Acute exacerbation of chronic obstructive pulmonary disease

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Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a clinical diagnosis characterized by worsening respiratory symptoms within a period of 14 days. The most common trigger is a viral upper respiratory tract infection (URTI). Cardinal symptoms of AECOPD are worsening dyspnea, increased frequency and severity of cough, and increased volume and/or purulence of sputum. Testing is aimed at assessing severity, evaluating for underlying triggers, and identifying coexisting conditions (e.g., pneumonia). Respiratory support (e.g., oxygen therapy, noninvasive positive pressure ventilation) may be required to treat hypoxemia and hypercapnia. The mainstays of pharmacological therapy are bronchodilators and systemic glucocorticoids. Antibiotics should be considered in certain patients with cardinal symptoms of AECOPD (especially an increase in the purulence of sputum) and those who require mechanical ventilation.

See also “COPD” and “Ventilation strategy for obstructive lung disease.”

AECOPD is a clinical diagnosis based on the development of cardinal symptoms of AECOPD (e.g., acute worsening dyspnea, increase in the purulence of sputum) over ≤ 14 days. It is often accompanied by tachypnea, tachycardia, and increased local or systemic inflammation. ^[2][3]

• Viral respiratory infections: most common cause of AECOPD ^[2][4]
  • Rhinovirus: most common ^[4]
  • Others: SARS-CoV-2, influenza, RSV, parainfluenza, metapneumovirus, adenovirus
• Bacterial infections: e.g., Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae
  • Risk factors for Pseudomonas aeruginosa infection include: ^[5][6]
    • Advanced COPD
    • Previous hospitalizations
    • Systemic glucocorticoid use
    • Previous isolation of P. aeruginosa
• Additional triggers: drugs (e.g., beta blockers), allergens, air pollution, stress, pulmonary embolism
• Risk factors: previous history of exacerbations, advanced GOLD grade ^[2]

Obtain history of smoking and environmental exposure in all patients with AECOPD. ^[2]

• Cardinal symptoms of AECOPD ^[2]
  • Worsening of dyspnea
  • Increased frequency and severity of cough
  • Increased volume and/or purulence of sputum
• Possible additional symptoms
  • Wheezing, tachypnea
  • Fatigue
  • Fever, chills
• Signs of AECOPD with life-threatening acute respiratory failure ^[2]
  • Severe hypoxemia
  • Increased work of breathing, e.g., use of accessory respiratory muscles, paradoxical breathing
  • Altered mental status

AECOPD is a clinical diagnosis; testing is aimed at assessing severity, identifying triggers, and ruling out complications and/or alternative diagnoses.

Approach

• Obtain pulse oximetry to assess oxygenation.
• Classify AECOPD severity using:
  • Focused clinical evaluation
  • Blood gas analysis
  • CRP level
• Consider chest imaging to rule out pneumonia.
• Obtain microbiological studies to identify triggers.
• Consider additional studies to exclude complications and/or differential diagnoses of AECOPD.

Acute respiratory conditions (e.g., pneumonia, pulmonary embolism) can be a cause, consequence, or comorbidity of AECOPD or may have a similar manifestation. Determining the sequence of symptoms is essential to avoid misdiagnosis.

AECOPD can be life-threatening. Do not delay treatment for testing in patients who present with respiratory failure or signs of respiratory distress.

Initial studies ^[2]

Risk stratification ^[2]

The following tests can help classify AECOPD severity.

• Pulse oximetry: adequate for assessing oxygenation in most patients
• Blood gas analysis
  • ABG: to assess for hypoxemia, hypercapnia, and/or acidemia
    • Baseline elevation in PaCO₂ (chronic hypercapnia) with normal pH is common.
    • A rise of PaCO₂ from baseline, PaCO₂ > 50 mm Hg, or a drop in pH may indicate hypercapnic respiratory failure.
  • VBG is an acceptable alternative to ABG for estimating pH but not for assessing systemic oxygenation.
• Routine laboratory studies: CRP level ≥ 10 mg/L may indicate moderate or severe exacerbation.

Elevated PaCO₂ with a normal pH in patients with known COPD is consistent with chronic CO₂ retention, while elevated PaCO₂ with a low pH suggests acute respiratory failure. ^[7]

Chest imaging ^[8]

• CXR
  • Best initial test to rule out pneumonia
  • Findings
    • See “CXR findings of pneumonia.”
    • May show CXR findings of COPD (e.g., barrel chest)
• Chest CT: may be considered in addition to CXR in certain patients, e.g., those with fever, a history of heart disease, or severe emphysema
• Thoracic ultrasound: may be used to assess for pulmonary edema, pneumothorax, pneumonia, and pleural effusion (see “POCUS in acute heart failure”)

Microbiological studies ^[2]

• Testing for viral URTIs: Choose tests, e.g., nasopharyngeal swab for respiratory viral panel and/or COVID-19 testing, based on local infection patterns. ^[9]
• Sputum Gram stain and culture ^[2]
  • Obtain in patients with any of the following:
    • Need for mechanical ventilation
    • History of frequent exacerbations
    • Severe airflow obstruction (i.e., GOLD grade 3 or 4)
  • May be used to guide antibiotic therapy

Additional studies ^[2]

Obtain additional studies based on clinical suspicion.

• Pulmonary embolus diagnostics, e.g., D-dimer, CTA chest
• Acute heart failure diagnostics, e.g., BNP/NT-proBNP, echocardiography
• Diagnostics for acute coronary syndrome and cardiac arrhythmias, e.g., ECG , troponin ^[10]
• Diagnostics for dyspnea, e.g., CBC to assess for anemia
• Serum vitamin D level: Obtain in all patients hospitalized with AECOPD. ^[2]

Pulmonary function testing is not routinely recommended during acute exacerbations. ^[11]

Most patients with COPD have baseline ECG abnormalities; compare current tracing to prior ECGs to avoid misdiagnosis. ^[10]

In patients presenting with respiratory exacerbation, consider differential diagnoses of AECOPD (e.g., AHF, pulmonary embolism), especially if there are no signs of infection.

See “Classification of stable COPD” for baseline classification.

Classification in primary care settings (Rome proposal) ^[2][3]

Research to validate the thresholds of clinical variables is ongoing. Use clinical judgment when determining the severity of an exacerbation. ^[3]

Classification in hospitalized patients ^[2]

See “Causes of dyspnea” for a more comprehensive list.

• Pulmonary causes of dyspnea
  • Pneumonia
  • Pneumothorax
  • Pulmonary embolism
  • Pleural effusion
• Cardiovascular causes of dyspnea
  • Heart failure
  • Acute coronary syndrome
  • Cardiac arrhythmias

The differential diagnoses listed here are not exhaustive.

Evaluate and treat patients simultaneously while assessing disease severity and the response to stabilization measures. Rapidly identify indications for ICU admission in AECOPD and any patients who require aggressive therapy.

All patients

• Oxygen therapy as needed to maintain SpO₂ 88–92%
• Start pharmacotherapy for AECOPD.
  • Start bronchodilators.
  • Consider systemic glucocorticoids.
  • Consider indications for antibiotic therapy in AECOPD.
  • Provide adjunct pharmacological agents if clinically indicated, e.g., diuretics.
• Consider indications for hospital admission in AECOPD, e.g., insufficient home/community support or severe symptoms.
• Continuously assess treatment response.

Patients with severe AECOPD

• Perform ABCDE survey.
• Maximize pharmacotherapy for AECOPD.
• Assess for signs of impending respiratory failure.
• Obtain serial ABGs.
• If patients have hypercapnia and/or persistent hypoxemia:
  • Titrate oxygen therapy to target SpO₂.
  • Consider a trial of NIPPV or high-flow nasal cannula therapy.
  • Consider indications for intubation in AECOPD.

Intubation in patients with COPD should be a last resort but should not be delayed in patients presenting with severe respiratory distress or who rapidly decline.

Oxygen therapy ^[2]

• Provide supplemental oxygen for patients with hypoxemia.
• Target SpO₂ range: 88–92% ^[2]
• Choose an oxygen delivery device.
  • Venturi mask: generally preferred over standard nasal cannula ^[2]
  • High-flow nasal cannula (HFNC): may improve outcomes in patients with acute hypoxemic respiratory failure
• Check blood gases frequently to ensure appropriate level of oxygenation and monitor for oxygen-induced hypercapnia (CO₂ narcosis).

Oxygen saturation that is too high poses a risk of oxygen-induced hypercapnia.

Noninvasive positive pressure ventilation (NIPPV) ^[2]

NIPPV is the preferred ventilation strategy for improving oxygenation and acidosis in AECOPD with acute respiratory failure.

• Indications for NIPPV in patients with AECOPD ^[2]
  • Respiratory acidosis (PaCO₂ ≥ 45 mm Hg and arterial pH ≤ 7.35)
  • Severe dyspnea with signs of increased work of breathing and/or respiratory muscle fatigue, e.g., use of respiratory accessory muscles
  • Persistent hypoxemia despite supplemental oxygen
• Procedure
  • BiPAP is most commonly used.
  • See “Mechanical ventilation” for contraindications for NIPPV and typical NIPPV settings.

Invasive mechanical ventilation ^[2]

Intubation and mechanical ventilation are especially high-risk and complication-prone procedures in AECOPD and should only be used as a last resort.

• Indications for intubation in AECOPD ^[2]
  • NIPPV is not tolerated or is inadequate, e.g., persistent respiratory acidosis or worsening mental status.
  • Life-threatening hypoxemia
  • Severe hemodynamic instability
    • Shock refractory to fluids and vasopressors
    • After respiratory and/or cardiac arrest
    • Severe cardiac arrhythmias
  • Impaired airway protection, e.g., in patients with:
    • Altered mental status
    • Persistent vomiting
    • Large volume aspiration
  • Persistent inability to clear respiratory secretions
• Important considerations
  • Maximize pharmacotherapy for AECOPD to avoid intubation if possible.
  • Ascertain code status.
  • Initiate countermeasures for high intubation risk before intubation, e.g.:
    • Preoxygenation with NIPPV and/or apneic oxygenation
    • Consider delayed sequence intubation.
    • See “High-risk indications for mechanical ventilation” for further examples of risks and preventive measures.
  • See “Ventilation strategy for obstructive lung disease” for typical ventilator settings.
• Postintubation management
  • Continue aggressive pharmacological treatment during mechanical ventilation.
  • Monitor for complications of mechanical ventilation commonly seen with COPD.

Intubation and mechanical ventilation of patients with AECOPD carry a significant risk of periprocedural cardiac arrest due to rapid oxygen desaturation, dynamic hyperinflation, circulatory shock, and/or severe respiratory acidosis.

Always check for advanced directives and ascertain the patient's code status (e.g., DNI order) prior to intubation.

Bronchodilators for AECOPD ^[2][11][12]

• Indication: : all patients with AECOPD
• Regimens (off-label)
  • SABA monotherapy, e.g., albuterol MDI OR albuterol nebulizer ^{[2][13][14][15]}
  • OR SABA/SAMA combination therapy, e.g., albuterol with ipratropium bromide MDI OR ipratropium nebulizer ^[11][12]
• Routes of administration: MDIs and nebulizers are equally effective for drug delivery. ^[14][16]
  • MDI: fewer adverse effects and less aerosolization of airborne infectious pathogens than nebulizer ^[17]
  • Nebulizer ^[18][19]
    • Consider in patients who are unable to use an MDI.
    • There is a lower risk of O₂-induced hypercapnia with air-driven than oxygen-driven bronchodilators.

Titrate dosage and frequency of medication to clinical effect and follow any local institutional protocols. Some sources recommend dosing SABA as frequently as every 20 minutes during severe AECOPD. ^[2][15]

Glucocorticoids ^[2][20][21]

Consider glucocorticoids in all patients with AECOPD.

• Route of administration
  • Systemic: Oral and IV agents are equally effective but oral agents are preferred. ^[2][21]
  • Inhaled corticosteroids may be considered as an alternative in AECOPD without respiratory failure or in patients for whom a systemic steroid-sparing approach is preferred. ^[22][23]
• Agents ^[2][24]
  • Systemic
    • Prednisone PO ^[2]
    • Methylprednisolone IV or methylprednisolone PO ^[21][23]
  • Inhaled: budesonide nebulizer ^[22]
• Duration: 5 days ^[20][22]

Antibiotics ^[2][20]

There is no consensus on the routine use of antibiotics for the treatment of AECOPD. Some studies have shown an association with faster symptom resolution and a decreased risk of treatment failure. ^[2]

• Indications for empiric antibiotic therapy in AECOPD ^[2]
  • All 3 cardinal symptoms of AECOPD
  • Increased sputum purulence and ≥ 1 other cardinal symptom of AECOPD
  • Use of mechanical ventilation (invasive or noninvasive)
• Route of administration: Oral route is preferred if possible. ^[2]
• Agents
  • Choose based on local resistance patterns for common respiratory pathogens. ^[2][25]
  • Consider empiric antibiotic treatment, e.g.:
    • Amoxicillin/clavulanate
    • Azithromycin
    • Doxycycline
  • For suspected pseudomonal infection , see “Empiric antibiotics for community-acquired pneumonia.”
• Duration: usually 5 days ^[25]

Following clinical stabilization, continue any previously prescribed bronchodilators for COPD maintenance therapy (e.g., long-acting beta-agonists) or start maintenance therapy. ^[2]

Before stabilization ^[2]

• Monitoring
  • Continuous pulse oximetry
  • Serial blood gas monitoring
  • Monitor fluid balance and consider diuretics for fluid overload.
• Manage comorbidities, e.g., heart failure, pulmonary embolism.
• Provide VTE prophylaxis for hospitalized patients. ^[2]
• Supplement vitamin D in patients with confirmed severe vitamin D deficiency (< 10 ng/mL). ^[2]

After stabilization ^[2]

• Initiate or continue nonpharmacological management of COPD, e.g., counseling on smoking cessation.
• Start or continue COPD maintenance therapy.
• Educate patients on proper inhaler technique. ^[26]
  • Describe and demonstrate when prescribing a new inhaler.
  • Identify common errors, e.g., inadequate exhalation prior to inhalation.
• Recommend avoidance of triggers (e.g., beta blockers, indoor air pollution).

Following clinical stabilization, continue any previously prescribed long-acting bronchodilators (i.e., LABA and/or LAMA) or consider starting them as indicated for COPD maintenance therapy. ^[2]

More than 80% of patients with AECOPD are treated as outpatients. ^[2]

Indications for hospital admission in AECOPD ^[2]

• Acute respiratory failure
• Severe symptoms
• New physical examination signs, e.g., cyanosis, edema
• Condition refractory to initial medical treatment
• Significant comorbidity
• Insufficient home/community support system

Indications for ICU admission in AECOPD ^[2]

• Life-threatening acute respiratory failure
  • New-onset confusion, lethargy, or coma
  • Severe hypoxemia (PaO₂ < 40 mm Hg) despite oxygen therapy
  • Severe hypercapnia/respiratory acidosis (pH ≤ 7.25) despite NIPPV
  • Invasive mechanical ventilation is required.
• Severe dyspnea refractory to aggressive medical treatment
• Hemodynamic instability requiring vasopressors

Discharge from hospital settings ^[27]

• Consider discharge following admission or period of ED observation in patients with all of the following:
  • Adequate response to initial treatment
    • Improved symptoms and physical examination
    • Blood gas parameters and FiO₂ requirement are at baseline.
  • No signs of respiratory failure
  • SABA is required less than every 4 hours.
  • No significant active comorbidity
• Consider using objective measures to guide disposition decisions, e.g.:
  • Risk stratification tools: e.g., the Ottawa COPD risk scale ^[28]
  • Ambulation assessment (e.g., 3-minute walk test) to rule out significant deterioration or hypoxemia prior to discharge
• Ensure the following prior to discharge:
  • Patient education
  • Recommended immunizations for COPD are up-to-date.
  • Home care resources and social support are adequate.
  • Arrangements for long-term oxygen therapy are made if indications for home oxygen therapy are present.
  • Outpatient follow-up within one week is scheduled. ^[21][29]

Clinical decision tools ^[30]

The following assessment measures may help to objectively identify patients at risk of poor medical outcomes.

• 3-minute walk test ^[31]
  • Patients undertaking the test are less likely to have a poor clinical outcome if:
    • They can complete a 3-minute walk at their own pace (with aids and/or home oxygen as needed)
    • Highest heart rate is < 120/minute
    • Lowest SpO₂ is ≥ 90%

• Offer supplemental oxygen to maintain target SpO₂ of 88–92%.
• Monitor symptoms and treatment effects.
  • Continuous pulse oximetry
  • Serial blood gas monitoring
• Provide respiratory support as needed.
  • Trial NIPPV before intubation (if applicable).
  • Check for indications for intubation in patients with AECOPD.
• Consider admission to ICU for deteriorating patients.
• Start pharmacological therapy for AECOPD.
  • Start bronchodilators in all patients (SABA with or without SAMA).
  • Consider systemic glucocorticoids.
• Consider indications for antibiotics in AECOPD.
• Identify and treat the underlying cause.
• Provide supportive care.