• Clinical science

Chronic obstructive pulmonary disease


Chronic obstructive pulmonary disease (COPD) is a preventable lung disease characterized by airway obstruction due to inflammation of the small airways. It is caused predominantly by inhaled toxins, especially smoking (in 90% of cases), but air pollution and recurrent respiratory infections may also play a role. Some patients are genetically predisposed to COPD, particularly those with α1-antitrypsin deficiency. COPD begins with chronic airway inflammation that usually progresses to emphysema, characterized by irreversible bronchial narrowing and alveolar hyperinflation, which can culminate in the loss of diffusion area. Oxygen absorption and carbon dioxide release become inadequate, leading to hypoxia and hypercapnia. Most patients will present with a combination of dyspnea and chronic cough with expectoration. In later stages, COPD may present 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. Arterial blood gas 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 depends on the GOLD stage but is mainly comprised of short and long-acting bronchodilators (beta agonists and parasympatholytics) and glucocorticoids. In advanced disease, patients often require oxygen supplementation, which is the only treatment that decreases mortality. COPD may cause complications such as pulmonary hypertension or respiratory failure, but the most significant complication is acute exacerbation of COPD (AECOPD).




  • Sex: >
  • The fourth most common cause of death worldwide
  • Prevalence in the USA: 6.3%


Epidemiological data refers to the US, unless otherwise specified.





Airflow limitation in patients with FEV1/FVC < 70%



FEV1 % of the predicted value
GOLD 1 mild ≥ 80%
GOLD 2 moderate 50–79%
GOLD 3 severe 30–49%
GOLD 4 very severe < 30%

Global Initiative for Chronic Obstructive Lung Disease (GOLD)

Patient group Risk Degree of severity Exacerbations/year Symptoms mMRC CAT
A Low risk and less symptomatic GOLD 1/2 ≤ 1 Mild symptoms < 2 < 10
B Low risk and more symptomatic Severe symptoms ≥ 2 ≥ 10
C High risk and less symptomatic GOLD 3/4 ≥ 2 Mild symptoms < 2 < 10
D High risk and more symptomatic Severe symptoms ≥ 2 ≥ 10





Clinical features

  • Main symptoms
    • Chronic cough with expectoration (expectoration typically occurs in the morning)
    • Dyspnea: initially only on exertion, later continuously
  • Other symptoms
    • Cyanosis
    • Tachycardia and tachypnea
    • Weight loss and cachexia
    • In cases of advanced COPD and/or cor pulmonale
      • Congested neck veins
      • Barrel chest
      • Use of accessory respiratory muscles due to diaphragmatic dysfunction
      • Peripheral edema (most often ankle edema)

Nail clubbing is not a typical finding in patients with COPD and its presence usually suggests comorbidities such as bronchiectasis, pulmonary fibrosis, or lung cancer!



Physical examination

  • Percussion
    • Hyperresonant lungs
    • Reduced diaphragmatic excursion
    • Relative cardiac dullness
  • Auscultation
    • Early inspiratory coarse crackles and wheezing
    • Prolonged expiratory phase; and decreased breath sounds: “silent lung” (silent chest) in advanced COPD
    • Heart sounds may be soft and distant.

Pulmonary function tests

Blood gas analysis (BGA) and pulse oximetry

  • Pulse oximetry: to assess O2 saturation
  • BGA: only indicated when O2 is < 92% or if the patient is severely ill
    • ↓ pO2: partial respiratory failure
    • ↓ pO2 and pCO2: global respiratory failure


  • Not required for routine diagnosis!
  • Chest x-ray: not sensitive, especially during early stages
    • Barrel chest
      • Horizontal ribs and widened intercostal spaces
      • Increased anteroposterior diameter
      • The diaphragm is pushed down and flattened.
      • Vertically oriented heart and a long narrow heart shadow
      • Hyperlucency with rarification of pulmonary peripheral vessels
      • Hyperinflated lungs with bullae or subpleural blebs
      • The retrosternal space is increased on lateral view due to emphysematous changes of the lung tissue.
  • CT chest: used to evaluate possible complications or prior to surgery


  • Laboratory studies:
    • α1-antitrypsin levels should be determined in all patients < 50 years of age.
    • ↑ Serum Hct
  • Sputum examination in cases of suspected pulmonary infection
  • Bronchoscopy: to identify the pathogen in severe and acute exacerbation of COPD of infective etiology, especially if antibiotic treatment fails


Differential diagnoses

Asthma COPD
Initial diagnosis

Common in children and teenagers

Common in the 2nd half of life
Etiology Allergic and non-allergic (analgesic-induced, infectious, chemical, or toxic) Primarily affects smokers
Clinical features Episodic: interspersed with symptom-free phases; sudden onset Chronic and progressive; gradual-onset
Obstruction Reversible Irreversible

Effect of medicines

Responds well to long-term inhaled glucocorticoids Responds well to parasympatholytics (e.g., ipratropium bromide)
Diffusion capacity Normal Reduced


The differential diagnoses listed here are not exhaustive.


General considerations

  • Cessation of tobacco use (single most effective step to slow decline in lung function)
  • Vaccinations
  • Pulmonary rehabilitation: physiotherapy with breathing exercises, such as pursed lip breathing
  • Supportive treatment (e.g., postural drainage)
  • Physical activity: maintains endurance and alleviates dyspnea
  • Vitamin D3 and calcium in cases of deficiency

Medical therapy according to GOLD

Severity First-line treatment Alternative treatment Medication as needed
  • No long-term treatment, but is treated when symptomatic
  • Monotherapy as in severity B
  • Short-acting β2-agonist and/or
  • Short-acting parasympatholytics
  • Combination therapy: long-acting parasympatholytics and long-acting β2-agonists
  • Combination therapy: inhaled corticosteroids and long-acting bronchodilator
  • Combination therapy: inhaled corticosteroids, long-acting parasympatholytics and/or long-acting β2-agonists
  • Triple therapy (possibly with PDE-4 inhibitor)
  • Combination therapy with bronchodilators
  • Long-acting parasympatholytics + PDE-4 inhibitor

CAT score refers to COPD assessment test and mMRC is a breathlessness scale

Low risk = FEV1/FVC ratio ≤ 0.7, FEV1≥ 50% predicted, and 0–1 exacerbations in the last year

High risk = FEV1/FVC ratio ≤ 0.7, FEV1 ≤ 50% predicted, and ≥ 2 exacerbations in the last year

Other treatment options

  • Theophylline
    • Mechanism of action: likely nonspecific phosphodiesterase (PDE) inhibition and adenosine receptor blockade
    • Indication: usually only severe and refractory disease
    • Metabolism: by the liver cytochrome P450 oxidase system, significant risk for drug interactions (e.g. ciprofloxacin, cimetidine) and variable serum concentrations
    • Side effects
      • Severe, refractory nausea and vomiting with abdominal pain
      • Tachycardia; that may degenerate into arrhythmias with severe intoxication
      • Central nervous system involvement (tremor; , agitation, insomnia, psychotic symptoms)
      • Hypotension and seizures with severe intoxication
    • Contraindications: damaged cardiac muscle
  • Continuous oxygen therapy: PaO2 ≤ 55 mm Hg or SaO2 ≤ 88 % at rest
    • Increases the chance of survival in patients with COPD
  • Mucolytics (e.g., N-acetylcysteine): liquifies mucus by reducing the disulfide bonds of mucoproteins
  • Surgery: may be beneficial in severe cases
    • Lung resection
    • Lung transplantation



Acute exacerbation of chronic obstructive pulmonary disease (AECOPD)

Since acute exacerbation of COPD is a life-threatening emergency, the patient's condition should be assessed as soon as possible and, if necessary, the patient should be admitted to the intensive care unit.

Chronic respiratory failure

  • Description:
    • 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-term oxygen therapy
      • Use of a portable respirator
      • Lung volume reduction surgery
      • Lung transplantation (only if absolutely necessary)
  • Criteria:
    • Long-standing partial respiratory failure (pO2 at rest < 60 mm Hg)
    • Global respiratory insufficiency failure (pO2 changes at rest < 60 mm Hg plus 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 grade IV and severe respiratory insufficiency failure that exhibit long-standing pO2 < 55 mm Hg, despite administration of optimal medication
      • Oxygen administration is regulated in a way that the pO2 value rises and pCO2 drops to a level of 60–70 mm Hg. Hypercapnia would lead to respiratory acidosis and disorientation and should be prevented.
  • Portable respiration
    • 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
    • Principle: : Surgical or endoscopic removal of severely affected emphysematous areas of the lung. This procedure reduces lung hyperinflation, which improves dyspnea and lung function.
  • Lung transplantation: It is considered the last resort in patients with emphysema associated with advanced COPD and severe diffusion dysfunction.

Other complications


We list the most important complications. The selection is not exhaustive.


  • 5-year survival rate: 40–70%, depending on severity of disease
  • 2-year survival rate: 50% in severe COPD
  • Long-term supplemental O2 therapy:Beneficial especially in COPD patients with resting hypoxemia
  • Cessation of tobacco use improves survival in general.