Obstructive and Restrictive Lung Disease Flashcards
What are the two general categories for drugs that treat obstructve airway conditions?
- Relievers - bronchodilators
- Preventers - anti-inflammatory
What is step 1 in asthma treatment?
SABA
Salbutamol
What is step 2 in asthma treatment?
SABA + ICS (200-800micrograms)
What is step 3 in asthma treatment?
SABA + LABA + ICS
What is step 4 in asthma treatment?
Increase ICS dose from step 3
Add fourth drug e.g. theophylline or a leukotriene receptor antagonist
What is step 5 in asthma treatment?
Use daily steroid tablet (prednisolone)
Maintain high dose ICS (2000micrograms)
Which immune cells are corticosteroid effcetive aginst in the mucose?
Eosinophils
What is a downside to corticosteroid use in asthma or COPD?
It weakens the immune system, and impairs the mucociliary escalator.
This increases chance of infection
In COPD chances of pneumonia infection are boosted
ICS have a ____ therapeutic ratio and are _______ due to being delivered directly to the organ of interest
High
Topical
Oral corticosteroids have a ___ therapeutic ratio
Low
Why is a spacer useful for administering asthma medication?
- Reduces oropharngeal and laryngeal side effects (gag reflex/nausea)
- Reduces systemic absorption (no swallowing)
- Acts as a holding chamber aiding inhalation
- Reduces particle size and velocity allowing the particle to embed deeper in the lungs increasing effectivity
What are cromones and what is their function?
Cromones are used in asthma and are propsed mast cell stabilisers
This means they can prevent pro-inflammatory mediator release
How are leukotrienes formed during asthma?
They are produced due to processes involving the lipids in the cell membrane
The enzyme phospholipase A2 detaches fatty acids from the second carbon group of the glycerol molecule that makes up a lipid
One of these acids is arachidonic fatty acids
When arachidonic acid is acted on by 5-lipoxygenase leukotienes are formed
What happens when cyclo-oxygenase acts on arachidonic acid?
Prostaglandins and thromboxanes are produced aiding inflammation and amplification
Which leukotriene is over produced in asthma?
LTD4
What is the effect of overproduction of leukotrienes in asthma?
- Trigger contraction and proliferation of smooth muscle
- Cause eosinophil influx (which release cationic proteins damaging epithelial cells)
- Increased mucus secretion, bu decreased transport
- Oedema
Lekotriene receptor antagonists are used in asthma, name one that is use dto bind to LTD4?
Montelukast
(taken orally)
What is anti-IgE and what is the name of one key form in relation to asthma called?
Monoclonal antibody
Omalizumab
Omalizumab has what effects?
Binds stongly to IgE inactivating it
Prevents pro-inflammatory mediators being released from basophils and mast cells
Boosted every 2-4 weeks via injection
Name two anti-IL5 drugs
- Mepolizumab
- Reslizumab
How does anti-IL5 therapy work?
TH2 cells produce IL-5 in the immune response aiding eosinophilic inflammation in asthma
The use of anti-IL5 therapy is that eosinophilic inflammation is much reduced
Name 2 LABAs
- Formeterol
- Salmeterol
What are the three different types of muscarinic receptors?
- M1 - enhance cholinergic reflex
- M2 - inhibit acetylcholine release
- M3 - mediate bronchoconstriction and mucus release
Muscarinic antagonists inhibit which type of muscarinic receptor?
M3
Name a SAMA
Ipratropium
Name two LAMAs
- Tiotropium
- Glycopyrronium
Methylxanthines act as ____________ and also ___________
Bronchodilators
Anti-inflammatory drugs
Name an example of a methylxanthine
Theophylline
What is the function of phosphodiesterase 4 enzymes?
Hydrolyse cAMP
What is the overall function of PDE4 inhibitors?
Prevent cAMP hydrolysis allowing high levels of cAMP in cells
Bronchial smooth muscle will become relaxed
PDE4 inhibitors are for use only in ____
COPD
Give an example of a PDE4 inhibitor
Roflumilast
Why are PDE4 inhibitors used infrequently?
Side effects suh as nausea, diarrhoea and headaches
What are mucolytics?
Drugs which reduce the viscocity of mucous and reduce inflammation
Give two examples of mucolytics?
- Carbocisteine
- Erdosteine
In an acute astha attack what treatment is given?
- Oral prednisolone (40mg)
- At least 60% oxygen aim for 94-98% SpO2
- Nebulised salbutamol
What are some treatment methods for COPD?
- Smoking cessation
- Immunisation
- Pharmacotherapy
- Oxygen
- Increase exercise
Name two LAMAs
- Titropium
- Aclidinium
Name two LABAs
- Olodaterol
- Formeterol
Name an ICS for COPD use
Beclometasone
Which antibiotic may be used for COPD?
Azithromycin
(also amoxicillin and doxycycline)
How is acute COPD treated?
- Nebulised high dose salbutamol and ipratropium
- Oral prednisolone
- Antibiotic (amoxicillin/doxycycline) if infection
- 24-28% O2
- Non-invasive ventilation
Which external factors can cause lung restriction?
- Skeletal causes (broken ribs, kyphoscoliosis)
- Muscle Weakness (intercostal/diaphragmatic)
- Obesity (due to compression)
What are the effects of lung compression from external sources?
- Reduced partial pressur eof oxygen
- Reduced partial pressure of carbon dioxide
- Reduced lung volumes
- Hypoxia
What is DPLD?
Diffuse Parenchymal Lung Disease
Interstitial lung disease
An umbrella term for lung diseases affecting the interstitium
What is the interstitium of the lungs?
The space and tissues surrounding the alveoli
What are the three main categories for DPLD (ILD)?
- Those with a known cause
- Those with an unknown cause (idopathic)
- Those associated with systemic disease
Why may hypoxia occur at a thickened alveolar/arteriolar barrier?
Carbon dioxide is very soluble and easily diffuses across to can be blown off
Oxygen will not be able to pass the barrier into the blood as easily potentially leading to hypoxia
Give two different causes for DPLD
- LVF - fluid in alveolar lumen due to a raised pulmonary venous pressure
- Sepsis, adult respiratory distress syndrome damage, altitude sickness - Non-cardiac pulmonary oedema
What is consolidation in the lungs?
Fluid within areas which there normally is not any fluid
What can cause consolidation on a chest X-ray?
- Pneumonia
- PE
- Alveolitis
- Cryptogenic pneumonia (not infectious)
What is alveolitis?
This is the infiltration of inflammatory fluid into the alveolar walls
It can be caused by:
- Drugs
- Toxic gases
- Fibrosing alveolitis
- Autoimmune disease
What is pneumoconiosis?
Dust disease
Restrictive lung disease that can be either fibrogenic (asbestosis, silicosis) or non-fibrogenic (siderosis (due to iron), stenosis, baritosis (due to barium))
What is carcinomatosis?
Body-wide spread of cancer and can contribute to DPLD
How do eosinophils contribute to DPLD?
They occur alongside all sides of inflammation which is present in DPLD
Symptoms of DPLD?
- Breathlessness
- Cough (without wheeze - no obstruction)
- Finger clubbing
- Lung crackles (inspiration)
- Central cyanosis
- Pulmonary fibrosis (chronic inflammation)
How is FEV1 affected in DPLD?
It is reduced
How is FVC affected in DPLD?
It is reduced
What happen to the FEV1/FVC ratio in DPLD?
It remains normal as both variables decrease in proportion
Aside from FEV1 and FVC what are the thee main checks which must be covered for diagnosing DPLD?
- Arterial oxygen saturation (should be lowered in DPLD)
- Chest X-ray (bilateral consolidation is common)
- Presence of antibodies (caused by infection)
How is DPLD treated?
- Cause is removed
- Inflammation is treated
- Oral prednisolone (systemic corticosteroids)
- ICS - if oral fails
- Oral azathioprine (immunosuppressor)
- Anti-fibrotic drugs (pirfenidone, nintedanib)
- Oxygen (if hypoxic)
- Lung transplant - end stage disease
In asthma, FVC is ______ but FEV1 is _________
Normal
Reduced
What type of graph can help diagnose lung conditions?
Flow volume curve
How does peak expiratory flow rate differ between obstructive and restrictive when compared to a normal result?
Obstructive - reduced
Restrictive - normal
How does FEV1 differ between obstructive and restrictive when compared to a normal result?
Both are reduced
How does FVC differ between obstructive and restrictive when compared to a normal result?
Obstructive - asthma (normal), COPD (reduced)
Restrictive - reduced
How does FEV1/FVC ratio differ between obstructive and restrictive when compared to a normal result?
Obstructive - Decreased (<75%)
Restrictive - The same, if not slightly increased (>75%)
What is bronchial challenge testing?
This involves putting strain on the airways and monitoring the response.
Tis can be done by exercise or by provoking a response through the introduction of allergens or chemicals
How will FEV1 and PEF be affected after asthma if the patient has asthma?
Both will decrease
What is DLCO?
Diffusing capacity of the lung for CO
Partial pressure of CO is measure ebfore and after inspiration and the difference indicates the ease at which oxygen can cross the barrier.
What is impulse oscillometry?
Non invasive technique using passive breathing to detrmine airway resistance
Pressure is measured at the mouth at different resonant frequencies
Name 3 obstructive airway diseases
- Asthma
- Emphysema
- Chronic Bronchitis
What is atopic asthma?
Asthma brought on by allergy
What is extrinsic asthma?
Asthma that has triggers out with the body
What is the asthma triad?
The three symptoms required for asthma
- Airway inflammation - usually eosinophilic
- Airway hyper-responsiveness - any stimulus can cause abnormal airway reactions
- Reversible airflow obstruction - the airway can dilate again
How can asthma “evolve” and become worse over time?
- Bronchoconstriction - causes brief symptoms
- Chronic aiway inflammation - can cause scarring
- Airway remodelling - airways are permanently changed by scarring
Describe the process of airway remodelling
The basement membrane thickens, collagen is deposited in the submucosa and hypertrophy of smooth muscle occurs
This will constrict airways reducing their efficiency
Asthma triggers will initiate _________ inflammation which causes release of inflammatory mediators and TH2 _________
Eosinophilic
Cytokines
What are TH2 cytokines responsible for and why are they important?
They produce IL 4, 5 and 13
These aid production of IgE antibodies
This promotes further eosinophilic activation and amplification
This can cause twitchy smooth muscle (hyper-reactivity)
How can airways become blocked in asthma?
Inflammation can lead to desquamation - shedding of epithelium into airways
Mucus plugging
How is athma diagnosed?
- History/examination
- Daily variation in peak flow rate
- Reduced FER
- Reversal of symptoms when inhling salbutamol
- Provocative tests to induce bronchospasms
What is COPD?
An umbrella term
It encompasses chronic bronchitis and emphysema
How does COPD develop?
The inhaltion of naxious particles over an extended timeframe
What does inhaltion of noxious chemicals do over time?
Causes:
- Mucociliary dysfunction
- Inflammation
- Tissue damage
Noxious chemicals will stimulate the recruitment of what into the alveoli?
Macrophages
Potentially also CD8+ T cells
Alveolar macrophages also activate neutrophils by releasing IL-8, LTB4 and oxygen radicals
How do neutrophils and macrophages damage lung tissue?
Both cells will release proteases which breaks down connective tissue in the lung parenchyma which causes mucus hyper secretion
Of the two, which is more reversible, chronic bronchitis ot emphysema?
Chronic bronchitis is partially reversible
Emphysema is not reversible at all
What happens when alveoli are destroyed in emphysema (COPD)?
Dead spaces are created - these areas are not availble for gas exchange and increase residual lung volume
Emphysema is due to an imbalance of _________ to ____-__________
Proteases
Anti-proteases
What is different about a cough in asthma and a cough in COPD?
COPD involves a productive cough
How does emphysema affect breath sounds?
It reduces them - dead spaces do not make sounds
What is the condition involving both asthma and COPD?
Asthma COPD Overlap Syndrome
Hard to diagnose
What is stridor?
An inspiratory wheeze due to obstruction
What may cause stridor in children?
Croup, epiglotitis, diphtheria, retropharngeal abscess, foreign bodies, anaphylaxis
What may cause stridor in adults?
Neoplasms, anaphylaxis, goitre (enlargement of thyroid gland), trauma
What is tracheomalacia?
The loss of cartilage rings in the trachea
This leads to negative pressure in inspiration causing the collapse of the trachea
How can stridor be investigated?
- Laryngoscopy - caution with acute epiglottitis
- Bronchoscopy
- Flow volume loop via spirometry
- CXR
- CT/thyroid scan
How can a laryngeal obstruction be treated?
- Underlying cause
- Reservoir mask with high flow oxygen
- Cricothyridotomy - incision through skin and cricoid membrane in life threatening situations due to obstruction
- Tracheostomy - incision into trachea
What may cause anaphylaxis?
- Food - nuts, shellfish
- Insect venom - bees, wasps
- Drugs - penicillin, aspirin
How can anaphylaxis be treated?
- IM adrenaline (EpiPen)
- IV antihistamine
- IV corticosteroid
- Nebulized bronchodilators
- Endotracheal intubation (if needed)
What causes snoring?
Relaxation of pharngeal dilator muscles during sleep
This causes upper airway narrowingleading to turbulent airflow and vibration of the soft palate and tongue base
What is sleep apnoea?
Complete upper airway collapse due to muscle relaxation during sleep
This prevents breathing
Microarousal is a process by which the body can awake itself to resolve this and awake the person
What does recurrent (more than 5 per hour) instances of sleep apnoae cause?
- Recurrent hypoxia
- Recurrent arousals and sleep fragmentation causing chronic fatigue
What are the risk factors for sleep apnoea?
- Post-operative period after anaesthesia
- Acromegaly, hypothyroidism
- Neurological - stroke, MS, mytonic dystrophy
- Drugs - benzodiazepines, opiates, alcohol
- Oropharngeal deformity
- Obesity
- Retrognathia - lower jaw set back so tongue is also set back lessening space in oropharynx
- Enlarged tonsils, adenoids
What are the three main consequences of sleep apnoea?
- Chronic fatigue
- Personality and mood changes
- Cognitive impairment
What are some indirect consequences of sleep apnoea?
- Risk of hypertension
- Activates sympathetic system and cortisol release
- Raised CRP
- Impaired endothelial function
- Impaired glucose breakdown
- Increased risk of strokes and cardiovascular events
How can sleep apnoea be diagnosed?
- Snoring
- Raised Epworth (sleepiness) score
- Overnight sleep studies - oximetry, domiciliary recording
- Full polysomnography - full sleep study
How can sleep apnoea be treated?
- Remove underlying cause
- Continuous postive airway pressure - airway mask can keep airway open
- Mandibular advancement device - moves jaw forward
- Surgery - removes soft palate meaning area becomes scarred and stiffens up reducing relaxation and collapsing
- Jaw broken and moved forward
