ATrain Education

 

Continuing Education for Health Professionals

Asthma: Calming the Airways

Module 6

Medication Management of Asthma

Pharmacologic therapy can prevent and control asthma symptoms, improve quality of life, reduce frequency and severity of symptoms, and reverse airflow obstruction. It is essential that medications be chosen based upon the specific criteria revealed when classifying the client’s asthma. The long-term management of asthma needs to change in response to the severity of symptoms, so a stepwise approach to medication management is important (see “Applying the Stepwise Approach,” below).

Using the stepwise approach, the client is evaluated based on observation of symptom severity, as well as pulmonary function testing (PFT). Medication is stepped up or down to deliver the lowest dose of medication that maintains good symptom control. Before looking at the steps, we will review the basic groups of medications available to treat asthma.

Asthma medications fall into two general classes: (1) controllers, long-term control medications taken daily to achieve and maintain control of persistent asthma, and (2) rescue, quick-relief medications taken to address acute airflow obstruction and bronchoconstriction. Clients who have persistent asthma need prescriptions for both. Clients with intermittent symptoms, such as exercise- or cold-induced asthma, typically need only a rescue inhaler that is used 15 to 30 minutes before exposure.

Controller (Long-Term) Medications

Corticosteroids

Corticosteroids are the most potent and effective anti-inflammatory medications currently available. They block late-phase reaction to allergens, reduce airway hyper-responsiveness, and inhibit inflammatory-cell migration and activation. Corticosteroids are available in inhaled forms (inhaled corticosteroids, or ICS) and in oral or injectable forms. Inhaled corticosteroids are commonly used in the long-term control of asthma.

Short courses of oral systemic corticosteroids are often used to gain prompt control of symptoms when initiating long-term therapy; long-term oral systemic corticosteroid is used for severe persistent asthma. Intravenous steroids may be used in an inpatient setting to manage an acute exacerbation. When administered for quick relief, these last two routes are not considered controllers, but are classed as rescue strategies.

Numerous preparations exist either as metered dose inhalers (MDI) or dry powder inhalers (DPI) with varying strengths. Dosages are ranked as low, medium, or high by multiplying the strength of the dose in the specific MDI times the number of puffs taken per day (which might range from a low of 1 to a high of 8). Limiting the number of puffs needed by changing to a higher dose is a desirable strategy to simplify therapy.

Samples of inhaled corticosteroids and the number of puffs needed to receive appropriate therapy in children over 12 and adults are presented in the following table.

 

Number of Inhaled Corticosteroid (ICS) Puffs Needed
for Children >12 and Adults

Drug

Low daily dose

Medium daily dose

High daily dose

Beclomethasone HFA 
40 or 80 mcg/puff


80–240 mcg


240–480 mcg


>480 mcg

Budesonide DPI 
90, 180, 200 mcg/inhalation


180–600 mcg


600–1200 mcg


>1200 mcg

Flunisolide HFA 
80 mcg/puff


320 mcg


320–640 mcg


>640 mcg

Fluticasone HFA/MDI: 44, 110, 220 mcg/puff 

DPI: 50, 100, 250 mcg/puff


88–264 mcg 

110–300 mcg


264–440 mcg 

300–500 mcg


>440 mcg 

>500 mcg

Mometasone DPI 
200 mcg/inhalation


200 mcg


400 mcg


>400 mcg

Triamcinolone acetonide 
75 mcg/puff


300–750 mcg


750–1500 mcg


>1500 mcg

 

Dosing for children varies considerably, with levels generally being lower at the upper end of the low category and titrated downward from there. The doses are given as guidelines only, and individuals with case-specific requirements need to seek expert opinion from a trusted source.

What can be said about dosing for children is that, in spite of known risks, ICS is the preferred choice for long-term control for children of all ages. The adverse effect on growth in height for children on low-to-medium ICS is a reduction of ≤1 cm in the first year of therapy. These children should have their growth monitored.

For children requiring high-dose ICS for more than 1 year, especially if occasional courses of systemic corticosteroids are used, there may be increased risk of growth defects, reduced bone density, and cataract formation. Children should always be monitored for these known adverse effects. In children of ages 1 to 4, Budesonide suspension—typically given with a face mask and nebulizer—is the only FDA-approved ICS therapy. Fluticasone DPI is approved for children aged 4 and up.

Cromolyn Sodium and Nedocromil

Cromolyn sodium and nedocromil stabilize mast cells and interfere with chloride channel function. They are used as alternative—but not preferred—medication for the treatment of mild-to-persistent asthma. They may be used as preventive treatment before exercise or unavoidable exposure to known allergens. The main protection conferred in children by this class of medications is as adjunct therapy to reduce exacerbations leading to hospitalization.

Immunomodulators

Omalizumab (Xolair, an anti-IgE) is an injectable monoclonal antibody that prevents binding of IgE to the high-affinity receptors on basophils and mast cells. Omalizumab is used as adjunctive therapy for clients ≥12 years of age who have allergies and severe persistent asthma. Clinicians who administer omalizumab should be prepared and equipped to identify and treat anaphylaxis. This medication is reserved for clients whose asthma is not controlled using alternative therapies appropriate to their level of severity, in whom treatment fails to control symptoms adequately. The dose is given every 2 to 4 weeks and is calibrated to the client body weight and IgE activity before starting therapy.

Leukotriene Modifiers

Two leukotriene modifiers (LRTA) are available—montelukast (for clients >1 year of age) and zafirlukast (for clients ≥7 years of age). The 5-lipoxygenase pathway inhibitor zileuton is available for clients ≥12 years of age. As a group these medications are either adjunct or alternative treatments for mild persistent asthma. Zileuton has the added disadvantage of being hepatotoxic and requires liver function monitoring.

Long-Acting Beta Agonists (LABAs)

The principal action seen in LABAs is relaxation of smooth muscles in the upper airways through stimulation of beta2 receptors. Salmeterol and formoterol are bronchodilators that have a duration of at least 12 hours after a single dose; however, with chronic regular administration this effect is reduced to less than 5 hours.

Black box warnings have been added to all preparations containing LABA due to an increased number of deaths and severe exacerbations seen in clients using it. These results were seen largely in clients using LABA inappropriately, either in treating acute symptoms or as monotherapy.

The EPR 3 (2007) recommendations acknowledge that LABA is effective for the majority of clients whose asthma is not well-controlled with ICS alone; therefore, when weighing the risks and benefits of LABA the following points should be considered:

  • LABAs are not to be used as monotherapy for long-term control of asthma.
  • LABAs are used in combination with ICS for long-term control and prevention of symptoms in moderate or severe persistent asthma (step 3 care or higher in children ≥5 years of age and adults)
  • Of the adjunctive therapies available, LABA is the preferred therapy to combine with ICS in youths ≥12 years of age and adults.
  • Daily doses of LABA should not exceed 100 mcg of salmeterol or 24 mcg of formoterol.

Additional concerns exist with regard to the use of LABA’s in children. For clients ≥5 years of age who have moderate-to-persistent asthma or asthma inadequately controlled on low-dose ICS, the option to increase the ICS dose should be given equal weight to the option of adding LABA. For clients ≥5 years of age who have severe persistent asthma or asthma inadequately controlled on step 3 care, the combination of LABA and ICS is the preferred therapy.

Combination Products

Combination products include:

  • Fluticasone/salmeterol (Advair)
  • Budesonide/formoterol (Symbicort)
  • Mometasone/formoterol (Dulera)

These products combine fixed doses of ICS and LABA and are available in varying strengths and preparations, but they should not be used unless symptoms are severe.

Methylxanthine

Sustained-release theophylline is a mild to moderate bronchodilator used as an alternative, but not preferred, adjunctive therapy with ICS. Theophylline may also have mild anti-inflammatory properties. Monitoring of serum theophylline concentrations is essential.

Rescue (Quick Relief) Medications

Anticholinergics

Inhaled anticholinergic medications inhibit muscarinic receptors, thereby reducing vagal response of the airway. Ipratropium bromide (Atrovent MDI) provides additive benefit to SABA in moderate to severe asthma exacerbations and may be used as an alternative bronchodilator to clients unable to tolerate SABA. Tiotropium (Spiriva) MDI provides a longer duration of action. Ipratropium and albuterol are available as a combined MDI under the trade name of Combivent.

Short-Acting Beta Agonists (SABA)

Albuterol, levalbuterol, pirbuterol are all bronchodilators that relax smooth muscle and are used for relief of acute symptoms.

Systemic Corticosteroids

Oral or IV formulations are used for moderate and severe exacerbations or as adjunct therapy to SABA to speed recovery and prevent exacerbations.

The Stepwise Approach for Managing Asthma Medications

The stepwise approach to therapy, in which the dose and number of medications and frequency of administration are increased as necessary and decreased when possible, is used to achieve and maintain optimal control. Because asthma is a chronic inflammatory disorder of the airways with recurrent exacerbations, therapy for persistent asthma must emphasize efforts to suppress inflammation over the long term and to prevent exacerbations. Recommendations in the stepwise approach to therapy are based on the Expert Panel’s review (EPR 3) of the literature and cumulative experience.

Based on the table below, it is possible to apply the step approach to choosing an appropriate medication based on the severity of initial symptoms. As has been noted, the amount of ICS is increased at each step, with the addition of LABA or a combined ICS/LABA product such as Advair being added at Steps 3 or 4.

 

Step Therapy Recommendations for Children 0 to 4 years of age

Step 1

SABA prn

Albuterol

Step 2

Low-dose ICS

Budesonide respules 0.25–0.5 mg/day
OR
fluticasone 44 mcg, 2 puffs with spacer/mask BID

Step 3

Medium-dose ICS

Budesonide respules 0.5 mg BID or 1 mg daily
OR
fluticasone 110 mcg, 1 puff with spacer/mask BID

Step 4

Medium-dose ICS + LABA or montelukast

ICS (see Step 3) plus montelukast 4 mg daily
OR
Advair HFA 45/21 mcg, 2 puffs with spacer/mask BID

Step 5

High-dose ICS + LABA or montelukast

Montelukast 4 mg + fluticasone 220 mcg BID
OR
montelukast 4 mg + budesonide 1 mg BID
OR
Advair HFA 115/21 mcg, 2 puffs with spacer/mask BID

Step 6

High-dose ICS + oral steroids + LABA or montelukast

Prednisolone + Step 5 therapy

 

 

Step Therapy Recommendations for Children 5 to 11 years of age

Step 1

SABA prn

Albuterol

Step 2

Low-dose ICS

Fluticasone HFA 44 mcg, 1–2 puffs with spacer BID
Fluticasone 50 mcg Diskus, 1–2 puffs BID
Mometasone DPI 100 mcg once daily
Budesonide DPI 90–180 mcg BID
Beclomethasone HFA 40 or 80 mcg, 1 puff BID

Step 3

Medium-dose ICS
OR
low-dose ICS + LABA or montelukast

Fluticasone HFA 110 mcg, 1 puff with spacer BID
Mometasone DPI 200 mcg daily
Budesonide DPI 180 mcg, 2 puffs BID
Beclomethasone 80 mcg, 2 puffs BID

ALTERNATIVE:
Advair 45/21 mcg, 2 puffs with spacer BID
OR
Low-dose ICS (Step 2) + montelukast 5 mg
OR
Symbicort 80/4.5 mcg, 2 puffs with spacer BID

Step 4

Medium-dose ICS + LABA
(ICS + montelukast is non-preferred alternative)

Advair 45/21 mcg, 2 puffs with spacer BID
OR
Advair Diskus 100/50 mcg or 250/50 mcg, 1 puff BID
OR
Symbicort 160/4.5 mcg, 2 puffs with spacer BID

NOT PREFERRED:
Medium-dose ICS (Step 3) + montelukast 5 mg

Step 5

High-dose ICS + LABA (montelukast is non-preferred alternative)

Advair 115/21 mcg, 2 puffs with spacer BID
OR
Advair 250/50 mcg, 1 puff BID

NOT PREFERRED:
montelukast 5 mg + Fluticasone 220 mcg, 1 puff with spacer BID
OR
Montelukast 5 mg + mometasone 200 mcg, 1 puff BID

Step 6

High-dose ICS + oral steroids + LABA (montelukast is non-preferred alternative)

Prednisolone + Step 5 therapy

 

 

Step Therapy Recommendations for Children ≥ 12 years of age

Step 1

SABA prn

Albuterol

Step 2

Low-dose ICS

Fluticasone HFA 110 mcg, 1 puff BID
Fluticasone 50 mcg Diskus, 1–2 puffs BID
Mometasone DPI 200 mcg once daily
Budesonide DPI 90–180 mcg 1 puff BID
Beclomethasone HFA 80 mcg 1 puff BID; 40 mcg, 1–3 puffs BID
Ciclesonide 80 mcg, 1 puff BID
Triamcinolone 75 mcg, 2–5 puffs BID
Flunisolide HFA 80 mcg, 2 puffs BID

Step 3

Low-dose ICS + LABA
OR medium-dose ICS

Advair 45/21 mcg, 2 puffs BID
OR
Advair Diskus 100/50 mcg, 1 puff BID
OR
Symbicort 80 mcg 2 puffs BID

Low-dose ICS + montelukast (non-preferred alternative)

Medium-dose ICS: fluticasone HFA 220 mcg, 1 puff BID
mometasone DPI 200 mcg, 2 puffs daily or 1 puff BID
budesonide DPI 180 mcg, 2 puffs BID
beclomethasone HFA 80 mcg, 2–3 puffs BID
ciclesonide 160 mcg, 1 puff BID
triamcinolone 75 mcg, 6–10 puffs BID
flunisolide HFA 80 mcg, 3–4 puffs BID
NOT PREFERRED:
Low-dose ICS (Step 2) + montelukast

Step 4

Medium-dose ICS + LABA
(ICS + montelukast is non-preferred alternative)

Advair 115/21 mcg, 2 puffs BID
OR
Advair Diskus 250/50 mcg, 1 puff BID
OR
Symbicort 160/4.5 mcg, 2 puffs BID

NOT PREFERRED:
Medium-dose ICS (Step 3) + montelukast

Step 5

High-dose ICS + LABA
AND consider omalizumab for those with allergies

Advair 115/21 mcg or 230/21 mcg, 2 puffs BID
OR
Advair 250/50 mcg, 1 puff BID
OR
Advair 500/50 mcg, 1 puff BID

Step 6

High-dose ICS + oral steroids + LABA
AND consider omalizumab for those with allergies

Prednisolone + Step 5 therapy

 

If needed, oral steroids are given at Step 6 for severe asthma or if an exacerbation meets severity criteria at any step. Exacerbations requiring use of systemic steroids must be considered when assessing overall risk. Albuterol is used for intermittent symptoms but any time the Rules of Two apply—SABA >2x/week; night wakening with symptoms >2x/month; refill of rescue >2x/year)—clients need evaluation for step and triggers because they do not have good control.

If symptoms are well-controlled, the current step is maintained and regular follow-up occurs at 1- to 6-month intervals depending on symptom severity. If control is good for at least 6 months, a step down in therapy may be considered. Before stepping up therapy, inquire about adherence to current medications, demonstrate correct inhaler (or alternate device) technique, discuss adherence to environmental controls, and review co-morbidities. Alternate treatments such as montelukast or nedocromil are considered when side effects to preferred treatments exist.

The steps of care for managing asthma assist the healthcare team to determine whether the therapy being used matches severity of symptoms. Deciding which step of care is appropriate for a client depends on whether long-term control therapy is being initiated for the first time or whether therapy is being adjusted. Care is stepped up to regain control, and it is stepped down for clients who have maintained control for a sufficient length of time to determine the minimal amount of medication required to maintain control or reduce the risk of side effects.

The classification of asthma severity tables discussed earlier, which consider the severity of both impairment and risk domains, provide a guide for initiating therapy for clients who are not currently taking long-term control medications. Once therapy is selected, or if the client is already taking long-term control medication, the client’s response to therapy will guide decisions about adjusting therapy based on the level of control achieved in both the impairment and risk domains.

 

We can now combine our knowledge of severity classification, co-morbidities, environmental allergens and triggers, along with pharmacotherapy recommendations using the Stepwise approach to further assess Tom in view of our improved understanding and determine whether he could benefit from adjustment to his routine.

Recall that Tom’s asthma was initially classified as moderate-persistent. He received a short burst of systemic prednisone, an intermediate dose of ICS, and a SABA to use for acute symptom relief. Let us assume that the Tom’s ICS need is met using Fluticasone 220 mcg/puff and that he takes 440 mcg/day or 1 puff BID. At 6 weeks he had already used one whole canister of his SABA (albuterol), which led to further assessment of environmental triggers. Removal of the cat to reduce dander exposure was judged as not possible. Tom elected to proceed with immunotherapy for the cat dander but it will take several years before his treatment is completed.

 

 

Answers: 1-D, 2-B, 3-C, 4-C

Test Your Knowledge

  1. Tom’s need for re-assessment of medication regimen at this time is based primarily on:
    1. His use of Fluticasone does not meet the standard for medium-dose ICS.
    2. His ongoing poor control automatically dictate a step up in therapy.
    3. He has just started immunotherapy and requires a step down in therapy.
    4. His overuse of SABA is a significant concern regardless of other factors.
  2. Tom is currently receiving ICS therapy at:
    1. Step 2.
    2. Step 3.
    3. Step 4.
    4. Step 5.
  3. In considering alternatives to Tom’s current therapy, an acceptable alternative would be:
    1. Low-dose ICS + LABA.
    2. Low-dose ICS + montelukast.
    3. Medium-dose ICS + LABA.
    4. Medium-dose ICS + montelukast.
  4. Prior to considering a step up in therapy it would be necessary to ascertain:
    1. Exposure to inhalants, irritants and foods.
    2. Compliance with immunotherapy routine.
    3. Adherence to medication, MDI technique, and environmental controls.
    4. Compliance with lifestyle recommendations and medication to manage GERD.
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