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CLASSIFYING ASTHMA SEVERITY AND TREATMENT DETERMINANTS: NATIONAL GUIDELINES REVISITED

The Global Initiative for Asthma released new guidelines for asthma management in the year 2000 which emphasized looking at asthma not only in terms of severity, but also in terms of response to treatment, which is equivalent to control. In addition, the new GINA guidelines used this approach with children under the age of 5, which was a major difference from the NAEPP guidelines. GINA recommended using the NAEPP classification of asthma only for research purposes. Instead they suggested these three asthma classifications which were more a variation in mindset than anything else:

• Controlled: At this level, there are no daytime or nighttime symptoms, no activity restrictions and infrequent need for quick relief medicines (no more than twice a week). Peak flow is normal and there are no asthma attacks.
• Partly controlled: At this level, daytime symptoms are occurring more than twice a week, sometimes at night and occasionally they limit activity. Quick relief medicines are needed more than twice a week. Peak flow rate is less than 80 percent of the personal best and asthma attacks occur at least once a year.
• Uncontrolled: Asthma is classified as uncontrolled if there are 3 or more of the features of partially controlled asthma at least 3 times a week and asthma attacks are occurring weekly.

Asthma Severity: (Updated guidelines 2008)

GINA now reasons that classification of asthma by severity is useful when decisions are being made about management at the initial assessment of a patient. GINA therefore maintains that it is important to recognize that asthma severity involves both the

severity of the underlying disease and its responsiveness to treatment. Thus, asthma can present with severe symptoms and airflow obstruction and be classified as Severe Persistent on initial presentation, but respond fully to treatment and then be classified as Moderate Persistent asthma. In addition, severity is not an unvarying feature of an individual patient’s asthma, but may change over months or years.

Because of these considerations, the classification of asthma severity provided in table 3 above, which is based on expert opinion rather than evidence is not recommended as the basis for ongoing treatment decisions, but retains its value as a cross-sectional means of characterizing a group of patients with asthma who are not on inhaled glucocorticoid treatment, as in selecting patients for inclusion in an asthma study. Its main limitation is its poor value in predicting what treatment will be required and what a patients response to that treatment might be. Hence, a periodic assessment of asthma control has now been deemed more relevant and useful.²⁰

Asthma control:

According to GINA, asthma control may be defined in various ways. The term control may indicate disease prevention, or even cure. However, in asthma, where neither of these are realistic options at present, it refers to control of the manifestations of disease. Ideally this should apply not only to clinical manifestations, but to laboratory markers of inflammation and pathophysiological features of the disease as well. There is evidence that reducing inflammation with controller therapy achieves clinical control, but because of the cost and / or general unavailability of tests such as endobronchial biopsy and measurement of sputum eosinophils and exhaled nitric oxide, it is recommended that treatment be aimed at controlling the clinical features of disease, including lung function abnormalities. Table 4 provides the characteristics of controlled, partly controlled and uncontrolled asthma.

Table : 4 Levels of asthma control

Characteristic	Controlled (All of the following)	Partly Controlled (Any measure present in any week)	Uncontrolled
Daytime symptoms	None (twice or less/week)	More than twice/week	Three or more features of partly controlled asthma present in any week
Limitations of activities	None	Any
Nocturnal symptoms/awakening	None	Any
Need for reliever/rescue treatment	None (twice or less/week)	More than twice/week
Lung function (PEF or FEV1)	Normal	< 80% predicted or personal best (if known)
Exacerbations	None	One or more/year	One in any week

Complete control of asthma is commonly achieved with treatment, the aim of which should be to achieve and maintain control for prolonged periods ²¹, with due regard to the safety of treatment, potential for adverse effects and the cost of treatment required to achieve this goal.

Validated measures for assessing clinical control of asthma are the Asthma Control Test (ACT) (http://www.asthmacontrol.com), the Childhood Asthma Control Test (C-ACT), the Asthma Control Questionnaire (ACQ) (http://www.qoltech.co.uk/Asthma1.htm), the Asthma Therapy Assessment Questionnaire (ATAQ) (http://www.ataqinstrument.com) and the Asthma Control Scoring System.

DISCUSSION

The above guidelines rely on asthma symptoms and lung function values for determining asthma severity. However there are significant issues involved in developing asthma severity categorization methods that incorporate symptoms and objective measures of lung function on the same scale. For instance, continual symptoms have the same significance as a FEV1 below 60% predicted. This apparently makes sense to the clinician but is difficult to support scientifically since numerous studies have shown that there is poor correlation between reporting of asthma symptoms and objective measures of lung function.^22,23

Hence, patients cannot reliably predict changes in their lung function based on the symptoms they experience,²⁴ and physicians cannot accurately predict lung functions from examination of patients with asthma.

Another fundamental concern regarding the various guidelines is that they are based more on the concept of asthma control rather than asthma severity.²⁵ Symptoms and lung function indicate how well the manifestations of the disease are controlled, but do not reflect the severity of the underlying inflammation. As asthma is recognized to be an inflammatory airway disease, severity categorization should also be based on an assessment of airway inflammation. Nowadays, direct methods are available to assess airway inflammation. Induced sputum allows measurement of airway inflammatory cells and changes in sputum eosinophil counts may reflect deterioration in asthma control.²⁶ Bronchoscopy is increasingly used for bronchoalveolar lavage to measure airway inflammatory cell counts and airway biopsy is used to directly evaluate airway remodeling and inflammation.²⁷ Exhaled levels of nitric oxide²⁸ and tests of bronchial hyperresponsiveness²⁹ may indirectly reflect airway inflammation.

Two studies have directly evaluated the added value of incorporating measures of airway inflammation into an approach for asthma management. One study³⁰ randomized asthma patients to a treatment strategy based on either asthma severity categorized only clinically or asthma severity categorization along with methacholine inhalation challenge studies as a measure of bronchial hyperreactivity. Bronchial hyperreactivity was used in this study as an index of underlying airway inflammation.

The patients treated according to measures of bronchial hyperreactivity received higher doses of inhaled corticosteroids, but had significantly fewer episodes of asthma exacerbation and significantly more effective control of airway inflammation as determined by bronchial biopsies.

The vital importance of categorizing asthma severity is very evident. Higher doses of inhaled corticosteroids can only be justified if patients with more severe asthma can be identified. National guidelines on asthma management have attempted to address this issue by proposing asthma severity categorization methods. However, despite serious efforts to disseminate these guidelines, database evaluations have shown that current asthma care around the world fails to adhere to recommendations of these guidelines.³¹ This is a disturbing observation because underassessment of asthma severity results in ineffective treatment and an increase in morbidity and mortality in these patients.³² Various studies have shown that, in spite of methodologic flaws, if patients are managed according to the recommended guidelines, it would significantly improve patient care.³³

However, many investigators and clinicians have expressed concern that the current asthma management guidelines are symptom oriented and do not include measures of airway inflammation as a guide to the management of asthma. As studies of airway inflammatory responses progress, there is likely to be a place for the measure of airway inflammation in a future guideline. Without the endpoints necessary to assess airway inflammation, current recommendations for asthma severity categorization may lead to systematic under dosing of appropriate anti-inflammatory therapy with consequent exacerbation of the asthma attacks. Incorporating measures such as methacholine challenge testing and sputum eosinophil counts into future guidelines would improve the assessment of the underlying airway inflammation and help to appropriately adjust anti-inflammatory therapy.

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