Classification and guideline treatment Bronchial asthma Classification and guideline treatment Prepared by: Reem Ahmed Abd el Moneim PharmD 4

Bronchial asthma Source: Peter J. Barnes, MD

Classification According to etiology: 1-Allergic or extrinsic asthma 2-Non-allergic or intrinsic asthma 3-Mixed forms According to degree of severity: Grade 1: Intermittent Grade 2: Persistent, mild Grade 3: Persistent, moderate Grade 4: Persistent, severe

FEV1/PEFR Nocturnal symptoms Symptoms >80% predicted <2 times a month <1 time a week Stage 1 intermittent >80% predicted,variability 20-30% > 2 times a month > 1 time a week but <1 time a day Stage 2 Mild-persistant 60-80%predicted, variability >30% > 1 time a week daily Stage 3 Moderate-persistant <60%predicted, frequent continous Stage 4 Severe-persistant

According to level of asthma control: Characteristic Controlled (All of the following) Partly controlled (Any present in any week) Uncontrolled Daytime symptoms None (2 or less / week) More than twice / week 3 or more features of partly controlled asthma present in any week Limitations of activities None Any Nocturnal symptoms / awakening Need for rescue / “reliever” treatment More than twice / week Lung function (PEF or FEV1) Normal < 80% predicted or personal best (if known) on any day Exacerbation One or more / year 1 in any week

Asthma Management and prevention 1. Develop Patient/Doctor Partnership 2. Identify and Reduce Exposure to Risk Factors 3. Assess, Treat and Monitor Asthma 4. Manage Asthma Exacerbations

Reliever Medications Rapid-acting inhaled β2-agonists Short-acting oral β2-agonists Systemic glucocorticosteroids Theophylline Anticholinergics

Controller Medications Inhaled glucocorticosteroids Systemic glucocorticosteroids Long-acting inhaled β2-agonists Long-acting oral β2-agonists Theophylline Cromones Anti-IgE Leukotriene modifiers

Other treatment option Daily controller medication Stage Sustained release theophylline Low dose ICS Mild -Moderate dose ICS+either sustained release theophylline or long acting β 2 agonist or leukotriene inhibitor. -High dose ICS Moderate dose ICS+inhaled long acting β 2 agonist or leukotriene inhibitor Moderate Oral glucocorticoid Anti-IgE(omlizumab) High dose ICS+inhaled long acting β 2 agonist or leukotriene inhibitor Severe

Step 1 – As-needed reliever medication Treating to Achieve Asthma Control Step 1 – As-needed reliever medication Patients with occasional daytime symptoms of short duration A rapid-acting inhaled β2-agonist is the recommended reliever treatment (Evidence A) When symptoms are more frequent, and/or worsen periodically, patients require regular controller treatment (step 2 or higher)

Treating to Achieve Asthma Control Step 2 – Reliever medication plus a single controller A low-dose inhaled glucocorticosteroid is recommended as the initial controller treatment for patients of all ages (Evidence A) Alternative controller medications include leukotriene modifiers (Evidence A) appropriate for patients unable/unwilling to use inhaled glucocorticosteroids

Treating to Achieve Asthma Control Step 3 – Reliever medication plus one or two controllers For adults and adolescents, combine a low-dose inhaled glucocorticosteroid with an inhaled long-acting β2-agonist either in a combination inhaler device or as separate components (Evidence A) Inhaled long-acting β2-agonist must not be used as monotherapy For children, increase to a medium-dose inhaled glucocorticosteroid (Evidence A)

Treating to Achieve Asthma Control Step 4 – Reliever medication plus two or more controllers Selection of treatment at Step 4 depends on prior selections at Steps 2 and 3 Where possible, patients not controlled on Step 3 treatments should be referred to a health professional with expertise in the management of asthma

Treating to Achieve Asthma Control Step 5 – Reliever medication plus additional controller options Addition of oral glucocorticosteroids to other controller medications may be effective (Evidence D) but is associated with severe side effects (Evidence A) Addition of anti-IgE treatment to other controller medications improves control of allergic asthma when control has not been achieved on other medications (Evidence A)

Leukotriene-Inhibiting Drugs Leukotriene inhibitors are either leukotriene receptor antagonists or leukotriene synthesis inhibitors, which act by blocking 5-lipoxygenase activity. The leukotriene receptor antagonists include zafirlukast (Accolate) and montelukast (Singulair); zileuton (Zyflo) is the only leukotriene synthesis inhibitor.

Clinical recommendation -Leukotriene inhibitors are effective in the treatment of asthma but are less effective than inhaled corticosteroids (evidence A) -Leukotriene inhibitors added to inhaled corticosteroids are less effective than long-acting beta agonists added to inhaled corticosteroids in the treatment of asthma (evidence A) -Leukotriene inhibitors are alternative treatments in exercise-induced asthma and can be of benefit for children when oral therapy is preferred over inhalers (evidence B) -Leukotriene inhibitors are effective in the treatment of allergic rhinitis but are less effective than intranasal corticosteroids (evidence A)

Age and recommended oral dose Drug Therapeutic issues Age and recommended oral dose Drug Renal adjustments: none Hepatic adjustments: in mild to moderate disease Adults: 10 mg before bed Children six to 14 years: 5 mg before bed Children two to five years: 4 mg before bed Montelukast (Singulair) Hepatic adjustments: not defined Monitor hepatic enzymes every two to three months Administration with meals decreases bioavailability; take at least one hour before meals or two hours after Inhibits metabolism of warfarin (Coumadin), increasing prothrombin time Patients older than 11 years: 20 mg twice daily Children seven to 11 years: 10 mg twice daily Zafirlukast (Accolate) (Ventair)

Can inhibit metabolism of warfarin, theophylline, and propranolol (Inderal) Monitor hepatic enzymes every two to three months Patients older than 12 years: 600 mg four times daily Zileuton (Zyflo)

Anti-IgE treatment: Omalizumab(Xolair®) Omalizumab blocks the receptors on the surfaces of the mast cells and basophils to which antibodies attach, thereby preventing antibodies from attaching to the cells. As a result, the cells do not release their chemicals, and the allergic reaction and inflammation are prevented.

DOSING: Omalizumab is injected under the skin. The recommended dose is 150-375 mg every 2 to 4 weeks. The dose and frequency is based on body weight and levels of serum IgE, a type of antibody. Doses greater than 150 mg should be divided and administered at different sites so that no more than 150 mg is administered at each injection site.

SIDE EFFECTS Headaches, viral infections, upper respiratory tract infections and injection-site reactions such as pain, redness, swelling, itching and bruising. Use of omalizumab may also lead to serious, life-threatening allergic reactions (anaphylaxis).

Signs and symptoms of anaphylaxis -Wheezing, shortness of breath, cough, chest tightness, or trouble breathing. -Low blood pressure, dizziness, fainting, rapid or weak heartbeat, anxiety. -Flushing, itching or feeling warm. -Swelling of the throat or tongue, throat tightness, hoarse voice, or trouble swallowing.

It is recommended that patients be observed for these reactions for at least two hours after injection of omalizumab; however, these reactions can occur up to 24 hours or longer after the injections.  Cancer occurs more frequently in patients who take omalizumab.

Non pharmacological treatment: -Reduce exposure to indoor allergens -Avoid tobacco smoke -Avoid vehicle emission -Identify irritants in the workplace -Explore role of infections on asthma development, especially in children and young infants

Influenza Vaccination Influenza vaccination should be provided to patients with asthma when vaccination of the general population is advised However, routine influenza vaccination of children and adults with asthma does not appear to protect them from asthma exacerbations or improve asthma control