Peggy Choye, Pharm.D.
Spring 1998

Chronic Obstructive Lung Disease

1. Study Guide for Chronic Obstructive Lung Disease
2. Case Study

STUDY GUIDE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE

Define chronic bronchitis, emphysema, asthmatic bronchitis and peripheral airway disease. Table 26.2(p. 597) will help you distinguish between the clinical features of emphysema vs. chronic bronchitis. Keep mind that many of the patients with COLD will have components of both chronic bronchitis and emphysema. Know that patients with predominantly chronic bronchitis will often times have an increased hematocrit secondary to chronic hypoxemia. Additionally, they often have a respiratory acidosis(increased pCO2) with a compensatory metabolic alkalosis.(see page 598 and 599 for a more detailed explanation). Be able to explain what cor pulmonale is and why patients with chronic bronchitis are more likely to develop it than are patients with emphysema.

COLD is the fourth most common cause of death in the U.S. and is the second leading cause of disabilities. Cigarette smoking is implicated in 90% of cases of COLD.

The most useful tool to assess the course of COLD is the rate of decline of FEV1. Despite this, it has been recognized that the forced expiratory maneuver is not how one normally breaths and in some patients the FEV1 will not necessarily reflect symptoms or clinical status. What is the mean yearly rate of decline of FEV1 and how does it compare with an age matched individual without COLD? FEV1 does have prognostic implication. Persons with a FEV1> 1.0L have a slight increase in mortality when compared to an age and gender matched population. Persons with FEV1 values < 0.75L have an approximate mortality rate of 30% at 1 year and 95% at 10 years. There are cases however, of individuals with this degree of severity surviving beyond 10 years. The cause of death is usually the result of a medical complication such as acute respiratory failure, pneumonia, pulmonary embolus, pneumothorax or cardiac causes.

The American Thoracic Society statement on interpretation of lung function has led to the development of a staging system.

Stage I- FEV1> 50% predicted. This stage comprises the majority of patients and has minimal impact on health-related quality of life.

Stage II- FEV1 is 35-49% predicted. At this stage, COLD has a significant impact on health-related quality of life.

Stage III- FEV1 <35% predicted and has a profound impact on health related quality.

What is the only intervention known to improve survival rate? Know that smoking cessation can improve symptoms and patients quality of life.

Define acute respiratory failure in chronic obstructive lung disease? What are some of the acute clinical manifestations? List 5 causes that can precipitate acute respiratory failure in a patient with underlying COLD.

It is important that patients with COLD receive an adequate therapeutic trial of pharmacological agents even if a positive response is not observed on the basis of spirometry. Page 601 goes over the reasons. Keep patients on therapy for at least 2 weeks before re-assessing spirometry and any subjective improvement.

Anticholinergic agents have evolved as first line bronchodilator therapy for stable COLD patients. They appear to be more effective in patients with stable COLD than in patients with asthma. This may be because smooth muscle tone in COLD is more cholinergically mediated or there may be a lesser response to adrenergic agents due to a lack of mediators in modulating smooth muscle tone. For acute exacerbations however, B-agonists remain the drug of choice. Ipratropium is the only anticholinergic available via metered dose inhaler. It is also now available as a solution for nebulization so the need for atropine or glycopyrrolate should be decreased. Know the onset and duration and dose for ipratropium. Combining an anticholinergic with a B-agonist may be necessary for patients failing monotherapy. A recent study published in Chest 1994; 105:1411-19 showed improved bronchodilation when the combination was used. A combination product of ipratropium and albuterol in a single MDI is available in Europe and may be available in the U.S. in the future. The benefit of using combined therapy is that we are taking advantage of different mechanisms of action. Beta agonists act on the sympathetic system whereas anticholinergics act on the cholinergic system. Furthermore, anticholinergics work mainly in the proximal airways whereas beta agonists work more on the distal conducting airways. Additionally, beta agonists can improve mucocilliary clearance which is not seen with anticholinergics. The algorithm on page 608 can guide you in determining therapy in a step wise fashion.

Chronic use of theophylline does have a role in treating COLD. Patients not optimally responding to ipratropium and B-agonists , can be given a trial of theophylline. Realize that the benefit of theophylline may not always be measured objectively (eg, FEV1). Rather, the patient may experience subjective benefit such as improved exercise tolerance. Keep in mind the toxicity's associated with theophylline, especially in the elderly population. Know what factors influence clearance( see table 25.5 in the asthma chapter). Initially, use a dose to achieve a serum concentration of 8-12mcg/mi. If the patient has not improved, one can consider increasing the dose to achieve a concentration of around 17mcg/ml. One must monitor the patient closely for any untoward effects. If at this higher dose of theophylline, no benefits are realized by the patient, the drug should be discontinued. Be able to initiate dosing in a given patient and be prepared to adjust dosage if indicated. For patients with nocturnal symptoms, a long acting preparation of theophylline given at bedtime can be useful.

What patient characteristics determine a potential for benefit from chronic oral steroid administration? It is still unclear how long a trial of glucocorticoids is required to determine if the patient will benefit from such therapy. A trial of 2-3 weeks is recommended and an improvement in FEV1 of 20-25% should be regarded as a positive response.

What is the role of inhaled steroids in this patient population?

Steroids are often initiated in patients with acute exacerbation of chronic obstructive lung disease who are deteriorating or not responding to sympathomimetics and anticholinergics despite the limited data supporting its' use. Describe steroid dosing including a taper schedule in the acute setting.

What are the criteria for long-term oxygen therapy? Along with improving survival, what other beneficial effects are obtained with oxygen therapy?

What signs are suggestive of acute bronchial infection? Remember that patients may not present with fever, chills or increased white blood cell count. Know that RSV, Strep pnemonia, Moraxelia catarrhalis and H. flu are the common organisms responsible for exacerbations. Be able to recommend appropriate antibiotic therapy keeping in mind resistance patterns at your institution.

Know when patients should receive pneumoccal vaccine and influenza vaccine.

How to manage cor pulmonale is important. One of the best treatments is the use of supplemental oxygen. This will relieve the pulmonary hypertension through dilation of the pulmonary vasculature, thereby decreasing the force against which the right ventricle pumps. Diuretics may be useful, but be aware of the risks and when it is safe to implement such therapy. Digoxin generally has no role in the treatment of cor pulmonale.

Mucolytics, expectorants and respiratory stimulants do not play a big role in COLD therapy. However, be aware of the different expectorant/mucolyties that occasionally may be useful for certain patients.

Tables 11 and 12 from Am J Resp Crit Care Med 1995;152:s97-sl06 review indications for hospitalization and ICU admission for acute COLD exacerbation.

TABLE 11. INDICATIONS FOR HOSPITALIZATION OF PATIENTS WITH COPD

1. Patient has acute exacerbation characterized by increased dyspnea, cough, or sputum production, plus one or more of the following:

• Inadequate response of symptoms to outpatient managemen
• Inability to walk between rooms (patient previously mobile)
• Inability to eat or sleep due to dyspnea
• Conclusion by family and/or physician that patient cannot manage at home, with supplementary home care resources not immediately available
• High-risk co-morbid condition, pulmonary (e.g., pneumonia) or nonpulmonary
• Prolonged, progressive symptoms before emergency visit
• Altered mentation
• Worsening hypoxemia
• New or worsening hypercarbia

2. Patient has new or worsening cor pulmonale unresponsive to outpatient management

3. Planned invasive surgical or diagnostic procedure requires analgesics or sedatives that may worsen pulmonary function pulmonary function

4. Co-morbid condition, e.g., severe steroid myopathy or acute vertebral compression fractures, has worsened

Other indications for hospitalization may apply to patients undergoing pulmonary rehabilitation (see Pulmonary Rehabilitation).

Table 12. INDICATIONS FOR ICU ADMISSION OF PATIENTS WFTH ACUTE COPD EXACERBATION

1. Severe dyspnea that responds inadequately to initial emergency therapy

2. Confusion, lethargy, or respiratory muscle fatigue (the last characterized by paradoxical diaphragmatic motion)

3. Persistent or worsening hypoxemia despite supplemental oxygen or severe/worsening respiratory acidosis (pH < 7.30)

4. Assisted mechanical ventilation is required, whether by means of endotracheal tube or noninvasive technique

Guidelines for inpatient management of COLD.

Identify cause of exacerbation, e.g., infection and direct specific therapy accordingly.

Use a B2-agonist via MDI with spacer or solution for nebulization. In the setting of acute exacerbation, the half-life of beta agonists is shortened, therefore every 30-60 minutes maybe necessary if tolerated. Ipatropium may be added since there is evidence to suggest that they may act synergistically. The dosing frequency is q 4-8 hours. Theophylline can be given to achieve a serum concentration or 8-12mcg/ml, however its role is not clear cut in the acute setting.

Refer to prior question for the role of steroids.

One may confuse the treatment of asthma with that of COLD. Table 1 from Chest 1995;170:Sl98-205 outlines the differences in response with various pharmacologic agents as seen with asthma vs. COLD.

Table 1. Differences in Therapeutic Approaches to Asthma and COPD

Required Reading:

Noyes MA, Stratton MA, Chronic Obstructive Lung Disease, In: Pharmacotherapy: A Pathophysiologic Approach, third edition, 1997:591-613.

Supplemental Reading:

American Thoracic Society Statement: Standards of the Diagnosis and Care of Patients with Chronic Obstructive Pulmonary Disease. Am J Resp Crit Care Med 1995; 152:s77-s120.

Chest 1995; 107:s171-s213 (this entire supplement is devoted to the management of COLD).

CHRONIC OBSTRUCTIVE LUNG DISEASE CASE

GB is a 60 year old male seen in the ER with complaints of increasing shortness of breath, increased production of green-yellow sputum and fever over the past 4 days. Significant history includes chronic bronchitis most likely secondary to cigarette smoking (2 packs per day since his early 20's). Patient is admitted about 3 times per year for exacerbation of COLD however has never required intubation. He has no known allergies. Medications on admission include, albuterol MDI 2 puffs QID and Theodur SR 400mg q 12 hours.

Vitals on admission were BP 140/70 P 120 RR32 T I 00.2

Height and weight 5'8"/80kg

Significant physical exam revealed decreased air entry bilaterally and diffuse expiratory wheezing.

Labs:

• ABG on room air 7.34/50/50 (pH/pCO2/pO2)
• Na 138 K 3.9 Cl 98 HCO3 26 BUN 12 Cr 1.1
• WBC 14.0 with 80% neutrophils
• CXR- no evidence of pneumonia
• T'heophylline level obtained 6 hours post dose was 9mcg/ml
• Peak flow rate 120L/min (normal PEFR for a 5'8" 60year old without COPD is around 520). Comparable information can be obtained from PEFR and FEV1.

Patient was placed on oxygen 1L via nasal cannula with subsequent ABG of 7.34/50/62

1. Outline an initial medication treatment plan for this patient. Include monitoring parameters?
2. What medications should GB be sent home on?

ANSWERS TO COPD CASE

1. Begin albuterol 0.5ml q 1-2 hours via nebulizer. If no improvement, add ipratropium 2.5ml every 6 hours via nebulizer. Some clinicians will choose to begin corticosteroids, although it is not always necessary. If chosen, methylprednisolone 0.5mg IV every 6 hours is the dose commonly used. May continue theophylline.

Obtain gram stain of sputum, blood and urine cultures and begin antibiotic therapy to cover the most likely pathogens. A second or third generation cephalosporin and erythromycin is a reasonable choice.

Parameters to monitor:

• improvement in initial symptom of shortness of breath and increased sputum production.
• Vital signs(temperature, HR, BP)
• physical exam for improvement in air entry and diminished wheezing. Monitor for potential drug toxicity such as tremulousness with beta agonists.
• improvement in WBC, ABG or oxygen saturation via pulse oximetry. improvement in FEV1 or peak flow rate

2. Discontinue the heparin and change ceftizoxime to an oral antibiotic such as a second generation cephalosporin, ampicillin (unless beta lactamase resistance is prevalent at your institution), amoxicillin/clavulanate or TMP/SMX. Continue to complete a 7-10 day course.

Change methylprednisolone to prednisone 40mg daily and continue for 7 –10 days. Some

clinicians choose to rapidly taper the steroid over 7-10 days and others will stop the steroid without a taper. Since the entire duration of therapy is no more than 2 weeks, the risk of adrenal suppression is low. The patient should be counseled to contact his physician should he become symptomatic when the steroids are stopped.

• Reduce ipratropium to 2 puffs qid and change albuterol to MDI, 2 puffs qid. Can continue theophylline and consider a trial off at a later date should he do well with regular use of ipratropium. He should avoid accidentally getting ipratropimn into his eyes since it can elicit a cholinergic response resulting in blurred vision. Ask him to demonstrate inhaler technique. If he has difficulty with the metered dose inhaler despite proper education, have him try with a spacer device.

If this hospitalization occurred during the months of October-January, he should receive an influenza vaccine. Given at this time allows for adequate antibody response before the peak flu season. Check to see when he last received pneumococcal vaccine. If it has been at least six years, a booster dose can be administered. Generally, vaccines should be given after the infection has resolved.

GB improved over the next 3 days and is ready for discharge. He was off oxygen and his ABG on room air was 7.38/39/70. Vitals signs were BP 130/70, RR 16, P90, T98. Sputum gram stain on admission showed many WBC's and a predominance of gram negative coccobacilli (most likely to be H. flu). Pulmonary exam revealed improved breath sounds and minimal expiratory wheezing. His medications currently are albuterol 0.5ml q 4 hours via nebulizer, ipratropium MDI 4 puffs q 6 hours, methylprednisolone 40mg IV q 12 hours, Theodur 400mg q 12 hours, ceftizoxime 1 gm q 8 hours and heparin 5000units SQ q 12 hours. You also found on previous records that his baseline PEFR when he is stable is around 280 L/min.

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