Asthma

 Asthma is a disease that affects the airways (bronchi) of the lungs.

 Asthma is characterized by a predisposition to chronic airway inflammation and bronchoconstriction
 The inflammation and bronchoconstriction cause airflow obstruction, which results in expiratory airflow
limitation (difficulty with exhalation).
 This results in recurrent episodes of wheezing, breathlessness, chest tightness and coughing, which are the
classic symptoms of asthma
 The inflammation and bronchoconstriction in asthma is reversible with medication (and sometimes
spontaneously).
 The most common complication of asthma is exacerbations, which can range from mild to severe, and in
some cases can be fatal.
Diagnosis
 Most types of asthma have activation of inflammatory mediators (e.g., histamine, leukotrienes, cytokines)
and an increase in inflammatory cells (e.g., mast cells, eosinophils) contributing to the disease
 Some patients have a genetic predisposition to the development of severe allergic asthma, which is mediated
by immunoglobulin E (igE), or severe eosinophilic asthma
 An asthma diagnosis is confirmed with spirometry and pulmonary function tests
 These should be measured at the patient' s baseline, and after use of a short- acting bronchodilator (e.g.,
albuterol) to test for reversibility (i.e.,if the FEV1 increases by more than 12% with the use of bronchodilator).
 Peak expiratory flow rate (PEFR) is measured using a peak flow meter. This is typically used for monitoring
asthma control as part of the asthma action plan, but it can be used at initial diagnosis to test for variability in
expiratory airflow limitation.
 Patients will use the peak flow meter twice daily for a period of two weeks to check the PEFR;
 if the average daily PEFR variability is greater than 10%, this suggests a diagnosis of asthma.
 SPIROMETRY:TESTS LUNG FUNCTION (HOW WELL THE LUNGS WORK)
1. FEV1 How much air can be forcefully exhaled in one second.
2. FVC After taking a deep breath, the maximum volume of air that is exhaled (how much air is exhaled)
3. FEV1/FVC The percentage of total air capacity ("vital capacity") that can be forcefully exhaled in one
second (the speed of the exhale).
CLASSIFYING ASTHMA SEVERITY
Components of Severity Intermittent Persistent
Mild Moderate Sever
Daytime symptoms < 2 days/week > 2 days/week but not daily Daily Throughout the day
Nighttime awakenings < 2x/month 3-4x/month > lx/week but not Often (7x/week)
nightly
Rescue inhaler use < 2 days/week > 2 days/week ,but not daily Daily Several times per day
or >1x/day
Activity limitations None Minor limitation Some limitation Extremely limited
Lung function FEV1(% > 80% Normal > 80% Normal 60-80% Reduced 5% 60% Reduced 5%
predicted) FEV1/FVC
Recommended Step for Step 1 Step 2 Step 3 Step 4 or 5
Initiating Treatment
•Normal FEV1/FVC by age: 8-19 years. 85%; 20-39 years, 80%; 40-59 years. 75%; 60-80 years,70%
CONTROLLING RISK FACTORS
  Patients with asthma should avoid exposure to tobacco smoke
 An annual influenza vaccine is recommended in all patients with asthma > 6 months of age.
 Patients age 2-64 years should receive one dose of the pneumococcal polysaccharide vaccine (PPSV23, Pneumovax 23)
 Any patient with persistent asthma and a clear connection of symptoms with exposure to an allergen should have skin
or in vitro testing to assess sensitivity.
 Treatment with subcutaneous allergen immunotherapy should be used, if indicated, based on the test results.
DRUG TREATMENT
 Inhaled forms deliver drugs directly into the lungs, have reduced toxicity and are the preferred delivery vehicle.
 Drugs used to treat asthma long-term are classified as relievers (rescue inhalers) or controllers (maintenance drugs)
 Rescue inhalers can be used preventively for exercise-induced bronchospasm (EIB)
 Relievers, or rescue inhalers, rapidly open airways within minutes of inhalation to make breathing easier.
 Controllers, or maintenance inhalers, are taken on a chronic, daily basis to reduce inflammation and maintain asthma
 Inhaled corticosteroids (ICS) are the mainstay of treatment for patients with asthma.
ASTHMA MEDICATION CLASS
Relievers (Rescue Drugs) Note
Inhaled low-dose ICS + formoterol  Combines an inhaled corticosteroid (ICS) and a long-acting beta-2
agonist (LABA)
 Used intermittently (as needed) for acute asthma symptoms
 Combination proven to have reduced exacerbations over SABA alone
Inhaled short-acting beta-2 agonists (SABAs)  Used intermittently (as needed) for acute asthma symptoms
 Quickly reverse bronchoconstriction
Systemic steroids  Injections: used during exacerbations
 Oral: used during exacerbations or for severe asthma that is difficult to
control with other drug combinations
Inhaled epinephrine  Available OTC, can be used for acute treatment of mild symptoms in
intermittent asthma only
Inhaled short-acting muscarinic antagonists  Can be used in combination during exacerbations
Controllers (Maintenance Drugs) Note
Inhaled corticosteroids (ICS)  First-line for all patients with persistent asthma;
Inhaled long-acting beta-2 agonists (LABAs)  Used in combination with ICS (should never be used alone due to
increased risk of serious adverse outcomes)
Oral leukotriene receptor antagonists  Alternative option to LABA in combination with ICS; can also be added
(LTRAs) to ICS/LABA treatment
 Most commonly used in children
Theophylline (oral or IV)  Least desirable option for add-on treatment due to significant adverse
effects, drug interactions and the need to monitor serum drug
concentrations
Inhaled long-acting muscarinic antagonists  Can be used as add-on treatment in patients with a history of
(LAMAs) exacerbations despite ICS/ LABA treatment
Injectable monoclonal antibodies (SC or IV)  Add-on treatment in persistent severe asthma of a specific type:
Omalizumab: for severe allergic asthma Mepolizumab, reslizumab,
benralizumab and dupilumab: for severe eosinophilic asthma

DETERMINE TREATMENT STEP BASED ON ASTHMA SEVERITY

  Step 1 (Intermittent Asthma) As-needed low-dose ICS + formoterol or low-dose ICS taken whenever SABA is taken
 Step 2 (Mild Persistent Asthma) Daily low-dose ICS or as-needed low-dose ICS + formoterol
 Step 3 (Moderate Persistent Asthma) Low-dose ICS + LABA
 Step 4 (Severe Persistent Asthma) Medium-dose ICS + LABA
 Step 5 (Severe Persistent Asthma) High-dose ICS + LABA, refer for further assessment
BETA-2 AGONISTS
 These medications bind to beta-2 receptors, causing relaxation of bronchial smooth muscle, which leads to
bronchodilation.
 SABAs are used as needed (rescue therapy) for acute asthma symptoms.
 LABAs are used as part of maintenance therapy beginning in Step 3 of treatment and only in combination with an ICS.
Short-Acting Beta-2 Agonists (SABAs)
Drugs Note
Albuterol SIDE EFFECTS
Levalbuterol  Nervousness, tremor, tachycardia, palpitations, cough, hyperglycemia , decrease K
Racepinephrine MONITORING
Epinephrine  Number of days of SABA use, symptom frequency, peak flow, pulmonary function tests, BP, HR,
blood glucose, K
NOTES
 Levalbuterol contains R-isomer of albuterol
 Epinephrine inhaler is FDA-approved for mild symptoms in intermittent asthma only. Not
discussed in guidelines.
Long-Acting Beta-2 Agonists (LABAs)
Salmetrol  Increase risk of asthma-related deaths, should only be used in asthma patients who are currently
receiving but are not adequately controlled on a long-term asthma control medication (an inhaled
corticosteroid)
 Increase risk of asthma-related hospitalizations in pediatric and adolescent patients I
 Maintenance inhaler only; not for acute bronchospasm
INHALED CORTICOSTEROIDS
 They block the late-phase reaction to the allergen, reduce airway hyper-responsiveness, and are potent and effective
anti-inflammatory medications.
 ICSs reduce symptoms, increase lung function, improve quality of life and reduce the risk of exacerbations.
 They are used as-needed in combination with formoterol for rescue treatment with acute symptoms, and individually
or in combination for maintenance/controller treatment.
DRUG Notes
Bedomethasone  High doses for prolonged periods of time can cause adrenal suppression,I ncrease risk of fractures,
Budesonide growth retardation (in children) and immunosuppression
Fluticasone  Cause Dysphonia (difficulty speaking), oral candidiasis (thrush), cough
Mometasone  To prevent oral candidiasis, rinse mouth and throat with warm water and spit out after each use,
or use a spacer device if using a MDI
 Budesonide is the only ICS available as a nebulized solution; used commonly in young children

LEUKOTRIENE MODIFYING AGENTS

  Leukotriene receptor antagonists (LTRAs) inhibit leukotriene mediators of airway inflammation. This reduces airway
edema, constriction and inflammation.
 Montelukast inhibits leukotriene D4 (LTD4)
 Zafirlukast inhibits both LTD4 and LTE4.
 Zileuton, a 5-lipoxygenase inhibitor, inhibits leukotriene formation
Drug Notes
Montelukast Warning
Zafirlukast  Neuropsychiatric events; monitor for signs of aggressive behavior, hostility, agitation, hallucinations,
Zileuton depression, suicidal thinking
Monitor
 LFTs (zafirlukast and zileuton), mood or behavior changes (montelukast)
Note
 Zafirlukast: protect from moisture and light; dispense in original container
 Montelukast 10 mg daily in the evening
 Montelukast Age 6-14 years: 5 mg daily in the evening
 Montelukast Age 1-5 years: 4 mg daily in the evening
THEOPHYLLINE
 Theophylline blocks phosphodiesterase, causing an increase in cyclic adenosine monophosphate (cAMP) and release of
epinephrine from adrenal medulla cells.
 This results in bronchodilation, but it also causes diuresis, CNS and cardiac stimulation and gastric acid secretion.
 Use of theophylline is limited by decrease , effectiveness, drug interactions and adverse effects.
Theophylline  Caution in patients with cardiovascular disease, hyperthyroidism, PUD and seizure disorder
 Cause increase HR, insomnia, tremor and nervousness
 Signs of toxicity: persistent vomiting, arrhythmias, seizures
Note
 To convert aminophylline to theophylline, multiply by 0.8*; to convert theophylline to aminophylline,
divide by 0.8
 Therapeutic range: 5-15 mcg/mL (measure peak level at steady state, after 3 days of oral dosing)
 Active metabolites are caffeine and 3-methylxanthine
 Aminophylline contains 80% theophylline
ANTICHOLINERGICS
 Anticholinergics inhibit muscarinic cholinergic receptors and reduce the intrinsic vagal tone of the airway, leading to
bronchodilation.
 Short-acting anticholinergics (e.g., ipratropium) are sometimes used in combination with SABAs in hospitalized patients
experiencing an acute exacerbation.
 A long-acting anticholinergic, tiotropium is FDA-approved for asthma in patients 6 years of age and older with a history
of exacerbations despite ICS/LABA therapy
OMALIZUMAB
 Omalizumab is a monoclonal antibody that inhibits IgE binding to the IgE receptor on mast cells and basophils.
 It is indicated for moderate to severe persistent, allergic asthma in patients 6 years of age and older if a skin test to a
perennial allergen is positive and symptom control on inhaled corticosteroids is inadequate (Step 5 or 6 treatment).
Omalizumab  Anaphylaxis has occurred as early as after the first dose but also has occurred beyond 1 year after
beginning treatment
 Monitor Baseline IgE, FEV1, peak flow, s/sx of anaphylaxis and infection
  Given SC every 2 or 4 weeks
INTERLEUKIN RECEPTOR ANTAGONISTS
 Interleukin is a cytokine responsible for the growth, differentiation, recruitment, activation and survival of eosinophils
 Monoclonal antibodies can be used to inhibit interleukin from binding to receptors.
 Mepolizumab, reslizumab and benralizumab are IL-5 receptor antagonists, and dupilumab is an IL-4 and IL-3 receptor
antagonist.
 All are indicated for management of severe asthma with an eosinophilic phenotype
 Mepolizumab is indicated in patients > 12 years of age and given SC once every four weeks.
 Reslizumab is indicated in adult patients only, and is given IV once every four weeks has a boxed warning for
anaphylaxis
 Benralizumab is indicated for patients > 12 years of age and given SC once every four weeks x three doses, then every
eight weeks.
 Dupilumab is indicated for patients > 12 years of age and given SC every other week.
SPECIAL SITUATIONS
EXERCISE-INDUCED BRONCHOSPASM
 SABAs are preferred to prevent most EIB.
 They are taken 5 - 15 minutes before exercise and last 2-3 hours.
 If a longer duration ofsymptom control is needed, salmeterol (a LABA), can be taken 30 minutes before exercise.
 If the patient is using a LABA for asthma maintenance, they should not use additional doses for EIB.
 LABAs should never be used alone for persistent asthma.
 Montelukast is taken two hours prior to exercise and lasts up to 24 hours.
PREGNANCY
 A short-acting beta-agonist is a must.
 ICS are preferred controllers, typically budesonide.
Important note
 Different classes of controller medications for asthma and chronic obstructive pulmonary disease (COPD).
 ICS and ICS/LABA combinations are preferred for asthma, whereas LABA, LAMA or LAMA/LABA combinations are
preferred for COPD.
 Some ICS/LABA combinations are approved for COPD and can be used in select patients (see COPD chapter for
treatment recommendations).
 Drugs that can increase theophylline levels due to CYP1A2 inhibition include: cimetidine, ciprofloxacin, fluvoxamine,
propranolol, zafirlukast and zileuton.
 Drugs and conditions that can decrease theophylline levels: carbamazepine, fosphenytoin, phenobarbital, phenytoin,
primidone, rifampin, ritonavir, tobacco/marijuana smoking, St. John’s wort, levothyroxine, high-protein diet and
charbroiled meats.
 Drugs that can increase theophylline levels due to CYP3A4 inhibition include: clarithromycin and erythromycin.