Obstructive Diseases Flashcards
1
Q
Where do obstructive diseases affect?
A
The airways
2
Q
What are examples of obstructive diseases?
A
Asthma, COPD- chronic bronchitis/emphysema
3
Q
What is ACOS?
A
Asthma/COPD overlap syndrome (smokers with features of both)
4
Q
ACOS is essentially COPD with what?
A
Reversibility and some eosinophilic inflammation which is steroid responsive
5
Q
Asthma is a chronic inflammatory disease of where?
A
Small and large airways
6
Q
What is the basic underlying disease process in asthma?
A
Airway inflammation
7
Q
How many levels of branching does the bronchial tree consist of?
A
23
8
Q
What is the conducting zone of the bronchial tree?
A
The first 16-17 branches which play no role in gas exchange
9
Q
What is the respiratory zone of the bronchial tree?
A
The last 6-7 branches which is where gas exchange takes place
10
Q
What zone of the respiratory tree involves the bronchi?
A
Conducting zone
11
Q
Which zone of the respiratory tree involves the respiratory bronchioles, alveolar ducts and sacs?
A
Respiratory zone
12
Q
What is the size roughly of the small and large airways?
A
Small- <2mm, large- >2mm
13
Q
Where will inhaled particles <5 microns get past?
A
Carina
14
Q
Where will inhaled particles <2 microns get past?
A
8th branch of bronchioles
15
Q
What three things must a patient have to have asthma?
A
- Eosinophilic airway inflammation
- Airway hyper-responsiveness
- Reversible airway obstruction
16
Q
What does bronchoconstriction in asthma cause?
A
Brief symptoms
17
Q
What does chronic airway inflammation in asthma cause?
A
Exacerbations of asthma
18
Q
What does airway remodelling in asthma cause?
A
Irreversible fixed airway obstruction
19
Q
What are triggers treated with in asthma?
A
Allergen avoidance
20
Q
What is eosinophilic inflammation treated with in asthma?
A
Anti-inflammatory corticosteroids and maybe cromones
21
Q
What are mediators of asthma and when are they released?
A
Released upon antigen binding to IgE- histamine, leukotrienes, cytokines
22
Q
What medication can be given to block mediators in asthma?
A
Anti-histamines/leukotrienes, anti-IgE, anti-IL5
23
Q
What drugs are used to treat hyper-reactive muscle in asthma?
A
Drugs which stimulate the sympathetic nervous system to relax the airways- bronchodilators, beta2 agonists, muscarinic antagonists
24
Q
What are the only drugs which restore normal mucosal architecture?
A
Corticosteroids
25
What are the most important drugs to consider as possible causes of asthma?
NSAIDs and beta-blockers
26
How is asthma diagnosed?
History and exam, diurnal variation of peak flow rate, reduced FVC/FEV1 ratio, reversibility to inhaled salbutamol, provocation testing leads to bronchoconstriction
27
What can COPD lead to?
Chronic bronchitis or emphysema
28
What 5 things can chronic bronchitis cause?
- Mucus hypersecretion
- Chronic neutrophilic inflammation
- Mucociliary dysfunction
- Altered lung microbiome
- Smooth muscle spasm and hypertrophy
29
Which out of emphysema and chronic bronchitis is partially reversible and which is irreversible?
Emphysema- irreversible
| Chronic bronchitis- partially reversible
30
What are characteristics of COPD?
Exacerbations and reduced lung function
31
What are symptoms of COPD?
Breathlessness, cough with sputum production, worsening QOL
32
What does cigarette smoke cause macrophages and airway epithelial cells to secrete?
Neutrophil chemotactic factors- IL8 and LTB4
33
What does neutrophils and macrophages releasing proteases do in COPD?
Breaks down connective tissue in the lungs and stimulates mucus hypersecretion
34
What might also be involved in the destruction of alveolar wall epithelial cells in COPD?
CD8+ T cells
35
What does an imbalance of proteases and antiproteases lead to in COPD?
Inflammatory changes in the airways including damage of the respiratory mucosa
36
What is neutrophil elastase?
An enzyme which can damage the cilia
37
What causes the loss of ciliated cells in COPD?
Recurrent bacterial infections
38
How do you assess COPD?
Assess symptoms, degree of airflow limitation using spirometry, risk of exacerbations, comorbidities
39
What are high risk factors for COPD?
2 or more exacerbations in one year, <50% FEV1
40
What lung sound will chronic bronchitis show?
Wheezing
41
What lung sound will emphysema show?
Reduced breath sounds
42
What is the chronic cascade in COPD?
Progressive fixed airway obstruction, impaired alveolar gas exchange, type 2 respiratory failure, pulmonary hypertension, cor pulmonale, death
43
What classifies ACOS?
COPD with blood eosinophilia >3%
44
Will mucosal architecture ever be restored in ACOS?
No
45
Is there reversibility to salbutamol in ACOS?
Yes
46
is there diurnal variability in COPD?
No
47
What do intermittent attacks of bronchoconstriction in asthma result in?
Tight chest, wheezing, difficulty breathing, cough
48
Chronic asthma causes changes to the bronchioles as a result of long standing inflammation. What are some examples of these changes?
- Increase smooth muscle mass
- Accumulation of fluid (oedema)
- Increased mucus
- Epithelial damage
- Sub-endothelial fibrosis
49
Airway narrowing and bronchoconstriction in asthma do what to PEFR and FEV1?
Decrease them
50
What are two bronchial components of asthma?
Bronchial hypersensitivity and hyperresponsiveness
51
What two phases does an asthma attack comprise?
Immediate bronchospasm and delayed inflammation
52
Describe the stages of non-atopic asthma?
Allergen, phagocytosis by dendritic cell, low level TH1 response, cell mediated immune response involving IgG and macrophages
53
Describe the stages of atopic asthma?
Allergen, phagocytosis by dendritic cells, strong TH2 response, antibody mediated response involving IgE
54
What does the initial presentation of an antigen stimulate in allergic asthma?
Adaptive immune response
55
What do eosinophils differentiate and activate in response to?
IL5 from TH2 cells
56
What do airway mast cells differentiate and activate in response to?
IL4 and IL13 from TH2 cells
57
What happens on subsequent presentation of an antigen in allergic asthma?
The allergen cross-links the IgE receptor
58
What does cross linking of the IgE receptor in allergic asthma cause release of?
Intracellular Ca++
59
In allergic asthma, what does Ca++ cause release of to cause airway obstruction?
Secretory granules containing histamine and more
60
In allergic asthma, what does Ca++ cause release of to cause inflammation?
Release of platelet activating factor and prostaglandins to attract cells
61
What are reliever (bronchodilator) drugs used in asthma?
Beta2 agonists, CysLT receptor antagonists
62
What are controller/preventer (anti-inflammatory) drugs used in asthma?
Glucocorticoids, cromones, monoclonal IgE antibodies
63
What asthma drugs have bronchodilator and anti-inflammatory effects?
Methylxanthines
64
What is step 1 of asthma treatment?
Mild asthma- prescribe SABA to be used as needed
65
When do patients need to move to step 2 of asthma treatment?
When the SABA is needed more than once daily
66
What is step 2 of asthma treatment?
Add inhaled glucocorticoid
67
If there is still inadequate control, what is step 3 of asthma treatment?
Add a LABA
68
If once added, a LABA is beneficial for asthma, what should you do?
Continue LABA
69
If once added, a LABA is beneficial but not adequate for asthma, what should you do?
Increase dose of ICS but keep up LABA
70
If once added, a LABA is not beneficial for asthma, what should you do?
Take off LABA, increase dose of ICS
71
If asthma is still poorly controlled, what is step 4 of asthma treatment?
Increase dose of ICS and add-on therapy e.g. CysLT1 antagonist, methylxanthine, oral beta2 agonist
72
If still uncontrolled, what is step 5 of asthma treatment?
Introduce oral steroid, refer to specialist
73
How do beta adrenoceptor agonists cause smooth muscle relaxation?
Decrease intracellular Ca++ and activate large K+ conductance channels
74
What are salbutamol and terbutaline examples of?
SABAs
75
When are SABAs taken?
As required
76
How are SABAs taken?
Usually inhaled, can be oral for children and IV for emergencies but these are unlikely
77
How long do SABAs last?
They act rapidly and last 3-5 hours
78
Apart from relaxation of smooth muscle, what other functions do SABAs have?
Increase mucus clearance, decrease mediator release from mast cells and monocytes
79
What are some side effects of SABAs?
Fine tremor, tachycardia, dysrhythmia, hypokalaemia
80
What are salmeterol and formoterol examples of?
LABAs
81
How long do LABAs last?
8 hours roughly
82
What is the most important rule for prescribing LABAs?
Never use alone- always co-administer with glucocorticoid
83
Where are CysLT1 receptors usually found?
Mast cells and infiltrating inflammatory cells
84
What are montelukast and zafirlukast examples of?
CysLT1 receptor antagonists
85
How are CysLT1 receptor antagonists administered?
Orally
86
When are CysLT1 receptors not used?
For severe, acute relief
87
What are some side effects of CysLT1 receptor antagonists?
Headaches, GI disturbance
88
What are theophylline and aminophylline examples of?
Methylxanthines
89
What does theophylline activate to increase anti-inflammatory actions of glucocorticoids?
Histone deacetylase
90
What are methyxanthines used in combination with?
Beta2 agonist and steroid
91
How are methyxanthines administered?
Orally
92
What side effects can methylxathines cause at normal concentrations?
Nausea, vomiting, abdominal discomfort and headache
93
What side effects can Methylxanthines cause at high concentrations?
dysrhythmias, seizures, hypotension
94
What makes Methylxanthines problematic?
Many drug interactions including some antibiotics
95
What is the main glucocorticoid hormone?
Hydrocortisone
96
What are glucocorticoids used for in asthma?
Prophylaxis
97
How are glucocorticoids usually delivered?
Inhaled
98
How do glucocorticoids enter the cell membrane?
Diffusion
99
What are some side effects of inhaled glucocorticoids?
Hoarse/weak voice, candidiasis
100
When can oral prednisolone be used?
In acute, severe, rapidly deteriorating asthma alongside inhaled steroids
101
What are cromones used for?
2nd line treatment only really used in children
102
What are cromones often described as?
Mast cell stabilisers (suppress histamine release from mast cells)
103
What is an example of a cromone?
Sodium cromoglicate
104
What do monoclonal IgE antibodies do?
Suppress mast cell response to allergen
105
How are monoclonal antibodies given?
IV
106
What is the treatment for an acute asthma attack? (OH SHIT MAN)
```
OH- oxygen
S- salbutamol nebulised
H- hydrocortisone IV/oral
I- ipratropium nebulised with salbutamol
T- theophylline
M- magnesium sulphate
AN- anaesthetist
```
107
What is the acute treatment for COPD? (iSOAP)
```
I- ipratropium
S- salbutamol
O- oxygen (24-28% in venture mask)
A- antibiotics (amoxicillin if non-severe)
P- prednisolone
```
108
What 4 things indicate severe asthma?
Inability to complete sentences, tachycardia, tachypnoea, PEFR < 50% predicted
109
1 or more of what 5 things indicate life-threatening asthma?
PEFR <33% predicted, hypoxaemia, hypercapnia, silent chest, exhaustion
110
What can treatment for COPD do?
Slow, but not reverse disease progression, ease chronic symptoms and prevent acute exacerbations
111
How do muscarinic receptor antagonists work?
By blocking activation of M3 muscarinic receptors by ACh to prevent bronchoconstriction
112
What is an example of a SAMA?
Ipratropium
113
What is an example of a LAMA?
Tiotropium
114
Which receptors does ipratropium block?
M1, 2 and 3
115
Which receptor does tiotropium block?
M3
116
Block of which muscarinic receptors is desirable and which is not?
M3 and M1 are desirable but M2 is not
117
What does a combination of a LAMA and a LABA cause in COPD?
Increased FEV1 and smooth muscle relaxation
118
What risk comes with steroids (particularly oral) in COPD?
Pneumonia
119
What are mucolytics such as carbocysteine used for in COPD?
To reduce sputum viscosity
120
What are PDE4 inhibitors used for in COPD but what are their side effects?
Used to reduce exacerbations but can cause nausea, diarrhoea, headache and weight loss
121
What does O2 therapy do in patients with daytime hypoxaemia?
Prolongs life by slowing progression of cor pulmonale
122
How are corticosteroids used in COPD?
Combination with a LABA to reduce exacerbations in eosinophilic COPD
123
What can happen if an inhaled drug hits the larynx?
Atrophy
124
What is omalizumab?
Anti-inflammatory anti-IgE
125
How is omalizumab administered?
Injections every 2-4 weeks
