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.