Asthma Flashcards
What is asthma?
A common chronic inflammatory condition of the airways in which there is reversible airway obstruction
Classically asthma has which 3 pathophysiological characteristics?
- Airflow limitation (reversible spontaneously or w/ treatment)
- Airway hyperresponsiveness to a wide range of stimuli
- Bronchial inflammation with T cells, mast cells, eosinophils with associated plasma exudation, oedema, smooth muscle hypertrophy, matrix deposition, mucus plugging and epithelial damage
What are the symptoms and signs of poorly controlled asthma?
- Intermittent dyspnoea
- Wheeze
- Cough
- Sputum
- Chest tightness
Often worse at night and reversible
Give a differential diagnosis for wheeze
- asthma
- COPD
- acute viral or bacterial bronchitis
- acute ventricular failure
- anaphylaxis
- PE
- pneumothorax
- inhalation of foreign body
- sleep apnoea
- obstructive heart failure
- lung cancer
Which clinical features increase the probability of asthma in adults?
- Wheeze, SoB, chest tightness
- Diurnal variation
- Response to exercise, allergen, cold air
- Symptoms after aspirin or B-blocker
- History of atopy
- Family history of atopy/asthma
- Widespread wheeze heard on auscultation
- Unexplained low FEV1 or PEF
- Unexplained peripheral blood eosinophilia
What investigations are used to confirm the diagnosis of asthma?
- FEV1/FVC ratio - <80% of predicted
- FEV1 - <80% of predicted
- Bronchodilator should show 15% improvement in spirometry^
If both above are normal but there are signs/symptoms of asthma then do pulmonary function tests before and after a methacoline challenge(*)
- Peak expiratory flow rate - on walking, prior to taking bronchodilator and before bed after bronchodilator, compare patient’s to personal best/normal values for height + gender (reference) -> show diurnal variation
- Chest X-ray - normal or hyper-inflated (exclude pneumothorax)
- FBC - normal or raised eosinophils and/or neutrophilia
- Bronchial challenge test - positive - methacholine or histamine, tests airway hyperresponsiveness, good for those mainly presenting with cough, don’t do in those w poor lung function/history of brittle asthma or in kids
- Immunoassay for allergen-specific IgE - positive
- Skin prick allergy testing - positive
- Sputum eosinophillia - increased
- Exercise test (children) - FEV1 decreases
- Trial of corticosteroids - prednisolone, measure lung function before + after (>15% improvement)
What are the aims of asthma treatment?
to..
- abolish symptoms
- restore normal or best possible lung function
- reduce risk of severe attacks
- enable normal growth in children
- minimise absence from school/employment
How are aims of asthma treatments met?
- patient and family education about asthma
- patient and family participation in treatment
- avoidance of identified causes where possible
- use of the lowest effective doses of convenient medications to minimise short term and long term side effects
What extrinsic factors can be controlled to manage asthma?
- Avoid causative allergens (dustmites, pets, moulds, foods)
- Avoid active/passive smoking
- Investigate all possible occupational causative agents
- No beta-blockers in eye drop or tablet form
- Aspirin intolerent individuals should avoid dietary salicylates and NSAIDs
How are asthma medications delivered to patients and why is this important/useful?
- As aerosols or powders directly into lungs
- Delivered direct to the airways and first-pass metabolism in the liver is avoided
- Lower doses necessary and systemic unwanted effects minimised
What is the stepwise management of asthma?
- Step 1: occasional short-acting inhaled B2 agonist as required for symptom relief (eg. salbutamol), if used more than once daily or night-time symptoms, move to step 2
- Step 2: add standard dose inhaled steroid (eg. beclometasone)
- Step 3: add long-acting B2 agonist (eg salmeterol), continue inhaled corticosteroid, if no effect stop LABA and increase ICS. Leukotriene receptor antagonist (eg montelukast) or oral theophylline may be tried or LAMA
- Step 4: increase high-dose inhaled corticosteroids up to 2000μg, plus regular LABA plus either LTRA or modified release oral theophylline or B2 agonist or LAMA
- Step 5: add regular oral CS (prednisolone) at lowest possible dose (on top of prev therapy/ICS)
- Step 6: hospital admission / referral
Both national and international guidelines have been published on the stepwise treatment of asthma, based on which 3 principles?
- Asthma self management with regular asthma monitoring using PEF meters + individual treatment plans that are discussed with each patient + written down
- The appreciation that asthma is an inflammatory disease + that anti-inflammatory therapy should be started even in mild cases
- Use of short-acting inhaled bronchodilators (eg salbutamol) only to relieve breakthrough symptoms. Increased use of bronchodilator treatment to relieve increasing symptoms is an indication of deteriorating disease
Why do we use B2-Adrenoreceptor agonists for asthma?
- Selective for respiratory tract
- Do not stimulate B1 adrenoreceptors on myocardium
- Potent bronchodilators as they relax bronchial smooth muscle
- Relieve symptoms but do little for underlying inflammation
- SABAs (salbutamol + terbutaline) - 2 puffs when required, for mild asthma only
- LABAs (salmeterol + formoterol) - must always be given with inhaled CS
What is the mechanism of action of B2-agonists?
- B2 receptors found in smooth muscle of bronchi, GI, uterus + blood vessels
- Stimulates Gs pathway -> increased cAMP -> PKA -> Phosphorylates MLK -> smooth muscle relaxation
- Improved airflow in constricted airways
- B2-agonists also stimulate Na/K-ATPase pumps
- Causing shift of K+ from extracellular to intracellular compartment
- Useful adjunct in treatment of hyperkalaemia
What are side-effects of B2 agonists?
Acitvation of B2-receptors in other tissues accounts for the common ‘fight or flight’ adverse effects
- Tachycardia
- Palpitations
- Anxiety
- Tremor
- Increased serum glucose conc
- Muscle cramps (LABAs)
How do antimuscarinic bronchodilators help in asthma? Examples?
- M3 receptors found in large airways
- Peripheral lung tissue contains M3 and M1 receptors
- Stimulated by ACh -> parasympathetic effect (eg. bronchoconstriction)
- Blocking receptors -> bronchodilation
- Non-selective short acting muscarinic antagonists:
- Ipratropium bromide
- Long acting antimuscaranic:
- Tiotropium
List precipitating factors, including drugs, for an asthma attack
- Dust mite (+ its faeces), pollen, fur
- Viral infections
- Cold air
- Exercise
- Vapours + fumes: cig smoke, perfume, exhaust fumes
- Emotion
- Drugs: NSAIDs, beta-blockers
What would you say to a patient on how to reduce exposure to allergens including house dust and house dust mite?
- Keep windows and doors closed
- Keep pets out of bedroom / house
- Minimise household humidity
- Use “mite-proof” cases on mattresses and pillows; wash bed linens frequently in hot water
- Install a high-efficiency media filter in your furnace and air conditioning unit
- Discourage smoking
- Avoid household pets
- Identify + remove occupational exposure asap
Inhaled corticosteroids:
- examples
- common indications
- beclometasone, budesonide, fluticasone
- asthma: treat airways inflammation and control symptoms at ‘step 2’ of therapy where asthma is not adequately controlled by a short-acting B2-agonist alone
- COPD: control symptoms + prevent exacerbations in pts who have severe airflow obstruction on spirometry and/or recurrent exacerbations. ICS are usually prescribed in combo w/ LABA and/or LAMA (antimuscarinic bronchodilator)
What is the mechanism of action of inhaled corticosteroids?
- corticosteroids pass through plasma membrane
- interact w/ receptors in cytoplasm
- activated receptor then passes into nucleus
- to modify transcription of large # of genes
- pro-inflammatory interleukins, cytokines, chemokines downregulated
- while anti-inflammatory proteins upregulated
- in airways:
- reduced mucosal inflammation
- widens airways
- reduces mucus secretion
- this improves symptoms and reduces exacerbations in asthma + COPD
What are the important adverse effects of inhaled corticosteroids?
- immunosuppressive -> oral candidiasis
- hoarse voice
- COPD -> cause pneumonia
- few systemic adverse effects
What are the indications for systemic corticosteroids (eg. prednisolone)?
- to treat allergic or inflammatory disorders eg. anaphylaxis, asthma
- suppression of autoimmune disease, eg. IBD, inflammatory arthritis
- in treatment of some cancers as part of chemo or to reduce tumour-associated swelling
- hormone replacement in adrenal insufficiency or hypopituitarism
What is the mechanism of action of systemic corticosteroids?
- exert mainly glucocorticoid effects
- bind to cytosolic glucocorticoid receptors
- receptors translocate to nucleus
- bind to glucocorticoid-response elements -> regulate gene expression
- systemic CS commonly prescribed to modify immune response
- they upregulate anti-inflammatory genes
- downregulate pro-inflammatory genes (cytokines, TNF-a)
- direct actions on inflammatory cells incl suppression of circulating monocytes + eosinophils
- metabolic effects -> inc gluconeogenesis
- also have mineralocorticoid effects -> stimulate Na+ and water retention and K+ excretion in renal tubule
What are the important adverse effects of systemic corticosteroids?
- immunosuppression -> inc risk of infection
- metabolic: DM, osteoporosis
- Inc catabolism -> prox muscle weakness, skin thinning w/ easy bruising + gastritis
- mood + behavioural: insomnia, confusion, psychosis + suicidal
- hypertension, hypokalaemia, oedema (from mineralocorticoid actions)
- suppresses pituitary ACTH secretion, switching off stimulus for normal adrenal cortisol production, in prolonged tx -> adrenal atrophy
- if corticosteroids withdrawn suddenly -> acute Addisonian crisis w/ CV collapse
- slow withdrawal required to allow recovery of adrenal fxn
- symptoms of chronic glucocorticoid deficiency occur during tx withdrawal -> fatigue, weight loss, arthalgia
How do leukotriene antagonists work? (eg. Zileuton, Monteleukast)
- LTs = inflammatory mediators released by mast cells, cause bronchoconstriction + inc mucus production
- LTRAs useful in pts who still have symptoms despite taking high-dose ICS or oral CS and in pts with asthma induced by aspirin
2 main MOAs:
- Inhibition of 5-lipoxygenase pathway: drugs such as Zileuton block this pathway, inhibiting the synthethic pathway of leukotriene metabolism
- Antagonism of cysteinyl-leukotriene type 1 receptors: agents such as Montelukast block actions of cysteinyl leukotrienes at CysLT1 receptor on target cells such as bronchial sm muscle. Help improve asthma symptoms, reduce asthma exacerbations and limit markers of inflammation eg. eosinophils
Side effects: GI disturbances, headache
Clinical features can be used to determine the severity of an acute asthma attack.
What are the clinical features of a ‘severe’ attack?
- inability to complete sentences
- pulse > 110bpm
- RR > 25/min
- PEFR 33-50% predicted value or pt’s best
What are the clinical features of a ‘life threatening’ attack?
- silent chest
- cyanosis
- feeble resp rate
- exhaustion
- bradycardia or hypotension
- confusion or coma
- normal PaCO2 (should be low due to hyperventilation, normal means pt fatigued)
- PEFR <33% predicted value or patient’s best
- PaO2 <8kpa, SaO2 <92%
What is the emergency management of acute asthma?
- assess severity of attack - tachycardia? inability to speak? high RR?
- if PEFR <150L/min -> call ambulance + warn ITU if severe
- sit pt up, give 40-60% O2, via non-rebreathe bag
- aim to maintain O2 sats at 94-98%
- nebulised salbutamol 5mg or terbutaline 10mg
- plus ipratropium bromide 0.5mg nebulised w/ O2
- hydrocortisone 200mg i.v. (4 hourly / 24hrs)
- prednisolone 60mg orally (continued for 2/52)
- Abx if infection (CXR focal shadowing, purulent sputum)
- CXR to exclude pneumothorax
- monitor peak flow + sats, reassess regularly
- ABG -> if PaCO2 >7kPa -> ventilate
- give 1 of following infusions if no improvement:
- salbutamol 3-20 ug/min, or
- terbutaline 1.5-5.0 ug/min, or
- magensium sulphate 1.2-2g over 20 mins
- if still no improvement -> transfer to ITU
What measures should be taken prior to hospital discharge to prevent asthma recurrence?
patients before discharge must have:
- been stable on discharge medication for 24h (given a tapering dose of prednisolone)
- had inhaler technique checked
- PEFR must be >75% predicted or pts best + durnal variability <25%
- steroid (inhaled/oral) and bronchodilator therapy
- own a PEF meter + have mgmt plan
- GP appointment within 1 week
- resp clinic appt within 4 weeks
What are ways patients can be encouraged to take their asthma medications?
- simplification of treatment regimes
- education (patient + family)
- self-management plans (based on monitoring of PEFR and symptoms and written action plan showing patient how to act in exacerbations)
- During an attack, pt should be advised to:
- sit up
- inhaler - 1 puff every minute for 5 mins or until symptoms resolve
- if no improvement, call 999, carry on w/ 1 puff/5mins until help arrives
What is the difference between reliever and preventer inhalers?
- most people w/ asthma given reliever inhaler (blue) (SABA), used to relieve symptoms within few mins
- if a patient needs to use a reliever often, they may also need a preventer inhaler (steroids) - helps to reduce inflammation and sensitivity of airways, stopping symptoms from occurring, used everyday even without symptoms
- combination inhalers used if either of above don’t work
How would you explain the use of a preventer inhaler (eg. beclomethasone) to a patient ?
“(Name of inhaler) is a preventer – it helps to reduce the swelling in the airways and stops them from being so sensitive. You use this to lower the risk of severe attacks. I would like you to inhale …(x puff(s))…(x time(s) a day)…everyday. It’s really important that you don’t miss doses, as regular use is key to keeping your asthma/COPD under control”
Remind the patient to rinse mouth after use if the inhaler contains a steroid due to risk of oral candidiasis.
How would you explain the use of a reliever inhaler (eg. salbutamol) to a patient?
“(Name of inhaler) is a reliever. This is useful to help relieve immediate wheezing/asthma attacks. It works by relaxing the airways so that you can breathe more easily. You shouldn’t need this more than 3 times a week if your asthma is well controlled. Ask your GP for a review if you are using this more frequently. I would like you to inhale (x puff(s)) when you feel short of breath.”
What kinds of reliever inhalers are there?
- metered dose inhalers (MDIs) - give medicine in a spray form eg. ventolin, airomir, salamol - here spacers can be used to make inhalers more effective and reduce side-effects (eg. oral candidiasis)
- breath actuated inhalers (BAIs) such as easi-breathe, airmax, and autoinhaler automatically release a spray of medicine when you begin to inhale
- dry powder inhalers (DPIs), such as accuhaler, give the medicine in a dry powder instead of a spray
Spacers are used to improve drug deposition to the lungs in patients who cannot master their aerosol inhaler technique. They are useful in reducing side effects of high dose inhaled corticosteroids by reducing the amount of drug deposited in the mouth. Commonly used spacers are Volumatic and AeroChamber.
What are the steps in demonstrating how to use a spacer to a patient?
- prepare inhaler (shake aerosol inhaler)
- attach inhaler mouthpiece to the spacer device
- breathe out gently as far as is comfortable
- seal lips around the spacer mouthpiece
- release 1 dose into the spacer device
- breathe in and out through the spacer mouthpiece several times
- administer second dose if needed + finish
Spacer should be washed w/ detergent once a month and left to air-dry, don’t use wipes as drug particles will stick to sides.
How do you assess a patient’s inhaler technique?
- ask pt to carry out procedure themselves whilst you observe
- most pt’s techniques will require tweaking
- point out the positives, then introduce room for improvement
demonstrate > observe > fine tune > repeat as necessary
Explain to a patient how to measure their PEFR
- ensure PEFR meter set to zero
- sit up straight or stand
- take a deep breath
- place your mouth around the mouthpiece of the PEFR meter, ensuring a tight seal w/ your lips
- exhale as forcefully as you possibly can manage
- note the PEFR reading
- repeat this process a further 2 times
- the highest reading of the 3 should be taken as the overall result
