Introduction

See section 1, "Overall Methods Used To Develop This Report," for literature search strategy and tally of results for the EPR—3: Full Report 2007 on this component, Measures of Asthma Assessment and Monitoring. Two Evidence Tables were prepared: 1, Predictors of Exacerbation; and 2, Usefulness of Peak Flow Measurement.

Recommendations for "Component 1: Measures of Asthma Assessment and Monitoring" are presented in five sections: "Overview of Assessing and Monitoring Severity, Control, and Responsiveness in Managing Asthma;" "Diagnosis of Asthma;" "Initial Assessment: Characterization of Asthma and Classification of Asthma Severity;" "Periodic Assessment and Monitoring of Asthma Control Essential for Asthma Management;" and "Referral to an Asthma Specialist for Consultation or Comanagement." The recommendations are based on the opinion of the Expert Panel and review of the scientific literature.

Overview of Assessing and Monitoring Asthma Severity, Control, and Responsiveness in Managing Asthma

Diagnosing a patient as having asthma is only the first step in reducing the symptoms, functional limitations, impairment in quality of life, and risk of adverse events that are associated with the disease. The ultimate goal of treatment is to enable a patient to live with none of these manifestations of asthma, and an initial assessment of the severity of the disease allows an estimate of the type and intensity of treatment needed. Responsiveness to asthma treatment is variable; therefore, to achieve the goals of therapy, followup assessment must be made and treatment should be adjusted accordingly. Even patients who have asthma that is well controlled at the time of a clinical assessment must be monitored over time, for the processes underlying asthma can vary in intensity over time, and treatment should be adjusted accordingly.

The functions of assessment and monitoring are closely linked to the concepts of severity, control, and responsiveness to treatment:

• ▪ Severity: the intrinsic intensity of the disease process. Severity is most easily and directly measured in a patient who is not currently receiving long-term control treatment.
• ▪ Control: the degree to which the manifestations of asthma (symptoms, functional impairments, and risks of untoward events) are minimized and the goals of therapy are met.
• ▪ Responsiveness: the ease with which control is achieved by therapy.

An important point linking asthma severity, control, and responsiveness is that the goals are identical for all levels of baseline asthma severity. A patient who has severe persistent asthma compared to a patient who has mild persistent asthma, or a patient who is less responsive to therapy may require more intensive intervention to achieve well-controlled asthma; however, the goals are the same: in well-controlled asthma, the manifestations of asthma are minimized by therapeutic intervention.

Although the severity of disease is most accurately assessed in patients before initiating long-term control medication, many patients are already receiving treatment when first seen by a new health care provider. In such cases, severity can be inferred from the least amount of treatment required to maintain control. This approach presumes that the severity of asthma is closely related to its responsiveness to treatment. Although this assumption may not be true for all forms of asthma and all treatments, it does focus attention on what is important in managing patients who have asthma: achieving a satisfactory level of control.

Both asthma severity and asthma control can be broken down into two domains: impairment and risk. Impairment is an assessment of the frequency and intensity of symptoms and functional limitations that a patient is experiencing or has recently experienced. Risk is an estimate of the likelihood of either asthma exacerbations or of progressive loss of pulmonary function over time.

• ▪ An assessment of the impairment domain for determining the severity of disease (in patients on no long-term-control treatment before treatment is initiated) or the level of control (after treatment is selected) usually can be elicited by careful, directed history and lung function measurement. Standardized questionnaires like the Asthma Control Test (ACT) (Nathan et al. 2004), the Childhood Asthma Control Test (Liu et al. 2007), the Asthma Control Questionnaire (Juniper et al. 1999b), the Asthma Therapy Assessment Questionnaire (ATAQ) control index (Vollmer et al. 1999), and others have been developed to facilitate and standardize the assessment of the impairment domain of asthma control. Some patients, however, appear to perceive the severity of airflow obstruction poorly (Bijl-Hofland et al. 2000; Kikuchi et al. 1994). These patients may have unconsciously accommodated to their symptoms, or perhaps they have mistakenly attributed these symptoms to other causes, like aging, obesity, or lack of fitness, so that they do not report them readily. For these patients, some other measure, such as spirometry, may identify that the degree of airflow obstruction is poorly recognized or perceived by the patient. A trial of therapy can be initiated and lead to unexpected improvement in quality of life ("I did not realize how much better I could feel until my asthma was treated.").
• ▪ Assessment of the risk domain—that is, of adverse events in the future, especially of exacerbations and of progressive, irreversible loss of pulmonary function—is more problematic. Some assessment of the risk of exacerbations can be inferred from the medical history. Patients who have had exacerbations requiring emergency department (ED) visits, hospitalization, or intensive care unit (ICU) admission, especially in the past year, have a great risk of exacerbations in the future (Adams et al. 2000; Eisner et al. 2001; Lieu et al. 1998). Conversely, the achievement of good control of asthma symptoms and airflow obstruction from treatment with an inhaled corticosteroid (ICS) lowers the risk for asthma exacerbations in the future (Bateman et al. 2004). It is not known, however, whether the minimum treatment to control symptoms necessarily reduces the risk of exacerbations. Some patients who have few current symptoms or impairment of quality of life may still be at grave risk of severe, even life-threatening exacerbations (Ayres et al. 2004). Finally, little is known about the prevalence of a heightened risk of progressive loss of pulmonary function among patients who have asthma or whether any current treatment can prevent it.
• ▪ The test most used for assessing the risk of future adverse events is spirometry, especially forced expiratory volume in 1 second (FEV₁) expressed as a percent of the predicted value or as a proportion of the forced vital capacity (FVC) or FEV₁/FVC. The need for a simple, easily applied, more accurate test has prompted study of "biomarkers" whose deviations from normal might correlate with the severity of risk. Many biomarkers have been proposed—airway hyperresponsiveness, blood or sputum eosinophils or eosinophilic cationic protein (ECP), fractional exhaled nitric oxide concentration (FeNO), serum immunoglobulin E (IgE), number of positive skin tests, concentration of hydrogen ion, inflammatory mediators, or various metabolites in an exhaled breath condensate (EBC). Few studies, however, have validated or "anchored" assessment of these markers by analyzing their relationship to the rate of adverse events or decline in pulmonary function over time. Further complicating the matter is that the relationship between normalization of a biomarker and normalization of risk of an adverse event may depend on the specific treatment given. What is found true for treatment with an ICS may not be true for treatment with a leuktotriene receptor antagonist (LTRA) or an inhaled long-acting beta₂-agonist (LABA), or vice versa.
  In the future, assessment of a combination of historical features and of biomarkers may allow accurate estimation of the risk of future adverse events, but it must be kept in mind that laboratory tests only indirectly estimate control of risk. In the end, only symptoms, exacerbations, and quality of life over time are the measures of asthma control.
• ▪ Assessment of response to therapy is important, but there is inconsistency about the definition and measurement of "response." In general, response to therapy describes the ease with which adequate control is achieved by therapy. In a randomized controlled trial (RCT) of interventions to achieve asthma control, decreased symptoms, decreased use of short-acting beta₂-agonist (SABA) for quick relief, improved functioning, improvement in FEV₁, reduction in exacerbations, fewer ED visits, and decreased side effects from medication were equally weighted to develop a composite score that defines a responder to therapy (Bateman et al. 2004). The investigators observed that a composite definition of a responder correlates with asthma control. In a recent editorial, Stempel and Fuhlbrigge (2005) noted that, in published clinical trials, response to therapy based on pre- or postbronchodilator FEV₁ varied widely in statistical significance, depending on the research design and number of subjects included to attain statistical power. Furthermore, when response is defined solely by FEV₁, it can be influenced by disease activity independent of the intervention. It may be significant to characterize other responses, such as decreased airway responsiveness as measured by the response to methacholine, frequency of exacerbations, and decrease in nighttime awakening. This area of work is currently developing and will be influenced by the outcome measures chosen by researchers conducting intervention studies. Agreement is needed on what clinically significant outcomes characterize response to therapy. Agreement is also needed on the time needed to assess response accurately (Zhang et al. 2002), but this time may vary according to treatment. It will take longer to determine whether a patient has responded to a treatment whose principal benefit is reduction in the rate of exacerbations, such as an anti-IgE monoclonal antibody (Bousquet et al. 2004), than to a treatment that acts as an acute bronchodilator.

Another concept closely related to assessing and predicting response to therapy is resistance to therapy. Of adult patients who have asthma, approximately 5 percent have poorly controlled asthma, with frequent symptoms and exacerbations despite use of high-dose ICS (Barnes and Woolcock 1998). Little is known about why some patients who have asthma do not respond well to therapy. A high prevalence of comorbidity—such as uncontrolled gastroesophageal reflux disease (GERD), allergic rhinitis, and psychiatric illness—has been described in this population (Heaney et al. 2003). Patients who have a poor response to appropriate therapy require referral to and consultation with an asthma specialist.

Diagnosis of Asthma

The Expert Panel recommends that the clinician trying to establish a diagnosis of asthma should determine that (EPR—2 1997):

• ▪ Episodic symptoms of airflow obstruction are present.
• ▪ Airflow obstruction is at least partially reversible.
• ▪ Alternative diagnoses are excluded.

Box 3-1 lists key indicators for considering a diagnosis of asthma. A careful medical history, physical examination, pulmonary function tests, and additional tests will provide the information needed to ensure a correct diagnosis of asthma. Each of these methods of assessment is described in this section.

Box 3-1

KEY INDICATORS FOR CONSIDERING A DIAGNOSIS OF ASTHMA. Consider a diagnosis of asthma and performing spirometry if any of these indicators is present. These indicators are not diagnostic by themselves, but the presence of multiple key indicators increases (more...)

Clinical judgment is needed in conducting the assessment for asthma. Patients who have asthma are heterogeneous and present signs and symptoms that vary widely from patient to patient as well as within each patient over time.

MEDICAL HISTORY

The Expert Panel recommends that a detailed medical history of the new patient who is thought to have asthma should address the items listed in figure 3-1 (EPR—2 1997). The medical history can help:

Figure 3-1

SUGGESTED ITEMS FOR MEDICAL HISTORY*

• ▪ Identify the symptoms likely to be due to asthma. See figure 3-2 for sample questions.
• ▪ Support the likelihood of asthma (e.g., patterns of symptoms, family history of asthma or allergies).

Figure 3-2

SAMPLE QUESTIONS* FOR THE DIAGNOSIS AND INITIAL ASSESSMENT OF ASTHMA

PULMONARY FUNCTION TESTING (SPIROMETRY)

The Expert Panel recommends that spirometry measurements—FEV₁, forced expiratory volume in 6 seconds (FEV₆), FVC, FEV₁/FVC—before and after the patient inhales a short-acting bronchodilator should be undertaken for patients in whom the diagnosis of asthma is being considered, including children ≥5 years of age (EPR—2 1997). These measurements help to determine whether there is airflow obstruction, its severity, and whether it is reversible over the short term (Bye et al. 1992; Li and O'Connell 1996). (See box 3-2 for further information.) Patients' perception of airflow obstruction is highly variable, and spirometry sometimes reveals obstruction much more severe than would have been estimated from the history and physical examination.

Box 3-2

IMPORTANCE OF SPIROMETRY IN ASTHMA DIAGNOSIS. Objective assessments of pulmonary function are necessary for the diagnosis of asthma because medical history and physical examination are not reliable means of excluding other diagnoses or of characterizing (more...)

Spirometry typically measures the maximal volume of air forcibly exhaled from the point of maximal inhalation (FVC) and the volume of air exhaled during the first second of this maneuver (FEV₁). Spirometry is generally valuable in children ≥5 years of age, although some children cannot conduct the maneuver adequately until after age 7. Healthy young children complete exhalation of their entire vital capacity in a few seconds, but it can take older patients much longer, especially patients who have airflow obstruction, because expiratory flow is so low at low lung volumes. In these patients, sustaining a maximal expiratory effort for the time necessary for complete exhalation may be more than 12 or 15 seconds—long enough for some patients to find the maneuver uncomfortable or associated with light headedness. This accounts for the interest in measurement of the FEV₆ as a substitute for measurement of FVC in adults. In adults, FEV₆ has been shown to be equivalent to FVC for identifying obstructive and restrictive patterns, using the American Thoracic Society (ATS) algorithm, and to be more reproducible and less physically demanding than FVC (Swanney et al. 2004). Airflow obstruction is indicated by a reduction in the values for both the FEV₁ and the FEV₁/FVC (or FEV₁/FEV₆) relative to reference or predicted values. See figure 3-3a and 3-3b for an example of a spirometric curve for this test. Predicted values for FEV₁/FVC are based on National Health and Nutrition Examination Survey (NHANES) data, National Center for Health Statistics, Centers for Disease Control and Prevention (CDC).

Figure 3-3a

SAMPLE SPIROMETRY VOLUME TIME AND FLOW VOLUME CURVES

Figure 3-3b

REPORT OF SPIROMETRY FINDINGS PRE- AND POSTBRONCHODILATOR

Significant reversibility is indicated by ATS standards as an increase in FEV₁ of >200 mL and ≥12 percent from the baseline measure after inhalation of a short-acting bronchodilator (e.g., albuterol, 2–4 puffs of 90 mcg/puff) (ATS 1995; ATS/ERS et al. 2005; Pellegrino et al. 2005). Some studies indicate that an increase ≥10 percent of the predicted FEV₁ after inhalation of a short-acting bronchodilator may be less subject to bias than measuring percent change from baseline and may have a higher likelihood of separating patients who have asthma from those who have chronic obstructive pulmonary disease (COPD) (Appleton et al. 2005; Brand et al. 1992; Dales et al. 1988; Meslier et al. 1989). Some patients who have signs and symptoms of asthma may not demonstrate reversibility until after a 2- to 3-week trial of oral corticosteroid therapy is administered to help improve their asthma control. Furthermore, the spirometry measured after a single treatment with SABA or after a short course of oral systemic corticosteroid treatment plus acute administration of a bronchodilator may not indicate the patient's best achievable lung function; thus, followup spirometry measures are indicated as asthma control improves.

Abnormalities of lung function are categorized as restrictive and obstructive defects. A reduced ratio of FEV₁/FVC or FEV₁/FEV₆ indicates obstruction to the flow of air from the lungs, whereas a proportionately reduced FVC (or FEV₆ in adults) with a normal or increased FEV₁/FVC (or FEV₁/FEV₆) ratio suggests a restrictive pattern. The severity of abnormality of spirometric measurements is evaluated by comparison of the patient's results with reference values based on age, height, sex, and race (ATS 1995). Furthermore, chronic asthma may be associated with decreased lung function with a loss of response to bronchodilator. Although asthma is typically associated with an obstructive impairment that is reversible, neither this finding nor any other single test or measure is adequate to diagnose asthma. Many diseases are associated with this pattern of abnormality. The patient's pattern of symptoms (along with other information from the patient's medical history) and exclusion of other possible diagnoses also are needed to establish a diagnosis of asthma. In severe cases, the FVC also may be reduced due to trapping of air in the lungs.

When pulmonary function measures are obtained, measuring pulmonary function before and after bronchodilator treatment to determine reversibility is recommended. The degree of airway reversibility correlates with airway inflammation, as measured by sputum eosinophilia and FeNO (Covar et al. 2004a). In addition, those patients who have the greatest degree of reversibility in response to SABA may be at the greatest risk of developing fixed airflow obstruction and have the greatest loss of lung function (Ulrik and Backer 1999). The postbronchodilator FEV₁ measure can then be used to follow lung growth patterns over time (Covar et al. 2004b).

The Expert Panel recommends that office-based physicians who care for asthma patients should have access to spirometry, which is useful in both diagnosis and periodic monitoring. Spirometry should be performed using equipment and techniques that meet standards developed by the ATS (EPR—2 1997). Correct technique, calibration methods, and maintenance of equipment are necessary to achieve consistently accurate test results (ATS/ERS et al. 2005). Maximal effort by the patient in performing the test is required to avoid important errors in diagnosis and management. Training courses in the performance of spirometry that are approved by the National Institute for Occupational Safety and Health are available (800–35–NIOSH).

The Expert Panel recommends that when office spirometry shows severe abnormalities, or if questions arise regarding test accuracy or interpretation, further assessment should be performed in a specialized pulmonary function laboratory (EPR—2 1997).

DIFFERENTIAL DIAGNOSIS OF ASTHMA

The Expert Panel recommends consideration of alternative diagnoses, as appropriate. Box 3-3 lists examples of possible alternative diagnoses for asthma that may be considered during the evaluation of medical history, physical examination, and pulmonary function. Additional studies are not routinely necessary but may be useful when considering alternative diagnoses (EPR—2 1997):

Box 3-3

DIFFERENTIAL DIAGNOSTIC POSSIBILITIES FOR ASTHMA. Infants and Children Upper airway diseases

• ▪ Additional pulmonary function studies (e.g., measurement of lung volumes and evaluation of inspiratory loops) may be indicated, especially if there are questions about possible coexisting COPD, a restrictive defect, VCD, or possible central airway obstruction. A diffusing capacity test is helpful in differentiating between asthma and emphysema in patients, such as smokers and older patients, who are at risk for both illnesses.
• ▪ Bronchoprovocation with methacholine, histamine, cold air, or exercise challenge may be useful when asthma is suspected and spirometry is normal or near normal. For safety reasons, bronchoprovocation testing should be carried out by a trained individual in an appropriate facility and is not generally recommended if the FEV₁ is <65 percent predicted. A positive methacholine bronchoprovocation test is diagnostic for the presence of airway hyperresponsiveness, a characteristic feature of asthma that also can be present in other conditions (e.g., allergic rhinitis, cystic fibrosis, COPD, among others). Thus, although a positive test is consistent with asthma, a negative bronchoprovocation may be more helpful to rule out asthma.
• ▪ Chest x ray may be needed to exclude other diagnoses.
• ▪ Allergy testing (see component 3—Control of Environmental Factors and Comorbid Conditions That Affect Asthma).
• ▪ Biomarkers of inflammation. The usefulness of measurements of biomarkers of inflammation (e.g., total and differential cell count and mediator assays) in sputum, blood, urine, and exhaled air as aids to the diagnosis and assessment of asthma is currently being evaluated in clinical research trials (see "Monitoring Asthma Control With Minimally Invasive Markers and Pharmacogenetics," in the following section on "Periodic Assessment and Monitoring of Asthma Control Essential for Asthma Management").

Recurrent episodes of cough and wheezing are due most often to asthma in both children and adults. Underdiagnosis of asthma is a frequent problem, especially in children who wheeze when they have respiratory infections. These children are often labeled as having bronchitis, bronchiolitis, or pneumonia even though the signs and symptoms are most compatible with a diagnosis of asthma. The clinician needs, however, to be aware of other causes of airway obstruction leading to wheezing (See box 3-3.). See also "Diagnosis and Prognosis of Asthma in Children" in the section "Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age," for more detailed discussion about the diagnosis of asthma in young children.

Cough variant asthma

Although chronic cough can be a sign of many health problems, it may be the principal—or only—manifestation of asthma, especially in young children. This has led to the term "cough variant asthma." Monitoring of PEF or methacholine inhalation challenge, to clarify whether there is bronchial hyperresponsiveness consistent with asthma, may be helpful in diagnosis. The diagnosis of cough variant asthma is confirmed by a positive response to asthma medication (Dicpinigaitis 2006). Treatment should follow the stepwise approach to long-term management of asthma.

Vocal cord dysfunction often mimics asthma

VCD is characterized by episodic dyspnea and wheezing caused by intermittent paradoxical vocal cord adduction during inspiration (sometimes with abnormal adduction during expiration as well). The cause of VCD is not well understood, although some patients develop VCD in response to irritant triggers, such as fumes, cold air, and exercise. Although VCD is clearly distinct from asthma, it is often confused with asthma, leading to inappropriate medication of affected individuals with anti-asthma medications. Asthma medications typically do little, if anything, to relieve symptoms if the patient has pure VCD. VCD should be considered in the differential of difficult-to-treat, atypical asthma patients. It is important to note, however, that VCD and asthma may coexist and that VCD may complicate asthma management. Elite athletes, in particular, are prone to both exercise-induced bronchospasm (EIB) and VCD, so careful workup is warranted for athletes who present with exercise-related breathlessness (Rundell and Spiering 2003). During severe VCD episodes, respiratory distress may be severe and lead to intubation. Once the trachea is intubated, the wheezing and distress abate in VCD but not in asthma.

VCD can be difficult to diagnose. Variable flattening of the inspiratory flow loop on spirometry is strongly suggestive of the diagnosis, but abnormalities of the inspiratory loop may well be absent between episodes. The diagnosis of VCD comes from indirect or direct vocal cord visualization during an episode, during which the abnormal adduction can be documented. Therapy generally consists of speech therapy and relaxation techniques (Bucca et al. 1995; Christopher et al. 1983; Newman et al. 1995).

Several conditions that may coexist with asthma can complicate diagnosis: ABPA, OSA, and GERD (See "Component 3: Control of Environmental Factors and Comorbid Conditions That Affect Asthma.").

Initial Assessment: Characterization of Asthma and Classification of Asthma Severity

The Expert Panel recommends that clinicians use information obtained from the diagnostic evaluation, and any additional information, if necessary, to (EPR—2 1997):

• ▪ Identify precipitating factors
• ▪ Identify comorbid conditions that may aggravate asthma
• ▪ Assess the patient's knowledge and skills for self-management
• ▪ Classify asthma severity

Once the diagnosis of asthma has been established, the next step in the initial assessment is to characterize the patient's asthma in order to guide decisions for selecting therapy. This characterization is a basic description of the patient's asthma phenotype.

As noted earlier, the usefulness of measurements of biomarkers of inflammation (e.g., total and differential cell count and mediator assays) in sputum, blood, urine, and exhaled air as aids to the diagnosis and assessment of asthma is currently being evaluated in clinical research trials (See "Monitoring Asthma Control With Minimally Invasive Markers and Pharmacogenetics," in the following section on "Periodic Assessment and Monitoring of Asthma Control Essential for Asthma Management.").

CLASSIFY ASTHMA SEVERITY

The Expert Panel recommends that clinicians classify asthma severity by using the domains of current impairment and future risk (Evidence B—secondary analyses of clinical trials, and Evidence C—observational studies, for assessing impairment; Evidence C, for distinguishing intermittent versus persistent asthma by risk of exacerbations; Evidence D, for distinguishing different categories of persistent asthma by varying frequencies of exacerbations).

Asthma severity is the intrinsic intensity of disease. Initial assessment of patients who have confirmed asthma begins with a severity classification because the selection of type, amount, and scheduling of therapy should then correspond to the level of asthma severity. This initial assessment of asthma severity is made immediately after diagnosis, or when the patient is first encountered, generally before the patient is taking some form of long-term control medication. Assessment is made on the basis of current spirometry and the patient's recall of symptoms over the previous 2–4 weeks, because detailed recall of symptoms decreases over time. If the assessment is made during a visit in which the patient is treated for an acute exacerbation, then asking the patient to recall symptoms in the period before the onset of the current exacerbation will suffice until a followup visit can be made.

For population-based evaluations, clinical research, or subsequent characterization of the patient's overall severity, asthma severity can be inferred after optimal therapy is established by correlating levels of severity with the lowest level of treatment required to maintain control. For clinical management, however, the emphasis is to assess asthma severity prior to initiating therapy and, then, assess control for monitoring and adjusting therapy.

The severity classification of asthma shown in figures 3-4 a, b, and c uses the two domains of current impairment and future risk. The specific measures for classifying severity—symptoms, use of SABA for quick relief, exacerbations, and pulmonary function—that were presented in EPR—2 remain in the current report, although they have been organized into the new framework of measures of impairment and risk. As noted in the "Overview" section of this component, the distinction between impairment and risk emphasizes the need to consider separately asthma's effects on quality of life and functional capacity on an ongoing basis (i.e., in the present) and the risks asthma presents for adverse events in the future, such as exacerbations and progressive loss of pulmonary function. Clinical trial data demonstrate that these "domains" of asthma may respond differentially to treatment. Data further suggest that, in estimating severity or control in either domain, different manifestations of asthma must be assessed, because they do not necessarily correlate with each other (Bacharier et al. 2004; Colice et al. 1999; Fuhlbrigge et al. 2002; Strunk et al. 2002). Thus, a composite of measures, with a distinction between domains of impairment and risk, will be useful in classifying severity.

Figure 3-4a

CLASSIFYING ASTHMA SEVERITY IN CHILDREN 0–4 YEARS OF AGE *Notes:

Figure 3-4b

CLASSIFYING ASTHMA SEVERITY IN CHILDREN 5–11 YEARS OF AGE *Notes:

Figure 3-4c

CLASSIFYING ASTHMA SEVERITY IN YOUTHS ≥12 YEARS OF AGE AND ADULTS *Notes:

Assessment of Impairment

Assessment of severity requires assessing the following components of current impairment:

• ▪ Symptoms

  • — Nighttime awakenings
  • — Need for SABA for quick relief of symptoms
  • — Work/school days missed
  • — Ability to engage in normal daily activities or in desired activities
  • — Quality-of-life assessments
• ▪ Lung function, measured by spirometry: FEV₁, FVC (or FEV₆), FEV₁/FVC (or FEV₆ in adults). Spirometry is the preferred method for measuring lung function to classify severity. Peak flow has not been found to be a reliable variable for classifying severity (Eid et al. 2000; Llewellin et al. 2002), but it may serve as a useful tool for monitoring trends in asthma control over time (See section, "Monitoring Lung Function.").

Secondary analyses of clinical trial data and observational studies using the EPR—2 1997 or similar Global Initiative for Asthma (GINA) criteria have confirmed that the parameters for the impairment domain (symptom, activity levels, and pulmonary function) reflect increasing gradients of severity in adults (Antonicelli et al. 2004; Diette et al. 2004; EPR—2 1997; Schatz et al. 2003, 2005b).

Whether the ranges of pulmonary function for severity of asthma previously defined in guidelines (EPR—2 1997) apply well to children has been questioned in cross-sectional studies that found normal FEV₁ values (many over 90 percent predicted) in a majority of the children, 5–18 years of age, regardless of their asthma severity as classified on the basis of symptoms (Bacharier et al. 2004; Paull et al. 2005; Spahn et al. 2004). Two of those studies reported that, in contrast to FEV₁ measures, FEV₁/FVC decreased with increasing asthma severity and thus appeared to be a more sensitive measure of severity (Bacharier et al. 2004; Paull et al. 2005). On the other hand, analysis of a large, longitudinal study of children confirmed a relationship between the severity of airflow obstruction and the risk of exacerbations (Fuhlbrigge et al. 2001). Increasing risk correlated with the FEV₁ cutoffs for increasing levels of severity as defined in EPR—2 (Fuhlbrigge et al. 2006). It is emphasized that these studies also found that even children who had normal values of lung function experienced exacerbations. In addition, children who have low lung function are at greatest risk of developing fixed airflow obstruction over time (Rasmussen et al. 2002). Cumulatively, these studies underscore the importance of measuring several variables in the assessment of asthma. Making treatment decisions for children should be based on frequency and severity of past exacerbations and symptoms, with pulmonary function measures as an additional guide. FEV₁ appears to be a useful measure indicating risk for exacerbations; FEV₁/FVC appears to be a more sensitive measure of severity in the impairment domain. The Expert Panel has updated the pulmonary function measures for assessing asthma severity and control in children by adding suggested ranges for FEV₁/FVC.

Assessment of Risk

A closely related and second dimension of severity is the concept of risk of adverse events, including exacerbations and risk of death. Assessment of the risk of future adverse events requires careful medical history, observation, and clinician judgment. Documentation of warning signs and adverse events will be necessary when a patient is felt to be at increased risk. Patients who are deemed at increased risk of adverse outcomes will need close monitoring and frequent assessment by their clinicians.

• ▪ Exacerbations of asthma are acute or subacute episodes of progressively worsening shortness of breath, cough, wheezing, and chest tightness—or some combination of these symptoms. Exacerbations are characterized by decreases in expiratory airflow that can be documented and quantified by simple measurement of lung function (spirometry or PEF). Exacerbations of asthma can vary widely among individuals and within individuals, from very rare to frequent. Although the classification of severity focuses on the frequency of exacerbations, it is important to note that the severity of disease does not necessarily correlate with the intensity of exacerbations, which can vary from mild to very severe and life-threatening. Patients at any level of severity, even intermittent asthma, can have severe exacerbations. For example, a person who has intermittent asthma can have a severe exacerbation during a viral illness or when exposed to allergens to which he or she is sensitized or to noxious fumes and irritants. Accordingly, the Expert Panel has modified the designation of "mild intermittent asthma" in the previous guidelines (EPR—2 1997; EPR—Update 2002) to become "intermittent asthma" to emphasize that patients at any level of severity—including intermittent—can have severe exacerbations. The duration of exacerbations may vary from a few hours to a few days. These unpredictable variations in exacerbations can present treatment dilemmas for the clinician who strives to prevent future exacerbations and considers when to initiate chronic anti-inflammatory therapy.
  The frequency of exacerbations requiring intervention with oral systemic corticosteroids has been correlated in observational studies with the designation of persistent, rather than intermittent, asthma (Fuhlbrigge et al. 2001, 2006). Determination of whether the level of severity is mild, moderate, or severe will depend on consideration of both the frequency and the intensity of the exacerbations. No data are available to correspond specific numbers with each severity category. In general, the more frequent and the more intense the exacerbations (e.g., requiring urgent, unscheduled clinical care, hospitalization, or ICU admission), the greater the degree of underlying disease severity.
• ▪ Predictors that have been reported to be associated with increased risk of exacerbations (See Evidence Table 1, Predictors of Exacerbations.) or death include:

  • — Severe airflow obstruction, as detected by spirometry (Adams et al. 2000; Connolly et al. 1998; Fuhlbrigge et al. 2001, 2006; Kitch et al. 2004).
  • — Persistent severe airflow obstruction (Kitch et al. 2004).
  • — Two or more ED visits or hospitalizations for asthma in the past year; any history of intubation or ICU admission, especially if in the past 5 years (Belessis et al. 2004; Cowie et al. 2001).
  • — Patients report that they feel in danger or frightened by their asthma (Janson-Bjerklie et al. 1993; Ng 2000).
  • — Certain demographic or patient characteristics: female, nonwhite (Diette et al. 2002), nonuse of ICS therapy, and current smoking (Eisner et al. 2001).
  • — Psychosocial factors: depression (Eisner et al. 2005; Goodwin et al. 2004), increased stress (Goodwin et al. 2004), socioeconomic factors (Griswold et al. 2005).
  • — Attitudes and beliefs about taking medications (Adams et al. 2000; Apter and Szefler 2004).

For population-based management, risk stratification is used to identify patients at increased risk of morbidity and health care resource use. Several validated psychometric instruments have been shown to predict future risk of hospitalization and ED visits (Schatz et al. 2005a).

Periodic Assessment and Monitoring of Asthma Control Essential for Asthma Management

GOALS OF THERAPY: ASTHMA CONTROL

The purpose of periodic assessment and ongoing monitoring is to determine whether the goals of asthma therapy are being achieved and asthma is controlled. When asthma is not controlled, it is associated with significant asthma burden (Fuhlbrigge et al. 2002), decreased quality of life (Schatz et al. 2005b), and increased health care utilization (Schatz et al. 2005a; Vollmer et al. 2002). The level of asthma control (well controlled, not well controlled, or poorly controlled) is the degree to which both dimensions of the manifestations of asthma—impairment and risk—are minimized by therapeutic intervention. The level of control at the time of followup assessment will determine clinical actions—that is, whether to maintain or adjust therapy. In previous guidelines (EPR—2 1997; GINA 2002), parameters for control were selected on the basis of research that used individual outcomes for evaluating the effectiveness of asthma treatments. The composite list of goals reflected the Panel's opinions of a complete list of relevant outcomes that could define asthma control. A recent large international trial demonstrated that significant reductions in the rate of severe exacerbations and improvements in quality of life were achieved by aiming at achieving guideline-defined asthma control and by adjusting therapy to achieve it. At the end of 1 year, 30 percent of the patients achieved total control (i.e., the absence of any sign or symptom of asthma), and 60 percent had achieved well-controlled asthma (Bateman et al. 2004).

Interpretation of previous asthma guidelines, in which severity classifications before treatment corresponded to recommended steps of treatment, has raised questions about applying severity classifications once treatment is established and what elements of asthma should be used to monitor asthma during clinical followup (Graham 2006; Wolfenden et al. 2003). This update (EPR—3: Full Report 2007) clarifies the issue. For initiating treatment, asthma severity should be classified, and the initial treatment should correspond to the appropriate category of severity. Once treatment is established, the emphasis is on assessing asthma control to determine if the goals for therapy have been met and if adjustments in therapy (step up or step down) would be appropriate.

The Expert Panel recommends that asthma control be defined as follows (Evidence A):

Asthma Control

• ▪ Reduce impairment

  • — Prevent chronic and troublesome symptoms (e.g., coughing or breathlessness in the daytime, in the night, or after exertion)
  • — Require infrequent use (≤2 days a week) of SABA for quick relief of symptoms
  • — Maintain (near) "normal" pulmonary function
  • — Maintain normal activity levels (including exercise and other physical activity and attendance at work or school)
  • — Meet patients' and families' expectations of and satisfaction with asthma care
• ▪ Reduce risk

  • — Prevent recurrent exacerbations of asthma and minimize the need for ED visits or hospitalizations
  • — Prevent progressive loss of lung function; for children, prevent reduced lung growth
  • — Provide optimal pharmacotherapy with minimal or no adverse effects

See figures 3-5a, b, and c for classification of asthma control in three different age groups. Specific discussion of measures for assessment are in the following section. In general:

Figure 3-5a

ASSESSING ASTHMA CONTROL IN CHILDREN 0–4 YEARS OF AGE Notes:

Figure 3-5b

ASSESSING ASTHMA CONTROL IN CHILDREN 5–11 YEARS OF AGE Notes:

Figure 3-5c

ASSESSING ASTHMA CONTROL IN YOUTHS ≥12 YEARS OF AGE AND ADULTS Notes:

• ▪ Assessment of impairment is in the form of questions, such as those presented in figure 3-6 and within figure 3-7. The focus of these questions is to assess the degree of asthma control in the present. The key elements include current pulmonary function and patient's recall of symptoms, physical activity, quality of life, and need for SABA for quick relief of symptoms over the previous 2–4 weeks.
• ▪ Assessing the risk of exacerbations is through questions regarding the use of medications, particularly oral corticosteroids, or urgent care visits. Low FEV₁ is associated with increased risk for severe exacerbations (Fuhlbrigge et al. 2001).
• ▪ Assessment of the risk of progressive loss function, or, for children, the risk of reduced lung growth (measured by prolonged failure to attain predicted lung function values for age) requires longitudinal assessment of lung function, preferably using spirometry.
• ▪ Assessment of the risk of side effects from medication does not directly correspond to the varying levels of asthma control. For example, a patient might have well-controlled asthma with high doses of ICS and chronic oral corticosteroids but is likely to experience some adverse effects from this intense therapy. The risk of side effects can vary in intensity from none to very troublesome and worrisome; see component 4—Medications for discussion of potential adverse effects associated with different asthma medications. Although not directly correlated to control, the risk or evidence of side effects should be included in the overall assessment of the risk domain of asthma control.
• ▪ Future work on assessment of asthma control tools will define the relative value of including specific biological markers and test how well the tool predicts the risk of exacerbations.

Figure 3-6

SAMPLE QUESTIONS FOR ASSESSING AND MONITORING ASTHMA CONTROL Source: Adapted and reprinted from "Global Initiative for Asthma: Pocket Guide for Asthma Management and Prevention." NIH Publication No. 96-3659B. Bethesda, MD: Department of Health and Human (more...)

Figure 3-7

COMPONENTS OF THE CLINICIAN'S FOLLOWUP ASSESSMENT: SAMPLE ROUTINE CLINICAL ASSESSMENT QUESTIONS*

MEASURES FOR PERIODIC ASSESSMENT AND MONITORING OF ASTHMA CONTROL

The Expert Panel recommends that ongoing monitoring of asthma control be performed to determine whether all the goals of therapy are met—that is, reducing both impairment and risk (Evidence B); see figures 3-5 a, b, and c for assessing asthma control for different age groups.

The Expert Panel recommends that the frequency of visits to a clinician for review of asthma control is a matter of clinical judgment; in general, patients who have intermittent or mild persistent asthma that has been under control for at least 3 months should be seen by a clinician about every 6 months, and patients who have uncontrolled and/or severe persistent asthma and those who need additional supervision to help them follow their treatment plan need to be seen more often (EPR—2 1997).

The assessment measures for control monitor six areas described in this section and are recommended based on the opinion of the Expert Panel and review of the scientific literature. A seventh area, monitoring asthma control with minimally invasive markers, is of increasing interest, but many of these markers require further evaluation before they can be recommended widely for routine asthma care.

• ▪ Monitoring signs and symptoms of asthma
• ▪ Monitoring pulmonary function

  • — Spirometry
  • — Peak flow monitoring
• ▪ Monitoring quality of life
• ▪ Monitoring history of asthma exacerbations
• ▪ Monitoring pharmacotherapy for adherence and for potential side effects
• ▪ Monitoring patient–provider communication and patient satisfaction
• ▪ Monitoring asthma control with minimally invasive markers and pharmacogenetics (requires further evaluation)

Monitoring Signs and Symptoms of Asthma

The Expert Panel recommends that every patient who has asthma should be taught to recognize symptom patterns that indicate inadequate asthma control (Evidence A) (See also "Component 2: Education for a Partnership in Asthma Care."). Either symptom and/or PEF monitoring should be used as a means to determine the need for intervention, including additional medication, in the context of a written asthma action plan.

The Expert Panel recommends that symptoms and clinical signs of asthma should be assessed at each health care visit through physical examination and appropriate questions (EPR—2 1997). This is important for optimal asthma care.

The Expert Panel recommends that the detailed symptoms history should be based on a short (2–4 weeks) recall period (EPR—2 1997). Patients' detailed recall of symptoms decreases over time; therefore, the clinician may choose to assess over a 2-week, 3-week, or 4-week recall period. Symptom assessment for periods longer than 4 weeks should reflect more global symptom assessment, such as inquiring whether the patient's asthma has been better or worse since the last visit and inquiring whether the patient has encountered any particular difficulties during specific seasons or events. Figure 3-7 provides an example of a set of questions that can be used to characterize both global (long-term recall) and recent (short-term recall) asthma symptoms.

The Expert Panel recommends that assessment of the patient's symptom history should include at least four key symptom expressions (Evidence B, extrapolation from clinical trials; and Evidence C, from observational studies):

• ▪ Daytime asthma symptoms (including wheezing, cough, chest tightness, or shortness of breath)
• ▪ Nocturnal awakening as a result of asthma symptoms
• ▪ Frequency of use of SABA for relief of symptoms
• ▪ Inability or difficulty performing normal activities (including exercise) because of asthma symptoms

Monitoring Pulmonary Function

The Expert Panel recommends that, in addition to assessing symptoms, it is also important to assess pulmonary function periodically (Evidence B, extrapolation from clinical trials; and Evidence C, from observational studies). The main methods are spirometry and peak flow monitoring.

Low FEV₁ is associated with increased risk of severe asthma exacerbations (Fuhlbrigge et al. 2001). Regular monitoring of pulmonary function is particularly important for asthma patients who do not perceive their symptoms until airflow obstruction is severe. There is no readily available method of detecting the "poor perceivers." The literature reports that patients who had a near-fatal asthma exacerbation, as well as older patients, are more likely to have poor perception of airflow obstruction (Connolly et al. 1992; Kikuchi et al. 1994).

Spirometry

The Expert Panel recommends the following frequencies for spirometry measurements: (1) at the time of initial assessment (Evidence C); (2) after treatment is initiated and symptoms and PEF have stabilized, to document attainment of (near) "normal" airway function; (3) during a period of progressive or prolonged loss of asthma control; and (4) at least every 1–2 years to assess the maintenance of airway function (Evidence B, extrapolation from clinical trials). Spirometry may be indicated more often than every 1–2 years, depending on the clinical severity and response to management (Evidence D). These spirometry measures should be followed over the patient's lifetime to detect potential for decline and rate of decline of pulmonary function over time (Evidence C).

As noted previously, adjusting therapy according to the level of asthma control improves the patient's quality of life and reduces morbidity due to asthma (Bateman et al. 2004). Measures of control in this and related studies, as well as in numerous clinical trials that examine drug efficacy, include measures of lung function obtained by spirometry. Lung function declines in adults as they grow older, and adults who have asthma have greater declines, on average, than adults who do not have asthma and do not smoke. For children, lung function increases as they grow older, until maximal lung function is achieved, which occurs for most individuals by 20 years of age. Children who have asthma may have reductions in lung growth compared to children who do not have asthma. The postbronchodilator FEV₁ measure can be used to follow lung growth patterns over time (Covar et al. 2004a). Observations of reduced lung growth may reflect a progressive worsening of asthma control that should be treated accordingly.

Spirometry with measurement of the FEV₁ is also useful:

• ▪ As a periodic (e.g., yearly) check on the accuracy of the peak flow meter (Miles et al. 1995) for patients who are monitoring PEF.
• ▪ When more precision is desired in measuring lung function (e.g., when evaluating response to bronchodilator or nonspecific airway responsiveness or when assessing response to a "step down" in pharmacotherapy).
• ▪ When PEF results are unreliable (e.g., in some very young or elderly patients, when neuromuscular or orthopedic problems are present, or technical artifact is suspected (see below)) and the physician needs the quality checks that are available only with spirometry (Hankinson and Wagner 1993).

Peak Flow Monitoring

The Expert Panel recommends the following:

• ▪ If peak flow monitoring is performed, the written asthma action plan should use the patient's personal best peak flow as the reference value (EPR—Update 2002).
• ▪ Consider long-term daily peak flow monitoring for:

  • — Patients who have moderate or severe persistent asthma (Evidence B).
  • — Patients who have a history of severe exacerbations (Evidence B).
  • — Patients who poorly perceive airflow obstruction and worsening asthma (Evidence D).
  • — Patients who prefer this monitoring method (Evidence D).
• ▪ Long-term daily peak flow monitoring can be helpful to (EPR—Update 2002):

  • — Detect early changes in disease states that require treatment.
  • — Evaluate responses to changes in therapy.
  • — Afford a quantitative measure of impairment.
• ▪ Peak flow monitoring during exacerbations will help determine the severity of the exacerbations and guide therapeutic decisions in the home, school, clinicians' office, or ED (See "Component 2: Education for a Partnership in Asthma Care" and section 5, "Managing Exacerbations of Asthma.").
• ▪ Consider home peak flow monitoring during exacerbations of asthma for:

  • — Patients who have a history of severe exacerbations (Evidence B).
  • — Patients who have moderate or severe persistent asthma (Evidence B).
  • — Patients who have difficulty perceiving signs of worsening asthma (Evidence D).

PEF measurements, using either handheld mechanical or electronic metered devices, provide a means to obtain simple, quantitative, and reproducible assessments of the existence and severity of airflow obstruction. It must be stressed that peak flow meters function best as tools for ongoing monitoring, not diagnosis. Because the measurement of PEF is dependent on effort and technique, patients need instructions, demonstrations, and frequent reviews of technique. See "Component 2: Education for a Partnership in Asthma Care" for detailed instructions on using peak flow meters. The accuracy of peak flow monitoring devices may decrease over time (Irvin et al. 1997); therefore, measurements that are at odds with the clinical status of the patient may be related to technical and not physiologic factors, and consideration should be given to reviewing technique with the patient or replacing the device the patient is currently using. The patient's measured personal best peak flow is the most appropriate reference value for the patient's action plan.

In clinical trials, peak flow values have been used as major outcome measures to monitor both asthma control and treatment responses, short (Lazarus et al. 2001) and long term (Boushey et al. 2005). In the context of both impairment and risk domains for asthma severity reviewed previously, it should be noted that peak flow values may not correlate with other asthma outcome measures such as treatment failure (Leone et al. 2001) or asthma exacerbations (Lazarus et al. 2001). Although peak flow monitoring to guide chronic asthma management has been reported to be valuable in studies more reflective of clinical practice, the results are not consistent enough for this tool to be recommended uniformly for all asthma patients (Jain et al. 1998) (See Evidence Table 2, Usefulness of Peak Flow Measurement, and EPR—Update 2002.). Thus, the relative usefulness of peak flow measurements as monitoring tools can be individualized, based on the patient's age (decreased utility in preschool children and the elderly), socioeconomic status (minority and poor children show greatest benefit) (Yoos et al. 2002), asthma pattern (of questionable utility to monitor individuals who have histories of rapid onset of severe airflow obstruction), asthma severity (Llewellin et al. 2002), ability to perceive signs and symptoms of early worsening of asthma (Jain et al. 1998), and the clinician's and patient's opinions as to their contribution in achieving and maintaining acceptable asthma control.

Peak Flow Versus Symptom-Based Monitoring Action Plan

A systematic review of the evidence in 2002 concluded that, although studies available at that time were limited, studies did not clearly show that a peak flow monitoring-based action plan was better than a symptom monitoring-based plan in improving outcomes but that it did show similar benefits.

Evidence generated since the 2002 review does not change these recommendations.

The Expert Panel recommends the following:

• ▪ Either peak flow monitoring or symptom monitoring, if taught and followed correctly, may be equally effective (Evidence B).
• ▪ Whether peak flow monitoring, symptom monitoring, or a combination of approaches is used, self-monitoring is important to the effective self-management of asthma (Evidence A). The nature and intensity of self-monitoring should be individualized, based on such factors as asthma severity, the patient's ability to perceive airflow obstruction, availability of peak flow meters, and patient preferences. Patient preferences for objective measures or certain patient circumstances, such as inability either to perceive or to report signs and symptoms of worsening asthma, warrant the use of peak flow monitoring and justify the associated time, energy, and costs to the clinician and patient (Evidence D).
• ▪ Provide to all patients a written asthma action plan that includes daily treatment and recognizing and handing worsening asthma, including self-adjustment of medications in response to acute symptoms or changes in PEF measures. Written action plans are particularly recommended for patients who have moderate or severe persistent asthma, a history of severe exacerbations, or poorly controlled asthma (Evidence B). Either peak flow or symptom self-monitoring appears to increase patients' awareness of the disease status and control, thereby helping patients "tune in" to their disease; and action plans enhance clinician–patient communication. Thus, the nature of the plan, whether it is based on symptoms or based on peak flow, is not the important issue; rather, it is having a plan in place versus not having one at all. For additional discussion of written asthma action plans, see component 2—Education for Partnership in Asthma Care and section 4, "Managing Asthma Long Term in Children, School Issues."

Monitoring Quality of Life

The Expert Panel recommends that several key areas of quality of life and related loss of physical function should be assessed periodically for each person who has asthma (Evidence C). These include:

• ▪ Any work or school missed because of asthma
• ▪ Any reduction in usual activities (either home/work/school or recreation/exercise)
• ▪ Any disturbances in sleep due to asthma
• ▪ Any change in caregivers' activities due to a child's asthma (for caregivers of children who have asthma)

See figure 3-7 for sample questions that characterize quality-of-life concerns for persons who have asthma.

The goals of asthma treatment include improving quality of life for people who have asthma in addition to controlling symptoms, reducing the risk of exacerbations, and preventing asthma-related death. It is important, therefore, to examine how the disease expression and control are affecting the patient's quality of life. Several dimensions of quality of life may be important to track; these include physical function, role function, and mental health function. Clinical asthma status parameters correlate only moderately with quality-of-life measures. Correlations between symptoms and quality of life are often in the low-to-moderate range, while correlations with pulmonary function measures are quite weak. These observations suggest that perceptions and experiences of patients must be assessed directly and not imputed from measures of clinical status. Quality of life appears to be a distinct component of asthma health status, along with nighttime symptoms, daytime symptoms, and SABA use (Juniper et al. 2004).

In general, the impact of asthma is greater on the physical functioning component of life quality than on mental functioning (Adams et al. 2006; Graham et al. 2000; Stahl et al. 2003). However, when loss of physical functioning in valued life activities occurs, a higher correlation with quality of life is found among adults who have asthma. Valued life activities are those that individuals find most meaningful or pleasurable, and loss of these has been found to have a significant association with an increase in clinical asthma severity, patients' perception of asthma severity, and decrease in general physical function (Katz et al. 2004). Similarly, among adolescents who have asthma, quality of life was found to correlate with shortness of breath during exercise (Hallstrand et al. 2003). In contrast, in younger children (mean age of 9.3 ± 2.2 years), quality of life was more associated with the level of anxiety (Annett et al. 2001). Significant reduction in quality of life is also apparent when people who have asthma also have comorbid chronic conditions, such as diabetes, arthritis, heart disease, stroke, cancer, and osteoporosis (Adams et al. 2006).

The predictors of quality of life among people who have asthma may be related to levels of asthma severity. Lung function, however, was not found to be an independent predictor of quality of life at any level of severity, whereas shortness of breath was found to predict quality of life at all levels of asthma severity (Moy et al. 2001; Wijnhoven et al. 2001). Asthma symptom frequency has been found to be the most significant determinant of the subjective experience of asthma and perception of quality of life (Schatz et al. 2005a). Another important reason to monitor health-related quality of life is that it predicts health care utilization among patients who have asthma (Eisner et al. 2002; Magid et al. 2004) and for this reason may be a useful method of identifying patients who are at risk of exacerbation. Patients' reports of impaired quality of life to their primary care providers (PCPs) also were found to result in increased interventions, especially patient education and counseling, as well as medication changes (Jacobs et al. 2001).

Quality of life, perceptions of asthma control, and depression are psychosocial factors worth assessing over time, because they may affect directly the ability to engage in self-management of asthma and affect indirectly asthma morbidity and mortality outcomes. Both asthma-specific and generic quality-of-life measures are associated with patients' perceived control of asthma (Katz et al. 2002). The coping resources and specific coping style used by patients who have respiratory disease have been associated with quality of life. Among patients who have asthma, a more emotional or avoidant coping style, low self-efficacy, and low mastery feelings were found to be independently associated with poor quality of life (Hesselink et al. 2004).

Many instruments have been developed and tested to assess quality of life among persons who have asthma in all age groups. Both asthma-specific and generic quality-of-life instruments have been tested and validated (See box 3-4.). Specific measures are more useful for assessing an individual's response to treatment and are more sensitive than generic measures in detecting the impact of changes in asthma severity or control (Graham et al. 2000). Generic measures are more useful in assessing the broad impact of asthma on the quality of life and functioning in a population of people (Graham et al. 2000; Noonan et al. 1995) and for comparing populations across diagnoses of chronic illness (Graham et al. 2000; Mancuso et al. 2001).

Box 3-4

INSTRUMENTS FOR ASSESSING ASTHMA-SPECIFIC AND GENERIC QUALITY OF LIFE. Asthma-Specific Quality of Life ▪ Mini Asthma Quality of Life Questionnaire (Juniper et al. 1999a) ▪ Asthma Quality of Life Questionnaire (Katz et al. 1999; Marks (more...)

Most of these instruments, however, are more suited for use in research studies than in clinical settings. Certain concerns preclude the Expert Panel's recommendation of the general adoption of these instruments at this time for routine encounters. These concerns include lack of experience with the use of the instruments in clinical practice and the time involved in administering the surveys. A few questionnaires have been shortened (Juniper et al. 1996) or tested by alternate methods of administration, such as telephone surveys (Pinnock et al. 2005).

Still, the importance of this concept to people who have asthma warrants that clinicians assess and monitor the effect of asthma on quality of life. See figure 3-7 for sample questions that may be used in the clinical setting for characterizing quality-of-life concerns for persons who have asthma.

Monitoring History of Asthma Exacerbations

The Expert Panel recommends that, during periodic assessments, clinicians should question the patient and evaluate any records of patient self-monitoring (figure 3-7) to detect exacerbations, both those that are self-treated and those treated by other health care providers (Evidence C). Exacerbations of asthma are episodes of marked increases in symptoms and reductions in lung function that interfere with the ability to perform usual activities unless quick relief therapy, such as SABA and additional corticosteroid treatment, is used. (See section 5 on "Managing Exacerbations of Asthma," for the classification of severity of exacerbations.) The most common cause of severe exacerbations is infection with a respiratory virus, especially rhinovirus, but exacerbations may be brought on by exposures to allergens or irritants, air pollutants, certain medications, and, possibly, emotional stress. Exacerbations also can be triggered by withdrawal of ICS or other long-term-control therapy. (See "Component 3: Control of Environmental Factors and Comorbid Conditions That Affect Asthma" for a review of literature on causes of exacerbations.)

It is important to evaluate the frequency, rate of onset, severity, and causes of exacerbations. A history of previous exacerbations, especially in the past year, is the strongest predictor of future severe exacerbations leading to ED visits and hospitalizations (Adams et al. 2000; Eisner et al. 2001; Ford et al. 2001; Lieu et al. 1998). The patient should be asked about precipitating exposures and other factors. Specific inquiry into unscheduled visits to health care providers, telephone calls for assistance, and use of urgent or emergency care facilities is helpful. Severity of the exacerbation can be estimated by the increased need for oral corticosteroids. Finally, any hospitalizations should be documented, including the facility, duration of stay, and any use of critical care or intubation. To facilitate continuity of care, the clinician then can request summaries of all care received.

Monitoring Pharmacotherapy for Adherence and Potential Side Effects

The Expert Panel recommends monitoring the following factors at each visit: patient's adherence to the regimen, inhaler technique, and side effects of medications (Evidence C). See sample questions in figure 3-7 for assessing the patient's adherence to, concerns about, or adverse experiences with the drug regimen. See component 2—Education for a Partnership in Asthma Care for further discussion of patient's adherence to treatment.

Monitoring Patient–Provider Communication and Patient Satisfaction

The Expert Panel recommends that health care providers should routinely assess the effectiveness of patient–clinician communication (Evidence D). (See figure 3-7 for sample questions.) Open and unrestricted communication among the clinician, the patient, and the patient's family is essential to ensure successful self-management by the patient who has asthma. A patient's negative attitude toward medication and/or reluctance toward self-management are risk factors for severe exacerbations (Adams et al. 2000). Every effort should be made to encourage open discussion of concerns and expectation of therapy. See "Component 2: Education for a Partnership in Asthma Care" for specific strategies to enhance communication and patient adherence to the treatment plan.

The Expert Panel recommends that two aspects of patient satisfaction should be monitored: satisfaction with asthma control and satisfaction with the quality of care (Evidence D). Patients' satisfaction with their asthma care and resolution of fears and concerns are important goals and will increase adherence to the treatment plan (Haynes et al. 1979; Meichenbaum and Turk 1987). See figures 3-2, 3-7, and 3-8 for examples of questions to use in monitoring patient satisfaction.

Figure 3-8

VALIDATED INSTRUMENTS FOR ASSESSMENT AND MONITORING OF ASTHMA

Monitoring Asthma Control With Minimally Invasive Markers and Pharmacogenetics

The Expert Panel recommends some minimally invasive markers for monitoring asthma control—such as spirometry and airway hyperresponsiveness—that are appropriately used, currently and widely, in asthma care (Evidence B). Other markers, such as sputum eosinophils and FeNO, are increasingly used in clinical research and will require further evaluation in adults and children before they can be recommended as a clinical tool for routine asthma management (Evidence D).

The interest in minimally invasive markers of asthma control arises from concerns over the possible dissociation between the severity of symptoms and impairments in function in the present, and the severity of the risk of exacerbations or progressive loss of pulmonary function in the future. For example, in a patient who reported daily symptoms, twice weekly nocturnal awakenings from asthma, shortness of breath on climbing stairs, and two exacerbations requiring ED treatment in the previous 12 months when first seen, does the resolution of all symptoms while taking treatment with a low dose of an ICS necessarily mean that his/her risk of exacerbations in the future is now acceptably low? A similar question might be asked of a patient treated with a high dose of an ICS and a LABA. If symptoms are completely controlled, can treatment be tapered without jeopardizing the patient's protection against future exacerbations? Must high-dose therapy for asthma be continued in a patient whose symptoms and function are well controlled but whose spirometry reveals a severely reduced but stable airflow obstruction (e.g., FEV₁ = 55 percent predicted)? Thus, although direct questioning is the best approach for assessing impairment, measurements of "biomarkers" are being examined as a way of assessing risk and thereby guiding adjustments in treatment.

The goal is to find a marker for asthma akin to hemoglobin A1C for diabetes (Its elevation is an index of the control of diabetes, and its reduction by therapy is known to reduce the risks of cardiovascular and renal complications.). To be practical, the marker should be measurable with minimal discomfort and risk to the patient and at minimal cost.

Spirometry

Perhaps the oldest marker of asthma impairment and risk is maximal expiratory flow, most commonly measured as FEV₁ and expressed as a percentage of predicted. Two large, retrospective cohort studies have shown that a reduction in FEV₁ at an annual visit is associated with increases in the risk of an attack of wheezing and shortness of breath over the next 12 or 36 months for pediatric and adult cohorts, respectively, and that the risk is greatest for those who have values consistent with "severe asthma," as described by the guidelines (<60 percent predicted); the risk is next greatest for those who have an FEV₁ qualifying as "moderate asthma" (60–79 percent predicted); and the risk is least for those who have an FEV₁ for "mild asthma" (80–100 percent predicted) (Fuhlbrigge et al. 2001; Fuhlbrigge et al. 2006; Kitch et al. 2004). The validity is less well established of using a reduction in FEV₁ as a marker of increased risk of progressive loss of pulmonary function in patients.

Airway responsiveness is measured by delivering serially increasing doses of a provocative agent, like methacholine, and calculating the "provocative dose" causing a 20 percent fall in FEV₁ ("PC20"). Making this measurement is time consuming, expensive, and so far has been disappointing in predicting exacerbations in patients weaned from ICS treatment (Deykin et al. 2005). More promising, but still under investigation, is measurement of the PD15 to mannitol (Leuppi et al. 2005), possibly because it provokes bronchoconstriction indirectly, through the activation of mast cells in the bronchial mucosa. A system for delivering progressively increasing doses from simple inhaler devices has been developed (Leuppi et al. 2002), but at the time of this writing, the system has been approved for use only in Australia.

Sputum eosinophils

Two approaches to measuring the intensity of eosinophilic inflammation deserve mention. One is to analyze the cells and mediators in the sputum induced by inhalation of hypertonic saline aerosol (Djukanovic et al. 2002). The other is to measure the concentration of gases or volatile substances in exhaled air.

Analysis of induced sputum has attracted much attention, and analysis of the number or proportion of eosinophils in the sample holds up well in distinguishing patients who have or do not have asthma in repeatability, in association with other markers of asthma severity, and in predicting responsiveness to starting or withdrawing ICS treatment (Deykin et al. 2005). Its principal drawbacks are the difficulties in standardizing the methods for obtaining, preparing, and analyzing the samples, even across specialized centers, and the demands on the time of highly trained technical staff for obtaining and processing the samples. Still, a controlled prospective study has shown that adjusting ICS treatment to control sputum eosinophilia—as opposed to controlling symptoms, SABA use, nocturnal awakenings, and pulmonary function—significantly reduced both the rate of exacerbations and the cumulative dose of ICS (Green et al. 2002).

Fractional exhaled nitric oxide

Increases in FeNO are thought to reflect the intensity of eosinophilic inflammation of the bronchial mucosa. Like sputum eosinophil counts, measurement of FeNO distinguishes patients who do or do not have asthma, is repeatable, is associated with other markers of asthma severity, and, in some but not all studies, predicts responsiveness to starting or withdrawing ICS or oral corticosteroid treatment (Kharitonov et al. 1997; Pijnenburg et al. 2005; Taylor 2006). A device for measuring FeNO has been approved by the U.S. Food and Drug Administration (FDA); and a prospective, controlled study has shown that when ICS treatment was adjusted to control FeNO, as opposed to controlling the standard indices of asthma, the cumulative dose of ICS was reduced, with no worsening of the frequency of asthma exacerbations (Smith et al. 2005).

Other methods include measurement of compounds, like hydrogen ion (pH), isoprostanes, leukotriene metabolites, and products of nitrosylation in EBC (Hunt 2002). The condensate is collected by passing exhaled air through a cold tube for 10–20 minutes. Several studies have shown differences in the concentrations of various compounds in the EBC of healthy persons and those who have asthma, but work remains to be done to establish the range of normal values, repeatability, association with other markers of asthma severity, and responsiveness to treatment.

A recent study in children suggests that low pulmonary function and high indicators of markers of allergic airway inflammation—such as FeNO, blood eosinophil count, and IgE—predict greater response to ICS than to LTRAs in children (Szefler et al. 2005). Several studies indicate that monitoring biomarkers—such as measures of hyperresponsiveness, sputum eosinophils, and FeNO—can be used to guide treatment decisions (Green et al. 2002; Smith et al. 2005; Sont et al. 1999). Each of these studies has shown a reduction in asthma exacerbations with the biomarker-based treatment approach, as compared to treatment based on symptoms and pulmonary function, although the trend toward decreased exacerbations did not reach statistical significance in one of the studies (Smith et al. 2005). In addition, FeNO and sputum eosinophilis may be used in diagnosing asthma, as their sensitivity and specificity approach that of methacholine challenges, and both have sensitivities greater than SABA reversibility (Dupont et al. 2003; Smith et al. 2004).

Once these tools are refined for application to the clinical setting, they could be useful in guiding treatment selection to achieve and monitor asthma control quickly. It is important that tools for using biomarkers to diagnose or monitor asthma be tested in both children and adults, because the presentation of the disease may differ between age groups.

Pharmacogenetics in Managing Asthma

Pharmacogenetics is the study of the genetic causes of between-person variation in drug treatment response. To date, three genes have been identified that influence response to specific asthma medications: LTRA (Alox 5) (Drazen 1999; Lima et al. 2006), SABA (B2AR) (Israel et al. 2000, 2004; Silverman et al. 2003; Taylor et al. 2000), and ICS (CRHR1) (Tantisira et al. 2004). It is not clear that the functional variants responsible for these associations have been identified. The ADRB2 gene has been studied the most. Multiple studies have shown that individuals homozygous for Arg/Arg at position 16 of the protein have about a 3 percent reduction in peak flow when compared to Gly/Gly homozygotes. Because individuals having Arg/Arg homozygotes account for only 16 percent of the Caucasian population in the United States, this is a small amount of variability in the clinical phenotype in a small percentage of the population and thus is of questionable clinical significance. Studies of the influence of the homozygous Arg-16 genetic variant on response to LABA are inconclusive. Some studies show reduced lung function and increased symptoms (Wechsler et al. 2006); others show no adverse effects (Bleecker et al. 2006; Taylor et al. 2000) (see component 4—Medications). None of these genotypes, in isolation, explains a sufficient amount of variation in the drug-response phenotype to warrant clinical testing at this time. It is likely, however, that prediction of response to asthma treatment will be a clinical reality in the near future.

METHODS FOR PERIODIC ASSESSMENT AND MONITORING OF ASTHMA CONTROL

Each of the key measures used in the periodic assessment of asthma (i.e., signs and symptoms, pulmonary function, quality of life, history of exacerbations, pharmacotherapy, and patient–provider communication and patient satisfaction) can be obtained by several methods. The principal methods include the clinician's assessment and the patient's (and/or parent's or caregiver's) self-assessment. In addition, population-based assessment of asthma care is being developed in the managed care field.

Clinician Assessment

The Expert Panel recommends that patients who have intermittent or mild or moderate persistent asthma (i.e., requiring steps 1, 2, 3, or 4 treatment) that has been under control for at least 3 months should be seen by a clinician about every 6 months. Patients who have uncontrolled and/or severe persistent asthma (i.e., requiring steps 5 or 6 treatment) and those who need additional supervision to help them follow their treatment plan should be seen more often (EPR—2 1997).

The frequency of visits to a clinician for review of asthma control is a matter of clinical judgment. Clinical assessment of asthma should be obtained through medical history and physical examination with appropriate pulmonary function testing. Optimal followup assessment of medical history may be achieved best via a consistent set of questions (figure 3-7).

Patient Self-Assessment

The Expert Panel recommends that clinicians should encourage patients to use self-assessment tools to determine from the perspective of the patient and/or the patient's family whether the asthma is well controlled (EPR—2 1997). The two general methods are (1) a daily diary and (2) a periodic self-assessment form to be filled out by the patient and/or family member, usually at the time of the followup visits to the clinician. Patients are less likely to see completion of diaries and forms as a burden if they receive feedback from the clinician that allows them to see value in self-monitoring.

• ▪ The daily diary should include the key factors to be monitored at home: symptoms and/or peak flow, medication use, and restricted activity (See "Component 2: Education for a Partnership in Asthma Care."). Monitoring with a daily diary will be most useful to patients whose asthma is not yet under control and who are trying new treatments. It is also useful for those who need help in identifying environmental or occupational exposures that make their asthma worse.
• ▪ The self-assessment questionnaires that can be completed at office visits are intended to capture the patient's and family's impression of asthma control, self-management skills, and overall satisfaction with care. Several multidimensional instruments have been developed to assess control. Four of those that have been validated in more than one study for their psychometric quality are listed in figure 3-8. Two that have given permission are reproduced in that figure. Each of these four validated tools includes the impairment domain by measuring the dimension of symptoms, activity limitations, and need for quick relief medication, but not all include the physiological dimension of lung function. Only one includes a biological marker. Most of the questionnaires do not assess the risk domain of asthma control. Figure 3-9 is a sample self-assessment tool that incorporates both impairment and risk domains; however, this instrument has not had standardized assessment for validity and reliability.

Figure 3-9

SAMPLE* PATIENT SELF-ASSESSMENT SHEET FOR FOLLOWUP VISITS

Population-Based Assessment

Asthma care is of increasing interest in various health care settings. Important regulatory organizations for the health care industry (e.g., the National Committee on Quality Assurance) have included the care of persons who have asthma as a key indicator of the quality of managed care. In this context, periodic population-based assessment of asthma care has begun to emerge as an issue for patients and their clinical care providers. This type of assessment often uses population experience, such as hospitalization or ED visit rates, to examine care within different clinical settings and among different providers. Complex, standardized population surveys (including lengthy health-status instruments) are being tested experimentally in the managed care setting.

Referral to an Asthma Specialist for Consultation or Comanagement

The Expert Panel recommends referral for consultation or care to a specialist in asthma care (usually, a fellowship-trained allergist or pulmonologist; occasionally, other physicians who have expertise in asthma management, developed through additional training and experience) when (Evidence D):

• ▪ Patient has had a life-threatening asthma exacerbation.
• ▪ Patient is not meeting the goals of asthma therapy after 3–6 months of treatment. An earlier referral or consultation is appropriate if the physician concludes that the patient is unresponsive to therapy.
• ▪ Signs and symptoms are atypical, or there are problems in differential diagnosis.
• ▪ Other conditions complicate asthma or its diagnosis (e.g., sinusitis, nasal polyps, aspergillosis, severe rhinitis, VCD, GERD, COPD).
• ▪ Additional diagnostic testing is indicated (e.g., allergy skin testing, rhinoscopy, complete pulmonary function studies, provocative challenge, bronchoscopy).
• ▪ Patient requires additional education and guidance on complications of therapy, problems with adherence, or allergen avoidance.
• ▪ Patient is being considered for immunotherapy.
• ▪ Patient requires step 4 care or higher (step 3 for children 0–4 years of age). Consider referral if patient requires step 3 care (step 2 for children 0–4 years of age).
• ▪ Patient has required more than two bursts of oral corticosteroids in 1 year or has an exacerbation requiring hospitalization.
• ▪ Patient requires confirmation of a history that suggests that an occupational or environmental inhalant or ingested substance is provoking or contributing to asthma. Depending on the complexities of diagnosis, treatment, or the intervention required in the work environment, it may be appropriate in some cases for the specialist to manage the patient over a period of time or to comanage with the PCP.

In addition, patients who have significant psychiatric, psychosocial, or family problems that interfere with their asthma therapy may need referral to an appropriate mental health professional for counseling or treatment. These problems have been shown to interfere with a patient's ability to adhere to treatment (Strunk et al. 1985, 1987).

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