Clinical Assessment

The principal findings concerning the clinical assessment of patients with acute exacerbation of COPD were as follows:

• Patients presenting with acute exacerbation of COPD have a relatively high rate of abnormalities (such as infiltrates or pulmonary edema) on chest roentgenography (CXR), particularly when compared to previous series of patients with asthma, where relatively low rates of abnormalities have been found.
• Historical data and clinical signs and symptoms associated with two common comorbid conditions that often complicate the assessment of acute exacerbation of COPD-CHF and pneumonia-are significant but inexact predictors of two specific abnormalities on CXR, namely pulmonary edema and infiltrate, respectively.
• The prevalence of clinically unsuspected deep venous thrombosis (DVT) among patients hospitalized for acute exacerbation of COPD is high in some studies; however, few data are available to help quantify the risk for pulmonary embolus among patients with acute exacerbation of COPD with or without known DVT.
• Among patients presenting with acute exacerbation of COPD, forced expiratory volume in 1 second (FEV₁) during exacerbation is not well correlated with PaO₂ (partial pressure of oxygen) without supplemental oxygen, but is correlated with PaCO₂(partial pressure of carbon dioxide) and pH.
• Physician estimates of FEV₁during acute exacerbation of COPD are generally inaccurate. Peak expiratory flow rate (PEFR) is not sufficiently well correlated with FEV₁to substitute for it.
• Among patients on theophylline, neither clinical data on theophylline use (history of dosage, timing of last dose, past drug levels) nor other data (history of cigarette use, body weight) are accurate predictors of drug level during acute exacerbation of COPD.

Prognosis

Major findings related to prognosis were:

• While several factors are associated with worsening clinical condition in patients with acute exacerbation of COPD, no predictive model accurately predicts clinical outcomes, so ongoing clinical monitoring is needed for many patients.
• Among patients presenting with acute exacerbation of COPD and selected for outpatient treatment, cumulative relapse rates were between 11 percent and 17 percent at 48 hours and between 23 percent and 32 percent at 2 weeks. Hospitalization at index visit ranged from 24.2 percent to 71 percent among patients presenting to the emergency department (ED).
• Data from the previous history of individual patients-e.g., previous visit within 7 days, number of exacerbations in the past year, and relapsing on previous visits-were consistently identified as predictive of relapse. Also found to be predictive in several studies was baseline pulmonary function, as measured by FEV₁or FVC (forced vital capacity). Data describing acute respiratory physiology, such as FEV₁during exacerbation or arterial blood gases, predicted hospitalization or relapse. Data describing treatments used in the ED and clinical response were generally also predictive of hospitalization or later relapse.
• Among patients hospitalized for acute exacerbation of COPD and cared for in either ward beds or intensive care units, short-term or hospital mortality ranged from 4 percent to 26 percent. Study populations were not described well enough to explain these differences in overall mortality rates.
• The following were all associated with mortality due to acute exacerbation of COPD:

  1. Acute physiology (as measured by arterial blood gases, FEV₁during exacerbation, and scores from the Acute Physiology and Chronic Health Evaluation).
  2. Comorbid illness and other baseline, pre-exacerbation health status measures (such as body mass index and functional status).
  3. Cumulative or longitudinal data on the clinical course (e.g., baseline spirometry, number and frequency of previous acute exacerbations, and previous response to treatment of acute exacerbation of COPD).
• Acute respiratory physiology, as measured by blood gases, was predictive of the need for mechanical ventilation, as were baseline measures such as nutritional status.

Antibiotics

The antibiotic drugs studied were tetracycline, doxycycline, chloramphenicol, penicillin plus streptomycin, ampicillin, amoxicillin, and cotrimoxazole. The major findings related to these drugs were:

• Placebo-controlled randomized trials of antibiotic treatment of acute exacerbations of COPD show overall evidence of improvement in pulmonary function.
• The included trials suggest that patients with more evidence of bacterial infection (sputum purulence) and more severe illness (worse PEFR) benefit more from antibiotics; however, this has not been conclusively demonstrated.

Bronchodilators

The bronchodilators studied were:

• The anticholinergics ipratropium bromide and glycopyrrolate.
• The beta2-agonists albuterol (salbutamol).
• Fenoterol.
• Metaproterenol.
• Salmeterol.
• Terbutaline.
• The methylxanthines aminophylline and doxofylline.

The major findings related to this class of drugs were:

• Inhaled ipratropium and beta2-agonists were shown in comparative trials to have similar effects. However, neither class has demonstrated conclusive evidence of benefit in placebo or other no-treatment control trials. Most trials were too small to demonstrate a minimally clinically important benefit.
• Ipratropium is generally associated with fewer adverse effects than are the beta2-agonists, but it needs to be used cautiously in patients with pre-existing urinary retention problems. Beta2-agonists can cause cardiac arrhythmias in those predisposed to the condition. The arrhythmias are usually not life threatening.
• Bronchodilator therapy delivered by nebulizers and metered-dose inhalers (MDIs) show equivalent bronchodilation among patients with stable COPD. However, among patients with acute exacerbation of COPD, who may be unable to hold their breath, nebulizers may be necessary.
• Glycopyrrolate may have a synergistic effect in bronchodilation when given with a beta2-agonist.
• Parenteral aminophylline did not improve FEV₁, hospitalization rates, or relapse in three placebo-controlled trials. Parenteral doxofylline did show a significant improvement in FEV₁in a placebo-controlled trial. Moreover, methylxanthines have numerous, sometimes life-threatening, adverse effects and drug interactions.

Corticosteroids

Principal findings related to corticosteroid treatment were the following:

• Several randomized controlled trials provided strong evidence that a course of systemic corticosteroids provides benefit in patients hospitalized with acute exacerbation of COPD. The risk of treatment failure was reduced by approximately 10 percent, and FEV₁showed an improvement averaging about 0.1 liters in the first hours to days of treatment.
• Doses as low as prednisone 30 mg daily and duration as short as 3 days have been shown to be effective in single trials; however, the optimal dose and duration is not clear from available trials. A single well-designed trial found that there were no significant differences in clinical outcomes between a 2-week course of systemic corticosteroids and an 8-week course.
• Inhaled corticosteroids have not been tested adequately in patients with acute exacerbation of COPD.
• Adverse effects were common in patients treated for acute exacerbation of COPD with systemic corticosteroids. The most frequently observed adverse effect was hyperglycemia.

Mucous-Clearing Treatments

Considered under this heading were mucolytic drugs and physical therapy interventions. The principal findings were:

• Available studies show no benefit from any of the mucolytic drugs studied (ambroxol, bromhexine, domiodol, potassium iodide, and S-carboxymethyl cysteine) in improving ventilatory function in acute exacerbation of COPD. Some studies reported subjective improvement in symptoms associated with decreasing sputum viscosity.
• Studies of chest percussion also failed to show any benefit in improving short-term ventilatory function in patients with acute exacerbation of COPD.

NPPV

Major findings related to NPPV are the following:

• NPPV is an effective alternative to mechanical ventilation by endotracheal intubation for some patients with acute respiratory failure secondary to acute exacerbation of COPD.
• The selection of mask interface and/or ventilator mode can be important to patient cooperation and tolerance, and thus to the efficacy of the intervention. Each type of mask and ventilation mode comes with its own set of morbidities. The pressure-support ventilation (PSV) and continuous or bi-level positive airway pressure modes of ventilation appear to be best tolerated and most effective for correcting hypercarbia. Assist control ventilation (ACV) mode with NPPV is generally poorly tolerated unless volume and rate are adjusted to the individual patient.