210 - Asthma Flashcards by Lucy Knox

With regards to epidemiology what is the prevalence of asthma in the adult welsh population?

1:12 welsh adults

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According to epidemiological studies list 2 environmental factors that may increase you risk of developing asthma

Increased risk
• Caesarian delivery?
• Childhood antibiotic use
• Childhood use of paracetamol?
• Exposure allergen
• Sedentary life style
• Obesity
• Maternal smoking
• Pollution

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According to epidemiological studies list 2 environmental factors that may decrease you risk of developing asthma

Reduced Risk
• Vaginal delivery
• Breast feeding
• Infection: “The Hygiene Hypothesis”
• Exposure to rural environment
• Increase antioxidants

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List 3 pathological features of asthma that may be found at post mortem?

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

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List 2 mediators release by mast cells which cause bronchoconstriction clinically

Histamine, Prostaglandin D2, Leukotrienes (D4, E4)

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T-helper 2 lymphocytes release the cytokine IL-5 which promotes the differentiation of which inflammatory cell type?

Eosinophils

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In some individuals Non Steroidal Anti-inflammatory Drugs (NSAIDS) may worsen asthma. Which enzyme does this class of medication inhibit?

Cycloxygenase (II)

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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. What step of the asthma ladder is he currently on? (1 mark)

Step 2: low dose inhaled steroid + PRN B2 agonist

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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. 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 ICS then theophylline or leukotriene receptor antagonist

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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, RR26, Sats 94% on air. When you review her she has marked expiratory wheeze and is not able to talk full sentences.Grade her asthma severity

Severe 
Severe Asthma PEFR 33-55%
Unable to talk full sentences
Pulse >110
RR>25
Sats

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Salbutamol 5mg nebulised,Ipratropium bromide 500mcg nebulised, Prednisolone 40mg od po

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Miss B (Severe asthma attack, SOB, reducing sats) continues to deteriorate and the A&E sister is concerned. You do a blood gas:What concerns you about this blood gas?Value (Normal range)pH 7.35 (7.35-7.45)pCO2 6.0 (4.5-6kPA)pO2 10 (11.5.- 13)BE 1 (-1 /+1)Bicarb 25 (24/27)

Normal pCO2 ,worsening hypoxia.

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Mrs A is a 44 year old atopic asthmatic. She is currently taking symbicort 400/12 turbohaler 2 bd (eformoterol + budesonide). She is also taking uniphyllin (theophylline).What step of the asthma ladder is this patient currently on?

Step 4: on high dose inhaled steroids, LABA and theophylline

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What enzyme do theophylline tablets inhibit?

Phosphodiesterase: inhibiting the breakdown of cAMP

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State the side effects you are most likely to see in a patient taking a beclometasone inhaler?

Sore throat
Candidiasis
Hoarse voice
In patients taking 1mg/day beclometasone (or equivalent) we should also monitor carefully for systemic side effects

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For approximately how long would you expect to see the bronchodilatation effects of salmeterol?

12 Hours

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Which of the inflammatory mediators does montelukast block from reaching its receptor?

Leukotriene

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Name a drug or condition which can increase the half life of theophylline? And what symptoms could this cause?

Hepatic cirrhosis
CHF
Acute pulmonary oedema
Erythromycin
Fluconazole
Other drugs also inhibit metabolism of theophylline – Symptoms of toxicity include N&V, arrhythmias, restlessness, convulsions, coma

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Mary has come to her GP and described worsening asthma symptoms, what would you discuss before making changes to her drug treatment?

Possible triggers for worsening symptoms

Inhaler technique and compliance

Jack, aged 31years is using a Seretide 125 evohaler (fluticasone and salmeterol) inhaler and a salbutamol inhaler when required. His asthma has been well controlled for many years, with him rarely using his salbutamol inhaler and he has come for a review of his treatment.You decide that stepping down his treatment would be appropriate. Which of his drugs should be discontinued?

Salmeterol

But patient should remain on fluticasone and when required salbutamol so no reduction in dose count

What is Asthma?

A chronic inflammatory disorder of the airways- Airway hyper-responsiveness with airflow obstruction- reversible spontaneously or with treatment

How common is Asthma in wales?

1 in 10 children

1 in 12 adults

Globally, where is asthma more common?

In developed countries

What are the key symptoms of asthma?

Recurrent wheeze
Breathlessness
Cough
Chest tightness

What signs are seen in Asthma?

Diurnal variation - low peak flow in morning Obstructive spirometry pattern = FEV1/FEV < 70% Improvement by 12% with an inhaler Low PEFR

What signs/symptoms do you see in a severe asthma attack?

Tachycardia Hyper-expanded chest Severe dyspnoea Wheezing

In an asthma attack, what signs are a very bad sign?

Silent chest | Bradycardia

What are the different types of asthma?

Intrinsic - older onset, not obvious cause, more persistent, ?infection, exercise, stress, obesity Extrinsic - Occupational - Ectopic (IgE mediated)

What type of hypersensitivity reaction is seen in ectopic asthma?

Type 1 hypersensitivity | Against aeroallergens

What structural changes can be seen in asthma?

``` Loss of ciliated epithelium increased mucous production Thickening of basement membrane Fibroblast activation Smooth muscle hyper-responsiveness + hypertrophy ```

Describe the immune mechanism of asthma pathophysiology.

Allergen lands on airway epithelium Dendritic cell beneath detects it Presents it to a naive Th cell The Th cell then differentiates, in asthma more Th2 are formed rather than Th1 (non atopic response)Th2 stimulate atopic response- B cells + Plasma cells produce IgE- Mast cell degranulation (stimulated by IgE and IL-4 + 5)- Eosinophil - releases proteins (IL-5 stimulated)-> Bronchoconstriction

What is released in mast cell degranulation?

``` Histamine Serotonin Cytokines Leukotriene IL-5- Cause bronchoconstriction and mucous secretion ```

What factor in the immune response in asthma is directly related to the severity of asthma a pt has?

Eosinophil number

What is the sequence of an asthmatic response to an allergen?

Early phase - rapid Wheeze and cough Mast cell degranulation Late phase - hours after medication helps early symptoms- Symptoms reoccur- Infiltration of immune cells: eosinophils, basophils, lymphocytes, macrophages - cause epithelial damage and inflammation - Bronchoconstriction again

What are the steps in Asthma treatment?

``` 1st - SABA 2nd - Add inhaled Corticosteroid 3rd - LABA (must be with steroid) 4th - Leukotrienes or Xanthines 5th - Add oral steroid - specialist help ```

Name examples of SABAs.How do they work?

Salbutamol Terbutaline Increase cAMP - relax bronchial smooth muscle - inhibits release of inflam mediators- helps mucous clearance

What side effects do SABAs have?

Tremor Tachycardia Low K+

Name examples of inhaled corticosteroids.How do they work?

``` Beclometasone Fluticasone Budesonide Reduce immune cell infiltration + inflam mediators Reduces vascular permiability ```

What side effects do inhaled corticosteroids have?

Local: oral candida, hoarse voice, sore throat LT: osteopososis, infection risk, increased blood glucose, increase weight, reduce growth

Name examples of LABAs.How do they work?

Salmetrol, Formetrol Prolonged action due to lipid side chain Relax bronchial smooth muscle

Who can't use LABAs?

Under 5s | Must be taken with steroid

Name examples of Leukotrionine receptor antagonistsHow do they work?

Montelukast Zafirlukast Block leukotriene receptor on mast cells - reduce activation - reduce wheeze + bronchoconstriction and mucous

Who are leukotriene receptor antagonists particularly useful for?

``` Atopics Hayfever Exercise triggered Nocturnal NSAID sensitive ```

Name examples of XanthinesHow do they work?

Theophylline Aminophyline Inhibit phosphodiesterase which breaks down cAMP so increases cAMP - relaxes muscle + reduces inflam mediators

What is the risk with Xanthines?

Has a narror theraputic range Half life varies with other factors:- increases with : Cirrhosis, pul oedema, macrolides- decreases with : smoking, rafampicin

What are the side effects of Xanthines?

Nausea + vomiting tachycardia convulsions coma!

What are some other possible drug treatments of Asthma, not on the step wise approach / used in specialist care?

Omalizumab - anti IgE antibody Mepoluzimab - humanised monoclonal antibody against IL-5 - less eosinophil activation Antimuscarinics - acute attack IV magnesium sulphate - Acute attack Chromones - sodium chromoglicate - old fashioned, stabilised mast cells