Management of acute loss of asthma control in the yellow zone: A practice parameter

Asthma action plans have been recommended for all patients with asthma since the 1991 publication of the first National Heart, Lung, and Blood Institute (NHLBI) guidelines for the diagnosis and management of asthma. Establishment of a patient-provider partnership was a key component of the guidelines and the asthma action plan helped create this relationship by empowering patients to monitor their asthma status and take action when control deteriorated. The most recent iteration of the guidelines, the Expert Panel Report 3 (EPR3): Guidelines for the Diagnosis and Management of Asthma (EPR3), was developed by an expert panel commissioned by the National Asthma Education and Prevention Program Coordinating Committee, coordinated by the NHLBI of the National Institutes of Health. The EPR3 emphasized attainment of asthma control and recommended strategies to treat variations in symptoms that occur over a timeframe of months. In addition to long-term variability of asthma control, most patients with asthma experience intermittent loss of control in response to exposure to acute triggers occurring over a shorter timeframe, such as hours to days. An asthma action plan is the logical tool to instruct patients on how to recognize and respond to such rapid changes in control that occur in a setting outside a supervised medical facility, such as the home. A typical asthma action plan includes written instructions regarding treatment recommendations in the green zone (asthma doing well), the yellow zone (asthma deterioration detected, intervention needed), and the red zone (asthma exacerbation requiring urgent treatment). Responding to the symptoms of acute loss of control in the yellow zone with effective interventions can help prevent deterioration to the red zone, necessitating use of systemic corticosteroids and/or urgent medical care. The EPR3 recommends increasing administration of inhaled SABA (such as 2e6 puffs of albuterol) every 3 to 4 hours for 24 to 48 hours to treat home exacerbations of asthma. If there is insufficient improvement, it recommends adding a short course of oral systemic corticosteroids (Figure 5-4 of the EPR3). In other words, the intervention recommended in the yellow zone by the EPR3 is to increase the frequency of reliever SABA therapy. Guidelines providing evidence-based therapeutic options to manage patients who experience short-term loss of control are therefore lacking, and this practice parameter was written with the intent of addressing the gap. This document attempts to define criteria that indicate acute loss of control into the yellow zone and reviews therapeutic maneuvers to regain asthma control and prevent further progression into the red zone. These recommendations are based on a meticulous and critical review of the medical literature, and in situations where data are lacking, options are presented. The first recommendation in this practice parameter is that patients with asthma should be given a written and/or electronic asthma action plan. Although the format may vary, action plans most commonly follow the traffic light model. The green zone indicates asthma that is controlled, the yellow zone forewarns acute loss of control and an impending exacerbation, and the red zone indicates onset of a severe exacerbation requiring a course of systemic corticosteroids and contact with a health care provider. The action plans may be based on symptoms or on symptoms and peak expiratory flow (PEF), depending on the preference of the provider and the patient. The second summary statement describes criteria for recognition of a yellow zone episode. In particular, patients should be advised to take action when they experience an increase in asthma symptoms, increased use of reliever medications, a decrease in their PEF (if they monitor it), or the onset of nocturnal symptoms. In addition, patients with a history of loss of control in response to respiratory tract infections (RTIs) are advised to take action. The specific action to be taken is dependent on the severity of the episode and the individual response to previous episodes with those interventions. The ideal intervention should provide quick relief of symptoms, prevent progression to the red zone, be safe enough to initiate at home, be convenient and practical for selfadministration, be portable so that it is always available, and be cost effective. Obviously, the perfect intervention does not exist; however, some potential interventions have been studied and are discussed below. Potential interventions for yellow zone treatment include repetitive use of inhaled SABA administered through a metered dose inhaler or nebulizer, scheduled step-up of an ICS, and symptomdriven use of controller with reliever therapy, otherwise known as dynamic dosing or adjustable maintenance dosing (AMD). The regular scheduled use of SABA as the sole treatment for symptoms in the yellow zone is discouraged because it does not consistently prevent progression to the red zone and might increase the risk of progression. Patients who are treated with daily ICS therapy can be advised to increase their total 24-hour ICS dose, for example, by 4-fold. Increase in the frequency of ICS administration over 24 hours also may result in improved efficacy. The EPR2 guidelines had recommended doubling the dose of ICS; however, EPR3 discouraged the use of doubling ICS doses and instead mentioned that preliminary evidence indicates that quadrupling the dose of an ICS for 7 days, starting at the first appearance of worsening symptoms, may prevent exacerbations requiring oral systemic corticosteroids. The key concept acknowledged in this practice parameter is that each yellow zone episode may require a different amount of supplemental ICS dose to prevent progression. For that reason, symptom-driven ICS use and dynamic dosing are attractive alternative options. In this model, patients receive a larger amount of ICS as they experience increasing loss of asthma control and a smaller amount of ICS as control is achieved. The evidence for dynamic dosing appears to be more consistent to that supporting the scheduled use of increased ICS dose in 24 hours. Methods for administration of dynamic dosing include (1) separate use of reliever (ie, SABA) and controller inhalers in combination and (2) use of single inhalers that contain a reliever (SABA or quick-onset long-acting b agonists [LABA] such as formoterol) and a controller that is used for symptom relief (with accompanying escalation in controller therapy). Although the 2 approaches are effective, the use of a single inhaler with a reliever (ie, formoterol) and controller (ie, AMD) is more convenient and has been widely studied and used in other countries. A recent evidencebased review demonstrated that the AMD strategy can decrease exacerbations requiring oral corticosteroids (OCSs) compared with current best-practice strategies, although the authors do not recommend use of this approach in children and adolescents younger than 18 years because large-scale studies have not been conducted in this age group. Notably, although inhalers with the desired properties (ie, ICS with formoterol) are available in the United States, the FDA has not approved those inhalers for dynamic dosing or AMD therapy. In fact, the FDA specifically cautions against initiating use, or increasing the dose, of these inhalers during periods of acutely worsening asthma symptoms. As a result, these treatment options for yellow zone management of patients with asthma would be considered off-label in the United States, to be prescribed at the discretion and medical judgment of the individual provider, with additional extra caution to be exercised when using them in patients younger than 18 years. The practice parameter concludes by briefly discussing additional approaches with limited or no evidence. Although these approaches may be beneficial for individual patients in special circumstances, they are not recommended for general use. It is the hope of the Yellow Zone Workgroup that routine use of an effective yellow zone intervention for patients as part of an action plan will lead to decreased morbidity and improved quality of life for individuals with asthma. This document also highlights evidence gaps in yellow zone asthma management and strongly recommends conducting clinical trials to further validate the approaches explored in this document and to examine other effective options.