Acute exacerbation of chronic obstructive pulmonary disease

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Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is defined as the acute worsening of respiratory symptoms in a patient with COPD that necessitates additional therapy. The most common trigger of AECOPD is respiratory viral infection. Cardinal symptoms of AECOPD include worsening of dyspnea, increased frequency and severity of cough, and increased volume and/or purulence of sputum. AECOPD is a clinical diagnosis and the diagnostic workup serves primarily to assess the level of severity and evaluate for any underlying trigger and coexisting comorbidities. Management of AECOPD consists primarily of respiratory support, inhaled bronchodilator therapy, and systemic corticosteroids. Antibiotics should be considered in patients with severe AECOPD and patients who are mechanically ventilated. See also “COPD” and “Mechanical ventilation.”

• Infections
  • Viruses: Most cases of AECOPD are caused by respiratory viral infections. ^[1][2]
    • Rhinovirus: most common ^[1]
    • Others: influenza, RSV, parainfluenza, metapneumovirus, adenovirus
  • Bacterial infections, e.g., Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae
    • Risk factors for Pseudomonas aeruginosa infection include: ^[3][4]
      • Advanced COPD
      • Previous hospitalizations
      • Systemic glucocorticoid use
      • Previous isolation of P. aeruginosa
• Additional triggers: drugs (e.g., beta blockers), allergens, air pollution, stress
• Risk factors: previous exacerbation, advanced COPD stage ^[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
  • Fever, chills
• Signs of severe AECOPD
  • Respiratory failure, severe hypoxemia
  • Signs of increased work of breathing (e.g., accessory muscle use, tripod position)
  • Thoracoabdominal asynchrony
  • Respiratory acidosis
  • Altered mental status
  • Central cyanosis

General principles

• AECOPD is a clinical diagnosis (see “Cardinal symptoms of AECOPD”).
• The goals of diagnostic evaluation are to:
  • Identify triggers and/or complications (e.g., pneumothorax, ARDS)
  • Rule out alternate diagnoses
  • Identify comorbid diagnoses that affect management and/or prognosis (e.g., chronic respiratory acidosis)
  • Risk-stratify the severity of the exacerbation
  • Assess the response to treatment
• Consider empiric bronchodilator therapy if the diagnosis is unclear.

Testing should not delay urgent treatment in patients presenting with signs of respiratory failure or distress if clinical criteria of AECOPD are met.

Laboratory studies ^[2]

• Arterial blood gas: to assess the level of severity
  • Hypercapnia/respiratory acidosis: PaCO₂ and pH values may be variable.
    • Baseline elevations in PaCO₂ with normal pH is common.
    • A rise of PaCO₂ from baseline or a drop in pH is concerning for respiratory failure (see the “Classification” section for interpretation).
  • Hypoxemia: PaO₂ < 80 mm Hg
• Microbiological studies
  • Nasopharyngeal swab for respiratory virus detection (using NAAT) ^[5]
  • Sputum Gram stain and culture are recommended for patients with the following: ^[2]
    • Need for mechanical ventilation
    • Frequent exacerbations
    • Severe airflow limitation (GOLD class III)
• Additional workup for alternate diagnoses and relevant comorbidities: as guided by clinical suspicion
  • CBC
  • D-dimer
  • Troponin
  • BNP/NT-proBNP
  • Vitamin D level: should be checked in all hospitalized patients with AECOPD; < 10 ng/mL corresponds to severe deficiency ^[2]

PaCO₂ on blood gas should be interpreted in relation to the patient's baseline because of chronic CO₂ retention.

Imaging ^[2]

Imaging is not required to confirm the diagnosis but may be used to evaluate for potential triggers (e.g., pneumonia) and/or rule out other causes of dyspnea (see “Differential diagnosis of AECOPD”).

• Chest x-ray
  • See “Diagnosis of COPD” for typical chronic findings (e.g., barrel chest).
  • See “Diagnosis of pneumonia,” “Pulmonary causes of dyspnea,” and “Cardiac causes of dyspnea” for triggers and findings of alternate diagnoses.
• Ultrasound
  • Lung: to assess for pulmonary edema, pneumothorax, pneumonia, pleural effusion
  • Echocardiogram: to assess cardiac function and rule out CHF
  • Lower-extremity Doppler: to rule out VTE
• CTA chest: to rule out pulmonary embolism as directed by pretest probability (see “Wells criteria for PE”)

Additional testing

ECG ^[2]

• To rule out cardiac ischemia (see “ACS”) ^[6]
• To assess for arrhythmia

Pulmonary function testing ^[2]

Spirometry is not routinely recommended in the assessment of AECOPD. ^[7]

• Potential uses include:
  • Confirming the diagnosis for first-time patients (see “Diagnosis of COPD”)
  • Grading the severity of disease for prognostication ^[8]
• Interpretation of changes in FEV1: ^{[9][10][11][12]}
  • Can predict poor outcomes and treatment failure
  • Correlates poorly with the risk of subsequent exacerbations

Advanced testing

• All patients presenting with a new diagnosis of COPD should be screened for alpha 1 antitrypsin deficiency. ^[13]
• Consider bronchoscopy for clinically deteriorating patients with refractory pneumonia. ^[14]

The following system is recommended to classify AECOPD severe enough to require a hospital visit and is based on clinical and laboratory parameters. For baseline classification, see “COPD classification.” ^[2]

• Pneumonia
• Pneumothorax
• Pulmonary embolism
• CHF exacerbation
• Bronchiectasis
• Tuberculosis
• Obliterative bronchiolitis
• Atrial fibrillation/atrial flutter
• See also “Differential diagnosis of dyspnea.”

The differential diagnoses listed here are not exhaustive.

The overarching goal of treatment in AECOPD is to minimize the impact of the current exacerbation and prevent subsequent exacerbations. ^[2]

Approach to the management of AECOPD ^[2]

The ABCDE approach is indicated for all patients with respiratory distress. See “Classification of AECOPD” section for the clinical and laboratory parameters that define the following categories.

• AECOPD with life-threatening acute respiratory failure
  • Immediate assessment and oxygen supplementation
  • Immediate trial of NIPPV
  • Low threshold for intubation and mechanical ventilation
  • Aggressive pharmacological treatment (see “Pharmacological therapy for AECOPD”)
  • ICU admission
• AECOPD with non-life-threatening acute respiratory failure
  • Rapid assessment and oxygen supplementation
  • Consider a trial of NIPPV or HFNC.
  • Aggressive pharmacological treatment (see “Pharmacological therapy for AECOPD”)
  • Inpatient admission
  • ICU consult if the patient deteriorates
• AECOPD without respiratory failure
  • Oxygen supplementation
  • Standard pharmacological treatment (see “Pharmacological therapy for AECOPD”)
  • Decide outpatient vs. inpatient treatment ^[2]

Acute exacerbation of COPD may be a life-threatening emergency. Rapid assessment is recommended to identify patients who require aggressive care and admission to ICU.

Respiratory support

Oxygen therapy

• Supplemental oxygen (see “Oxygen therapy”)
  • Target SpO₂ 88–92%
  • Inappropriate O₂ therapy poses a risk of hypercapnia (CO₂ narcosis; See “O₂-induced hypercapnia”).
• HFNC oxygen therapy: rates up to 60 L/min ^[2]
  • Indicated in AECOPD with hypoxemic respiratory failure
  • An acceptable alternative to NIPPV or oxygen by simple face mask/NRB

Noninvasive positive pressure ventilation (NIPPV)

NIPPV is the recommended first-line ventilatory strategy in AECOPD with acute respiratory failure. NIPPV is associated with a decreased need for intubation, decreased hospital length-of-stay, and lower mortality. ^[2]

• Indications for NIPPV in patients with AECOPD (only one of the following is required): ^[2]
  • P_aCO₂ > 45 mm Hg and arterial pH ≤ 7.35 (i.e., respiratory acidosis)
  • Severe dyspnea with signs of increased work of breathing and/or respiratory muscle fatigue
  • Persistent hypoxemia despite supplemental oxygen
• Procedure
  • BiPAP is most commonly used.
  • See “NIPPV” for details and specific settings.

Invasive mechanical ventilation

Intubation and mechanical ventilation are especially high-risk and complication-prone procedures in AECOPD, and they are generally used as a last resort (see “High-risk indications for mechanical ventilation”). ^[15][16]

• Indications for intubation in patients with AECOPD ^[2]
  • Respiratory failure
    • Life-threatening hypoxemia
    • NIPPV intolerance or failure
    • Respiratory or cardiac arrest
  • Airway protection
    • Altered mental status
    • Persistent vomiting
    • Large aspiration
  • Pulmonary hygiene: persistent inability to clear respiratory secretions
  • Hemodynamic instability
    • Shock refractory to fluids and vasopressors
    • Severe cardiac arrhythmias
• Procedure: See “High-risk indications for mechanical ventilation” and “Ventilation strategy for obstructive lung disease.”
• 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 carries a significant risk of periprocedural cardiac arrest due to rapid oxygen desaturation, dynamic hyperinflation, circulatory shock, and/or severe respiratory acidosis! Countermeasures should be taken prior to performing these procedures (see “High-risk indications for mechanical ventilation”).

Pharmacological therapy for AECOPD ^{[2][17][18][19]}

Overview

The following are suggested pharmacological treatment combinations based on symptom severity.

• AECOPD without respiratory failure: standard pharmacological treatment
  • Bronchodilators: standard-dose inhaled SABA
  • Systemic corticosteroids ^[19]
  • Consider antibiotics if indicated.
  • Consider adjunctive treatment.
• AECOPD with respiratory failure (non-life-threatening or life-threatening): aggressive pharmacological treatment
  • Bronchodilators: high-dose inhaled SABA PLUS SAMA
  • Systemic corticosteroids
  • Oral or IV antibiotics
  • Adjunctive treatment

Bronchodilators

• Beta agonists
  • Inhaled SABAs (e.g., albuterol, levalbuterol): mainstay of treatment due to their rapid bronchodilator effect
    • High-dose inhaled SABA
      • Albuterol MDI ^[2]
      • OR albuterol nebulizer ^[2][20]
      • Patients with a good clinical response to a trial of high-dose inhaled SABAs may be transitioned to the standard dose if they remain stable.
    • Standard dose inhaled SABA: albuterol MDI
    • Route of application: There is no difference in effectiveness between MDIs and nebulizers. ^[2][20][21]
      • Consider a nebulizer in patients who are sicker, i.e., unable to effectively use an inhaler.
      • MDI is associated with decreased adverse effects and less aerosolization of airborne infectious pathogens. ^[22]
  • Inhaled LABA (with or without combination inhaled corticosteroid) should be either continued if it has been part of the patient's chronic therapy or started just prior to discharge. ^[2]
• Anticholinergics: inhaled SAMA (e.g., ipratropium bromide; nebulizer , ipratropium bromide inhaler )
• Combined therapy: ipratropium bromide/albuterol sulfate nebulizer

Corticosteroids

• Systemic glucocorticoids
  • Indications: Consider in all patients with AECOPD. ^[2]
  • Commonly used regimens: ^[2][23]
    • Prednisone (oral) ^[2]
    • Methylprednisolone (oral) ^[18]
    • Methylprednisolone (IV) ^[18][24]
  • Considerations
    • Oral agents are equally as effective as IV agents. ^[2][18]
    • A 5-day course is usually sufficient for most patients but some patients may benefit from a longer course and/or a steroid taper. ^[19]
• Inhaled corticosteroids
  • Indications: Consider as an alternative to systemic corticosteroids in AECOPD without respiratory failure or in patients in whom a systemic steroid-sparing approach is desired. ^[19][24]
  • Suggested regimen: budesonide ^[19]

Antibiotics ^[2]

The routine use of antibiotics in AECOPD is controversial, but antibiotics are associated with enhanced symptom resolution and a lower risk of treatment failure in patients with moderate to severe AECOPD. ^[2]

• Indications for empiric antibiotic therapy in AECOPD (presence of any of the following) ^[2]
  • ≥ 3 cardinal symptoms of AECOPD
  • ≥ 2 cardinal symptoms of AECOPD if there is increased sputum purulence
  • Mechanical ventilation is required.
• Recommended regimen
  • See “Empiric antibiotic therapy for community-acquired pneumonia” and “Empiric antibiotic therapy for hospital-acquired pneumonia.”
  • Commonly used agents ^[2]
    • Aminopenicillin with clavulanic acid (e.g., amoxicillin-clavulanic acid )
    • Macrolide (e.g., azithromycin )
    • Tetracycline (e.g., doxycycline )
  • In suspected Pseudomonas aeruginosa infection , see “Empiric antibiotic therapy for community-acquired pneumonia in an inpatient setting.”
• Duration of treatment
  • A 5–7 day course is recommended for inpatients and outpatients.
  • Improved sputum purulence and dyspnea are markers of effectiveness.

Adjunctive treatment and supportive care ^[2]

• Smoking cessation and counseling
• Supplement vitamin D for confirmed deficiency. ^[2]
• Diuretics for fluid overload
• VTE prophylaxis
• Nutritional support
• Treatment of associated comorbidities (e.g., ACS, heart failure, pulmonary embolism)
• Isolation precautions to prevent transmission of suspected respiratory pathogens

Monitoring

• Symptom surveillance and severity assessment, as clinically indicated
• Continuous pulse oximetry
• Serial blood gas monitoring

Indications for hospital admission ^[2]

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

Indications for ICU admission ^[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

Clinical decision tools ^[25]

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

• 3-minute walk test ^[26]
  • 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%

Respiratory support

• Supplemental oxygen to maintain target SpO₂ 88–92%
• Continuous pulse oximetry
• Serial blood gas monitoring
• Trial NIPPV before intubation (if applicable).
• Evaluate for indications for intubation in patients with AECOPD.
• Consider admission to ICU for deteriorating patients.

Medical therapy

• Start pharmacological therapy for AECOPD.
  • Inhaled SABA
  • Consider addition of an anticholinergic agent
  • Systemic corticosteroids
• Consider indications for empiric antibiotic therapy in AECOPD.
• Identify and treat the underlying cause.
• Provide supportive care.