Asthma is a disease characterized by widespread obstruction of airways. The obstruction is reversible--either spontaneously or with therapy. Last month I reviewed an unusual presentation of this disease, as well as ways of diagnosing and assessing the severity of asthma. This month, I wanted to review the new treatment guidelines and the thinking behind them so that it might be easier to approach therapeutic decisions in a variety of clinical circumstances.

Current knowledge suggests that asthma is a chronic disease, active even when the patient is asymptomatic; it is characterized by continuous airway inflammation and its physiologic consequences.(1) It needs to be stressed that the management of asthma is both pharmacologic and non-pharmacologic.

Therapy must therefore be primarily directed toward an overall reduction of airway inflammation and, additionally, must deal with the specific management of exacerbations. While asthma is a disease of intricate physiology and genetics, it is clear that the setting in which it occurs is important. In the U.S.A. there is no question that the patient's socio-economic(2) and the medical support system available to the patient(3) are important determinants of morbidity and mortality. Much effort has been undertaken to modify these risk factors.

Patient (and Parent) Education

The Guidelines for the Diagnosis and Management of Asthma(4) appropriately stress the central role of patient education. Key points for the clinician to incorporate in the overall plan are:

General Principles

Asthma is a chronic disease. The approach to management can be presented in simple terms but needs re-emphasis since the asthma may be variable and the patient's response to the environment and to his/her prescribed regimen may change. Patient education begins at the time of diagnosis and should be integrated with continuing care. While the treatment plan and education usually begins with the physician, many hospitals, groups and even individual practitioners use their nursing/respiratory therapy personnel to assume some of the management responsibilities of asthma care. This continuing input and accessibility is particularly important to assure compliance and to make sure the patient does not run out of medication.

Specific Measures

• Describe the clinical course of asthma generally and (specifically) as it relates to your patient.
• Allay anxiety
• Explain and simplify the treatment plan.
• Write instructions.
• Quiz the patient about the treatment plan.
• Provide "measurement instruments" (e.g., diaries, peak flow meters) so that the patient can monitor the severity of his or her disease.
• Demonstrate the use of meter-dose inhalers, spacers and other respiratory care devices while the patient is in the office. Re-inforce at subsequent visits.

Environmental Control Measures

Environmental irritants and allergens can be causes of asthma flare-up. The physician should encourage the patient to recognize known or potential triggers for his or her asthma . These non-pharmacologic responses to these triggers are common sensical but can have a significant impact on asthma care (Table 1).

Pharmacologic Management

For the vast majority of patients, pharmacologic management of asthma can be safe and effective, reducing symptoms, improving activity tolerance, preventing attacks and maintaining near normal lung function. Effective pharmacologic therapy requires a knowledge of the classes of agents available. Effective pharmacologic therapy requires a knowledge of the classes of agents available, their actions, side-effects and modes of delivery, as well as a rationale for the approach to management. Tailoring of individual regimens will depend on patient preferences, compliance issues, side-effects, convenience and cost.

The two main therapeutic classes of drugs for asthma are anti-inflammatory agents and bronchodilators.

Anti-inflammatory agents reduce the inflammatory component of the disease which is manifested by airway edema, inflammatory cells infiltration, mucous hypersecretion and smooth muscle hyperresponsiveness. Corticosteroids are the most-effective and reliable anti-inflammatory agents (Table 2).

For the treatment of acute short term asthma exacerbations, I usually administer a short course (7-14 days) of oral/parenteral steroids with or without tapering (steroid burst).

Corticosteroids (Table 3) are the most effective/reliable anti-inflammatory agents. Acute short term oral/parenteral steroids with or without tapering (steroid burst) over one to two weeks is usually effective in treating severe acute exacerbations (e.g., prednisone 40 to 80 mg daily in adults or 1-2 mg/kg in children).

For stable asthma, inhaled steroids are the anti-inflammatory agents of choice and are well tolerated over extended periods with minimal systemic effects, although some preparations, particularly at high doses, may suppress the hypothalamic pituitary axis (HPA). In children this may retard growth.

The concern about HPA suppression with the long term use of nebulized (meter dose inhaler administered) corticosteroids, particularly in children, requires that alternative anti-inflammatory agents (or adjuncts) be considered:

• Cromolyn sodium available as a spray or as a powder for inhalational use.
• Nedocromil sodium avaiIable as a spray.
• Antileukotriene agents (receptor blockers and synthesis inhibitors, e.g., zafirlukast, AccolateR) are soon to be released. These are oral agents currently recommended for the management of mild to moderate disease. Their role as first line or replacement agents has yet to be worked out.

Bronchodilator Therapy

These agents are used for the rapid control of symptomatic asthma. They are used by most asthmatics for the temporary relief of their symptoms. The following classes of bronchodilator therapy (Table 4) are currently used for the management of asthma.

1. Asthma is not an FDA approved indication for these agents.

2. A=aerosol, O=oral, P=parenteral

3. S=short (<2 hours), I=intermediate (4-6 hours), L=long (12 hours or greater)

While oral and parenteral bronchodilators do afford some flexibility, and are said to insure better compliance, most of these agents are administered by aerosol to reduce systemic side-effects. Methylxanthines, however, are not effective when administered as an aerosol and are consequently much less popular at this time.

If you encounter a patient with a poor response to one or another bronchodilator, try combinations which have additive effects: beta-agonist + methylxanthine or beta agonist + anticholinergic.

General Approach to Management (Adults)

(Modification from NAEP and other guidelines)(4),(5)

Current approaches, using extensive algorithms, are based on a clinical staging scheme of asthma severity (Table 5).

* With greater variability consider methylxanthines, long acting beta agonist by inhaler, steroid burst. NOTE: All these regimens call for the regular use of anti-inflammatory agents (primarily steroid inhalers), but recommend bronchodilators only as needed.

Special Considerations for Pregnant Asthmatics

The treatment of asthma in pregnancy follows the same general principles as that of the non-gravid asthmatic. It is generally desirable for the welfare of both mother and child to keep the patient relatively free from asthma. Inhaled medications are preferred so as to minimize systemic absorption but the latter should be given when the disease is not controlled by inhaled medication. Table 6 lists the FDA risk factor category of commonly used asthma medications. However, it needs to be stressed that the greatest risk to the fetus is uncontrolled asthma.

A = Controlled studies no risk
B = No evidence of risk in humans
C = Risk cannot be ruled out
D = Positive evidence of risk
X = Contraindicated in pregnancy

Investigational Regimens

In addition to the treatments outlined above, many new approaches and agents are in clinical trials or the research pipeline:

Preliminary Clinical Trials Not Approved(6),(13)

• Methotrexate: Many small studies with variable efficacy. Potential for serious toxicity. Not recommended at this time for routine care.
• Cyclosporin A: Immunosuppressive agent which arrests T-lymphocyte division and mast cell mediator release. Role in asthma uncertain. Potential for serious toxicity.
• Gold salts: Many small studies. Efficacy and role still uncertain.
• IV Immunoglobulins: May act as blocking antibody for IgE. Role uncertain.
• Ketotifen: Mast cell mediator release inhibitor. Widely used in other countries. Trials in U.S. have not demonstrated efficacy.
• Triacetyl oleandomycin: Related to macrolide antibiotics. Used for weaning protocol from oral steroids. Presumably works by altering steroid metabolism.

In Development(14),(21)

• Long acting/selective anticholinergics
• Selective phosphodiesterase inhibitors
• Neurokinin-receptor antagonists
• Colchicine
• Lidocaine (aerosol)
• Monoclonal antibodies directed against adhesion molecules (anti-inflammatory)
• Potassium channel activators

Conclusion

Educating patients as to the nature of their asthma and teaching them how to avoid or remove environmental irritants are the foundation of an asthma management program. Any program must be tailored to the patient and his or her particular needs. Complementing this approach is an impressive array of agents available to manage both the inflammatory component of asthma, as well as its acute exacerbation. Virtually all degrees of asthma require anti-inflammatory therapy. The agents of choice in this category are inhaled steroids. Alternatives, as well as adjunctive medications, exist in the form of cromolyn, nedocromil and most recently anti-leukotriene agents. Acute exacerbations require bronchodilator agents administered for symptoms, acute decompensation or prophylactically for specific syndromes (e.g., exercise induced bronchospasm).

Undoubtedly, many physicians, especially those practicing in other countries where environmental conditions and even genetic patterns may differ, have other experiences and therapeutic results which we'd like to hear about. I invite each of you to post comments so that all our Cyberounds^® colleagues throughout the world can find common therapeutic ground.