Respiratory Medicine Flashcards
1
Q
What is FEV1, what is a normal value?
A
FEV1= Forced expiratory volume in 1 second
- In which a person takes a maximal inspiration and then exhales maximally as fast as possible. The important value is the fraction of the total “forced” vital capacity expired in 1 second
- Healthy individuals can expire approximately 80% of the vital capacity in one second
2
Q
What is FEF25?
A
Flow is greatest at the start of expiration, it declines linearly with volume. FEF25 = flow at point when 25% of total volume to be exhaled has been exhaled
3
Q
What is does a low FVC suggest?
A
FVC—Forced vital capacity; the total volume of air that can be exhaled during a maximal forced expiration effort
A low FVC = airway restriction
4
Q
FEV1/FVC is <0.7, what does this indicate?
A
If the ratio is below 0.7 = airway obstruction
5
Q
FEV1/FVC is normal but FVC is low, what does this indicate?
A
If the ratio is high i.e. normal but the FVC is low = airway
6
Q
What is the difference between type 1 and type 2 respiratory failure?
A
- TYPE 1 RESPIRATORY FAILURE:
• pO2 (partial O2 pressure) is low
• pCO2 (partial CO2 pressure) is low or normal
• With Type 1 = 1 change = low pO2 then normal/low CO2
• Pulmonary embolism (form of ventilation-perfusion mismatch) most commonly causes Type 1
- TYPE 2 RESPIRATORY FAILURE:
• pO2 is low
- pCO2 is high
- With Type2=2changes=lowpO2+highpCO2
• Alveolar Hypoventilation causes Type 2
7
Q
What can cause respiratory failure?
A
Respiratory failure can occur as a result of:
• Impaired ventilation:
- Neural problems e.g. due to narcotics, encephalitis, a cerebral space-occupying lesion, motor neurone disease (resulting in neuromuscular weakness) etc
- Mechanical problems e.g. airway obstruction (type 1, if severe type 2, e.g. obstructive sleep apnoea (OSA) - relaxation of pharynx
- Impaired perfusion, if extensive e.g. cardiac failure or multiple pulmonary emboli
- Impaired gas exchange defects, if severe e.g. emphysema or diffuse pulmonary fibrosis
8
Q
Give 5 signs of hypercapnia
A
Signs of hypercapnoea (high CO2):
- Bounding pulse
- Flapping tremor
- Confusion
- Drowsiness
- Reduced consciousness
9
Q
How would you manage Type 1 Respiratory failure?
A
Management:
TYPE1 RESP FAILURE:
- Treat the underlying cause
- Give O2 (35-60%) by face mask to correct the hypoxia
- If PaO2 does not rise above 8kPa then give assisted ventilation
10
Q
How would you manage type 2 respiratory failure?
A
TYPE2 RESP FAILURE:
In type II failure, the respiratory centre is likely to have become desensitised to CO2 levels, and hypoxia will now be its main driving force, thus oxygen therapy should be given with care!
- Give controlled oxygen therapy, starting at 24% O2
- Recheck the ABG after 20 minutes – if the PaCO2 is steady or lower, then you can increase the O2 to 28%.
- If the PaCO2 has risen >1.5kPa– then consider giving a respiratory stimulant such as doxapram (1.5-4mg/min IV) or assisted ventilation.
- You can also see CO2 retention as physical signs – the patient will become drowsy and confused
- If this fails consider intubation / ventilation
11
Q
What is the difference between obstructive and restrictive respiratory disease?
Give examples of each
A
Restrictive vs. Obstructive Respiratory Disease:
- Obstructive:
• FEV1/FVC below 0.7 - FEV1 lower than FVC
- E.g.:
ASTHMA:
- Variable airflow obstruction
- Reversible
COPD:
- Relatively fixed airflow obstruction
- May be a mixture of restrictive and obstructive disease
- Restrictive:
- FEV1/FVC above 0.7
- FVC & FEV1 below 80% predicted value
- Due to restriction, lung volumes are small and most of breath is out in first second
- Interstitial lung disease:
- FIBROSING ALVEOLITIS
- SARCOID
12
Q
What is transfer co efficent?
How does it change?
A
- Transfer Co-efficient:
- Measure of ability of oxygen to diffuse across the alveolar membrane
- Can calculate by inspiring a small amount of carbon monoxide (not too much since can kill) then hold breath for 10 seconds at total lung capacity (TLC) then the gas transferred is measured
- Low in:
- Severe emphysema
- Fibrosing alveolitis
- Anaemia
- Pulmonary hypertension
- Idiopathic pulmonary fibrosis
- COPD
- High in:
- Pulmonary haemorrhage - can absorb O2 very efficiently due to bleeding resulting in more red blood cells being available
13
Q
What is asthma?
A
- Asthma is the most common chronic respiratory disorder encountered in clinical practice.
- It affects over 10% of children and around 5-10% of adults, with the prevalence of asthma increasing.
- Not only does asthma account for a significant morbidity burden it should be remembered that around 1,000 people die in a year from asthma in the UK, 30-40 of whom are children.
- Asthma may be defined as a chronic inflammatory disorder of the airways secondary to type 1 hypersensitivity.
- The symptoms are variable and recurring and manifest as reversible bronchospasm resulting in airway obstruction.
- The immune response is CD4 mediated, and the lungs will show an eosinophil infiltrate
- asthma exists where the obstruction is reversible by >15%, and COPD exists where it is reversible by <15%.
- Asthma often ‘flares up’ with viral infections – which often cause a loud wheeze.
- Asthma may present at any age although it typically develops in childhood
It should be remembered that it is common for young children to wheeze when they develop a virus (‘viral-induced wheeze’). This makes the diagnosis of asthma in younger children difficult.
14
Q
What are the three characteristics of asthma?
A
Three main characteristics of asthma (very important this got asked many times in exams):
- Airflow limitation – this is usually reversible, either spontaneously, or with treatment
- Airway hyper-responsiveness – this occurs to a wide range of stimuli
- Inflammation of the bronchi – with infiltration by eosinophils, T cells and mast cells. there is associated plasma exudate, oedema, smooth muscle hypertrophy, mucus plugging and epithelial damage.
15
Q
How can you test for airway hyper responsiveness?
A
You can test for airway hyper-responsiveness by asking the patient to inhale gradually increasing amounts of methacholine or histamine. This is known as a bronchial provocation test. This will induce transient airflow limitation in 20% of the population – and these are the patients that exhibit airway hyper-responsiveness.
16
Q
What are the two types of asthma?
A
17
Q
What are the two types of allergic asthma?
A
The disease can either be intrinsic (aka cryptogenic); where no causatory factor can be found, or extrinsic, where there is a definite external cause.
- Intrinsic – this often starts in middle age, and is sometimes called late onset asthma. No trigger can be identified.
-
Extrinsic – this usually occurs in atopic individuals who have positive skin prick test results. This type of asthma causes 90% of childhood cases, and 50% of adults with chronic asthma. It is often accompanied by eczema.
- Non-atopic individuals can develop asthma in later life via sensitisation to e.g. occupational agents, aspirin, or as a result of taking β-blockers for hypertension or angina.
Extrinsic asthma involves a type I hypersensitivity reaction to inhaled allergens (there is also a delayed phase reaction, type IV hypersensitivity which occurs hours-days after
18
Q
What are the risk factors for asthma?
A
A number of factors can increase the risk of a person developing asthma:
- personal or family history of atopy
- antenatal factors: maternal smoking, viral infection during pregnancy (especially RSV)
- low birth weight
- not being breastfed
- maternal smoking around child
- exposure to high concentrations of allergens (e.g. house dust mite)
- air pollution
- ‘hygiene hypothesis’: studies show an increased risk of asthma and other allergic conditions in developed countries. Reduced exposure to infectious agents in childhood prevents normal development of the immune system resulting in a Th2 predominant response
19
Q
What is atopy?
In which families does it run in?
How does it present?
What are people with asthma also commonly allergic to?
A
ATOPY:
- individuals who readily develop IgE (produced by B cells) against common environmental antigens
- There is a strong correlation between the levels of IgE and the severity of asthma and airway hyper-responsiveness
- Serum IgE levels are affects by several genetic and environmental factors
- The trait runs in families (i.e. genetic component)
- The ADAM33 gene is associated with airway hyper-responsiveness, and airway remodelling
- The PHF11 gene is associated with increased IgE production
- Environmental factors:
- Early childhood exposure to allergens and maternal smoking has a major influence on IgE production
- Hygiene hypothesis
- Focusing on atopy, patients with asthma also suffer from other IgE-mediated atopic conditions such as:
- atopic dermatitis (eczema)
- allergic rhinitis (hay fever)
Notes:
- A number of patients with asthma are sensitive to aspirin.
- Patients who are most sensitive to asthma often suffer from nasal polyps. (N.B. the nose is part of the respiratory tract from a histological point of view)
- The allergens for asthma are very similar to those that cause rhinitis. Rhinitis is inflammation of the mucosal lining of the upper respiratory tract, particularly affecting areas near the nose; thus causing a constant runny nose.
20
Q
What is occupational asthma?
Give some common triggers?
When does it present?
A
Occupational asthma
- Around 10-15% of adult asthma cases are related to allergens in the workplace.
- Patients may either present with concerns that chemicals at work are worsening their asthma or you may notice in the history that symptoms seem better at weekends / when away from work
- It is usually diagnosed by observing reduced peak flows during the working week with normal readings when not at work.
- Diagnosis: serial measurements if PEF at work and away from work
- Exposure to the following chemicals is associated with occupational asthma:
- isocyanates - the most common cause. Example occupations include spray painting and foam moulding using adhesives
- flour
- platinum salts
- soldering flux resin
- glutaraldehyde
- epoxy resins
- proteolytic enzymes
- Typically the onset is 3-6 months after you start working at the place, although it can take years to develop.
- Check for possible occupational asthma by asking employed people with suspected new-onset asthma, or established asthma that is poorly controlled:
- Are symptoms better on days away from work?
- Are symptoms better when on holiday?
21
Q
What is the pathophysiology of asthma?
A
Pathophysiology:
- Primary abnormality in asthma is narrowing of the airway which is due to smooth muscle contraction, thickening of the airway wall by cellular infiltration and inflammation and the presence of secretions within the airway lumen
- Exposure to the antigen will make CD4 T cells differentiate into T helper cells (Th2 type, as opposed to Th1), and they will begin to secrete IL-4 and IL-5.
- IL-4 will cause B cells to become plasma cells and being secreting IgE.
- IL-5 will act on eosinophils and mast cells, making them reactive to the new antigen. Other factors are also released that are chemotaxic for eosinophils.
- Inflammation:
- Mast cells:
- Are increased in the epithelium, smooth muscle and mucous glands in asthma
- Become sensitised when IgE binds to mast cell receptor - mast cell will then respond to allergen if it binds to IgE
- When an allergen binds to IgE bound to the mast cell
- Mast cells releases:
- Histamine (seconds) - results in bronchoconstriction (via H1 receptor) and inflammation
- Tryptase (good indicator of mast cell activity since only found in mast cells)
- Prostaglandin 2 (minutes) - type of eicosanoid
- Cysteine leukotrienes (cys-LTs) (minutes) and more potent than histamine - results in bronchoconstriction (via cys-LT1 receptor) and inflammation
- Cytokines; TNF-alpha, IL-3 (increases number of mast cells), -4 (causes IgE synthesis) & -5 - synthesised in hours - results in inflammation and airway remodelling
- All of which act on smooth muscle, small blood vessels, mucus-secreting cells and sensory nerves causing the immediate asthmatic reaction
- Eosinophils:
- Found in large numbers in the bronchial wall and secretions of asthmatics
- Attracted to the airway by cytokines IL-3 & IL-5, these mediators also prime eosinophils for enhance mediator secretion
- When activated, eosinophils release LTC4 and basic proteins such as major basic protein (MBP), eosinophilic cationic protein (ECP) and eosinophilic peroxidase (EPX) that are toxic to epithelial cells
- Both the number and activation of eosinophils are rapidly decreased by corticosteroids
• Dendritic cells & lymphocytes:
- Abundant in mucous membranes of the airways and the alveoli
- Dendritic cells play a role in the initial uptake and presentation of allergens to lymphocytes
- T helper lymphocytes show activation and release of their cytokines is a key part in the activation of mast cells
Changes in the lung after allergen challenge:
- 30 mins after challenge; there is bronchoconstriction
- 3 hours after; the initial bronchoconstriction decreases, then inflammation occurs due to the vasodilation which decreases blood flow and thus leads to a build up of white blood cells, increased vascular permeability and unregulated adhesion molecules
- 6 hours after; There is worsening inflammation resulting in eosinophils (who are attracted to the site by chemotaxis due to IL-5) releasing their mediators that result in a second wave of bronchoconstriction
- Bronchodilators (the β-adrenergics) are good at treating the initial phase reaction; the late phase reaction tends not to respond well.
- Steroids (and other anti-inflammatories) are good for preventing the inflammation that causes the late phase reaction.
- The late phase reaction is more likely in poorly controlled / chronic asthma, where there is already a reasonable aggregation of eosinophils in the mucosa.
Effects of the bronchoconstriction and inflammation on lung function:
- Distal airway hyperinflation and collapse (and obviously reduced gaseous transfer to these regions)
- Mucus plugging of the bronchi – due to increased number of goblet cells – and these also secrete more than normal goblet cells
- Bronchial inflammation
- Curschmann’s spirals – these are bits of epithelium that have been shed, and can be seen on histology of the mucous plugs
- Charcot-Layden crystals – crystals that are formed as a result of eosinophil aggregation
- Thickening of the bronchial basement membrane – this is particularly important, and occurs via the process of remodelling (more on this below lolz). The submucosa becomes thickened, and this means that when the smooth muscle does contract, there is excessive narrowing of the airway in response to the contraction.
- Effects on the epithelium – the epithelium loses many of its columnar ciliated cells, and these are replaced with over-active mucous secreting cells. The mucosa also releases lots of inflammatory proteins. It is also likely to get damaged in the inflammatory processes, and this (along with the excess mucous production) increases the risk of infection.
- Effects on smooth muscle – the smooth muscle is hypertrophied, and also undergoes changes which make it more likely to contract, and more likely to stay contracted for longer.
22
Q
List 4 symptoms and 4 clinical signs of asthma
A
Symptoms
- Diurnal variability(symptoms worse at night or early in the morning)
- cough: often worse at night
- periodic dyspnoea/SOB
- wheeze
- chest tightness
- attacks are due to triggers/Provoking factors; allergens, infections, exercise, cold air
Signs
- polyphonic expiratory wheeze on auscultation
- reduced peak expiratory flow rate (PEFR)
Acute asthma features (more on this below):
- worsening dyspnoea, wheeze and cough that is not responding to salbutamol
- tachypnoea
- prolonged expiratory time
- reduced chest expansion
- bilateral expiratory polyphonic wheeze
- maybe triggered by a respiratory tract infection
23
Q
Define uncontrolled asthma
A
Uncontrolled asthma:
This describes asthma that has an impact on a person’s lifestyle or restricts their normal activities
This guideline uses the following pragmatic thresholds to define uncontrolled asthma:
- 3 or more days a week with symptoms or
- 3 or more days a week with required use of a SABA for symptomatic relief or
- 1 or more nights a week with awakening due to asthma.
24
Q
list 4 Differential diagnoses of asthma
A
Differential diagnosis:
- COPD
- GORD
- Large airway obstruction by foreign body/tumour
- Pneumothorax
- Pulmonary fibrosis
- Bronchiolitis, croup (children)
- bronchiectasis
25
Q
What investigations would you request for asthma and in what order?
A
Investigations:
N.B. Cant diagnose a child under 5.
LUNG FUNCTION TESTS:
1.Spirometry:
- It is a test which measures the amount (volume) and speed (flow) of air during exhalation and inhalation.
- It is helpful in categorising respiratory disorders as either obstructive (conditions where there is obstruction to airflow, for example due to bronchoconstriction in asthma) or restrictive (where there is restriction to the lungs, for example lung fibrosis).
- Key metrics include:
- FEV1: forced expiratory volume - volume that has been exhaled at the end of the first second of forced expiration
- FVC: forced vital capacity - volume that has been exhaled after a maximal expiration following a full inspiration
- Typical results in asthma:
- FEV1 - significantly reduced
- FVC - normal
- FEV1% (FEV1/FVC) < 70%
2.Peak expiratory flow rate (PEFR):
- This is the most useful test in asthma.
- Patients should take two readings per day, to show the variability of the disease.
- In patients with suspected asthma, you should get them to take two weeks worth of measurements whilst at work, and 2 weeks whilst at home, to prove the cause of the disease.
- It can also show variation between exercise/rest, night/day, before/after bronchodilator
3.Carbon monoxide transfer test- normal in asthma
Airway inflammation measures:
Fractional exhaled nitric oxide (FeNO):
- nitric oxide is produced by 3 types of nitric oxide synthases (NOS).
- one of the types is inducible (iNOS) and levels tend to rise in inflammatory cells, particularly eosinophils
- levels of NO therefore typically correlate with levels of inflammation.
Airway hyperreactivity measures (only in adults, rarely done as its dangerous, don’t know with brittle asthma):
Direct bronchial challenge test with histamine or methacholine
Other investigations to consider:
- chest x-ray: particular in older patients or those with a history of smoking, good at excuding pneumothorax (which is also a complication of asthma)
- skin prick tests – you should perform these on all newly diagnosed asthmatics to help find a cause
- Blood and sputum tests – you can test these for high number of eosinophils; and this may help form your diagnosis, but is not diagnostic on its own
- Trial of corticosteroids – this can be very useful in children at first presentation.
- Exercise test – often used in children, a negative result does not exclude asthma
26
Q
Outline the management of asthma
A
Management:
- Optimal control should include assessment of a combination of the patient’s symptoms and their PFTs.
- The goal for optimal control is to have the patient asymptomatic with normal PFTs
- Controlling extrinsic factors- You may want to try and reduce the risk of a person coming into contact with a provoking factor. Dust mite faeces is a major cause, and so changing bedding regularly is a good way to manage this risk.
- Patients should also avoid taking β- blockers in any form. This is an absolute contra-indication.
- 50% of those with occupational asthma will have no problems if they are kept away from the cause. The other 50% may still continue to have symptoms, and will have bad exacerbations if they back into contact with the causing agent.
STEPWISE TREATMENT:
For adults ( ages 17+):
- short-acting beta2 agonist (SABA) regas reliever therapy
- SABA+ low dose ICS – first line maintenance therapy
- SABA+ low dose ICS+ LTRA (Montelukast)- review treatment response in 4-8 weeks
- SABA+ low dose ICS +LABA +/- LTRA
- MART* regimen (that has low dose ICS in it) +/- LTRA
- MART* regimen (that has moderate ICS in it) +/- LTRA OR fixed dose regimen of moderate dose ICS, LABA and SABA +/- LTRA
- Any options from:
- Increasing the ICS to a high maintenance dose (this should only be offered as part of a fixed-dose regimen, with a SABA used as a reliever therapy)
- a trial of an additional drug (for example, a long-acting muscarinic receptor antagonist or theophylline)
- seeking advice from a healthcare professional with expertise in asthma.
Maintenance and reliever therapy (MART)*
- a form of combined ICS and LABA treatment in which a single inhaler, containing both ICS and a fast-acting LABA, is used for both daily maintenance therapy and the relief of symptoms as required
- MART is only available for ICS and LABA combinations in which the LABA has a fast-acting component (for example, formoterol)
27
Q
What are the different kinds of beta 2 agonists?
Give examples of each
A
Beta2-agonists:
- Are beta-2 selective i.e. work only in lungs (B1 is heart & B3 is adipose tissue) - however is high doses the B2-agonists are not selective and will act on other receptors
- When B2 agonist binds to B2 receptor coupled with Gs protein this results in adenyl cyclase converting ATP to cyclic AMP and increases in cyclic AMP leads to bronchodilation
- Beta-agonists also inhibit mast cell activity thereby reducing inflammatory response
- Short acting Beta agonist (SABA) (4 hours):
- SALBUTAMOL (partial agonist)
- TERBUTALINE
- Prescribed as two puffs as required
- Long acting Beta agonist (LABA) (12 hours):
- SALMETEROL
- FORMOTEROL (full agonist)
- Longer acting since are more lipophilic so remain in tissue for longer
- At high concentrations e.g. in badly controlled asthmatics a tolerance may develop due to B2-receptor desensitisation
28
Q
What are the different kinds of muscarinic antagonists and give examples of each?
A
Muscarinic antagonists:
- Short-acting e.g. IPRATROPIUM
- Long acting e.g. TIOTROPIUM - has high affinity and disassociates slowly from muscarinic receptors
- Act on airway M3 receptors
- Normally ACh (parasympathetic) binds to M3 receptor bound to Gq protein resulting in phospholipase C converting phosphate to DAG resulting in protein kinase C production that results in smooth muscle contraction
- Muscarinic antagonists prevent ACh from binding since they bind to the M3 receptor thereby blocking ACh action
29
Q
What are methylxanthines and give examples?
A
Methylxanthines:
- These are phosphodiesterase (PDE) inhibitors they prevent the conversion of cyclic-AMP to 5’-AMP resulting in a build up of cyclic-AMP and thus increased smooth muscle relaxation
- Long-acting; THEOPHYLLINE (non-selective so has wide range of side effects e.g. CVS, CNS & GI tract) & AMINOPHYLLINE
30
Q
What inhaled corticosterioids used in asthma?
A
Inhaled corticosteroids (ICS):
- All patients who have regular persistent symptoms need regular treatment with inhaled corticosteroids
- There are two types of corticosteroids; mineralocorticoids (aldosterone - involved in Na+ retention) and glucocorticoids (hydrocortisone - ensures glucose levels are correct, anti- inflammatory properties)
- Hydrocortisone has anti-inflammatory properties but also has significant mineralocorticoid action so is not suitable as a treatment
- Examples: BECLOMETASONE, BUDESONIDE
- Glucocorticoids interfere with gene transcription
- Glucocorticoid receptor is found on promoter region of DNA has zinc fingers that anchor receptor to DNA and recognise discrete sequences
- There is either a + Glucocorticoid response element (GRE) - increases transcription or - GRE - decreases transcription on the glucocorticoid receptor
- -GRE results in the suppression of cytokines e.g. TNF, IL-5 and IL-3 thereby reducing inflammation and thus reducing symptoms
- +GRE results in increased lipocortin which inhibits PLA2 meaning there is a decrease in arachidonic acid and thus a decrease in prostaglandins and leukotrienes resulting in reduced inflammation and thus reducing symptoms
- Side effects
- Susceptibility to infection due to cytokine suppression
- Metabolic such as osteoporosis and muscle wasting
31
Q
What other agents have bronchodilator effects?
A
Other agents with bronchodilator activity:
- Leukotriene receptor antagonist e.g. MONTELUKAST
- Oral corticosteroid needed for those not controlled on inhaled
- corticosteroids e.g. PREDNISOLONE
Steroid-sparing agents:
- METHOTREXATE
- CICLOSPORIN
- iv immunoglobulin
- anti-IgE monoclonal antibody - OMALIZUMAB
32
Q
What are the categories of acute asthma?
A
33
Q
What does a normal pCO2 in an acute asthma attack indicate?
A
- In addition, a normal pCO2 in an acute asthma attack indicates exhaustion and should, therefore, be classified as life-threatening.
Pulsus paradoxis – on inspiration, the diastolic pressure
34
Q
What is pulsus parodoxus?
A
Pulsus paradoxus – on inspiration, the diastolic pressure decreases by 10mmHg. This is present in about 45% of cases of asthma.
35
Q
What is the management of acute asthma?
A
Hospital management – ideally you should start treatment before doing investigations!
-
Do an ABG – it may be life-threatening if:
- CO2 > 5kPa (high)
- O2 <8kPa (low)
- Low pH
- Start on 100% O2 (non-rebreathing mask) with the patient sat upright in bed- aim for 94-98% ( do not delay this even in the absence of pulse oximetry)
- Give 5mg salbutamol via nebulizer on 100% O2
- Give hydrocortisone 100mg IV or 50mg prednisolone orally. Give both if very unwell
- Give 0.5mg ipratropium bromide via nebulizer
- Do CXR to exclude pneumothorax if failed to respond to treatment
If life-threatening signs are present:
- Inform ITU and seniors
- Give magnesium sulphate 1.2-2g IV over 20 minutes
- Change the nebulized salbutamol every 15 minutes, or give 10mg continuously per hour. Only give more ipratropium every 4-6 hours
- Repeat PEF every 15-30 minutes to assess the situation. If improving then gradually reduce O2 and nebs. If not, try and find senior, keep giving nebs, and consider aminophyline.
- Check pulse oximetry – aiming for sats >92%
- Check blood gases every 2 hours, and definitely within 2 hours of admission
- Record PEF’s and β-agonists when given / carried out
- A maximum of 60mg/day of prednisolone can be given (orally)
- You can give 200mg hydrocortisone every 4 hours for a max of 24 hours
- Give oral prednisolone for 5 days after they are starting to recover
- Ventilation is an option – you would have to call an anaesthetist
- Patients have to have >75% predicted PEF for discharge
- After recovery from a severe asthma attack, oral corticosteroids should be continued until there are no residual symptoms, especially at night, and the peak expiratory flow rate is at least 80% of the person’s previous best.
- High doses of these drugs can be stopped abruptly if used for 3 weeks or less, or tapered off if they have been used for a longer period.
Brittle asthma – ‘catastrophic sudden severe asthma’
These patients are at risk from sudden death, even if their asthma is well controlled between attacks. An attack can come on very quickly within minutes.
36
Q
What is COPD?
A
CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)
- COPD is an umbrella term encompassing the older terms chronic bronchitis and emphysema.
- A disease state characterised by airflow limitation that is not fully reversible
- The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to certain particles
- Patients typically have recurrent exacerbations – some are mild while some need hospitlization
- CHRONIC BRONCHITIS: Cough with sputum for 3 months for 2 or more years
- EMPHYSEMA: Histologically its enlarged airspaces distal to terminal bronchioles, with destruction of alveolar walls
- In COPD the FEV1:FVC ratio is <70%. COPD can also be diagnosed in patients with FEV1:FVC ratio is >70% on the basis of clinical signs and symptoms – such as shortness of breath, or cough.
-
The three main pathological effects in COPD:
- Loss of elasticity of the alveoli
- Inflammation and scarring – reducing the size of the lumen, as well as reducing elasticity
- Mucus hypersecretion – reducing the size of the lumen and increasing the distance gasses have to diffuse
37
Q
List 5 causes of COPD
A
- Smoking (10-20% of all smokers will develop COPD)- MOST COMMON CAUSE
- Alpha-1 antitrypsin deficiency** - causes early onset COPD
- cadmium (used in smelting)
- coal mining
- cotton
- cement
- grain
**Mutations in the alpha-1 antitrypsin gene on chromosome 14 lead to reduced hepatic production of alpha-1 antitrypsin which normally inhibits the proteolytic enzyme - neutrophil elastase. Therefore it causes early-onset COPD due to proteolytic lung damage. (Also causes cirrhosis so more on this disease in hebas GI notes)
38
Q
What is the pathophysiology of COPD?
A
Pathophysiology:
Chronic bronchitis:
- There is airway narrowing and hence airflow limitation as a result of hypertrophy and hyperplasia of mucus secreting glands of the bronchial tree, bronchial wall inflammation and mucosal oedema
- Microscopically there is infiltration of the walls of the bronchi and bronchioles with acute and chronic inflammatory cells
- The epithelial layer may become ulcerated and, with time, squamous epithelium replaces the columnar cells (squamous metaplasia) when the ulcer heals
- The inflammation is followed by scarring and thickening of the walls, which narrows the small airways
- The small airways are particularly affected early in the disease, initially without the development of any significant breathlessness
- The initial inflammation is reversible and accounts for the improvement in airway function if smoking is stopped early
- In the later stages, the inflammation continues, even if smoking is stopped
- Patients chronic bronchitis are referred to as blue bloaters
Emphysema
- Defined as dilatation and destruction of the lung tissue distal to the terminal bronchioles
- Results in loss of elastic recoil, which normally keeps the airways open during expiration
- Leads to expiratory airflow limitation and air trapping
Premature closure of airways limits expiratory flow while the loss of - alveoli decreases capacity for gas transfer
- Patients with emphysema are referred to as the pink puffers
- Classification:
- Centri-acinar emphysema:
- Distension and damage of lung tissue is concentrated around the respiratory bronchioles, whilst the more distal alveolar ducts and alveoli tend to be well preserved
- Extremely common
- Pan-acinar emphysema:
- Less common
- Distension and destruction affect the whole acinus and in
- severe cases the lung is just a collection of bullae
- Associated with alpha-1 antitrypsin deficiency
- Irregular emphysema:
- Scarring and damage that affects the lung parenchyma patchily, independent of acinar structure
- Centri-acinar emphysema:
COPD
- Most have both emphysema and chronic bronchitis
- The combination of emphysema (loss of elastic recoil of the lung with collapse of small airways during expiration) and chronic bronchitis (airway narrowing) results in severe airflow limitation
- V/Q (ventilation perfusion) mismatch is partly due to damage and mucus plugging of smaller airways from the chronic inflammation and partly due to rapid closure of smaller airways in expiration owing to the loss of elastic support - this mismatch leads to a fall in PaO2 and increased work or respiration
- CO2 excretion is less affected by V/Q mismatch and many patients have low- normal PaCO2 values due to increasing alveolar ventilation in an attempt to correct their hypoxia (pink puffers)
- Other patients fail to maintain their respiratory effort and then their PaCO2 levels increase
- In the short term, this rise in CO2 leads to stimulation of respiration, but in the longer term, these patients often become insensitive to CO2 and come to depend on the hypoxaemia to drive ventilation
- Such patients appear less breathless and because of renal hypoxia, they start to retain fluid and increase erythrocyte production (leading eventually to polycthaemia) - they become bloated and cyanosed (blue) and have a typical blue bloater appearance
Cigarette smoke:
- Causes mucus gland hypertrophy in the larger airways and leads to an increase in neutrophils, macrophages and lymphocytes in the airways and walls of the bronchi and bronchioles
- These cells release inflammatory mediators (elastases, proteases, IL-1,-8 & TNF-alpha) that attracts inflammatory cells (further amplify the process), induce structural changes and break down connective tissue (protease-antiprotease imbalance) in the lung resulting in emphysema
- Inactivates the major protease inhibitor alpha-1 antitrypsin
39
Q
What is the difference between blue bloaters and pink puffers?
A
Pink Puffers and Blue Bloaters:
- Pink Puffers – have a near normal PaO2, and a normal or low PaCO2 (due to hyperventilation). They ‘puff’ to increase their alveolar ventilation – and by doing so they are able to keep their blood gas values normal. These patients generally have emphysema or at least a higher degree of emphysema than bronchitis. These are likely to enter type I respiratory failure.
- Blue Bloaters – these have decreased alveolar ventilation. They have a low PaO2 and a high PaCO2. They are cyanosed but not breathless (because their respiratory centre has become sensitised). They rely on hypoxic drive to maintain adequate ventilation. They often go on to develop cor pulmonale. These patients are more likely to be type II respiratory failure. ‘Bloater’ – due to cor pulmonale.
40
Q
What are the different kind of wheezes?
A
Often a wheeze is polyphonic- this means it is made up of many different notes, and thus this shows it is caused by many abnormal airways. Wheeze is normally caused by abnormal small airways. A monophonic wheeze is caused by a single airway obstruction, and is more likely to be cancer.
41
Q
List 5 symptoms and 5 clincial signs of COPD
A
Clinical features:
Symptoms:
- cough: often productive (white or clear sputum)
- dyspnoea
- wheeze
- frequent exacerbations
- symptoms made worse by cold/damp weather or pollution
Signs:
- Tachypnoea
- Use of accessory muscles of respiration
- Hyperinflation of lungs (barrel chest)
- Reduced chest expansion
- Resonant chest sounds – suggestive of hyperinflation
- Reduced cricosternal angle <3cm- this is reduced due to hyperinflation
- Quiet breath sounds – over areas of emphysematous bullae
- Wheeze
- Pursed lip breathing**- helps to prevent alveolar and airway collapse
- Prolonged expiration - because their FEV1 is low, they have to have a prolonged expiratory phase to allow for adequate respiration
Later signs:
- Cyanosis
- Cor pulmonale - This is right sided heart failure, as a result of pulmonary hypertension
- peripheral oedema (this happens in severe cases)
42
Q
List 4 differentials of COPD
A
Differential diagnosis:
- Asthma
- CHF
- Bronchiectasis
- Pneumoconiosis / asbestosis
- Allergic fibrosing alveolitis
43
Q
What is the diagnostic criteria for COPD?
A
Diagnosis:
- NICE recommend considering a diagnosis of COPD in patients over 35 years of age who are smokers or ex-smokers and have symptoms such as exertional breathlessness, chronic cough or regular sputum production.
- The following investigations are recommended in patients with suspected COPD:
- post-bronchodilator spirometry to demonstrate airflow obstruction: FEV1/FVC ratio less than 70%
- chest x-ray:
- hyperinflation
- bullae: if large, may sometimes mimic a pneumothorax
- flat hemidiaphragm
- Decreased peripheral vascular markings
- Long narrw heart shadow/ cylindrical heart
- also important to exclude lung cancer
- full blood count: exclude secondary polycythaemia
- body mass index (BMI) calculation
- High resolution CT scans are used particularly to show emphysematous bullae
- In advances cases ABGs may show hypoxia +/- hypercapnia
- Alpha-1 antitrypsin levels and genotypes are worth measuring in premature disease or lifelong non-smokers
44
Q
How is the severity of COPD determined?
A
45
Q
Outline the management of COPD
A
General management
- >smoking cessation advice: including offering nicotine replacement therapy, varenicline or bupropion
- annual influenza vaccination
- one-off pneumococcal vaccination
- pulmonary rehabilitation to all people who view themselves as functionally disabled by COPD (usually Medical Research Council [MRC] grade 3 and above)
Bronchodilator therapy
- a short-acting beta2-agonist (SABA) or short-acting muscarinic antagonist (SAMA) is first-line treatment
- for patients who remain breathless or have exacerbations despite using short-acting bronchodilators the next step is determined by whether the patient has ‘asthmatic features/features suggesting steroid responsiveness’
There are a number of criteria NICE suggest to determine whether a patient has asthmatic/steroid responsive features:
- any previous, secure diagnosis of asthma or of atopy
- a higher blood eosinophil count - note that NICE recommend a full blood count for all patients as part of the work-up
- substantial variation in FEV1 over time (at least 400 ml)
- substantial diurnal variation in peak expiratory flow (at least 20%)
note: NICE do not recommend formal reversibility testing as one of the criteria.
If No asthmatic features/features suggesting steroid responsiveness:
- add a long-acting beta2-agonist (LABA) + long-acting muscarinic antagonist (LAMA)
- if already taking a SAMA, discontinue and switch to a SABA
Asthmatic features/features suggesting steroid responsiveness
- LABA + inhaled corticosteroid (ICS)
- if patients remain breathless or have exacerbations offer triple therapy i.e. LAMA + LABA + ICS
- if already taking a SAMA, discontinue and switch to a SABA
- NICE recommend the use of combined inhalers where possible
Oral theophylline
- NICE only recommends theophylline after trials of short and long-acting bronchodilators or to people who cannot used inhaled therapy
- the dose should be reduced if macrolide or fluoroquinolone antibiotics are co-prescribed
Oral prophylactic antibiotic therapy
- azithromycin prophylaxis is recommended in select patients
- patients should not smoke, have optimised standard treatments and continue to have exacerbations
- other prerequisites include a CT thorax (to exclude bronchiectasis) and sputum culture (to exclude atypical infections and tuberculosis)
- LFTs and an ECG to exclude QT prolongation should also be done as azithromycin can prolong the QT interval
Mucolytics: should be ‘considered’ in patients with a chronic productive cough and continued if symptoms improve
Cor pulmonale
- features include peripheral oedema, raised jugular venous pressure, systolic parasternal
- heave, loud P2
- use a loop diuretic for oedema, consider long-term oxygen therapy
- ACE-inhibitors, calcium channel blockers and alpha blockers are not recommended by NICE
Surgery
- Some patients who have a large emphysematous bullae may benefit form a bullectomy. This enables adjacent areas of collapsed lung to re-expand into the space, and function again. This improves VQ mismatch.
- Another option – you can put a valve in on bronchoscopy – this will allow air out of an emphysematous bullae, but not allow air in, and this eventually allows the bullae to collapse.
- Another option is lung volume reduction surgery. This aims to increase the elastic recoil of the lung. Patients have to be carefully selected, and have an FEV1 <1L. it improves symptoms, but does not improve mortality.
- Lung transplant can be performed on certain patients with end stage emphysema. It has a 3-year survival of 75%, and again, the treatment improves symptoms, but does not really affect quality of life.
Factors which may improve survival in patients with stable COPD:
- smoking cessation - the single most important intervention in patients who are still smoking
- long term oxygen therapy in patients who fit criteria
- lung volume reduction surgery in selected patients
COPD: long-term oxygen therapy
- NICE guidelines on COPD clearly define which patients should be assessed for and offered long-term oxygen therapy (LTOT).
- Patients who receive LTOT should breathe supplementary oxygen for at least 15 hours a day.
- Oxygen concentrators are used to provide a fixed supply for LTOT.
- Assess patients if any of the following:
- very severe airflow obstruction (FEV1 < 30% predicted). Assessment should be ‘considered’ for patients with severe airflow obstruction (FEV1 30-49% predicted)
- cyanosis
- polycythaemia
- peripheral oedema
- raised jugular venous pressure
- oxygen saturations less than or equal to 92% on room air
- Assessment is done by measuring arterial blood gases on 2 occasions at least 3 weeks apart in patients with stable COPD on optimal management.
- Offer LTOT to patients with a pO2 of < 7.3 kPa or to those with a pO2 of 7.3 - 8 kPa and one of the following:
- secondary polycythaemia
- peripheral oedema
- pulmonary hypertension
- In terms of smoking, NICE advise the following:
- do not offer LTOT to people who continue to smoke despite being offered smoking cessation advice and treatment, and referral to specialist stop smoking services.
- NICE suggest that a structured risk assessment is carried out before offering LTOT, including:
- the risks of falls from tripping over the equipment
- the risks of burns and fires, and the increased risk of these for people who live in homes where someone smokes (including e‑cigarettes)
46
Q
How does an acute exacerbation of COPD present?
A
Acute exacerbations of COPD are one of the most common reasons why people present to hospital in developed countries.
Features:
- increase in dyspnoea, cough, wheeze
- there may be an increase in sputum suggestive of an infective cause
- patients may be hypoxic and in some cases have acute confusion
47
Q
What are the most common causes of a COPD exacerbation?
A
The most common bacterial organisms that cause infective exacerbations of COPD are:
- Haemophilus influenzae (most common cause)- this is a Gram-negative coccobascillus.
- Streptococcus pneumoniae- Gram-positive diplococcus.
- Moraxella catarrhalis
Respiratory viruses account for around 30% of exacerbations, with the human rhinovirus being the most important pathogen.
48
Q
How is an acute exacerbation of COPD managed?
A
Management:
- Give controlled oxygen to mainan sats at 88-92%:
- Perform repeat ABGs (e.g. every 20 minutes) to assess for a rise in PaCO2
- If PaCO2 has risen > 1.5kPa consider use of CPAP or other assisted ventilation
- PaCO2 is dependent on VENTILATION – i.e. the volume of air inhaled and exhaled
- PaO2 is dependent on alveolar gas transfer (“OXYGENATION”) and the percentage of oxygen inhaled
- VENTILATION and OXYGENATION are not the same!
- In COPD, the normal respiratory drive, (usually driven by PaCO2) is not longer effective – the feedback mechanism between respiratory rate and PaCO2 has been lost. So, a patient may be adequately oxygenating due to the quality of O2 inhaled, but may not be adequately ventilating to “blow off” CO2
- Rising PaCO2 can lead to reduced level of consciousness and is a poor prognostic factor L
- Give nebulised salbutamol (2.5-5mg in solution), and ipratropium (0.5mg)
- give prednisolone 30 mg daily for 5 days
- it is common practice for all patients with an exacerbation of COPD to receive antibiotics. NICE do not support this approach. They recommend giving oral antibiotics ‘if sputum is purulent or there are clinical signs of pneumonia’
- the BNF recommends one of the following oral antibiotics first-line: amoxicillin or clarithromycin or doxycycline.
49
Q
How would you differentiate COPD vs Asthma?
A
50
Q
Give 5 causes of lung fibrosis in the upper zone
A
Fibrosis predominately affecting the upper zones use acronym ‘CHARTS’
- coal worker’s pneumoconiosis/progressive massive fibrosis
- hypersensitivity pneumonitis (also known as extrinsic allergic alveolitis)
- histiocytosis
- ankylosing spondylitis (rare)
- Radiation
- Tuberculosis
- silicosis
- sarcoidosis
51
Q
Give 5 causes of lung fibrosis affective the lower zone
A
Fibrosis predominately affecting the lower zones
- idiopathic pulmonary fibrosis
- most connective tissue disorders (except ankylosing spondylitis) e.g. SLE
- drug-induced: amiodarone, bleomycin, methotrexate
- asbestosis
52
Q
What are the the four main clinical features in fibrotic lung conditions
A
- Dry cough
- Dyspnoea (progressive)
- Digital clubbing
- Diffuse inspiratory crackles
53
Q
What is EXTRINSIC ALLERGIC ALVEOLITIS?
Give 3 examples?
Give 3 risk factors
A
EXTRINSIC ALLERGIC ALVEOLITIS (also known as hypersensitivity pneumonitis)
- It is a condition caused by hypersensitivity induced lung damage due to a variety of inhaled organic particles.
- It is thought to be largely caused by immune-complex mediated tissue damage (type III hypersensitivity) although delayed hypersensitivity (type IV) is also thought to play a role in EAA, especially in the chronic phase.
- There is diffuse granulomatous inflammation of the lung parenchyma
- It is a type of interstitial lung disease
- There are acute, subacute and chronic forms.
- Acute and subacute forms cause a pneumonitis which can be recurrent.
- Chronic disease can cause fibrosis, emphysema and permanent lung damage
- It is usually a disease of adults but bird fancier’s lung can occasionally present in children
- Examples:
- bird fanciers’ lung: avian proteins
- farmers lung: spores of Saccharopolyspora rectivirgula (formerly Micropolyspora faeni) – one of the most common
- Cheese-worker’s lung - exposure to cheese mould, Penicillium casei.
- malt workers’ lung: Aspergillus clavatus
- mushroom workers’ lung: thermophilic actinomycetes*
Risk factors:
- Pre-existing lung disease
- Specific occupations including farmers, cattle workers, ventilation system workers, vets and those jobs that involve working with chemicals
- Bird keeping
- Regular use of hot tubs
54
Q
Explain the pathophysiology of extrinsic allergic alveolitis
A
Pathophysiology:
- The allergic response to the inhaled antigen involves both cellular immunity and the deposition of immune complexes (TYPE 3 HYPERSENSITIVITY REACTION) resulting in inflammation through the activation of complement via the classical pathway
- Some of the inhaled antigen may lead to inflammation by directly activating the alternate complement pathway
- These mechanisms attract and activate alveolar and interstitial macrophages so that continued antigenic exposure results in the progressive development of pulmonary fibrosis
- In the acute phase; the alveoli are infiltrated with acute inflammatory cells
- With chronic exposure, granuloma formation and obliterative bronchiolitis occur
- Farmers lung:
- Fungus in mouldy hay is inhaled
- If individual is already sensitised to the organism, a type III immune complex hypersensitivity reaction follows
- Clinically there is acute dyspnoea (difficulty breathing) and cough a few hours after inhalation of the antigen
- One of the earliest features is bronchiolitis
- Later, chronic inflammatory cells are seen in the interstitium together
- with non-caveating granulomas
- The inflammatory process may resolve on WITHDRAWAL of the antigen but if there is chronic exposure then pulmonary fibrosis (build up of scar tissue, makes lungs stiff) will develop
55
Q
How does extrinsic allergic alveolitis?
A
Presentation:
Acute- occurs 4-8 hrs after exposure:
- SOB
- dry cough
- flu-like illness with fever
- malaise
- chills
- generalised aches and pains
- Symptoms are directly related to level of exposure,
- signs: fever, tachypnoea and bibasal fine inspiratory crackles. Wheeze is rare .
- In very severe cases, patients may develop life-threatening respiratory failure with cyanosis
- Resolution occurs 24-48hrs following removal of the antigen
Subacute:
- Syx less severe and more gradual onset
- Productive cough
- Dyspnoea
- Fatigue
- Anorexia
- Weight loss
- Signs same as acute
- It can present as recurrent pneumonia.
- After the exposure is removed it can take weeks or months for symptoms to resolve
Chronic:
- often no systemic symptoms except weight loss and gradual diminution of exercise tolerance due to dyspnoea.
- Cyanosis
- Clubbing
- Other signs: tachypnoea, type 1 respiratory failure, inspiratory crackles over lower lung fields, eventually, chronic hypoxemia, pulmonary hypertension with right heart failure
- If the source of antigen is removed only partial improvement of symptoms
- There may also be acute exacerbations in those with chronic disease
56
Q
List 3 differentials of extrinsic allergic alveolitis
What investigations would you request and what would you expect to see?
What is the management of extrinsic allergic alevolitis?
A
Differential diagnosis:
- Infection (bacterial, fungal, viral including tuberculosis).
- Connective tissue disorders causing interstitial lung disease.
- Pulmonary fibrosis (including idiopathic).
- Asthma.
- Sarcoidosis.
- Histoplasmosis.
- Drug-induced interstitial lung disease
Investigations:
- Blood tests:
- inflammatory markers e.g. raised WCC, ESR but-these are nonspecific.
- There may be serum antibodies detectable – non specific .
- No eosinophilia
- CXR:
- acute form this may be normal in some or show diffuse micronodular interstitial shadowing.
- In the subacute form, there may be micronodular or reticular opacities in the mid/upper lung fields.
- In the chronic form, there may be features of fibrosis with loss of lung volume
- Bronchoalveolar lavage: shows lymphocytosis and the CD4/CD8 ratio is reduced to less than 1
- CT scanning: high-resolution CT is a good way to evaluate the stage of disease and usually shows typical changes
- Lung function testing:
- can be normal
- Spirometry shows a restrictive defect in acute and subacute forms but there may be a mixed restrictive/obstructive picture in the chronic form.
- Reduced gas transfer during attacks
- Transbronchial or open lung biopsy: this may show characteristic histopathological features.
Management:
Acute:
- Remove allergen
- In severe acute cases where there is cyanosis or resp distress- admit and give oxygen
Severe acute and subacute:
- Avoid allergen
- Oral prednisolone (corticosteroid) followed by reducing dose
Chronic:
- Avoid exposure to allergen
- Long term Corticosteroids e.g. prednisolone
- Resistant cases give azathioprine
Complications: Pulmonary fibrosis, Cor pulmonale, Type 1 resp failure, spontaneous pneumothorax
57
Q
What is intersitial lung disease and what are the two main types?
A
INTERSITIAL LUNG DISEASES
- Interstitial lung diseases (ILDs) affect the lung interstitium, i.e. the space between the alveolar epithelium and the capillary endothelium, causing inflammation and fibrosis.
- The two main types of interstitial lung disease are pulmonary fibrosis and sarcoidosis. Other types include:
- occupational lung diseases (pneumoconiosis),
- Drug induced ILD (e.g. amiodarone, methotrexate)
- Hypersensitivity ILD (extrinsic allergic alveolitis)
- Secondary to connective tissue disorders
- Sarcoidosis tends to occur in younger adults, and can also affect any other organ system in the body, although in 90% of cases the lungs are involved
- Sarcoidosis has a more benign prognosis and in many cases, resolves by itself
- Pulmonary fibrosis tends to occur in older adults, and causes significant morbidity and mortality
58
Q
What is idiopathic pulmonary fibrosis?
List 4 RF?
A
IDIOPATIC PULMONARY FIBROSIS
- This is a relatively rare, progressive, chronic pulmonary fibrosis of unknown aetiology.
- Commonest cause of interstitial lung disease
- There is patchy fibrosis of the interstitium and minimal or absent inflammation, acute fibroblastic proliferation and collagen deposition
- INVOLVES THE LOWER LOBES - The alveolar walls are affected predominantly in the subpleural regions of the lower lobes.
- Also known as cryptogenic organising pneumonia
- Pulmonary fibrosis has a very poor prognosis – the median age of survival is only 3-4 years.
Risk factors:
- Factors implicated in triggering the aberrant wound healing include:
- Cigarette smoking
- Infectious agents (CMV, Hep C, EBV)
- Occupational dust exposure (metals, woods)
- Drugs - methotrexate, imipramine (anti-depressant)
- Chronic gastro-oesophageal reflux disease (GORD)
- Genetic predisposition
59
Q
What is the pathophysiology of IPF?
A
Pathophysiology:
- The pathogenesis of IPF is unknown
- It is thought that repetitive injury to the alveolar epithelium, caused by currently unidentified environmental stimuli leads to the activation of several pathways responsible for repair of the damaged tissue
- However in IPF, the wound healing mechanisms become uncontrolled, leading to the over-production of fibroblasts and deposition of increased extracellular matrix in the interstitium (fibrosis) with little inflammation
- The structural integrity of the lung parenchyma (functional tissue of organ) is therefore disrupted; there is loss of elasticity and the ability to perform gas exchange is impaired, leading to progressive respiratory failure
60
Q
How does IPF present?
What may you see on examination?
A
Clinical presentation:
Symptoms:
- progressive breathlessness
- dry cough
- considerable weight loss
- fatigue/malaise.
Signs O/E include:
- Reduced chest expansion
- Final bi-basal end inspiratory crackles
- Finger Clubbing (2/3 patients)
- Cyanosis
- Over time this disease progresses to cause pulmonary hypertension, cor pulmonale and type 1 respiratory failure.
- Important: his histological pattern is called “Usual Interstitial Pneumonitis” (UIP) – it’s the most common pattern of lung disease that IPF shows.
- Other patterns of the disease can include DIP (Desquamative Interstitial Pneumonitis) and Bronchiolitis Obliterans
61
Q
Give three differential diagnoses of IPF
A
Differential diagnosis:
- COPD
- Asthma
- Bronchiectasis
- congestive heart failure,
- lung cancer
- hypersensitivity pneumonitis
62
Q
What investigations would you request for IPF?
A
Investigations:
Aims of investigation in IPF are to confirm the presence of pulmonary fibrosis and exclude identifiable (a potentially reversible) causes
- Blood
- FBC (raised ESR), Rh factor (+ve 50% patients), ANA (30% +ve)
- CXR
- Irregular, reticulo-nodular shadows, often in lower zones, sometimes called the reticulonodular pattern
- CXR is often normal
- High resolution CT
- Needed for diagnosis as it confirms it
- Ground-glass opacification
- “Honeycombing” i.e. basal layers of small, cystic airspaces with irregularly thickened walls composed of fibrous tissue
- Traction bronchiectasis - the fibrotic process distorts the normal lung architecture, pulling the airways open and causing bronchiectasis
- Subpleural reticulation
- “Mosaicism”
- Basal distribution i.e. abnormalities are more pronounced at the bases
- Lung Function Tests (spirometry)
- Restrictive Pattern FEV1/FVC ratio greater than 70% but FVC
- low i.e less than 80% predictive value)
-
ABG
- Hypoxaemia
- Transbronchial or open lung biopsy to confirm histological diagnosis
- Assists in defining the type of ILD that is present most commonly its usual interstitial pneumonia (UIP)
63
Q
What is the management if IPF?
A
Management:
- Serial lung function testing is used to monitor disease progression
- Pulmonary rehabilitation
- Best supportive care:
- Oxygen e.g ambulatory (portable) oxygen if they need it
- Palliative care i.e. opiates
- Smoking cessation advice
- Pirfenidone - an antifibrotic agent that can slow the rate of FVC decline (need to check eligibility)
- Treat GORD since it contributes to repetitive alveolar epithelial damage – give PPIs
- Lung transplant
- DO NOT GIVE STEROIDS
64
Q
What is sarcoidosis?
A
SARCOIDOSIS
- Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology.
- It is characterised by non-caseating granulomas
- It most commonly affects the lungs (>90% of cases) and lymphatic system, but can affect any organ.
- When it affects the lungs, we refer to it as an interstitial lung disease.
- Many cases are asymptomatic, although some patients can have very severe disease.
- Sometimes they give the appearance of TB on chest x-ray.
65
Q
Who does sarcoidosis primarily affect?
A
Epidemiology:
- Usually affects young people (ages 20-40 years)
- More common in women
- African-Caribbeans are affected more frequently and more severely than Caucasians - particularly by extra-thoracic disease
- First degree relatives have an increased risk of developing sarcoidosis
- (particularly in Caucasians)
- Lungs are most commonly affected, followed by eyes and skin.
- The liver is also often affected, but this is rarely clinically significant
- Rarely it an affect the heart and nervous system
- Between 10-30% of patients will have a chronic or progressive disease course. The rest will typically resolve spontaneously, although this can take several year
66
Q
What is the pathology of sarcoidosis?
How does it present?
A
Pathology:
- A granuloma is a collection of WBC’s (mononuclear cells and macrophages) , surrounded by lymphocytes, plasma cells, mast cells, fibroblasts, and collagen. They can occur in any organ, but in sarcoidosis most commonly occur in the lung and lymphatics.
- In the lung they tend to be distributed along the line of lymph nodes – Hence the association of sarcoidosis and hilar CXR changes
Clinical presentation:
- Many patients are asymptomatic -Up to 50%!
- Acute sarcoidosis: erythema nodosum (red lumps form on the shins and less commonly thighs and forearm), bilateral hilar lymphadenopathy, swinging fever, polyarthralgia
- Insidious symptoms:
- Dry cough
- Dyspnoea (usually progressive)
- Malaise
- Weight loss
- Chest pain
67
Q
List 5 signs of sarcoidosis
A
Signs:
- A restrictive pattern may be seen on spirometry
- Bilateral hilar Lymphadenopathy
- Crackles on auscultation
- Erythema nodsoum
- Sarcoidosis is often a differential for a patient with lots of non-specific signs!
Other Features:
- Hepatomegaly
- Splenomegaly
- Bell’s palsy
- Eyes: uveitis, conjunctivitis and cataracts.
- skin: lupus pernio - blueish-red/purple nodules and plaques over nose, cheek and ears
- hypercalcaemia: macrophages inside the granulomas cause an increased conversion of vitamin D to its active form (1,25-dihydroxycholecalciferol)
- Enlargement of lacrimal & parotid glands
68
Q
What syndromes are associated with sarcoidosis?
A
Syndromes associated with sarcoidosis
- Lofgren’s syndrome is an acute form of the disease characterised by bilateral hilar lymphadenopathy (BHL), erythema nodosum, fever and polyarthralgia. It usually carries an excellent prognosis
- In Mikulicz syndrome* there is enlargement of the parotid and lacrimal glands due to sarcoidosis, tuberculosis or lymphoma
- Heerfordt’s syndrome (uveoparotid fever) there is parotid enlargement, fever and uveitis secondary to sarcoidosis
69
Q
What investigations would you request for sarcoidosis?
A
- There is no one diagnostic test for sarcoidosis and hence diagnosis is still largely clinical.
- Bloods:
- FBC – may cause anaemia or raised WCC
- ESR – often raised
- U+E
- Ca2+- raised in 10% of patients
- LFTs – may be deranged
- Raised immunoglobulins
- Serum ACE (angiotensin converting enzyme)
- Elevated in 60% of cases
- Falls with treatment
- Not routinely used for diagnosis or monitoring of treatment (lung function and CXR are better indicators)
- CXR:
- Often discovered incidentally on CXR.
- The classical finding is hilar lymphadenopathy,
- Other changes may include fibrosis and lung infiltrates
- CXR is used to stage the disease
- 90% of patients with sarcoidosis will show CXR change
STAGING
- stage 0 = normal
- stage 1 = bilateral hilar lymphadenopathy (BHL)
- stage 2 = BHL + interstitial infiltrates
- stage 3 = diffuse interstitial infiltrates only without BHL
- stage 4 = Progressive pulmonary fibrosis ± bulla (honeycombing on CXR)
- Other investigations*
- spirometry: may show a restrictive defect
- tissue biopsy: non-caseating granulomas (Suitable biopsy sites include lung and liver tissue, lymph nodes and lacrimal glands)
- Broncheoaleolar lavage – can show increased lymphocytes and neutrophils
CT/MRI – useful in some cases to assess the extent of pulmonary involvement - ECG - may show arrhythmias or bundle branch block
- Hand X-ray – sometimes shows punched out lesions in the peripheral phalanges
70
Q
What is the management and prognosis of sarcoidosis?
A
Management:
- Stage 0 and 1 – usually resolve spontaneously
- Stage 2+ and acute disease – may improve with NSAIDs and bed rest
- Patients with asymptomatic and stable stage 2 or 3 disease who have only mildly abnormal lung function do not require treatment
- prednisolone 40mg for 4-6 wks, then gradually decline dose over 1yr depending on symptoms.
- Indications for steroids
- patients with chest x-ray stage 2 or 3 disease who are symptomatic.
- hypercalcaemia
- eye involvement – uveitis
- cardiac involvement
- neuro involvement
- in severe illness give IV methylprednisolone
- If steroid-resistant then: Methotrexate or Infliximab
- Patients should also have regular ophthalmology assessment for eye manifestations of the disease as Sarcoidosis can cause optic neuritis which can cause blindness if untreated.
Prognosis:
- <5% of patients with sarcoidosis will die as a result of complications of their disease
- 20% of patients will have chronic or progressive disease – the rest will either resolve spontaneously or respond well to treatment
- Those that do die of their complications typically develop severe pulmonary fibrosis, and may also develop pulmonary hypertension
71
Q
List 5 occupational lung disorders
A
OCCUPATIONAL LUNG DISORDERS:
• Response to inhaling something at work
• Can be; fumes, dust, gas or vapour causing:
- Acute bronchitis and even oedema from irritants such as sulphur dioxide, chlorine, ammonia or the oxides of nitrogen
- Pulmonary fibrosis from inhalation of inorganic dust e.g. coal, silica, asbestos, iron and tin
- Occupational asthma - this is the commonest industrial lung disease in the developed world
- Hypersensitivity pneumonitis
- Bronchial carcinoma due to asbestos, polycyclic hydrocarbons and radon in mines
- Pneumoconiosis - term used to describes a range of interstitial lung diseases caused by inhalation of mineral dusts, resulting in interstitial fibrosis
- They are usually occupational diseases (but not always)
- Examples include coal workers pneumoconiosis, silicosis, asbestosis
- Where the process of pneumoconiosis occurs alongside rheumatoid arthritis, it is called CAPLAN’S SYNDROME.
- Differentials: COPD, heart failure, cardiomyopathy
- There is no treatment or cure.
72
Q
What is COAL WORKER’S PNEUMOCONIOSIS?
A
- It is sometimes referred to as ‘black lung disease’, is an occupational lung disease caused by long term exposure to coal dust particles.
- Pneumoconiosis = accumulation of dust in the lungs and the response of the bodily tissue to its presence, most commonly used in relation to coal worker’s pneumoconiosis.
- It is most commonly experienced by those who have been involved in the coal mining industry and severity is linked to the extent of exposure.
- Often there is a long lead time between the first exposure and the development of the disease.
- Coal dust particles are ingested by alveolar macrophages in the small airways and alveoli which then die, releasing enzymes and causing fibrosis
73
Q
When does coal workers pneumoconiosis usually present?
A
Diagnosis is usually 15-20 years after initial exposure to the coal dust.
74
Q
Explain the pathophysiology of coal workers pneumoconiosis
A
Pathophysiology:
- Coal dust (2-5 μm in size) is inhaled and enters the lungs.
- The dust reaches the terminal bronchioles and there it is engulfed by alveolar and interstitial macrophages.
- The dust particles are then moved by the macrophages via the mucociliary elevator and removed from the body as mucus.
- In coal miners who are exposed over many years, the system is overwhelmed and the macrophages begin to accumulate in the alveoli, which starts an immune response, causing damage to the lung tissue.
75
Q
How does coal workers pneumoniosis present?
A
Presentation:
Exposure to coal dust can lead to one of two presentations:
1.Simple pneumoconiosis:
- Is the commonest type of pneumoconiosis.
- Patients are often asymptomatic.
- Produces fine micro nodular shadowing in the chest x-ray
- Its presence increases the risk of lung diseases such as COPD.
- Simple pneumoconiosis may lead to Progressive Massive Fibrosis (PMF), occurring in around 30% of those with stage 3 grading.
Staging
- The disease is graded on the appearance of the chest X-ray using categories outlined by the International Labour Office:
- Category 1: some opacities but normal lung markings visible
- Category 2: large number of opacities but normal lung markings visible
- Category 3: large number of opacities with normal lung not visible
2.Progressive Massive Fibrosis
- Dust exposure causes patients to develop round fibrotic masses which can be several centimetres in diameter, with necrotic central cavities
- These are most commonly in the upper lobes.
- The exact pathogenesis is not known.
- Patients are often symptomatic and have both breathlessness on exertion and cough, some may have black sputum.
- Lung function testing shows a mixed obstructive/restrictive picture.
- Rheumatoid factor and anti-nuclear antibodies are both often present in the serum of patients with PMF and also in those suffering from asbestosis or silicosis
- There is apical destruction and disruption of the lung resulting in emphysema and airway damage
76
Q
What investigations would you request for coal workers pneuomoconiosis ?
How would you manage it
A
Investigations:
- Chest x-ray: upper zone fibrosis
- Spirometry: restrictive lung function tests - a normal or slightly reduced FEV1 and a reduced FVC
Management:
- Avoid exposure to coal dust and other respiratory irritants (e.g. Smoking).
- Manage symptoms of chronic bronchitis
- Patients may be eligible for compensation via the Industrial Injuries Act.
77
Q
What is silicosis?
How is it diagnosed and treated?
A
SILICOSIS:
- Uncommon but seen in stonemasons, sand-blasters, pottery and
- ceramic workers and foundry workers involved in fettling
- Caused by the inhalation of silica particles (silica dioxide) which is very
- fibrogenic
- Silica is particularly toxic to alveolar macrophages and readily initiates fibrogenesis
- CXR appearance show diffuse nodular pattern in upper and mid-zone and thin streaks of calcification (egg-shell calcification) of the hilar nodes
- Spirometry shows a restrictive ventilatory defect
- Patients have progressive dyspnoea and an increased incidence of TB
- Manage by avoiding exposure to silica and claim compensation
78
Q
What is asbestosis ?
How is it diagnosed and treated?
A
- Type of Interstitial Lung Disease - distinct cellular infiltrates and extracellular matrix deposition in lung distal to the terminal bronchiole i.e. diseases of the alveolar/capillary interface
- Fibrosis of the lungs caused by asbestos dust, which may or may not be associated with fibrosis of the parietal or visceral layers of the pleura
- LOWER LOBE FIBROSIS
- Progressive disease characterised by breathlessness and progressive dyspnoea and accompanied by finger clubbing and bilateral basal end-inspiratory crackles
- Also causes pleural plaques and increases risk of mesothelioma and bronchial adenocarcinoma
- The severity of asbestosis is related to the length of exposure. This is in contrast to mesothelioma where even very limited exposure can cause disease.
- Only symptomatic management is known e.g. corticosteroids
98
Q
What paraneoplastic syndromes are associated with what lung cancers?
A
100
Q
Outline the staging system for SCLC
A
Staging:
- Non-small cell carcinoma is staged using the TNM system (see below).
- Small cell is generally very aggressive, and is staged as either limited or extensive.
- TNM staging is used for non-small cell carcinoma*à
113
Q
List different kind of Pleural Fluid Samples and their causes
A
154
Q
What is the difference between community acquired and hospital acquired pneumonia?
A
155
Q
What are the most common causes of pneumonia?
A
164
Q
What is the discharge critera for pneumonia and what is the post discharge advice given?
A
Discharge criteria and advice post-discharge
NICE recommend that patients are not routinely discharged if in the past 24 hours they have had 2 or more of the following findings:
- temperature higher than 37.5°C
- respiratory rate 24 breaths per minute or more
- heart rate over 100 beats per minute
- systolic blood pressure 90 mmHg or less
- oxygen saturation under 90% on room air
- abnormal mental status
- inability to eat without assistance.
They also recommend delaying discharge if the temperature is higher than 37.5°C.
NICE recommend that the following information is given to patients with pneumonia in terms of how quickly their symptoms should symptoms should resolve:
180
Q
How do you screen for latent TB?
A
Screening for latent tuberculosis
- The Mantoux test (tuberculin skin test) is the main technique used to screen for latent tuberculosis:
- purified protein derivative (PPD) injected intradermally
- result read 2-3 days later
- Stimulates type 4 hypersensitivity reaction
- If positive then indicates immunity and thus contact with TB
- Won’t easily distinguish infection from disease
- the interferon-gamma assay/blood test is used in a number of specific situations such as:
- the Mantoux test is positive or equivocal
- people where a tuberculin test may be falsely negative which maybe due to:
- miliary TB
- sarcoidosis
- HIV
- lymphoma
- very young age (e.g. < 6 months)
- IGRAs use antigens specific to M. tuberculosis to distinguish between this and BCG vaccine or environmental mycobacteria
- IGRAs demonstrate exposure to M.tuberculosis but NOT ACTIVE INFECTION
182
Q
Describe the management of TB
List the side effects of the drugs used
A
- Contact tracing- Offer latent TB testing to household contacts to close work and school contacts to patients who have been diagnosed with active TB
- Patients with TB require 6 MONTHS of treatment - First 2 months all 4 drugs, and last 4 months just rifampicin and isoniazid
- The treatment for latent tuberculosis is 3 months of isoniazid (with pyridoxine) and rifampicin OR 6 months of isoniazid (with pyridoxine)
- Patients with meningeal tuberculosis are treated for a prolonged period (at least 12 months) with the addition of steroids
- MDR-TB should be treated with at least four effective antibiotics for 18 to 24 months is recommended.
- Compliance is critical to reduce relapse and resistance
- To aid compliance there are special clinics called DOT (Direct Observed Therapy) where they give medication under supervision 3 times a week.
- DOT usually given to:
- homeless people with active tuberculosis
- patients who are likely to have poor concordance
- all prisoners with active or latent tuberculosis
