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Asthma

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Title: Asthma


1
Asthma
  • J.B. Handler, M.D.
  • Physician Assistant Program
  • University of New England

2
Abbreviations
  • SOB-shortness of breath
  • ASA- aspirin
  • P.E.- physical exam
  • EOS- eosinophils
  • RR- respiratory rate
  • ABG- arterial blood gas
  • Nl- normal
  • CxR- chest x-ray
  • SaO2- saturation of oxygen
  • OP- out patient
  • V/Q- ventilation/perfusion
  • DM- diabetes mellitus
  • ß- beta
  • EIA-exercise induced asthma
  • PRN- as needed
  • HTN- hypertension
  • D/C- discontinue
  • SO2- sulfate
  • NO2- nitrate
  • GERD- gastroesophageal reflux disease
  • PO- by mouth
  • Alt- alternative
  • NSAID- non-steroidal anti-inflammatory drug

3
Definition
  • A clinical syndrome of unknown etiology with
    three components1. Recurrent episodes of airway
    obstruction that resolve spontaneously or
    following treatment.2. Exaggerated
    bronchoconstrictor response to stimuli that have
    little/no effect on non-asthmatics.3.
    Inflammation of the airways.

4
Case 1
  • A 45 y/o white male presents with paroxysms of
    severe coughing lasting up to 1 hour, resolving
    spontaneously. He had a recent URI. No prior
    history of pulmonary problems. No hx of smoking.
    Currently feels well.
  • P.E Healthy appearing male, NAD Vesicular
    breath sounds throughout both lung fields without
    wheezing, ronchi or crackles.
  • What is your differential diagnosis?

5
Differential Diagnosis
  • New/superimposed respiratory infection-
    bronchitis, pertussis, etc.
  • Asthma
  • Allergies
  • Toxin or pollutant exposure
  • Early signs of new disease
  • Psychogenic cough dx only of exclusion

6
Epidemiology
  • 5 of child/adult U.S. population
  • Can develop any time in life (often lt25 y.o.)
  • 500,000 hospitalizations, 5,000 deaths/yr.
  • 15 million OP visits/yr.
  • gt6 billion dollars/annually

7
Pathogenesis
  • Genetic predisposition.
  • Inflammatory infiltrates (lymphocytes,
    neutrophils, eosinophils, mast cells).
  • Injury to airway epithelium denudation.
  • Thickened airway wall from
  • Inflammation, collagen deposition, smooth muscle
    hypertrophy.
  • Hypertrophy and hyperplasia of airway glands.
  • Airway hyperresponsiveness.

8
Pathogenesis
  • Episodic airway narrowing smooth muscle
    constriction, thickening of airway epithelium and
    mucus secretion into the airway lumen mucus
    inspissates.
  • Local release of bioactive mediators or
    neurotransmitters during attacks contributes to
    airway constriction.
  • End result is acute, reversible obstruction of
    the airway lumen to airflow.

9
Pathophysiology
  • ??Airway resistance medium and small
    airways??work of breathing.
  • Diffuse airway obstruction.
  • ?Airway reactivity to variety of stimuli.
  • V/Q mismatch low V/Q contributes to hypoxemia
    when present.
  • Tachypnea results in ?PCO2. If PCO2?, ominous
    sign of ventilatory failure.

10
Airway Obstruction
AllRefer Health
11
Asthma Microscopic
Images.google.com
12
Asthma Mucous Plugging
13
Mediators Acute Response
  • Acetylcholine neurotransmitter released via
    intrapulmonary branches of vagus nerve? increases
    bronchial smooth muscle contraction
    ?bronchoconstriction.
  • Histamine endogenous bronchoconstrictor in mast
    cells, basophils, lungs. Vasodilator properties
    promote capillary leakage in presence of
    inflammation.

14
Mediators Acute Response
  • Kinins- bradykinin activated by enzymes
    (kallikreins) released by mast cells-
    bronchoconstrictor.
  • Leukotrienes biochemical mediators released by
    mast cells, EOS and macrophages-potent smooth
    muscle constriction increase mucus secretion and
    activate airway inflammatory cells.

15
Asthma Triggers
  • Atopy association of allergies- inhaled
    allergens can trigger attacks- dust mites, cats,
    seasonal pollens, hay fever, etc.
  • Single largest risk factor for developing asthma.
  • Non-specific triggers URIs, sinusitis, tobacco
    smoke, ozone, GERD, weather, stress, exercise,
    SO2, NO2, and others.
  • Aspirin allergy- cross reactivity with other
    NSAIDs, but not selective COX-2 agents.
  • Absence of triggers not unusual as well.

16
Clinical Presentation
  • History attacks of coughing, wheezing, SOB,
    anxiety, chest tightness. Associations-
    allergies, irritants, ASA. Highly variable
    presentation.
  • Episodes often at night and early AM when airway
    reactivity is highest.
  • P.E ?P RR, ?secretions, ?expiratory phase,
    wheezing, mucosal swelling.
  • Note with severe asthma, wheezing may decrease
    or stop?decreased airflow.

During asthma episode/attack
17
Pulmonary Function Testing
  • Spirometry easily obtainable FVC, FEV1,
    FEV1/FVC.
  • PEFR-Peak expiratory flow rate-(L/min)- varies
    with age, gender, height hand-held device good
    for following asthma severity as an adjunct to
    PFTs.
  • Spirometry or PEFR following bronchodilator
    assess responsiveness to treatment.

18
Spirometry of Asthmatic
  • Lung volumes ?TLC, FRC, RV FVC normal or
    slightly?
  • Lung flow ?FEV1, ?FEV1/FVC (lt70 means
    obstruction), ?PEFR.
  • DLCO- normal
  • Spirometry in between asthmatic attacks may or
    may not be normal depends on asthma
    severity/classification (see below).

19
Case 1
  • One year ago, he had a similar episode which
    responded to antibiotics.
  • In the last year he has noted episodic coughing
    when using a dictaphone or speaking for extended
    periods of time.
  • Some episodes with exercise- no pattern.
  • PFTs done on 2 occasions when asymptomatic have
    been entirely normal.
  • Symptoms rapidly respond to short courses of oral
    prednisone.

20
Pulmonary Testing
  • Provocative testing (If spirometry nl)-
    Methacholine challenge to induce Sx and decrease
    in FEV1 (by 20 or more). If negative, asthma
    very unlikely.
  • Arterial blood gases (ABGs)- measure pH, PCO2,
    PO2. Respiratory Alkalosis with ?PCO2 is common
    during attack. If PCO2 is normal or high during
    an attack ? impending respiratory failure. ?PO2
    indicates severe V/Q mismatch.
  • CxR- Often normal vs hyperinflation.

21
Case 1
  • During methacholine challenge testing, he has
    abrupt onset of severe coughing with a gt20 drop
    in FEV1 and FEV1/FVC.
  • Treatment with inhaled ß-agonist aborts the
    attack.
  • PFTs return to normal following albuterol.

22
Asthma Complications
  • Infection including pneumonia
  • Exhaustion, dehydration
  • Oxygenation failure
  • Ventilation failure lose drive to inflate
    alveoli
  • Death

23
Classification of Severity
  • Applies to clinical features of chronic, stable
    asthma.
  • Mild intermittent asthma- Symptoms ? 2x/week-
    No symptoms and normal PEFR between attacks-
    Night symptoms ? 2x/month- FEV1 and PEFR ? 80
    predicted- PEFR variability ?20

In between attacks
Current, Chapter 9
24
  • Mild persistent asthma- Symptoms gt 2x/week,
    lt1x/day- Night symptoms gt 2x/month- FEV1 or
    PEFR ? 80 predicted- PEFR variability 20-30

In between attacks
Current, Chapter 9
25
  • Moderate persistent asthma- Daily symptoms
    daily use of inhaled short acting ß2 agonists
    - Night symptoms gt1x/week- FEV1 or PEFR
    gt60 to lt80 predicted - PEFR variability
    gt30

In between attacks
Current, Chapter 9
26
  • Severe persistent asthma- Symptoms daily and
    frequent- may be continuous- Frequent night
    symptoms- FEV1 or PEFR ?60 predicted- PEFR
    variability gt30
  • Note Exacerbations of symptoms are common in
    patients with asthma and often limit activities
    in moderate to severe forms.
  • In between attacks

Current, Chapter 9
27
Long Term Treatment Goals
  • Minimize chronic symptoms that impair normal
    activity.
  • Minimize exacerbations/hospitalizations.
  • Limit side effects of medications.
  • Cornerstone treatment of persistent asthma- daily
    anti-inflammatory therapy with inhaled
    corticosteroids.
  • Stepped care approach (Current, table 9-3).
  • Long term control vs. quick relief meds.

28
Quick Relief Beta Adrenergic Agents
  • Most efficacious brondchodilators for acute
    symptoms.
  • Also used to prevent exercise induced asthma
    (EIA).
  • ?2 agonists selectively relax bronchial smooth
    muscle- bronchodilate while limiting cardiac
    stimulation.

29
Quick Relief Beta Adrenergic Agents
  • Albuterol, others Rapid onset of action (lt5)
    most effective agents for acute bronchospasm. Use
    of a spacer may improve delivery.
  • MDI 1-2 puffs (0.18mg) up to 6 puffs q6hr
    delivery may improve with spacer.
  • Nebulizer doses (2.5 mg) are 14x more potent than
    MDI (2 inhalations)- more effective for severe
    asthmatic exacerbations (ED, hospitalized).

30
Inhalers and Spacers
AllRefer Health
31
Quick Relief Anticholinergic Meds
  • Reverse vagally mediated bronchoconstriction and
    mucus production.
  • Ipratropium bromide (Atrovent) via inhaler 2-4
    puffs (18mcg/puff) q6h as an alternative or
    adjunct (in moderate to severe exacerbations) to
    short acting B-agonists not as effective.
  • Not useful for EIA or allergy induced asthma

32
Long Term Control Inhaled Corticosteroids
  • Low to high dose, local Corticosteroids most
    important and effective for long term control in
    persistent asthma.
  • Reduce chronic and acute inflammation mild
    persistent asthma and worse.
  • Inhaled preparations for prevention dose
    titrated to symptom relief may take weeks for
    optimal efficacy adrenal suppression unlikely.

33
Inhaled Corticosteroids
  • Several agents- varying potency (Fluticasone,
    Beclomethazone, Flunisolide et. al.).
  • Usually 2x or 3x daily dosing
  • Follow by H2O or mouth wash gargle to avoid local
    yeast (Candida) infection.

34
Long Term Control Long Acting ?-agonists
  • Used for long term (8-12 hrs) bronchodilation and
    EIA not for acute episodes.
  • Especially beneficial for night time symptoms.
  • Salmeterol (Serevent) 50mcg 2x/d. Formoterol is
    new with similar effects.

35
Salmeterol Safety Concerns
  • Two large clinical trials? salmeterol ?s asthma
    exacerbations and asthma related deaths (small
    number of patients, but statistically
    significant).
  • Black-box warning on labeling since 2005
  • Little change in prescribing since.
  • Message Use with caution. Confine use only to
    patients already on inhaled corticosteroids with
    ongoing symptoms.

36
Leukotriene Modifiers
  • Leukotriene modifiers Inhibit synthesis
    (Zileuton/Zyflow) or action (Zafirlukast/Accolade)
    of leukotrienes inhibit inflammatory mediators
    decreases need for rescue inhaler. Modest
    efficacy for patients with mild persistent
    asthma.
  • Alternative to low dose inhaled steroids in
    treatment of mild persistent asthma.

37
Mediator Inhibitors
  • Chromolyn, Nedocromil- mild improvement in airway
    function in mild persistent or EIA. Inhibit mast
    cell release of mediators of inflammation
    inhibit asthmatic response to allergens.
  • Alternative to IC for some patients with mild
    persistent asthma and allergies. Limited
    usefullness.
  • Excellent safety profile

38
Systemic Corticosteroids
  • Systemic steroids are used in Rx of moderate to
    severe asthma exacerbations marked
    anti-inflammatory properties speed (6 hours) the
    resolution of airway obstruction and reduce rate
    of relapse oral or IV dosing.
  • Long term use may be required in some patients
    with severe persistent asthma.

39
Systemic Corticosteroids
  • Prednisone et. al. (40-60 mgs/daily for
    out-patient care) higher doses required if
    severity requires hospitalization.
  • Safe when used for short term treatment (see
    below) of moderate to severe exacerbations.
  • May occasionally be needed (short term course) in
    some patients with mild asthma during severe
    exacerbations.

40
Systemic Corticosteroids
  • Dangers Supraphysiologic dosing over time leads
    to long term risks Adrenal suppression, HTN,
    osteoporosis, glucose intolerance/DM, easy
    bruisability, weight gain, etc.
  • Goal Pulse dosing followed by taper and D/C,
    overlapping with ? dosing of inhaled agents which
    have minimal systemic side effects.
  • Tapering dose (days to weeks) allows return of
    adrenal-pituitary axis.

41
Interest Only
  • Phosphodiesterase inhibitors- aminophylline,
    theophylline- less effective and potentially
    toxic adjunctive Rx for mod to severe persistent
    asthma.
  • Toxicity- Low therapeutic/toxic ratio- GI
    (nausea, abd. pain), CNS stimulation (anxiety,
    HA,tremors, seizures)and Cardiac (arrhythmias,
    tachycardia).
  • Must monitor serum theophylline levels to
    maintain therapeutic range (10-20 ug/ml).

42
Still OtherIO
  • Oral ?-agonists- terbutaline, albuterol tablets-
    usually add little to inhaled agents may be
    useful as an adjunct terbutaline causes tremors.
  • Immunosuppresive agents Methotrexate,
    cyclosporine, trolandomycin- for patients
    unresponsive to other drugs or where steroids
    contraindicated.

43
Combination Meds
  • Advair Diskus Combination inhaler with
    Fluticasone in varying strengths combined with a
    fixed dose (50mcg) of Salmeterol, one inhalation
    b.i.d, decreases number of inhalers and
    inhalations.
  • Combivent Albuterol ipratropium

44
Case 1 Many Years Later
  • He remains asymptomatic and has reduced meds over
    time. Rare coughing episodes rapidly respond to
    albuterol inhaler.
  • Meds
  • Fluticasone MDI 220mcg 2x/d
  • Abuterol MDI (90mcg/puff)- 2-3 puffs prn
  • Notes breathing is best when teaching PA students
    at UNE!

45
Mild Persistent Asthma
  • Long Term Control
  • Daily meds
  • Either low dose inhaled steroid or
    Cromolyn/Nedocromil
  • Alternative Leukotriene modifier
  • If needed increase dose of ICs
  • Quick Relief
  • Short acting B2 agonist
  • Frequent or increasing use of B2 agonist suggests
    need for additional therapy.

Current, Chapter 9
46
Moderate Persistent Asthma
  • Long Term Control
  • Daily meds
  • Low, medium or high dose inhaled streroid
  • If needed, add long acting bronchodilator-B2
    agonist (esp for night time Sx)
  • Alt SR theophylline
  • Quick Relief
  • Short acting inhaled B2 agonist
  • Frequent or increasing use of B2 suggests need
    for additional therapy

Current, Chapter 9
47
Severe Persistent Asthma
  • Long Term Control
  • Daily meds
  • High dose inhaled corticosteroid
  • Long acting bronchodilator-B2 agonist
  • Alt SR theophylline
  • Oral steroid therapy often needed for long
    periods.
  • Quick Relief
  • Short acting B2 agonist
  • Frequent or increasing use of B2 suggests need
    for additional therapy

Current, Chapter 9
48
Mild Asthma Exacerbations
  • Stepped care incremental therapy
  • Most are treated at home with quick response to
    ?d dose/frequency of short acting rescue
    ß-agonist.
  • These drugs may be needed every 3-6 hours for a
    short course.
  • Inhaled corticosteroids may need to be added
    (MIA) or dose ?d (x2) if already taken (PA)
    full effect will take weeks.

PA- persistent asthma
MIA- mild intermittent asthma
49
Mild Asthma Exacerbations
  • If already taking an inhaled corticosteroid, the
    dose is doubled during an acute exacerbation
    until PEFR return to normal.
  • If unresponsive, an oral systemic corticosteroid
    may be needed for a short course, then tapered,
    returning to inhaled corticosteroids.

50
Moderate/Severe Attacks
  • Some patients (caution) managed as out patient-
    require very close monitoring via phone.
  • Most patients warrant hospitalization.
  • Supplemental O2 as needed to maintain SaO2gt90.
  • Continuous O2 saturation monitoring via oximetry
    if hospitalized.

51
Moderate/Severe Attacks
  • Reversal of airway obstruction-
    repetitive/continuous use of high dose ß-agonists
    usually via nebulizer.
  • Early administration of systemic corticosteroids
    IV high dose.
  • Serial measurement of lung function PEFR or
    spirometry to monitor course.
  • ABGs often helpful pH, PO2, PCO2.

52
Moderate/Severe Attacks
  • Never sedate during acute asthma exacerbation
    will ?ventilatory drive.
  • Dropping PO2 lt60mm Hg (O2 satlt90) and rising
    PCO2gt 42mm Hg are evidence of impending
    respiratory/ventilatory failure and warrant
    treatment in the ICU.
  • Intubation may be required- initiate before
    patient has respiratory arrest.

53
Moderate/Severe Attacks
  • Rehydration IV usually warranted- BP will drop
    once on ventilator.
  • Bronchodilators are maintained on ventilator.
  • IV Magnesium Sulfate has some usefulness for
    bronchial relaxation.
  • Once improved, discharge considered once FEV1 or
    PEFR?70 of predicted or personal best.
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