Lecture 12- Asthma Flashcards
What is Asthma?
A chronic inflammatory disease of the airways, characterised by recurring symptoms, airflow obstruction and broncho spasm.
Variable episodic airflow obstruction: reversible either spontaneously or without treatment.
Asthma symptoms
wheezing coughing Airflow obstruction Dyspnea sputum production chest tightness shortness of breath
These become worse at night-time
Asthma facts
- very common chronic disease
- 1/6 adults and 1/4 children
- > 600,000 kiwis
- > 500,000 kiwis take meds
- $800M economic burden
- most common cause of hospital admission in kids (hosp rates double in past 30 yrs)
- More common in developed countries
- YLD: 1st males and 3rd females
Is it more common in males or females? What age?
Adults : females more common
Kids: Males more common
Girls>boys
Highest in ages 18-44
Asthma can be..
Episodic: acute exacerbations interspersed with symptom-free periods
Chronic: daily AW obstruction which may be mild, moderate or severe AND acute exacerbations
Life Threatening: slow onset or fast-onset (fatal within 2 hours)
How would you Diagnose Asthma?
1) Physical examination: Wheezing (not specific to asthma)
2) History of: Recurrent wheeze, dyspnea, cough, chest tightness and reversible airflow limitation and diurnal variation
3) Lung Function test: evidence of variable airflow obstruction
4) Symptoms above worsen due to: exercise, animals with fur/feathers, dust-mites, moulds, smokes, pollen, weather change, laughing or crying excess
5) Other: family history, atopic disease (allergic rhinitis, urticaria or eczema)
Atypical Presentation
- Dyspnea without wheezing
- Chronic cough
- Increased shortness of breath at nighttime
- Allergic rhinitis with wheezing
Types of Lab studies done
- Lung Function Tests
- Skin allergy test and serologic studies
- radiographic studies
Lung Function Tests
1) Peak Expiratory Flow (PEF): cheap, easy to do, useful to monitor treatment process but not good to diagnose as everyones so variable
2) Spirometry (FEV1): Better diagnostic tool, not suitable for young patients
Asthmatic Spirometry
Big drop: FEV1
Drop in : FVC
FEV1/FVC
Post-bronchodilator Reversibility testing: FEV1 increases (if > 400mL it’s likely you have asthma, a good distinguisher from COPD)
Serologic Studies
Eosinophil count:
>4% or 300-400/mm^3
> 800/mm^3 suggests the presence of other disorders
Increased Serum IgE level
Allergy Tests for
Pollens dust mites mold and mold spores animal Dander Insect allergens Smoking
What are the Two major models of Asthma
Allergy and non-allergy
Up to 90% of early-onset asthma could be allergic
Atopic (allergy) Asthma
- Most common
- usually early-onset
- Triggered by environmental antigens
- A positive family history
- often preceded by allergic rhinitis, urticaria or eczema
Principle cells of Inflammation
Eosinophils: (late-phase)
Mast Cells: exercise-induced asthma and acute phase response
Macrophages: release pro-inflam mediators
T cells: central role in inflammation responses
Neutrophils: corticosterol resistance
Basophils: also in late-phase response to allergin exposure
Dendritic: Present allergin to inflamm cells
Appearance of asthma microslide
Changed SM and goblet cells, thicker BM, higher density of inflammatory cells and a damaged epithelial layer
Types of response to an allergen challenge in atopic sufferers
1) Acute-Phase Response (APR): inhalation causes an immediate fall in lung function (~5-10minutes). Can sometimes be reversed w/o treatment
2) Late-phase response (LPR): Beginning about 4-6 hours after allergen challenge. Lung function lower and persistent
3) Dual phase
Lung function journey of responses after an allergen challenge
1) Acute-Phase: drops to 50% within 30 mins, returns to normal within 2 hours
2) Late-Phase: post 4 hour drop to ~40%, takes around 20hrs to return
3) Dual-phase: lung function can be extremely bad (~30%) for 24hr
Draw flow diagram page 12.9
…
Genetic Involement of Asthma
~30 SNPs have been related to asthma, but nothing is certain
- A genetic predisposition to Th2 rather then Th1
- When a body decides to go down a Th pathway (decided by genes) it naturally inhibits the other pathway
Th2 and Th1
Th1: produce IFN-y, IL-2 and TNF-alpha
Main cell partner is macrophage
Th2: secrete cytokines (IL-4, IL-5)
main cell partner is B-cell
Th2 pathway
1) causes type 1 hypersensitivity/atopy: such as eczema, hayfever, asthma
2) Chronic airway inflammation
3) Bronchial hyper responsiveness
Non-atopic Asthma
- Majority is late-onset
- Maybe associated with respiratory tract infections
- other risk factors: medication induced asthma (NSAIDS, beta-blockers, aspirin)
Key Mediators in asthma
Leukotrienes Prostanoids Acetyl Choline Chemokines IgE Nitric Oxide Granule Proteins Adhesion molecules in inflammation
Leukotrienes
- de novo synthesis of mast cells & eosinophils
- Potent mediator (LTC4) causing prolonged broncho-constriction
- increases mucus secretion + vascular permeability > edema
- L receptor antagonists recomended as 2nd line of treatment
Prostanoids
- Produced by mast cells and eosinophils
- Potent bronchoconstrictors (PGD2)
Acetyl Choline (ACh)
- Release from intrapulmonary motor nerves
- causes SM contraction in airways
- stimulates muscarinic receptors
Chemokines
- recruit or chemotaxis of inflamm cells
- CK receptor inhibitors for CCr3 and CCR4 are in development for therapy
IgE
- Triggering mast cell
- cause airway inflammation
- humanized monoclonal AB targeting IgE is developed for therapy ‘Xolair’
Nitric Oxide
- Higher levels in Asthma
- So production reflects level/severity of airway inflamm
- Exhaled NP measurement used to monitor inflamm extent for asthma control
Granule Proteins
- Mast cells, basophils, neutrophils and eosinophils release them
- MBP major basic protein
- ECP eosinophil cationic protein
Adhesion molecules
Integrins: primary mediators of cell-extracellular matrix adhesion
important for transendothelial migration of inflamm cells into airways
