Allergy and Asthma

• Differentials of asthma

  • Hyperventilation in teenagers
  • Viral induced wheeze
  • Primary ciliary dyskinesia
  • Bronchiectasis
  • Cystic fibrosis
  • Vocal cord dysfunction
  • Persistent bacterial bronchitis
• Clinical presentation of asthma

  • Shortness of breath (exercise/interval)
  • Expiratory wheeze
  • Cough (nocturnal)
  • Episodic
  • Reversible
  • Diagnosis based on likelihood and assessment
  • Rationale for diagnosis needs documentation
• IgE mediated Nasal symptoms

  • Sneezing
  • Runny nose
  • Nasal congestion
• IgE mediated oral symptoms

  • discomfort in mouth
  • swelling of lips
• IgE mediated skin symptoms

  • itching
  • hives
  • reddening
• IgE mediated shock symptoms

  • loss of consciousness
  • lethargy
  • blue-white lips and/or nails
• IgE mediated eye symptoms

  • itching
  • redness
  • swelling of eyelids
• IgE mediated respiratory symptoms

  • raspy voice
  • wheezing
  • whistling sound when breathing
  • coughing
  • difficulty breathing
• IgE mediated digestive symptoms

  • abdominal pain
  • nausea
  • diarrhoea
• Causes of IgE mediated reactions

  • Drugs
  • Antibiotics, Nonsteroidal anti-inflammatory drugs, Biologicals, Contrast agents, Blood
  • Infection
  • Virus
  • Acute viral syndrome, hepatitis, Epstein-Barr, Herpes simplex
  • Bacteria
  • Streptococcal, Coxsackie, H pylori
  • Chronic parasites
  • Cutaneous fungal infections
  • Foods
  • peanut, tree nuts, milk, eggs, wheat, soy, fish, shellfish, sesame
• Clinical presentations of allergy

  • Anything presented via dendritic cell can be perceived as non-self or pathogenic antigens
  • These antigens can then trigger an IgE mediated reaction
• Re-exposure to allergen-immediate phase

  • Cross-linking of two IgE (to ensure there is not misfiring)
  • Degranulation of mast cells and basophils
  • Release of vasoactive amines, lipid mediators, chemokines and other cytokines
• IgE Fc receptor (FcER1) present on mast cells in tissue, basophils in blood and B lymphocytes (to a lesser extent)
• In Type 1 hypersensitivity reactions mast-cell activation is induced by secretion of IgE antibodies. Initial exposure to the antigen causes the priming of Th2 cells, and their release of IL-4 causes the B cells to switch their production of IgM to IgE antibodies which are antigen-specific. The IgE antibodies bind to mast cells and basophils, sensitising them to the antigen.
• When an antigen enters the body again, it crosslinks the IgE bound to sensitised cells, causing the release of preformed mediators including histamine, leukotrienes and prostaglandins. This leads to widespread vasodilation, bronchoconstriction, and increased permeability of vascular endothelium.
• Type 1 hypersensitivity reactions can be divided into two stages - immediate, in which release of pre-formed mediators causes the immune response, and the late-phase response 8-12 hours later, where cytokines released in the immediate stage activate basophils, eosinophils, and neutrophils even though the antigen is no longer present.
• Treg cells suppress tumour immunity, promote immune tolerance and lymphocyte homeostasis. They are activated by IL-2 and TGF-B, and release TGF-B, IL-10, IL-35, STAT6 and FOXP3.
• Th1 cells promote tumour immunity, drive autoimmunity and are effective against intracellular pathogens. They are activated by IL-12 and release IFN-gamma, LT-alpha, STAT4 and T-bet.
• Th2 cells are effective against extracellular pathogens and are relevant in allergy and asthma. They are activated by IL-4 and release IL-4, IL-5, IL-13, STAT6 and GATA3.
• Th17 cells have controversial tumour immunity, break immune tolerance and are relevant in autoimmunity and against extracellular bacteria. They are activated by TGF-B, IL-6 and IL-21, and release IL-17A, IL-17F, IL-22, IL-21, CCL20, STAT3 and ROR-gamma-t
• Treg cells help maintain the balance between Th1 and Th2 populations by releasing IL10 and TGFB.
• If the proportion of Th2 increases, humoral response is increased IgE secretion.
• IgE is used for eosinophil activation, historically leading to helminth death.
• IL4 from dendritic cells or memory B cells presenting an allergen promotes naive T cells to differentiate into Th2 cells and undergo clonal expansion. IL-4 and IL-13 from these Th2 cells promotes the conversion of naive B cells into memory B cells and class switching from IgM to IgE. Also promotes IgE memory by B cell clonal expansion
• Activated mast cells (or basophils) release Biogenic amines (e.g. histamine) and lipid mediators (e.g. PAF, PGD2, LTC4) which lead to vasodilation, vascular leak, bronchoconstriction and intestinal hypermobility. They also release cytokines (e.g. TNF) and enzymes (e.g. tryptase) that along with the lipid mediators lead to inflammation and tissue damage.
• In the late phase of allergic reactions, Th17 cells are produced preferentially, releasing IL-17 and IL-22 to increase inflammatory cell migration and activation, eosinophil activation leading to release of mediator, chemokines and proinflammatory cytokines. Presence of the allergen further activates basophils and mast cells to degranulate.
• Eosinophils

  • elevated in lungs and blood in asthma
  • allergy and parasitic infections
  • activated by cytokines
  • release toxins, leukotrienes and cytokines
  • activation causes bronchial hyperactivity
• Chronic Allergic reaction

  • persistent inflammation
  • prolonged or repetitive exposure antigens
  • characterised large numbers of innate and adaptive immune cells
  • substantial changes in the extracellular matrix and alterations in the number, phenotype and function of structural cells in the affected tissues
• Fibroblasts

  • implicated in normal healing process and scar formation
  • deposit extracellular matrix
  • cause thickening of basement membrane