Asthma and Food Allergy

Question 1

Asthma

Answer 1

Respiratory syndrome in which affected patients have episodic shortness of breath, wheezing, coughing (productive or nonproductive), and chest tightness or pain.

These symptoms occur because the airway is obstructed and flow is non-laminar

Question 2

Atopy

Answer 2

Presdisposition to Th2 responses and IgE production to common, harmless substances

Question 3

Types on non-allergic asthma

Answer 3

1. True non-allergic asthma
2. Diseases that mimick allergic and non-allergic asthma

Question 4

Asthma is not a disease. but a . . .

Answer 4

. . .syndrome

Question 5

If a patient has asthma symptoms but no known allergies, the diagnosis is . . .

Answer 5

. . . non-allergic asthma until proven otherwise

Question 6

Symptoms vs signs

Answer 6

• Symptom: Something the patient reports
• Sign: Something the physician observes

Question 7

Looking for asthma on physical exam

Answer 7

• Tachypnea
• Coughing
• Wheezing / musical respiratory noises
• Signs of other allergic diseases (Dark blue under eyes indicating venous congestion, red, swollen, puffy eyes, edema and pale blue lining nose, eczema, atopic dermatitis, hives, cyanotic fingernails)

Question 8

The biggest part of diagosing any allergic disease

Answer 8

History!!!!

Question 9

Clinical tests for allergy

Answer 9

1. Aeroallergen skin test: Droplet + skin prick which produces a hive in ~15-20 minutes. Has the advantage of being functional, not just correlative. It is thus a specific test.
2. Serology for allergic IgE: May demonstrate possibility of allergy, but not all individuals who are positive will be allergic. Not totally sensitive or specific.
3. Inhalant challenge: Patient enters a room with an aeroallergen of known concentration and response is observed.

Question 10

Quantitative documentation of airway obstruction

Answer 10

• Spirometry
• Set of pulmonary function tests
• Give the forced vital capacity or FVC (total amount of air exhaled on forced exhalation) and the forced expiratory volume in 1 second or FEV1 (the volume exhaled in the first second on forced exhalation)

Question 11

Healthy FEV1/FVC

Answer 11

~0.8 or 80%

Question 12

Pathologic demarkation for FEV1/FVC

Answer 12

<0.7

A finding of 0.7 or below is diagnostic for airway obstruction

Question 13

Reversible airway obstruction diagnosis

Answer 13

This diagnosis is made if the patient has airway obstruction (FEV1/FVC) which then improves (usually by ~12%) following inhalation of a beta-2 receptor agonist

Here the diagnosis of asthma is very likely to be made in context

Question 14

Differential diagnosis for allergic asthma

Answer 14

• Exercise-induced asthma
• Cold-induced asthma
• Viral infection-induced asthma
• Asthma induced by NSAID

Question 15

Differential diagnosis for entire asthma syndrome

Answer 15

• COPD (obstruction generally not reversible)
• Cystic fibrosis
• Pulmonary embolism
• Heart failure (leading to pulmonary edema)
• Tumor or stenosis in trachea
• Vocal cord spasm
• GERD and aspiration
• Panic disorder

Question 16

Potential causes of reduced airflow

Answer 16

• Increased mucus production
• Hypertrophy or spasm of bronchial smooth muscle
• Vascular leakage from airway-associated vessels causing occlusive edema
• Chronic structural changes (thickening of lamina reticularis and bronchial smooth muscle), aka airway remodeling. May start as reversible and become irreversible.

Question 17

Ohm’s law for fluid mechanics

Answer 17

ΔP = F x R

ie, difference in pressure between x and y is equal to the flow rate between x and y times the resistance between x and y

Question 18

Resistance in fluid mechanics

Answer 18

Question 19

airway/bronchial hyper-responsiveness

Answer 19

The bronchoconstrictive and coughing response that is maladaptive in asthma

Question 20

The most potent bronchoconstricting agents known

Answer 20

The cysteinyl leukotrienes (LTC₄, LTD₄, and LTE₄)

Question 21

What molecular mechanisms account for bronchoconstriction in asthma?

Answer 21

1. IgE-mediated MC degranulation
2. Action of histamine and other vascular activators on endothelium, leading to occlusive edema on the bronchus
3. Action of cysteinyl leukotrienes on bronchial smooth muscle to tightly constrict it

Question 22

IL-4

Answer 22

promotes B cells to undergo isotype switching to IgE production and the development of Th2 cells

Question 23

IL-13

Answer 23

induces B cell isotype switching to IgE synthesis. In addition, IL-13 powerfully stimulates airway mucosal goblet cells to increase mucus production, and it induces “transdifferentiation” other airway cells into new goblet cells. Recall that acute asthma attacks are notable for mucus hypersecretion, and that patients with asthma have airway mucosal goblet cell hypertrophy and hyperplasia

Question 24

IL-5

Answer 24

arguably the most important cytokine with respect to eosinophils, and is critical to their development and survival. Eosinophil recruitment to and activation in the airways is a classic and important part of allergic asthma. As effector cells in allergic asthma, upon activation, eosinophils release granule contents such as myeloperoxidase and eosinophil peroxidase, leading to the generation of reactive oxygen species that contribute to tissue damage (including to airway epithelial cells, see below) and the further activation of airway mast cells (you can start to see some positive feedback loop here). In addition, eosinophils are important sources of a number of cytokines, such as Transforming Growth Factor (TGF)-beta, IL-4, and IL-13. Eosinophils are very (but not totally) dependent on this cytokine, and it therefore became a rational target for asthma therapy (see below).

Question 25

late phase allergen response

Answer 25

influx and activation of eosinophils, basophils, and other inflammatory cells. renewed or continued inflammation and symptoms occur without repeated allergen exposure

Question 26

How is it thought that allergic asthma starts?

Answer 26

* Activation and damage of airway epithelium * Presence of PAMPs/DAMPs * Production of TSLP, IL-25, IL-33 by epithelium * Activation of local dendritic cell * Migration to draining lymph node and activation of T cell to Th2 with bronchial addressing * Activation and class-switching of B cell to IgE * Sensitization of mast cells

Question 27

Non-immunological effects of epithelial activation that may lead to airway obstruction

Answer 27

* Activated epithelial cells induce differentiation of fibroblasts into myofibroblasts * Increased collagen II and III, laminin, and tenascin production * Contribution to airway remodeling and thickening of airway walls * Activated epithelial cells may activate eosinophils to produce TGF-b * TGF-b-mediated fibrosis * Myofibroblasts migrate on new fibrotic scaffold and differentiate into smooth myocytes (hyperplasia of bronchial smooth muscle)

Question 28

Common triggers for allergic asthma

Answer 28

* Animal dander * Cockroaches * Dust mite allergen * Pollens * Molds

Question 29

Prevention and Treatment of allergic asthma

Answer 29

* Allergen avoidance * Allergen immunotherapy (reintroduction/challenge therapy). 90% effective, but takes 3-5 years and money. Promotes IgE class switching to IgG4, providing protection. * Rescue medications: bronchodilators (b2 agonists, a1 antagonists). Fast acting, but don't really address underlying issue. Still, may be used preventatively in some cases as well. * **Albuterol** * **LABAs (long-acting beta agonists), actually useful preventatively in combination with below** * **Tiotropium (long acting alpha antagonist, useful preventatively, antimuscarinic)** * Controller medications: Anti-inflammatories. Slow acting, not going to help much during an asthma attack, but will prevent asthma attacks or make them more manageable in future * **Corticosteroids** * **Montelukast (cysteinyl leukotriene antagonist)** * **Omalizumab (anti-IgE)** * **Dupilumab (anti-IL-4R and IL-13R common alpha chain)**

Question 30

Differential for food allergy

Answer 30

* Lactose intolerance (or other intolerance) * Celiac's * Staphylococcal food poisoning * Post-prandial flushing syndromes caused by some carcinoid tumors * Vasovagal responses * GI structural abnormalities * Food intoxication * Phobia, panic, behavioral aversion

Question 31

Staphylococcal enterotoxin A targets. . .

Answer 31

. . . **the vomitting center of the brain via vagal afferent neurons in the gut.**

Question 32

Manifestations of food allergies

Answer 32

* GI symptoms: nausea, vomitting, diarrhea, abdominal pain, upset/discomfort * Mucocutaneous symptoms: Urticaria, angioedema, flushing, rash * Respiratory symptoms: Acute rhinitis, conjunctavitis, bronchospasm * Systemic symptoms: anaphylaxis

Question 33

Rhinitis

Answer 33

Nasal congestion and runny nose

Question 34

Urticaria

Answer 34

hives

Question 35

Angioedema

Answer 35

Swelling of the skin

Question 36

Pollen-food cross-reactivity

Answer 36

Some **thin-skinned fruits** (e.g., **apples, pears, peaches, plums, cherries**) and other foods contain proteins that structurally resemble pollen proteins These fruit proteins tend to be heat and acid labile, so they cause local symptoms only, not anaphylaxis "I'm fine with Granny's apple pie, but I can't eat raw apples"

Question 37

Food-dependent exercise induced anaphylaxis

Answer 37

Condition in which a patient develops anaphylaxis only after eating a given food around the time of (i.e., shortly before or shortly after) exercise The peptides derived from foods are different when they are digested in a resting state vs. in an exercising state.

Question 38

Post-prandial flushing syndromes

Answer 38

After a meal, a patient may experience flushing, diarrhea, bloating, nausea, vomiting, wheezing, and tachycardia. This is due to the rapid release of vasoactive mediators such as serotonin by a tumour.

Question 39

Vasovagal responses

Answer 39

after eating a patient may have tachycardia (rapid heart rate), nausea, vomiting, and lightheadedness

Question 40

Adverse food reactions that seem to be a mixture of IgE mediated mast cell activation and cell-mediated inflammation

Answer 40

* **food induced or exacerbated atopic dermatitis** (i.e., eczema made worse by eating certain foods) * **food induced contact dermatitis**, where skin contact with a food causes a localized rash * **allergic eosinophilic esophagitis and gastritis**, where ingestion of one or more trigger foods leads to the accumulation of eosinophils into the walls of the esophagus or stomach, respectively * **food triggered asthma**, in which eating a trigger food induces wheezing, shortness of breath (aka, dyspnea), cough, and chest tightness.

Question 41

Desensitization

Answer 41

Generally **temporary** state in which mast cells are rendered non-responsive to an allergen. But **to remain desensitized, the patient must continue being exposed to the allergen** – if exposure is stopped for more than 24-72 hours, sensitization recurs (that is, the patient is going to have an allergic reaction if s/he is reexposed to the allergen after this break in exposure)

Question 42

Treatments for food allergy-mediated anaphylaxis

Answer 42

* Epinhephrine * Oral activated charcoal * Albuterol (when respiratory symptoms are involved) * Prednisone (to prevent late-phase) * Diphenylhydramine (to prevent late-phase)

Question 43

How to run a skin prick test

Answer 43

1. Wash area 2. Make markers for +, -, and letters for allergens 3. + control is pure histamine 4. - control is diluent (50% glycerin) 5. Experimental protein at fixed concentration in diluent 6. **Also include a nonstandard pure antigen if you can**, because most standard antigens provided by companies do not contain the full range of possible allergenic epitopes 7. Prick ever so slightly and twist 8. Wait 15 minutes and read

Question 44

Histopathology of asthma

Answer 44

* Goblet cell hypertrophy * Eosinophilia * Active inflammation * Smooth muscle hypertrophy * Fibrosis (sometimes)

Question 45

Tiotropium

Answer 45

Anti-cholinergic. Long term bronchodilator for asthma

Question 46

Vitiligo

Answer 46

Disease causing skin color loss in blotches/patches. Autoimmunity against melanocytes, Type II hypersensitivity

Question 47

Angioedema without itching or urticaria

Answer 47

Probably not allergic. More likely bradykinin mediated. Binds directly to endothelial cells to mediate edema.

Question 48

The antihistamine tree

Answer 48

Antihistamines are broken down into anti-H1 and anti-H2 Anti-H1 is broken down into 1st generation and 2nd generation

Question 49

Ranitidine

Answer 49

Anti-H2 antihistamine. Often perscribed in combination with a 2nd generation anti-H1

Question 50

Strider

Answer 50

Type of high pitch, musical noise in lung auscultation

Question 51

\_\_\_\_ may mimic bronchial smooth muscle constriction in allergic asthma. This can be detected by \_\_\_\_.

Answer 51

**Laryngeal angioedema** may mimic bronchial smooth muscle constriction in allergic asthma. This can be detected by **change in the patient's voice. Ask, "is this the way your voice normally sounds?" This is not necessarily of allergic etiology.**