13.1 Circadian biology of Asthma Flashcards
What is the definition of asthma?
- Chronic inflammatory condition of the airways characterized by bronchial hypersensitivity to a variety of stimuli (triggers) leading to variable airway obstruction
- Day to day diurnal variability in symptoms
- Can be measured using peak expiratory flow rate (PEFR), is a person’s maximum speed of expiration
What are the phenotypes of asthma?
- Cough-variant
- Eosinophilic
- Non eosinophilic
- LATE onset asthma
- NSAID related asthma
- Occupational
- Chronic asthma with fixed airflow obstruction
- Exercise induced bronchospasm
- Allergic asthma
- IgE mediated
Explain the pathophysiology of asthma
- Best described as chronic eosinophilic bronchitis/bronchioloitis
- Airway inflammation with cellular infiltration by T helper 2 cells, lymphocytes, eosinophils and mast cells
- Cytokine production (platelet activating factor PAF)/ interluekins (including IL5) and leukotrienes
- Large and small airway involvement
- Airway inflammation with cellular infiltration by T helper 2 cells, lymphocytes, eosinophils and mast cells
- Resulting airway obstruction from:
- Inflammatory cell infiltration
- Mucus hypersecretion and plugging
- Smooth muscle contraction
- Can result in chronic and (sometimes) irreversible airway damage (through remodelling with smooth muscle hypertrophy/ hyperplasia)
Draw the difference between a normal bronchiole and an asthmatic bronchiole
What are the risk factors of asthma?
- Boys>Girls
- Women>Men
- Family history
What are the common triggers of asthma?
- Weather
- Food
- Pollution
- Cigarette smoke
- Emotion/ stress
- Mould/ damp
- Pets
- Exercise
- Dust
- Pollen (e.g. this would be seasonal)
- Drugs including NSAIDs
- LRTi (lower respiratory tract infections)
- Viral respiratory illness (rhinovirus, influenza, RSV, parainfluenza, human metapneumovirus), sinus infections
What is the difference in signs and symptoms between acute and chronic asthma?
-
ACUTE
- SOB
- Cough +/- green phlegm (meaning INCREASE in neutrophils in sputum thus, inflammatory)
- Chest pain/ tightness
- Difficulty completing sentences
- Wheeze
-
CHRONIC
- Coughing and wheezing are the most common symptoms of childhood Asthma
- Breathlessness, chest tightness or pressure, and chest pain also are reported
- Poor school performance and fatigue may indicate sleep deprivation from nocturnal symptoms
What are some symptoms of life-threatening asthma?
- Cyanosis
- Arrythmia
- Hypotension
- Altered conscious level
- Exhaustion
What are some symptoms of near-fatal asthma?
- Raised PaCO2
- Required mechanical ventilation with raised inflation pressures
What are good questions to ask in an asthma history?
- How many times a week do you use SABA
- What are your triggers/ Pets
- How many courses of steroids in the last year
- How often do you forget to use your inhalers
- Smoking status
- Job
- Exercise
- Anxiety element
- “Vocal hygiene”
What are the markers of a poor prognosis (treatment) of astma?
- Poor adherence
- Previous acute admissions and/or intubation
- 3+ different classes of asthma medication
- Psychosocial dysfunction
- Inadequately treated disease
- Smoking
On a respiratory examination how can you tell someone has asthma?
- Wheezing is a high-pitched, expiratory sound produced when air forced through narrow airways
- Asthma wheeze tends to be polyphonic (varied in pitch)
-
ACUTELY
- May have low oxygen levels
- High respiratory rate/ other visible signs of respiratory distress
- PEFR (peak expiratory flow rate) tends to go down
What are the differential diagnosis of asthma?
- COPD – fixed airflow obstruction
- Upper airway obstruction (stridor)
- Inducible laryngeal obstruction
- Foreign body
- Hyperventilation syndrome
- Pattern of breathing where you breathe more quickly and deeply than normal
- Causes INCREASE CO2 levels in blood
- Pattern of breathing where you breathe more quickly and deeply than normal
- Anxiety
- Gastro-oesophageal syndrome
- Pulmonary oedema
- Eosinophilic vasculitis
- A family of rare diseases characterized by inflammation of the blood vessels, which can restrict blood flow and damage vital organs and tissues
- Respiratory bronchiolitis
- Common lung infection in young children and infants. It causes inflammation and congestion in the small airways (bronchioles) of the lung
- Interstitial lung disease
- Pulmonary Hypertension
Explain diagnosis of Inducible laryngeal obstruction
- Also, on flow-volume loop inspiration flow is much less than normal
- Can be characterised by inspiratory noise
What investigations should be done with someone with asthma?
-
PEFR variability
- Twice daily 2-4 weeks
- +ve if >20% variability
-
Spirometry
- FEV1/FVC ratio <70%
- 400ml/ 20% increase in FEV1 after SABA
-
FeNO
- Marker of eosinophilic inflammation (IL-4/IL-13 mediated)
- +ve if >40
-
Bronchial provocation
- Inhalation of noxious stimulant results in a drop in FEV1 of 20%
What should happen if someone has good asthma control?
- No daytime symptoms
- No night-time awakening due to asthma
- No need for rescue medication
- No exacerbations
- No limitations on activity including exercise
- Normal lung function (in practical terms FEV1 and/or PEF>80% predicted or best)
- Minimal side effects from medication.
Explain the pharmacological steps with someone with asthma (getting worse)
Explain the mechanism of action of SABA (&inhalers vs nebulisers where used)
- E.g. Salbutamol (short acting B2 agonist)
- Bronchodilator
- Targets B2 receptors in bronchial smooth muscle –> cAMP (relaxes)
- Systemic absorption causes tachycardia/ hypertension/ lactic acidosis/ hypokalaemia
- Excreted urine after metabolism in liver
- Onset ~5minutes
- Lasts up to 6 hours
- Inhalers at home and nebulisers at hospital
Explain the mechanism of action of leukotriene antagonists
e.g. Montelukast
- Blocks cysteinyl-leukotrienes binding to cysteinyl-leukotrienes receptors
-
Prevents:
- Eosinophil recruitment
- Bronchoconstriction
- Mucus secretion
- Plasma exudation
- Be careful in psychiatric history
What is the mechanism of action or oral/inhaled corticosteroids?
Give examples of ICS (inhaled corticosteroids) and oral corticosteroids
-
ICS:
- Beclemetasone
- Budesonide
- Fluticasone
- Mometasone
- Oral
- Prednisilone
- Dexamethasone
What to do when introducing someone to using an inhaler?
- Pick the right inhaler for the right person
- Check technique
- If young and active
- If poor compliance
- Sore throat (poor deposition into lung)
- Oral thrush
- Use spacer (if required)
- Mouthwash
Explain the mechanism of action of omalizumab
Explain the mechanism of action of benralizumab
-
INHIBITION
- Activation/proliferation eosinohils
- Proliferation B cells
-
ACTIVATES
- Eosinophil apoptosis
Explain the mechanism of action of dupilumab
- Is a fully human monoclonal antibody that BLOCKS shared receptor component for IL-4/IL-13 (prevent Th2 binding to it)
- Causes a decrease in:…
Explain the step by step acute treatment of someone coming in with asthma issues
- A B C
- Oxygen to maintain O2 sats >94%
- Corticosteroids
- Oral > parenteral
- Nebulised bronchodilators
- Salbutamol
- IV MgSO4 if acute severe asthma not responding to initial
-
Antibiotics ONLY if suspicion of superimposed bacterial infection
- E.g. Amoxicillin
How can we make sure asthma patient’s are getting ongoing care?
- Self management plans (shown in picture has traffic light system)
- Patient education
- Use of apps/ telemedicine
- Annual GP review
- Practice/ Asthma Nurse
- Secondary care review for more advanced cases
