Asthma is a chronic, inflammatory disease of the airways affecting 22 million Americans, of whom 6 million are children. It is the leading cause of missed school days and lost productivity for the caregiver who must leave work to care for the child. Hospitalizations remain high, at more than 497,000 annually, and there is a disparate impact on African-Americans and Puerto Ricans. The good news is that deaths from asthma have decreased, fewer patients who have asthma report limitations to activities, and an increasing proportion of people who have asthma receive formal patient education.

Expert Panel Guidelines

In 2007, the National Asthma Education and Prevention Program (NAEPP) published its third report, Guidelines for the Diagnosis and Management of Asthma, based on the findings of the Expert Panel Report-3 (EPR-3). The EPR-3 followed the EPR-2, released in 1997, and an interim update published in 2002. The EPR-2, while helping greatly with the treatment of asthma, was a report based on expert opinion.

The advantage of the EPR-3 is that it is evidence-based. Each article reviewed for inclusion in the EPR-3 was graded for quality of evidence. I have alluded to the level of evidence in the body of this article, so I will give readers a brief idea of what is meant by quality of evidence. Evidence A means that the conclusion/recommendation was reached based on substantial numbers of randomized clinical trials with a substantial number of participants. Evidence B means that the conclusion/recommendation was based on fewer studies, with fewer participants. Evidence C conclusions/recommendations are based on nonrandomized trials and observational studies. Finally, evidence D means that the conclusion/recommendation was based on panel consensus judgment. So in the EPR-3, many of the conclusions/recommendations are based on evidence obtained from randomized clinical trials with many participants, meaning that these statements carry substantial support from within the research community.

Once a diagnosis of asthma is made, its severity is classified. Classification of the severity of asthma is based on two domains: impairment and risk, as seen in Figure 1. Impairment encompasses the review of symptoms the patient is currently experiencing, frequency of short-acting beta2 agonist (SABA) use, the results of spirometry (forced expiratory volume in 1 second, FEV1) and forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC)), number of nighttime awakenings, and the degree of limitation of daily activities. Risk is defined as the risk for future exacerbations of asthma, based on the number of asthma attacks/flares and the need for bursts of systemic corticosteroids. Symptoms usually included in the assessment of impairment are frequency of cough, wheeze, shortness of breath, and chest tightness.

The severity of asthma corresponds to the most frequently occurring symptom or worst assessment finding. For example, if a patient has daily symptoms, awakens nightly, uses SABA daily, has some limitation, and a near normal FEV1, the patient’s asthma would be classified as severe persistent (Figure 1). There is a similar chart used to classify asthma in children 5 to 11 and 0 to 4 years of age. Spirometry is introduced in the 5 to 11 years of age population, as children younger than age 5 are often not good candidates for spirometry. So the first step in caring for a patient with asthma beyond diagnosis is classification of severity. There are four levels of severity: intermittent asthma and persistent asthma split into three categories: mild, moderate, and severe, based on the symptoms and problems described above. The stepwise approach to therapy is based on the classification of severity (Figure 2).

Figure 1. Classifying asthma severity in youths >12 years-of-age and adults. From EPR-3: www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm, page 74.
Figure 2. Level of treatment based on classification of asthma severity. From EPR-3: www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm, page 74.

Asthma Medication Decisions

Before discussing the steps of therapy, it would be useful to discuss asthma medications. All patients with asthma, regardless of severity, need to have a rescue inhaler, which is a SABA: albuterol (ProAir, Proventil, or Ventolin), levalbuterol (Xopenex), or pirbuterol (Maxair). A SABA is used for quick relief of sudden symptoms or for the prevention of exercise-induced bronchospasm, taken 15 to 30 minutes before exercise. Patients with intermittent asthma need only a SABA. All patients with persistent asthma need an anti-inflammatory drug, since that is the nature of asthma. Most commonly, inhaled corticosteroids (ICS) are the anti-inflammatory drugs of choice, since they reduce the inflammation caused by a wide spectrum of inflammatory mediators (TNF, cytokines, histamines, etc) released from a variety of proinflammatory cells (mast cells, eosinophils, epithelial cells, etc). Inhaled corticosteroids are recommended, since they are effective and avoid the severe side effects of systemic corticosteroids. Inhaled corticosteroids include beclomethasone (Qvar), budesonide (Pulmicort), flunisolide (Aerobid), fluticasone (Flovent), mometasone (Asmanex), and triamcinolone (Azmacort). Usual dosages are found in EPR-3. Less frequently used anti-inflammatory drugs are the nonsteroidal preparations: sodium cromolyn (Intal) and nedocromil (Tilade).

Moderate and severe persistent asthma are often treated with a combination of an ICS and a long-acting beta adrenergic (LABA). The two common LABAs are formoterol (Foradil) and salmeterol (Serevent). LABAs are inhaled twice daily, along with their ICS counterpart. Recently, the safety of LABAs was questioned. The EPR-3 and others have reviewed the use of LABAs and concluded that they are used as an adjunct to ICS for providing long-term control of symptoms (evidence A); LABAs are not recommended as monotherapy for asthma (evidence A), LABAs are not recommended for treating acute symptoms or exacerbations of asthma (evidence D), and LABAs may be used prior to exercise for prophylaxis of exercise-induced bronchospasm. A discussion of the safety of LABAs is found in the EPR-3 on pages 231-234. There are two combination ICS/LABA products: fluticasone + salmeterol (Advair) available as a dry powder inhaler (DPI) and hydrofluoroalkane (HFA) MDI, and formoterol + budesonide (Symbicort) available as an HFA inhaler.

Another category of drugs is the leukotriene receptor antagonists (LTRAs). These drugs act to block the binding of leukotrienes to proinflammatory cells in the airways. The most frequently used drug in this category is montelukast (Singulair), which seems to be most effective in allergic asthma. Finally, the newest category of drugs is the immunomodulator. The drug omalizumab (Xolair) prevents the binding of IgE to its receptor, thereby inhibiting the IgE-mediated asthma cascade before it begins. Omalizumab is a subcutaneously injected drug, administered once or twice a month. The dose is based on IgE level and body weight. It is reserved for severe asthma not controlled by the other drugs I have listed.

The Stepwise Approach

The stepwise approach for managing asthma in youths =12 years of age and adults is depicted in Figure 3. Step 1 therapy consists of a SABA prn. Since the patient has only intermittent symptoms, this is the only treatment necessary. For patients with mild persistent asthma, the patient should take a low-dose ICS daily and SABA prn. At each level of therapy, alternative therapy is listed. The alternative is used only when the patient cannot tolerate the recommended therapy. It is very important to remember that ICS is the treatment of choice and the evidence is overwhelmingly in favor of ICS over the alternative. At steps 3 and 4, either the dose of ICS is increased, a LABA is added, or both (step 4). At steps 5 and 6, the ICS dose increases further and omalizumab is considered. Also at step 6, chronic oral corticosteroids (usually prednisone) are considered. While the medications used at each step are important, they represent only part of the plan of care. As can be seen in Figure 3, there are a number of boxes peripheral to the six steps. If care at or beyond step 4 is required, consultation with an asthma specialist (pulmonologist, allergist, or immunologist) is recommended. Accompanying each step, the patient must receive appropriate education about asthma, steps in environmental control, and how to manage comorbidities (sinusitis, rhinitis, gastroesophageal reflux, obstructive sleep apnea, or allergic bronchopulmonary aspergillosis). Also, if patients require steps 2 to 4, the care team must consider subcutaneous allergen immunotherapy (allergy shots) for patients who have allergic asthma. A similar step-wise approach is used for the other two age groups. Neither of those approaches includes omalizumab, since it is not approved for children under age 12.

Figure 3. Stepwise approach for managing asthma in youths >12 years-of-age and adults. From EPR-3: www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm, page 343.
Figure 4. Classifying asthma severity in youths >12 years of age and adults. From EPR-3: www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm, page 74.

Follow-up

The goal for therapy is to control asthma by reducing impairment and reducing risk. Once the patient has been started on the appropriate step and has received education on triggers, environmental controls, symptoms, etc, control is assessed at 2- to 6-week intervals with regular follow-up contacts at 1- to 6-month intervals. Reduced impairment is defined as prevention of chronic and troublesome symptoms, infrequent use (<2 days/week) of SABA for quick relief of symptoms, near normal pulmonary function, and the meeting of patient and family expectations of and satisfaction with asthma care. Reducing risk is defined as prevention of recurrent exacerbations and progressive loss of lung function, as well as provision of optimal pharmacotherapy.

When assessing control, the clinician will use many of the same markers as are used in the initial assessment: symptoms, nighttime awakenings, interference with normal activities, SABA use, and FEV1 or peak flow. In addition, the patient (>12 years of age) will be asked to complete a validated quality of life questionnaire. Questionnaires also are available for children, but are not part of the EPR-3 control charts for younger children (<12 years of age). These questionnaires include the Asthma Therapy Assessment Questionnaire (ATAQ), the Asthma Control Questionnaire (ACQ), and the Asthma Control Test (ACT: page 80 of EPR-3).

Risk is assessed by noting the number of exacerbations requiring OCS, loss of lung function, and treatment-related adverse effects. As with classifying severity, classifying control is based on the most frequent or worst assessment finding, or questionnaire score. As can be seen in Figure 4, control is classified as well controlled (the goal), not well controlled, or very poorly controlled. The key here is to determine what to do at each of these levels of control. If the patient is well controlled, therapy is maintained with regular follow-up. If control is maintained for at least 3 months, the clinician may consider going down one step in therapy (eg, from step 4 to step 3). If the asthma is not well controlled, therapy is stepped up by one step and reevaluated in 2 to 6 weeks. If treatment side effects occur, alternative therapy is considered. If the asthma is very poorly controlled, a short course of OCS is considered and therapy is increased by one to two steps, and reevaluated in 2 weeks. Alternative therapy is considered in the event of side effects. Before stepping up therapy, the clinician should review adherence to medication, inhaler technique, environmental control, and comorbid conditions.

Use of the EPR-3 to guide the diagnosis and therapy of asthma has improved from the EPR-2 by providing an evidence base. Clinicians may be assured that when following the EPR-3 guidelines, therapy is being administered based on the best evidence available at the time the guidelines were written.


Tim Op’T Holt, EdD, RRT, AE-C, FAARC, is professor, cardiorespiratory care, University of South Alabama, Mobile.

Resources

National Heart Lung and Blood Institute. National Asthma Education and Prevention Program. Expert Panel Report-3: Guidelines for the Diagnosis and Management of Asthma. Full Report 2007. www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm.

American Association for Respiratory Care. Indoor Asthma Triggers and the Respiratory Therapist. www.epapartnershiparcf.org/courses/lecture_hall.cfm. Online CRCE program.

American Association for Respiratory Care. Allergy Skin Testing and Smoking Cessation-The Expanded Role of the Respiratory Therapist. www.epapartnershiparcf.org/courses/lecture_hall.cfm. Online CRCE program.

Association of Asthma Educators. www.asthmaeducators.org/Resources/resources.htm. Free online asthma education resources.