Management of Chronic Obstructive Pulmonary Disease Exacerbations and Acute Bronchitis

Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) affects approximately 14 million Americans and is currently the fourth leading cause of death in the United States. It is currently the only leading cause of death with an increasing mortality rate, and healthcare costs associated with the disease are estimated at 32 billion dollars per year. Between 1980 and the year 2000, the mortality rate for women with COPD tripled whereas the rate for men increased 13%.1

Pathogenesis

COPD is a disease that encompasses both chronic bronchitis and emphysema and is associated with chronic inflammation of the small airways and destruction of alveoli. Inflammation is mediated by neutrophils that release protease enzymes, resulting in the eventual destruction of alveoli.2 Chronic inflammation causes fibrosis, which, in the lung, leads to airway constriction. The excess mucus associated with COPD then gets trapped in the narrowed airways, causing air trapping and bron-chospasm. Occlusion of terminal bronchioles can result in the death of the distal alveoli. The narrowed airways, hyperinflation, and reduced gas exchange abilities caused by alveoli destruction results in respiratory failure. Chronic hypoxia results in an increased pulmonary vascular resistance and can eventually lead to pulmonary hypertension and right heart failure.

Risk Factors

The most important risk factor associated with the development of COPD is cigarette smoking. The irreversible damage done to lung tissue through smoking causes an acceleration of the normal age-related decline in lung function. Smokers are more than ten times more likely than nonsmokers to die of COPD. Other risk factors for the development of COPD are family history of COPD, middle to old age, as well as environmental pollutants, including second-hand smoke. Genetic disorders, such as α-1-antitrypsin deficiency can also lead to early onset emphysema and COPD.

Diagnosis

The diagnosis of COPD needs to be considered in any patient with a chronic cough, sputum production, and a history of exposure to cigarette smoking. Dyspnea is a key feature of COPD, however, it may not be present until later in the disease. The objective diagnosis of COPD is made by spirometry, and postbronchodilator spirometry values are the mainstay for classification of the disease (see Table 4.1). Postbronchodilator spirometry confirms irreversible lung disease consistent with COPD.

Table 4.1 Classification of COPD

The diagnosis of an acute exacerbation of COPD is based largely on changing symptoms in an individual with known COPD. An increased volume, purulence, or tenacity of sputum associated with increased dyspnea are common characteristics of COPD exacerbations. Commonly, patients will also have increased cough, wheeze, and fever. Dyspnea is the most consistent complaint associated with exacerbations. Other symptoms include malaise, fatigue, and a reduction in exercise capacity. For those patients with underlying severe COPD, a reduced level of consciousness is an indicator of a severe exacerbation. Exacerbations can mimic several other illnesses, including pneumonia, congestive heart failure, pneumothorax, pleural effusion, pulmonary embolism, and an arrhythmia.

To help elicit the severity of an exacerbation, the time duration of symptoms, as well as the volume and purulence of sputum should be ascertained. The degree of breathlessness associated with coughing is also an important indicator of severity, as is a history of hospitalizations, including admissions to the intensive care unit.

Inpatient Versus Outpatient Management

The diagnosis of an exacerbation, although largely a clinical one, can be aided by specific tests that help ascertain the severity of illness and, thereby, guide management. In the office setting, a peak expiratory flow (PEF) rate can be measured easily. A value < 100 L/min is generally considered to indicate a severe exacerbation. If spirometry is available in the office, a forced expiratory volume in 1 second (FEV₁) of < 1.00 L or < 40% of predicted value also corresponds with a severe exacerbation. Severe exacerbations are best managed in the inpatient setting, at times requiring admission to the intensive care unit with positive pressure ventilation.

Arterial blood gas (ABG) analysis is an important tool in the hospital setting. When performed, results should be compared with the patient's baseline ABG values because patients with long-standing COPD may have underlying abnormalities even when “well.” In general, a PaO₂ < 60 mmHg and/or a SaO₂ > 90% with or without a PaCO₂ < 50 mmHg while breathing room air is consistent with respiratory failure. Furthermore, a PaO₂ < 50 mmHg with a PCO₂ < 70 mmHg and a pH < 7.30 is indicative of a life- threatening exacerbation and needs prompt critical care management.

The decision to manage an exacerbation at home or in the hospital is not always as obvious as this, however, and encompasses several factors, including underlying disease severity.

Those with severe underlying disease having an exacerbation are much more likely to require hospital-level care than those with mild disease. Other indications for hospital-based treatment of exacerbations include poor home support, older age, and significant comorbid illness. The onset of new symptoms, such as dyspnea at rest, or new signs, such as cyanosis or peripheral edema, would also indicate a need for hospital-based care. Furthermore, if there is diagnostic uncertainty, an emergency room visit to exclude other causes for the symptoms or signs is warranted. Table 4.2 shows a summary of recommended indications for hospital-based treatment.

Table 4.2 Criteria for inpatient management

Management

Supplemental Oxygen

Although giving oxygen to a dyspneic, hypoxic patient should be an intuitive response, many physicians worry about the risk of hypercapnea and the possibility of reducing respiratory drive as a result of giving too much oxygen to a patient with chronic disease. Prevention of hypoxia initially outweighs concerns for hypercapnea, and regulated oxygen delivery with appropriate oxygen saturation goals can reduce the incidence of hypercapnea. Venturi masks are the preferred mode of choice when selecting an oxygen supplementation device because the amount of oxygen delivery can be controlled. An ABG can be done approximately half an hour after initiation of therapy to check for an insidious rise in arterial carbon dioxide levels. An oxygen saturation of 90 to 92% and a PaO₂ of 60 to 65 mmHg gives good oxygen saturation and is less likely to lead to hypercapnea. Values much < a PaO₂ of 60 mmHg give little added benefit and increase the risk of CO₂ retention.

Bronchodilator Therapy

Bronchodilator therapy is recommended by the GOLD guidelines, and has been shown to be beneficial in exacerbations of COPD. Patients should increase the dose and or frequency of current bronchodilator therapy initially to every four hours.

The current GOLD3 guidelines suggest that a β-2-agonist be initiated first and, if there is not a significant response, an anticholinergic medication should be added quickly thereafter. The guidelines, although stating that β-2-agonists should be used first, do so because of a larger body of evidence supporting their efficacy. The guidelines go on to state that there is no evidence to show a difference in efficacy between the different classes of short-acting bronchodilators. The use of combination therapy is still controversial because there is little evidence to support its use. Bronchodilators have been shown to increase the FEV₁ and forced vital capacity (FVC) by 15 to 29%.

The possibility of adding methylxanthine medications, such as intravenous aminophylline or oral theophylline, to patients with severe exacerbations can be considered. The evidence for use of these medications is inconsistent and generally only exhibits modest improvements in lung function, with an increased rate of adverse events. If these medications are going to be used, it is recommended that serum theophylline levels be monitored.

Corticosteroid Therapy

Corticosteroid therapy is proven to reduce symptoms and improve both gas exchange and airflow in randomized control trials. Steroid therapy for acute COPD exacerbations has also been proven to reduce treatment failures at 30 and 90 days as well as to reduce length of hospital stay. Significant improvements in FEV₁ have been shown on day 1 of therapy, however, this difference was no longer significant after 2 weeks of therapy. The optimal dose and duration of corticosteroid therapy is still unknown and the length of steroid taper is left to the judgement of the clinician. There is evidence that 10 to 14 days of therapy beginning with 30 to 40 mg of pred-nisolone daily is an appropriate compromise between efficacy and safety, however, the strength of the recommendation is weak and based only on expert consensus opinion.3,4 There is strong evidence that 10 days of therapy improves FEV₁ and FVC and has more rapid resolution of symptoms than 3 days of treatment, however, there was no difference in recurrence rate at 6 months between the two therapies.5

Antibiotics

Bacterial infections are common cause of COPD exacerbations, and the use of antibiotics expedite improvement. Antibiotic therapy is shown to be most useful in patients with severe exacerbations. Patients with increased volume or purulence of sputum as well as with dyspnea are more likely to benefit from antibiotics than those without these three symptoms. Meta-analysis, however, supports the use of antibiotic therapy in patients with purulent sputum plus either increased volume of sputum or dyspnea.6 Antibiotic therapy has been shown to shorten symptom duration as well as improve PEF rates during a COPD exacerbation. Patients with severe exacerbations requiring mechanical ventilation have also been shown to benefit from the use of antibiotic therapy.

The most common bacterial causes of mild exacerbations of COPD are Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenza. Studies have shown a correlation between the type of bacterial infection and the underlying disease severity. Those patients with mild disease tend to have S. pneumoniae-predominant infections. A s the COPD advances and patients' FEV₁ is reduced, the bacterial infections are more likely to include organisms such as M. catarrhalis, H. influenza, and, in severe underlying disease, Pseudomonas aeruginosa. Patients with very severe COPD (stage IV), frequent use of antibiotics, and recent hospitalizations are at increased risk for pseudomonal infections.

When choosing an antibiotic, the underlying disease severity, frequency of previous antibiotic use, as well as the severity of the exacerbation must be considered. For patients with both mild disease and mild exacerbations not requiring hospitali-zation, S. pneumoniae, M. catarrhalis, and H. influenza, as well as Chlamydia pneumoniae and viruses are most often the causative agents. For those patients with more severe disease (stages II–IV) with moderate to severe exacerbations requiring hospitalization for treatment, the same organisms must be considered, however, the Enterobacteriaceae, including Klebsiella pneumoniae and Escherichia coli also play a role. Patients with the most severe disease and severe exacerbations may have any of the organisms previously described. The risk of a pseudomonal infection must also be assessed in these individuals, and appropriate antibiotic coverage should be selected. The optimal length of antibiotic treatment has not been determined, however, it is recommended that patients be treated for 3 to 10 days once starting antibiotics. Table 4.3 is an overview of antibiotic choices associated with exacerbation severity and probable pathogens.

Table 4.3 Antibiotic treatment in COPD exacerbation

Sputum Gram's stain is generally not beneficial and sputum cultures can be reserved for those patients who fail first-line therapy.

Noninvasive Positive Pressure Ventilation

Noninvasive mechanical ventilation has been shown repeatedly to improve outcomes in patients with COPD exacerbations. It is given as a combination of continuous positive airway pressure (CPAP) and pressure support ventilation (PSV). It has been shown to increase blood pH and to reduce pCO₂ and treatment time, as well as to reduce the severity of breathlessness within the first 4 hours of treatment. Hospital stays are decreased with the use of noninvasive positive pressure ventilation (NIPPV), and the rate of mortality and intubation is markedly reduced as well. One-year mortality rates have been shown to be less in those receiving NIPPV than in those receiving either conventional mechanical ventilation or maximal medical therapy alone. The following are indications for the use of NIPPV:

• Paradoxical abdominal motion associated with moderate to severe dyspnea

• Acidosis (pH < 7.35) in the moderate to severe range as well as hypercapnea PaCO₂ < 6.0 kPa, 45 mmHg.

• Respiratory rate < 25 minute

Patients need to be followed closely and monitored for improvement in their ABG values in a high-dependency unit or intensive care unit setting.

There are several contraindications for the use of NIPPV, including respiratory arrest, cardiovascular instability (hypotension, arrhythmias, and myocardial infarction), impaired mental status, inability to cooperate, somnolence, high aspiration risk because of copious or viscous secretions as well as recent gastroesophageal surgery, craniofacial trauma/fixed nasopharyngeal abnormality, burns, and extreme obesity.

Noninvasive ventilation can be deemed successful when pH improves, dyspnea is relieved, the exacerbation is alleviated without the need for intubation, and the patient is able to leave the hospital.

Invasive Ventilation

Patients should be considered for invasive ventilation if they meet one or more of the following criteria:

• Patients with severe dyspnea, use of accessary muscles and paradoxical abdominal motion

• Impending respiratory failure and life-threatening acid—base disturbances, i.e.:

  • acidosis (pH < 7.25)

  • hypercapnea (PaCO₂) < 60 mmHg, 8.0 kPa

• Respiratory frequency < 35 breaths per minute

• Respiratory arrest

• Impaired mental status, somnolence

• NIPPV failure or contraindications

• Cardiovascular complications, including hypotension, shock, or heart failure

• Other complications, including metabolic abnormalities, sepsis, pneumonia, pulmonary embolism, barotrauma, and massive pleural effusion

Other Beneficial Treatments

Adequate nutrition has also proven to be helpful in COPD exacerbations. Patients too dyspneic to eat may require short-term tube feeding and fluid administration. The immobilized patient will benefit from subcutaneous heparin to reduce the risk of thromboembolic disease while recovering. Chest percussion, either mechanical or manual, may benefit patients producing large quantities of sputum (< 25 mL/day), or those with lobar atelectasis.

Discharge Planning

Patients recovering from an acute COPD exacerbation will require close follow up and very often require home care. To be discharged from the hospital, patients should not require bronchodilator treatments more often than every 4 hours. Clinical stability should be apparent for 12 to 24 hours before discharge, and the patient's ABG analysis should be stable as well. COPD sufferers should be able to sleep and eat without severe dyspnea, and previously mobile patients should be able to walk unassisted across a room. If the patient requires home oxygen, arrangements need to be made, and the patient and/or caregiver educated to understand the correct use of the oxygen and all of the current medications.

Approximately 4 to 6 weeks after discharge from the hospital, the patient should be reevaluated regarding the need for home oxygen, inhaler technique, and overall ability to cope with the disease. Outpatient pulmonary rehabilitation soon after discharge has been shown to improve exercise capacity and overall health status at 3 months out of hospital.

As in the day-to-day management of COPD, the management of an exacerbation requires close follow up and the intervention of a multidisciplinary team to help guide the patient back to health.

Acute Bronchitis

Acute bronchitis is defined as an acute respiratory illness with a predominant cough. The cough may or may not be productive. Up to 5% of adults in North America report an episode of acute bronchitis in the past year, approximately 90% of which will be evaluated by their physician. This makes acute bronchitis one of the top ten acute office visits in primary care.

Evaluation

The evaluation of acute bronchitis involves excluding pneumonia and other more serious causes of cough. The patients' comorbidities play an important role in the clinician's ability to confidently diagnose acute bronchitis. In patients with underlying congestive heart failure, COPD, or immunocompromised states, the level of suspicion for other entities must be high. However, in the immunocompetent patient with a cough of < 2 to 3 weeks duration and otherwise normal vital signs, the diagnosis of acute bronchitis can often be made with confidence. Studies have concluded that a normal physical examination including normal breath sounds, the absence of rales, focal consolidation, or egophony, as well as stable vital signs (normal temperature < 38 °C, respiratory rate < 24 breaths per minute, and heart rate < 100 /minute) all but eliminates the need for a chest x-ray to exclude pneumonia.7

Etiology

More than 90% of all cases of acute bronchitis are caused by nonbacterial sources. The prominent viruses implicated in acute bronchitis infecting the lower respiratory tract include influenza A and B as well as respiratory syncytial virus and parainflu-enza. Adenovirus and rhinovirus cause infections of the upper respiratory tract. It is thought that up to 5 to 10% of all acute bronchitis can be caused by bacterial organisms such as Mycoplasma pneumoniae, C. pneumoniae, and Bordetella pertussis. These are generally associated with a more chronic persistent cough. There is little or no evidence that the common organisms associated with pneumonia (S. pneumoniae, M. catarrhalis, and H. influenza) cause acute bronchitis in immu-nocompetent patients.

Management

Studies have revealed no reduction in the duration of symptoms associated with antibiotic treatment and, therefore, they are not recommended for treatment regardless of the duration of cough. If there is high clinical suspicion for pertussis in a patient with a prolonged cough (< 2–3weeks), patients should tested and treated to reduce transmission rates. The most common proven pathogen associated with acute uncomplicated bronchitis is influenza. Newer antiviral agents will help with symptomatology associated with influenza, however, they need to be taken within 48 hours of the onset of symptoms to be effective. Clinical suspicion in the midst of an outbreak must be high.

Symptomatic treatments include the use of albuterol metered-dose inhalers with spacer devices for those patients with a bronchospastic component to their cough. If limited to patients with wheeze or bronchial hyperresponsiveness, β-2-agonists are effective in reducing the length and severity of cough associated with acute bronchitis. The use of anticough agents, such as dextromethorphan and codeine, have a modest effect on the duration and severity of cough in patients with acute bronchitis and a cough of 2 to 3 weeks duration. Other methods for reducing cough frequency and severity include reducing dust and pollen exposure, as well as the use of humidifiers, although these have very limited evidence (but are generally low cost and very low-risk forms of treatment).

The most important management aspect of acute bronchitis for patient satisfaction seems to be communication. Many patients will arrive at their primary care physician's office with a persistent cough, expecting antibiotics. This is likely because of preconceived notions exacerbated by past primary care physicians treating acute bronchitis with antibiotics. The following points may assist with the sometimes difficult discussion regarding why antibiotics are not being prescribed.

• Give the patient realistic expectations regarding the duration of the cough (10–14 days after the office visit)

• Refer to the symptoms as a “chest cold” rather than bronchitis because this term is less associated with a need for antibiotic therapy

• Personalize the risk for the patient associated with the use of antibiotics (i.e., yeast infections, gastrointestinal upset, risk of C. difficile, rare but serious reactions)

• Discuss the overuse of antibiotics and the development of resistant strains of bacteria7

These points may improve overall patient satisfaction with the appointment, while administering appropriate therapy for their illness.