Acute Exacerbation of COPD

Background

• Acute exacerbation of COPD is characterized by increased dyspnea and/or cough and sputum production that worsens in < 14 days, may be accompanied by tachypnea or tachycardia, and is often associated with increased inflammation due to infection, pollution, or other airway insult.
• Exacerbations are commonly caused by viral or bacterial infections (most commonly the human rhinovirus [common cold], influenza, para-influenza, and metapneumovirus); other triggers include exposure to pollution (for example tobacco smoke, ozone, or occupational exposures) or ambient temperature changes.
• In-hospital mortality for patients with COPD exacerbations is around 2.5% in general; all-cause mortality within 5 years of hospitalization may be as high as 50%.
• Prevention of acute exacerbations includes complete smoking cessation, appropriate vaccinations (pneumococcal, influenza, COVID-19, pertussis, and shingles immunizations), and review of adherence to medications including proper inhaler technique and adherence to supplemental oxygen therapy. Shielding measures such as mask wearing, minimizing social contact (but not leading to social isolation), and frequent handwashing during winter months in patients at risk of exacerbation may also be helpful.

Evaluation

• A diagnosis is made based on clinical findings of an acute change in symptoms beyond normal daily variation.
• Ask about risk factors such as exacerbation history (particularly in past year), noncompliance with supplemental oxygen and/or inhaler regimen, chronic bronchitis, infections, and exposure to environmental pollution.
• Features suggesting severe exacerbation include the use of accessory respiratory muscles, paradoxical chest wall movement, new or worsening central cyanosis, peripheral edema, hemodynamic instability, signs of right heart failure, and reduced alertness.
• Tests to help identify cause and severity of exacerbation and to identify alternative pulmonary and cardiac diagnoses include:
  • complete blood count looking for leukocytosis
  • metabolic panel for electrolyte or glucose abnormalities
  • chest x-ray to rule out new infiltrate
  • electrocardiogram (ECG) for detecting ongoing ischemia
  • n-terminal Pro-Brain Natriuretic Peptide (Pro-BNP) or brain natriuretic peptide (BNP) to help differentiate heart failure from COPD exacerbation

Management

Site of Care

• Use hospital-at-home care (home visits by respiratory clinicians) for patients with COPD exacerbations without acidotic respiratory failure (Strong recommendation).
  • Hospital-at-home care reduces hospital readmission compared to standard hospital care in eligible patients with COPD exacerbation.
  • Hospital admission is indicated if there are severe symptoms or signs, considerable comorbidities, or there is inadequate home support.
• Intensive care unit admission is indicated if the patient has:
  • severe dyspnea that is unresponsive to initial emergency treatment
  • changes in mental status, such as confusion, lethargy, or coma
  • persistent or worsening respiratory status with hypoxemia (partial pressure of arterial oxygen [PaO₂] < 5.3 kilopascal [kPa] or 40 mm Hg) and/or respiratory acidosis (pH < 7.25)
  • need for mechanical ventilation
  • hemodynamic instability with need for vasopressors

Medications

• In all patients:
  • Use short-acting beta-2 agonists (SABAs) with or without anticholinergics as the preferred initial bronchodilators.
  • Use corticosteroids (oral or IV), such as prednisolone 40 mg/day orally for 5-14 days, to shorten recovery time and improve lung function and hypoxemia.
• Use antibiotics in selected patients.
  • Give antibiotics to patients who are in intensive care or hospitalized with severe COPD exacerbations, when indicated, where they reduce treatment failure and mortality.
  • Give antibiotics for 5 days in COPD patients with purulent sputum and 1 or more of the following symptoms: increased dyspnea or sputum production.
  • Select antibiotics based on the local bacterial resistance pattern; initial treatment is typically an aminopenicillin with clavulanic acid, a macrolide, or a tetracycline.
  • Procalcitonin is a potential marker for infection but is not suggested for use in guiding therapy decisions in acute exacerbations of COPD.
  • Commonly used selected antibiotics include:
    • amoxicillin-clavulanate 875 mg orally twice daily or 500 mg orally 3 times daily
    • levofloxacin 500 mg orally or IV once daily
    • azithromycin 500 mg orally once daily for 3 days, or 500 mg once on day 1 then 250 mg once daily on days 2-5 or azithromycin 500 mg IV for at least 2 days, followed by 500 mg orally once daily to complete 7-10 day course
    • doxycycline 100 mg orally twice daily or 200 mg on day 1, then 100 to 200 mg/day IV for at least 24-48 hours after symptoms and fever have subsided
    • clarithromycin extended-release tablets (Biaxin XL) 1 g (2 tablets) orally once daily with food for 7 days, or conventional clarithromycin (Biaxin) 500 mg orally every 12 hours
    • moxifloxacin (Avelox) 400 mg orally or IV once daily for 5 days (reserve for patients without alternative options)
• Vitamin D supplementation is recommended in patients hospitalized for exacerbation who have severe deficiency (< 10 ng/mL [< 25 nmol/L]).

Additional Treatment Measures

• Titrate oxygen to improve hypoxemia.
• Implementation of airway clearance techniques may reduce the need for additional ventilatory assistance.
• Initiate noninvasive positive pressure ventilation (NPPV) in patients partial pressure of with arterial carbon dioxide (PaCO₂) ≥ 6-6.5 kPa (45-48.8 mm Hg) on arterial blood gas, respiratory acidosis (pH ≤ 7.35), severe dyspnea with accessory muscle use and paradoxical abdominal movement, and respiratory rate > 24 breaths/minute (Strong recommendation).
• In hospitalized patients, at all times monitor fluid balance, administer thromboembolism prophylaxis, and identify and treat associated conditions such as heart failure, arrhythmias, or pulmonary embolism. Adjunctive therapies that may be appropriate (based on individual patient) include:
  • diuretics
  • anticoagulants
  • nutritional support or interventions
  • comorbidity treatments
  • thromboembolism prophylaxis (appropriate in all hospitalized patients with COPD due to increased risk of deep vein thrombosis and pulmonary embolism)
  • smoking cessation
  • lung volume reduction
• Follow up at 1-4 weeks and again after 12-16 weeks.
• Consider pulmonary rehabilitation after acute exacerbation of COPD which may reduce mortality and readmission risk.
• Prevention of exacerbations may include medications such as:
  • long-acting inhaled bronchodilators
  • inhaled corticosteroids
  • phosphodiesterase-4 (PDE4) inhibitors, such as roflumilast (most effective in patients with prominent chronic bronchitis component to their COPD)
  • immunizations (such as pneumococcal, influenza, COVID-19, and tetanus, diphtheria, and acellular pertussis vaccination)
  • prophylactic antibiotics
  • oral mucolytics
• Consider intensification of combination inhalers after acute exacerbation requiring hospitalization.