68: ASTHMA

INTRODUCTION Definition = Bronchial hyperirritability and chronic airway inflammation with subsequent obstruction to airflow after exposure to stimuli Wheezing is most common characteristic All that wheezes is not asthma Most things that wheeze, and some that do not, are asthma Asthma can present w/o wheezing and is commonly missed with that presentation EPIDEMIOLOGY Prevalence 10% and Prevelence is INCREASING Asthma mortality increased in the 1980s Higher rates in blacks, low SES Adult onset is more common in women PATHOPHYSIOLOGY Bronchial hyperreactivity and airway inflammation; recent advances in knowledge show that airway inflammation is the predominant cause of both acute and chronic asthma Control of the airway: the role of the Autonomic Nervous System Cholinergic innervation from the vagus nerve stimulates bronchoconstriction, goblet cell secetion, and pulmonary vessel vasodilation; this can be triggered by stimulation in the upper or lower airway; efficacy of atropine suggests this is an important mechanism Adrenergic innervation from sympathetic system releases norepinpehrine which binds to Beta2 receptors and alpha receptors B2 causes bronchodilation, water secretion, and also has effects on inflammatory cells Alpha receptors cause bronchoconstriction although the number of alpha receptors is thought to be small and the role of alpha receptors in asthma is not thought to be significant Control of airway inflammation The first step is a trigger of inflammation The trigger stimulates the EARLY asthmatic response The trigger stimulaties airway mast cells causing histamine release, production of prostaglandins, luekotrienze, enzymes, interleukins Release of messengers and inflammatory mediators causes a viscous circle of inflammation Mechanisms other than histamine and mast cells occur within hours to days and cause the LATE asthmatic response Machrophages, T lymphocytes (helper T cells) promotes inflammation involving neutrophils, interferons, & cytockines Inflammatory mediators stimulate migration of inflammatory cells from the circulation into the airway submucosa: eosinophils, basophils, mast cells, lymphocytes, neutorphils Cells that are drawn to the airway are then activated by

helper T cells and platelet activating factor Active inflammation produces tissue stimulation and damage

Chronic effects of asthma Airway remodelling: airway wall thickening, fibrosis, gland metaplasia, increased smooth muscle Airway remodelling may be the basis for patients with chronic asthma being resistant to therapy Ultimately may lead to chronic airflow limitation Triggers Viral infections Miscellaneous Allergens Environmental agents (pollen, dust, mites) Animals Occupational antigens Drugs: aspirin, BB Occupational antigens Smoke Pollution Exercise Summary of EARLY ASTHMATIC RESPONSE Mediators: Histamine, Prostaglandins, Leukotrienes, cytokine Effects: bronchospasm, airway edema, mucous pluggind, vascular leak Drugs: Beta agonists to cause bronchodilation and mast cell stabilization Summary of LATE ASTHMATIC RESPONSE Mediators: Eosinophils, Leukotrienes, Prostaglandins, Interleukins, PAF Effects: bronchospasm, edema, mucus production, vascular leak, epithelial damage, airway remodelling Drugs: corticosteroids and anti-leukotrienes for anti-inflammatory effects Aspirin induced Asthma Triad: aspirin sensitivity, asthma, nasal polyps More common in women than men; uncommon in kids ASA and NSAIDS Exact mechanism is unknow (? COX inhibition related) Treatment with leukotriene antagonists may be especially beneficial Exercise induced asthma Often are able to exercise but the asthma worsens after the exercise Peak symptoms occur 10 minutes after exertion and recovery w/i 1-2hrs Exact etiology is unkown Menstrual related asthma Increased asthma exacerbations during menstruation ? hormonal related Psychologic factors Emotional states may trigger bronchospasm Atopic Allergic Asthma Produciton of IgE antibodies when eposed to everyday allergens Most common type of asthma overall, especially in kids Other atopic features: eczema, allergic rhinitis, conjunctivitis, fhx

CLINICAL FEATURES Presentations Triad = cough, dyspnea, wheezing Wheezing is present in the majority but may be ABSENT with very severe exacerbations due to the lack of movement of air Persistent cough, night cough, recurrent pneumonias, chronic bronchitis, poor exercise tolerance, recurrent chest colds Consider dx w/ history of cough, wheeze, rattly chest Prolonged cough: consider asthma, common presentation that is commonly misdiagnosed as recurrent bronchitis or bronchiolitis History When did wheeze begin, how bad is it, is it getting worse? Longer duration predicts that it will be harder to treat History of asthma, visits to ED, admissions, intubations, ICU admissions, lost consciousness, been on ventilator, steriod use currently and in past? What medications, what have you given the child, when was last dose, what is maintenance regimen, improvement w/ medications? Triggers: URTI, cold, dust, smoke, pets, exercise, ASA, pollens, grass Fhx of asthma or atopy: 2 parents/60% with asthma, 1 parent 20%, no parents with asthma/6% will have asthma Atopy: eczema, allergies PMHx: BPD, CHD, GER, pneumonias Shx: smokers or pets in house Physical Examination Gen: distressed, LOC, cyanosis, able to talk in full sentences, tripod position Agitation or altered LOC is a BAD SIGN Vitals: tacchypneic, tacchycardic, low 02 sat, pulsus paradoxis Resp: AMU, indrawing, nasal flaring, wheeze (may be absent if severe), hyperinflation, hyperresonant, rales may be present Length of sentences is a good marker of airflow restriction AMU correlates best with severity: SCM use = < 50% predicted PEFR CVS: general ABD: HSM b/c of hyperinflation Hydration status Clues to impending respiratory failure Severe anxiety/irritability Lethargy, somnolence, fatigue Persistent tachypnea despite tx Poor air entry (airflow obstruction so bad) Marked retractions and AMU Pa02 < 50 on oxygen or PaC02 > 40 Formal Dx = PFTS = Variable airflow obstruction FEV1 improves > 12% (minimum of 200ml) 15 min after B2 agonist FEV1 improves > 20% after 14 days of steroids FEV1 varies > 20% spontaneously

Q: NAME 10 RISK FACTORS FOR DEATH FROM ASTHMA?

Prior sudden severe exacerbations Prior intubation Prior ICU admission Prior hospitalization (2 or more in last year) Prior ED visits (3 or more in last year) Prior ED or hospital admission in the last month Current use of corticosteroids or recent withdrawl Difficulty perceiving severity of airflow obstruction Use of > 2 MDI of ventolin per month Comorbidities Psychosocial problem Illicit drug use (cocaine and heroin)

INVESTIGATIONS CBC CXR

Increased wbc from stress of rxn or epinephrine Eosinophilia common Findings:may be normal but usu hyperinflation, flat diaphragms, increased bronchial markings; look for pneumothorax, pneumomediastinum Routine CXR for known asthmatic w/ mild attack is unnecessary Indications Sick: moderate to severe presentations First wheeze/young (<1yo) Atypical hx: suspecting other dx Suspected pneumonia: high fever, focal findings, etc Should use whenever possible as clinical estimate of degree of airflow obstruction is not very good Measure FEV1 and PEFR Not really useful until > 5 - 6 yo Useful to guide admission vs outpt management Trends are more important than absolute numbers MILD: > 70% of predicted or personal bes MOD: 50 - 70% SEVERE: < 50%

PFTs Pulsoximetry Initial room air sat is best predictor of severity and also shown to predict RTED rates: < 91% = admission NB: sats will drop with ventolin b/c of B2 vasodilation of non-ventilated lung

ABGs Indicated in severly ill, those who do not respond to bronchodilators and if hypercarbia suspected Normal PCO2 is a concern b/c they should have a low PCO2 b/c of hyperventilation

DIFFERENTIAL DX CHF (cardiac asthma) COPD exacerbation Pneumonia Pulmonary embolism Anaphylaxis ARDS Aspiration Endobronchial constriction: tumor, lymph node, FB Upper airway obstruction: Vocal cord dysfunction, tumors, edema, FB GERD

BRONCHODILATORS Short Acting Beta - Agonists (Salbutamol/Ventolin) MOA: bronchodilation by beta 2 effect, may decrease mast cell mediator releas Mild to moderate: q20 min X 3 then q1hr X 3 and decide on admission Severe: continuous Onset: effect w/i minutes Duration: 3 - 6 hrs Dose: 5 mg Clinical effects: shown to decrease admission rates, decrease length of stay, decreased RTED, decrease morbidity and mortality Ventolin iv Theoretical advantage of delivery to non-ventilated lung No evidence for iv ventolin vs continuous ventolin neb: Brian Rowe metanalysis Combine iv ventolin with continuous nebs if using Consider in severe, treatment resistent presentations Bolus: 10 ug/kg over 5 min Infusion: 0.2 ug/kg/min Complications: hypokalemia Long Acting Beta - Agonists Serevent (Salmeterol) Last 12 hours Onset is 20 min thus not very applicable to the acute attack Anticholinergics (Atrovent) MOA: blocks muscarinic receptors thus decreases vagal tone leading to

BD Only used as an adjunct, never alone Dose: Peds 250 ug vs Adult 500 ug Frequency: q20 min X 3 then q4hr (traditionally a q4hr drug but the only effect shown has been in the severe group with q20 min dosing) Maximum effect is seen within 30 - 120 minutes T1/2 is 4hrs Evidence: metanalysis showed to be beneficial in moderate and severe presentations with multiple doses (2 - 3 doses q 20 min even though it is a q4hr drug); no effect with single dose; no benefit after steroid has taken effect Benefit in mild asthma has never been shown Some patients seem to respond better than others but there is no way to predict

CORTICOSTERIODS Mechanisms of action = decreases bronchoconstriction and late inflammation (2 - 8hrs) by Decreases arachadonic acid production thus decreases prostaglandin and leukotrienes ------> decreases bronchoconstriction Also inhibits chemotaxis of eosinophils and neutrophils thus reduces inflammation and late response Also stabilizes bv walls and decreases mucosal edema which increases the response to beta agonists Also increases the numbers of beta receptors in bronchial smooth muscle wall Timing Generally takes effect at 6-24hrs Some evidence of improvement in PFTs at 2hrs in those not responding to beta agonists Side Effects Fluid retention: may precipitate CHF Hyperglycemia Hypokalemia Psychosis Rare: HTN, PUD, AVN (can occur with short courses but very rare) Addrenal suppression isnt an issue unless > 4 courses per year Evidence Good evidence for decreased admission rates: NNT 8 Good evidence for decreased RTED rates: NNT 13 Oral/iv/im has been shown to be superior to inhaled Oral has been shown to be equal to iv/im Some early evidence that dex 0.6 mg/kg and repeat at day 2 may be as effective as prednisone X 5/7 (problem with randomization in study) Options Oral steriods are preferred route unless cant tolerate (vomiting or sick) Prednisone 40 - 60 mg po od X 5/7 (no taper) Methylprednisone 1 - 2 mg/kg iv q6hr X 4 then 1 mg/kg q8hr Indications ALL ED presentations unless very mild or one time trigger

Especially indicated for ongoing triggers (URTI) Given early so that effect has started by d/c ? first time wheezer that you think is not likely to be bronchiolitis Cautiously consider steroid use in children exposed to varicella: consult ID. Recommendation now is for lower dose, and consider VZIG Inhaled Corticosteriods (ICS) Low dose ICS is mainstay of chronic mx Brian Rowe Metanalysis: Prednisone X 5/7 + ICS was better than prednison alone thus continue use even for those given 5/7 course (shown to decrease admission rates) Continue ICS for 10 - 14 days total and have GP reassess Flovent 125 ug/puff 2 puffs bid

OTHER AGENTS Theophylline Heliox Magnesium Racemic Epi Epinephrine

Methyxanthine BD but not as good as beta agonists Exact MOA unkown: ? cAMP, PG May increase mucociliary clearance and thus decrease late phase Aminophylline: 85% theophylline NO benefit for routine use in ED Consider if already on Target is 5 - 15 ug/ml Multiple drug interaction Cardiac arrythmias with high levels Very narrow therapeutic window RCT: no benefit over ventolin Different mixtures: 60:40, 80:20 Has been shown to improve PFTs and ABGs in non-intubated patients Has been shown to decrease peak airway pressures in intubated patients MOA: improves laminar flow thus allows better exhalation Only indicated in severe presentations Metanalysis shows effect in severe subgroup (adults): Rowe Limited evidence in peds MOA: smooth muscle relaxant thus BD +/- antiinflammatory Dose 25 mg/kg iv X 1 Consider in young who could have bronchiolitis

Subcutaneous epinephrine: 0.3 - 0.5 ml of 1:1000 sc; good for initial mx of the severe, crashing asthmatic who is moving very little air Epinephrine infusions: 0.1 ug/kg/min Replaced by iv ventolin Leukotriene Antagonists Leukotrienes are potent inflammatory mediators Montelukast (Singular) 10 mg po qd

Zafirlukast (Accolate) 20 mg po bid chronic therapy or 20 - 160 mg acute Use in acute therapy is being studied Singulair iv is being studied for ED use General Notes No evidence for fluids helping to clear secretions Steroids are not contraindicated in pregancy MDI + spacer is as good as nebulizers (many studies)

ED MANAGEMENT OF MILD/MODERATE ASTHMA Ventolin + atrovent (if moderate) q20 min X 3 + prednisone 40 - 60 mg po May avoid prednisone if responds to one ventolin Reassess after 3 nebulizers Consider discharge Ventolin q1hr X 3 Reassess each hour Admit after 3rd hour if needed Discharge instructions Prednisone X 5/7 ICS X 10 - 14 Ventolin Q4hr X 2 day then prn (more if needed) F/U with GP when prednisone finished to reassess AVOID avoid allergens and triggers EDUCATE about disease, medications, goals of treatment, monitoring RTED instructions: wheezing not controlled w/ medication, rapid breathing; call EMS if increased respiratory distress, cyanosis, apnea, or decreased LOC Admission indications Moderate to severe presentation Poor response to treatment Initial Sa02 < 91 on room air PEFR of < 60% a/f treatment Persistent vomiting of medications Underlying high risk disease Previous hx of near fatal attacks requiring ICU, intubation Poor compliance, poor access, social issues

ED MANAGEMENT OF SEVERE ASTHMATICUS Definitions Acute severe asthma = bronchospasm that is refractory to outpatient therapy Status asthmaticus = severe bronchospasm that does not respond to aggressive therapy within 30 - 60 min Fatal asthma = death Near - Fatal asthma = respiratory arrest or evidence of respiratory failure Slow - onset near fatal asthma: gradual deterioration over days Rapid - onset near fatal asthma: sudden, severe asthmatic

exacerbation that presents with collapse and respiratory arrest General Approach Airway: look, listen, feel manage Breathing: look, listen, feel, manage Circulation: look, listen, feel, manage Adjuncts: CXR, cap gas, monitors, blood work Initial treament: ventolin, atrovent, magnesium, steriods Complete hx and physical examination Airway Managment Allow patient to sit up Generally try to avoid intubation = many complications arise after intubation (barotrauma, hyperinflation, etc) thus aggressive Rx and avoiding intubation is preferred if possible RSI: good preoxygenation, lidocaine, ketamine, succinylcholine Impending Respiratory failure Severe anxiety/irritability Lethargy, somnolence, fatigue Persistent tachypnea despite tx Poor air entry (airflow obstruction so bad) Marked retractions and AMU Pa02 < 50 on oxygen or PaC02 > 40 or rising Treatment Hierarchy for severe asthma STAGE I 100% oxygen, iv fluids V - ventolin: continuous ventolin nebulizers A - atrovent: add atrovent nebulizers X 3 M - methyprednisolone: 1 mg/kg iv/im M - magnesium: 25 mg/kg iv/im X 1 STAGE II Ventolin iv bolus: 10 ug/kg over 10 min Ventolin iv infusion: 0.2 ug/kg/min and incr by 0.1 ug/kg/min Continue ventolin nebulizers Consider intubation STAGE III Intubate and ventilate Subcutaneous epinephrine 0.3 - 0.5 ml im Ketamine 2 mg/kg iv Heliox Sevoflourane anesthestic: consult anesthesia Is there any role for BIPAP Seems counterintuitive May decrease the work of breathing Case reports and case series of it working Mechanical Ventilation Sedate (ketamine) and paralyze (rocuronium) RR: 8 breaths per minute TV: 6 ml/kg Fio2: 100%

Inspiratory flow rate: increase from 60 to 100 PEEP: nobody knows, avoid unless having trouble oxygenating Keep peak airway pressures under 50 cm H20 Plateau pressures are actually more predictive of barotrauma Permissive hypercapnia: as long as pH is > 7.15 you dont care what the PCO2 is (it may run up into the 100s) Complications of mechanical ventilation Pneumothorax Pneumomediastinum Obstructed tube from secretions Hyperinflation/breath stacking/high intrathoracic pressures Hypotension and cardiac arrest Deteriorating patient that is being ventilated Remove from the ventilator Stop bagging Sqeeze the chest Decompress the chest Fluid bolus Epinephrine prn Arrest: cardiopulmonary bypass has been used!

DISPOSITION Predictors of ED relapse: 17% in 2 weeks in one metanalysis Several ED visits in the last year More use of outpatient medications Longer duration of symptoms before presentation CAEP guidelines predictors of relapase Previous near death Recent ED visits Frequent hospitalizations Steroid dependant or recent use Sudden attacks Allergic or anaphylactic triggers Prolonged duration of current attack Poor compliance Returning to env with triggers APPROACH TO CHRONIC MANAGEMENT OF ASTHMA

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Environmental control Inducers: identify and reduce/prevent exposure to allergens such as pets, house dust mites, viral infections, pollens, etc Triggers: identify and reduce/prevent exposure to pets, smoking, respiratory irritants, cold air, exercise, stress Environmental control more important than medications Education About disease nature, inducers, triggers Monitor: at home by s/s, PEFR, PFTs

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Written plan for exacerbations: increase ICS and B agonist Written plan for when to come to ER Written plan for when to phone ambulance B agonist use prn Add low dose ICS if ..... B2 agonist needed > 3 times/wk (excluding 1 doses/day before exercise) Initial dose is 400 - 1000 ug/d beclomethasone or equivalent Flovent low dose: 125 ug bid Flovent medium dose: 125 ug two puffs bid Flovent high dose: 250 ug two puffs bid Flovernt very high dose: 250 ug two puffs qid Increase ICS dose Adjuvant treatment Add additional tx if inadequate control on moderate doses (beclomethasone 500 - 1000 ug/d) Options: long acting B2 agonist, leukotriene receptor antagonist, cromolglycate, nedocromil Oral Steroids Add for frequent s/s on above or PEFR < 60% predicted Daily or alternate day Prednisone 30 - 60 mg/d adult or 1 -2 mg/kg pediatric

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ASTHMA MEDICATIONS Advair Singulair ETC