28. Asthma and Chronic Obstructive Pulmonary Disease - Timothy H. Self, PharmD

28-1. Asthma


Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role, in particular mast cells, eosinophils, T-lymphocytes, neutrophils, and epithelial cells. In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night and in the early morning. Asthma affects about 22 million Americans and is the most common cause of missed school days for children. Morbidity and mortality caused by asthma are unacceptably high; death rates are greatest in inner-city African Americans and Hispanics.

Types and Classifications

• Childhood-onset (atopic): Positive family history of asthma, allergy to tree or grass pollen, house dust mites, cockroaches, household pets, and molds

• Adult-onset: Frequently a negative family history and negative skin tests to common aeroallergens

Classification of severity for children over 12 and adults is shown in

Figure 28-1. This classification is extremely important in defining treatment options (see

Figures 28-2 to

28-4). Classification of severity is taken from the National Institutes of Health (NIH) National Asthma Education and Prevention Program, Expert Panel Report 3, 2007 (EPR-3). See EPR-3 for classification of severity for ages 0-4 years and 5-11 years.

Clinical Presentation

• Episodic wheezing, coughing, chest tightness, and shortness of breath that is worse at night, in the early morning, and with exercise


• Asthma is an inflammatory airway disease and also a disease with bronchospasm.

• Common triggers of symptoms include aeroallergens; respiratory viral illness; exercise (especially in cold, dry air); environmental smoke; and fumes.

• Drug-induced asthma includes that caused by aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and β-blockers. Low to moderate-dose β1-selective agents such as atenolol or metoprolol XL can be used if the patient has concurrent post-myocardial infarction or congestive heart failure and does not have severe asthma; COX-2 inhibitors can be used in aspirin-sensitive asthma.

• There is a complex interaction among inflammatory cells (e.g., mast cells, eosinophils, Th2-type lymphocytes); mediators (e.g., leukotrienes); and cytokines (e.g., IL-4, IL-5).

• The result is airway inflammation (mucus and swelling in the lining of the airways) and airway hyperreactivity.

• Early-phase response to inhaling an aeroallergen occurs immediately; late-phase response occurs 4-12 hours later.

• Asthma is commonly worsened by poorly controlled concurrent allergic rhinitis, sinusitis, and gastroesophageal reflux disease (GERD); it may also worsen in the premenstrual or perimenstrual period.

Diagnostic Criteria

• The main basis for diagnosis is a detailed history of episodic symptoms that are typically worse at night and in the early morning and that are associated with common triggers.

[Figure 28-1. Classification of Asthma Severity (Ages ≥ 12 and Adults)]

[Figure 28-2. Stepwise Approach for Managing Infants and Young Children (0-4 Years of Age)]

• Reversible airway obstruction (improvement in pulmonary function tests [FEV1] of > 12% after inhaling a short-acting β2 agonist) is often detected.

• Exclude alternate diagnoses (e.g., chronic obstructive pulmonary disease, vocal cord dysfunction).

Treatment Principles and Goals

• Optimal long-term management of asthma includes four major areas: objective assessment and monitoring, environmental control, pharmacologic therapy, and patient education as a partnership.


Figure 28-3. Stepwise Approach for Managing Asthma in Children 5-11 Years of Age: Treatment]

[Figure 28-4. Stepwise Approach for Managing Asthma ≥ 12 Years of Age and Adults: Treatment]

• Treatment goals are to achieve asthma control by reducing impairment:

• Prevent chronic and troublesome symptoms (e.g., coughing or breathlessness in the daytime, during the night, or after exercise).

• Require infrequent use (< 2 days/week) of inhaled SABA for quick relief of symptoms.

• Maintain (near) "normal" pulmonary function.

• Maintain normal activity levels (including exercise and other physical activity and attendance at work or school).

• Meet patients' and families' expectations of and satisfaction with asthma care.

• Treatment goals are to achieve asthma control by reducing risk:

• Prevent recurrent exacerbations of asthma and minimize the need for ED visits or hospitalization.

• Prevent progressive loss of lung function; for children, prevent reduced lung growth.

• Provide optimal pharmacotherapy with minimal or no adverse effects.

• A stepwise approach to managing asthma is shown in Figure 28-2 (ages 0-4), Figure 28-3 (ages 5-11), and Figure 28-4 (ages ≥12 and adults). These treatment guidelines are from EPR-3. See

Table 28-1 for long-term control medications.

• Inhaled corticosteroids are the most efficacious drugs for long-term management of persistent asthma. Addition of a long-acting inhaled β2 agonist is recommended for patients with moderate or severe persistent asthma.

• Omalizumab (Xolair): Anti-IgE therapy is primarily indicated for severe persistent asthma patients who have frequent emergency department visits and hospitalizations despite optimal therapy. It is given subcutaneously every 2-4 weeks.

• Drug therapy is used for acute exacerbations of asthma. See

Table 28-2 for quick-relief medications and

Figure 28-5 for management of asthma exacerbations.


• Optimal management for the great majority of patients will result in a dramatic reduction in symptoms (including nocturnal and early morning symptoms), as well as reduced acute care visits, fewer lost work or school days, and reduced need for quick-relief medications.

• Monitoring peak expiratory flow (PEF) using a peak flow meter at home is required. Green zone is 80-100% of personal best value. Yellow zone is 50-79% of personal best and indicates that consultation with a health care professional is advisable. Red zone, or < 50% of personal best, indicates that a written action plan should be implemented, and if there is no quick response, immediate medical attention should be sought.

• Spirometry is performed in the physician's office

Mechanism of Action

For more details, see the section on mechanism of action in EPR-3.

Long-term control medications


• Corticosteroids are anti-inflammatory. They block late reaction to allergen and reduce airway hyperresponsiveness. They inhibit cytokine production, adhesion protein activation, and inflammatory cell migration and activation.

• Corticosteroids reverse β2-receptor downregulation and inhibit microvascular leakage.

Cromolyn and nedocromil

(Note: Since the release of EPR-3, cromolyn nebulizer solution and nedocromil MDI became unavailable in the United States in 2008. Cromolyn MDI may be available in the United States through the end of 2009. These drugs are included here for completeness.)

• Cromolyn and nedocromil are anti-inflammatory. They block early and late reaction to allergen, interfere with chloride channel function, stabilize mast cell membranes, and inhibit activation and release of mediators from eosinophils and epithelial cells.

• Cromolyn and nedocromil inhibit acute response to exercise, cold dry air, and SO2.

Long-acting β2 agonists

• With bronchodilation, smooth muscle relaxation follows adenylate cyclase activation and an increase in cyclic adenosine monophosphate (AMP), producing functional antagonism of bronchoconstriction.

• In vitro, long-acting β2 agonists (LABAs) inhibit mast cell mediator release, decrease vascular permeability, and increase mucociliary clearance.

• Compared with short-acting inhaled β2 agonist, salmeterol has a slower onset of action (15-30 minutes). Formoterol has an onset of action within 3 minutes. Both LABAs have a duration of action ≥ 12 hours.

[Table 28-1. Long-Term Asthma Control Medications]

[Table 28-2. Quick-Relief Asthma Medications]


• With bronchodilation, smooth muscle relaxation results from phosphodiesterase inhibition and possibly adenosine antagonism.

• Methylxanthines may affect eosinophilic infiltration into bronchial mucosa as well as decrease T-lymphocyte numbers in epithelium.

• Methylxanthines increase diaphragm contractility and mucociliary clearance.

Leukotriene modifiers

• Leukotriene receptor antagonist; selective competitive inhibitor of CysLT1 receptors

• 5-Lipoxygenase inhibitor

Anti-IgE therapy

• Omalizumab (Xolair) is a humanized monoclonal anti-IgE antibody that binds circulating IgE, thus inhibiting the allergic inflammatory cascade that results when aeroallergens bind to IgE on mast cells.

Quick-relief medications

Short-acting inhaled β2 agonists

• With bronchodilation, smooth muscle relaxation follows adenylate cyclase activation and an increase in cyclic AMP, producing functional antagonism of bronchoconstriction.


• With bronchodilation, there is competitive inhibition of muscarinic cholinergic receptors.

• Anticholinergics reduce intrinsic vagal tone to the airways. They may block reflex bronchoconstriction secondary to irritants or to reflux esophagus.

• Anticholinergics may decrease mucus gland secretion.

Patient Instructions and Counseling

• Patient education is absolutely essential for optimal asthma management.

• Emphasize the need to take controller-preventer medications every day, even when the patient feels well and is having no breathing problems.

• Instruct the patient regarding the dangers of overuse of short-acting inhaled β2 agonists. (The patient should contact a physician if the usual dose does not give quick relief or start the written action plan given by physician.)

• Demonstrate the correct use of the metered dose inhaler (MDI), the MDI plus spacer, and the dry powder inhaler (DPI), and then observe the patient using the devices. Most patients do not perform well initially; the devices can be difficult to use at first (see

Figure 28-6 for MDI or MDI

[Figure 28-5. Management of Asthma Exacerbations: Emergency Department and Hospital-Based Care]

[Figure 28-6. Steps for Using an Inhaler]


Table 28-3. Directions for Use of Peak Flow Meter]

spacer use). For DPIs, remember to stress that inhalation must be rapid and deep.

• Demonstrate correct use of peak flow meters, and observe the patient using them (Table 28-3). Explain about the green, yellow, and red zones (including the written action plan).

• Teach how to prevent exercise-induced asthma.

• Be sure patients receive an influenza vaccination every fall.

Adverse Drug Effects

For more details, see the section on adverse drug effects in EPR-3.

Long-term control medications

Inhaled corticosteroids

• Inhaled corticosteroids may cause coughing, dysphonia, and oral thrush (candidiasis).

• In high doses, systemic effects may occur, although studies are not conclusive, and the clinical significance of these effects (e.g., adrenal suppression, osteoporosis, growth suppression, skin thinning, and easy bruising) has not been established.

Cromolyn and nedocromil

• Approximately 15-20% of patients complain of an unpleasant taste from nedocromil. Cromolyn is quite safe with very few side effects.

Long-acting inhaled β2 agonists

• Tachycardia, skeletal muscle tremor, hypokalemia, or prolongation of QTc interval can occur in an overdose.

• Always use in combination with inhaled corticosteroid in long-term management of asthma. (Use alone could mask inflammation and increase risk of severe exacerbations.)


• Dose-related acute toxicities include tachycardia, nausea and vomiting, tachyarrhythmias (supraventricular), central nervous system stimulation, headache, seizures, hematemesis, hyperglycemia, and hypokalemia.

• Adverse effects at usual therapeutic doses include insomnia, gastric upset, aggravation of ulcer or reflux, increase in hyperactivity in some children, and difficulty in urination in elderly males with prostatism.

Leukotriene modifiers

• Montelukast and zafirlukast are usually well tolerated.

• Zileuton can cause liver dysfunction.

Quick-relief medications

Short-acting inhaled β2 agonists

• Tachycardia, skeletal muscle tremor, hypokalemia, increased lactic acid, headache, and rarely hyperglycemia can occur.

• In general, the inhaled route causes few systemic adverse effects; patients with preexisting cardiovascular disease, especially the elderly, may have adverse cardiovascular reactions with inhaled therapy.


• Drying of mouth and respiratory secretions, increased wheezing in some individuals, and blurred vision if sprayed in eyes can occur.

Systemic corticosteroids

• With short-term use, reversible abnormalities in glucose metabolism, increased appetite, fluid retention, weight gain, mood alteration, hypertension, peptic ulcers, and rarely aseptic necrosis of the femur can occur.

• Consideration should be given to coexisting conditions that could be worsened by systemic corticosteroids, such as herpes virus infections, varicella, tuberculosis, hypertension, peptic ulcer disease, and strongyloidiasis.

Drug-Drug and Drug-Disease Interactions

• For zafirlukast, administration with meals decreases bioavailability. Take at least 1 hour before or 2 hours after meals.

• Zileuton and zafirlukast may increase the effect of warfarin and increase theophylline levels.

• Well-known inducers of cytochrome P450 (carbamazepine, phenobarbital, phenytoin, and rifampin) are documented to decrease the effect of systemic corticosteroids.

• Examples of drugs that may increase the effect of systemic corticosteroids include erythromycin, clarithromycin, itraconazole, oral contraceptives, and conjugated estrogen.

Parameters to Monitor

• Refill record for daily controller-preventer medications and quick-relief medications

• Reduction in symptoms (including nocturnal and early morning symptoms)

• Emergency department visits, hospitalizations, and unscheduled office visits

• Need for "bursts" of systemic corticosteroids

• Lost work or school days and the need for quick-relief medications

• PEF using a peak flow meter at home

In addition, if the patient also has rhinitis or GERD, monitor refills to ensure optimal control. (If rhinitis and GERD are not well controlled, asthma control will likely suffer.)


• Theophylline is no longer used extensively in asthma, but when it is used, knowledge of its kinetics is essential because of its high risk.

• Other drugs, disease states, smoking, age, and diet can all affect theophylline kinetics and dose requirements (see

Table 28-4).

• Therapeutic serum theophylline concentrations are 5-15 mcg/mL (not the old recommendation of 10-20 mcg/mL; see EPR-3).

• Elimination half-life in an otherwise healthy nonsmoking adult is about 8 hours. In a smoker, it is about 4 hours, and in a small child (1 year or older), it is about 4 hours.

• Neonates have greatly prolonged elimination half-life.

• Elimination half-life in decompensated heart failure or cirrhosis is about 24 hours.

• Volume of distribution is about 0.5 L/kg.

• High-fat meals may cause "dose dumping" for some products (check product literature).


• MDIs should be stored at room temperature, between 59°F and 86°F; if left in a car in freezing or near-freezing temperatures, aerosol particles will be too large to inhale into the lungs.

• MDIs should be "primed" (one dose released) only with first use or in the case of a prn agent used only once every 2 weeks. (Frequent priming is unnecessary and wastes expensive medications.)

• HFA MDIs need special attention regarding weekly cleaning of the actuator (see manufacturers' instructions)

• MDI dust cap should be left on inhaler when not in use. Check mouthpiece for foreign objects before inhaling.

Nondrug Therapy

• An essential component of optimal asthma management is environmental control.

• Without good control of the environment at home, school, and work, drug therapy will often be inadequate.

• Have the patient identify known asthma triggers, and help the patient identify potential triggers not yet realized. (Do not forget someone smoking at home or work!)

28-2. Chronic Obstructive Pulmonary Disease (COPD)


COPD is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases. COPD is a major cause of death and suffering in the United States and around the world. It is the fourth leading cause of chronic morbidity and mortality in the United States.

Types and Classifications

Some clinicians still refer to chronic bronchitis and emphysema in characterizing different levels of COPD (e.g., emphysema patients have destructive damage to the alveolar walls, whereas chronic bronchitis is associated with chronic productive cough). According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2008 update, COPD severity classification is as follows:

[Table 28-4. Factors Affecting Serum Theophylline Levels]

• I. Mild: FEV1/FVC < 0.7 and FEV1 ≥ 80% predicted

• II. Moderate: FEV1/FVC < 0.7 and 50% < FEV1 < 80% predicted

• III. Severe: FEV1/FVC < 0.7 and 30% ≤ FEV1 < 50% predicted

• IV. Very severe: FEV1/FVC < 0.7 and FEV1 < 30% predicted or FEV1 < 50% predicted plus chronic respiratory failure.

In addition, examples of factors affecting the severity of this disease include frequency of exacerbations, presence of other disease states, overall health status, and severity of symptoms.

Clinical Presentation

• Shortness of breath

• Cough and sputum production

• Usually, a history of cigarette smoking for several years

• In the more severe form, respiratory failure and heart failure


• COPD is usually caused by long-term smoking; it may also be caused by exposure to other noxious particles and gases.

• Chronic inflammation is found throughout the airways but via different inflammatory cells and mediators than those that cause asthma. Thus, the response to inhaled corticosteroids is much less than that seen with asthma.

• An imbalance of proteinases and antiproteinases is found in the lung.

• A rare hereditary cause of emphysema is α1-antitrypsin deficiency.

• Pathologic changes are found in the central and peripheral airways as well as the alveoli and pulmonary vasculature.

• The following pathological changes are also found:

• Mucus hypersecretion

• Ciliary dysfunction

• Airflow limitation

• Lung hyperinflation

• Gas exchange abnormalities

• Secondary pulmonary hypertension

• Cor pulmonale

Diagnostic Criteria

• History of cigarette smoking or exposure to other noxious particles or fumes

• Chronic cough and sputum production

• Spirometry (e.g., reduced FEV1)

• Other lung diseases ruled out

Treatment Principles and Goals

• Management of COPD includes the following principles and goals: prevent progression of disease, relieve symptoms, enhance health status, increase exercise tolerance, prevent and treat exacerbations and complications, and decrease mortality.

• Bronchodilators are central to the symptomatic treatment of COPD; these agents will increase exercise capacity without necessarily improving the FEV1.

• Inhaled bronchodilators are preferred to oral bronchodilators for initial therapy; the specific choice of agent depends on patient response.

• Long-acting inhaled bronchodilators are more effective and convenient but more expensive. Examples of long-acting bronchodilators include the once-daily anticholinergic tiotropium (Spiriva) and twice-daily LABAs (formoterol and salmeterol—discussed in Section 28-1).

• Short-acting inhaled β2 agonists are preferred for prn use in patients already receiving LABAs and anticholinergics.

• Inhaled corticosteroids are reserved for COPD patients with severe or very severe disease (Stage III or IV) and frequent exacerbations.

• Theophylline is an option for maintenance therapy in patients who are not optimally controlled with β2 agonists and anticholinergics.

Therapy at each stage

(See the GOLD 2008 update.)

For each stage, patients should avoid risk factors (e.g., cease smoking) and receive an influenza vaccine each autumn. Also, pneumococcal vaccine should be administered per current guidelines.

• Stage I: Mild COPD

• Use short-acting bronchodilator as needed.

• Stage II: Moderate COPD

• Add scheduled therapy with one or more long-acting bronchodilators and rehabilitation.

• Stage III: Severe COPD

• Use scheduled therapy with one or more long-acting bronchodilators.

• Add inhaled corticosteroids if patient has recurrent exacerbations.

• Stage IV: Very severe COPD

• Same treatments as for stage III, and consider surgical treatment.

• Long-term O2 therapy if patient experiences chronic respiratory failure.

Drug therapy for acute exacerbations of COPD

• Inhaled albuterol, ipratropium, or both

• Systemic corticosteroids (e.g., prednisolone 30 mg/d for 14 days)

• O2

• Oral antibiotics for purulent sputum as well as increased sputum volume and increased dyspnea

• Choice of oral antibiotic depends on severity:

• Mild exacerbation: Use amoxicillin, doxycycline, or trimethoprim-sulfamethoxazole (alternatives include β-lactam plus β-lactamase inhibitor, azithromycin, or second- or third-generation cephalosporins).

• Moderate exacerbation: Use a β-lactam plus β-lactamase inhibitor (alternatives are respiratory fluoroquinolones such as moxifloxacin or levofloxacin).

• Severe exacerbation with risk factors for Pseudomonas aeruginosa infection: Use ciprofloxacin or levofloxacin (high dose, 750 mg). If parenteral treatment is needed, use the same fluoroquinolones or an antipseudomonal β-lactam.


• Spirometry: FEV1

• Symptoms of dyspnea, cough, sputum production, and change in sputum color and volume

• PaO2

• Exercise tolerance or fatigue

Long-term drug therapy

• See content under Section 28-1 for specific drugs.

• Tiotropium is a once-daily anticholinergic bronchodilator that is an option for step 1 treatment of moderate to severe COPD. It is administered by a DPI (HandiHaler). Each dose must be loaded, and deep inhalation does not have to be forceful but must be sufficient to hear the capsule vibrate. Another tiotropium delivery device, Respimat Soft Mist Inhaler (multidose), is available outside the United States.

Nondrug therapy

• Smoking cessation—nicotine replacement therapy, bupropion (Zyban), varenicline (Chantix), support groups, and counseling

• Oxygen therapy

• Nutritional support

• Psychosocial support

• Pulmonary rehabilitation

Smoking cessation is the most important of these therapies.

28-3. Key Points


• Asthma is primarily an inflammatory airway disease.

• It is commonly undertreated, resulting in much unnecessary suffering and economic loss.

• Managing patients via the principles of the National Institutes of Health guidelines (EPR-3) has been clearly shown to reduce emergency department visits and hospitalizations and to improve patient quality of life.

• Optimal long-term management includes objective assessment, environmental control, drug therapy, and patient education working in a partnership.

• Patients with persistent asthma need daily controller therapy (anti-inflammatory agents).

• Inhaled corticosteroids are the most efficacious agents to control asthma and are the preferred first-step drug treatment for all ages of mild persistent asthma.

• Inhaled long-acting inhaled β2 agonists are the preferred treatment to add to inhaled corticosteroids for patients with moderate persistent or severe persistent asthma.

• Short-acting inhaled β2 agonists are the agents of choice for quick relief of symptoms.

• Pharmacists should teach patients how to use inhalers (MDI, MDI-spacer, and DPI) by demonstrations and observation of the patient.

• Pharmacists should instruct patients on how to use peak flow meters, including color-coded zone management with a written action plan. Written action plans may be peak flow based, symptom based, or both.

• Patients must clearly understand the purpose of daily controller or preventer medications versus quick-relief medications. Show patients airway models or colored pictures of normal versus inflamed airways.

Chronic Obstructive Pulmonary Disease

(See the GOLD 2008 update.)

• The overall approach to managing stable COPD should be characterized by a stepwise increase in treatment and should be tailored to reduce symptoms and enhance quality of life.

• Health education can play a role in improving skills, ability to cope with COPD, and health status. It is effective in accomplishing certain goals, including smoking cessation in some patients.

• None of the existing medications for this disease has been shown to modify the long-term decline in pulmonary function that is the hallmark of this COPD. Drug treatment for COPD is used to improve symptoms or decrease complications.

• Bronchodilators are central to the symptomatic management of this disease. They include β2 agonists, anticholinergics, and theophylline.

• Inhaled therapy with long-acting agents is preferred for reasons of efficacy and convenience.

• Combining bronchodilators may improve efficacy and decrease the risk of side effects compared with increasing the dose of a single bronchodilator.

• Regular treatment with inhaled corticosteroids should be prescribed only for symptomatic patients with severe or very severe COPD and recurrent exacerbations.

• Chronic treatment with systemic corticosteroids should be avoided because risks outweigh benefits.

• The long-term administration of oxygen (> 15 hours per day) to COPD patients with chronic respiratory failure has been shown to increase survival.

• Patients with COPD benefit from exercise training programs; they show improvement with respect to both exercise tolerance and symptoms of fatigue and dyspnea.

• Influenza vaccine can reduce serious illness in COPD patients. Pneumocococcal polysaccharide vaccine is recommended for patients with COPD who are 65 years of age or older and for patients under 65 years of age who have an FEV1 < 40% predicted.

28-4. Questions


Asthma is primarily due to which underlying problem?

A. Pulmonary fibrosis

B. Infection

C. Inflammation

D. Bronchospasm

E. Granulomas



Which objective measure for routine monitoring of asthma is available at home?




D. O2 saturation

E. PD20



Which device requires slow inhalation?

A. Diskus

B. Turbuhaler

C. Aerolizer


E. Rotadisk



How many seconds is optimal for breath holding after inhaling from an MDI?

A. 4

B. 5

C. 15

D. 2

E. 10



When a peak flow meter is used, what percentage of the personal best value is the yellow zone?

A. < 50

B. < 60

C. 50-79

D. 60-89

E. 40-60



What are the trade names for long-acting inhaled β2 agonists?

A. Foradil and Serevent

B. Pulmicort and Flovent

C. Aerobid and Combivent

D. Maxair and Atrovent

E. Flovent and Ventolin



Which disease states decrease theophylline elimination and often result in reduced dosage requirements?

A. Hepatitis

B. Heart failure (decompensated)

C. Hypertension

D. A, B, and C

E. A and B



Which drugs are preferred for long-term treatment of moderate persistent asthma?

A. Budesonide + formoterol

B. Fluticasone + salmeterol

C. Beclomethasone + ipratropium

D. A or B

E. B or C



Which drug is a once-daily anticholinergic bronchodilator?

A. Atrovent

B. Serevent

C. Foradil

D. Spiriva

E. Proventil



For patients with asthma or COPD exacerbations who are not responding adequately to inhaled bronchodilators, what is the agent of choice to add to manage the acute exacerbation?

A. Fluticasone

B. Budesonide

C. Cromolyn

D. Theophylline

E. Prednisone



Which drug may increase serum theophylline concentrations?

A. Clarithromycin

B. Hydrochlorothiazide

C. Carbamazepine

D. Rifampin

E. Phenytoin



Which side effect of inhaled corticosteroids is reduced by spacer devices?

A. Hoarseness

B. Decreased bone density

C. Thinning of skin

D. Oropharyngeal candidiasis

E. Cataracts



The therapeutic range for theophylline per the NIH guidelines for asthma management is

A. 5-15 mcg/mL

B. 8-12 mcg/mL

C. 10-20 mcg/mL

D. 15-25 mcg/mL

E. 10-15 mcg/mL



Which asthma controller drug is given qhs?

A. Accolate

B. Singulair

C. Xolair

D. Intal

E. Medrol



Which disease state may worsen asthma?

A. Coronary artery disease


C. Diabetes

D. Hypertension

E. Arthritis



Which class of drugs is indicated only in severe COPD patients who have frequent exacerbations?

A. Long-acting inhaled β2 agonists

B. Anticholinergics

C. Short-acting inhaled β2 agonists

D. Inhaled corticosteroids

E. Methylxanthines


The next two questions relate to Case Study 28-1.

Case Study 28-1 Medication Profile


Patient name

Thomas Johnson



5689 Washington St.


Date of birth



Drug allergies

Aspirin sensitivity






75 kg



(1) Asthma (childhood onset, moderate persistent)


(2) Allergic rhinitis


(3) Hypertension




Rx #


Drug and strength







Accolate 20 mg


1 bid





Albuterol MDI


2 puffs q4h







bid as dir.




T. Jones

Lopressor 50 mg


1 bid





Albuterol MDI


2 puffs q4h


Pharmacist notes: 3/16—discussed proper use of MDI and observed patient use. Coached Mr. Johnson to inhale slowly (he was inhaling fast); he used the MDI correctly for the other steps.


Which class of drugs is preferred in Mr. Johnson for optimal control of asthma?

A. Anticholinergics

B. Inhaled corticosteroids

C. Methylxanthines

D. Mast cell stabilizers

E. Oral corticosteroids



What is an appropriate alternative to Lopressor in Mr. Johnson?

A. An ACE inhibitor

B. Propranolol 40 mg bid

C. Clonidine

D. Hydralazine

E. Atenolol 200 mg daily


The next two questions relate to Case Study 28-2.

Case Study 28-2 Medication Profile


Patient name

Mrs. S. T. Adams



7129 James Ave.


Date of birth



Drug allergies







55 kg



(1) COPD—53 pack/year Hx smoking (quit 2 years ago)


(2) Cirrhosis




Rx #


Drug and strength







Serevent Diskus


1 bid





Albuterol MDI


2 puffs q4h prn





Atrovent MDI


2 puffs q6h





Uniphyl 600 mg


1 qd 6 PM


Pharmacist Notes: 2/18—discussed proper use of Diskus and observed patient use; taught Mrs. Adams to inhale deeply and rapidly (she was inhaling slowly for < 2 seconds). Also observed use of MDI (she forgot to exhale gently before pressing down on MDI).


What concerns should the pharmacist have in this situation regarding theophylline?

A. Cirrhosis is well documented to decrease elimination of theophylline.

B. The milligrams per kilogram dose is too low.

C. Mrs. Adams should be on a q12h product.

D. Theophylline SR should be dosed in the morning, not evening.

E. Long-acting inhaled β2 agonists increase theophylline clearance.



The patient has a friend who has COPD and has told her about Spiriva. Mrs. Adams wants to know the opinion of the pharmacist. You would say:

A. I'll call your doctor and suggest a new prescription for Spiriva.

B. Spiriva is a third-line drug for COPD; I would not use it now.

C. Spiriva is a good drug, but I want to talk to your doctor about starting a medicine called Flovent.

D. Since you have a prescription for Atrovent, I will call your doctor and suggest changing from Atrovent to Spiriva.

E. I think Symbicort would be better for you.



Which drug is best for long-term management of mild persistent asthma?

A. Cromolyn

B. Montelukast

C. Nedocromil

D. Theophylline

E. Budesonide



Which total daily dose of prednisone is best for home management of an acute exacerbation of asthma in a 60-kg adult?

A. 5.0 mg

B. 60.0 mg

C. 10.0 mg

D. 20.0 mg

E. 7.5 mg



Which drug is most likely to cause an asthma exacerbation in a patient sensitive to aspirin?

A. Ibuprofen

B. Acetaminophen

C. Celecoxib

D. Salsalate

E. Sodium salicylate



Which type of inhaler does not work well in very cold temperatures?

A. Diskus

B. Turbuhaler

C. Aerolizer


E. Rotahaler


28-5. Answers


C. Although asthma certainly does have a bronchospastic component, it is primarily due to inflammation, so good control of inflammation dramatically reduces bronchospasm. A good indicator of disease control is the rare need for short-acting inhaled β2 agonists.



A. Peak flow meters are inexpensive and relatively easy to use. Good measurement of peak expiratory flow requires appropriate technique, and if good technique is used, patients have valuable objective evidence of asthma control (or exacerbation).



D. Dry powder inhalers for asthma therapy that are currently available require rapid inhalation. MDIs require slow inhalation to minimize impaction of aerosol in the mouth and throat.



E. Ten seconds is best; there is no need to hold longer. If 10 seconds is uncomfortable, 4-5 seconds is acceptable.



C. The yellow zone is 50-79%, which indicates suboptimal control. (The red zone is < 50%, which indicates that the crisis action plan should be started and medical attention should be sought.)



A. Foradil (formoterol) and Serevent (salmeterol).



E. Hepatitis and decompensated heart failure both can dramatically reduce theophylline clearance.



D. (A. budesonide + formoterol or B. fluticasone + salmeterol.) See Figures 28-2 and 28-3.



D. Atrovent is also a quick-relief agent, but it is not as efficacious in asthma and has a slower onset than albuterol and other short-acting inhaled β2 agonists.



E. Prednisone or other systemic corticosteroids (e.g., methylprednisolone) are well documented to be efficacious in asthma and acute exacerbations of COPD.



A. Clarithromycin is documented to increase serum concentrations. Hydrochlorothiazide does not affect serum theophylline concentrations, and the remaining choices are all documented to decrease serum theophylline concentrations.



D. Oropharyngeal candidiasis or thrush is correct. The other side effects are not reduced by spacers.



A. The currently accepted range for asthma is 5-15 mcg/mL (not the old range of 10-20 mcg/mL). There is no benefit in exceeding 15 mcg/mL, and many patients receive benefit at lower doses.



B. Because asthma is a disease of circadian rhythm and is worse between 2:00 am and 6:00 am, it is best to give this once-daily drug at bedtime.



B. GERD can worsen asthma if it is not properly treated. The exact mechanisms are debated, but there is excellent documentation that asthma improves if this condition is well managed.



D. This class of drugs should not be used routinely in COPD patients with mild disease. In severe disease, inhaled corticosteroids are indicated, especially if there are frequent exacerbations. Remember that in asthma, inhaled corticosteroids are the best agents for long-term control, but in COPD their role is limited.



B. Inhaled corticosteroids are the preferred treatment (see Figures 28-2 and 28-3 for treatment choices). The pharmacist should share the NIH guidelines with Mr. Johnson's prescriber to help ensure optimal care. In addition, the pharmacist should educate the patient regarding the purpose of the medications and proper use of inhalers (e.g., the pharmacist should observe the patient using the device).



A. An ACE inhibitor should be efficacious with few side effects (monitor for cough); β-blockers should be avoided in Mr. Johnson unless he is post-myocardial infarction or had congestive heart failure (in which case, use a low dose of a β1-selective blocker and monitor carefully).



A. Cirrhosis is well documented to decrease elimination of theophylline. Ensure a check of a steady-state theophylline level (peak) and anticipate dose reduction (usually 50% dose reduction in liver disease).



D. Because the patient has prescriptions for Atrovent and Serevent, a logical change here would be to discontinue the short-acting anticholinergic Atrovent and add the long-acting once-daily anticholinergic tiotropium (Spiriva).



E. Budesonide is an inhaled corticosteroid, the class of drugs recommended to treat even mild persistent asthma.



B. Sixty milligrams is an appropriate dose. If it is started as soon as the patient is in the red zone and not responding quickly to short-acting inhaled β2 agonists, usually only a few days of treatment will be required (usually < 1 week).



A. Ibuprofen has the same mechanism of action as aspirin and will predictably trigger symptoms in an aspirin-sensitive patient (i.e., increased production of leukotrienes). COX-2 inhibitors are safe (celecoxib). Acetaminophen is the choice agent for minor pain in these patients.



D. MDIs release large aerosol particles that do not penetrate deeply into the lungs in cold temperatures. Dry powder inhalers are acceptable.


28-6. References


Berger WE, Qaquandah PV, Blake K, et al. Safety of budesonide inhalation suspension in infants aged six to twelve months with mild to moderate persistent asthma or recurrent wheeze. J Pediatr. 2005; 146:91-95.

Dolovich MB, Ahrens RC, Hess DR, et al. Device selection and outcomes of aerosol therapy: Evidence-based guidelines: American College of Chest Physicians/American College of Asthma, Allergy, and Immunology. Chest. 2005;127:335-71.

Fanta CH. Asthma. N Engl J Med. 2009;360: 1002-14. (Drug Therapy Review)

Hendeles L, Jenkins J, Temple R. Revised FDA labeling guideline for theophylline oral dosage forms. Pharmacotherapy. 1995;15:409.

National Institutes of Health (NIH). Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma, 2007. NIH Publication 07-4051. Bethesda, Md.: NIH. Available at:

Self TH, Chrisman CR, Mason DL, Rumbak MJ. Reducing emergency department visits and hospitalizations in African American and Hispanic patients with asthma: A 15-year review. J Asthma. 2005;42:807-12.

Shannon M. Life-threatening events after theophylline overdose: A 10-year prospective analysis. Arch Intern Med. 1999;159:989-94.

Strunk RC, Bloomberg GR. Omalizumab for asthma. N Engl J Med. 2006;354:2689-95.

Weiss KB, Sullivan SD. The health economics of asthma and rhinitis: I. Assessing the economic impact. J Allergy Clin Immunol. 2001;107:3-8.

Chronic Obstructive Pulmonary Disease

Calverley P, Pauwels R, Vestbo J, et al. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: A randomised controlled trial. Lancet. 2003;361:449-56.

Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Gig Harbor, Wash.: Medical Communications Resources. Available from:

Gross NJ. Tiotropium bromide. Chest. 2004;126: 1946-53.

Pauwels R, Lofdahl CG, Laitinen LA, et al. Long term treatment with inhaled budesonide in persons with mild COPD who continue smoking. N Engl J Med. 1999;340:1948-53.

Rigotti NA. Treatment of tobacco use and dependence. N Engl J Med. 2002;346:506-12.

Tashkin DP, Celli B, Senn S, et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008;359:1543-54.

Wedzicha JA, Calverley PMA, Semungal TA, et al. The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide. Am J Respir Crit Care Med. 2008;177:19-26.