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Asthma Primer. Wayne Kradjan, Pharm. D. Definition of Asthma. A chronic inflammatory disorder of the airways… In susceptible individuals, this inflammation causes episodes of wheezing, breathlessness, chest tightness and coughing, particularly at night or early morning.
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Asthma Primer Wayne Kradjan, Pharm. D.
Definition of Asthma • A chronic inflammatory disorder of the airways… • In susceptible individuals, this inflammation causes episodes of wheezing, breathlessness, chest tightness and coughing, particularly at night or early morning. • Usually associated with widespread but variable airflow obstruction (bronchospasm) that is often reversible, either spontaneously or with treatment. • Inflammation also causes an increase in bronchial hyperresponsiveness to a variety of stimuli (triggers)
Large, “central” airways Small, “peripheral”Airways Only site ofgas exchange
Causes of Airflow Obstruction • Bronchospasm- Hyperresponsiveness and narrowing of airways (bronchi) due to muscle spasm. • Airway edema (swelling of walls) • Mucous plugging • All made worse by airway inflammation
Bronchial Hyperresponsiveness • More easily induced bronchospastic response to a variety of stimuli that may not otherwise cause a response in the general population. • Allergens • Chemicals, irritants • Exercise • Response may also be more intense and prolonged • Non-asthma patients may develop a transient BHR after viral upper respiratory infection.
Asthma Triggers • Allergens (seasonal/ perennial) • Grass, weeds, pollen, mold, mildew • Animal dander, saliva, dust mites • Chemical irritants and fumes • Cigarette smoke, pollution, perfume • Household cleaners, occupational • Viral infections, rhinitis, sinusitis, (“post nasal drip”) • Gastroesophageal reflux (GERD) • Exercise; cold, dry air • Extreme emotions • Drugs (aspirin, beta blockers)
Measuring Airflow Obstruction • Assessing air outflow • Peak flow: Maximum rate (L/min) of airflow out of the lung during a forced exhalation. • FEV1: Forced expiratory volume in one second. Actual volume (L) of air expired in the first second of a forced exhalation. • FVC: Forced vital capacity. Totalvolume of air expired during a forced exhalation.
Obstructive Airways Disease: Sequence of Events Inflammation, nerve exposure Hyperresponsiveness “Trigger”: allergen or irritant exposure(cold air, exercise) Bronchospasm ( FEV1, peak flow)mucous, edema, cough OBSTRUCTION
Epidemiology • 5% of US population • 5,000 deaths per year in US • Higher incidence in inner city, especially African Americans and Hispanic populations. • Racial vs. socioeconomic?
Environmental Factors • Increased time spent indoors • Indoor allergens (molds, mites, cockroaches) • Tobacco smoke exposure • maternal smoking risk for child • Increased childhood infections associated with lower risk • Having older or multiple siblings or day care center attendance may lower risk (more childhood infection) • Hygienic hypothesis
Childhood onset • Most common chronic disease of children (6.9% of population) • More likely to be allergic basis • Common: child with positive family history of asthma and allergy to tree and grass pollen, house dust mites, household pets and molds. • 30-70% markedly improve or symptom free as adult
Adult onset • May be allergic or non-allergic • Often negative family history and negative skin tests to common allergens • Often history of nasal polyps, aspirin sensitivity and chronic sinusitis • Environmental exposure: wood dust, chemicals, pollutants at workplace or in air • Chemical sensitizers: viral infection, tobacco smoke, diet, perfume
Expert Panel 2 Report Guidelines for the Diagnosis and Management of Asthma NIH Publication #97-4051A National Institutes of Health.National Heart, Lung and Blood InstituteMay 1997 http://www.nhlbi.nih.gov/guidelines/index.htm Schering, Astra-Zeneca, or Glaxo-Wellcome
Update on Selected Topics 2002 Guidelines for the Diagnosis and Management of Asthma NIH Publication #02-5075 National Institutes of Health.National Heart, Lung and Blood InstituteNovember 2002 http://www.nhlbi.nih.gov/guidelines/asthma/asthsumm.htm J Allergy Clin Immunol. 2002;110:S1-S219 (Nov supplement)
Step Approach to Classification • Mild Intermittent • Sxs <2/week, PM sxs < 2/month • PFTs >80%, < 20 variability • Mild Persistent • Sxs 3-6x/ week; PM sxs 3-4/month • PFTs >80%, 20-30% variability • Moderate Persistent • Sxs daily; PM sxs > 5 per/month • PFTs 60-80%, >30% variability • Severe Persistent • Sxs continual; PM sxs frequent • PFTs <60%, >30% variability • Acute exacerbations
Staging:Further Considerations • Seasonality • Nocturnal symptoms • Exercise induced • Peak flow monitoring • Daily fluctuations • Cough variant • “Wheezy bronchitis” in children
“Reliever”, “Rescue” Drugs • Rapid acting bronchodilators • beta adrenergic agonists • intermediate duration (3-6 hrs) • Often called “short acting” • metered dose inhaler (MDI),dry powder inhaler (DPI, breath actuated),solution for nebulization • Albuterol (salbutamol)(Proventil, Ventolin) • Levalbuterol (Xopenex) • Bitolterol (Tornalate) • Metaproterenol (Alupent, Metaprel) • Pirbuterol (Maxair) • Terbutaline (Bricanyl, Brethine) • (Epinephrine, isoproterenol, isoetharine)
Anticholinergicbronchodilators • Ipratropium (Atrovent)Tiotropium (Spiriva) • MDI (Atrovent and Spiriva) • Also combination with albuterol: Combivent • Solution for nebulization (Atrovent) • Also combination with albuterol:DuoNeb (500 mcg/2.5 mg) • Slower onset, longer acting than albuterol • Atrovent QID; Spiriva QD • Dry mouth and blurred vision • Greater role in COPD than in asthma
“Controller” Drugs:Antiinflammatory • Inhaled corticosteroids • Beclomethasone (Beclovent, Vanceril) • Budesonide (Pulmicort)(Turbuhaler, and Respules) • Flunisolide (Aerobid, Aerobid M) • Fluticasone (Flovent)(Advair = combo with salmeterol) • Triamcinolone (Azmacort) • Important to note • Low, intermediate, high dose • dosage form and strengths
Non-Steroid “Controllers”Antiinflammatory • Mast cell stabilizers(inhaled: MDI or nebs) • Cromolyn (Intal) • Nedocromil (Tilade) • Leukotriene modifiers(Oral) • Lipooxygenase inhibitor: Zileuton (Zyflo) • Receptor blockers: Zafirlukast (Accolate) Montelukast (Singulair)
Long acting bronchodilators • Inhaled beta agonist • Salmeterol (Serevent MDI and Diskus) • Formoterol (Foradil Aerolizer) • Night time, exercise or adjunct to anti-inflammatory drugs • Oral beta adrenergic agonists • albuterol, metaproterenol, terbutaline • sustained release for night timeProventil Repetabs, Volmax • syrups for children (albuterol, metaproterenol
Salmeterol (Serevent) Diskus50 mcg/dose; 60 doses Open door toreveal mouthpiece Slide lever. “Click” indicates dose in place.Dose counter advances. Hold level to holdpowder in place.Inhale quickly.Close door to reset.
Long acting bronchodilators (continued) • Theophylline • rapid acting, sustained release(many products recently removed from the market) • intravenous (aminophylline) • Possibly mild anti-inflammatory • Increased diaphragm contractility(“diaphragmatic inotrope”) • Primarily reserved for COPD
Other asthma medications • Oral or injectable steroids • Prednisone, prednisolone, methylprednisolone • “burst therapy” for rapid decline • Emergency and hospital use • Methotrexate • Allergy desensitization • Soluble IL-4 receptor (IL4R) to bind IL-4 and prevent binding of IL-4 to tissue receptors. 3 mg Q week via inhalation • Olizumab: recombinant monoclonal antibody to IgE 150-300 mg SC Q 2- 4 weeks
Therapeutic goals:Individualize to patient • Minimal, infrequent episodes • Freedom from symptoms;Day and night. • Maintain normal activity including exercise • Maintain best possible pulmonary function • Consider what is realistic • Prevent acute episodes • < 3 beta agonist per week • No emergency room visits or hospitalizations.
Therapeutic goals (cont.) • Avoid medication adverse effects • Prevent asthma related death • Meet patient/family expectations • Patient/family education: • symptoms • triggers • metered dose inhaler technique(have patient demonstrate) • “reliever” vs “controller” drugs • peak flow meter monitoring(Green, yellow and red zones)
Environmental Control • Same as for allergic rhinitis • Bedding • Carpets • Stuffed animals • Pets • Avoidance of allergens and triggers
Step Approach to Classification and Therapy • Mild Intermittent • PRN bronchodilators • Mild Persistent • Symptoms 3-6 times/ week • Add antiinflammatory • Moderate Persistent • Combinations of antiinflammatories and long acting bronchodilators • Severe Persistent • Acute exacerbations
Staging:Further Considerations • Seasonality • Nocturnal symptoms • Exercise induced • Peak flow monitoring • Daily fluctuations • Cough variant • “Wheezy bronchitis” in children
COPD: Chronic Obstructive Pulmonary Disease • Any lung condition causing longstanding airflow limitation with impaired expiratory outflow… • …airflow obstruction due to chronic bronchitis (and/or) emphysema • Generally progressive, may be accompanied by airway hyperreactivity, and may be partially reversible • …caused by abnormal inflammatory reaction to chronic inhalation of particles • 2-10% of US population over age 554th to 5th leading cause of death
Pulmonary function:Bronchodilator tone • Peak expiratory flow rate (PEFR) in liters/ minute • Forced expiratory volume in one second (FEV1) in liters • Normal values vary according to sex, age, height • Reported as absolute values or • Percentage of normal or of personal best • Establish patient zones • Green = 80-100% of normal • Yellow = 50-79% of normal • Red = <50% of normal
Peak Expiratory Flow Rate • First blast of air exhaled by the patient reaches this flow rate almost immediately. • The flow rate quickly slows as more air is exhaled. • Less elastic recoil by lung • Indirect measure of lumen size of large airways and strength of expiratory muscles during maximal effort.
Directions for use of Peak Flow Meter • “zero the pointer” • Move indicator to bottom of numbered scale on meter. • Stand upright • Breathe in as deeply and completely as possible • Close lips around mouthpiece to form tight seal • Do not put tongue in opening • Quickly blow out as hard and fast as you can. • Note reading; repeat 3 times