Updated: 3/8/2020

Asthma

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Topic
Snapshot
  • A five-year-old with severe asthma is being treated in the ER with a IV aminophylline drip. The child is slowly becoming sleepy and less responsive. Physical exam reveals less wheezing than on admission. Representative lung histology is shown.
Introduction
  • Definition
    • episodic and reversible bronchoconstriction 
      • with bronchioles being the most susceptible respiratory segment
    • result of
      • inflammation
      • bronchial smooth muscle hypertrophy and hyperactivity
      • mucus plugging
Classification
  • Types
    • extrinsic
      • typically seen in children with a genetic predisposition
      • type I hypersensitivty to an inhaled (external) allergen
        • proceeds by specific stages
          • sensitization
            • CD4 TH2 cells produce cytokines (IL-4 and IL-5) when initially stimulated by an allergen 
              • IL-4 induces antibody isotype switch to IgE 
              • IL-5 induces eosinophil activation
          • early activation
            • mast cells are activated by cross-linking of IgE and release immune activating substances (histamine, leukotrienes, and acetylcholine) when allergen is presented again 
              • histamine results in bronchoconstriction, chemotaxis for immune cells, and mucus production
              • acetylcholine results in bronchoconstriction (parasympathetic mediated)
              • leukotrienes C4, D4, and E4 induce bronchoconstriction
          • late activation
            • eosinophils are activated    
              • recruited by eotaxin
              • produce major basic protein, which causes further constriction/damage in the airways  
    • intrinsic
      • non-allergen mediated
      • induced by
        • infection
          • viral URI (RSV, rhinovirus, and parainfluenza virus)
        • behavioral
          • exertion and stress
        • chemical
          • drug sensitivity (NSAIDs and aspirin)
          • ozone produced free-radicals
    • status asthmaticus
      • life-threatening asthma attack that does not respond to standard treatments
Presentation
  • Symptoms
    • wheezing
    • cough
    • mucus production
    • note: a child who is becoming sleepy and less responsive is most likely failing, retaining CO2 (case intro) and needs intubation
  • Physical exam
    • tachycardia
    • tachypnea with use of accessory muscles
      • result of reduced I/E ratio
      pulsus paradoxus
      • result of increased lung volume and vascular resistance
    • auscultation
      • prolonged expiratory wheezes (sometimes inspiratory)
      • high pitched sibilant rhonchi
      • dyspnea
      • persistent cough with hyperinflation of the lungs
Imaging
  • Chest radiograph
    • normal or hyperinflation
Studies
  • Labs
    • ABG
      • may initially show respiratory alkalosis
      • if CO2 is normal, respiratory failure may be imminent 
      • elevated CO2 (respiratory acidosis) are ominous signs and patient likely requires intubation
  • Pulmonary function tests 
    • peak flows are diminished
    • obstructive pattern may be seen when symptomatic (↓ FEV1/FVC)
      • improvement with bronchodilator administration
    • high airway resistance
  • Methacholine challenge  
    • provacative measure of hyperactivity in a well patient
    • functions as a muscarinic cholinergic agonist
    • reduction of FEV1 by > 20% is diagnostic of asthma
  • Skin testing
    • may result in hypersensitivity response to allergen when presented into skin (really diagnoses atopy, not asthma)
  • Histological changes 
    • terminal bronchioles
      • mucus plugs
        • Curschmann's spirals  
          • presence of trapped epithelial cells killed by eosinophil produced major basic protein
        • Charcot-Leyden crystals
          • aggregated eosinophils
      • increased mucus-producing cells
    • bronchi
      • thickened basement membrane
        • unique to asthma
      • hypertrophy of submucosal glands and smooth muscle
        • also seen in other lung disorders including chronic bronchitis
      • increased immune cell presence
 
Treatment
  • Acute exacerbation
    • oxygen
    • inhaled beta-2 agonists  
      • short acting preferred (e.g albuterol)
      • appropriate for exercise induced asthma
        • administer before exertion in known asthmatics
    • systemic corticosteroids (PO or IV)
  • Status asthmaticus
    • oxygen, bronchodilators, and steroids
    • sympathomimetic bronchodilators (e.g. epinephrine)
    • intubation and mechanical ventilation
  • Maintenance treatment
    • inhaled corticosteroids (mainstay)
    • long-acting bronchodilators (beta-2 agonists)
      • in combintation with inhaled corticosteroids (increased risk of death if used without inhaled corticosteroid)
    • montelukast
    • cromolyn
      • rarely used; supplemental treatment for exercise-induced asthma
    • theophylline
      • phosphodiesterase inhibitor; rarely used
    • ipratropium bromide
      • an anticholinergic that inhibits the contraction of smooth muscle
      • used in the elderly with an asthmatic component to their COPD
    • tiotropium
      • more recently shown to be efficacious and safe
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(M1.PL.15.75) A 6-year-old boy is brought to the pediatrician by his foster father because he is concerned about the boy's health. He states that at seemingly random times he will have episodes of severe difficulty breathing and wheezing. Upon questioning, the pediatrician learns that these episodes do not appear to be associated with exercise, irritants, or infection. The pediatrician suspects the child has a type of asthma that is associated with eosinophils. In this type of asthma, what is released by the eosinophils to cause bronchial epithelial damage? Tested Concept

QID: 106823
1

IL-5

17%

(9/54)

2

Major basic protein

52%

(28/54)

3

IgM

2%

(1/54)

4

IL-8

7%

(4/54)

5

Interferon-gamma

17%

(9/54)

M 1 C

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(M1.PL.15.75) A 16-year-old boy with a history of severe, persistent asthma presents to the emergency department with severe shortness of breath and cough. He states that he was outside playing basketball with his friends, forgot to take his inhaler, and began to have severe difficulty breathing. On exam, he is in clear respiratory distress with decreased air movement throughout all lung fields. He is immediately treated with beta-agonists which markedly improve his symptoms. Prior to treatment, which of the following was most likely observed in this patient? Tested Concept

QID: 106790
1

Inspiratory stridor

26%

(38/149)

2

Increased breath sounds

15%

(23/149)

3

Friction rub

2%

(3/149)

4

Kussmaul's sign

5%

(7/149)

5

Pulsus paradoxus

50%

(74/149)

M 1 C

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(M1.PL.15.75) A 6-year-old male is brought to the pediatrician by his mother because she is concerned about his breathing. She states that every once in a while he seems to have bouts of coughing but doesn't have any significant difficulty breathing. She demands that the pediatrician begin treatment with albuterol as she is convinced that her child has asthma. The pediatrician, not fully convinced, states that he will run a test that will help to rule out asthma as a diagnosis. To which of the following tests is the pediatrician referring? Tested Concept

QID: 106808
1

Pulmonary function tests

12%

(14/121)

2

Methacholine challenge test

85%

(103/121)

3

CT scan

1%

(1/121)

4

Chest ragiograph

0%

(0/121)

5

Allergy testing

1%

(1/121)

M 2 B

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(M1.PL.13.62) A 4-year-old boy presents to the Emergency Department with wheezing and shortness of breath after playing with the new family pet. Which of the following immunological factors is most involved in generating the antibodies necessary for mast cell Fc-receptor cross-linking and degranulation? Tested Concept

QID: 100865
1

IL-2

8%

(5/60)

2

IL-4

58%

(35/60)

3

IL-5

20%

(12/60)

4

IL-10

8%

(5/60)

5

IL-13

3%

(2/60)

M 1 C

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(M1.PL.13.128) A 12-year-old female presents to your office complaining of several brief episodes of shortness of breath of varying severity. Which of the following substances would lead to a decrease in FEV1 of 20% if the patient has asthma? Tested Concept

QID: 100931
1

Methacholine

75%

(48/64)

2

Epinephrine

2%

(1/64)

3

Ipratroprium

6%

(4/64)

4

Norepinephrine

6%

(4/64)

5

Albuterol

11%

(7/64)

M 2 E

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(M1.PL.13.25) A patient presents with difficultly breathing after adopting a new kitten. The cell pictured in Figure A plays a role in what phase of this disease process? Tested Concept

QID: 100828
FIGURES:
1

Sensitization

19%

(10/54)

2

Early Activation

50%

(27/54)

3

Late Activation

28%

(15/54)

4

Resolution

2%

(1/54)

5

Remodeling

0%

(0/54)

M 1 D

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(M1.PL.12.7) A 7-year-old male is admitted to the hospital with his fourth episode of wheezing and dyspnea. His symptoms are exacerbated by mold and pollen. Which of the following is most likely to be observed in this patient? Tested Concept

QID: 100810
1

Abnormal chest radiograph

3%

(2/63)

2

Normal FEV1

0%

(0/63)

3

Sputum eosinophils

90%

(57/63)

4

Normal FEV1/FVC

3%

(2/63)

5

Ground glass opacities on chest CT

3%

(2/63)

M 1 D

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