Sharon Connor, Pharm.D.
Spring 1998

Asthma

1. Introduction
2. Diagnosis
3. Classification
4. Management
5. Conclusion
6. Case #1
7. Case #2

Objectives

1. Discuss the pathophysiology and underlying causes of asthma.

2. List precipitating factors of an asthma attack.

3. Assess the severity of asthma based on presenting symptoms, physical exam, spirometry.

4. Develop a treatment plan based on the severity of asthma diagnosed. Develop a treatment plan for an acute exacerbation as well as the management of chronic asthma.

5. List nonpharmacologic interventions in the management of asthma.

6. Discuss the role of beta-agonists in the management of asthma.

7. Discuss the role of anti-inflammatory agents in the management of asthma.

8. Communicate to the patient instructions for the use of medications to control asthma. Include rationale, dosing, duration of use, possible adverse effects and how they should be managed.

9. Communicate to the patient the instructions for use of peak flow meters for monitoring and management of asthma. Discuss the use of the green, yellow and red zone including rationale.

10. List the goals in the management of asthma.

All exam questions will come from these objectives. The handout provided serves as an outline to guide you through the reading materials and application of the reading to the objectives.

Required readings:

Self TH, Kelly HW. Asthma in Applied Therapeutics: The Clinical Use of Drugs, 6th ed.

Young LE, Koda-Kimble MA, eds.. Vancouver, WA:Applied Therapeutics, Inc.1995.

This chapter has many examples and discussions on pediatric asthma. You will not be tested on pediatric asthma as it is covered elsewhere.

Suggested readings:

National Heart, Lung and Blood Institute. Expert Report Panel II: Guidelines for the Diagnosis and Management of Asthma. National Asthma Education and Prevention Program. Publication No. 95-4051. April 1997. Available on-line at the NHLBI home page-http://www.nhlbi.nih.gov/nhlbi/nhlbi.htm

Barnes PJ. Inhaled Glucocorticoids for Asthma. New Eng J Med 1995;332:868-875.

I. Introduction

A. Definition

1. Asthma is a chronic inflammatory disorder of the airways

2. Characterized by:

1. Reversible airflow obstruction
2. Airway hyperreactivity
3. Airway inflammation

B. Pathophysiology

1. Airway hyperresponsiveness

2. Acute airflow limitation due to:

1. Acute bronchoconstriction which varies according to the stimulus
2. Swelling of the airway wall
3. Chronic mucus plug formation
4. Airway wall remodelling

C. Risk factors for asthma

1. Predisposing factors

1. Atopy-propensity to produce abnormal amounts of IgE in response to exposure to environmental allergens

2. Causal factors

1. Indoor/Outdoor allergens (mites, animal, cockroach, pollens, fungi)
2. Aspirin
3. Occupational sensitizers

3. Contributing factors

1. Respiratory infections
2. Small size at birth
3. Air pollution
4. Smoking (Active and Passive)

D. Factors that exacerbate asthma: Triggers

1. Allergens
2. Respiratory infections
3. Exercise and hyperventilation
4. Weather
5. Sulfur dioxide
6. Foods, additives, drugs

II. Diagnosis

A. Medical history

1. Symptoms and pattern of symptoms

2. Precipitating or aggravating factors

3. Family history

4. Development of disease

5. Living situation

B. Clinical presentation

1. After exposure to a precipitant, the asthmatic patient may develop immediate symptoms (early asthmatic response), or the symptoms may be delayed (late asthmatic response).

1. Early asthmatic response results from airway smooth muscle constriction and edema.
2. Late asthmatic response is caused by the cellular phase of the inflammatory reaction. Involves accumulation of inflammatory cells.

2. Classic triad: wheezing, cough and shortness of breath

3. Signs and symptoms of severe exacerbation

1. Heart rate >130/minute
2. Respiratory rate >30
3. Pulsus paradoxus >10mmHg
4. Diaphoresis
5. Accessory muscle use
6. Altered mental status: anxiety, confusion, somnolence

C. Laboratory studies

1. Spirometry

2. Complete blood count

3. Sputum examination and stain for eosinophilia (sputum eosinophilia are highly characteristic of asthma)

4. Complete pulmonary function studies

5. Chest x-ray

6. Arterial blood gases- during an acute exacerbation to assess severity

III. Classification

Classifying asthma severity is important in guiding therapeutic recommendations.

Asthma may be classified as chronic, exercise induced or an exacerbation. We will focus on chronic asthma and exacerbations (signs and symptoms of acute exacerbation mentioned above).

A. Stepwise approach to classification of chronic asthma

IV. Management

A. Asthma can be effectively controlled in most patients, although it cannot be cured

B. The major factors contributing to asthma morbidity and mortality are underdiagnosis, inappropriate treatment and insufficient education

C. The goal of management is to achieve control of asthma defined as:

-Minimal chronic symptoms, including nocturnal symptoms

-Minimal exacerbations

-No emergency visits

-Minimal need for prn beta-agonists

-No limitations on activities including exercise

-Peak flow circadian variation of less than 20 percent

-Normal peak expiratory flow rate

-Minimal or no adverse effects from medication

D. Medications used in the management of asthma

1. Long-term control medications

National Heart, Lung and Blood Institute. Expert Report Panel II: Guidelines for the Diagnosis and Management of Asthme.
National Asthma Education and Prevention Program. Publication No. 95-4051. April 1997 p. 33-4

2. Quick-Relief Medications

E. Asthma exacerbation management

1. Home treatment

2. Emergency Room and Hospital Based Care

F. Stepwise Approach to the Management of Chronic Asthma

G. Nonpharmacologic

1. Devices for medication delivery

1. MDI's: most popular, convenient, efficacious -GOOD TECHNIQUE REQUIRED!
2. Nebulizers

2. Spacing devices

1. Decreased oropharyngeal deposition, increased lung delivery
2. Allows evaporation of propellant prior to inhalation
3. Good technique still important but requires less coordination

3. Peak flow meters

1. Measure peak expiratory flow rate (L/min)
2. May be used in the home to monitor asthma
3. Establishing personal best, then green, yellow and red zones
4. Patient education

• How and when to use a peak flow meter
• How to record peak flows in a diary
• How to interpret the measurements
• How to respond to change
• What information to communicate to the health care professional

V. Conclusion

Effective control of asthma can be accomplished through:

1. Education of patients to develop a partnership in asthma management

2. Assessment and monitoring of asthma severity with both symptom reports and measures of lung function

3. Avoidance or control asthma triggers

4. Establishing individual medication plans for long term management

5. Establishing plans for monitoring exacerbations

6. Providing regular follow-up care

CASE #1

JK is a 34 year old asthmatic who presents to the emergency room with complaints of cough and increasing shortness of breath. She feels like she is getting a cold. She has been using her abuterol MDI more frequently for the past three days and has used it 8 times in the last 2 hours with minimal relief. She states she also uses another inhaler but cannot remember the name. She tried obtaining a peak flow reading with the latest reading obtained being 100 L/min. She says that her asthma always gets worse when the weather changes.

PMH: asthma, hospitalized 2 times in the past, no ICU admissions, treated with steroids 3 times in the past 6 months, allergic rhinitis

ALL: NKDA

PE: WDWN female unable to talk in complete sentences

Vitals: P 140, BP 118/70, RR 36, T 98.6

HEENT: wnl

Chest: (+) accessory muscle use, poor air entry, few wheezes

Extrem: no cyanosis

Nuero: oriented to person and time but not place

Labs: peak flow 100 L/min (personal best 420 L/min)

ABG (room air) pH 7.47, pCO₂ 30, pO₂ 60

Chest x-ray: no infiltrates

SH: 1 pack per day for 15 years

Assessment: Acute asthma exacerbation

Questions

1. What precipitating factors (triggers) may have provoked this asthma attack?

2. What information in the history and physical exam aid in the assessment of severity?

3. What would be the initial treatment for JK's asthma exacerbation?

JK is much improved after 2 days in the hospital. You question the patient further as to past medication use. She remembers now that she used a fluticasone MDI she thinks 2 puffs twice a day but quit using it about one month ago because she was feeling great and did not think she had any refills anyhow.

4. JK is now ready for discharge. What chronic treatment would you recommend for JK? (Include drug, dose, patient instructions and monitoring parameters)

5. JK returns to the clinic and states she is feeling much better. Her peak flow readings have improved and are consistently 400-420 L/min. What other information do you need? What recommendations would you make?

CASE #1 Answers

1. Triggers:

• Possible viral upper respiratory tract infection.
• Weather: Adverse weather conditions such as freezing temperatures, high humidity, thunderstorms and episodes of acute pollution brought on by weather conditions have been associated with asthma exacerbations.
• patient with PMH of allergic rhinitis
• Another important aspect is that this patient has been noncompliant with her steroid inhaler.

2. Assessment of severity from the history and physical exam.

• failure of albuterol to control symptoms
• history of steroid use in the past
• history of hospitalization x2

Physical Exam:

• unable to talk in complete sentences
• oriented to person, time but not place (altered mental status)
• pulse of 140
• respiratory rate of 36
• accessory muscle use
• few wheezes

Spirometry

• peak flow 100 L/min (26% of personal best)
• ABG's:increased pH, and decreased pO₂ and pCO₂

3. What would be the initial treatment for JK's asthma exacerbation?

-Oxygen-Start with 30-40% via ventimask or 5L via nasal cannula

-Medications:

Bronchodilators: relax airway smooth muscle, enhance mucociliary clearance, decrease vascular permeability, may modulate mediator release from mast cells and basophils

-Albuterol 2.5 mg via nebulizer q20 minutes for 3 doses then reduce to q 1-2 hours as symptoms improve.

or

-Metaproterenol 15mg nebulized q20 minutes for 3 doses then reduce based on symptoms

Monitor for response: regression of initial findings which includes talking in complete sentences, decrease in pulse and respiratory rate, no accessory muscle use, better air entry (may see wheezes as ventilation improves), improvement in peak flow, improvement in oxygenation

Monitor for adverse effects: increased heart rate, muscle tremors

Anti-inflammatory medications

-Steroids: exact mechanism not fully understood. Interference with arachidonic acid metabolism and the synthesis of leukotrienes and prostaglandins, reduction in microvascular leakage, inhibition of cytokine production and secretion, prevention of the directed migration and activation of inflammatory cells and increased responsiveness of beta receptors of the airway smooth muscle.

Methylprednisolone 40-60mg IV q6 hours for 48-72 hours

-rationale: severe unresponsive asthma with history of steroid use in past

Monitor for adverse effects: blood pressure, potassium and blood sugar

Role of theophylline: If patient has been on theophylline in the past and presents with a sub-therapeutic theophylline level IV aminophylline may be used. In patients who have not received theophylline previously or who have therapeutic concentrations, it is controversial whether it is of benefit in the emergency room.

Anticholenergics: If symptoms do not improve anticholinergic medication may be added.

Ipratropium bromide is a bronchodilator that blocks postganglionic efferent vagal pathways. When inhaled, these agents produce bronchodilation by reducing intrinsic vagal tone to the airways. Less potent bronchodilators than beta-agonists and slower onset of action (30- 60 min). May have an additive effect when nebulized together with a short acting beta agonist.

4. Chronic management. The goal is to achieve and maintain control of JK's asthma.

Convert IV steroid to oral steroid. Prednisone 40mg qd x 1week. Taper is not needed since patient is not steroid dependent and has been on oral steroids for less than 2 weeks.

You decide to assess the severity of JK's asthma prior to admission. She states that in the 2 weeks before she was admitted she was using her albuterol MDI every day sometimes 2-3 times a day. She complained of symptoms almost daily due to her asthma. She woke up once or twice a week with coughing and shortness of breath. Since she did not feel well she started using her peak flow meter with reading in the 200-300 range, never better than 300 L/min.

In which category of asthma is JK and why?

These finding put JK in the Moderate Persistent category of asthma. Why?: daily albuterol, wakes up at night frequently with symptoms, peak flow in the yellow zone.

Long term options for JK's pharmacologic management include:

1. The use of an inhaled corticosteroid daily: Fluticasone 220mcg 2 puffs twice a day since she has used this in the past. Have JK use this inhaler with a spacer for optimalmedication delivery. Steroids at present are the most effective controllers of asthma.

2. Long acting bronchodilator, especially for nighttime symptoms: long acting beta-agonist (salmeterol 2 puffs bid-has a long onset of action therefore never use in the acute setting or prn) or sustained release theophylline.

3. Short-acting bronchodilator to be used as needed. Albuterol 2 puffs every 4-6 hours as needed not to exceed 4x a day.

Assessment parameters:

• improvement in peak flow readings
• reduction in asthma symptoms
• frequently of albuterol use
• frequency of oral steroid use
• reduction in number of ER visits and hospitalizations
• avoidance of adverse effects of medications
• compliance

Side effects:

Albuterol/Salmeterol: palpitations, nervousness, tremor, hypokalemia

Fluticasone: oral candidiasis, hoarseness

Patient counseling:

Reinforcement of proper inhaler technique at each visit (make the patient demonstrate technique each time!)

Rinse mouth out after each use to prevent oral candidiasis

Encourage peak flow monitoring

Total management:

1. The first step is EDUCATION. This patient did not understand the role of her steroid MDI in the management of her asthma. She also needs education regarding the proper use of her peak flow meter to manage her asthma.

2. Assessment and monitoring of asthma severity with symptom reports and measures of lung function. JK may be taught to use her peak flow meter to manage her asthma. She should be instructed on how to use the zone system to monitor the worsening of her asthma. She may also keep a log of her exacerbations and use of albuterol.

3. She may be made aware of the triggers and avoid them when possible or know what action to take when exposed.

4. Establish an individual plan for long term management. If JK improves on this regimen and steps down to the Mild Persistent category we may be able to cut back on some medications.

5. A plan for monitoring exacerbations should be set.

6. Regular follow-up care. Constant reinforcement of proper inhaler technique and peak flow monitoring.

5. JK returns to the clinic feeling much better. What other information do you need? What recommendations would you make?

Before making a recommendation, you need to know how much she has been using her albuterol, is she waking at night at all, has she needed oral steroids for management, is she having any symptoms. If she has had no symptoms and uses her albuterol 1x/week and no oral steroids you may be able to reduce her medications. She may no longer need the salmeterol now that her asthma is controlled. Asthma classification and therapy may be managed in a stepwise fashion. A patient may not stay in a specific classification. Once asthma control is achieved and maintained for at least 3 months, a gradual stepwise reduction of the maintenance therapy should be tried in order to identify the minimum therapy required to maintain control. This may improve patient compliance and avoid adverse effects from medications.

CASE #2

RF is a 25 year old male who comes to the clinic complaining of shortness of breath, increasing cough and trouble sleeping at times. Upon further questioning you find that he has these symptoms about 2x a week and has been awakened during the night 3x in the last month with coughing and shortness of breath. Current medications include albuterol 2 puffs q6 hours prn.

1. What information aids in the assessment of severity? In which category does RF fall?

2. What therapy do you recommend for RF?

CASE #2 Answers:

1. Symptoms >1x/week, affects sleep 3x in last month. RF is classified as a Mild Persistent asthmatic.

2. Therapy: An anti-inflammatory agent needs to be added to therapy.

Options for RF's therapy include the addition of inhaled corticosteroids, cromolyn sodium, nedocromil sodium or sustained release theophylline. Again, corticosteroids are currently the most effective anti-inflammatory medications for the treatment of asthma.

Cromolyn sodium: partly inhibits the IgE-mediated mediator release from human mast cells. Also has a cell-selective and mediator-selective suppressive effect on other inflammatory cells.

Nedocromil sodium: inhibits activation of and mediator release from several types of inflammatory cells.

Side effects: minimal

The same management technique and monitoring parameters mentioned above need to be followed for each asthmatic patient.

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