Asthma

    Based on CTS update 2012

    www.respiratoryguidelines.ca

    and MKSAP 16

    Introduction

    • Definition:
      • Asthma is defined as an inflammatory disorder of the airways characterized by paroxysmal or persistent symptoms such as dyspnea, chesttightness, wheezing, sputum production and cough, associated with variable airflow limitation and avariable degree of airway hyperresponsiveness to endogenous or exogenous stimuli.
    • 53% asthmatics are not controlled

     

    Epidemiology

    • 4000 deaths/year in US, and many are preventable. 
    • 5% of population have asthma in U.S.
      • Much less prevalence in developing countries.
      • Thought to be due to lack of early antigen exposure.
      • 70-90% have demonstrated allergies with skin testing and history.
    • Causes: "Barn theory" - letting kids play in dirt and have pets.
      • "Air pollution theory"
      • New onset adult asthma also common.
      • Genetics also important.
      • "Genetics" "Environmental" are important factors.

    Pathogenesis

    • Airway inflammation through a number of mechanisms.
      • Many eosinophils, mast cells etc... all involved.
      • Subephithelial fibrosis, airway mucosal hyperplasia, and increase in smooth muscle mass.
      • Eventually subepithelial fibrosis leads to irreversible airway obstruction over time. (smoking makes it much worse).

     

    • Typically after exposure to allergens, there is an "early phase" inflammation that is usually milder and lasts a few hours.  However 50% will have "late phase" inflammation lasting several hours to days and is much more severe.
    • After longstanding inflammation one can get permanent airflow obstruction due to airway remodeling.

    Symptoms

    • Most common is a cough.
    • Vary over time:
      • Breathlessness
      • Chest tightness
      • Coughing
      • Wheezing
    • Worse at night, early morning, or with triggers
    • Triggers
      • Viral URTI (most common)
      • Allergens (if atopic)
      • Exercise (cooling and drying of airways)
      • Emotion
    • Colds "go to chest" >10days to resolve
    • Symptomatic response to therapy: increases probability but not enough to dx.
    • Rule out conditions:
      • Vocal Cord Dysfunction
        • Typically vocal cords produce stridor at the upper airways.
      • Early Heart Failure
        • ​Can cause wheezing, used to be called "cardiac asthma".
      • Cystic Fibrosis
        • Check clubbing.       

    Diagnosis

    • Hallmark is to prove a "reversible airway obstruction"
      • NOTE: airway obstruction will become irreversible if the person smokes.  It starts to resemble COPD.
    • Preferred objective measures of lung function ages ≥6yo.
    • History & Physical

    Spirometry

    • First line test: To prove patient has reversible airway obstruction.
    • Pulmonary Function Tests
      • PFT Children >6yo < 12yo Adults >12yo
        Reduced FEV1/FVC Less than LLN (age/sex/height/ethnicity)
        < 0.8-0.9

        Less than LLN

        <0.75-0.8

        AND AND AND

        Increase in FEV1

        after bronchodilator

        or course of therapy

        ≥ 12% ≥12% (and minimum ≥200mL)

     

    • Peak Flow: considered second best because it's effort dependent.
      • PFT Children 6-12yo Adults >12yo

        Increase after bronchodilator

        or controlled therapy

        ≥20% 60 L/min (min ≥20%)
        OR OR OR
        Diurnal variation Not recommended

        >8% based upon twice

        daily readings

        >20% based on multiple daily

        readings

     

    Bronchial Challenge Testing

    • Indicated for patients with suspected asthma who have normal PFTs.
    • Typically done in specialized labs with lots of monitoring (can be dangerous!)
    • Methacholine Challenge:
      • Very Sensitive!! NOT specific [i.e. good negative predictive value 98%]
        • PC20 < 4 mg/mL
          (4-16 mg/mL is borderline > 16 mg/mL is negative)
        • Lots of false positives. (recent URTI's etc.)
    • Exercise challenge
      • ≥10-15% decrease in FEV1 post-exercise (after stop in 2-5min)
    • Causes of false positive methacholine challenge test:
      • Post-infectious cough
      • Post-nasal drip
      • GURD
      • COPD
      • CHF

    Allergy Testing

    • Check if patient is sensitized to various allergens.
    • Helps identify triggers in asthma that is difficult to control.
    • Allergen specific serum IgE testing also skin testing not accessible.

     

    Exhaled Nitric Oxide Testing

    • Elevated NO makes it likely that patient has active airway inflammation.
    • Unclear to what extent this can be used to monitor response to treatment.
    • Inhaled corticosteroids can reduce exhaled nitric oxide, at this time helps guage adherence.
    • Area of active research

     

    Types of Asthma

    • Useful to distinguish on history

     

    • Reactive Airways Dysfunction Syndrome
      • A type of occupational asthma.
      • Results from single LARGE exposure to high levels of irritant (i.e. bleach, ammonia, chlorine gas)
        • Major exposure leads to significant airway injury --> persistent airway inflammation/dysfunction/hyperresponsiveness.
      • Usually don't have prior asthma hx.
      • Symptoms can go on for years.
      • Spirometry usually normal.
      • Persistently Positive Bronchial Challenge Test (methacholine etc..)
    • Occupational Asthma
      • Irritants and allergens in workplace sensitize patients, and produce airway hyperactivity when re-exposed.  Typically "early response" in a few hours, and "late response" for several hours to days.
      • Symptoms improve when on vacation? or on weekends?
      • Obtain peak flow rates before work, at work, on vacation. (keep in mind circadian rhythm to lung function)
    • Virus Induced Asthma
      • Many viruses:
        • Rhinovirus (upper airway)
        • RSV, Influenza (lower airway)
      • Usually several days after URI symptoms.
      • May need "action plan" to increase ICS or LABA dose during this time.
      • May take weeks to return to baseline.
    • Cough Variant Asthma
      • No wheezing or chest tightness
      • Managed same way, often misdiagnosed.
    • GERD Induced Asthma
      • May need to treat GERD aggressively to help asthma control.
      • However only helps if relationship between GERD symptoms and asthma is obvious.
    • ABPA
      • Allergic Bronchopulmonary Aspergillosis
      • Small group of asthmatics and CF that have ABPA
        • Often if asthma difficult to control.
        • CXR: infiltrates (bronchiectasis on CT)
      • Sensitization of airway to aspergillus (fumigatas) - fungus colonizes abnormal airways in CF.
        • Leads to pulmonary inflammation and ineffective clearing of fungus.
      • Diagnosis: If suspect, measure total IgE levels.  Very elevated in ABPA
        • Also antibodies to aspergillus, skin testing (peripheral eosinophilia) if available.
      • Treatment:
        • Systemic costicosteroids (weeks to months of treatment)
        • Usually no antifungal therapy, but some evidence can decrease steroid dose.
          • Usually only done for refractory cases: Itraconazole or voriconazole is used.
      • Complications: if untreated can get worsening pulmonary fibrosis, decreasing lung function.
    • Exercise Induced Asthma
      • Breathing cold dry air worsens asthma.
      • Symptoms peak 5-10min after exercise, resolves in ~half hour.
      • Can do exercise-challenge spirometry.
      • Treatment: use SABA 15min before exercise protects for 3h.
        • Can consider LTRA, also shown beneficial for exercise asthma.
      • Non-pharmacologic:
        • If cold weather, wear mask.  Gradual entry into exercise.  Indoors.
    • Vocal Cord DysfunctionVocal Cord Dysfunction.png
      • Often mimics asthma.
      • Presents as inspiratory wheezing (stridor) coming from the upper airways.  
      • Typically abrupt onset / termination atypical of asthma.
      • Flow volume loop shows flattening of inspiratory phase; laryngoscopy: abnormal abduction of the vocal cords.
      • Often vocal cord dysfunction.
      • Treatment: SLP therapy to help "relax" airways when they feel symptoms.
        • ​Heliox helps in acute cases.
    • ​Aspirin Sensitive Asthma
      • Samter's Triad: ​Severe asthma, ASA sensitivity, nasal polyps.
      • History and/or aspirin challenge.
      • Can desensitize to ASA if needs for cardiac health.

     

    Treatment

    Approach

    1. Confirm diagnosis
    2. Discuss:
      • Trigger avoidance
      • Inhaler technique
      • Adherence
      • Written action plan (verbal not effective!)
    3. Sputum Eosinophils (costly, must inhale hypertonic saline, collect/process sputum)
      1. Only works if pt has eosinophilic asthma (others have neutrophilic etc..)
    4. FeNO (Fraction of exhaled nitric oxide)
      1. Cost $5000
      2. Up in all causes of airway inflammatin

    Control Criteria

    • Based on Symptoms and peak flows compared to baseline.
      • .AsthmaControlDefinition.png

     

     

    Pharmacologic

    • Two types of medications:
      • Relievers (control symptoms): SABA, SAAC
      • Controllers (reduce exacerbations, continues control): ICS

     

    Screen shot 2012-06-29 at 12.23.15 AM.png

     

    • Reliever Therapy: 
      • SABA (salbutamol) - all asthma pts should have this.
      • Can also use formoterol (in Symbicort) as it is fast acting (see note below)
    • First Line: Low dose ICS
    • Second Line: 
      • Adults: change to low dose ICS/LABA combo.
      • In Children (6-11y): can trial medium dose ICS monotherapy.  If not working, add LABA.
      • (LTRA  for >6yo are approved even for monotherapy (if will not take inhaled steroids).)
    • Third Line:
      • LTRA add-on (CONSENSUS)

     

    Breakdown:

    • Anti-IgE - (Zolaire - adalizumab) - only last line, for a subset of patients with uncontrolled allergic asthma.
    • Anticholinergics:
      • SAAC (ipratropium) - for asthma exacerbations
      • LAAC (tioptropium) - helps improve symptoms for those not controlled in ICS.
        • So can either add LAAC or LABA to ICS.
    • LABA (Formoterol, salmeterol)
      • LABA should not be used as monotherapy in Asthma (increases mortality)
    • Inhaled Corticosteroids (ICS)
      • Decrease the number and activity of inflammatory cells.
      • Use LOWEST ICS dose to provide asthma control.
      • Decrease symptoms and exacerbations.
      • Synergistic with LABA (increase B2 receptors).
      • Inhibits the "delayed phase" allergy response in airways.
      • Side Effects:
        • Local: Hoarseness, Oral Thrush, Cough.
          • Recommend adherence to asthma regimen (use spacer and rinse mouth after use).
          • Reduce ICS dose to safest lowest amount.  
          • Use Nystatin mouth wash if needed.
        • Systemic: Weight gain, adrenal suppression, osteopenia, glaucoma, skin thinning.
          • Risks very low (mostly in elderly).
    • Leukotriene Receptor Antagonists (LTRA) (Montelukast [Singulair], Zafirlukast [Accolate], Zileuton [Zyflo])
      • Leukotrienes promote asthma (mucous secretion, vasodilation, inflammation).
      • Anti-inflammatory and bronchodilator effect.
      • Improve symptoms, QOL, prevent exercise-induced sx, but not first line. 
      • Side/Effect:
        • Neuropsychiatric (Anxiety, Agitation, Hallucination, Depression). [uncommon, reported]
        • Zileutin can cause hepatotoxicity [monitor].
    • Theophylline
      • Very narrow therapeutic margin, target drug levels closely.
      • In the guidelines, but rarely used.
      • Targer 5-12 mcg/mL.
      • Many drug interactions (increased level with other drugs such as fluoroquinolones).
        • Cousel on side effects: tremor, headache, nausea, palpitations.
        • High risk of cardiac arrhythmias and seizure.
      • DO NOT use for acute exacerbation, only chronic... 
    • Anti-IgE Antibody
      • Recombinant antibody, blocks Fc portion of IgE.
      • Reduces exacerbations, improve symptoms, reduces systemic and ICS dose.
      • Only reserved for severe asthma refractory to therapy with evidence of allergies. (IgE level 30-700 IU [normal 0-90]).  --> very expensive.
      • Requires monitoring with anaphylactoid reactions. (1 in 1000)  Observe 2h post-dose x3 doses then x1h thereafter.

     

    ICSequivalence.png

     

    • Notes:
      • LABA monotherapy w/o steroid associated with risk of mortality, do not use as monotherapy in asthma.
    • NOTE: Reliever Therapy:
      • Classically a SABA (i.e. salbutamol)
      • Can use formoterol (NOT salmeterol) by itself or symbicort (budesonide/formoterol).
        • For moderate/severe only (because)
        • Max daily is 8 puffs symbicort (2 puffs BID + reliever dose), maximum is due to formoterol (does not matter what strength steroid).
        • Can do symbicort one puff BID to two puffs BID maintenance. (usuaually 2 puffs BID unless have tremor or another issue).
        • Xenhale (also has formoterol): not approved for on-demand therpay.

    Action Plan

    • WRITTEN action plan.
    • "yellow zone"
    • Intermittent ICS
      • popular mgmt strategy for kids/adults non-adherent.  Evidence not support this!!!
    • Escalating ICS:
      • Double (2 puffs BID, as long as not exceeding laba component)
      • RCTs: no benefit.
      • Only 4-fold or greater increase in ICS for 7-14d.  (only adults with severe exacerbations in past year).
      • Not recommended in preschoolers, children, adolescents.
      • If fixed dose ICS/LABA - unknown what to do except symbicort.
      • If symbicort, can increase to 4 puffs BID...
    • Steroids at home
      • Small trial in kids
      • For those who had severe exacerbation at home, who fail to respond to SABA, can do this.

     

    Medications

     

    Acute Exacerbations

    • At Home:
      • Can instruct to increase frequency of SABA use and even a short course of steroids.
      • Can use peak flow meters:
          • Mild: >70% of predicted or personal best
          • Moderate: PEF 40-70%
          • Severe: PEF <40%
        •  
      • If no response or severe, must see an MD.
    • Often present in respiratory alkalosis.
      • If see normal or slightly elevated pCO2 --> imminent respiratory arrest!!!
      • Indication for intubation:
        • Indications for intubation

          • Reduced LOC
          • Agonal respirations
          • Escalating work of breathing
          • Fatigue despite aggressive bronchodilating therapy.
    • Management:
    1. Supplemental Oxygen
    • If hypoxic, keep O2 sat >90%.  (if requires large amounts of O2, consider alternative dx, HF/PE/PNA/pneumotx)
    1. Bronchodilators (FIRST LINE)
      • Inhaled bronchodilators
      • High-Dose SABA: ventolin (or albuterol in US) 2.5-5mg by neb q20m x3, then 2.5-10mg q1-4h PRN)
      • Anticholinergic: Ipratropium 0.5mg q20m x3 (or followed by q4h)
      • If severe exacerbation: may not get optimal drug delivery with inhaler or spacer.
        • Can deliver bronchodilators by nebulizer.
    2. Steroids
      • IV is better (esp if concern over reliability of oral route)
        • Methylprednisolone 40-125mg IV x1 dose (dilute in 50mL of D5W or NS, infuse over 15-30m) OR:
        • Hydrocortisone 250-500mg IV (dilute in 50-100mL of D5W or normal saline) give over 15-30m
      • Oral: 50mg of prednisone x 5-10 days) (or 1mg/kg/d, shouldn't need more).
        • If coming in on lower doses, can increase to higher 1mg/kg dose.
        • Taper unclear (no evidence), can be on 40mg/day for 10-14 days and can stop abruptly.  In practice beyond the week tendency to taper. 
    3. Adjunct Therapies: 
      (Less evidence, inconsistently included in guidelines)
      • Magnesium: 2mg Magensium Sulfate IV x1 over 20min x1 dose (monitor BP during+ 3m post)
      • Helium-Oxygen Mix (Heliox): 60% helium, 40% O2
      • NIPPV: Limited experience may reduce need for intubation, not studied well.
    4. F/U peak flows or bedside spirometry
      • if no improvement --> admit.
      • If sustained improvement >70% for >1hr --> can d/c home.
      • if PEF < 40% pred despite 1hour of aggressive bronchodilators --> admit to ICU!
    5. For SEVERE asthma
      • In addition to steroids, ventolin, atrovent, magnesium:
        • Can do continuous bronchodilators (salbutamol 5mg, ipratropium 500mcg)
        • Epinephrine
          • IM: 0.3-0.5 mg (=0.3-0.5 mL of 1:1000 solution) over 5-10m q20m prn
          • IV: 0.1mg of 1:10,000 (0.1 mg/mL) IV --> dilute 1mL ampoule of 1:1000 in 9mL of NS --> 1:10,000 --> and inject 1mL over 5-10m (can repeat q5-15m) 
            (Dilute 1mL ampoule of 1:1000 in 9mL of NS = 1:10,000)
          • IV Infusion: Dilute 4mL of 1:1,000 sol'n (1mg/mL) in 250mL of D5W (16 mcg/L) and infuse at 1-4 mcg/min (4-15mL/hr)

    Refractory Asthma

    • Some patients require chronic steroids.
    • Causes (r/o:)
      • Inadequate adherence to inhaled medications
      • Ongoing smoking
      • Ongoing occupational exposures
      • Allergic rhinitis, chronic sinusitis.
    • Close F/U, patient education, asthmatic specialist.
    • Refer to respirology or allergy medicine (esp if large allergy component)
    • NEED written personalized asthma action plan.

    Asthma and Pregnancy

    • During pregnancy
      • 1/3 better control, 1/3 worse, 1/3 same.
      • Associated with:
        • Low birth weight, premature labour, pre-eclampsia, infant mortality.
        • Better asthma control reduces risk to mom and fetus.
    • Difficult to distinguish dyspnea due to pregnancy vs. asthma.
      • Use spirometry to help.
    • NOTE: Skin testing not indicated in prengnacy
    • NOTE: Bronchial challenge testing is CONTRAINDICATED in pregnancy.
    • May need empiric treatment.
      • Systemic corticosteroids --> small risk of congenital abnormalities, but uncontrolled asthma has a worse prognosis.
      • SABA, ICS all safe in prengnacy (Budesonide has most safety data).
        • LABA preferred second line
        • LTRA have been used as well, but most try to minimize therapy.
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