Chronic Obstructive Pulmonary Disease (COPD) and Acute Exacerbations

OVERVIEW: What every practitioner needs to know

Are you sure your patient has chronic obstructive pulmonary disease? What should you expect to find?

• Chronic obstructive pulmonary disease (COPD) is characterized by the progressive development of airflow limitation that is not fully reversible. COPD is comprised of chronic bronchitis and emphysema. The pathology of COPD is an abnormal inflammatory response by the lungs to inhaled noxious particles or gases. It is the fourth leading cause of chronic morbidity and mortality in the United States. COPD exacerbations are defined as “an event in the natural course of the disease characterized by a change in the patient’s baseline dyspnea, cough, and/or sputum that is beyond normal day to day variations, is acute in onset, and may warrant a change in regular medications in a patient with underlying COPD.” COPD exacerbations are associated with increased airway and systemic inflammation. Many COPD exacerbations are due to upper respiratory tract viral infections and environmental factors, such as pollution and weather. COPD exacerbations are a common cause of admission to hospitals and can affect a patient’s functional status, morbidity, and mortality. Lung function after a COPD exacerbation may not recover after 3 months. As the severity of underlying COPD progresses, the frequency and severity of COPD exacerbations increases.

• Increased shortness of breath is the main symptom of an exacerbation. Other common symptoms include wheezing, chest tightness, increased cough and sputum, change in the color of sputum, and fever. Nonspecific complaints include tachycardia, tachypnea, malaise, insomnia, sleepiness, fatigue, depression, and confusion. Airway inflammation causes airway edema, bronchospasm, and increased sputum production, which can lead to worsening airflow limitation and hyperinflation, which is the main cause of dyspnea. Eliciting history of dyspnea, sputum volume, and sputum purulence has implication for antibiotic therapy.

• Tachypnea, signs of prolonged expiration (pursed lip breathing), wheezing, crackles, use of accessory muscles, confusion, and new onset cyanosis are key physical findings.

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How did the patient develop chronic obstructive pulmonary disease? What was the primary source from which the infection spread?

• COPD exacerbations are associated with increased airway and systemic inflammation. They are caused by complex interactions between the host, respiratory viruses, airway bacteria, and environmental pollution. They are frequently triggered by upper respiratory infections, especially during winter months. Rhinovirus is the most common virus associated with a COPD exacerbation. Other viral pathogens isolated from patients with COPD exacerbations are coronarvirus, respiratory syncytial virus, influenza, parainfluenza, and adenovirus.

• The influenza vaccine has decreased the number of exacerbations caused by influenza. COPD exacerbations caused by respiratory viruses have been found to be more severe, associated with longer recovery times, associated with greater falls in lung function, associated with higher airway inflammation, and have more chance of hospital admission than exacerbations without respiratory viruses detected.

• The role of bacteria in COPD exacerbations is confounded by the fact that airway bacterial colonization in the stable state is associated with the same organism as those isolated during exacerbations. Pathogenic bacteria have been found in the distal airways in 30-50% of exacerbations at bronchoscopy. The most common bacterial pathogens isolated from patients with COPD exacerbations are Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa. Purulent sputum is a marker of bacterial infection, as COPD exacerbations associated with purulent sputum are more likely to produce positive bacterial cultures. It is controversial whether atypical bacteria, such as chlamydia, legionella, and mycoplasma, can be implicated in COPD exacerbations.

• Environmental pollution, such as ozone, particulates, sulfur dioxide, and nitrogen dioxide, can lead to increased COPD exacerbations.

Which individuals are of greater risk of developing chronic obstructive pulmonary disease?

• COPD exacerbations become more frequent and more severe as the severity of underlying COPD increases. The most reliable predictor of COPD exacerbations appears to be a history of having exacerbations. Common causes of COPD include cigarette smoking, air pollution, airway hyperresponsiveness, and alpha 1 antitrypsin deficiency.

Beware: there are other diseases that can mimic chronic obstructive pulmonary disease:

• The differential diagnosis of COPD exacerbations includes pneumonia, congestive heart failure, pneumothorax, pleural effusion, pulmonary embolism, and cardiac arrhythmia.

What laboratory studies should you order and what should you expect to find?

Results consistent with the diagnosis

• An arterial blood gas indicating a PaO2 less than 60 and/or a SaO2 less than 90% with or without a PaCO2 greater than 50 indicates respiratory failure. Moderate to severe acidosis (pH < 7.36) plus hypercapnea (PaCO2 > 45-60) is an indication for mechanical ventilation.

• The C-reactive protein (CRP) was studied as a biomarker for COPD exacerbations and was found to be neither sufficiently sensitive nor specific alone. The combination of CRP with any increased major exacerbation symptom, such as dyspnea, sputum volume, or sputum purulence, increased the sensitivity and specificity.

What imaging studies will be helpful in making or excluding the diagnosis of chronic obstructive pulmonary disease?

• A chest x-ray (preferably PA and lateral) is useful in identifying alternative diagnoses. An EKG can assist in diagnosing right ventricular hypertrophy, arrhythmias, and ischemia. Chest CT is specific for diagnosing COPD and identifying bullae but does not provide much information in diagnosing a COPD exacerbation. Spirometry is not recommended during an acute exacerbation, as it can be difficult for a sick patient to perform the test properly.

What consult service or services would be helpful for making the diagnosis and assisting with treatment?

If you decide the patient has chronic obstructive pulmonary disease, what therapies should you initiate immediately?

• Pulmonary consultation may beneficial for further management of COPD exacerbations. ICU services are warranted when patients develop respiratory failure.

• It is important to consider the cause of the exacerbation, the degree of reversible bronchospasm, recent drug use, and contraindications to treatment when initiating therapy. Evaluation of the airway and breathing should be the primary goal to determine whether noninvasive or invasive ventilation is needed. An Inhaled beta-2 agonist with or without an inhaled anticholinergic should be delivered via spacer or nebulizer. Corticosteroids can be administered intravenously. Antibiotics can be administered if it thought that the patient has an intercurrent infection.

1. Anti-infective agents

If I am not sure what pathogen is causing the infection, what anti-infective should I order?

Antibiotics given at exacerbations can offer a small but significant benefit in treatment failure and mortality. Use of antibiotics is indicated in patients with all three of the major symptoms of increased dyspnea, sputum volume, and sputum purulence; two of the three major symptoms, of which one is sputum purulence; and exacerbations requiring invasive or noninvasive mechanical ventilation. Antibiotic benefit is greatest in patients with more severe disease.

Empiric treatment requires knowledge of local bacterial prevalence and microbiological guidance. Antimicrobial therapy should be tailored to sputum culture sensitivity results. Concerns about resistant flora have prompted some physicians to use broader spectrum antibiotics empirically, but no evidence supports the first line use of such agents. In studies evaluating the efficacy of antibiotic treatment, tetracycline, amoxicillin, and trimethoprim-sulfamethaxozole were the most common antibiotics and treatment duration ranged from 3 to 14 days. The emergence of increasing resistance, especially among S. pneumoniae, has prompted the use of broader spectrum antibiotics.

One algorithm proposes no antibiotics for mild COPD exacerbations (<1 cardinal symptom). For moderate or severe COPD exacerbations (at least two of three cardinal symptoms), risk factors of age older than 65 years of age, FEV1 less than 50% of predicted, three or more exacerbations, and presence of cardiac disease should be considered. Antibiotic selection in simple COPD exacerbations (no risk factors) include macrolides (azithromycin, clarithromycin), cephalosporins, (cefuroxime, cefpodoxime, cefdinir), ketolide (telithromycin), doxycycline, and trimethoprim-sulfamethaxazole. Antibiotic selection for complicated COPD (1 or more risk factors) includes fluoroquinolones (moxifloxacin, gemifloxacin, levofloxacin), amoxicillin/clavunate, and ciprofloxacin if there is risk for Pseudomonas. A different antibiotic class should be selected if there was recent antibiotic exposure within 3 months.

In hospitalized patients, patients with risk factors for Pseudomonas should be treated with levofloxacin, cefepime, ceftazidime, or piperacillin-tazobactam after a sputum gram stain and culture are performed. Patients without risk factors for Pseudomonas should be treated with levofloxacin, moxifloxacin, ceftriaxone, or cefotaxime.

Table I. Suggested Antibiotic Treatment for Various Organisms