Topic Editor: Grant E. Fraser, M.D., FRACGP, FACRRM, ASTEM

Review Date: 3/10/2013

Definition

Exacerbation of Chronic Obstructive Pulmonary Disease (COPD) is a sustained worsening of symptoms beyond normal variations. It is most commonly due to a respiratory infective cause, is acute in onset, often involves hyperinflation, increased respiratory secretions, and increased airway inflammation. In some patients with advanced COPD, an exacerbation can progress to respiratory failure.

Description

• COPD exacerbation is an acute worsening of respiratory symptoms that leads to considerable morbidity and mortality, along with impacting health-related quality of life
• The overall health care burden of COPD is most significantly impacted by the number and severity of COPD exacerbations
• COPD exacerbations are most commonly triggered by bacterial and/or viral respiratory infections, however, environmental pollution amplifies inflammation of the lower respiratory tract leading to tissue damage and worsening symptoms
• COPD Exacerbations can be classified into 3 Types:
• Type 1: All 3 of the following are present
• An increase in sputum volume
• An increase in sputum purulence
• An increase in dyspnea
• Type 2: Any 2 of the following 3 are present
• An increase in sputum volume
• An increase in sputum purulence
• An increase in dyspnea
• Type 3: Any 1 of the following Symptoms, plus at least one minor symptom
• An increase in sputum volume
• An increase in sputum purulence
• An increase in dyspnea
• Minor symptoms include: Fever without another cause, increased wheezing, increased cough, increased respiratory rate of >20% above baseline, or increased heart rate >20% above baseline
• Early diagnosis and treatment of exacerbations improve the patient's quality of life and reduces morbidity and mortality

Epidemiology

Incidence/Prevalence

• COPD was the third leading cause of death in the U.S. in 2008, and was the underlying cause of approximately one in 20 deaths
• In the U.S., approximately 500,000 hospitalizations per year are due to exacerbations
• The estimated inpatient mortality due to COPD exacerbation ranges widely from 4-30% depending upon the subgroup studied and other factors
• The prevalence of COPD is increasing worldwide, and is estimated to become the third leading cause of death by 2020, attributable in part to the increasing use of tobacco
• The frequency of exacerbations is generally 2.5–3/year, however, more exacerbations are typical in those with severe COPD

Age

• The incidence of COPD is higher in people >40 years of age and increases steeply with age, with the highest prevalence in those aged 60 years

Gender

• Studies have historically shown a male>female prevalence of COPD, however, recent data from developed countries indicate similar COPD prevalence between genders
• Men are at higher risk for mortality in COPD exacerbation

Risk Factors

• Chronic hypersecretion of mucous
• Exposure to pollutants
• Infections (particularly respiratory)
• Low body mass index
• Older age
• Poor exercise capacity
• Poor health status
• Previous hospitalization for COPD exacerbation
• Pulmonary hypertension
• Tobacco smoking (continuing to smoke despite having COPD)

Etiology

• COPD exacerbation may be precipitated by a multiplicity of factors; however, the most common is a respiratory tract infection
• The interaction between the host, bacteria, viruses, and environmental pollution amplifies inflammation of the lower respiratory tract leading to tissue damage and thus exacerbating symptoms
• Infectious etiology:
• Bacterial infection: Bronchoscopic studies have shown that50% of exacerbations are due to bacterial infection. The most common causes are: Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus parainfluenzae, and Pseudomonas aeruginosa
• Viral infection: Cell culture and serological studies suggest that 20% of exacerbations are due to viral infections. The most common are rhinovirus (common cold), influenza, parainfluenza, respiratory syncytial virus (RSV), picornaviruses, coronaviruses, and metapneumovirus
• Atypical infections: Mycoplasma pneumoniae and Chlamydia species are atypical pathogens, which can be responsible for exacerbations
• Non-infectious
• Environmental pollution: Increase in environmental pollution such as black smoke particulate matter, sulphur dioxide (SO2), ozone (O3), and nitrogen dioxide (NO2) is associated with increased exacerbation of COPD
• Pulmonary embolism: In cases with no clear infectious etiology, consideration of pulmonary embolism is required. In some reviews, up to 25% of patients requiring admission for "COPD exacerbation" had pulmonary embolism as the underlying cause

[Outline]

• Definition
• Description
• Epidemiology
• Etiology

History

• The patient may present with the history of:
• Acute onset of breathlessness
• Chest tightness
• Comorbid conditions like:
• Cardiac arrhythmia
• Congestive heart failure
• Pleural effusion
• Pneumonia
• Pneumothorax
• Cough (increasing)
• Dyspnea (increasing)
• Fatigue
• Fever
• Limitation of daily exercise
• Previous exacerbations
• Previous need for invasive or non-invasive ventilation
• Sputum that is increased or more purulence
• Tachypnea

Physical findings

• On physical examination, the following findings may be observed:
• Auscultation may reveal "silent chest" or bilateral extensive rhonchi/crepitations
• Barrel shaped/cobbler's chest
• Central cyanosis
• Clubbing of nails
• Decreased level of consciousness (generally due to delirium or hypercapnia)
• Distant heart sounds
• Hemodynamic instability (with arrhythmia, sepsis, or PE)
• Hyperinflation of chest
• Hypertension
• Paradoxical chest wall movement
• Peripheral edema
• Pulsus paradoxus
• Pursed lip breathing
• Signs of cor pulmonale
• Tracheal tug present
• Use of accessory respiratory muscles
• Chronic bronchitis patients are commonly referred to as "blue bloaters" as their propensity is obesity and right heart failure (cor pulmonale) with edema
• Emphysema patients are commonly referred to as "pink puffers" as their propensity is barrel chest, cachexia, and muscle wasting

[Outline]

• History
• Physical findings

Blood test findings

• Complete blood count (CBC): Polycythemia indicating arterial hypoxemia, leukocytosis indicating infection, and anemia are often present
• Serum electrolytes: Electrolyte imbalance (hyponateremia, hypokalemia), hyperglycemia, metabolic acid-base disorders may be present
• Arterial blood gas (ABG): Use to assess the severity of exacerbation. Hypercapnia and hypoxia may be present. PaO2 <60 mm of Hg with or without PaCO2 <50 mmHg is suggestive of respiratory failure. Venous blood gas is adequate in most cases, so long as pulse oximetry is generating a quality wave form

Other Laboratory test findings

• Sputum culture and sensitivity: Can be of value to identify the bacterial pathogen involved. There is debate on the value of such testing as it rarely results in modification of antimicrobial therapy. Exceptions include patients who have received recent antibiotics. It is important that sputum specimen is of high quality (coughed up from the lung) and is not "spit"

Radiographic tests

• Chest X-ray: To exclude other pathological conditions that may coexist with or mimic COPD
• CT pulmonary angiogram: To evaluate for pulmonary embolism
• V/Q scan: To evaluate for pulmonary embolism

Other diagnostic tests

• Electrocardiogram (ECG): May be used to evaluate for coexisting cardiac problems such as right heart hypertrophy, arrhythmias, and cardiac ischemic or infarction
• Pulse oximetry: May be used in evaluating the patient's oxygen saturation and providing/adjusting supplemental oxygen therapy
• Spirometry and peak expiratory flow (PEF): Routine use of spirometry and PEF are not recommended due to lack of accuracy during acute exacerbation

[Outline]

• Blood test findings
• Other Laboratory test findings
• Radiographic tests
• Other diagnostic tests

• Acute respiratory distress syndrome
• Asthma
• Bronchiectasis
• Bronchiolitis obliterans
• Cardiac arrhythmia
• Cardiac tamponade
• Congestive heart failure
• Fractured ribs
• Malignancy involving lungs
• Pleural effusion
• Metabolic disorders (eg, diabetic ketoacidosis, acute renal failure, etc)
• Pneumonia
• Pneumothorax
• Pulmonary embolism

General Treatment

• Treatment goals are to reduce the symptoms of exacerbation and decrease relapse
• Depending upon the severity of the exacerbation, the patient may be treated in the outpatient or inpatient setting. Some cases are successfully managed in the outpatient setting, with some cases require hospitalization, with severe cases requiring ICU admission
• Multiple factors should be considered in evaluating the exacerbation: severity of underlying COPD, presence of comorbidities, history of previous exacerbations, severity of symptoms, degree of dyspnea (such as rest dyspnea), and arterial or venous blood gas results
• Hospital management of exacerbations includes oxygen therapy, medications, and when required, ventilatory support
• In cases where ventilatory support is required, non-invasive ventilation [Continuous Positive Pressure (CPAP) or BiLevel Positive Pressure (BiPAP)] may be required. As a final resort, invasive ventilation may be utilized

Non pharmacological treatment

Oxygen therapy:

• Low-dose oxygen therapy
• It is useful in acute respiratory failure during exacerbation to prevent hypoxemia
• Supplemental oxygen should be adjusted to obtain adequate oxygen saturation (PaO2 > 8.0 kPa, 60 mm Hg, or SaO2 > 90%)
• Monitor arterial blood gas level every 30–60 minutes after starting oxygen therapy to ensure adequate oxygenation without CO2 retention or acidosis. Important to note that VBG is adequate for CO2 evaluation – an ABG is only required in cases where oximetry is unable to register
• Ventilatory support: The goals of ventilatory support in acute respiratory failure are to improve symptoms and decrease mortality and morbidity. Mechanical ventilatory support can be delivered via positive pressure devices using either a nasal or facial mask (noninvasive ventilation includes CPAP or BiPAP), or via an endotracheal tube or a tracheostomy (invasive ventilation)
• Noninvasive mechanical ventilation (NIV) is recommended in moderate to severe dyspnea, acidosis (pH =7.35), and/or hypercapnia (PaCO2 > 6.0 kPa, 45 mm Hg) in the conscious or semiconscious patient. Several randomized trials in acute respiratory failure indicate that NIV reduces mortality and intubation rate, with a success rate of 80% to 85%
• Invasive mechanical ventilation is recommended in the following cases: life-threatening episodes of acute respiratory failure, respiratory or cardiac arrest, inability to tolerate NIV or NIV failure, severe acidosis (pH < 7.25) and/or hypercapnia (PaCO2 > 8.0 kPa, 60 mm Hg), diminished or severely decreased consciousness, or significant aspiration. The major adverse events associated with mechanical ventilation are risk of ventilator-acquired pneumonia, barotrauma, and weaning failure
• Other treatment includes proper hydration (fluid administration), nutrition, and low-molecular weight heparin as a prophylaxis for deep venous thrombosis in immobilized patients

• Commonly used drugs for COPD exacerbation are antibiotics, bronchodilators, and corticosteroids, known as the ABC approach

• Antibiotic use in the treatment of exacerbation remains controversial. The main etiology of exacerbation is lower respiratory infection in which bacterial infection is more common. Hence antibiotics should be used in patients with 2-3 cardinal signs
• Increased dyspnea
• Increased sputum volume
• Increased sputum purulence
• Antibiotics are also indicated in patient who require mechanical ventilation
• Antibiotic use depends upon local bacterial resistance patterns. The most commonly recommended agents are aminopenicillins with or without clavulanic acid, macrolides, tetracyclines, second or third-generation cephalosporins, and in some cases, fluoroquinolones
• In patients with recurrent exacerbations and severe airflow limitation, sputum culture or gram stain is recommended to determine appropriate antimicrobial therapy

• Short-acting inhaled beta2 agonists (albuterol and terbutaline) and anticholinergic agents (ipratropium and tiotropium) are the preferred bronchodilators for the treatment of exacerbations as they improve symptoms relating to decreased FEV1
• No significant difference in FEV1 has been documented between use of metered dose inhalers and nebulizers in cases of COPD exacerbation
• Methylxanthines (theophylline): Used as a second-line therapy in selected patients with insufficient response to short acting bronchodilators, a bolus dose is usually followed by infusion in critically ill patients

• Systemic corticosteroids in COPD exacerbation improve FEV1 and arterial hypoxemia, shorten the recovery period, decrease hospital stay, and reduce the risk of relapse and treatment failure. Prednisolone 30–40 mg/day for 7–10 days is recommended. The use of oral or injectable steroids remains an issue of contention, with modest doses generally being felt to be a reasonable intervention

Medications indicated with specific doses

Short acting-beta 2-agonist

• Albuterol [Oral]
• Adult dosing
• Albuterol [Inhaled]
• Adult dosing
• Levalbuterol
• Adult dosing
• Metaproterenol [Inhaled]
• Adult dosing
• Pirbuterol [Inhaled]
• Adult dosing
• Terbutaline [Oral]
• Adult dosing
• Terbutaline [SC]
• Adult dosing

• Salmeterol
• Adult dosing
• Formoterol
• Adult dosing
• Arformoterol [Inhaled]
• Adult dosing
• Indacaterol [Inhaled]
• Adult dosing

• Ipratropium [Inhaled]
• Adult dosing
• Tiotropium [Inhaled]
• Adult dosing
• Aclidinium [Inhaled]
• Adult dosing

• Theophylline [IV]
• Adult dosing
• Theophylline [Oral]
• Adult dosing
• Aminophylline [Oral]
• Adult dosing
• Aminophylline [IV]
• Adult dosing

• Roflumilast
• Adult dosing
• Albuterol/ipratropium [Inhaled]
• Adult dosing
• Budesonide/formoterol [Inhaled]
• Adult dosing
• Fluticasone/salmeterol [Inhaled]
• Adult dosing

• Prednisone
• Adult dosing
• Methylprednisolone [Injectable]
• Adult dosing
• Methylprednisolone [Oral]
• Adult dosing

• Budesonide [Inhaled]
• Adult dosing
• Fluticasone [Inhaled]
• Adult dosing
• Ciclesonide [Inhaled]
• Adult dosing
• Mometasone [Inhaled]
• Adult dosing
• Beclomethasone [Inhaled]
• Adult dosing

• Amoxicillin [Oral]
• Adult dosing
• Amoxycillin/clavulanic
• Adult dosing
• Azithromycin [Oral]
• Adult dosing
• Doxycycline [Oral]
• Adult dosing
• Tetracycline [Oral]
• Adult dosing
• Sulfamethoxazole/trimethoprim [Oral]
• Adult dosing

Dietary or activity restriction

• Both overweight and underweight impacts prognosis of COPD. As such, nutritional intervention should be aimed at maintaining ideal body weight
• Avoid high-carbohydrate diets and extremely high caloric intake to reduce the risk of hypercarbia
• Creatine supplementation to increase fat free mass and peripheral muscle strength is reasonable in selected cases
• Pulmonary rehabilitation is recommended to improve the quality of life including dyspnea, fatigue, emotional function and physical activities

Disposition

Admission criteria

• Comorbidities such as congestive heart failure, acute coronary syndrome, pulmonary embolism, pneumonia, arrhythmia, diabetes mellitus, and renal or liver failure
• Failure to respond to outpatient management
• Inability to eat or sleep due to worsening symptoms
• Inadequate home situation
• Increase in the severity of symptoms such as dyspnea
• Onset of new physical signs such as cyanosis or peripheral edema
• Recurrent exacerbation
• Significant hypercapnia or hypoxemia

Discharge Criteria

• Ambulatory patients with oxygen saturation (>92%)
• Ability to complete a 6-minute walk test
• Adequate gas exchange and hypoxia which can be treated at home with temporary oxygen therapy
• No need for inhaled beta-agonist therapy which can only be administered within a hospital setting
• Ability to sleep and eat properly

[Outline]

• General Treatment
• Medications indicated with specific doses
• Dietary or activity restriction
• Disposition

Monitoring

• Follow up patient within 1 week of discharge to evaluate ongoing status, and improvement of symptoms. Evaluation is required to adjust the treatment regimen
• Monitor the patient's need for supplemental oxygen
• Repeat investigation, if results are abnormal Pulmonary function tests, serially, are often indicated (+/- DLCO study) in patients with COPD

Complications

• Arrhythmias
• Arterial hypoxemia
• Bullous lung disease
• Cor pulmonale
• Death
• Depression
• Hypoxia
• Infections
• Malnutrition
• Pneumothorax
• Poor sleep quality
• Pulmonary hypertension
• Respiratory failure
• Recurrent pneumonia
• Secondary polycythemia

[Outline]

• Monitoring
• Complications

Prognosis

Factors associated with poor prognosis in COPD include

• Advanced age
• Continued smoking
• Comorbid conditions such as cor pulmonale, alpha 1 antitrypsin deficiency, and pulmonary hypertension
• Discontinuation of treatment
• Initial FEV1 value <50% or continuous decline in FEV1
• Lack of health care facilities
• Lack of knowledge of disease
• Low hematocrit
• Malnutrition
• Poor response to bronchodilators

Associated conditions

• Asthma
• Atrial fibrillation
• Cardiovascular diseases
• Depression
• Diabetes
• Dyslipidemia
• Heart failure
• Hypertension
• Lung cancer
• Osteoporosis
• Respiratory infection
• Sleep apnea
• Underweight

Synonyms/Abbreviations

Abbreviations:

• AECOPD

ICD9-CM

• 491.21 Obstructive chronic bronchitis with (acute) exacerbation

ICD-10-CM

• J44.1 Chronic obstructive pulmonary disease with (acute) exacerbation

[Outline]

• Prognosis
• Associated conditions
• Synonyms/Abbreviations
• ICD9-CM
• ICD-10-CM

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