S t e p w i s e Tre a t m e n t o f A s t h m a John A. Fornadley,
MD
KEYWORDS Bronchospasm Intermittent bronchospasm Persistent bronchospasm KEY POINTS Asthma management is based on severity of disease. Overmedication or undermedication of asthma is a concern. Uncontrolled asthma may lead to irreversible lung disease.
Step therapy for treatment of asthma has proven a successful means of guiding practitioners through marked changes in management strategy and of gaining better control over this difficult disease process. In the middle to late twentieth century, asthma therapy was not providing satisfactory control of the disease. Physician visits, self-reported reactive airway disease prevalence, and deaths due to asthma increased between 1960 and 1990.1–4 Even more troubling was that a percentage of the deaths were attributed to the bronchodilator therapy, specifically exacerbations of disease related to long-acting beta2agonist (LABA) use. Even without these concerns, bronchodilator therapy did not seem to be the definitive therapy to manage asthma. Scientific work in the 1960s included the discovery of IgE and a better delineation of the role of inflammation in reversible airway disease.5 In combination with recently developed inhaled corticosteroids, this provided a better understanding of the disease as well as a pathway that could make a substantial positive impact on the quality of life for a patient with asthma. Several challenges surrounded the acceptance of this radical algorithm change. The first was the need to educate and change practice patterns of the wide range of practitioners treating asthma, which required informing them and gaining their acceptance of the strategy. Unlike a new medication or adjunctive therapy, the concept of inflammation-based therapy for asthma represented a marked philosophic change. Because physicians tend to gather their continuing education from the medical journals and societies related to their specific field, there was a need to reach out to several disparate societies and journals to get information to the practitioners regarding changes in the therapy of asthma.
Department of Surgery, Penn State University, 500 University Drive, Hershey, PA 17036, USA E-mail address: [email protected] Otolaryngol Clin N Am 47 (2014) 65–75 http://dx.doi.org/10.1016/j.otc.2013.09.014 0030-6665/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
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Asthma therapy is also complicated by the variability of the disease from lifethreatening exacerbations to a completely normal quality of life between episodes. This disease process does not lend itself to simply starting a medication and continuing it routinely for years, as in the case of hypertension or types of cardiac disease. There is a legitimate concern among physicians and patients about overmedication or undermedication of asthma. Without guidelines, it was unclear when it would be most appropriate to start medications. Unfortunately, with the medications involved, there were side effect profiles that made overuse undesirable. Steroid therapy, which represented a critical new role in asthma care, is known to have side effects that include growth retardation, decreased immunocompetence, and multiple systembased complications. All branches of medicine recognize a strong desire to limit steroid use, which complicates acceptance of the new regimen. In asthma, these limitations must be balanced against the risk of progression of disease and the inability to stabilize the airway by other means. Beta agonists have a somewhat diminished but still vital role in the more modern therapy approach. These agents also suffer from reported complications, including electrolyte disorders, cardiac dysrhythmias, and sudden death.2,4 This change in asthma management occurred at a time when clinical practice guidelines were less well understood and certainly less trusted. Current data on the value of evidence-based guidelines were obviously not available and the physicians of the time were concerned that guidelines were intended to restrict testing and control medical practices for the benefit of third-party payers. It was in this medical environment that the National Asthma Education and Prevention Program (NAEPP), under the auspices of the National Heart, Lung, and Blood Institute, performed a thorough literature review and created a guideline pathway for asthma that was published in 1991.6 The guidelines have been revised in 1997, 2002, and most recently in 2007. The guideline divided asthma into categories of intermittent or persistent, with the latter category being subdivided into mild, moderate, or severe. This categorization then provided the clinician with a step therapy based on the severity of the asthma. These pathways have largely succeeded in changing the way asthma is managed, starting in the last decade of the twentieth century. The intervening time has allowed statistical analysis to identify actual improvement in asthma management as measured by fewer emergency visits and deaths. From 1991 to 2006, progress in the field, new medications, and updated data resulted in the need for changes to the asthma management algorithm. The stepwise approach has grown necessarily more complicated, but the overall principles remain. The guideline continues to provide some rigidity but allows physician judgment and insight. In the current version, the guidelines include patient education and some patient responsibilities. Although some of the elegant simplicity of the 1991 algorithm is lost, the present update allows better active consideration of allergic components of the disease. In addition, there are more options for effectively allowing medication use to step up when needed and step down when possible. The now-familiar four categories of asthma remain unchanged. The step approach for asthma therapy has increased these to six steps. The care recommendations are stratified for patient ages of 0 to 4 years, 5 to 11 years, and 12-plus years to allow for better treatment of pediatric medication variances. The initial step, as before, is the diagnosis of asthma. The goal is to identify asthma, evaluate and exclude other diagnoses, and determine the severity of the disease. Patient history, spirometry (in patients older than 5 years), and the exclusion of other diagnoses is important in arriving at the correct diagnosis. The severity of the disease is important in determining how to initiate therapy. The control aspect of disease is vital
Stepwise Treatment of Asthma
in monitoring and controlling therapy. Severity is defined as the intrinsic intensity of the disease process. This parameter is important for the initiation of therapy (Table 1). The initial assessment is the first and arguably the most critical step, because it has a role in both diagnosis and the direction of initial therapy. The steps of the initial assessment are illustrated in Table 1. Note that the diagnosis includes a history of symptoms and types of precipitating factors, not only spirometry. Spirometry is nevertheless required in patients 5 years and older. These historical data combined with the results of spirometry assist the clinician in making the diagnosis of asthma and provides for patient stratification into a defined level of asthma severity. Because this clinical information is vital to the correct categorization of the patient’s level of asthma, the clinician should be familiar with Table 1 when taking the asthma history. In addition to categorization into intermittent versus persistent, and as mild, moderate, or severe, the patients are also grouped according to age. Based on the level of findings, the clinician is directed to a subsequent algorithm that indicates the recommended medical therapeutic selection (Table 2). CRITICAL CHANGES IN THE THIRD REVISION
The updated guidelines reflect a identified need to monitor the control of asthma. Whereas the initial evaluation of the patient with asthma is to determine at which step to initiate therapy, the reassessments are geared to determine the control of therapy and the need to adjust medications. The evaluation with ongoing therapy is to assess whether the patient’s quality of life has improved by the control of symptoms as outlined in the written physician-patient plan. The evaluation should allow a determination of whether medication use should increase (step up) or decrease (step down). This permits the best quality of life with minimal medication use. In addition to the medication therapy, the guidelines make education a central component to therapy. This includes assuring that the patient understands selfmonitoring of asthma control and can identify signs of acute exacerbation or generalized worsening of disease. Education also encompasses the correct way of physically taking the medications and the decision process for the use of rescue medications. Finally, education extends to the lifestyle changes vital to minimizing asthmatic episodes. Emphasis is placed on a written asthma plan, which is to be created individually for the patient and reviewed regularly between the patient and physician. Allergic disease also receives recognition and therapeutic recommendations in the 2007 version of the guidelines.7 The second expert panel acknowledged the inflammatory component of asthma and the genetic disposition to atopic disease as a major factor. However, the most recent guideline takes the singular step of advocating allergy immunotherapy in cases where a clear connection exists “between symptoms and exposure to an allergen to which the patient is sensitive.”8 This is an important comment for several reasons. Patients with asthma have a higher risk of adverse response to immunotherapy. There have been questions in the literature about whether allergy immunotherapy is sufficiently helpful in the control of asthma to make it worth the risks of adverse reaction. The inclusion of immunotherapy by the expert panel seems to address these concerns, approving the use of immunotherapy in mild to moderate persistent disease, at least in cases in which a direct link to asthma can be appreciated.9 Recommendations that are more specific are possible when patients are grouped into 0 to 4 year olds and 5 to 11 year olds. The latter group was represented as a portion of the adult recommendations in earlier versions of the expert panel recommendations.
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Table 1 Initial visit: classifying asthma severity and initiating therapy (in patients who are not currently taking long-term control medications)
Level of severity (columns 2–5) is determined by events listed in column 1 for both impairment (frequency and intensity of symptoms and functional limitations) and risk (of exacerbations). Assess impairment by patient’s or caregiver’s recall of events during the previous 2 to 4 weeks; assess risk over the last year. Recommendations for initiating therapy based on level of severity are presented in the last row. Abbreviations: EIB, exercise-induced bronchospasm; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; ICS, inhaled corticosteroid; SABA, short-acting beta2-agonist. a Normal FEV1/FVC by age: 8–19 y, 85%; 20–39 y, 80%; 40–59 y, 75%; 60–80 y, 70%. b Data are insufficient to link frequencies of exacerbations with different levels of asthma severity. Generally, more frequent and intense exacerbations (eg, requiring urgent care, hospital or intensive care admission, and/or oral corticosteroids) indicate greater underlying disease severity. For treatment purposes, patients with 2 exacerbations may be considered to have persistent asthma, even in the absence of impairment levels consistent with persistent asthma. From National Heart, Lung, and Blood Institute. Asthma care quick reference. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthma_qrg.pdf. Accessed September 17, 2013.
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Table 2 Stepwise approach for managing asthma long-term
The stepwise approach tailors the selection of medication to the level of asthma severity or asthma control. The stepwise approach is meant to help, not replace, the clinical decision making needed to meet individual patient needs. Abbreviations: EIB, exercise-induced bronchospasm; ICS, inhaled corticosteroid; LTRA, leukotriene receptor antagonist; SABA, short-acting beta2-agonist (inhaled). a Treatment options are listed in alphabetical order, if more than one. b If alternative treatment is used and response is inadequate, discontinue and use preferred treatment before stepping up. c Theophylline is a less desirable alternative because of the need to monitor serum concentration levels. Based on evidence for dust mites, animal dander, and pollen; evidence is weak or lacking for molds and cockroaches. Evidence is strongest for immunotherapy with single allergens. The role of allergy in asthma is greater in children than in adults. d Zileuton is less desirable because of limited studies as adjunctive therapy and the need to monitor liver function. e Clinicians who administer immunotherapy or omalizumab should be prepared to treat anaphylaxis that may occur. f Before oral corticosteroids are introduced, a trial of high-dose ICS 1 LABA 1 either LTRA, theophylline, or zileuton, may be considered, although this approach has not been studied in clinical trials. From National Heart, Lung, and Blood Institute. Asthma care quick reference. Available at: http:// www.nhlbi.nih.gov/guidelines/asthma/asthma_qrg.pdf. Accessed September 17, 2013.
Stepwise Treatment of Asthma
STEPPING THROUGH THE PROCESS OF STEPWISE CARE The Asthma Diagnosis
The frequency of symptoms, nighttime awakenings, and use of short-acting beta2agonists (SABA) combined with spirometry data are the first level used to categorize the severity of asthma. Next it is categorized by intermittent versus persistent. The persistent category is subdivided into mild-moderate or severe. The diagnosis of severity is based on these four categories (see Table 1). Once asthma severity is categorized, the clinician has guidelines to choose from six levels of therapy. Having more levels of therapy than categories of severity allows a different starting point for pediatric and adult patients. It also provides more flexibility in stepping up and down the regimen for patients who require only subtle changes in therapy. Alternative therapies are noted as appropriate (see Table 2). In all age groups, intermittent asthma is managed with step 1 therapy. This primary level therapy is the use of a SABA on an as-needed basis. There is no alternative treatment needed or appropriate at this level. Mild persistent asthma is the second category. At this level, alternative therapies can be considered. Essentially, the primary or recommended therapy is low-dose inhaled corticosteroids. An alternative therapy includes cromolyn, leukotriene receptor antagonists, or (5 years and older) theophylline. This provides the option to withhold inhaled corticosteroids if there is a strong patient or parental concern. Although these two alternative therapies are considered equivalent for the management of mild intermittent asthma, studies indicate that inhaled corticosteroids may better prevent inflammation, and decrease risk of exacerbation and subsequent airway remodeling. Step 2 is also the first level at which subcutaneous allergen immunotherapy should be considered for patients with allergic disease that clearly relates to asthma exacerbations. The data are considered stronger for allergy exacerbating asthma in children and the best evidence seems to support allergy against dust mites, animal dander, and pollen.9 Moderate persistent asthma is initially treated with step 3 therapy. This involves the use of low-dose inhaled corticosteroids plus an LABA or the use of medium-dose inhaled corticosteroids alone. An alternative for adults is to avoid the LABA by substituting leukotriene receptor antagonists or theophylline. A similar option exists for children 5 to 11 years old. The youngest children requiring step 3 therapy are managed using medium-dose inhaled corticosteroids alone. Severe persistent asthma is managed in adults using medium dose inhaled corticosteroids and LABA. An alternative of medium dose inhaled corticosteroids with theophylline or a leukotriene receptor antagonist is also an option. Some adults may exhibit such a severe level of asthma that they require initiation with therapy above step 4 care. Step 5 is high-dose inhaled corticosteroids, combined with LABA, with consideration given to the use of oral steroids. Once step 5 or step 6 is reached, allergy immunotherapy is no longer a recommendation. At this level of asthma, the risk of triggering a significant exacerbation outweighs the benefits of allergy immunotherapy. At this level of severity in the allergic population, omalizumab may be used as replacement for allergy immunotherapy for step 5 and 6 care.10 Step 6 is not used as a starting level, but has been added to the guidelines to provide a rational increased level of care for patients experiencing incomplete control on follow-up visits. Step 6 includes oral corticosteroids in all age groups in addition to high-dose inhaled corticosteroids. LABA is recommended all age groups at level 6. As previously noted, patient’s should leave the initial visit with medical therapy based on the severity of the disease. They should receive education about the disease
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Table 3 Follow-up visits: assessing asthma control and adjusting therapy
Level of control (columns 2–4) is based on the most severe component of impairment (symptoms and functional limitations) or risk (exacerbations). Assess impairment by patient’s or caregiver’s recall of events listed in column 1 during the previous 2 to 4 weeks and by spirometry and/or peak flow measures. Symptom assessment for longer periods should reflect a global assessment, such as inquiring whether the patient’s asthma is better or worse since the last visit. Assess risk by recall of exacerbations during the previous year and since the last visit. Recommendations for adjusting therapy based on level of control are presented in the last row. Abbreviations: ACQ, Asthma Control Questionnaire; ACT, Asthma Control Test; ATAQ, Asthma Therapy Assessment Questionnaire; EIB, exercise-induced bronchospasm; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; SABA, short-acting beta2-agonist. a Minimal important difference: 1.0 for the ATAQ; 0.5 for the ACQ; not determined for the ACT. b ACQ values of 0.76–1.4 are indeterminate regarding well-controlled asthma. c Data are insufficient to link frequencies of exacerbations with different levels of asthma control. Generally, more frequent and intense exacerbations (eg, requiring urgent care, hospital or intensive care admission, and/or oral corticosteroids) indicate poorer asthma control. From National Heart, Lung, and Blood Institute. Asthma care quick reference. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthma_qrg.pdf. Accessed September 17, 2013.
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process and ways to monitor their process by means of either symptoms or expiratory flow measures. Lifestyle adjustment information and careful allergy history and testing as appropriate are recommended. Once therapy has been initiated, follow-up visits are crucial to the step-wise nature of the treatment. Despite all guidelines, the best measure of success in therapy is how the patient progresses. If additional medication is needed, it is important to identify this early in the process and step up the treatment. Similarly, if satisfactory disease control is achieved, reducing medications (step down) will limit the risk of medicine side effects. During the initial phase of asthma therapy, follow-up every 2 to 6 weeks may be necessary. Ongoing asthma management can vary from 1 to 6 months, with spirometry every 1 to 2 years. Follow-up of approximately 3 months is considered most reasonable if the patient is a candidate for decreased therapy. Certainly, if control of asthma is insufficient, visits that are more frequent will be required in order to step up the therapy in a timely fashion. Although the initial diagnosis is geared mostly to the severity of asthma, follow-up visits are mostly concerned with the level of control achieved on the given step of therapy. Table 3 defines the asthma has well controlled, not well controlled, or very poorly controlled, based on the most severe component of the patient’s impairment. The impairments include nighttime awakenings, interference with normal activity, need for rescue inhaler use (not including exercise-induced bronchospasm). Objective measures of lung function include forced expiratory volume in 1 second (FEV1) or peak flow as a percentage of personal best. In children ages 5 to 11 years, the FEV1 to forced vital capacity (FVC) ratio is a helpful alternative metric. As an example, adults who wake fewer than two times a month are considered well controlled, whereas those who wake more than four times a week are considered very poorly controlled. Normal activity should be completely free of interference in wellcontrolled asthma. A patient who has asthma that is not well controlled has some limitation, whereas the patient with poorly controlled asthma is extremely activity-limited. SABA therapy several times a day is an indicator of poor control, whereas more than two days a week is considered not well controlled, and fewer than twice a week defines well-controlled asthma. At follow-up visits, a patient with well-controlled asthma maintains the same level of medication. The patient is considered for a step down to lower medical regimen if control remains satisfactory for at least 3 months. Patients whose asthma is considered not well controlled or poorly controlled should be evaluated carefully. Before simply adding medications, consideration should be given to the presence of any underlying illness or an unfavorable lifestyle adjustment that has precipitated the unfavorable change. Additionally, the clinician should assess patient compliance to medication regimen and patient understanding and use of satisfactory techniques (particularly for inhalers). Reassessment of allergic disease and the use of environmental controls should be undertaken. If there is no specific deficiency in the present therapy, and the patient is experiencing problems with control, treatment will need to move up at least one step in therapy. When considering stepping up therapy, two schools of thought have emerged. One is to increase the therapy gradually, one step at a time, while keeping the patient under careful surveillance. This minimizes the additional use of medications and avoids overshooting the appropriate treatment endpoint. The disadvantage of this therapy is that a patient with moderate or severe asthma who is experiencing poor control might experience significant problems, including need for emergency room intervention, before satisfactory control is achieved. The other option is to advance the therapy two or three steps to a near-maximal therapy, often including oral corticosteroids.
Stepwise Treatment of Asthma
The goal is to achieve rapid control of the asthma exacerbation, and then withdraw medical therapy down to a level that allows for a normal lifestyle. The more aggressive approach has reasonable literature support. The belief is that rapid use of additional steroids will decrease airway inflammation and eventually allow patient management at a lower level than if the medications are increased gradually (allowing airway inflammation to be present for a longer time). SUMMARY
Therapy for asthma has undergone substantial changes in the past three decades, prompted by a better understanding of the role of inflammation in reversible airway disease. Improved therapies and a workable algorithm of step therapy guidelines have provided an improved quality of life for the patient with asthma. REFERENCES
1. Sly RM. Mortality from asthma, 1979–1984. J Allergy Clin Immunol 1988;82(5 Pt 1): 705–17. 2. Wijesingh M, Weatherall M, Perrin K, et al. International trends in asthma mortality rates in the 5- to 34 year age group: a call for closer surveillance. Chest 2009; 135(4):1045–9. 3. Mannino DM, Homa DM, Pertowski CA, et al. Surveillance for asthma—US 1960– 1995. MMWR CDC Surveill Summ 1998;47(SS-1):1–2. Available at: http://www. cdc.gov/mmwr/preview/mmwrhtml/00052262.htm. 4. Barger LW, Vollmer WM, Felt RW, et al. Further investigation into the recent increase in asthma death rates: a review of 41 asthma deaths in Oregon in 1982. Ann Allergy 1988;60(1):31–9. 5. Ishizaka T, Ishizaka K. Molecular basis of reaginic hypersensitivity. Prog Allergy 1975;19:60–121. 6. Guidelines for the diagnosis and management of asthma. National Heart, Lung and Blood Institute. National Asthma Education Program Expert Panel Report. J Allergy Clin Immunol 1991;88(3 pt 2):425–534. 7. National Asthma Education and Prevention Program. 2007 guidelines of the national heart lungs and blood institute; Expert Panel Report 3 (EPR-3): guidelines for the diagnosis and management of asthma-summary report 2007. J Allergy Clin Immunol 2007;120(Suppl 5):S94–138. 8. Hurst DS, Gordon BR, Fornadley JA, et al. Safety of home-based and office allergy immunotherapy: a multicenter prospective study. Otolaryngol Head Neck Surg 1999;121(5):553–61. 9. Lin SY, Erekosima N, Suarez-Cuervo C, et al. Allergen specific immunotherapy for the treatment of allergic rhinoconjunctivitis and/or asthma: comparative effectiveness review 111; ARHQ pub 13 EHC061-EP 2013. 10. Chapman KR, Cartier A, He´bert J, et al. The role of omalizumab in the treatment of severe allergic asthma. Can Respir J 2006;13(Suppl B):1B–9B.
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KEYWORDS Bronchospasm Intermittent bronchospasm Persistent bronchospasm KEY POINTS Asthma management is based on severity of disease. Overmedication or undermedication of asthma is a concern. Uncontrolled asthma may lead to irreversible lung disease.
Step therapy for treatment of asthma has proven a successful means of guiding practitioners through marked changes in management strategy and of gaining better control over this difficult disease process. In the middle to late twentieth century, asthma therapy was not providing satisfactory control of the disease. Physician visits, self-reported reactive airway disease prevalence, and deaths due to asthma increased between 1960 and 1990.1–4 Even more troubling was that a percentage of the deaths were attributed to the bronchodilator therapy, specifically exacerbations of disease related to long-acting beta2agonist (LABA) use. Even without these concerns, bronchodilator therapy did not seem to be the definitive therapy to manage asthma. Scientific work in the 1960s included the discovery of IgE and a better delineation of the role of inflammation in reversible airway disease.5 In combination with recently developed inhaled corticosteroids, this provided a better understanding of the disease as well as a pathway that could make a substantial positive impact on the quality of life for a patient with asthma. Several challenges surrounded the acceptance of this radical algorithm change. The first was the need to educate and change practice patterns of the wide range of practitioners treating asthma, which required informing them and gaining their acceptance of the strategy. Unlike a new medication or adjunctive therapy, the concept of inflammation-based therapy for asthma represented a marked philosophic change. Because physicians tend to gather their continuing education from the medical journals and societies related to their specific field, there was a need to reach out to several disparate societies and journals to get information to the practitioners regarding changes in the therapy of asthma.
Department of Surgery, Penn State University, 500 University Drive, Hershey, PA 17036, USA E-mail address: [email protected] Otolaryngol Clin N Am 47 (2014) 65–75 http://dx.doi.org/10.1016/j.otc.2013.09.014 0030-6665/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
oto.theclinics.com
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Fornadley
Asthma therapy is also complicated by the variability of the disease from lifethreatening exacerbations to a completely normal quality of life between episodes. This disease process does not lend itself to simply starting a medication and continuing it routinely for years, as in the case of hypertension or types of cardiac disease. There is a legitimate concern among physicians and patients about overmedication or undermedication of asthma. Without guidelines, it was unclear when it would be most appropriate to start medications. Unfortunately, with the medications involved, there were side effect profiles that made overuse undesirable. Steroid therapy, which represented a critical new role in asthma care, is known to have side effects that include growth retardation, decreased immunocompetence, and multiple systembased complications. All branches of medicine recognize a strong desire to limit steroid use, which complicates acceptance of the new regimen. In asthma, these limitations must be balanced against the risk of progression of disease and the inability to stabilize the airway by other means. Beta agonists have a somewhat diminished but still vital role in the more modern therapy approach. These agents also suffer from reported complications, including electrolyte disorders, cardiac dysrhythmias, and sudden death.2,4 This change in asthma management occurred at a time when clinical practice guidelines were less well understood and certainly less trusted. Current data on the value of evidence-based guidelines were obviously not available and the physicians of the time were concerned that guidelines were intended to restrict testing and control medical practices for the benefit of third-party payers. It was in this medical environment that the National Asthma Education and Prevention Program (NAEPP), under the auspices of the National Heart, Lung, and Blood Institute, performed a thorough literature review and created a guideline pathway for asthma that was published in 1991.6 The guidelines have been revised in 1997, 2002, and most recently in 2007. The guideline divided asthma into categories of intermittent or persistent, with the latter category being subdivided into mild, moderate, or severe. This categorization then provided the clinician with a step therapy based on the severity of the asthma. These pathways have largely succeeded in changing the way asthma is managed, starting in the last decade of the twentieth century. The intervening time has allowed statistical analysis to identify actual improvement in asthma management as measured by fewer emergency visits and deaths. From 1991 to 2006, progress in the field, new medications, and updated data resulted in the need for changes to the asthma management algorithm. The stepwise approach has grown necessarily more complicated, but the overall principles remain. The guideline continues to provide some rigidity but allows physician judgment and insight. In the current version, the guidelines include patient education and some patient responsibilities. Although some of the elegant simplicity of the 1991 algorithm is lost, the present update allows better active consideration of allergic components of the disease. In addition, there are more options for effectively allowing medication use to step up when needed and step down when possible. The now-familiar four categories of asthma remain unchanged. The step approach for asthma therapy has increased these to six steps. The care recommendations are stratified for patient ages of 0 to 4 years, 5 to 11 years, and 12-plus years to allow for better treatment of pediatric medication variances. The initial step, as before, is the diagnosis of asthma. The goal is to identify asthma, evaluate and exclude other diagnoses, and determine the severity of the disease. Patient history, spirometry (in patients older than 5 years), and the exclusion of other diagnoses is important in arriving at the correct diagnosis. The severity of the disease is important in determining how to initiate therapy. The control aspect of disease is vital
Stepwise Treatment of Asthma
in monitoring and controlling therapy. Severity is defined as the intrinsic intensity of the disease process. This parameter is important for the initiation of therapy (Table 1). The initial assessment is the first and arguably the most critical step, because it has a role in both diagnosis and the direction of initial therapy. The steps of the initial assessment are illustrated in Table 1. Note that the diagnosis includes a history of symptoms and types of precipitating factors, not only spirometry. Spirometry is nevertheless required in patients 5 years and older. These historical data combined with the results of spirometry assist the clinician in making the diagnosis of asthma and provides for patient stratification into a defined level of asthma severity. Because this clinical information is vital to the correct categorization of the patient’s level of asthma, the clinician should be familiar with Table 1 when taking the asthma history. In addition to categorization into intermittent versus persistent, and as mild, moderate, or severe, the patients are also grouped according to age. Based on the level of findings, the clinician is directed to a subsequent algorithm that indicates the recommended medical therapeutic selection (Table 2). CRITICAL CHANGES IN THE THIRD REVISION
The updated guidelines reflect a identified need to monitor the control of asthma. Whereas the initial evaluation of the patient with asthma is to determine at which step to initiate therapy, the reassessments are geared to determine the control of therapy and the need to adjust medications. The evaluation with ongoing therapy is to assess whether the patient’s quality of life has improved by the control of symptoms as outlined in the written physician-patient plan. The evaluation should allow a determination of whether medication use should increase (step up) or decrease (step down). This permits the best quality of life with minimal medication use. In addition to the medication therapy, the guidelines make education a central component to therapy. This includes assuring that the patient understands selfmonitoring of asthma control and can identify signs of acute exacerbation or generalized worsening of disease. Education also encompasses the correct way of physically taking the medications and the decision process for the use of rescue medications. Finally, education extends to the lifestyle changes vital to minimizing asthmatic episodes. Emphasis is placed on a written asthma plan, which is to be created individually for the patient and reviewed regularly between the patient and physician. Allergic disease also receives recognition and therapeutic recommendations in the 2007 version of the guidelines.7 The second expert panel acknowledged the inflammatory component of asthma and the genetic disposition to atopic disease as a major factor. However, the most recent guideline takes the singular step of advocating allergy immunotherapy in cases where a clear connection exists “between symptoms and exposure to an allergen to which the patient is sensitive.”8 This is an important comment for several reasons. Patients with asthma have a higher risk of adverse response to immunotherapy. There have been questions in the literature about whether allergy immunotherapy is sufficiently helpful in the control of asthma to make it worth the risks of adverse reaction. The inclusion of immunotherapy by the expert panel seems to address these concerns, approving the use of immunotherapy in mild to moderate persistent disease, at least in cases in which a direct link to asthma can be appreciated.9 Recommendations that are more specific are possible when patients are grouped into 0 to 4 year olds and 5 to 11 year olds. The latter group was represented as a portion of the adult recommendations in earlier versions of the expert panel recommendations.
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Table 1 Initial visit: classifying asthma severity and initiating therapy (in patients who are not currently taking long-term control medications)
Level of severity (columns 2–5) is determined by events listed in column 1 for both impairment (frequency and intensity of symptoms and functional limitations) and risk (of exacerbations). Assess impairment by patient’s or caregiver’s recall of events during the previous 2 to 4 weeks; assess risk over the last year. Recommendations for initiating therapy based on level of severity are presented in the last row. Abbreviations: EIB, exercise-induced bronchospasm; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; ICS, inhaled corticosteroid; SABA, short-acting beta2-agonist. a Normal FEV1/FVC by age: 8–19 y, 85%; 20–39 y, 80%; 40–59 y, 75%; 60–80 y, 70%. b Data are insufficient to link frequencies of exacerbations with different levels of asthma severity. Generally, more frequent and intense exacerbations (eg, requiring urgent care, hospital or intensive care admission, and/or oral corticosteroids) indicate greater underlying disease severity. For treatment purposes, patients with 2 exacerbations may be considered to have persistent asthma, even in the absence of impairment levels consistent with persistent asthma. From National Heart, Lung, and Blood Institute. Asthma care quick reference. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthma_qrg.pdf. Accessed September 17, 2013.
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Table 2 Stepwise approach for managing asthma long-term
The stepwise approach tailors the selection of medication to the level of asthma severity or asthma control. The stepwise approach is meant to help, not replace, the clinical decision making needed to meet individual patient needs. Abbreviations: EIB, exercise-induced bronchospasm; ICS, inhaled corticosteroid; LTRA, leukotriene receptor antagonist; SABA, short-acting beta2-agonist (inhaled). a Treatment options are listed in alphabetical order, if more than one. b If alternative treatment is used and response is inadequate, discontinue and use preferred treatment before stepping up. c Theophylline is a less desirable alternative because of the need to monitor serum concentration levels. Based on evidence for dust mites, animal dander, and pollen; evidence is weak or lacking for molds and cockroaches. Evidence is strongest for immunotherapy with single allergens. The role of allergy in asthma is greater in children than in adults. d Zileuton is less desirable because of limited studies as adjunctive therapy and the need to monitor liver function. e Clinicians who administer immunotherapy or omalizumab should be prepared to treat anaphylaxis that may occur. f Before oral corticosteroids are introduced, a trial of high-dose ICS 1 LABA 1 either LTRA, theophylline, or zileuton, may be considered, although this approach has not been studied in clinical trials. From National Heart, Lung, and Blood Institute. Asthma care quick reference. Available at: http:// www.nhlbi.nih.gov/guidelines/asthma/asthma_qrg.pdf. Accessed September 17, 2013.
Stepwise Treatment of Asthma
STEPPING THROUGH THE PROCESS OF STEPWISE CARE The Asthma Diagnosis
The frequency of symptoms, nighttime awakenings, and use of short-acting beta2agonists (SABA) combined with spirometry data are the first level used to categorize the severity of asthma. Next it is categorized by intermittent versus persistent. The persistent category is subdivided into mild-moderate or severe. The diagnosis of severity is based on these four categories (see Table 1). Once asthma severity is categorized, the clinician has guidelines to choose from six levels of therapy. Having more levels of therapy than categories of severity allows a different starting point for pediatric and adult patients. It also provides more flexibility in stepping up and down the regimen for patients who require only subtle changes in therapy. Alternative therapies are noted as appropriate (see Table 2). In all age groups, intermittent asthma is managed with step 1 therapy. This primary level therapy is the use of a SABA on an as-needed basis. There is no alternative treatment needed or appropriate at this level. Mild persistent asthma is the second category. At this level, alternative therapies can be considered. Essentially, the primary or recommended therapy is low-dose inhaled corticosteroids. An alternative therapy includes cromolyn, leukotriene receptor antagonists, or (5 years and older) theophylline. This provides the option to withhold inhaled corticosteroids if there is a strong patient or parental concern. Although these two alternative therapies are considered equivalent for the management of mild intermittent asthma, studies indicate that inhaled corticosteroids may better prevent inflammation, and decrease risk of exacerbation and subsequent airway remodeling. Step 2 is also the first level at which subcutaneous allergen immunotherapy should be considered for patients with allergic disease that clearly relates to asthma exacerbations. The data are considered stronger for allergy exacerbating asthma in children and the best evidence seems to support allergy against dust mites, animal dander, and pollen.9 Moderate persistent asthma is initially treated with step 3 therapy. This involves the use of low-dose inhaled corticosteroids plus an LABA or the use of medium-dose inhaled corticosteroids alone. An alternative for adults is to avoid the LABA by substituting leukotriene receptor antagonists or theophylline. A similar option exists for children 5 to 11 years old. The youngest children requiring step 3 therapy are managed using medium-dose inhaled corticosteroids alone. Severe persistent asthma is managed in adults using medium dose inhaled corticosteroids and LABA. An alternative of medium dose inhaled corticosteroids with theophylline or a leukotriene receptor antagonist is also an option. Some adults may exhibit such a severe level of asthma that they require initiation with therapy above step 4 care. Step 5 is high-dose inhaled corticosteroids, combined with LABA, with consideration given to the use of oral steroids. Once step 5 or step 6 is reached, allergy immunotherapy is no longer a recommendation. At this level of asthma, the risk of triggering a significant exacerbation outweighs the benefits of allergy immunotherapy. At this level of severity in the allergic population, omalizumab may be used as replacement for allergy immunotherapy for step 5 and 6 care.10 Step 6 is not used as a starting level, but has been added to the guidelines to provide a rational increased level of care for patients experiencing incomplete control on follow-up visits. Step 6 includes oral corticosteroids in all age groups in addition to high-dose inhaled corticosteroids. LABA is recommended all age groups at level 6. As previously noted, patient’s should leave the initial visit with medical therapy based on the severity of the disease. They should receive education about the disease
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Table 3 Follow-up visits: assessing asthma control and adjusting therapy
Level of control (columns 2–4) is based on the most severe component of impairment (symptoms and functional limitations) or risk (exacerbations). Assess impairment by patient’s or caregiver’s recall of events listed in column 1 during the previous 2 to 4 weeks and by spirometry and/or peak flow measures. Symptom assessment for longer periods should reflect a global assessment, such as inquiring whether the patient’s asthma is better or worse since the last visit. Assess risk by recall of exacerbations during the previous year and since the last visit. Recommendations for adjusting therapy based on level of control are presented in the last row. Abbreviations: ACQ, Asthma Control Questionnaire; ACT, Asthma Control Test; ATAQ, Asthma Therapy Assessment Questionnaire; EIB, exercise-induced bronchospasm; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; SABA, short-acting beta2-agonist. a Minimal important difference: 1.0 for the ATAQ; 0.5 for the ACQ; not determined for the ACT. b ACQ values of 0.76–1.4 are indeterminate regarding well-controlled asthma. c Data are insufficient to link frequencies of exacerbations with different levels of asthma control. Generally, more frequent and intense exacerbations (eg, requiring urgent care, hospital or intensive care admission, and/or oral corticosteroids) indicate poorer asthma control. From National Heart, Lung, and Blood Institute. Asthma care quick reference. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthma_qrg.pdf. Accessed September 17, 2013.
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process and ways to monitor their process by means of either symptoms or expiratory flow measures. Lifestyle adjustment information and careful allergy history and testing as appropriate are recommended. Once therapy has been initiated, follow-up visits are crucial to the step-wise nature of the treatment. Despite all guidelines, the best measure of success in therapy is how the patient progresses. If additional medication is needed, it is important to identify this early in the process and step up the treatment. Similarly, if satisfactory disease control is achieved, reducing medications (step down) will limit the risk of medicine side effects. During the initial phase of asthma therapy, follow-up every 2 to 6 weeks may be necessary. Ongoing asthma management can vary from 1 to 6 months, with spirometry every 1 to 2 years. Follow-up of approximately 3 months is considered most reasonable if the patient is a candidate for decreased therapy. Certainly, if control of asthma is insufficient, visits that are more frequent will be required in order to step up the therapy in a timely fashion. Although the initial diagnosis is geared mostly to the severity of asthma, follow-up visits are mostly concerned with the level of control achieved on the given step of therapy. Table 3 defines the asthma has well controlled, not well controlled, or very poorly controlled, based on the most severe component of the patient’s impairment. The impairments include nighttime awakenings, interference with normal activity, need for rescue inhaler use (not including exercise-induced bronchospasm). Objective measures of lung function include forced expiratory volume in 1 second (FEV1) or peak flow as a percentage of personal best. In children ages 5 to 11 years, the FEV1 to forced vital capacity (FVC) ratio is a helpful alternative metric. As an example, adults who wake fewer than two times a month are considered well controlled, whereas those who wake more than four times a week are considered very poorly controlled. Normal activity should be completely free of interference in wellcontrolled asthma. A patient who has asthma that is not well controlled has some limitation, whereas the patient with poorly controlled asthma is extremely activity-limited. SABA therapy several times a day is an indicator of poor control, whereas more than two days a week is considered not well controlled, and fewer than twice a week defines well-controlled asthma. At follow-up visits, a patient with well-controlled asthma maintains the same level of medication. The patient is considered for a step down to lower medical regimen if control remains satisfactory for at least 3 months. Patients whose asthma is considered not well controlled or poorly controlled should be evaluated carefully. Before simply adding medications, consideration should be given to the presence of any underlying illness or an unfavorable lifestyle adjustment that has precipitated the unfavorable change. Additionally, the clinician should assess patient compliance to medication regimen and patient understanding and use of satisfactory techniques (particularly for inhalers). Reassessment of allergic disease and the use of environmental controls should be undertaken. If there is no specific deficiency in the present therapy, and the patient is experiencing problems with control, treatment will need to move up at least one step in therapy. When considering stepping up therapy, two schools of thought have emerged. One is to increase the therapy gradually, one step at a time, while keeping the patient under careful surveillance. This minimizes the additional use of medications and avoids overshooting the appropriate treatment endpoint. The disadvantage of this therapy is that a patient with moderate or severe asthma who is experiencing poor control might experience significant problems, including need for emergency room intervention, before satisfactory control is achieved. The other option is to advance the therapy two or three steps to a near-maximal therapy, often including oral corticosteroids.
Stepwise Treatment of Asthma
The goal is to achieve rapid control of the asthma exacerbation, and then withdraw medical therapy down to a level that allows for a normal lifestyle. The more aggressive approach has reasonable literature support. The belief is that rapid use of additional steroids will decrease airway inflammation and eventually allow patient management at a lower level than if the medications are increased gradually (allowing airway inflammation to be present for a longer time). SUMMARY
Therapy for asthma has undergone substantial changes in the past three decades, prompted by a better understanding of the role of inflammation in reversible airway disease. Improved therapies and a workable algorithm of step therapy guidelines have provided an improved quality of life for the patient with asthma. REFERENCES
1. Sly RM. Mortality from asthma, 1979–1984. J Allergy Clin Immunol 1988;82(5 Pt 1): 705–17. 2. Wijesingh M, Weatherall M, Perrin K, et al. International trends in asthma mortality rates in the 5- to 34 year age group: a call for closer surveillance. Chest 2009; 135(4):1045–9. 3. Mannino DM, Homa DM, Pertowski CA, et al. Surveillance for asthma—US 1960– 1995. MMWR CDC Surveill Summ 1998;47(SS-1):1–2. Available at: http://www. cdc.gov/mmwr/preview/mmwrhtml/00052262.htm. 4. Barger LW, Vollmer WM, Felt RW, et al. Further investigation into the recent increase in asthma death rates: a review of 41 asthma deaths in Oregon in 1982. Ann Allergy 1988;60(1):31–9. 5. Ishizaka T, Ishizaka K. Molecular basis of reaginic hypersensitivity. Prog Allergy 1975;19:60–121. 6. Guidelines for the diagnosis and management of asthma. National Heart, Lung and Blood Institute. National Asthma Education Program Expert Panel Report. J Allergy Clin Immunol 1991;88(3 pt 2):425–534. 7. National Asthma Education and Prevention Program. 2007 guidelines of the national heart lungs and blood institute; Expert Panel Report 3 (EPR-3): guidelines for the diagnosis and management of asthma-summary report 2007. J Allergy Clin Immunol 2007;120(Suppl 5):S94–138. 8. Hurst DS, Gordon BR, Fornadley JA, et al. Safety of home-based and office allergy immunotherapy: a multicenter prospective study. Otolaryngol Head Neck Surg 1999;121(5):553–61. 9. Lin SY, Erekosima N, Suarez-Cuervo C, et al. Allergen specific immunotherapy for the treatment of allergic rhinoconjunctivitis and/or asthma: comparative effectiveness review 111; ARHQ pub 13 EHC061-EP 2013. 10. Chapman KR, Cartier A, He´bert J, et al. The role of omalizumab in the treatment of severe allergic asthma. Can Respir J 2006;13(Suppl B):1B–9B.
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