U13W1 - asthma and COPD

Question 1

How prevalent is COPD?

Answer 1

Develops in 35 to 40% of smokers
Most common in over 40yrs
Present in 2% of the population.

Question 2

What are the risk factors associated with COPD?

Answer 2

Modifiable: Smoking - up to 50% of smokers develop COPD, occupational pollution, environmental pollution.
Nom-modifiable: Alpha 1 antitrypsin deficiency, variant of nicotinic ACh receptor altes addictiveness of smoking, history or childhood respiratory infections or asthma.

Question 3

What are the two main components of the pathophysiology of COPD?

Answer 3

Emphysema - irreversible enlargement of dairspaces distal to the terminal bronchiole often accompanied with alveolar wall destruction
Bronchitis - persistant cough with sputum form 3month consecutivly for 2years or more in absence of other identifiable disease. Inflammation of the bronchi and upper airway

Question 4

What is the pathogenesis of emphysema?

Answer 4

Smoking/pollutant -> ROS
Pollutant/damage -> inflammation leads to increased inflammatory mediators and ROS, recruitement of neutrophils alongside macrophages, T cells and B cells.
Proteases are released from immune cells and eithelial cells such as neutrophil elastase.
In patients with alpha 1 antitrypsen deficient cannot defend against protease activity
Leads to protease-antiprotease imbalance.
Damage to respiratory epithelium and parenchymal lung damage.
Damage to alveoli -> loss of elastic recoild and radial tension-> enlarged alveoli and air trapping, collapsed airway = functional obstruction.
Reducation in respirayory capillaries - reduced gas exchange.

Question 5

What are the histological changes seen in a patient with emphysema?

Answer 5

Increased airspaces - hyperinflation
Loss of regular acinar structure - decreased SA or alveolar sacs and ducts due to destruction of alveolar walls.
Increased neutrophil infiltrate.

Question 6

What is the clinical determinant of chronic bronchitis?

Answer 6

Productive cough for 3 months in at least 2 consecutive years.

Question 7

What are some general changes in the airway of a person with chronic bronchitis?

Answer 7

Lumen - obstruction, increased mucus production, abnormaly dehydrated mucus in appearance, pulmonary edema.
Epithelium - inc goblet cells in small airways, neutrophils infiltrate, may become sqaoumous metaplasia or dysplasia due to mutagenic effects of cigarette smoke, fibrosis
Underlying glands - hypertrophy and hyperplasia of underlying gland, increased thickness and number - contributes to mucus plugging.
Smooth muscle - higher level fo proliferation, hypersensitive.

Question 8

What signs and symptoms do we see in patients with chronic bronchitis?

Answer 8

Prooductive cough
Central Cyanosis - blue bloater presentation
Cor pulmonale
Wheeze on exhalation
Obsese
Peripheral odema

Question 9

How can smoking trigger asthma?

Answer 9

Substances settlint in the lining of the airways
Damages the cilia and causes the elungs to make more mucous than normal

Question 10

What are some signs that asthma is getting worse?

Answer 10

Require high doses or medication or more frequent inhaler use to continue with daily activities.
Decrease in exercise tolerance.
More nighttime wakening
Increase in hospitalisations
Fixed airflow obstruction indicates airway remodeling (BM thickening has occurred)

Question 11

What clinical assessments are done for a suspected asthma case?

Answer 11

Sputum analysis - white blood cell composition
Blood analysis - allergy testing, total IgE, specific IgE test in response to specific allergens,
Spiromtery - FEV1, FVC, FEF25-75, FEF50, FEF75, Peak flow test
Reversibility test - spirometer and bronchodilator
Exhaled nitric oxide test - high in conditions with inflammatory airways

Question 12

What are the main treatment barriers in asthma?

Answer 12

Difficult to avoid triggers/allergens
Poor adherence with controller medication
Inappropriate inhlaer technique
Inadequate patient education

Question 13

What are some common asthma triggers?

Answer 13

Infections - cold, viral respiratory, sinusitis, bronchitis
Inhaled allergens - pollen, feathers, dust mites, animal danders, feathers
Irritant inhalants - cold air, air pollution, smoke, chemical resins
Drugs - aspirin, beta blockers
Flood - sulfites in shrimp for example
Exercise

Question 14

What differential diagnosis are important to consider in asthma?

Answer 14

COPD - progressive and chronic
Acute bronchitis - productive cough and wheezing
Pneumonia - also norm fever and severe and sudden
heart failure - left sided cause pulmonary odema
GERD - chronic cough and wheeze if airway irritated
Anaphylaxis - also hives, itching and swelling
Foreign body aspiration - children, consider history
Pulmonary embolism - chest pain, history and risk factors

Question 15

What are the main drug recommendations for each class?

Answer 15

SABA - salbutamol
LABA - salmeterol
Inhaled corticosteroid - beclometasone or budesonide
Oral Corticosteroid - prednisolone
Biologics - moalizumab

Question 16

What is the mechanism of salmeterol in the treatment of asthma?

Answer 16

Class - LABA
Chem - adrenaline analogue
Pharmacology - agonist at beta 2 adrenergic receptors in bronchial smooth muscle this is GPCR, activated G protein subunit
Activates adenylate cyclase - increase cAMP production etc etc …. smooth muscle relaxation, dilating the airways.
Clinical: long term management and control of symptoms, night time symptoms, mainly due to longer set in time.

Question 17

Compare and contrast salbutamol and salmeterol

Answer 17

Salbutamol = SABA, rapid onset, lasts for 4-6hrs, immediate relief normally as needed
Salmeterol = LABA, sustained effect lasts for 12 hours, maintenance (twice daily), slower onset of action

Question 18

What are some of the unintended effects of prednisolone in asthmatic?

Answer 18

Increased hepatic gluconeogenesis, lipolysis and catabolism
Decrease hepatic glucose uptake
Increase renal GFR, Ca2+ excretion and urate excretion.

Question 19

What are some of the physiological effects of prednisolone?

Answer 19

Inhibits the activation of various immune cells, T-lymphocytes, B-lymphocytes, macrophages and mast cells - hence less inflammatory medaitors and impaired immune response to antigens and allergens
Decreases vasodilation, capillary permeability, reduced oedema and inflammation in affected tissues.

Question 20

Compare and contrast the use of prednisolone and budesonide in asthmatics.

Answer 20

Prednisolone - starts as pro-drug prednisone, metabolised in liver to active prednisolone, high systemic effects due to high oral bioavailability, longer duration of action 1/2x a day, used for wide range of systemic inflammatory and autoimmune condition

Budesonide - high topical effects, low systemic bioavailability as strong first pass effect in liver, so normally inhaled and reduced whole body side effects, shorter duration of action, normally used for loacalised inflammatory conditions such as asthma, COPD or allergic rhinitis.

Question 21

What is another term used to describe spirometry?

Answer 21

Pulmonary Function Testing

Question 22

What are the different lung capacities?

Answer 22

Inspiratory capacity - tidal volume + inspiratory reserve
Vital capacity - Inspiratory capcity + expiratory reserve volume
Functional residual capacity - Expiratory reserve and residual volume
Total lung capacity - vital capacity plus residual lung volume

Question 23

What are the different volumes that make up the lungs?

Answer 23

Inspiratory reserve volume
Tidal volume
Expiratory reserve volume
Residual volume

Question 24

What is the different size of the different lung volumes?

Answer 24

Inspiratory reserve volume - 3000mL
Tidal volume - 500mL
Expiratory reserve volume - 1200mL
Residual volume - 1200mL

Question 25

How does obstructive pulmonary disease present on spirometry?

Answer 25

Decreased (slightly) FVC
Decreased FEV1
Decreased FEV1/FVC
Decreased FEF25-75, 50 and 75
Decreased PEFR
Decreased slope or curve.

Question 26

What is meant by FEF25-75, 50 and 75?

Answer 26

25-75 the average midmaximal expiratory flow
50% - FEF at 50% forced vital capacity
75% - FEF at 75% vital capacity

Question 27

How does restrictive pulmonary disease present on spirometry?

Answer 27

Decreased (a lot) FVC
Decreased FEV1 (slightly)
FEV1/FVC - normal
FEF25-74 - normal to increased
PEFR - normal
FEF50 - normal
FEF75 - normal
Slope of FV curve - normal to increased,

Question 28

What features are common in airway remodelling of asthma?

Answer 28

Thickened basement membrane
Hypertrophy and hyperplasia of smooth muscle
Subepithelial fibrosis
Submucosal glands and goblet cell enlargement
Neovascularisation – further worsen V/Q mismatch – low V/Q mismatch – alveolar dead space. Also worsends immune cell migration and edema – exacerbating problems.
Epithelial alteration – desqaoumousisation
Cartilage degradation – increased proteglycan degradation, reduces cartilage integrity, reduced resistance to bronchospasm as often replaced by smooth muscle.
Caused by inc growth factors and inflammatory mediators.

Question 29

What is meant by persistent symptoms and corticosteroid resistance in asthma?

Answer 29

Persistent symptoms - remaining and difficult to control symptoms such as wheezing, coughing, SOB and chest tightness worse on allergen exposure even with treatment

Often aligns with corticosteroid resitenace - where conventional inhlaed corticosteroids are less effect at controlling airway inflammation and symptoms.

Question 30

What comorbidities is asthma often associated with?

Answer 30

Other atopic conditions - dermatitis, food allergies, allergic rhinitis.
May develop nasal polyps
Non atopic conditions: GERD, obseity, psychiatric conditions.

Question 31

Why might a doctor decide to give omalizumab rather than mepolizumab?

Answer 31

Omalizumab - targets IgE - key in allergic asthma, where the specific allergen is known, utilised with IgE levels are utilsed
Mepolizumab - severe eosinophilic asthma, where high eosinophilic levels
Choices also based on variable safety profiles of different drugs, patient tolerance to side effects, contraindications, response to previous treatment and characteristics of their asthma. Availability and cost may also factor.

Question 32

How to use a peak flow meter?

Answer 32

1. Ensure device is clean and indicator reset to bottom of sca;
2. Ask patient to stand up to use full lung capacity
3. Inhale filling lungs completely
4. Place mouthpiece of peak flow in your mouth, make tight seal with lips, do not put tongue over mouthpiece
5. Blow our as hard and as fast as you can in single breath - should push indicator along
6. Record measurement - this is peak flow
7. Repeat two times for consistency of measurement
8. Record highest value. (NOT mean)
9. clean device, norm dissasabmle and waist in warm water, mild detergent and air dry before next use.

Question 33

What are the different division of the airways?

Answer 33

Trachea
Bronchi (primary, secondary, tertiary)
Bronchioles
Terminal bronchioles
Respiratory bronchiles
Alveolar ducts
Alveolar sacs

Question 34

What is the anatomy and relevant innervation in the conducting zone?

Answer 34

Conducting zone - brings air into and out of the lungs
Includes nasal cavity to terminal bronchioles.
Walls of smooth muscle
Sympathetic -adrenergic neurons on beta 2 receptors - relaxation and dilation
Parasympathetic - cholinergic neruons on muscarinic receptors - constriction and contraction

Question 35

What is the function of the respiratory zone in the airways?
Relevant anatomy

Answer 35

Lined with alveloi for gas exhcnage
Start with respiratory bronchioles
Alveolar ducts - completely lined with alveoli, no cilia and little smooth muscle
Alveolar sacs - lined with alveoli, alveolar walls rimmed with elastic fibres and type 1/2 pneumocytes and contain alveolar macrophages.

Question 36

Why are the respiratory bronchioles considered transitional structures?

Answer 36

Have cilia and smooth muscle
But considered part of gas exchange region as alveoli occasionally bud off their walls

Question 37

What is the role of type 1 and type 2 pneuomocytes?

Answer 37

Type 1 - gas exchange as sqaoumous.
Type 2 - secrete pulmonary surfactant to reduce surface tension of alveoli, regnerative capacity for type 1 and type 2.

Question 38

What are the gross pathological changes in asthmatic lungs during an asthma attack?

Answer 38

Hyperinflation - regional or diffuse
Tenacious, viscid mucous plugs in airways.
Narrowed diameter of bronchi with increased mucous

Question 39

What are the microscopic changes in the appearance of an asthmatic lung during an asthma attack?

Answer 39

Mucous plug - contain neuts, eosino,
Hyaline thickening of the basement mebrane
Hypertrophy of smooth muscle, mucus glands and goblet cells
Enlarged blood vessels - congested

Question 40

Describe the pathogenesis of sensitization process in asthma.

Answer 40

Allergen exposure
Processing of allergen by professional antigen presenting cell (Normally an alveolar macrophages)
T cell activation by processed allergen (three activation signals including IL4/2) becomes Th2. Secrete Type 2 cytokines IL3,4,5,13,GM-CSF)
In lymph node activated T follicular helper interact with B cell, particularly IL4, encourages differentiation to a plasma cells then class switching from IgM to IgE.
IgE binds to Fc epislon receptor on mast cell surface.

Question 41

What happens in the immediate phase of an asthma attack?

Answer 41

Second antigen exposure
IgE-allergen complex forms on the surface of mast - triggers mast cell degranulation
Mediators include:
Histamine - bronchoconstriction and vasodilation
PGD2 - increase vascular permeability, pro-inflammatory
PAF2 - recruits and activates leukocytes, increase PG and leukotrienes, bronchoconstrictor
LTC4 - mucus secretion and smooth muscle contraction
Bradykinin
Tyrptase - damage to ECM
TNFalpha - promote inflammation, active leukocytes and endothelium.
Overall physiological effect - airway narrowing from bronchospasm, airflow limitations, edema, thick mucus plug

Question 42

What is the pathogenesis of a late inflammatory asthma response?

Answer 42

Activated Th2 releases cytokines to recruit and activate eosinophils and some basophils
Mast cell degranulation - mediators recuit eosinophils and basophils. (IL5, GM-CSF and IL3)
Increased vascular permeability, chemokines and upregulated adhesion molecules help recuit to the area.
Release proteases such as MBP and ECP - damage lung tissue.
Also release mediators such as IL-13 to further perpetuate the Th2 response.
Overall physiological response - destruction of epithelium, desquamation, chronic inflammatory changes, risk of airway remodelling including subepithelial fibrosis and smooth muscle hypertrophy.

Question 43

What is the key features of the process underpinning chronic asthma?

Answer 43

Chronic low grade inflammation, extends beyond muscularis.
Hence less susceptible to inhlaed medications
Thickening of basement membrane secondary to inflammation.

Question 44

What [art of the airway is mainly affected by asthma?

Answer 44

The large and small conducting airway.

Question 45

What is asthma?

Answer 45

A chronic inflammatory disease of the small and large conducting airways
Caused variable construction of airflow
Characterised by inflammation, bronchospasm and hyperresponsiveness of the airways.

Question 46

What is the mechanism underpinning the hyigeine hypothesis?

Answer 46

Early exposure to a range of microbes can be beneficial or protective against the development of asthma
Educate the airway immune systems to develop tolerance against stimulant antigens
Thought to have epigenetic explanations.
Similar with exposure to the maternal microbiota.

Question 47

What is the epithelial barrier hypothesis related to asthma?

Answer 47

Local epithelial damage and decreases barrier intergirty of the mucosa can lead to type 2 inflammation which can manifest as asthma.
Colonising opportunistic pathogens and infective agents penetrate subepithelial triggering and immune and inflammatory response
This further cause more damage decreases repair response, and increases microbial dysbiosis and decreased biodiversity
Acts as a cycle promoting long term inflammation.

Question 48

What is the role of sensory nerve dysfunction in asthma?

Answer 48

Increases parasympathetic stimulation - causes mucus secretion and bronchoconstriction.
Inflammatory process - alterl nerve phenotype, increase nerve densirt and provoke neuronal mediators release.

Question 49

What is the mechanism of non-type 2 asthma?

Answer 49

Characterised by Th1, Th17 lymphocytes.
Innate immune response may also contribute.
Action of neutrophils and paucigranulocytic subtypes (lymphocyte driven)

Absence of eosinophils or T2-high response.

Question 50

Separate the environmental triggers for asthma into passive and active.

Answer 50

Passive - 2nd hand smoke, air pollution and pets
Active - occupation, smoking, exercise etc.

Question 51

What are the symptoms of asthma?

Answer 51

Symptoms are episodic - can be worse or better - diurnal variability - fluctuate at different times of day, typically worse at night
SOB
Chest tightness
Dry cough
Wheeze. (polyphonic on auscultation)

Question 52

What is the appropriate inhaler technique for a dry power inhaler?

Answer 52

1. Check dose left and expiry date
2. Remove mouth piece
3. Hold upright and shake thoroughly 3-5 times
4. Stand (or sit) up straight slightly lift up chin
5. Push down on inhaler between thumb and forefinger until clicks - dose is now released into inhlaer
6. Breath out slowly away from inhaler until lungs are empty
7. Secure mouth to create seal with lips/teeth around mouthpiece (above tongue)
8. Breath in deeply through mouth
9. Hold breath for 10 seconds
10. Breath out slowly through mouth away from mouth piece
11. Replace cap
12. Wait 60-90s repeat if needed
13. Rinse out mouth with water to reduce risk of side effects.

Question 53

How to use a pressurised meaturised dose inhaler (pMDI) ?

Answer 53

1. test and prime inhlaer (when new or not used in 5+ days) - cap off, shake, point away from you, test spray the require number of times
2. Check dose counter
3. Hold inhlaer up right, take cap, off, check nothing in mouth piece
4. Sit or stand up straight, chin up slightly
5. Breath out away from inhaler until empty
6. Mouth over inhaler - begin to breath in slowly, whilst doing so press cap down once and continue breathing in deeply/slowly until lungs are full
7. Hold breath for ten seconds
8. Slowly breath out away from inhaler
9. Recap inhlaer and rinse out mouth

Question 54

How to adapt the pMDI inhlaer technique to use a spacer?

Answer 54

Ensure spacer valve is facing upwards
Remove mouth piece cap from spacer
Insert inhlaer (after shking) into spaces
Put out over space before releasing dose
Inhale, remove spacer keep mouth closed then hold breath.

Question 55

What is the guidance around the use of prednisolone in asthma patients?

Answer 55

mild to moderate asthma, severe or life threatening acute asthma - adult (12yrs+) should taken 40-50mg daily for at least five days, child 1-2mg/kg once daily for up to 3 days

If already taken for 5 days increase child dosage to 2mg/kg.

Should be kept at lowest dose for adequate control, short courses only, if given long term orally should be given a steroid treatment card with info on side effects and drug prescription details.

Question 56

What is a specialist asthma centre?

Answer 56

Is led by atleast two consultants with a specific interest in severe asthma
Provides more focused attention from respiratory experts.
Is a tertiary centre - can offer specialist tests should as spirometry and specialist treatment such as biologics.
Aim to identify and reduce triggers, identify subtype of asthma, help with side effects, treat conditions linked to severe asthma such as sleep apnoea.

Question 57

What MDT may be found at a specialist asthma clinic?

Answer 57

Specialist asthma physician
Speciaist asthma trained nurse
Physiotherapist
Pulmonary function scientist - help complete and interpret lung function tests
Dietitian
Speech therapist - help identify and treat vocal cord dysfunction.
Psychologist - anxiety and depression are common in severe asthma population.

Question 58

What is the pathophysiology of chronic bronchitis in COPD?

Answer 58

Exposure to inhaled noxious or irritating stimuli
1. Mucus hypersecretion - large airways have nelarged submucosal glands in trachea and bronchi (mediated by histamine and IL-3), also increase in goblet cells in the small airways
2. Acquired CFTR dysfunction - mediated by cigarette smoking, abnormal and dehydrated mucus
3. Inflammation - lymph and neuts cause cellular damage, destruction of epithelium.
Effect can be exaggerated by not necessary caused by a respiratory tract infection.

Question 59

What is COPD?

Answer 59

Persistent respiratory symptoms, airflow limitations due to airflow/alveolar abnormalities
Due to functional obstruction of airflow.
Caused by exposure to inhaled noxious gaseous particles or irritants.