Asthma and Food Allergy Flashcards
Asthma
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
Atopy
Presdisposition to Th2 responses and IgE production to common, harmless substances
Types on non-allergic asthma
- True non-allergic asthma
- Diseases that mimick allergic and non-allergic asthma
Asthma is not a disease. but a . . .
. . .syndrome
If a patient has asthma symptoms but no known allergies, the diagnosis is . . .
. . . non-allergic asthma until proven otherwise
Symptoms vs signs
- Symptom: Something the patient reports
- Sign: Something the physician observes
Looking for asthma on physical exam
- 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)
The biggest part of diagosing any allergic disease
History!!!!
Clinical tests for allergy
- 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.
- Serology for allergic IgE: May demonstrate possibility of allergy, but not all individuals who are positive will be allergic. Not totally sensitive or specific.
- Inhalant challenge: Patient enters a room with an aeroallergen of known concentration and response is observed.
Quantitative documentation of airway obstruction
- 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)
Healthy FEV1/FVC
~0.8 or 80%
Pathologic demarkation for FEV1/FVC
<0.7
A finding of 0.7 or below is diagnostic for airway obstruction
Reversible airway obstruction diagnosis
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
Differential diagnosis for allergic asthma
- Exercise-induced asthma
- Cold-induced asthma
- Viral infection-induced asthma
- Asthma induced by NSAID
Differential diagnosis for entire asthma syndrome
- 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
Potential causes of reduced airflow
- 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.
Ohm’s law for fluid mechanics
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
Resistance in fluid mechanics
airway/bronchial hyper-responsiveness
The bronchoconstrictive and coughing response that is maladaptive in asthma
The most potent bronchoconstricting agents known
The cysteinyl leukotrienes (LTC4, LTD4, and LTE4)
What molecular mechanisms account for bronchoconstriction in asthma?
- IgE-mediated MC degranulation
- Action of histamine and other vascular activators on endothelium, leading to occlusive edema on the bronchus
- Action of cysteinyl leukotrienes on bronchial smooth muscle to tightly constrict it
IL-4
promotes B cells to undergo isotype switching to IgE production and the development of Th2 cells
IL-13
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
IL-5
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).
late phase allergen response
influx and activation of eosinophils, basophils, and other inflammatory cells. renewed or continued inflammation and symptoms occur without repeated allergen exposure
How is it thought that allergic asthma starts?
- 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
Non-immunological effects of epithelial activation that may lead to airway obstruction
- 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)
Common triggers for allergic asthma
- Animal dander
- Cockroaches
- Dust mite allergen
- Pollens
- Molds
Prevention and Treatment of allergic asthma
- 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)
Differential for food allergy
- 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
Staphylococcal enterotoxin A targets. . .
. . . the vomitting center of the brain via vagal afferent neurons in the gut.
Manifestations of food allergies
- GI symptoms: nausea, vomitting, diarrhea, abdominal pain, upset/discomfort
- Mucocutaneous symptoms: Urticaria, angioedema, flushing, rash
- Respiratory symptoms: Acute rhinitis, conjunctavitis, bronchospasm
- Systemic symptoms: anaphylaxis
Rhinitis
Nasal congestion and runny nose
Urticaria
hives
Angioedema
Swelling of the skin
Pollen-food cross-reactivity
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”
Food-dependent exercise induced anaphylaxis
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.
Post-prandial flushing syndromes
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.
Vasovagal responses
after eating a patient may have tachycardia (rapid heart rate), nausea, vomiting, and lightheadedness
Adverse food reactions that seem to be a mixture of IgE mediated mast cell activation and cell-mediated inflammation
- 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.
Desensitization
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)
Treatments for food allergy-mediated anaphylaxis
- Epinhephrine
- Oral activated charcoal
- Albuterol (when respiratory symptoms are involved)
- Prednisone (to prevent late-phase)
- Diphenylhydramine (to prevent late-phase)
How to run a skin prick test
- Wash area
- Make markers for +, -, and letters for allergens
- control is pure histamine
- control is diluent (50% glycerin)
- Experimental protein at fixed concentration in diluent
- 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
- Prick ever so slightly and twist
- Wait 15 minutes and read
Histopathology of asthma
- Goblet cell hypertrophy
- Eosinophilia
- Active inflammation
- Smooth muscle hypertrophy
- Fibrosis (sometimes)
Tiotropium
Anti-cholinergic. Long term bronchodilator for asthma
Vitiligo
Disease causing skin color loss in blotches/patches. Autoimmunity against melanocytes, Type II hypersensitivity
Angioedema without itching or urticaria
Probably not allergic. More likely bradykinin mediated. Binds directly to endothelial cells to mediate edema.
The antihistamine tree
Antihistamines are broken down into anti-H1 and anti-H2
Anti-H1 is broken down into 1st generation and 2nd generation
Ranitidine
Anti-H2 antihistamine. Often perscribed in combination with a 2nd generation anti-H1
Strider
Type of high pitch, musical noise in lung auscultation
____ may mimic bronchial smooth muscle constriction in allergic asthma. This can be detected by ____.
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.
