2- overview of obstructive airways disease Flashcards
what is
a) obstructive disease?
b) restrictive disease?
a) airways problem
b) lung problem
what are the obstructive airway syndrome?
- asthma
- chronic bronchitis
- emphysema
what is ACO?
asthma/COPD overlap syndrome i.e. smokers with features of both asthma & COPD
- COPD with blood eosinophilia
- responds better to inhaled corticosteroids which help exacerbation reductions
- more reversible to salbutamol
- difficult to distinguish ACO from type 2 asthmatic smokers who have airway remodelling
what does atopic mean?
allergy
what are extrinsic and intrinsic asthma triggers?
extrinsic trigger like allergen or intrinsic if no obvious trigger factor
what are the 3 key principles of asthma?
- type 2 inflammation = characterised predominantly by eosinophils in mucosa and submucosa in 95% of cases (type 2 high). some cases where eosinophils not predominant and more neutrophil (type 2 low asthma)
- airway hyperresponsiveness = because of type 2 inflammation, sensitive airway to become unstable, twitching and obstruction in response to stimuli
- reversible airflow obstruction = melt away eosinophil with corticosteroid or relax muscle with medication →reverses obstruction
what is the evolution of asthma?
bronchoconstriction = brief symptoms
type 2 airway inflammation = exacerbations
if don’t treat type 2 eosinophilic inflammation the body lays down collagen (scar tissue = fibrosis) in the mucosa and in basement membrane - no drug dissolves it = airway remodelling
what happens in remodelling of airways in asthma?
there is thickening of basement membrane and collagen deposition in mucosa, submucosa and basement membrane
= also smooth muscle hypertrophy & hyperplasia
what is the process of type 2 inflammation?
allergen binds to dendritic cell (antigen presenting cell) via chemical mediator, TSLP. moves to nearest lymph node where activates nearest T cells to become activated and they can interact with B cells and Th2 cells release cytokines (3 key ones: IL-4, IL-5, IL-13)
IL-5 is attractant for eosinophils (they protect body from parasites) - when eosinophils apoptose they release basic proteins (cytotoxic), leukotrienes & cytokines
Mast cells & basophils link with Ig and release histamine
Leukotrienes stimulate goblet cells in epithelium to produce lots of mucus and affect mucociliary clearance
IL-4 stimulates IgE production
IL-13 affects smooth muscle
what does IL 4,5 & 13 do?
IL 4 = stimulates IgE production
IL 5 = attractant for eosinophils
IL 13 = affects smooth muscle
what are 3 biomarkers that indicate type 2 inflammation?
- blood/sputum eosinophilia (IL-5)
- raised FeNO (fractional exhaled nitric oxide) (IL-13)
- raised total or specific IgE (IL-4)
what drugs to patients with type 2 high respond to?
respond well to corticosteroids & biologics (which act on type 2 pathway)
what is management for eosinophilic inflammation (part of inflammatory cascade)?
anti-inflammatory medication = corticosteroids & theophylline
what is management for mediators & Th2 cytokines (in inflammatory cascade for asthma)?
antileukotrienes or antihistamines
(anti-IgE, anti-interleukin 5)
what is management for twitchy smooth muscle (hyperreactivity) as a result of inflammatory cascade in asthma?
bronchodilators = beta 2 agonists, muscarinic antagonists
what is difference about appearance of normal vs asthma pathology of cells?
normal is the structured, neat looking respiratory epithelium (pseudostratified columnar epithelium) and asthma is all jumbled and chaotic looking
what is the only drug shown to normalise the the appearance of jumbled asthma cell pathology?
corticosteroids
what are the triggers of asthma?
allergens (animal dander, dust mites, pollens, moulds)
other things: exercise, viral infection, smoke, cold, chemicals, drugs (NSAIDs, beta blockers)
how does asthma present clinically?
- episodic symptoms & signs
- diurnal variability (worse in morning)
- non productive cough
- wheeze due to turbulent airflow
- family history of asthma
- ask about associated comorbidites
what are associated type 2 inflammation comorbidities?
- allergic rhinoconjunctivitis (hay fever)
- chronic rhinosinusitis with nasal polyps
- atopic dermatitis (eczema)
- eosinophilic esophagitis
- urticaria (hives - skin rash)
what is used to help assist diagnosis of asthma?
- history & examination
- diurnal variation of peak flow rate
- reduced forceful expiratory ratio = reversibility to inhaler salbutamol
- provocation testing →bronchospasm
- exercise
-histamine/methacholine/mannitol
- exercise
what is involved in COPD development?
noxious particles or gases (smoking or certain gas stoves) = inflammation →tissue damage & mucociliary dysfunction
what are symptoms of COPD?
breathlessness & worsening quality of life
what are characteristics of COPD?
- exacerbations
- reduced lung function
what is type 2 high inflammation?
eosinophilic inflammation
what is type 2 low inflammation?
neutrophilic inflammation
what happens type 2 low inflammation in COPD?
neutrophilic inflammation (type 2 low normally) = sticky mucus that blocks airway, smooth muscle hypertrophy, loose alveolar
what is disease process in COPD low?
- the toxins activate alveolar macrophage to release neutrophil chemotactic factors like cytokine IL-8
- neutrophils arrive and release mediators, oxygen radicals & proteases (like trypsin)
- cause alveolar wall destruction (emphysema) and mucus hypersecretion (chronic bronchitis) = progressive airflow limitation
what is chronic bronchitis?
type of COPD involving mucus hypersecretion & mucociliary dysfunction
= characterized by chronic neutrophilic inflammation (type 2 low)
what are some affects of chronic bronchitis?
- altered lung microbiome due to chronic inflammation & mucus accumulation
- in response to chronic inflammation & irritation, the smooth muscle spasm & hypertrophy = further narrowing the airways
is chronic bronchitis reversible?
- some aspects of chronic bronchitis are partially reversible with treatment e.g. bronchodilators help relax smooth muscle & improve airflow
what is emphysema?
progressive lung disease that primarily affects the alveoli - an effect of COPD
the neutrophils produce proteases which destroy the alveoli making impaired gas exchange and loss of bronchial support (this is irreversible)
what is genetic problem that can cause emphysema?
antiprotease
what should be assessed in COPD for diagnosis & management?
- assess symptoms
- assess degree of airflow limitation using spirometry
- assess risk of exacerbations
- assess comorbidities
what are the chronic symptoms of COPD?
- Daily productive cough
- Progressive breathlessness
- Frequent infective exacerbations viral/bacterial
- Chronic bronchitis-mucous hypersecretion
- Emphysema- reduced breath sounds
is COPD atopic or non atopic?
non-atopic (non-allergic)
what is the chronic cascade in COPD?
progressive fixed airflow obstruction →impaired alveolar gas exchange →respiratory failure (decreased oxygen and increased CO2) →pulmonary hypertension→RV hypertrophy/failure →death
