Pulmonary

COPD Exacerbation: From Diagnosis to Treatment

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