therapy. The viral or bacterial infections cause more deterioration that may last longer than 24 hours. Also, co-morbidities such as cardiovascular disease or metabolic syndrome, lung carcinoma, muscle weakness and osteoporosis (due to catabolic mechanism with increased work of breathing) and depression are complications of COPD.
Weight loss with increased work of breathing is typical. Among the late complications the respiratory failure is included and the pulmonary heart disease, which is due to the Euler-Liljestrand mechanism and direct vascular loss in a pulmonary emphysema. Pulmonary hypertension may lead to right heart failure with, for example, hepatomegaly or ascites.
Prevention of COPD
The most effective preventive method is risk factors avoidance. It has been shown that middle-aged smokers who were able to successfully stop smoking experienced a significant improvement in the their prognosis with slow progression of the disease.For this purpose, the detailed medical reconnaissance and surveillance is essential as well as assisting with substitution drugs and anti-depressants in order to facilitate the cessation.
In occupational COPD, immediate avoidance of inhaled noxious substances is crucial. Also vaccines against pneumococcal and influenza are indexed to avoid acute exacerbations due to these infections.
Learn more about COPD
To learn more about this topic you may test the course “Respiratory Medicine” by Prof. Jermey Brown for free! An extra lecture about COPD is included!
The answers are below the references.
1. What does not belong to the symptoms of COPD?
- Chest pain
2. Which is the best diagnostic tool for COPD?
- Chest X-ray
- Laboratory diagnostics
3. Which is the best to describe the Pink buffer?
- bronchial COPD type
- strong dyspnoea
- pronounced oedema
- pyknic type
4. A 62-year-old male smoker for the last 35 years came to the emergency with excessive sweating and difficulty breathing with productive cough. He has a history of difficulty breathing and productive cough from the past 3 years. On physical examination, the temperature is 101° Fahrenheit, pulse 124/min and BP 130/90 mm hg. He was pale and his lips were bluish. On auscultation of the chest, bilateral crepitations were present on the base of the lungs, more on the right side. Chest X-ray was done in the emergency, shown in the figure. Which is the correct statement?
- Patient is having acute asthma, as chest x-ray shows hyperinflation.
- Patient is having emphysema due to active smoking.
- Patient is having chronic bronchitis along with lobar pneumonia.
- Patient is having right heart failure and pulmonary edema.
5. What are the findings in the chest x-ray (image)?
- Hyperinflation and infiltration showing bronchopneumonia
- Hyperdense are in the right lung due to pulmonary edema and bronchopneumonia
- Hyperinflation of the lungs, narrow mediastinum, hyperlucency through lung fields bilaterally
- Calcification of the hillar lymph nodes, 2–3rd rib fracture on the right side