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Daily inhaled corticosteroids significantly reduce exacerbations and hospitalizations in patients with persistent asthma and are significantly more effective as first-line long-term control agents than any alternative agents (Sin et al., 2004) (SOR: A). Long-acting p-agonists (LABAs) are more effective than leukotri-ene antagonists as add-on-therapy to inhaled steroids. Because most benefits of inhaled corticosteroid (ICS) are achieved at lower doses, adding a LABA to a low or medium dose of ICS is preferred over using a higher dose of ICS. LABAs should not be used as monotherapy because of higher risk of death (FDA black-box warning) (NAEPP EPR-3; Ram et al., 2005) (SOR: A). Adding ipratropium bromide to albuterol nebulizer treatments for patients with severe airflow obstruction in the acute ED setting produces additional bronchodilation, resulting in fewer hospital admissions (Plotnick and Ducharme, 2000; Rodrigo and Castro-Rodriguez, 2005) (SOR: A).

Theophylline is an acceptable (but not preferred) alternative to LABA for second-line long-term control treatment in combination with inhaled corticosteroids, but theophylline or aminophylline should not be used in the acute treatment of ED or in-hospital patients (SOR: A).

Teaching patients to engage in effective self-management improves clinical outcomes (Gibson et al., 2002) (SOR: A).

(tiotropium), leukotriene antagonists, inhaled mast cell stabilizers (cromolyn, nedocromil), and theophylline. Although each has demonstrated efficacy, none is as effective as inhaled corticosteroids. When low-dose inhaled corticosteroids are not providing complete remission, the clinician may add a second medication or increase the inhaled steroid dose to moderate levels. In a controlled trial of an inhaled LABA (formoterol) versus theophylline versus a leukotriene antagonist (zafirlukast) as second-line agents added to inhaled corticosteroid therapy, Yurdakul and colleagues (2002) found that the LABA was more effective in preventing exacerbations and had fewer side-effects than the other options. A Cochrane review of 12 controlled trials also found that LABAs were more effective than leukotriene antagonists as add-on therapy to inhaled steroids (Ram et al., 2005). Concern persists, however, that LABAs can increase mortality when used as monotherapy in the absence of inhaled corticosteroids (Abramson et al., 2003b). Randomized controlled trials now show that adding tiotropium bromide to low-dose inhaled corticosteroid (ICS) therapy is superior to doubling the dose of the ICS and equivalent to adding a LABA (Peters, 2010). The leukotriene synthesis inhibitor zileuton appears to improve pulmonary function and decrease need for p-agonist, but causes significant elevations of liver transaminases in 2% to 3% of patients (Nelson et al., 2007).

Immunotherapy also appears to be effective. A Cochrane review found that allergen immunotherapy reduces asthma symptoms and use of asthma medications at a level similar to that of inhaled corticosteroids (Abramson et al., 2003a). A newer third-line therapy is the once- or twice-monthly injection of monoclonal anti-IgE antibodies (omalizumab), an expensive therapy that is associated with a 98% to 99% reduction in free IgE and significantly fewer exacerbations of asthma, even allowing some patients to be weaned from inhaled corticosteroids (Walker et al., 2003).

Components of Severity

Classification of Asthma Severity (Youths >12 years of age and adults)

Intermittent

Persistent

Mild

Moderate

Severe

Impairment

Normal FEVj/FVC:

8-19 yr 85»/o 20 —39 yr 80°/,) 40 -59 yr 75°/ö 60 -80 yr 70°/o

Symptoms

<2 days/week

>2 days/week but not daily

Daily

Throughout the day

Nighttime awakenings

<2x/month

3-4x/month

>lx/week but not nightly

Often 7x/week

Short-acting betaj-agoriist use for symptom control (not prevention of EIB)

£2 days/week

>2 days/week but rot >lx/day

Daily

Several times per day

Interference with normal activity

None

Minor limitation

Some limitation

Extremely limited

Lung function

• Normal FEV, between exacerbations

• FEVj/FVC normal

• FEVj/FVC norma

• FBVFVC reduced 5%

* FEVt <60% predicted

• FEVi/FVC reduced >5%

0-1/year

(see note)

Risk

requiring oral systemic

Consider seventy and interval since l3st exacerbation. Frequency and f n severity may fluctuate over time for patients in any severity category.

Relative annual risk of exacerbations may be related to FEVj

Figure 18-5 Classification of asthma severity in adolescents 12 years or older and adults. (From Guidelines for the Diagnosis and Management of Asthma; National Asthma Education and Prevention Program (NAEPP) Coordinating Committee, 2007. http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm.

Intermittent asthma

Persistent asthma: daily medication Consult with specialist if step 4 care or higher is required. Consider consultation at step 3.

Step 1

Preferred: SABA PRN

Step 2

Preferred: Low-dose ICS Alternative: Cromolyn, LTRA, Nedocromil, or Theophylline

Step 3

Preferred: Low-dose ICS + LABA OR

Medium-dose ICS Alternative: Low-dose ICS + either LTRA, Theophylline, or Zileuton

Step 4

Preferred: Medium-dose ICS + LABA Alternative: Medium-dose ICS + either LTRA, Theophylline, or Zileuton

Step 5

Preferred. High-dose ICS + LABA AND Consider Omalizumab for patients who have allergies

Step 6

Preferred.

High-dose

ICS + LABA + oral corticosteroid

Consider

Omalizumab for patients who have allergies

Each step: Patient education, environmental control, and management of comorbidities.

Steps 2-4: Consider subcutaneous allergen immunotherapy for patients who have allergic asthma (see notes).

Quick-relief medication for all patients

• SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms. up to 3 treatments at 20-minute intervals as needed. Short course of oral systemic corticosteroids may be needed.

• Use of SABA >2 days a week for symptom relief (not prevention of EIB) generally indicates inadequate control and the need to step up treatment

Step up if needed (first, check adherence, environmental control, and comorbid conditions)

Assess control

Step down if possible (and asthma is well controlled at least 3 months)

Key: Alphabetical order is used when more than one treatment option is listed within either preferred or alternative therapy. EIB, exercise-induced bronchospasm; ICS, inhaled corticosteroid; LABA, long-acting inhaled beta2-agonist;

LTRA, leukotriene receptor antagonist; SABA, inhaled short-acting beta2-agonist

Figure 18-6 Stepwise approach for managing asthma in adolescents (>12 years) and adults. (From Guidelines for the Diagnosis and Management of Asthma; National Asthma Education and Prevention Program (NAEPP) Coordinating Committee, 2007. http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm.)

Table 18-2 Estimated Comparative Daily Doses for Inhaled Corticosteroids for Adolescents (Age >12 Years) and Adults

Daily Dose (^g)

Drug

Amount

Low

Medium

High

Beclomethasone HFA

40 or 80 ^g/puff

80-240

>240-480

>480

Budesonide DPI

90, 80, or 200 ^g/inhalation

180-600

>600-1200

>1200

Flunisolide

250 ^g/puff

500-1000

>1000-2000

>2000

Flunisolide HFA

80 ^g/puff

320

>320-640

>640

Fluticasone

HFA/MDI

44, 110, or 220 ^g/puff

88-264

>264-440

>440

DPI

50, 100, or 250 ^g/inhalation

100-300

>300-500

>500

Mometasone DPI

200 ^g/inhalation

200

400

>400

Triamcinolone acetonide

75 ^g/puff

300-750

>750-1500

>1500

From National Heart, Lung and Blood Institute, NHI, Expert Panel 3 (EPR3). Guidelines for the Diagnosis and Management of Asthma. National Asthma Education and Prevention Program (NAEPP) Coordinating Committee, 2007. http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. HFA, Hydrofluoroalkane; DPI, dry powder inhaler; ¡MIDI; metered-dose inhaler.

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