SUMMARY: 

COPD characterized by the cardinal symptoms of increased dyspnea, cough, and sputum purulence or production/volume. Classification is via Gold’s Classification (see Diagnosis and Management of Stable COPD in ‘Related Topics’ below). Exacerbations involve increased airway inflammation, increased mucus production and increased gas trapping. They are commonly precipitated by respiratory tract infections, although there can be many triggers. Exacerbations contribute to disease progression and are associated with increased mortality and morbidity.

Symptoms

• Cardinal symptoms of COPD
  • Persistent dyspnea
  • Chronic cough (+/-wheeze)
  • Sputum production
• Exacerbation is seen in those with history of COPD with acute worsening of the following symptoms over < 14 days
  • Dyspnea
  • Sputum purulence
  • Sputum production/volume
  • Cough
  • Wheezing

Risk Factors

• Diagnosis of COPD with previous exacerbations
• Occupational and indoor air pollution
• Infections
• Tobacco smoke
• Medication nonadherence
• Presence of one or more comorbidity
• Vitamin D deficiency
  • It is recommended that all patients hospitalized for exacerbations should be tested for vitamin D deficiency and supplemented as needed 
• Greater percentage of emphysema or airway wall thickness measured by CT chest
• Presence of chronic bronchitis

Differential Diagnosis

• Pneumonia
  • Hypoxemia | Shortness of breath | Fever | Cough | Leukocytosis | Elevated inflammatory markers
• Pneumothorax
  • Worsening dyspnea | Pleuritic chest pain | Diminished breath sounds | Can be seen on chest x-ray or ultrasound
• Pulmonary Embolism
  • Sudden onset pleuritic chest pain | Tachycardia | Tachypnea | Hypoxia | Shortness of breath | Elevated D-dimer | Shown on CTA
• Pulmonary Edema secondary to acute decompensated heart failure
  • History of cardiac disease (not always)| Dyspnea | Pink frothy sputum with cough | Crackles on exam | Elevated BNP | Echocardiogram is helpful in evaluation | Chest x ray may show cardiomegaly and pleural effusions
• Cardiac arrythmia or myocardial infarction
  • Atrial fibrillation (A Fib) and atrial flutter can oftentimes cause shortness of breath | A Fib can oftentimes trigger COPD exacerbation or be a consequence of it | Evaluate with EKG | Troponin

Treatment

Determine if Patient Can Be Treated Outpatient or Requires Hospitalization

• Outpatient criteria includes: Mild disease to moderate disease | One of three cardinal symptoms | Not meeting criteria for inpatient hospitalization
• Inpatient criteria includes
  • Severe symptoms: Use of accessory respiratory muscles | Acute changes in mental status
  • Hypoxemia not improved with supplemental oxygen
  • PaCO2 >60mm Hg
  • Acute respiratory failure with RR >30 breaths per minute
  • Cyanosis | New peripheral edema
  • Failure to respond to initial management
  • Presence of serious co-morbidities (e.g., Heart failure | New arrhythmia)
  • Insufficient home support

Initial Bronchodilators for Every Patient

• Short acting inhaled beta-2 agonists (SABA) preferred via metered dose inhaler (preferred due to quick onset of action)
• 1 to 2 puffs every 1 hour for 2 or 3 doses then every 2 to 4 hours depending on patient’s response

Muscarinic Antagonists

• Ipratropium bromide, a short acting muscarinic antagonist, often used in combination with SABA: 2 inhalations by MDI every 4 to 6 hours
• Combination ipratropium-albuterol inhaler hand-held inhaler (HHN): Preferred in inpatient treatment 1 inhalation, every hour for 2 to 3 doses and then every 2 to 4 hours as needed guided by the response to therapy

Systemic Corticosteroids

• Improve FEV1, oxygenation and shorten recovery and hospitalization time
• Pulmonary rehabilitations (breathing exercises), nutritional and psychologic support
• 40 mg of prednisone for 5 days
  • Longer courses of steroids associated with increased risk of pneumonia and mortality 
  • Outpatient: Recommended only in those who present with breathlessness that affect daily activities
  •  Inpatient: Always get a course of systemic steroids

Note: European Respiratory Society/American Thoracic Society suggest a course of oral corticosteroids for 9–14 days in outpatients with COPD exacerbations in contrast to the GOLD guidelines 

Antibiotics

• Consider antibiotics if
  • Evidence of bacterial infection is present
  • Presence of three cardinal symptoms
  • At least two cardinal symptoms present with one being increased sputum purulence
  • Severely ill patients such as those who require mechanical ventilation
  • Procalcitonin is not recommended in antibiotic decision making  
• Patients with recurrent exacerbations should get sputum culture to guide antibiotic treatment
• Duration 5 to 7 days for hospitalized patients | No more than 5 days for outpatients
• First line
  • A 875/125mg BID
  • Second or third generation cephalosporins (e.g., Ceftriaxone, cefdinir)
  • Azithromcyin 500mg Day 1 followed by 250mg daily for 4 days 
  • Use of tetracyclines is recommended by GOLD guidelines, though a recent study has shown no benefit from Doxycycline use (see primary sources below) 
• Community resistance patterns should be taken into account

Magnesium 

• Magnesium sulfate infusion historically has been used for acute asthma exacerbations, but a recent study demonstrated benefit for acute COPD exacerbations 
• For patients with severe COPD exacerbation not improving with standard bronchodilator therapy give 2g IV Magnesium sulfate over 20 minutes   

Additional Inpatient Treatment Considerations

• Maintenance therapy
  • Initiate long-acting bronchodilators once patient is stable
  • Continue maintenance therapy through exacerbation
  • While hospitalized, initiate a home therapy regimen as soon possible to assess response

Complications of Recurrent COPD Exacerbations

• Increased mortality and morbidity
• Hospitalization
• Intubation
• Secondary lung infections

Prevention

• Smoking cessation
• Ensure vaccines up to date, including influenza, Covid-19, Tdap, and pneumococcal vaccines
• Maintenance bronchodilators
• Pulmonary rehab referral within 4 weeks of hospital discharge 
• Consider prophylactic antibiotics if a patient is prone to exacerbations after risk-benefit discussion including drug resistance and side effects such as GI upset
  • Azithromycin 250mg per day or 500mg three times a week
  • Erythromycin 250mg BID

Primary Sources – Learn More:

GLOBAL STRATEGY FOR PREVENTION, DIAGNOSIS AND MANAGEMENT OF COPD: 2023 Report 

Magnesium sulfate for acute exacerbations of chronic obstructive pulmonary disease 

Management of COPD exacerbations: a European Respiratory Society/American Thoracic Society guideline 

Doxycycline for outpatient-treated acute exacerbations of COPD: a randomised double-blind placebo-controlled trial 

Related ObG Topics:

Diagnosis and Management of Stable COPD

ACP Guidelines: Best Practices for Use of Short-Duration Antibiotics for Common Infections