- Clinical science
Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by airway obstruction due to inflammation of the small airways. It is caused predominantly by inhaled toxins, especially via smoking (90% of cases), but air pollution and recurrent respiratory infections can also cause COPD. Some individuals are genetically predisposed to COPD, particularly those with α1-antitrypsin deficiency (AATD). COPD begins with chronic airway inflammation that usually progresses to emphysema, a condition that is characterized by irreversible bronchial narrowing and alveolar hyperinflation. These changes cause a loss of diffusion area, which can lead to inadequate oxygen absorption and CO2 release, resulting in hypoxia and hypercapnia. Most affected individuals present with a combination of dyspnea and chronic cough with expectoration. In later stages, COPD may manifest with more severe symptoms such as tachypnea, tachycardia, and cyanosis. Diagnosis is primarily based on clinical presentation and lung function tests, which typically show a decreased ratio of forced expiratory volume (FEV) to forced vital capacity (FVC). Imaging studies, such as chest x-ray, are helpful in assessing disease severity and the extent of possible complications, but they are not required to confirm the diagnosis. ABG and pulse oximetry are useful for quickly assessing the patient's O2 status. All COPD patients should be staged according to the staging system of the Global Initiative for Chronic Obstructive Lung Disease (GOLD), which considers a variety of factors (e.g., exacerbations, symptom severity, FEV1). Treatment options depend on the GOLD stage and mainly consist of short- and long-acting bronchodilators (beta-agonists and parasympatholytics) and glucocorticoids. Individuals with advanced disease typically require oxygen supplementation, which is the only treatment that decreases mortality. COPD may cause complications such as pulmonary hypertension or respiratory failure; the most significant complication is acute exacerbation of COPD (See AECOPD).
- A chronic pulmonary disease characterized by persistent respiratory symptoms and airflow limitation (postbronchodilator FEV1/FVC < 0.70), which is caused by a mixture of small airway obstruction and parenchymal destruction.
- COPD was formerly subdivided into chronic bronchitis and emphysema. These terms are still widely used to describe patient findings and found as subclasses of COPD in outdated literature.
- Chronic bronchitis: productive cough (cough with expectoration) for at least 3 months each year for 2 consecutive years
- Emphysema: permanent dilatation of pulmonary air spaces distal to the terminal bronchioles, caused by the destruction of the alveolar walls and the pulmonary capillaries required for gas exchange.
Tobacco use (90% of cases)
- Smoking is the major risk factor for COPD, but those who have quit ≥ 10 years ago are not at increased risk. 
- Passive smoking
- Exposure to air pollution or fine dusts
- Recurrent pulmonary infections and tuberculosis
- Premature birth
- Tobacco use (90% of cases)
- Endogenous factors
Global initiative for chronic obstructive lung disease (GOLD) classifications
- Classifies COPD according to the severity of airflow limitation (GOLD 1-4) and the ABCD assessment tool, which takes into account the modified British Medical Research Council (mMRC) dyspnea scale, COPD assessment test (CAT), and risk of exacerbation.
- Previously, COPD was classified into chronic bronchitis and emphysema based on clinical findings. The use of these terms to classify types of COPD is now considered outdated because most individuals with COPD have a combination of both. However, these terms are still widely used to describe patient findings and found as subclasses of COPD in outdated literature.
Classification based on airflow limitation in patients with FEV1/FVC < 70%
|FEV1 % of the predicted value|
|GOLD 1 (Class I)|| || |
|GOLD 2 (Class II)|| || |
|GOLD 3 (Class III)|| || |
|GOLD 4 (Class IV)|| || |
Classification using combined assessment tools
|Patient group||Degree of severity||Exacerbations per year||Symptoms||mMRC Dyspnea Scale||CAT score|
|A|| || || || || |
|B|| || || |
|C|| || || || || |
|D|| || || |
- CAT score = COPD assessment test score
- mMRC Dyspnea Scale = Modified Medical Research Council Dyspnea Scale
- Low risk = FEV1/FVC ratio ≤ 0.7, FEV1≥ 50% predicted, and 0–1 exacerbation in the last year
- High risk = FEV1/FVC ratio ≤ 0.7, FEV1 ≤ 50% predicted, and ≥ 2 exacerbations in the last year
Classification based on underlying pathophysiologic changes
Emphysema is divided into the following subtypes:
- Centrilobular emphysema (centriacinar emphysema)
- Panlobular emphysema (panacinar emphysema)
Other classifications or types
- Cicatricial emphysema
- Giant bullous emphysema
- Senile emphysema
Chronic inflammation: results from significant exposure to noxious stimuli
- Caused by increased oxidative stress (most commonly due to cigarette smoke) as well as by increased release of reactive oxygen species by inflammatory cells
- Increased number of neutrophils, macrophages, and CD8+ T lymphocytes → release of cytokines → amplification of inflammation and structural changes of lung parenchyma (e.g., growth factor release)
Promotes goblet cell proliferation, mucus hypersecretion, and impaired ciliary function → chronic productive cough
- Reid index: The ratio of the width of the mucus-secreting glands to the combined width of the epithelium and cartilage in the bronchial tree. > 0.5 is characteristic of .
- Overproduction of growth factor → peribronchiolar fibrosis → narrowing of airway → obliteration → emphysema (airflow limitation)
- Smooth muscle hyperplasia of the small airways and pulmonary vasculature (mainly due to hypoxic vasoconstriction) → pulmonary hypertension → cor pulmonale
Bronchopulmonary inflammation ↑ proteases, and nicotine use (or other noxious stimuli) inactivates protease inhibitors (especially α1-antitrypsin) → imbalance of protease and antiprotease → ↑ elastase activity → loss of elastic tissue and lung parenchyma (via destruction of the alveolar walls), which causes:
- Enlargement of airspaces → ↓ elastic recoil and ↑ compliance of the lung → ↓ tethering of small airways → expiratory airway collapse and obstruction → air trapping and hyperinflation → ↓ ventilation (due to air-trapping) and ↑ dead space → ↓ DLCO and ↑ ventilation-perfusion mismatch (Va/Q) → hypoxemia and hypercapnia
- ↓ Blood volume in pulmonary capillaries → ↑ dead space → ↓ DLCO and ↑ Va/Q → hypoxemia and hypercapnia
- Imbalance of oxidants and anti-oxidants and an overabundance of free radicals → contributes to chronic inflammation and inactivation of anti-elastase → exacerbates breakdown of elastic tissue
- Bronchopulmonary inflammation ↑ proteases, and nicotine use (or other noxious stimuli) inactivates protease inhibitors (especially α1-antitrypsin) → imbalance of protease and antiprotease → ↑ elastase activity → loss of elastic tissue and lung parenchyma (via destruction of the alveolar walls), which causes:
- Symptoms are minimal or nonspecific until the disease reaches an advanced stage.
- Common presenting findings:
- Chronic cough with expectoration (expectoration typically occurs in the morning)
Dyspnea and tachypnea
- Initial stages: only on exertion
- Advanced stages: continuously
- Pursed-lip breathing
- End-expiratory wheezing, crackles, muffled breath sounds, and/or coarse rhonchi on auscultation
- Often weight loss and cachexia
In cases of advanced COPD and/or cor pulmonale:
- Congested neck veins
- Barrel chest
- Asynchronous movement of the chest and abdomen during respiration
- Use of accessory respiratory muscles due to diaphragmatic dysfunction
- Hyperresonant lungs; , reduced diaphragmatic excursion, and relative cardiac dullness on percussion
- Decreased breath sounds on auscultation: “silent lung” (silent chest on auscultation)
- Prolonged expiratory phase
- Peripheral edema (most often ankle edema)
- Right ventricular hypertrophy with signs of right heart failure
- Secondary polycythemia
- Nail clubbing in the case of certain comorbidities (e.g., bronchiectasis, pulmonary fibrosis, lung cancer)
- According to their clinical appearance, patients with COPD are often categorized as either “Pink Puffer” or “Blue Bloater”.
|Pink Puffer||Blue Bloater|
|Clinical features|| |
|PaO2|| || |
|PaCO2|| || |
- Patients with COPD in association with AATD
Spirometry and/or body plethysmography
- FEV1/FVC < 70% (Tiffeneau-Pinelli index)
- Normal or decreased FVC
- Decreased FEV1: used to classify COPD according to GOLD (see classification above)
- Increased FRC and RV
- Increased intrathoracic gas volume
- Assesses reversibility of bronchoconstriction
- Results: FEV1/FVC < 0.7 is diagnostic of COPD (in patients with typical clinical features and exposure to noxious stimuli). ;
- FEV1 > 12% (reversible bronchoconstriction): Asthma is more likely than COPD.
- If spirometry is normal, COPD can be excluded.
Always TaLCk FRanCly. It ReleaVes HIGH stress in COPD.
Blood gas analysis (BGA) and pulse oximetry
- Pulse oximetry: assess O2 saturation
- BGA: only indicated when O2 is < 92% or if the patient is severely ill (e.g., altered mental status, acute exacerbation)
- Indications: not required for routine diagnosis but often used as an initial modality, mainly to rule out alternative conditions (e.g., pulmonary fibrosis, bronchiectasis)
- Not sensitive, especially during the early stages of COPD
- Can be used to determine the etiology for an acute COPD exacerbation (e.g., pneumonia, congestive heart failure)
- Signs of hyperinflated lungs (barrel chest)
- Hyperlucency of lung tissue (decreased lung markings)
- Increased anteroposterior diameter
- Diaphragm pushed down and flattened
- Horizontal ribs and widened intercostal spaces
- Long narrow heart shadow
- Parenchymal bullae or subpleural blebs (pathognomonic of emphysema)
- The retrosternal space is increased on lateral view due to emphysematous changes in the lung tissue.
- Evaluate possible complications (e.g., pneumothorax, ARDS).
- Plan surgery (e.g., lung volume reduction, lung transplantation).
- Rule out differential diagnoses (e.g., bronchiectasis, lung cancer).
- In most patients with COPD: centriacinar emphysema
- In patients with AATD: panacinar emphysema , bronchiectasis, bullae
- Laboratory studies
- Gram stain and sputum culture: in the case of suspected pulmonary bacterial infection (e.g., fever, productive cough, new infiltrate on chest x-ray)
- Bronchoscopy: to identify the pathogen in severe and acute exacerbation of COPD with infective etiology, especially if antibiotic treatment fails
- Liver biopsy in patients with AATD: PAS-positive, spherical inclusion bodies in periportal hepatocytes
Consider AATD in patients with COPD who are < 60 years of age, have no smoking history, and/or have basilar-predominant COPD.
- See “Differential Diagnosis” in .
The differential diagnoses listed here are not exhaustive.
- Cessation of tobacco use (single most effective step to slow the decline in lung function)
Pneumococcal: reduces the incidence of community-acquired pneumonia and invasive pneumococcal diseases
- Age 19-64 years: Administer .
Age ≥ 65 years
- Vaccinated: Administer PPSV23 (should be at least 5 years after the previous PPSV23 dose and at least 1 year after PCV13).
- Not vaccinated or unknown vaccination history: Administer followed by PPSV23
- Influenza (annual): reduces serious illness and death in COPD patients
- Pneumococcal: reduces the incidence of community-acquired pneumonia and invasive pneumococcal diseases
- Pulmonary rehabilitation (indicated in patients with GOLD B, C, and D): physiotherapy with breathing exercises
- Supportive treatment (e.g., postural drainage)
- Vitamin D3 and calcium in cases of deficiency
Medical treatment in COPD reduces the severity of symptoms, improves overall health status, and lowers the frequency and severity of exacerbation. The first-line treatment of COPD consists of bronchodilators, inhaled corticosteroids, and phosphodiesterase (PDE) type 4 inhibitors.
Bronchodilators: either parasympatholytics (see ) or β2-agonists
- Long-acting parasympatholytics (long-acting muscarinic antagonists, LAMAs): tiotropium bromide
- Long-acting β2-agonists (LABAs): salmeterol, formoterol
- Short-acting parasympatholytics (short-acting muscarinic antagonists, SAMAs): ipratropium bromide
- Short-acting β2-agonists (SABAs): salbutamol, fenoterol
- Inhaled corticosteroids (ICS): budesonide, fluticasone, beclomethasone
- PDE type 4 inhibitors: roflumilast
|Exacerbations per year||Mild symptoms||Severe symptoms|
|≤ 1 exacerbation|| |
|≥ 2 exacerbation or ≥ 1 exacerbation requiring hospitalization|| |
For all groups: a SABA and/or SAMA can be added as needed
- If dyspnea persists
If exacerbations still occur
- LABA and LAMA or
- LABA and ICS
- If exacerbations still occur, escalate to triple therapy:
- If exacerbations still occur with LABA, LAMA, and ICS triple therapy:
- If increasing purulent sputum and/or mechanical ventilation is involved: add empiric treatment with aminopenicillin with clavulanic acid, macrolide, or tetracycline
Other treatment options
- Mechanism of action: adenosine receptor blockade and nonspecific PDE inhibition
- Indication: usually only severe and refractory COPD
- Metabolism by the liver cytochrome P450 oxidase system
- Significant risk for drug interactions (e.g., ciprofloxacin, cimetidine) and variable serum concentrations
- Side effects: Drug monitoring is necessary because theophylline has a very low therapeutic index and elimination time varies among individuals.
- Contraindications: damaged cardiac muscle
Long-term oxygen therapy (LTOT) indicated in the case of:
PaO2 ≤ 55 mm Hg or SaO2 ≤ 88 % at rest
- Increases the chance of survival in patients with COPD
- Supplemental O2 can worsen hypercapnia
- The target oxygen saturations is 90–93%.
- PaO2 between 55 and 60 mmHg or SaO2 of 88 % if there is evidence of pulmonary hypertension, congestive cardiac failure, or polycythemia
- PaO2 ≤ 55 mm Hg or SaO2 ≤ 88 % at rest
- Mucolytics (e.g., N-acetylcysteine) liquefy mucus by reducing the disulfide bonds of mucoproteins.
- Surgery may be beneficial in severe cases
- Chronic respiratory failure occurs in the advanced stages of COPD due to progressive emphysematous changes and loss of diffusion surface area.
- Depending on the severity and etiology, treatment includes:
- Long-standing partial respiratory failure (pO2 at rest < 60 mm Hg)
- Global respiratory insufficiency failure (pO2 changes at rest < 60 mm Hg and pCO2 > 45 mm Hg)
Long-term oxygen therapy (LTOT): 16 hours oxygen administration per day (minimum dosage) is associated with lower mortality rates.
- Indication: patients with COPD GOLD D and severe respiratory insufficiency failure that exhibit long-standing pO2 < 55 mm Hg, despite administration of optimal medication
- Principle: A type of non-invasive respiration done overnight when the patient is asleep. This allows recovery of the respiratory muscles and in turn permits better respiratory function during the day.
- Lung volume reduction surgery
- Lung transplantation: It is considered the last resort in patients with emphysema associated with advanced COPD and severe diffusion dysfunction.
- Acute exacerbation: See AECOPD.
- Alveolar hypoventilation → hypoxic pulmonary vasoconstriction → pulmonary hypertension → cor pulmonale (right heart failure)
- Pulmonary cachexia
- Secondary spontaneous pneumothorax due to rupture of bullae (especially in bullous emphysema)
We list the most important complications. The selection is not exhaustive.
- 40–70% of all COPD patients survive the first 5 years after diagnosis
- Survival rates vary significantly depending on the severity of the disease. 
- Measures that improve survival
- Cessation of tobacco use
- Long-term supplemental O2 therapy is the only treatment that improves mortality.