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Asthma in AdultsJessica Lo MS3, SUNY DownstateMay 2014Introduction1 in 12 people in the U.S. have asthma = 25 million people (CDC 2011)7 million are children$56 billion per year in medical costs, missed school days and missed work days >3000 deaths due to asthma in the U.S. (2010)Numbers growing every year

What is Asthma?Chronic inflammatory disease of the airways causing airflow obstructionObstructive lung diseaseBronchial hyperresponsivenessSymptoms typically wax and waneREVERSIBLE (at least partially)Triad of:BronchoconstrictionInflammation and edema of airway wallsMucus production/plugging

Asthma - Pathophysiology2 mechanismsIntrinsic non-immune related, caused by vagal stimulation (e.g. viral infection, exercise, cold air)Extrinsic immune-related, caused by mast cell activation and degranulation (e.g. allergens)

Asthma - PathophysiologyExtrinsicAllergens bound by dendritic cells and presented to T- and B-cellsT-cells secrete cytokines causing B-cell production of IgEIgE coats mast cells; cross-linking causes mast cell degranulation and release of histamine, leukotrienes, and inflammatory cytokines

Asthma - Pathophysiology2 phases of asthma attackEarly phaseWithin several minutesAllergen exposure by sensitized individual causes mast cell degranulation and release of histamines, prostaglandins, leukotrienes, etc.Can also be through vagal stimulation by irritantBronchoconstriction via smooth muscle contraction, edema via blood vessel dilation and increased permeability, and mucus productionLate phaseHours laterRecruitment of other inflammatory and immune cells, e.g. eosinophils, basophils, neutrophils, T-cells, monocytes, dendritic cellsFurther release of inflammatory mediatorsClinical Features - HistoryRespiratory symptoms in presence of triggers that resolve with avoidance of trigger or with asthma medicationE.g. allergens, exercise, cold air, smoke, infection, aspirinSymptomsWheezeCough, often worse at nightDyspneaChest tightnessSymptoms typically episodic and often worse at nightPersonal or family history of asthma, allergies, or other atopic diseasesHistory of chronic cough, nighttime cough, or recurrent bronchitis as a childClinical Features PhysicalScattered, high-pitched musical wheezesCommonly expiratory, but can also be inspiratoryUsually varies in tone and duration over time, starts and stops at different points of respiratory cycleSevereTachypneaTachycardiaProlonged expiration (decreased I:E ratio)Tripod positionUse of accessory muscles of respirationPulsus paradoxus (decrease in SBP >12mmHg during inspiration)Absence of wheeze may indicate severe bronchoconstrictionExtra-pulmonaryNares pale, swollen mucosa suggest of allergic rhinitis; nasal polyps suggest aspirin sensitivitySkin atopic dermatitis

Nasal polypsDiagnosis of AsthmaHistoryPhysical examSpirometryFEV1/FVC ratio 12% or 200ml with administration of short-acting bronchodilator (e.g. albuterol)Decrease in FEV1 >20% with bronchoprovocation test (methacholine or mannitol inhalation)Peak expiratory flow>20% variability over several recordings

Other StudiesCBC with diff may show eosinophilia (>15% or >1500/microL)CXRMay show pneumonia (possible exacerbating factor)Also used to rule out other causes of asthma-like symptomsPoorly controlled asthma may have atelectasis due to mucus pluggingAllergy tests identify triggersTotal serum IgE when considering use of omalizumab as therapyClassifying Asthma SeverityIntermittentSymptoms 2 days/weekNighttime awakenings 2x/monthUse of short-acting beta2-agonist 2 days/weekMild persistentSymptoms >2 days/week but less than dailyNighttime awakenings 3-4x/monthUse of short-acting beta2-agonist >2 days/week but not daily and not >1x/weekModerate persistentSymptoms dailyNighttime awakenings >1x/week but not nightlyUse of short-acting beta2-agonist dailySevere persistentSymptoms throughout the dayNighttime awakenings often 7x/weekUse of short-acting beta2-agonist several times a day

Classifying Asthma Severity & Initial Treatment

Management of Asthma by Severity

Reassessment and Adjusting Therapy

Asthma Medications

Asthma Medications Mechanisms of Action

Asthma MedicationsShort-acting beta2-agonists (SABA)E.g. Albuterol, levalbuterol, pirbuterol, metaproterenolUse: PRNMechanism: bronchial smooth muscle relaxationSide effects: increase HR, tremors, arrhythmias, irritabilityLevalbuterol marketed to have fewer side effectsLong-acting beta-agonists (LABA)E.g. salmeterol, formoterol, arformoterolUse: usually added to treatment if moderate persistent asthma or worse. Used as twice daily controller Mechanism and side effects same as short-acting

Asthma MedicationsInhaled corticosteroids (ICS)E.g. beclomethasone, budesonide, flunisolide, fluticasone, mometasoneUse: added for mild persistent or worse. Twice daily controllerMechanism: decreases inflammation by inhibiting cytokine productionSide effects: dysphonia, thrush, reflex coughSystemic corticosteroidsE.g. prednisone, prednisolone, methylprednisolone (IV)Use: moderate to severe exacerbations. Usually given for 3-10 days to avoid adrenal suppressionSide effects: adrenal suppression, leukocytosis, immune suppression, Cushings syndrome, neuropsychiatric disturbance, osteoporosis, cataractsAsthma MedicationsAnticholinergicsE.g. ipratropium, tiotropiumUse: in combination with SABA for mild/moderate persistent asthmaMechanism: inhibit muscarinic cholinergic receptors to reduce vagal tone bronchodilationSide effects: dry mouth, blurred vision, urinary obstructionMethylxanthinesE.g. theophyllineUse: add-on or alternative for moderate or severe persistent; used rarelyMechanism: inhibits phosphodiesterase, leading to increased cAMP smooth muscle relaxationSide effects: tachycardia, nausea/vomiting, sleep disturbance, arrhythmias and seizures in overdose; narrow therapeutic indexLeukotriene modifiersE.g. montelukast, zafirleukast, zileutonUse: as alternative or add-on to ICS or LABAMechanism: leukotriene receptor antagonist (montelukast, zafirleukast) or leukotriene synthesis inhibitor (zileuton). Leukotrienes responsible for eosinophil infiltration of airwaysSide effects: elevated transaminases, hepatotoxicity (zileuton)

Asthma MedicationsMast cell stabilizersE.g. cromolyn, nedocromilUse: maintenance/controller. Add-on or alternate to ICS or LABAMechanism: prevents activation and degranulation of mast cell by membrane stabilization (cromolyn) and prevents release of inflammatory mediators by by neutrophils, eosinophils, monocytes, and macrophages (nedocromil)Side effects: sore throat, unpleasant tasteAnti-IgEE.g. OmalizumabUse: moderate to severe persistent asthma. Good for patients with allergies. Subcutaneous administrationMechanism: prevents IgE binding to mast cellsSide effects: anaphylaxis

Urgent Care SettingAssessmentPhysical tachypnea, HR >120, diaphoresis, use of accessory muscles, inability to speak full sentences, pulsus paradoxusPeak flow meter PEF