Week 210 - Asthma Flashcards
What is Atopy?
A genetic predisposition towards the development of immediate hypersensitivity reactions against common ** environmental antigens**.
How many people are affected by Asthma?
There are 300 million individuals of all ages, ethnic groups and countries that are affected by Asthma worldwide.
What are the two general types of Asthma?
- Extrinsic (otherwise known as Atopic)
- Intrinsic (otherwise known as Non-atopic)
Which sub-type of T-Helper cell is Pro- atopic - Th1 or Th2?
Th 2 - pro atopic; pro asthmatic.
Th 1 is non atopic.
Are Eosinophils “acid loving” or “base loving”?
Eosinophils are “acid loving” white cells. They stain brick red with Eosin staining.
What are the main inflammatory cells in the airway??
- Mast cells: These are the key cell of the innate immune system. They produce a variety of pre-formed and newly-formed inflamatory mediators.
- B lymphocytes: These produce antigen specific IgE (immunoglobulin E), in response to stimulation by interleukin-4 and interleukin-13 cytokines.
Of less importance….
- Dendritic cells - Antigen presenting cells.
- Epithelial cells - Secrete pro-inflammatory mediators (Thymic stromal lymphopoietin)
- Macrophages - Also express receptors which bind IgE and IgG
Antigen specific IgE (immunoglobulin E) is produced by what?
B lymphocytes.
What are the typical early phase clinical signs of Asthma?
Patient develops:
- wheeze
- cough
- SOB
- mucus production.
What are the typical late stage signs of Asthma?
Patient presents with:
- Initial response, but later symptom recurrence.
- Chest tightness
- Worsening SOB
- Bronchodilators do not fully reverse the airway obstruction.
What is the hygiene hypothesis?
It is hypothesized that exposure to certain microbes by early infection or from the environment may drive T cell production** towards the non atopic (Th 1)** phenotype, thereby reducing the occurence of Asthma.
What is Sodium cromoglycate used for?
Sodium Cromoglycate is:
- A mast cell stabiliser
- Used in the treatment of Asthma (usually in children).
Which drug should an Asthmatic taking Salbutamol not be taking, and why?
- What: Beta-Blockers (i.e. Atenolol)
- Why: Salbutamol is a Beta-Agonist. Beta-blockers are Beta-Antagonists. These drugs will be acting in opposition, rendering them both ineffective.
What is Omalizumab used for?
- This is a recombinant DNA- derived humanised monoclonal antibody
- Specifically binds to free human IgE (immunoglobulin E)
- ** AKA: Anti IgE antibody that aids atopic (not non-atopic) asthmatics.**
Why does Omalizumab not help obese asthmatics?
- IgE (immunoglobulin E) is an inflammatory mediator released in atopic asthma.
- Omalizumab blocks production of IgE.
- Asthma caused by obesity does not trigger IgE release as part of an immune cascade.
- This monoclonal antibody anti-IgE treatment will therefore be ineffective.
How does Omalizumab work?
- Binds to free Ige (Immunoglobulin E), decreasing the amount of cell bound IgE
- Decreases expression of receptors that have a high affinity for IgE (i.e. FceRI receptors)
- Decreases the amount of inflammatory mediators released by cells such as mast cells, Basophils, or Eosinophils.
- These collectively decrease allergic inflammation, and prevent exacerbation of asthma.
What is Mepoluzimab?
Mepoluzimab is a…
- Humanised monoclonal antibody
- Recognises IL 5 (Interleukin 5 - this is a cytokine of the innate immune response).
- Reduces Eosinophil production and proliferation.
For which respiratory conditions are leukotrine receptor antagonists used in treatment?
Leukotrine antagonists are Helpful in:
- Cold air induced asthma
- Exercise induced asthma
- Aspirin induced asthma
How is** aspirin** thought to induce Asthma?
- A very complex question that is still being researched
- One theory suggests pharmacological effect on COX enzymes.
- Inhibition of COX enzymes inhibits synthesis of bronchodilatory prostaglandins
What spirometry result is diagnostic of COPD?
- Ratio of FEV (Forced expiratory volume)/FVC (forced vital capaciity) = less than 0.7
- This question is covered in MI WEEK in my year 2 library.
In which age group do most asthmatics first present to the GP?
0-4 years (67.7%).
When taking a focussed history from a patient you suspect to have asthma, what are the key points to cover?
- Exercise induced?
- Wheeze?
- SOB (shortness of breath) and/or tight chest?
- Nocturnal cough
- “Tummy ache” (Paeds)
- History of URTIs (Upper Respiratory Tract infections)?
- Are there any nasal symptoms?
- Is this Atopic? (i.e., any eczema, hayfever, allergies, smoking history, Family history)
What are the (important to remember) differential diagnosis for a presenting wheeze in a child under 1 year?
- Viral - Recurrent URTIs - Bronchiolitis - see slide for others (lecture 2 wednesday)
What is the commonest Acute lower respiratory tract infection (LRTI) in infancy?
Bronchiolitis.
What are the clinical signs of Bronchiolitis?
- Respiratory distress:
- Tachynopea
- Grunting
- Subcostal and Intercostal recession -
Also:
- Tracheal tug
- Nasal flaring
- Hyperinflation with palpable liver edge.
- Widespread fine crepitations throughout respiratory cycle.
- Hypoxia
- Fever in most (<38.5C)
What is Harrison Sulcus?
Harrison’s sulcus is a horizontal groove along the lower border of the thorax corresponding to the costal insertion of the diaphragm; It is usually caused by chronic asthma or obstructive respiratory disease.
What is the salute sign in children with wheeze?
The allergic salute sign is the upward rubbing of the nose (often in children), in allergic rhinitis, asthma, or other conditions of the respiratory tract productive of nasal mucus.
What are the side effects of steroids used for the treatment of Asthma?
- Infections in and around the mouth (Candida)
- Cushings syndrome
- Adrenal Suppression (high dose exogenous steroids inhibit endogenous production)
- Reduced resistance to chickenpox
What is a “PEEP sign” in a child?
Positive End Expiratory Pressure.
- In a child, this may present as constant crying or an O shaped mouth, which keeps the airway open a little bit.
What is the definition of Asthma?
“Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role.
The chronic inflammation causes an associated increasein airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning.
These episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment.”
What is the estimated number of people that die prematurely each year as a result of Asthma?
It is estimated that around 250,000 people die prematurely each year as a result of asthma.
What is the difference between atopic and non-atopic Asthma?
Cause:
- Atopic - ID’able inducing agent
- Non-Atopic - No obvious cause
Who gets it:
- Atopic - Majority in children and young adults
- Non-atopic - Often more persistent into adulthood/later life, often more severe
Which % of Asthma is related to atopy?
It is estimated that approximately 30-60% of asthma is related to atopy.
Which immunoglubulin is usually elevated in patients with atopic asthma?
IgE (Immunoglobulin E)
Are concordance rates for atopic asthma higher in monozygotic twins, or dizygotic twins?
Concordance rates for atopic asthma are higher in monozygotic twins than dizygotic twins.
Name three Environmental risk factors for developing Asthma.
- Smoking
- Pollution
- Occupation
Which Cytokines do T-Helper-1 cells produce?
- IFN Gamma
- IL2 (Interleukin 2)
- IL 10 (Interleukin 10)
- TNF (Tumour necrosis factor) alpha/beta
Which cytokines to T-Helper-2 cells help to produce?
- IL3
- IL4
- IL5
- IL6
- IL13
- GM-CSF
Week 210. According to epidemiological studies list 2 environmental factors that may increase your risk of developing **asthma **
• Childhood antibiotic use
• Childhood use of
paracetamol?
• Exposure allergen
• Sedentary life style
• Obesity
• Maternal smoking
• Pollution
Week 210
List 3 pathological features of asthma that may be found at post mortem?
Any of the following
• Inflammation: eosinophilic
• Mucus plugging
• Airway remodelling:– Airway wall thickening:
50-300% (Bronchial smooth muscle hypertrophy
+ airway oedema)
– Mucus gland hyperplasia
– Loss of surface epithelium
– Sub-epithelial fibrosis
Week 210
List 2 mediators, released by mast cells, which cause
bronchoconstriction clinically.
- Histamine
- Prostaglandin D2
- Leukotrienes (D4, E4)
Week 210
T-helper 2 lymphocytes release the cytokine IL-5
which promotes the differentiation of **which **inflammatory cell type?
Eosinophils
Week 210
In some individuals Non Steroidal Anti-inflammatory
Drugs (NSAIDS) may worsen asthma. Which enzyme
does this class of medication inhibit?
**Cycloxygenase (II) **
(Otherwise known as the COX 2 enzyme)
Week 210
Mr X is an 34 year old asthmatic on inhaled budesonide (200mcg bd) and PRN salbutamol. He attends your surgery as he is not sleeping at night due to cough and wheeze.What step of the asthma ladder is he currently on?
Step 2: low dose inhaled steroid + PRN B2 agonist
Week 210
Mr X is an 34 year old asthmatic on inhaled budesonide (200mcg bd) and PRN salbutamol. He attends your surgery as he is not sleeping at night due to cough and wheeze. If you were to increase his treatment name a class of drugs that you would add to his therapy?
Try LABA first and if ineffective consider increasing Inhaled CorticoSteroid then theophylline or leukotriene receptor antagonist.
Week 210
You are the A&E SHO on call. Miss B is a known
asthmaticwho presents withcough and SOB. On arrival the paramedics show you her ambulance card. Observations are as follows.Pulse 120, RR 26, Sats 94% on air. When you review her she hasmarked expiratory wheezeand is not able to talk full sentences.Grade her asthma severity.
Severe
Week 210
You are the A&E SHO on call. Miss B is a known
asthmatic who presents with cough and SOB. On arrival the paramedics show you her ambulance card.
Observations are as follows. Pulse 120, RR 26, Sats
94% on air. When you review her she has marked
expiratory wheeze and is not able to talk full sentences. **Name 3 meds you would consider starting her on. **
- Salbutamol 5mg nebulised
- Ipratropium bromide 500mcg nebulised
- Prednisolone 40mg od po
Week 210
You are the A&E SHO on call. Miss B is a known
asthmatic who presents with cough and SOB. On arrival the paramedics show you her ambulance card.
Observations are as follows. Pulse 120, RR 26, Sats
94% on air. When you review her she has marked
expiratory wheeze and is not able to talk full sentences.You do a blood gas. what concernes you about this blood gas?
Normal pCO2 with worsening hypoxia
Week 210
Mrs A is a 44 year old atopic asthmatic. She currently
taking symbicort tubohaler 400/12 (eformoterol +
budesonide 400). She is also taking uniphyllin
(theophylline). What step of the Asthma ladder is she on?
Step 4: on high dose inhaled steroids, LABA and
theophylline