Pathology of bronchial asthma

How many people are currently being treated for asthma in the UK?

5.4 million

In 2016/2017 how many people died that year from asthma attacks?

~1500 (45% didn't seek medical assistance before emergency medical care could be provided).

What is bronchial asthma?

A disease characterised by widespread narrowing of the peripheral airways in the lungs, varying in severity over short periods of time either spontaneously or in response to treatment.

What are some early environmental influences in life (extrinsic factors) which can lead to asthma?

- Maternal smoking- if mother smokes during pregnancy the baby is more likely to develop asthma.
- Intrauterine nutrition - a child that isn't well nourished because of placental insufficiency is more likely to have asthma.
- Avoidance of dietary and environmental allergens in first few years of life will more likely lead to development of asthma.

What did the Italian avoidance study show?

- Looked at children and worked out if they had ben exposed to dirt by looking for antibodies against Hep-A (commonly found in dirt - oral and faecal transmission).
- Found that children with evidence to exposure to dirt who had antibodies to Hep A were far less likely to develop asthma as they grew up that those who has cleaner childhoods with no antibodies to Hep A.

What are some specific triggers of asthma?

- Excreta of house dust mites
- Exercise
- Pollen
- Cold air (dries out airway because it carries less moisture so there are nerve endings which are closer to inhaled irritants in the airway)
- Animal fur/dander
- Fungal spores
- Occupational factors
- Drugs (e.g. aspirin)
- Environmental pollutants

What are the main histological changes of asthma?

- Smooth muscle: hypertrophy and hyperplasia. Responds to excessive coughing and has to work harder and therefore gets thicker.
- Mucus: hypersecretion of mucus and mucus plugs can form which block peripheral airways.
- Epithelium: becomes damaged and can fall off the basement membrane. Cilia can be lost and therefore capacity to move mucus via the mucociliary escalator is reduced. This has consequences against infection defence.
- Basement membrane: becomes hugely thickened (major clue for pathologists).

What could be seen on electron micrograph from bronchial biopsy?

- In a healthy subject, 1/10 cells are goblet cells and the rest are ciliated epithelium.
- In subject with mild symptomatic asthma there can be almost complete loss of epithelium.

What is the role of leukocytes in bronchial asthma?

- Macrophages take up antigen and present it on its surface via MHC2 to CD4+ Th2 cells.
- The Th2 cells then become activated through 3 signals (antigen/t-cell receptor & MHC/CD receptor, CD80/86 to CD20 and cytokines).
- Activated Th2 then secrete IL-4/5 which cause B cells to undergo clonal expansion and maturation and then differentiate into effector plasma cells and memory.
- IL-5 can also activate eosinophils and mast cells
- Plasma cells secrete anti-specific IgE which bind to mast cells. When the antigens binds to these IgE and cross links the receptors on the mast cell they degranulate.

What are the early preformed mediators released from the mast cells?

- Histamines
- Proteases
- Proteoglycans
- Eosinophil chemotactic factors

What are the later mediators released?

- Cytokines
- Leukotrienes
- Prostaglandins

What do eosinophils release and what does it cause?

Major basic protein which causes epithelial desquamation leading to histological changes. (Causes loss of ciliary cells)

What do the early mediators cause?

Histamine causes contraction of airway smooth muscle, increased vascular permeability and increased bronchial secretions.
Chemotactic factors cause infiltration of airways by neutrophils and eosinophils.

What do later mediators cause?

leukotrienes C4, D4, E4 and prostaglandin D2 cause contraction of airway smooth muscle, increased vascular permeability and increased bronchial secretions.