L5 - asthma Flashcards
Asthma
chronic inflammatory disorder of the airways causing recurrent episodes of wheezing, breathlessness, chest tightness and coughing
asthma episodes
usually associated with widespread but variable airway obstruction that is often reversible either spontaneously or with treatment
asthma mechanism
airway inflammation –> Bronchial hyperresponsiveness –> recurrent reversible airway obstruction
Hygiene hypothesis
exposure to microbial components early in life skews immune respons
Th2–> Th1
Hygiene hypothesis limitations
respiratory allergies increased earlier than food allergies
Helminth infections
measles and respiratory viruses
helminth infections
high Th2 levels but decreased allergic disease
Measles and respiratory viruses
high Th1 levels but not protective against allergic disease and can increase risk
Hygiene hypothesis year
1989
Old friends hypothesis
early and regular exposure to harmless microorganisms train the immune system to react appropriately to threats
Aspects of old friends
maternal microbes, childhood contact, hygiene, caesarians, pets, farms etc.
And genetics
Old friends hypothesis year
2003
Risk factors
respiratory infections, allergens, work, medication, genetics, food additives, pollutants, tobacco, obesity
Asthma genetics
polygenic with over 150 related genes
1 parent asthma risk
25%
2 parents asthma risk
50%
Asthma twin studies
70% variation in disease susceptibility
Epigenetics
transcriptional dynamic alterations leading to changes in gene expression
Asthma mutations in 4 areas
triggering and regulating immune system, regulation of Th2 differentiation, lung function remodelling and disease severity or positional cloning
Th2 eosinophilic
early and later onset disease with severity range
associated with allergy
non-allergic variants
Non-Th2 non-eosinophilic
obesity, smoking, neutrophilic
associated with more severe disease
Asthma pathology
contracted smooth muscle, blood vessels infiltrated by immune cells, decreased lumen diameter, inflammation, swelling and excess mucus
Airway inflammation
protection against invaders, recruitment of inflammatory cells, swelling, mucus secretion, airway constriction
Bronchial hyperresponsiveness
hallmark of asthma
degree of this correlates with asthma severity
causes by inflammation
dynamic and reversible
Acute asthma response
binding of allergen to membrane-bound IgE on mast cells
release of mediators and bronchoconstriction
Late asthma response
~50% of patients
influx of inflammatory cells, mainly eosinophils leading to oedema and bronchoconstriction
Airway remodelling
development of specific structural changes in airway wall in asthma accompanying long-standing and severe asthma inflammation
Airway smooth muscle cells
hypertrophy and hyperplasia in response to growth factors released from inflammatory and epithelial cells leading to narrowing of the airway lumen
inflammatory mediators, irreversible fixed airflow obstruction
Blood vessels in asthma
increased mucosal bloodflow
angiogenesis in response to growth factor VEGF
microvascular leakage from post-capillary venues - oedema and plasma exudation into lumen
Mucus hyper secretion in asthma
hyperplasia of submucosal glands, increased epithelial goblet cells
mucus plugs occlude asthmatic airways
Potent inducers of mucus hypersecretion
Il-13 and neutrophil elastase
Fibrosis
aberrant repair to persistent epithelial injury
thickens basement membrane
vascular remodelling with inner airway wall thickening
decreased baseline airway calibre and amplification of airway smooth muscle shortening
Hypertrophy and hyperplasia of airway smooth muscle
increased smooth muscle strength and airway hyperresponsiveness
Connective tissue deposition
increased airway smooth muscle constraint
thickening and fibrosis of all layers
decreased airway distensibility and reduced effectiveness of bronchodilators
hypertrophy and hyperplasia of mucus gland
decreased lumen calibre and amplification for airway smooth muscle shortening
loss of alveolar attachments
predisposition closure and collapse
Asthma treatments
usually controlled using inhaled corticosteroids and bronchodilators
