Chronic Obstructive Pulmonary Disease (COPD)

Overview

Definition

Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by airflow limitation resulting from airway disease and/or parenchymal destruction.

Types

The subtypes may have differing presentations and response to therapy. Patients may have any combination of both.

• Chronic bronchitis: 
  • Clinically defined
  • Productive cough > 3 months per year for at least 2 consecutive years 
  • Must be in the absence of other causes of chronic cough
• Emphysema: 
  • Pathologically or radiologically defined 
  • Destruction and permanent dilation of alveolar sacs

Epidemiology

• Worldwide: 
  • Prevalence: 11.7% (expected to rise)
  • Annual deaths: 3 million 
  • 4th leading cause of death (soon to be 3rd)
• In the United States:
  • Prevalence: 16 million people
  • Annual deaths: > 140,000
  • 3rd leading cause of death
• Age:
  • Prevalence peaks around 50–60 years of age 
  • Age of onset is lower for heavy smokers.
• Sex:
  • More prevalent in men
  • Rates in women are rising.
  • Mortality rate equal among men and women

Etiology

• Cigarette smoking (90% of cases)
• 2nd-hand smoke
• Air pollution 
• Occupational exposure to toxins 
• Alpha-1 antitrypsin (AAT) deficiency

Risk factors

• Premature birth
• Low body weight
• Lower socioeconomic status
• Poor nutrition
• Childhood respiratory disorders
• Preexisting airway reactivity

Pathophysiology

Chronic bronchitis

Inhaled agents cause chronic inflammation in the airways, which lead to progressive airway obstruction through:

• Damage to endothelial cells → ↓ mucocilliary clearance
• Mucous gland hyperplasia → mucous hypersecretion and plugging
• Airway edema and smooth muscle hyperplasia → luminal narrowing
• Peribronchial fibrosis → bronchial distortion

Emphysema

In normal lungs, there is a balance between:

• Proteases → break down elastin and connective tissue as part of normal tissue repair:
  • Neutrophil elastase
  • Matrix metalloproteinase (MMP)
  • Cathepsins
• Antiproteases → balance protease activity:
  • AAT
  • Secretory leukoprotease inhibitor derived from airway epithelium
  • Elafin
  • MMP tissue inhibitor

In emphysema:

• Inflammatory response → activated neutrophils release proteases
• Protease activity exceeds antiprotease activity → tissue destruction
• Alveolar destruction leads to:
  • Enlarged alveoli
  • ↓ Elastic recoil
  • ↑ Compliance
• Consequences:
  • Airway closure during expiration → obstruction
  • Air trapping → lung hyperinflation

Morphologic patterns:

• Centriacinar emphysema (associated with cigarette smoking):
  • Destruction of the respiratory bronchioles and a central portion of the acini
  • More severe in the apical lung fields
• Panacinar emphysema (associated with AAT deficiency):
  • Destruction of all parts of the acinus
  • More severe in the basal lung fields

Effects of the pulmonary vasculature

• Tissue destruction → ↓ ability to oxygenate blood
• Hypoxemia → vasoconstriction in small pulmonary arteries → ↑ vascular resistance
• Chronic hypoxemia → vascular remodeling → irreversible pulmonary hypertension

Clinical Presentation

Symptoms

Patients suffer from chronic, progressive symptoms with acute exacerbations.

General:

• Progressive dyspnea (particularly with exertion)
• Chronic cough
• Sputum production
• Chest tightness
• Weight gain or loss
• Fatigue

Acute exacerbation:

• Worsening dyspnea
• Increased cough 
• Purulent sputum production
• Wheezing
• Fever may or may not be present.

Physical examination

When examining a patient with possible COPD, look for the following findings:

Vitals:

• Tachypnea
• Hypoxia

General:

• Muscle wasting
• Barrel chest: increased anteroposterior chest wall diameter from hyperinflation

Pulmonary:

• Visual:
  • Respiratory distress (acute exacerbations)
  • Accessory muscle use
  • Pursed lip breathing
• Auscultation:
  • Prolonged expiration
  • Wheezing
  • Diminished breath sounds
• Palpation and percussion:
  • Hyperresonance on percussion
  • Reduced chest wall expansion

Extremities:

• Digital clubbing
• Cyanosis

Findings suggestive of cor pulmonale:

• Jugular venous distension
• Peripheral edema

Clinical phenotypes

Signs and symptoms are associated more frequently with either chronic bronchitis or emphysema. However, patients often present with a mixture of features.

Chronic bronchitis (“blue bloater”):

• Patients are generally overweight.
• Frequent, productive cough
• Peripheral edema
• Cyanosis

Emphysema (“pink puffer”):

• Patients are generally thin.
• Barrel chest
• Infrequent cough
• Pursed lip breathing
• Accessory muscle use
• Tripod positioning
• Hyperresonant chest

Diagnosis

Pulmonary function tests

Pulmonary function tests are used to confirm COPD diagnosis. Testing is indicative of obstruction, which is largely irreversible.

Spirometry:

• ↓ Forced expiratory volume in 1 second (FEV₁): maximum volume of air forcefully expired 1 second after maximal inspiration
• ↓ Forced vital capacity (FVC): maximum volume of air forcefully expired after maximal inspiration
• Greater loss of FEV₁ than FVC → ↓ FEV₁/FVC ratio:
  • FEV₁/FVC: < 70%
  • FEV₁/FVC: < 50% indicates severe disease.
• ↑ Residual volume and total lung capacity (air trapping)
• Emphysema:
  • ↓ Diffusing capacity for CO: 
    • Also known as transfer factor
    • Due to loss of surface area for gas exchange
  • Rapid fall in expiratory flow (dynamic airway collapse) → produces a concave pattern

Post-bronchodilator test: 

• Used to assess the reversibility of the obstructive condition
• Minimal reversibility in COPD

Staging

In addition to COPD diagnosis, spirometry results may be used in conjunction with symptoms to help stage severity. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria are as follows:

Supporting evaluation

Laboratory studies:

• Arterial blood gas (ABG):
  • Hypoxemia:
    • Progressive
    • Often worse during acute exacerbation
  • Hypercapnia:
    • Develops as FEV₁ falls
    • pH is usually near normal due to renal compensation (↑ serum HCO₃)
• ↑ BNP in cor pulmonale
• AAT testing: Consider if COPD symptoms are present (not in typical demographic):
  • Younger
  • Nonsmoker
  • Concomitant, unexplained liver disease

Chest X-ray:

• Barrel-shaped chest 
• Wide intercostal spaces
• Horizontal ribs 
• Flattened, low diaphragm 
• Hyperlucency
• Attenuated peripheral vascular markings (due to parenchymal destruction)

Management and Complications

Principles

• Improve symptoms.
• Decrease exacerbations.
• Improve patient function.
• Improve quality of life.

General management

• Smoking cessation (critical in slowing lung function decline)
• Vaccinations for:
  • Pneumococcal pneumonia
  • Influenza
• Pulmonary rehabilitation:
  • Guided exercise and behavioral interventions
  • Goal is to improve functional capacity.
• O₂ therapy:
  • If O₂ saturation is < 88% in a stable patient (PO₂ < 55 mm Hg)
  • If concurrent pulmonary hypertension, right-sided heart failure, or polycythemia

Medical therapy

• Bronchodilators: 
  • Short acting (used as needed for rescue):
    • Beta-2 adrenergic agonists (e.g., albuterol)
    • Anticholinergics (e.g., ipratropium bromide)
  • Long acting:
    • Beta-2 adrenergic agonists (e.g., salmeterol, formoterol, indacaterol)
    • Anticholinergics (e.g., tiotropium, aclidinium, umeclidinium)
• Phosphodiesterase-4 inhibitors: 
  • Option: roflumilast
  • Reduces inflammation
  • Can increase FEV₁ and reduce exacerbations
• Inhaled corticosteroids: 
  • Options: budesonide, fluticasone
  • Can produce both marginal improvements and adverse effects
• Theophylline (oral bronchodilator)
• Mucolytics

Surgical intervention

Surgery is reserved for severe cases not controlled with medical therapy to improve quality of life.

• Bullectomy: removal of giant bullae to relieve local compression
• Lung volume reduction: resection of the most diseased parts of the lung to decrease hyperinflation
• Lung transplant: indicated in end-stage lung disease

Management of acute exacerbations

• Outpatient or inpatient therapy depending upon severity
• Short-acting bronchodilators:
  • Scheduled every 4–6 hours
  • Continuous nebulization may be needed for severe bronchospasm.
• Systemic steroids
• Antibiotics are indicated for:
  • Purulent sputum
  • Evidence of pneumonia
  • Patients requiring hospitalization
• Controlled O₂ therapy for acute respiratory failure:
  • Nasal cannula
  • Noninvasive ventilation:
    • Hypercapnia and hypoxemia
    • Significant effort to breathe
  • Invasive ventilation:
    • Severe respiratory failure
    • May be difficult to wean patients with severe COPD

Complications

• Respiratory failure
• Respiratory infections (pneumonia)
• Pulmonary hypertension → cor pulmonale
• Long-term complications of steroids → osteoporosis
• Weight loss or cachexia
• Bullae rupture → secondary spontaneous pneumothorax

Differential Diagnosis

• Asthma: a chronic, inflammatory condition characterized by reversible airflow obstruction in the lower airways. Patients present with intermittent or persistent wheezing, cough, and dyspnea. Diagnosis is usually confirmed with a pulmonary function test showing a reversible, obstructive pattern. Management varies based on severity and includes bronchodilators and inhaled corticosteroids for inflammation control.
• Bronchiectasis: a chronic condition with bronchial dilation and destruction as a result of inflammation and infection. Symptoms include dyspnea, chronic cough, and purulent sputum. The diagnosis is made with imaging (X-ray and CT). Management includes bronchodilators and antibiotics for acute exacerbations.
• Bronchiolitis obliterans: a chronic, obstructive disease of the small airways usually caused by repeated cycles of inflammation and scarring. Patients present with cough and persistent, progressive dyspnea. Pulmonary function tests are used for diagnosis. Management includes steroids and bronchodilators.
• Heart failure: an inability to produce normal cardiac output to meet metabolic needs. Patients present with dyspnea, hypoxia, and peripheral edema. BNP will be elevated and pulmonary edema may be seen on X-ray. Echocardiography confirms the diagnosis. Management relies on diuresis and medical optimization of cardiac function with beta blockers and ACE inhibitors.
• Cystic fibrosis: an autosomal recessive disorder leading to dysfunction of chloride channels, which results in hyperviscous mucus and the accumulation of secretions. Patients often have chronic respiratory infections, failure to thrive, and pancreatic insufficiency. The gold standard for diagnosis is the sweat chloride test, which can be complemented by genetic testing. Management includes cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy and system-specific strategies for supportive care. 
• Pulmonary embolism: obstruction of the pulmonary arteries most often due to thrombus migration from the deep venous system. Signs and symptoms include pleuritic chest pain, dyspnea, tachypnea, and tachycardia. Severe cases can result in hemodynamic instability or cardiopulmonary arrest. Chest CTA is the primary method of diagnosis. Management includes oxygenation, anticoagulation, and thrombolytic therapy for unstable patients.