Asthma Flashcards
Three characteristics of asthma
- Airflow limitation - usually reversible
- Airway hyper-responsiveness - to a wide range of stimuli
- Bronchial inflammation
Prevalence of asthma
Prevalence increased over last 30yrs
15% of population affected
More common in developed countries
Aetiology of asthma
So many factors!
- Environmental allergen exposure
- Occupational
- Viral infections
- Cold air
- Drugs
- Emotion
- Irritants
- Genetic
How is airway hyper-responsiveness elicited in clinic?
Patients asked to inhale gradually increasing concentrations of histamine or methacholine
Severity can be measured based on the concentration of the drug that produces a 20% fall in FEV1
*Can also be assessed by exercising or inhaling cold/ dry air
Discuss inflammation associated with asthma
Mast cells increased in the epithelium, smooth muscle and mucous glands
Mast cells release histamine and other mediators that cause vasodilation, smooth muscle constriction and act on sensory nerves - causing asthmatic reaction
Discuss smooth muscle remodelling in asthmatics
Hyperplasia of helical bands of smooth muscle
Smooth muscle contracts more easily and remains contracted
Smooth muscle secretes cytokine that help sustain the inflammatory response
Discuss the respiratory epithelium in asthmatics
Loss of ciliated columnar cells which makes the epithelium more vulnerable to infection
Epithelial damage leads to increased expression of NO synthase so measuring exhaled NO is a good way to measure continuing inflammation
Stepwise management of asthma
Step 1: inhaled short-acting b2 agnonists
Step 2: + inhaled steroid of 200-800ug per day
Step 3: + LABA such as formoterol and assess, if inadequate control, increase steroid dose to 800ug (if not already). No response to LABA, discontinue and try leukotriene receptor antagonist or SR theophylline
Step 4: increase steroid to 2000ug and add a 4th drug (whiever type isn’t currently used)
Step 5: daily steroid tablet + high dose corticosteroid + refer to specialist
Discuss early and late responses in asthma
Early: exposure to allergen and production of IgE antibodies due to overexpression of Th-2 T cells. IgE binds to mast cells and causes release of mediators from mast cells causes vascular leakage and smooth muscle contraction. Return to baseline within 1-2hrs
Late reaction: influx of inflammatory cells (mainly eosinophils), release of inflammatory mediators causing airway narrowing after 3-4hrs with maximal effect after 6-12hrs. More difficult to reverse than early reaction
Which immune cell is most associated with asthma?
Eosinophils - found in large numbers in the bronchial wall and secretions of asthmatics
Corticosteroids reduce the number of eosinophils
What clinical features lead to the diagnosis of acute severe asthma?
- Patient cannot complete sentences in one breath
- RR >25/min
- Pulse >110/min
- PEFR <50% predicted or best
Investigations for asthma
- Lung function: reduced FEV1/FVC ratio, increased RV, >15% improvement in FEV1 when bronchodilator given
- PEFR: morning and evening measurements
- Bronchial provocation
- Chest x-ray to exclude aspergillosis and pneumothorax
- Skin prick tests to identify allergen
Differences between COPD and asthma
COPD:
- adults, neutrophils, persistent symptoms, anticholinergics most effective, steroids of little use
Asthma:
- children most commonly, esoinophils, variable symptoms, b2 agonists most effective, steroids beneficial
Discuss antimuscarinic bronchodilators
e.g. ipratropium bromide
Large airways mainly contain M3 receptors, peripheral lung tissue contains M1 and M3 receptors
Anti-muscarinics inhibit antagnoise the acetylcholine receptor which inhibits the parasympathetic nervous syetm in the airways which functions to increase secretions and constriction
What is theophylline?
Phosphodiesterase inhibiting drug used in therapy for respiratory diseases
