Asthma/COPD Flashcards
1
Q
Patient with COPD who has never smoked
A
Alpha 1 anti trypsin deficiency
2
Q
what is cor pulmonae
A
right sided hypertrophy and heart failure due to increased vascular resistance
3
Q
difference between obstructive and restrictive disease
A
Obstructive-airways
Restrictive- lungs
4
Q
examples of obstructive lung disease
A
Asthma, COPD (chronic bronchitis, emphysema)
5
Q
what is asthma COPD overlap syndrome
A
Asthma and COPD
smokers with COPD who are eosinophilic and show reversibility with bronchodilators and are steroid responsive
6
Q
Cause of airway obstruction in COPD
A
invagination of mucosa
smooth muscle constriction
alveolar wall attachments to bronchioles break away
in emphysema
7
Q
Extrinsic vs Intrinsic asthma
A
extrinsic-identifiable cause
intrinsic-unknow cause
8
Q
Type II Inflammation - what this involves and what types of asthma is this associated with
A
TH2 cells, type II lymphoid cells, B cells which produce IgE, type II cytokines (IL4, IL5, IL13)
Effector cells- eosinophils, basophils, mast cells
associated with allergic asthma, exercise induced asthma and late-onset eosinophilic asthma
9
Q
Asthma triad
A
T2 airway inflammation (eosinophils) Airway Hypersensitivity (twitchiness) Reversible airflow obstruction
10
Q
Dynamic evolution of asthma
A
- Bronchoconstriction
- Chronic airway inflammation
- Airway remodelling
11
Q
Hallmarks of asthma remodelling
A
BM thickening, collagen deposition in the submucosa and smooth muscle hypertrophy
12
Q
key cytokines in asthma
A
IL4, IL5, IL13
13
Q
Influence of Leukotriene D4
A
attracts eosinophils, makes goblet cells secrete mucous
14
Q
Endotypes which indicate type II high asthma
A
present cytokines IL4, IL5, IL13
raised total or specific IgE
Eos >300
Raised FeNO
15
Q
why should asthmatics never be treated with B2 agonists alone
A
Doesn’t get rid of problem
16
Q
how do we measure airflow obstruction
A
peak flow or spirometry
17
Q
how do we measure bronchiole hypersensitivity
A
challenge testing
18
Q
how do we measure airway inflammation
A
invasive bronchoscopy
19
Q
Presentation of asthma
A
Episodic S+S i.e. there is a trigger
Diurnal variability-worse at night and early morning
non-productive cough
wheeze
TH2 comorbidities
Responsiveness to steroids and beta2 agonists
FHX of asthma
20
Q
Presentation of asthma
A
Episodic S+S i.e. there is a trigger may be atopic Diurnal variability-worse at night and early morning non-productive cough wheeze TH2 comorbidities Responsiveness to steroids and beta2 agonists FHX of asthma
21
Q
Investigations in Diagnosis of asthma
A
the diagnosis of asthma is a clinical one
should have at least 1 of the 4 symptoms and have variable airflow obstruction
History and examination
Diurnal variability of peak flow rate
Spirometry/peak flow-reduced FER OF <0.75
Reversibility to inhaled salbutamol of >0.15
Provocation testing- exercise, histamine, methacholine, mannitol
FeNO
Blood eosinophils
Blood IgE
22
Q
Signs and Symptoms of COPD
A
Usually smoker Chronic, not episodic non-atopic FER <0.7 usually no reversibility to bronchodilators Respiratory failure (paO2 down, PaCO2 up) pulmonary hypertension RV failure
Productive cough, wheeze, Breathlessness
Exacerbations
Reduced breathing sounds (emphysema)
23
Q
Treatment of asthma (SIGN GUIDELINES)
A
- Low dose ICS with SABA
- Add LABA
- stop LABA, increase ICS or just increase ICS or add LTRA, theophylline or LAMA
- increase ICS or add on 4th drug (LTRA, theo, LAMA)
- low dose oral steroid
Step 4 and 5-refer to specialist care
24
Q
Treatment of COPD
A
Non-Pharmacological
exercise, smoking cessation, vaccines (flu, pneumococcal), pulmonary rehab, o2
Pharmacological
LABA/LAMA (non-eosinophilic)
ICS/LABA
ICS/LABA/LAMA
PDE4 inhibitors- Roflumilast
Mucolytics- Carbocisteine
Antibiotics
25
What type of inflammation is asthma associated with
eosinophilic
26
Two conditions that make up COPD and their features
Neutrophils release protease which cause alveolar wall destruction (emphysema) and mucus hypersecretion (bronchitis)
Emphysema- alveolar wall destruction therefore a loss of bronchiole support, impaired gas exchange (irreversible)
chronic bronchitis- chronic neutrophilic inflammation, mucus hypersecretion, impaired mucocilary function, change in lung microbiome (more G-), smooth muscle spasm and hypertrophy (partially reversible)
27
Diagnosis of COPD
Assess symptoms
Spirometry-FER <0.75
assess risk of exacerbations assess comorbidities
28
Which COPD patients are 'high risk'
2 or more exacerbations in 1 year, FEV1 <0.5
29
how stop further decline in COPD
smoking cessation
30
What does spirometry measure
forced expiratory volumes, rates
31
what is helium and N2 washout used for
static lung volume, residual volume, TLC, FC
32
whole body plethysmography
measuring changes in volume within an organ or whole body
33
when would you have reduced CO transfer factor
interstitial lung disease, COPD (emphysema), anemia, pulmonary oedema
34
Spirometry for asthma
normal FVC, reduced FEV1
| FER <0.75
35
spirometry of COPD
reduced FVC and FEV1
| FER <0.7
36
spirometry of COPD
```
reduced FVC (emphysema, gas trapping) and FEV1
FER <0.7
```
37
PEFR in obstructive vs restrictive
reduced in obstructive
| normal in restrictive
38
FEV1 in obstructive vs restrictive
both reduced
39
FVC in obstructive vs restrictive
o-asthma normal, COPD reduced
| r- reduced in proportion to FEV1
40
FER in obstructive vs restrictive
normal in Restrictive
<0.75 asthma
<0.7 in COPD
41
FEV1 response to B2 agonists
>0.15 asthma
<0.15 COPD
no effect in restrictive
42
Bronchiole challenge testing
Concentration of allergen to reduce FEV1 by 20%
43
Two types of drugs for airflow obstruction
preventer- anti inflammatories
| relivers- bronchodilators
44
Corticosteroids
| uses, oral form, inhaled from
Used in asthma and COPD
may cause Pneumonia in COPD
Oral=Prednisolone (exacerbations)
Inhaled= Beclomethasone
beclomethasone is used as monotherapy or in combo in asthma, only used in combo in COPD
Targets eosinophils
45
Practical management of asthma
induce remission with oral steroids then maintain with inhaled steroids- never use inhaled steroids in acute unstable asthma
46
Actions of spacer device
reduces particle size to less than 5 micrometres so can get past carina
reduces velocity therefore gag
reduced systemic absorption
reduced oropharyngeal and laryngeal S/E
47
Cromones
eg cromoglicate
mast cell stabilisers (anti-inflammatory)
only used in asthma, affective in atopic children (EIB)
inhaled only
poor efficacy
48
Anti-Leukotriene
| example drug, use ect
eg Montelukast- 1/ day tablet
only used in asthma as an add on-best drug for EIB and allergic rhinitis
49
Name the three monoclonal antibodies used in severe asthma and examples of each
Anti-IgE: Omalizumab
Anti-IL5/Anti-IL5R alpha: Mepolizumab, Benralizumab
Anti-IL4R alpha: Duplimab
50
Anti-Leukotriene
| example drug, use ect
eg Montelukast- 1/ day tablet
only used in asthma as an add on-best drug for EIB, allergic asthma and allergic rhinitis
51
short acting B2 agonists
salbutamol
52
long acting b2 agonists
salmeterol, formoterol
53
side effects of b2 agonists
tachycardia, fine tremor, hypotension, hypokalaemia
54
Action of muscarinic antagonists
Block M3 receptors
| mostly used in COPD
55
short acting muscarinic antagonist
ipratropium
56
long-acting muscarinic antagonist
tiotropium
Glycopyrronium
aclidinium
umeclidinium
57
Examples of methylxathines
```
Theophylline
Aminophylline (acute attacks)
non-selective phosphodiester inhibitor is an adenosine antagonist
used in asthma, sometimes COPD
P450 interactions
```
58
Examples of methylaxthines
Theophylline (add on in asthma, SE limit therapy)
Aminophylline (acute attacks)
non-selective phosphodiester inhibitor is an adenosine antagonist
used in asthma, sometimes COPD
P450 interactions
59
Mucolytics
Carbocisteine, erdosteine
add on in COPD
increased sputum viscosity
60
Mucolytic
Carbocisteine, erdosteine
add on in COPD
increased sputum viscosity
61
Treatment of acute asthma
```
Oxygen
Salbutamol (nebulised)
Hydrocortisone (IV) or Oral prednisolone(40mg, 5/7 days)
Ipratropium (nebulised)
Theophylline, aminophylline
Magnesium
ANaesthetists
```
62
Treatment of acute COPD
Oxygen
Salbutamol (neb)
Ipratropium (neb)
Antibiotic (amoxicillin/doxy)
Prednisolone
physio for sputum exportation
NIV, ITU
63
GOLD
looks at FEV1
1 OVER 80
2 50-79
3 30-49
4 LESS THAN 30
64
Symptoms of asthma
Non-productive cough, wheeze, tight chest, breathless
65
SIGN diagnosis of asthma
start treatment then test
start on SABA- if good response diagnose with asthma
if poor response test spirometry + bronchodilator reversibility+ other tests
66
when should asthma patients be referred to secondary care+red flags
- all occupational asthma
- up to stage 4
- severe/life threatening asthma
- fever, myalgia, weight loss
- crackles, clubbing, stridor
67
Inaudible laryngeal obstruction
inappropriate abduction of vocal cords
Sensitivity to strong smells, exercise- severe breathlessness- stridor- cant breathe in-feeling of something stuck in the throat
not an allergic phenomenon
68
Drugs that won't work with smoking
steroids
| macrolides
69
Allergic Broncho-pulmonary Aspergillosis
symptoms
pathology
treatment
allergic response to aspergillus, involves mucus plugging and proximal bronchiectasis
Total IgE >1000, elevated aspergillus IgE
Treatment: Steroids and Itraconazole
70
Atopic triad of allergic asthma and treatment options
Asthma, eczema, rhinitis
allergy avoidance
anti-histamines
montelukast
Omalizumab (binds to Fc of IgE)
71
Eosinophilic asthma aetology
| treatment
late onset, mostly women
steroid resistant
Mepolizumab, Benralizumab
72
why is normal co2 is acute asthma worrying
Should have low co2 due to hyperventilation- a normal co2 is very bad-phone intensive
73
should be use CPAP in acute asthma
CPAP not indicated for acute asthma
74
moderate acute asthma
increasing symptoms
PEF >50-75%
no symptoms of acute severe asthma
75
acute severe asthma
any 1 of:
- PEF >33-50%
- RR >25/min
- HR >110/min
- inability to complete full sentences in 1 breath
76
life-threatening asthma
- altered consciousness (PEF<33%)
- Exhaustion (SpO2 <92%)
- Arrhythmia (PaO2 <8KPa)
- Hypotension (normal PaCo2 4.6-6KPa)
- Cyanosis
- Silent chest
- Poor respiratory effort
77
Near fatal asthma
Raised PaCo2 and/or requiring mechanical ventilation with increased ventilation pressures
78
effect of ACh on airways
| effect of VIP and NO on airways
ACh causes bronchoconstriction and mucus hypersecretion via M3 receptors
VIP and NO cause bronchodilation
79
effect of sympathetics on airways
no direct innervation, but will stimulate adrenal gland which releases adrenaline
- bronchodilation due to adrenaline acting on B2 adrenoceptors
- decreased mucus
- increased mucocilary clearance
- vascular smooth muscle contraction (a1)
80
gold square
x axis=symptoms
| y axis=exacerbations
81
criteria for bullectomy
bullae occupying for than 50% of thoracic cavity
82
Two types of NIV
expiratory positive airways pressure-lowers work of breathing, reduced pCo2
inspiratory positive airways pressure- increased TV and Pco2
83
process of contraction in ASM
ACh stimulates M3 ACh GCRP, activating Gq/11 which activates PLC.
PLC causes conversion of PIP to IP3.
IP3 activates the Ca2+ channels in the SR to release calcium from SR
causes depolarisation of other calcium channels and more calcium enters
increased intracellular calcium-contraction
84
Describe how calcium causes the contraction of ASM
calcium and calmodulin make calcium-calmodulin
calcium-calmodulin activates MLCK
Active MLCK will phosphorylate cross bridges
Phosphorylated MLC
85
What causes relaxation of ASM
Dephosphorylation of MLC by myosin phosphorylase
Adrenaline activates GPCR which activates GS which causes conversion of ATP to cAMP
cAMP activates PKA which phosphorylates and stimulates myosin phosphotase and inhibits MLCK
86
how is cAMP deactivated
by PDE-turned into 5AMP
87
Immediate and delayed phases of an asthma attack
immediate- bronchospasm-Type I hypersensitivity
| delayed- type IV hypersensitivity
88
response to allergen by non-atopic individual
TH1 response, cell mediated response involving IgG and macrophages
89
Atopic individual
Strong TH2 response, antibody mediated IgE response
90
what response predominates in mild-moderate asthma
TH2
91
what response predominates in severe asthma
TH2 and TH1 contributes
92
cascade of events with cells in Asthma
- Allergen presented to T CD4+ cell by APC
- T CD4+ cell converts to TH0 which differentiates to TH1 and TH2
- TH2 will activate B cell via IL4 and B cells will form plasma cells which secrete IgE antibodies
93
Influence of TH2 cells on effector cells
TH2 produces IL4, IL5, IL13
IL4 activates B cells to make more plasma cells which secrete IgE
IL5 activates eosinophils which express IgE receptors
IL4 and IL13 activate mast cells to degranulate
94
Effect of IgE binding to mast cell
stimulates calcium entry into mast cells and the release of intracellular calcium stores
- Smooth muscle contraction: release of histamine and leukotrienes
- Attracting inflammatory cells: release of chemotaxins, prostaglandins ect
95
two types of steroid hormone secreted by adrenal cortex
not stored, synthesised on demand
Glucocorticoid-cortisol which reduced inflammatory responses
mineralocorticoid-aldosterone (unwanted in treatment of inflammatory conditions)
96
Mechanism of glucocorticoids
enter cells by diffusion across cell membrane
combine with GRa so it dissociates from inhibitory shock proteins
activated receptor translocates to nucleus via importins
with nucleus, homodimers form
transcription of specific genes is switched on or off
97
effect of glucocorticoids on inflammatory and anti-inflammatory genes
Glucocorticoids increase anti-inflammatory genes by recruiting histone deacylase
Glucocorticoids decrease inflammatory genes by aceylation of histones
98
Effect of glucocorticoids on inflammatory cells
TH2-apoptosis
Eosinophils-apoptosis
mast cells-reduced no and reduced Fce expression
99
What component of asthma does glucocorticoids supress
Inflammation
100
Most common side effects of ICS
```
Dysphonia (weak and hoarse voice)
oropharyngeal candidiasis (thrush)
```
101
which phase of breathing fails in COPD
Expiration
102
Systemic effects of SAMA and LAMA
Quaternary ammonium group (atropine) reduces absorption and systemic effects of SAMA/LAMA
103
Location of muscarinic ACh receptors in airways and types of receptors
M1-ganglia (fast, nicotinic receptors)
M2-postganglionic neuron terminals- reduce release of ACh (inhibitory autoreceptors)
M3-ASM-contraction due to ACh
104
what type of muscarinic antagonists are preferred for asthma treatment
selective-we don't want to block M2- preference for agents which prefer M3 signalling
SAMA, ipratropium is non-selective
LAMAs are selective
105
Management of an acute exacerbation of asthma within community setting
40mg Prednisolone 5/7 days
smoking cessation, allergy avoidance
2 day f/u safety net
106
investigation for patient with 3 or more COPD exacerbations in 6 months
HRCT to check for bronchiectasis
