Updated: 7/16/2018

Asthma

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Questions
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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)
          • Oozone 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)
    • 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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Questions (13)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.PL.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? Review Topic

QID: 106823
1

IL-5

40%

(2/5)

2

Major basic protein

0%

(0/5)

3

IgM

0%

(0/5)

4

IL-8

20%

(1/5)

5

Interferon-gamma

20%

(1/5)

M1

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PREFERRED RESPONSE 2

(M1.PL.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? Review Topic

QID: 106790
1

Inspiratory stridor

20%

(14/71)

2

Increased breath sounds

14%

(10/71)

3

Friction rub

1%

(1/71)

4

Kussmaul's sign

4%

(3/71)

5

Pulsus paradoxus

55%

(39/71)

M1

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PREFERRED RESPONSE 5

(M1.PL.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? Review Topic

QID: 106808
1

Pulmonary function tests

3%

(2/61)

2

Methacholine challenge test

92%

(56/61)

3

CT scan

2%

(1/61)

4

Chest ragiograph

0%

(0/61)

5

Allergy testing

2%

(1/61)

M1

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PREFERRED RESPONSE 2

(M1.PL.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? Review Topic

QID: 100810
1

Abnormal chest radiograph

14%

(1/7)

2

Normal FEV1

0%

(0/7)

3

Sputum eosinophils

86%

(6/7)

4

Normal FEV1/FVC

0%

(0/7)

5

Ground glass opacities on chest CT

0%

(0/7)

M1

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PREFERRED RESPONSE 3

(M1.PL.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? Review Topic

QID: 100865
1

IL-2

12%

(1/8)

2

IL-4

50%

(4/8)

3

IL-5

38%

(3/8)

4

IL-10

0%

(0/8)

5

IL-13

0%

(0/8)

M1

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PREFERRED RESPONSE 2

(M1.PL.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? Review Topic

QID: 100931
1

Methacholine

67%

(8/12)

2

Epinephrine

0%

(0/12)

3

Ipratroprium

8%

(1/12)

4

Norepinephrine

8%

(1/12)

5

Albuterol

17%

(2/12)

M1

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PREFERRED RESPONSE 1
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(M1.PL.18) IL-5 plays an essential role in which of the following disease processes? Review Topic

QID: 100821
1

Septic shock

0%

(0/10)

2

Viral infection

10%

(1/10)

3

Transplant rejection

10%

(1/10)

4

Extrinsic asthma

80%

(8/10)

5

Sarcoidosis

0%

(0/10)

M1

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PREFERRED RESPONSE 4

(M1.PL.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? Review Topic

QID: 100828
FIGURES:
1

Sensitization

25%

(1/4)

2

Early Activation

25%

(1/4)

3

Late Activation

50%

(2/4)

4

Resolution

0%

(0/4)

5

Remodeling

0%

(0/4)

M1

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PREFERRED RESPONSE 3
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