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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.

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) (), the Childhood Asthma Control Test (), the Asthma Control Questionnaire (), the Asthma Therapy Assessment Questionnaire (ATAQ) control index (), 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 (; ). 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 (; ; ). 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 (). 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 (). 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 (FEV 1 ) expressed as a percent of the predicted value or as a proportion of the forced vital capacity (FVC) or FEV 1 /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 beta 2 -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 beta 2 -agonist (SABA) for quick relief, improved functioning, improvement in FEV 1 , 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 (). The investigators observed that a composite definition of a responder correlates with asthma control. In a recent editorial, noted that, in published clinical trials, response to therapy based on pre- or postbronchodilator FEV 1 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 FEV 1 , 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 (), 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 (), 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 (). 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 (). Patients who have a poor response to appropriate therapy require referral to and consultation with an asthma specialist.

The Expert Panel recommends that the clinician trying to establish a diagnosis of asthma should determine that (): ▪ Episodic symptoms of airflow obstruction are present. ▪ Airflow obstruction is at least partially reversible. 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. 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.

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 ( ). The medical history can help: ▪ Identify the symptoms likely to be due to asthma. See for sample questions. ▪ Support the likelihood of asthma (e.g., patterns of symptoms, family history of asthma or allergies).

The upper respiratory tract, chest, and skin are the focus of the physical examination for asthma. Physical findings that increase the probability of asthma are listed below. The absence of these findings does not rule out asthma, because the disease is by definition variable, and signs of airflow obstruction are often absent between attacks. ▪ Hyperexpansion of the thorax, especially in children; use of accessory muscles; appearance of hunched shoulders; and chest deformity. ▪ Sounds of wheezing during normal breathing, or a prolonged phase of forced exhalation (typical of airflow obstruction). Wheezing may only be heard during forced exhalation, but it is not a reliable indicator of airflow limitation. ▪ Increased nasal secretion, mucosal swelling, and/or nasal polyps. ▪ Atopic dermatitis/eczema or any other manifestation of an allergic skin condition.

The Expert Panel recommends that spirometry measurements—FEV 1 , forced expiratory volume in 6 seconds (FEV 6 ), FVC, FEV 1 /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 ( ) . These measurements help to determine whether there is airflow obstruction, its severity, and whether it is reversible over the short term (; ). (See 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.

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 (FEV 1 ). 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 FEV 6 as a substitute for measurement of FVC in adults. In adults, FEV 6 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 (). Airflow obstruction is indicated by a reduction in the values for both the FEV 1 and the FEV 1 /FVC (or FEV 1 /FEV 6 ) relative to reference or predicted values. See and for an example of a spirometric curve for this test. Predicted values for FEV 1 /FVC are based on National Health and Nutrition Examination Survey (NHANES) data, National Center for Health Statistics, Centers for Disease Control and Prevention (CDC).

Significant reversibility is indicated by ATS standards as an increase in FEV 1 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) (; ; ). Some studies indicate that an increase ≥10 percent of the predicted FEV 1 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) (; ; ; ). 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 FEV 1 /FVC or FEV 1 /FEV 6 indicates obstruction to the flow of air from the lungs, whereas a proportionately reduced FVC (or FEV 6 in adults) with a normal or increased FEV 1 /FVC (or FEV 1 /FEV 6 ) 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 (). 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 (). 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 (). The postbronchodilator FEV 1 measure can then be used to follow lung growth patterns over time (). 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 ( ) . Correct technique, calibration methods, and maintenance of equipment are necessary to achieve consistently accurate test results (). 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 ( ).

The Expert Panel recommends consideration of alternative diagnoses, as appropriate. 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 (): ▪ 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 FEV 1 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 .). 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.

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 (). Treatment should follow the stepwise approach to long-term management of 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 (). 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 (; ; ). 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.").

The Expert Panel recommends that clinicians use information obtained from the diagnostic evaluation, and any additional information, if necessary, to (): ▪ Identify comorbid conditions that may aggravate asthma ▪ Assess the patient's knowledge and skills for self-management 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.").

The identification of factors that precipitate worsening of asthma—such as exposure to allergens (e.g., pets, molds, seasonal pollens), irritants (e.g., environmental tobacco smoke (ETS) and industrial pollutants (such as sulfur dioxide and ozone), or respiratory viruses (including "common cold" viruses)—can assist in educating the patient to avoid unnecessary exposures or at least to be alert to exposures that might indicate a need for increased treatment. Information obtained from the medical history (See .) will aid this assessment. See "Component 3: Control of Environmental Factors and Comorbid Conditions That Affect Asthma" for additional tools to assess allergies and other relevant exposures, as well as key messages for patient education on this topic.

It is also important to identify whether the patient has chronic comorbid conditions that may complicate the presentation or the treatment of asthma, such as sinusitis, rhinitis, GERD, OSA, or ABPA (See "Component 3: Control of Environmental Factors and Comorbid Conditions That Affect Asthma."). Identification of these comorbid conditions is helpful, because treating them adequately may improve overall control of asthma and lessen requirements for asthma medications.

Successful management of asthma requires that the patient or patient's caregiver have a fundamental understanding of and skills for following the therapeutic recommendations, including pharmacotherapy and measures to control factors that contribute to asthma severity. Initial assessment of the patient, therefore, should include an evaluation of the patient's self-management skills. This evaluation will guide decisions about appropriate educational training. See component 2—Education for a Partnership in Asthma Care for detailed discussion and tools for integrating assessment and education into all phases of clinical management, including the initial patient assessment.

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.