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Asthma

Conventional Treatments for Asthma

Asthma is treated pharmacologically in a stepwise fashion depending on severity of symptoms. Asthma medications include quick-relief medications used to treat acute symptoms of an asthma attack and long-term control medications used to prevent further exacerbations. The goal of treatment is to optimize long-term control so that quick-relief medications, which have many side effects, can be minimized or eliminated (Simons 1999).

Quick-relief medications

Short-acting beta-2 agonists (SABAs).SABAs cause bronchodilation of the smooth muscles of the airway. These drugs relieve breathlessness, chest tightness, and other acute symptoms of an asthma attack. SABAs are usually prescribed together with a maintenance medication. Intensity of treatment depends on severity of symptoms: up to 3 treatments at 20-minute intervals as needed. Side effects of bronchodilators include rapid heart rate, increased blood pressure, increased blood sugar levels, irregular heart rhythms, and a variety of other responses (Wraight 2004). SABA medications include albuterol, levalbuterol, pirbuterol, bronkosol, isoproterenol, metaproterenol, and terbutaline. Use of SABA > 2 days a week for symptom relief generally indicates inadequate control and the need to step up treatment (see Stepwise Asthma Management; below).

Corticosteroids. Corticosteroids exert an immune-suppressing (i.e., anti-inflammatory) effect and can be administered systemically for a short course in acute or severe asthma to ease airway inflammation (Ohta 2011; Spahn 2008). However, systemic corticosteroids can lead to significant side effects including edema, osteoporosis, muscle weakness, chemical-induced diabetes, hypertension, adrenal gland dysfunction, cataracts, and glaucoma. They can also reduce calcium absorption from the gut and increase calcium loss from the kidneys (Pauwels 1998). To reduce the risk of these serious complications, the lowest dose possible should be taken to provide symptomatic control (Kaufman 2011).

Theophylline. Theophylline is a bronchodilator with modest anti-inflammatory properties. It can be used as an alternative stand-alone therapy for children older than 5 with persistent mild asthma. However, the toxic dose only slightly exceeds the effective dose, so patients must be carefully monitored (Wood 2009). Adverse effects include gastrointestinal symptoms, irregular heartbeat, seizures, and death (GINA 2011).

Inhaled anticholinergics. The neurotransmitter acetylcholine contributes to bronchoconstriction. Therefore, blocking the binding of acetylcholine to its receptors in the airways with inhaled anticholinergics inhibits this action. Anticholinergic medications are sometimes added to SABAs and help promote bronchodilation during an acute exacerbation (Ohta 2011).

Long-term control medications

Corticosteroids. Patients with asthma may require long-term use of inhaled corticosteroids (Ohta 2011; Spahn 2008). Potential adverse local effects associated with inhaled corticosteroids include thrush, hoarseness, reflex cough, and bronchospasm (GINA 2011). Long-term use of high-dose inhaled corticosteroids is associated with osteoporosis and adrenal dysfunction (Pauwels 1998). Commonly used inhaled corticosteroids include beclomethasone, budenoside, and triamcinolone.

Long-acting beta-2 agonists (LABAs). LABAs relax the airways and can provide up to 12 hours of bronchodilation (Wood 2009). They can be an add-on to long-term treatment for asthma that cannot be adequately controlled with inhaled corticosteroids alone. LABAs should not be used as stand-alone maintenance medications or to treat acute symptoms. The use of LABAs should be stopped if there is no response and the dose of inhaled corticosteroid is increased (Kaufman 2011). Studies have shown that LABAs can increase the risk of severe asthma attacks, asthma-related hospitalizations and death (GINA 2011). LABAs include salmeterol xinafoate and formoterol fumarate.

Leukotriene modifiers. Leukotriene receptor antagonists (blockers) and inhibitors of leukotriene synthesis help prevent or reduce inflammation, mucus production, swelling, and airway tightening. They are less effective than inhaled corticosteroids and thus are commonly used as an add-on therapy for poorly controlled, persistent asthma and exercise-induced asthma (Kupczyk 2011). Commonly used leukotriene modifiers include montelukast, zafirlukast and zileuton.

Mast cell stabilizers. Mast cell stabilizers (e.g., cromolyn and nedrocromil) prevent mast cells (a type of immune cell) from releasing histamine and related inflammatory mediators. These medications are very useful for preventing exercise-induced asthma when used prophylactically, but are not effective in treating an acute asthma attack. Mast cell stabilizers are also very safe but must be taken on a regular basis, even when free of symptoms (Merk Manual 2011).

Stepwise Asthma Management

The stepwise approach guidelines, developed by the National Institute of Health, are meant to assist clinical decision making and ensure that patient needs are met. The guidelines recommend consulting with an asthma specialist if step 4 or higher is required. Consider consultation at step 3. Advancement through these steps (“stepping up”) is based upon assessment of patient response to treatment while considering variables such as other medical conditions, adherence to treatment, and environmental factors (e.g., level of allergens in the air). If the patient responds well to treatment and symptoms are well-controlled for at least three months, then the physician may consider “stepping down” the patient to the next lower step in order to avoid medication side effects.

Intermittent asthma:

Step 1

Preferred: Short-acting beta-2 agonists (SABAs) as needed

Persistent asthma:

Step 2

Preferred: Low-dose inhaled corticosteroid (ICS)

Alternative*: Cromolyn, leukotrine receptor antagonist (LTRA), nedocromil, or theophylline

Step 3

Preferred: Low-dose ICS + long-acting beta-2 agonist (LABA) or medium-dose ICS

Alternative*: Low-dose ICS + LTRA or theophylline

Step 4

Preferred: Medium-dose ICS + LABA

Alternative*: Medium-dose ICS + LTRA or theophylline

Step 5

Preferred: High-dose ICS + LABA
[Note: Consider omalizumab for patients who have allergies]

Step 6

Preferred: High-dose ICS + LABA + oral systemic corticosteroid
[Note: Consider omalizumab for patients who have allergies]

*If alternative treatment is used and response is inadequate, discontinue it and use the preferred treatment before stepping up.