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Chronicles of Asthma

ASTHMA OVERVIEW:

Asthma, a common chronic inflammatory disease of the airways, may be classified as mild intermittent or mild, moderate, or severe persistent. Patients with persistent asthma require medications that provide long-term control of their disease and medications that provide quick relief of symptoms. Medications for long-term control of asthma include inhaled corticosteroids, cromolyn, nedocromil, leukotriene modifiers and long-acting bronchodilators. Inhaled corticosteroids remain the most effective anti-inflammatory medications in the treatment of asthma. Quick-relief medications include short-acting beta2 agonists, anticholinergics and systemic corticosteroids. The frequent use of quick-relief medications indicates poor asthma control and the need for larger doses of medications that provide long-term control of asthma. New guidelines from the National Asthma Education and Prevention Program Expert Panel II recommend an aggressive “step-care” approach. In this approach, therapy is instituted at a step higher than the patient’s current level of asthma severity, with a gradual “step down” in therapy once control is achieved.
PATHOPHYSIOLOGY:
Airway inflammation is the primary problem in asthma. An initial event in asthma appears to be the release of inflammatory mediators (e.g., histamine, tryptase, leukotrienes and prostaglandins) triggered by exposure to allergens, irritants, cold air or exercise. The mediators are released from bronchial mast cells, alveolar macrophages, T lymphocytes and epithelial cells. Some mediators directly cause acute bronchoconstriction, termed the “early-phase asthmatic response.” The inflammatory mediators also direct the activation of eosinophils and neutrophils, and their migration to the airways, where they cause injury. This so-called “late-phase asthmatic response” results in epithelial damage, airway edema, mucus hypersecretion and hyperresponsiveness of bronchial smooth muscle. Varying airflow obstruction leads to recurrent episodes of wheezing, breathlessness, chest tightness and cough.

DIAGNOSIS:
Asthma should be considered in patients with a history of recurrent wheezing, cough (particularly if the cough is worse at night), recurrent shortness of breath or chest tightness.

The diagnosis of asthma is also suggested if the symptoms worsen with exercise, viral illness, weather changes or exposures to airborne chemicals, dust, tobacco smoke or other allergens, such as animal dander, cockroaches, house dust mites, mold and pollens
When the diagnosis of asthma is considered, reversible airway obstruction should be documented by spirometry performed before and after the administration of a short-acting bronchodilator. Airway obstruction is indicated by a forced expiratory volume in one second (FEV1) and a decreased ratio of FEV1 to forced vital capacity (FVC) relative to predicted values. Reversibility of obstruction is indicated by an increase in FEV1 after bronchodilator treatment. In patients with asthma symptoms and normal spirometry, an assessment of the diurnal variation in peak expiratory flow (PEF) is useful in establishing the diagnosis.

CLASSIFICATION OF ASTHMA:
An expert panel for the National Asthma Education and Prevention Program (NAEPP) recently issued new guidelines that recommend the use of a revised classification system for asthma. Based on these guidelines, asthma is classified as:

1.mild intermittent.
2. mild persistent.
3. moderate persistent and 4.severe persistent

It is important to note that patients at any level of severity may have severe, life-threatening exacerbations.
PHARMACOTHERAPY FOR ASTHMA:-
Medications used in the treatment of asthma may be divided into two categories:

1. long-term control medications that are taken regularly and

2. quick-relief medications that are taken as needed to relieve bronchoconstriction rapidly.
(The quick-relief medications are also known as “rescue” medications.)

1. Long-term control medications include:
-anti-inflammatory agents (i.e., corticosteroids, cromolyn sodium [Intal], nedocromil [Tilade] and leukotriene modifiers) and

-long-acting bronchodilators.

2. Quick-relief medications include:-

-short-acting beta2 agonists, anticholinergics and

-. systemic corticosteroids.

Any patient with persistent asthma requires treatment with both long-term control and quick-relief medications.

LONG-TERM CONTROL MEDICATIONS:

1.CORTICOSTEROIDS

Corticosteroids remain the most potent and effective anti-inflammatory agents available for the management of asthma.6 They are useful in treating all types of persistent asthma in patients of all ages. For long-term use, inhaled steroids are generally preferred over oral steroids because the inhaled agents have fewer systemic side effects. Oral steroid therapy for long-term control is usually used only to treat refractory, severe, persistent asthma.

#Common side effects include cough, dysphonia, throat irritation and oropharyngeal candidiasis. The likelihood of local side effects, especially candidiasis, can be reduced if patients use a spacer, rinse their mouth after each use and use the inhaled steroids less frequently (twice daily rather than four times daily). Higher dosages may be associated with systemic adverse effects, including adrenal suppression, osteoporosis and growth delay in children.

2.Cromolyn Sodium and Nedocromil:-

Cromolyn and nedocromil are very safe agents with a mild to moderate anti-inflammatory effect. Both drugs inhibit the early-and late-phase asthmatic response to allergens and exercise. Nedocromil appears to be more effective than cromolyn in inhibiting bronchospasm induced by exercise, cold air and provocative testing.9 Because of their excellent safety profiles, cromolyn and nedocromil are good initial long-term control medications in children and pregnant women with mild persistent asthma.

#Cromolyn is available in a metered-dose inhaler (MDI), in capsules for oral inhalation and in a nebulizer solution. The usual dosages for adults are two to four puffs or one ampule of nebulizer solution three or four times daily; for children, one or two puffs or one ampule three or four times daily.

#Nedocromil is available only in an MDI. For adults, the dosage is two to four puffs two to four times daily; for children, one to two puffs two to four times daily. Four weeks of continued therapy may be required before the optimal effects of these drugs are achieved.

With both agents, a single dose can be taken 15 to 30 minutes before exercise to prevent exercise-induced bronchospasm for one to two hours. Cromolyn and nedocromil are both well tolerated although side effects such as cough, throat irritation and unpleasant taste have been reported

3.Salmeterol and Extended-Release Albuterol

Salmeterol (Serevent) is a long-acting beta2 agonist. Its mechanism of action and side effect profile are similar to those of other beta2 agonists. Unlike the short-acting agents, salmeterol is not intended for use as a quick-relief agent. It should not be used as a single agent for long-term control but instead should be used in combination with inhaled corticosteroids or other anti-inflammatory agents. Salmeterol is useful in the management of nocturnal and exercise-induced asthma. The drug is administered in an MDI in a dosage of two puffs every 12 hours. The inhalation powder formulation, salmeterol xinafoate (Serevent Diskus), is administered in a dosage of one puff every 12 hours. Several controlled studies have found that adding salmeterol to inhaled beclomethasone dipropionate produces greater improvement in asthma symptoms and less use of rescue medications than doubling the dosage of inhaled beclomethasone.

SHORT-ACTING BETA2 AGONISTS:-

Short-acting inhaled beta2 agonists are the agents of choice for relieving bronchospasm and preventing exercise-induced bronchospasm. Selective beta2 agonists, including albuterol, bitolterol (Tornalate), metaproterenol (Alupent), pirbuterol (Maxair) and terbutaline (Brethaire), are preferred to nonselective beta agonists, such as epinephrine, ephedrine and isoproterenol (Isuprel), because the selective agents have fewer cardiovascular side effects and a longer duration of action.

Inhaled beta2 agonists have a rapid onset of action (i.e., less than five minutes). Peak bronchodilation occurs within 30 to 60 minutes of administration, and the duration of action is three to eight hours.
: 3.Systemic Corticosteroids

Short-term systemic corticosteroid therapy is useful for gaining initial control of asthma and for treating moderate to severe asthma exacerbations.

The intravenous administration of systemic corticosteroids offers no advantage over oral administration when gastrointestinal absorption is not impaired. The recommended outpatient “burst” therapy for adults is prednisone, prednisolone or methylprednisolone in a dosage of 40 to 60 mg per day taken as one or two daily doses; for children, 1 to 2 mg per kg per day to a maximum dosage of 60 mg per day. Therapy is continued for three to 10 days or until symptoms resolve and the patient’s PEF improves to 80 percent of his or her personal best. The oral steroid dosage does not have to be tapered after short-course “burst” therapy if the patient is receiving inhaled steroid maintenance therapy.
4.Anticholinergics

Ipratropium (Atrovent) is a quaternary atropine derivative that inhibits vagal-mediated bronchoconstriction. Although this drug has not been proved to be effective for long-term asthma management, it may be useful as an adjunct to inhaled beta2 agonists in patients who have severe asthma exacerbations or who cannot tolerate beta2 agonists. Ipratropium has few side effects, but inadvertent eye contact can cause mydriasis.

APPROACH TO THERAPY

The 1997/2022 NAEPP report recommends a “step care” approach to asthma therapy.

The report discusses two appropriate approaches to initiating therapy for asthma.

1. One approach is to start therapy at the level consistent with the severity of the patient’s disease and increase treatment in steps if control is not obtained.

2. A second and more aggressive approach is to initiate therapy at a step higher than the patient’s current level of disease severity and gradually “step down” once control is obtained. No studies have directly compared the two approaches.

The NAEPP report recommends the second approach because some evidence suggests that initial aggressive treatment may yield greater clinical benefit.

Because asthma is a highly variable disease, the physician needs to individualize treatment strategies.

If initial therapy does not provide good control within one month, the treatment plan and even the diagnosis should be reevaluated.

FINAL NOTES:-

Asthma and its management still pose a challenge. However, recent advances in our understanding of the pathophysiology, diagnosis and monitoring of asthma can help physicians optimize treatment strategies.

Contemporary treatment guidelines emphasize an aggressive approach, with the prompt and liberal use of anti-inflammatory medication to achieve long-term control of this inflammatory disease.

It is increasingly recognized that successful asthma treatment requires a commitment from both patient and physician.

Patient education can empower persons with asthma to begin guided self-management of their disease. Such shared responsibility will help to ensure a favorable clinical outcome and an enhanced quality of life.

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