Infectious Diseases

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.

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

Table I.

Suggested Antibiotic Treatment for Various Organisms
Organism Antibiotics
Haemophilus influenzae Amoxicillin-clavulanate 500mg po three times daily or 875mg po twice dailyTrimethoprim-SulfamethaxazoleDS 1 tab po twice daily (resistance 7-10%) Fluoroquinolones: Moxifloxacin 400mg po daily, Levofloxacin 500mg po dailyMacrolides: Azithromycin 500mg po x 1, then 250mg daily x 4 days, Clarithromycin 500mg twice daily
Moraxella catarrhalis Trimethoprim-sulfamethoxazole DS 1 tab po dailyMacrolides: Erythromycin 500mg po four times daily,clarithomycin 500mg twice daily, Azithromycin 500mg x 1 then 250mg po daily x 4 days Tetracyclines: doxycycline 100mg po or IV twice dailyCephalosporins(oral): cefproxil 200-500 mg twice daily, cefpodoxime 200-400mg twice daily,cefuroxime 250-500mg twice daily, cefdinir 300mg twice daily Fluoroquinolones: moxifloxacin 400mg IV or po daily,levofloxacin 500mg IV or po dailyPenicillins: amoxicillin-clavulanate 875/125mg po twice daily
Streptococcus pneumoniae Amoxicillin 2-3 g po dailyDoxycycline100mg po twice dailyAmoxicillin 500-1000mg po three times dailyCefpodoxime 200mg po twice dailyPCN-resistant (PCN MIC >8):Levofloxacin 750mg po or IV dailyMoxifloxacin 400mg po or IV daily Ceftriaxone IVVancomycin 15mg/kg IV every 12 hoursLinezolid 600mg po or IV every 12 hours
Pseudomonas aeruginosa Use susceptibilities to guide final choices of antibiotic therapy. Piperacillin 3g IV every 4 hours or 4g IV every 6 hoursCefepime 1-2g IV every 8 hoursCeftazidime 2g IV every 8 hoursImipenem 1 g IV every 8 hoursMeropenem 1g IV every 8 hoursDoripenem 500mg IV every 8 hoursCiprofloxacin 400mg IV every 8 hours or 750mg po every 12 hoursAztreonam 2g IV every 8 hoursColistin 2.5mg/kg IV every 12 hours Polymixin B 0.75-1.25mg /kg IV every 12 hoursGentamicin 3mg/kg loading dose followed by 2mg/kg IV every 8 hours

2. Other key therapeutic modalities.

  • Oxygen therapy has an important role in COPD exacerbations. However, a patient with severe COPD who presents with hypercapnea and acidosis may develop suppression of the respiratory drive from uncontrolled oxygen therapy. Controlled oxygen administration should be tailored toward aiming for oxygen saturations of 88-92% in patients at risk for hypercapnea and 94-98% in patients without a history of previous respiratory acidosis. Arterial blood gases should be checked to determine response to treatment and changes in hypercarbia.

  • Short acting Beta-2 agonist bronchodilators improve shortness of breath in exacerbations. Anticholinergic agents may be effective in combination with a Beta-2 agonist in severe episodes, but evidence is uncertain. IV methylxanthines, such as theophylline, are second line agents for COPD exacerbations because of the limited evidence and the risk of drug interactions and adverse effects.

  • Systemic steroids improve outcomes in COPD exacerbations, as they improve dyspnea, FEV1, oxygenation, and health status; accelerate recovery of symptoms and lung function; and associated with fewer treatment failures and reduced length of hospital stay.

  • Noninvasive and invasive mechanical ventilation may be needed in cases of respiratory failure to provide support until the underlying cause of the respiratory failure can be treated.

  • Smoking cessation should be addressed in all patients still smoking.

What complications could arise as a consequence of chronic obstructive pulmonary disease?

What should you tell the family about the patient's prognosis?

  • Respiratory failure necessitating ICU admission is a serious consequence of a COPD exacerbation. Other sequelae of a COPD exacerbation include respiratory acidosis, hypoxemia, and altered mentation (from CO2 buildup).

  • COPD worsens over time, and it is difficult to predict this. Factors playing a role in the severity of COPD include continuation of smoking, being underweight, having other underlying medical illnesses, and lung function during exercise. Discussions about end of life care are important, especially before the patient becomes seriously ill.

  • The number of previous admissions for a COPD exacerbation, the severity of COPD, increased age, previous history of mechanical ventilation, poor nutritional status, high APACHE II score, and the development and severity of multiorgan system dysfunction have been identified as risk factors associated with increased mortality in patients admitted to an ICU.

How do you contract chronic obstructive pulmonary disease and how frequent is this disease?

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. hese include infections with rhinoviruses,coronaviruses, respiratory syncytial virus, influenza, parainfluenza, and adenoviruses.

The role of bacteria in COPD exacerbations is not clear-cut. The most common bacterial pathogens isolated from patients with COPD exacerbations are Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. It is controversial whether atypical bacteria, including chlamydia, legionella, and mycoplasma, are implicated in COPD exacerbations.

How can chronic obstructive pulmonary disease exacerbations be prevented?

The flu vaccine is recommended in all patients with COPD. One study showed a reduction in the risk for hospitalization for pneumonia and influenza and for mortality in COPD patients vaccinated for the flu. Pneumococcal vaccination has been shown to reduce the risk of pneumococcal pneumonia, but there is limited evidence of the effects in COPD exacerbations.

WHAT'S THE EVIDENCE for specific management and treatment recommendations?

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Rabe, KF, Hurd, S, Anzueto, A. "Global initiative for chronic obstructive lung disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary". Am J Respir Crit Care Med. vol. 176. 2007. pp. 532-55.

Wedzicha, JA, Seemungal, TA. "COPD exacerbations: defining their cause and prevention". Lancet. vol. 370. 2007. pp. 786-96.

Patel, I. "Exacerbations of chronic obstructive pulmonary disease: definition, aetiology and management". Clin Med. vol. 9. 2009. pp. 170-3.

Stoller, JK. "Clinical practice. Acute exacerbations of chronic obstructive pulmonary disease". N Engl J Med. vol. 346. 2002. pp. 988-94.

Snow, V, Lascher, S, Mottur-Pilson, C. "Evidence base for management of acute exacerbations of chronic obstructive pulmonary disease". Ann Intern Med. vol. 134. 2001. pp. 595-9.

Siddiqi, A, Sethi, S. "Optimizing antibiotic selection in treating COPD exacerbations". Int J Chron Obstruct Pulmon Dis. vol. 3. 2008. pp. 31-44.

http://prod.hopkins-abxguide.org/pathogens/bacteria/aerobic_gram-negative_cocci/haemophilus_influenzae.html?&contentInstanceId=255894.

Bourbeau, J. "Preventing hospitalization for COPD exacerbations". Semin Respir Crit Care Med. vol. 31. 2010. pp. 313-20.

Hurst, JR, Vestbo, J, Anzueto, A. "Evaluation of COPD longitudinally to identify predictive surrogate endpoints (ECLIPSE) investigators. Susceptibility to exacerbation in chronic obstructive pulmonary disease". N Engl J Med. vol. 363. 2010 Sep 16. pp. 1128-38.

Kamangar, N. "Chronic obstructive pulmonary disease". http://emedicine.medscape.com/article/297664-overview.

Ai-Ping, C, Lee, KH, Lim, TK. "In-hospital and 5-year mortality of patients treated in the ICU for acute exacerbation of COPD: a retrospective study". Chest. vol. 128. 2005. pp. 518-24.

Seneff, MG, Wagner, DP, Wagner, RP, Zimmerman, JE, Knaus, WA. "Hospital and 1-year survival of patients admitted to intensive care units with acute exacerbation of chronic obstructive pulmonary disease". JAMA. vol. 274. 1995. pp. 1852-7.

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