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Allergy and Immunology > First Aid, Chapter 7 Hypersensitivity Disorders, Asthma > Flashcards

First Aid, Chapter 7 Hypersensitivity Disorders, Asthma Flashcards

1
Q

What cells are increased in the airways of asthmatics?

A

Mainly eosinophils; however, neutrophils, lymphocytes, and other cells are also typical

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2
Q

Are mast cells increased in the airways of asthmatics?

A

Airway mast cells are primarily longstanding tissuedwelling cells. In asthma, the number of mast cells is not increased, but they are activated and show frequent degranulation

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3
Q

What cellular infiltrate in asthmatics is a hallmark of fatal asthma?

A

Neutrophilic accumulation

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4
Q

In asthma, airway cellular recruitment involves what proinflammatory processes?

A
  • Upregulation of adhesion molecule expression
  • Arachidonic acid metabolite production (including LTB4)
  • Chemokine synthesis (including IL-8, monocyte chemotactic protein 1 (MCP1), and RANTES)
  • Cytokine secretion (IL-1, IL-4, 5, 9, 10, 13, 16, TNFa IL-6, GM-CSF, and transforming growth factor beta [TGFB).
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5
Q

What do Th2 cytokines do in asthma?

A

Th2 cytokines (IL-4, 5, 13) induce isotype switching of B lymphocytes to IgE-producing plasma cells and support eosinophil survival, whereas others promote mast cell (stem cell factor, SCF) and basophil (IL-3) development.

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6
Q

What are the changes that occur in the airway smooth muscle in asthmatics?

A

Airway smooth muscle is hypertrophied in the smaller airways and hyperplastic in the larger airways.

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7
Q

How much is airway wall thickness increased in asthma?

A

Asthmatics have increased airway wall thickness (50–300% in fatal asthma and 10–100% in nonfatal asthma compared with nonasthmatics).

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8
Q

What tissues and layers does thickening occur in in asthmatics? What materials are some of the layers made of and what cells are they produced by?

A

Thickening occurs in smooth muscle, epithelium, submucosa, adventitia, and mucosal glands. Angiogenesis also occurs. Thickening of the lamina reticularis occurs below the basement membrane, composed largely of collagen types III and V, likely produced by myofibroblasts beneath the epithelium.

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9
Q

What are mucus plugs composed of?

A

Mucus, serum proteins, inflammatory cells, and cellular debris.

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10
Q

What causes excess mucus in asthma?

A

Excess mucus is due to hypertrophy and hyperplasia of submucosal glands, promoted by IL-9.

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11
Q

How does the epithelia in asthmatics become damaged?

A

Damage to the epithelial cells may be due to eosinophil-derived products, active radicals of oxygen, or proteins from neutrophils or mast cells (e.g., tryptase, chymase).

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12
Q

When epithelia is repaired in asthmatics, what is the resultant tissue like compared to normal tissue?

A

Instead of pseudostratified, ciliated columnar cells, the regenerated cells are simple, stratified, nonciliated epithelium or goblet cells.

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13
Q

What are characteristic features of asthmatic sputum?

A
  • Curschmann’s spirals: Associated with excess mucus production (see Figure 5-9).
  • Creola bodies: Clusters of surface airway epithelial cells (Figure 5-9).
  • Charcot-Leyden crystals (CLC): A classic finding. The CLC protein is produced in eosinophils and released in eosinophilic disorders, including asthma. These appear as colorless, needle-shaped structures (Figure 5-9).)
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14
Q

Does early life exposure to pet and farm animals protect against asthma?

A

No, just protects against allergies.

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15
Q

Sensitization to what allergen by age 6 is associated with persistent asthma by age 11?

A

Alternaria

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16
Q

Exposure to what allergen in older children correlates with wheezing and airway hyperresponsiveness?

A

Dust mites

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17
Q

What are the gender differences seen in asthma?

A

Boys have a higher prevalence than girls until the ages of 15–17; the opposite is seen after that age.

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18
Q

How do viruses and other infections associate with asthma?

A

Viruses and other infections are associated with asthma in several ways:

  • Viruses such as RSV may produce symptoms of asthma in infants (see Bronchiolitis section).
  • In asthmatics, viral infections are a common trigger.
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19
Q

What is the role of chromosome 5q?

A

On chromosome 5q, the genes 5q31-33, known as the interleukin-4 (IL-4) gene cluster, may play an important role in inflammation in atopy and asthma

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20
Q

What is the role of IL-4 in atopy?

A

IL-4 plays a key role in inducing synthesis of IgE and Th2 differentiation. A polymorphism in the IL-4 promoter was identified that increased transcription of IL-4 with resultant high serum levels of IgE.

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21
Q

What gene polymorphisms are associated with decreased responses to b2 agonists?

A

The β2-adrenoreceptor gene, also in this region, is highly polymorphic. Polymorphisms including Arg-16 → Gly and Gln 27 → Glu are associated with decreased responses to β2 agonists.

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22
Q

What is CD14? What is a polymorphism of CD14 associated with?

A

CD14, is a recognition coreceptor with TLR4 for endotoxin (bacterial lipopolysaccharide) and is important for innate responses to bacterial infection, leading to a shift towards Th1 cell responses. A polymorphism in a soluble form of CD14 (sCD14) was associated with high levels of sCD14 and low levels of IgE.

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23
Q

What is the significance of chromosome 20p13? What gene is found on it?

A

Chromosome 20p13 was found to contain a locus that was linked to asthma. On the locus, the disintegrin and metalloproteinase (ADAM 33) gene was associated with asthma. It may play a role in the function of airway smooth muscle leading to airway hyperreactivity or remodeling.

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24
Q

What are chitinase-like proteins (including chitotriosidase [CHIT 1] and YKL-40)?

A

An area of research as susceptibility genes for asthma.

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25
Q

What are diagnostic features of asthma?

A

Recurrent episodes of airflow obstruction (i.e., obstruction is at least partially reversible; an increase in forced expiratory volume in 1 second (FEV1) >200 mL and > 12% from baseline after inhaling short-acting β2 agonist [SABA] is specified in the American Thoracic Society definition of reversibility) or airway hyperresponsiveness (the airways react too readily and too much; demonstrated by methacholine challenge).

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26
Q

What causes loss of function over time with asthma?

A

Declining and irreversible loss of lung function over time is generally attributed to airway remodeling, which is thought to be a tissue response to recurrent injury or inflammation.

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27
Q

What are features of remodeling in asthma?

A
  • Subepithelial fibrosis
  • Increase in thickness of the small airways
  • Angiogenesis
  • Mucosal gland hypertrophy
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28
Q

What is the most frequent infectious cause of asthma exacerbations?

A

Rhinovirus

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29
Q

What percentage of children will have episodes of wheezing in the first 3 years of life attributable to viral respiratory tract infections?

A

Fifty percent, they often respond to asthma treatment even though they don’t have a diagnosis.

30
Q

What percentage of asthmatics will have symptoms prior to age 5?

A

50-80%

31
Q

What are the three types of wheezers in children?

A
  • Transient early wheezers, children who wheezed when they were younger than 3 years old and resolved by the time they were 6 years old, the most prevalent type
  • Persistent wheezers, children whose wheezing began when they were younger than 3 years old and continued through 6 years old
  • Late-onset wheezers, children whose onset of wheezing was at 6 years old
32
Q

What are the criteria for the asthma predictive index?

A

Any One of the Following Major Criteria:

  • parental asthma
  • physician diagnosis of atopic dermatitis
  • sensitization to aeroallegens

Any two of the following minor criteria:

  • sensitization to foods
  • > 4% of eosinophils
  • wheezing apart from colds
33
Q

What percentage of children with frequent wheezing and a positive API will have asthma during school years? What percentage of children with frequent wheezing with a negative API will not have asthma during school years?

A

Roughly, two thirds of children with frequent wheezing and a positive asthma predictive index will have asthma during school years; by contrast, > 95% of wheezing toddlers with a negative index did not have asthma during school years.

34
Q

What is the utility of the API? What are the guidelines that recommend use of API?

A

The 2007 National Heart Lung and Blood Institute (NHLBI) guidelines suggest the use of the asthma predictive index as a tool to help determine when to initiate long-term control therapy

35
Q

What are the guidelines to start long-term control therapy in children less than 4 years old?

A
  • At least four episodes of wheezing in the past year that lasted more than 1 day and affected sleep, and that had a positive asthma predictive index (see Table 7-8)
  • Consider for patients who require symptomatic treatment more than 2 days per week for more than 4 weeks
  • Consider in patients requiring oral steroids twice in 6 months
  • Consider during periods or seasons of previously documented risk (e.g., during seasons of viral respiratory infections)
36
Q

Which of the following is the biggest risk factor for persistent asthma at age 6 in a 3-year-old with recurrent wheezing? A. Asthma in a parent B. Asthma in a sibling C. Wheezing apart from colds D. Allergic rhinitis in a sibling

A

A. Asthma in a parent.

37
Q

What 4 components is the long-term management of asthma divided into?

A

Assessing and monitoring asthma severity and asthma control based on:

1) Impairment - frequency and intensity of symptoms and the functional limitation of the patient.
2) Risk - likelihood of exacerbation, decline in lung function, or adverse effects of medication.
3) Severity - intrinsic intensity of disease and should be assessed prior to a patient being on long-term control medications.
4) Control - degree to which asthma is controlled by treatment and the goals of treatment are met

38
Q

What environmental factors and comorbid conditions need to be controlled in asthmatics?

A

Allergens, ABPA, GERD, NSAID exacerbation

39
Q

What percentage of asthmatics have GERD? What is the mechanism of worsening asthma?

A

Up to 45-65%. Bronchospasm due to esophageal irritation and vagal reflex or microaspiration.

40
Q

What percentage of adults have asthma episodes triggered by NSAIDs?

A

5-10%.

41
Q

What is the mechanism of NSAID induced symptoms in samter’s triad? When is the onset of NSAID sensitivity?

A

These reactions are mediated by eicosanoid metabolism with leukotriene production, not IgE. Can be years after asthma and nasal polyps occur (if Samter’s triad).

42
Q

What is the onset of symptoms after exercise in exercise-induced asthma and when do they resolve?

A

Classically, symptoms have their onset after 10 minutes of aerobic activity and usually resolve 15–30 minutes after exercise.

43
Q

How is exercise-induced bronchospasm diagnosed?

A

Exercise-induced bronchospasm is diagnosed by an FEV1 decrease > 15% after exercise challenge test or history and an appropriate bronchodilator response.

44
Q

What are the treatments of exercise-induced bronchospasm and how effective are they?

A

SABA used shortly before exercise may last for 2–3 hours and be helpful in 80% of patients. A daily leukotriene receptor antagonist can help in 50% of patients.

45
Q

Do pregnant women have worsening or improvement of asthma? What percentage?

A

The classic rule of thumb is that, during pregnancy, approximately one third of asthmatic women improve, one third worsen, and one third remain the same.

46
Q

What are the perinatal risks in uncontrolled asthma in a pregnant woman?

A

Uncontrolled asthma increases perinatal mortality, preeclampsia, preterm birth, and the likelihood of a low-birth-weight infant.

47
Q

What are the preferred asthma medications during pregnancy?

A

Albuterol is the preferred SABA. Budesonide is the preferred inhaled corticosteroid.

48
Q

When classifying asthma severity in all ages, what are the two broad categories you evaluate?

A

Impairment and risk.

49
Q

When classifying asthma severity in children 0-4 years of age, what are the 4 categories within impairment you assess? What is the additional one in age 5-11 and >age 12/adults?

A

1) Symptoms (days per week)
2) Nighttime awakenings (number of times per week or month)
3) SABA use (days per week)
4) Interference with normal activity
Additional one is lung function.

50
Q

When classifying asthma severity in all ages, how does frequency of symptoms correlate to classification?

A

Intermittent - 2 days/week
Moderate Persistent-Daily
Severe Persistent-Throughout the day

51
Q

When classifying asthma severity in children 0-4 years of age, how do nocturnal awakenings correlate to classification?
How does this differ in age 5-11 and children>12/adults?

A 
Age 0-4
Intermittent: 0 
Mild Persistent: 1-2×/month 
Moderate Persistent: 3-4×/month 
Severe Persistent: >1×/week

Age 5-11
Intermittent: 1/week
Severe persistent: often nightly

52
Q

When classifying asthma severity in all ages, how does SABA use correlate to classification?

A

Intermittent - 2 days/week
Moderate Persistent-Daily
Severe Persistent-several times a day

53
Q

When classifying asthma severity in children 0-4 years of age, how does “exacerbations requiring oral steroids” correlate to classification? How does this differ in age 5-11/ >age12/adutls?

A

Age 0-4
Intermittent - 0-1/year
Mild/moderate/severe persistent - greater than or equal to 2 exacerbations in 6 months or >4 wheezing episodes/1year lasting >1day AND risk factors for persistent asthma

Age 5-11 and >12/adults
Intermittent/Mild persistent: 0-1/year
Moderate/severe persistent:
>= 2/year

54
Q

What step should you initiate therapy for each classification of asthma severity in children 0-4 and 5-11 years of age? What is the difference in age >=12 and adults?

A

Intermittent - step 1
Mild persistent - step 2
Moderate persistent - step 3 and consider short course of oral steroids.
severe persistent - step 4 and consider short course of oral steroids.

In children >=12 and adults, for severe persistent it is step 4 or 5 and consider short course oral steroids

55
Q

When assessing asthma control in all ages, what are the two broad categories you evaluate?

A

Impairment and Risk.

56
Q

When assessing asthma control in children 0-4 years of age, what are the 4 categories within impairment you evaluate? What is the additional category you evaluate in children 5-11? What is the additional category in age >=12/adults?

A

1) Symptoms (days per week)
2) Nighttime awakenings (number of times per week or month)
3) SABA use (days per week)
4) Interference with normal activity

Age 5-11:
The additional category in age 5-11 is lung function.

Age >=12/Adult

1) lung function
2) Validated questionnaires

57
Q

When assessing asthma control in children 0-4 years of age, what are the 2 categories within risk you evaluate? In age 5-11, age>=12/adults what is the additional category?

A

1) Exacerbations requiring oral steroids/year
2) Treatment related adverse effects
The additional category in age 5-11 is progressive loss of lung function.

58
Q

What makes a child’s asthma (age 0-4) well-controlled? What is the additional parameter in age 5-11? What are the 2 additional parameters in >=12/adults?

A

1) Symptoms less than or equal to twice a week
2) Nocturnal awakenings less than or equal to once a month
3) No interference with normal activity
4) SABA use less than or equal to twice a week
5) 0-1 exacerbations requiring oral steroids a year

Age 5-11 Additional parameter is lung function:
Age 5-11
FEV1 >80% predicted
FEV1/FVC > 80%

Age>=12/adult:
1) FEV1>=80% predicted/ or peak flow >80% personal best
2) Validated questionnaire
ATAQ - 0
ACQ =20
59
Q

What makes a child’s asthma (age 0-4) not well-controlled? What is the additional parameter in age 5-11?

A

1) Symptoms >2days/week or multiple times on greater than or equal to 2 days a week
2) Nocturnal awakenings >1x/month
3) Some interference with normal activity
4) SABA use >2 days/week
5) 2-3 exacerbations requiring oral steroids a year

Age 5-11 additional category
Lung function:
FEV1 60-80% predicted
FEV1/FVC 75-80%

Age>=12/adult:
1) FEV1 60-80% predicted/personal best peak flow
2) Validated questionnaire
ATAQ - 1-2
ACQ >= 1.5
ACT 16-19
60
Q

What makes a child’s asthma (age 0-4) very poorly controlled? What is the additional parameter in age 5-11? Age >12/adult?

A

1) Symptoms throughout the day
2) Nocturnal awakenings >1x/week
3) Extreme limitations in activity
4) SABA use several times a day
5) >3 exacerbations requiring oral steroids a year

Additional category age 5-11 lung function
FEV1 =12/adults:
FEV1

61
Q

When assessing asthma control in all ages, what are the recommended actions for each level of control?

A

Well-controlled: Maintain current step. Follow up every 1–6 months. Consider stepdown if well controlled >3 months.

Not well-controlled: Step up one step.

Very poorly controlled: Step up one to two steps. Consider short course of oral steroids.

62
Q

What is the normal FEV1/FVC for each age range?

A 
Normal FEV1/FVC: 
8–19 yr     85% 
20–39 yr   80% 
40–59 yr   75% 
60–80 yr   70%
63
Q

When classifying asthma severity in all age 5-11, how does lung function correlate to classification? Age >=12/adults?

A 
Age 5-11
Intermittent: Normal FEV1 between exacerbations FEV1 > 80% predicted; FEV1/FVC > 85%
Mild persistent:
FEV1 >80% predicted FEV1/FVC > 80% 
Moderate persistent:
FEV1 60–80% predicted; FEV1/FVC 75– 80%
Severe persistent:
FEV1 =12/adults:
Intermittent: Normal FEV1 between exacerbations FEV1 > 80% predicted; FEV1/FVC normal
Mild persistent:
FEV1 >80% predicted FEV1/FVC normal 
Moderate persistent:
FEV1 60–80% predicted; FEV1/FVC reduced 5%
Severe persistent:
FEV1  5%
64
Q

What is the step-wise approach for age 0-4 in managing asthma?

A

Step 1: SABA PRN
Step 2: Low-dose ICS (alternative cromolyn or montelukast)
Step 3: Medium-dose ICS
Step 4: Medium-dose ICS + LABA or montelukast
Step 5: High-dose ICS + LABA or montelukast
Step 6: High-dose ICS + LABA or montelukast
+
oral steroids

65
Q

What is the step-wise approach for age 5-11 in managing asthma?

A 
Step 1: SABA PRN
Step 2: Low-dose ICS (alternative cromolyn, LTRA, nedocromil, or theophylline)
Step 3: Low-dose ICS + LABA, LTRA, or theophylline or medium-dose ICS 
Step 4: Medium-dose ICS+ LABA (alternative Medium-dose ICS + LTRA or theophylline)
Step 5: High-dose ICS + LABA (alternative high dose ICS + LTRA or theophylline)
Step 6: High-dose ICS + LABA or montelukast
\+
oral steroids (alternative high-dose ICS + LTRA or theophylline +oral steroids)
66
Q

What is the step-wise approach for age >=12 and adults in managing asthma?

A

Step 1: SABA PRN
Step 2: Low-dose ICS (alternative cromolyn, LTRA, nedocromil, or theophylline)
Step 3: Low-dose ICS + LABA or medium-dose ICS (alternative low-dose ICS + LTRA, theophylline, or zileuton)
Step 4: Medium-dose ICS+ LABA (alternative Medium-dose ICS + LTRA or theophylline or zileuton)
Step 5: High-dose ICS + LABA and consider omalizumab
Step 6: High-dose ICS + LABA +oral steroids +consider omalizumab

67
Q

What is vocal cord dysfunction?

A

VCD is known as “the asthma imitator.” It is the paradoxical adduction of vocal cords during inspiration; however, it can happen in expiration as well.

68
Q

What are the clinical features of VCD?

A
  • Wheezing
  • Stridor
  • Hoarseness
  • Dysphonia
  • Chest tightness
  • Cough
69
Q

Who are the typical VCD patients?

A
  • Young female overachievers and athletes

- Middle-aged women with psychiatric history or health care association

70
Q

What are exam features of VCD? Do bronchodilators help? What does spiro in VCD show? How is it diagnosed?

A

Physical examination reveals inspiratory wheezing over larynx. Bronchodilators can worsen the condition. Spirometry shows reduced FEV1 and FVC with a preserved ratio as well as a blunted inspiratory loop. Diagnosis is confirmed with fiberoptic laryngoscopy while patient is symptomatic.

71
Q

What are the short term and long term treatments for VCD?

A

Short term: heliox inhalation, topical lidocaine spray, intermittent positive pressure ventilation

Long term: panting, speech therapy, botox injections into the vocal cords

Allergy and Immunology (68 decks)

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