A direct comparison of recommendations presented in the above guidelines for the diagnosis and management of acute exacerbation of chronic obstructive pulmonary disease (COPD) is provided below. The University of Michigan Health System (UMHS) and Department of Veterans Affairs, Department of Defense (VA/DoD) guidelines provide recommendations for the outpatient setting; Global Initiative for Chronic Obstructive Lung Disease (GOLD) addresses both hospital and home settings.
Diagnosis and Initial Assessment
The groups agree that an exacerbation of COPD is generally defined as a worsening of the patient’s baseline dyspnea, cough, and/or sputum that is: beyond normal day-to-day variations, acute in onset, and may necessitate a change in regular medication. There is further agreement that assessment of the severity of an exacerbation should be based upon medical history, symptoms, physical examination, and laboratory investigations (as indicated). Recommendations regarding diagnostic investigations are similar. All three groups recommend pulse oximetry. According to GOLD, chest x-rays, ECG, and measurement of arterial blood gases (for patients that require hospitalization) are valuable diagnostic evaluations. They recommend against routine use of spirometry and PEF. In addition to pulse oximetry, VA/DoD states that other diagnostic testing may include chest x-ray, ECG, arterial blood gas measurement and spirometry (if available, in patients who are able to perform the test and for whom there is baseline data available for comparison).
The UMHS guideline focuses only on Level I exacerbations, which can be treated as an outpatient. In this context, UMHS recommends pulse oximetry be performed, but states that the following examinations are generally not recommended: chest x-ray (may be reasonable in patients with fever, exposure to inhaled steroids, or >65 years of age), spirometry, arterial blood gas, and ECG. All three groups agree that sputum gram stains and cultures are not routinely recommended, but may be appropriate in patients who have been on recent/recurrent antibiotic therapy. Additional possible investigations cited by GOLD and VA/DoD for patients presenting to the ED include a whole blood count and selected biochemical tests.
There is overall agreement that patients with possible COPD acute exacerbations should have the following common differential diagnoses considered: pneumonia, pneumothorax, CHF, PE, pleural effusion, cardiac arrhythmia, and symptoms resulting from noncompliance with medications or oxygen therapy. VA/DoD also cites cardiac ischemia, upper airway infection or obstruction, and recurrent aspiration. GOLD notes that elevated serum levels of BNP, in conjunction with other clinical information, identify patients with acute dyspnea secondary to CHF.
There is overall agreement that adequate oxygen saturation (≥90%) should be achieved and maintained in patients experiencing COPD exacerbations. In the context of hospital management, GOLD recommends monitoring of arterial blood gases once oxygen is started to ensure satisfactory oxygenation without CO2 retention or acidosis. UMHS recommends oxygen be titrated for patients with oxygen saturation ≤88% to achieve resting and exercise oxygen saturation ≥90%.
The only guideline developer to address inpatient management of acute exacerbations, GOLD, states that NIV improves respiratory acidosis, increases pH, decreases the need for endotracheal intubation, and reduces PaCO2, respiratory rate, severity of breathlessness, the length of hospital stay, and mortality. GOLD provides indications and relative contraindications for NIV, as well as indications for the use of invasive mechanical ventilation.
Indications for referral to the ED cited by the groups include, but are not limited to: severe underlying COPD, frequent exacerbations, significant comorbidities, older age, diagnostic uncertainty, changes in mental status (e.g., confusion), inadequate outpatient disease management resources, new or worsening hypoxemia or hypercapnia, onset of new symptoms, severe dyspnea, and unstable vital signs. GOLD and VA/DoD agree that initiation of bronchodilator therapy and oxygen is appropriate prior to full assessment and treatment in the ED. GOLD provides criteria for immediate admission to an ICU.
There is overall agreement that bronchodilators are considered first-line therapy for management of acute exacerbations. GOLD and UMHS agree that inhaled SABA are usually preferred, and that the dose and/or frequency of existing SABA therapy should be increased. GOLD and UMHS further agree that an inhaled anticholinergic (UMHS specifies ipratropium) may be used in addition to SABA therapy, with the caveat that the effectiveness of combination therapy in the setting of acute exacerbation is questionable. All three groups agree that clinical response does not appear to differ between bronchodilator therapy delivered by nebulizer or by MDI with a spacer. Refer to Areas of Difference for additional information.
There is overall agreement that a course of corticosteroids should be considered in addition to bronchodilator therapy. UMHS and VA/DoD recommend 30-40 mg daily of oral prednisone for a duration of 10-14 days (UMHS) and up to 14 days (VA/DoD). GOLD’s guidance is slightly different in that it recommends of 30-40 mg prednisolone per day for 7-10 days (in either the inpatient or outpatient settings). For home management, GOLD notes that therapy with oral prednisolone is preferable, but adds that budesonide alone, or in combination with formoterol, may be an alternative (although more expensive) to oral glucocorticosteroids in the treatment of exacerbations and is associated with significant reduction of complications. While UMHS recommends prednisone, they do cite prednisolone as a commonly used corticosteroid as well.
The groups agree that antibiotics are appropriate for patients with at least two of the three cardinal symptoms of severe exacerbation (i.e., increased dyspnea, increased sputum volume, and increased sputum purulence), with GOLD and UMHS specifying that one of the two symptoms should be increased sputum purulence.
When choosing an antibiotic, all three groups recommend stratifying patients according to the level of complication, with all three using similar combinations of risk factors to stratify patients. There is overall agreement that appropriate antibiotics for patients with no risk factors/less severe exacerbations include: TMP/SMX, second or third generation cephalosporins, a tetracycline (UMHS and VA/DoD specify doxycycline), and macrolides (UMHS specifies azithromycin). There is further agreement that beta-lactams/beta-lactamase inhibitors and fluoroquinolones are generally appropriate for, and should be reserved for, patients with risk factors/more severe exacerbations. GOLD and UMHS agree that the fluoroquinolones levofloxacin and ciprofloxacin are indicated for patients at risk for infection with P. aeruginosa.
GOLD and VA/DoD address the use of methylxanthines in the treatment of exacerbations of COPD, with neither recommending their use. According to GOLD, the role of methylxanthines in the treatment of exacerbations of COPD remains controversial. GOLD adds that they are currently considered second-line intravenous therapy, used when there is inadequate response to short-acting bronchodilators. VA/DoD recommends methylxanthines be avoided both orally and systemically, as they may lead to side effects and have no proven efficacy in the setting of an acute exacerbation of COPD.
Hospital Discharge and Follow-Up
GOLD and UMHS agree that a follow-up should be conducted four to six weeks after hospital discharge for exacerbations of COPD, and that the following items should be reassessed: ability to cope in home/usual environment; FEV1 using spirometry; inhaler technique, understanding of recommended treatment regimen, and need for oxygen (LTOT and/or home nebulizer).
GOLD and UMHS recommend inhaled SABA as initial pharmacologic management of acute exacerbations, followed by the addition of an inhaled anticholinergic if a patient fails to respond to initial single-agent therapy, with both groups acknowledging that the evidence for the effectiveness of this combination is controversial/questionable. VA/DoD, in contrast, does not cite one short-acting bronchodilator over another, recommending either a SAAC or SABA (or a combination of both). They recommend that the choice of agent should be made on the basis of individual assessment and initial response to therapy.