Asthma Flashcards
What is asthma
Airways smooth muscle hyper responsiveness leading to periodic, at least partly reversible obstruction of the airways
What is the obstruction caused by
Inflammation/swelling of the mucosal lining.
What does the obstruction cause
Turbulent airflow - audible wheeze. Should hear in all lung fields
What are signs of pneumothorax
Hyper resonant and no breath sounds
What are signs of pneumonia
Bacterial infection of one lobe - dull percussion
What are signs of lung collapse
Blockage in proximal airway, dull percussion everywhere
How is asthma severity assessed
PEFR/FEV1 and response to bronchodilator (nebulised salbutamol 5mg given with pure O2)
Blood gases: oximetry <92%
Who are high risk asthma px
Poor compliance, psychosis, depression, denial, alcohol or drug abuse, obesity, social problems, severe stress from any source
What is cyanosis a sign of
Terminal sign of asthma (pO2 has to be around 50)
What does hypercapnia cause in the brain
Hypercapnia is a potent vasodilator - causes cerebral oedema
When should an asthma px be admitted
FEV1/PERF less than 50%, predicted 15-30 minutes after bronchodilator
What is the management for admitted severe asthma
Oxygen - high conc up to 100%
Hypercapnia is asthma reflects alveolar hypoventilation and not lung disease
Inhaled beta2-agonits (prevents bronchospasm)
Nebulised
Give continuously if necessary
Always nebulise with O2: may acute aggravate hypoxia in severe asthma; hypoxia and hypercapnia alter cardiac response to beta2-agonist
If px does not have access to nebuliser, breath in Ventolin through spacer
Ipatropium bromide 0.5 mg 4-6hourly added to beta2-agonist if acute severe or life threatening asthma
What is given IV in severe asthma
Single bolus of IV magnesium sulphate if PEF<50%
What is the role of steroids in acute asthma
Glucocorticoids: given orally
Reduction in airflow obstruction begins 1-3 hours, peaks 5-9 hours after single dose
Probably no need to give 0.6 mg/kg prednisolone in 24 hours; typical emergency regimens are 2-3 mg/kg hydrocortisone 4 hourly
What to do with acute asthma px with a good response to management
Continue oxygen, nebulised beta2-agonsits 4 hourly, glucocorticoids
Do not discontinue any existing inhaled glucocorticoid therapy
What to do with acute asthma px with a poor response to management
Continuous high flow oxygen Nebulised beta2-agonist every 15-30 mins Consider complications Hypokalaemia (beta agonists cause migration of potassium ions intracellularly) Coexisting problems Admit to intensive care
How is vent support given with asthma
Benzodiazepine and pancuronium sedation
Aim to correct hypoxaemia with permissive hypercapnia
What is allergic asthma
most easily recognised, usually commences in childhood. Associated with Fx. Usually presents eosinophilic airway inflammation. Good responses to ICS
What is non allergic asthma
sputum may be neutrophilic, eosinophilic or with few inflammatory cells. Less response to ICS
What is late onset asthma
more common in women. Tendency to non-allergic, higher doses of ICS
What is asthma with fixed airflow limitation
long standing asthma, airflow limitation thought to be due to airway wall remodelling
What is asthma with obesity
prominent resp symptoms, little eosinophilia
What are the inflammatory pathologies of asthma
Inflammatory infiltrate (Th2, mast cells and eosinophils)
Mucosal oedema:
Bronchial microvascular leak
Mucus hypersecretion: Blockage of airways
Bronchial smooth muscle contraction:
Action of inflammatory mediators
What are the remodelling pathologies of asthma
Reticular BM thickening
Airway smooth muscle thickening
Submucosal mucus gland hypertrophy
What drugs target b2 adrenoceptor?
Selective b2 adrenoceptor agonists:
Inhaled
Short acting: salbutamol
Long-acting: formoterol, salmeterol, vilanterol
What drugs target muscarinic receptors (M3)
Inhaled
Short-acting: Ipratropium
Long-acting: Tiotropium, Umeclidinium
What is the mechanism of muscarinic receptor antagonists
Anticholinergic: block effects of Ach released from cholinergic parasympathetic nerve fibres to smooth muscle and mucus glands
Prevents airway smooth muscle contraction
Prevents mucus hypersecretion
Less effects
What are the side effects of muscarinic receptor antagonists
dry mouth, palpitations, headache, dizziness, blurred vision
What is the mechanism of action of b2 agonists
High levels of cAMP relaxes bronchial smooth muscle and also inhibits release of bronchoconstriction mediators such as histamine
After inhalation, salbutamol reaches the lungs directly - acts within 3-5 minutes
What is vilanterol
long acting B2 agonist with bronchodilation up to 72 hours
What does tiotropium do
attenuates IL-13-induced goblet cell metaplasia
What does ICS therpay acheive
Reduces asthma symptoms
Increases lung function
Improve QoL
Reduces the risk of exacerbations, hospitalisations and death
How do corticosteroids work
Suppress Th2
Reduce the infiltration and activation of eosinophils, Th2 cells, and other inflammatory cells
What is Fluticasone Furoate
Long-acting ICS
Results in a longer duration of action and prolonged retention in the lung; enables it use as a once-daily ICS
Longer duration of action enables once-daily dosing: potential to improve px convenience and enhance compliance
What is Montelukast
Leukotriene Receptor Antagonist
Potent arachidonic acid-derived inflammatory mediators
CysLT1 receptor mediates the broncho constrictive and proinflammatory effects of cysteinyl-leukotrienes
Montelukast is a competitive antagonist of the CysLT1 receptor
Once daily oral administration
Who is montelukast best suited for
Asthma px with aspirin exacerbated resp disease (increased production of cysteinyl-leukotrienes)
What is T2 inflammation in asthma
Airway epithelium interacts with environment (allergens, viruses, smoke etc.)
Releases cytokines once activated
IL-33, IL-25 released
Signals to downstream cells to innate and adaptive
IL-C2 on innate
Th2 cell on adaptive ->product of naiive t cells
These produce Il-4 (tells B cells to make IgE), Il-5 (eosinophil maturation and migration from bone marrow), Il-13 (airway hyper responsiveness and remodelling)
How does anti-IL-5 work
inhibits eosinophils in airways - given 4 weekly
Mepolizumab (sc)
Reslizumab (iv)
Eosinophils central effector cell in asthma. Critically involved in the synthesis, maturation, homing and activation of eosinophils
How does anti-IgE work
Depletes IgE, reduces allergen induced mast cell activation and decrease expression of IgE high affinity receptors on amst cells, blocks effects of IgE on DCs
Decreases exacerbation rates
What is Tezepelumab
Anti-TLSP, anti-IL-33: dampens down entire airway. Blood eosinophil, exhaled NO and total IgE levels all fallen
What is the dominant cuase of asthma exacerabtion
Viruses - Rhinovirus most frequent trigger
What are the 3 families of antiviral cytokine interferon
T1 (IFN-alpha and beta) and Type 3 (IFN-lambda)
What do antiviral cytokines do
Block viral entry into cells
Control viral replication inside the cell
Induce apoptosis
Induce other cytokine’s -> recruitment of NK, CD4, CD8
How does Omalizumab work
DCs produce T1 IFN in response to viruses
DCs express IgE receptor - crosslinking this receptor impairs production of IFN
