1
Q
what is COPD?
A
a chronic progressive disorder characterised by airflow obstruction
2
Q
what is COPD diagnosed by?
A
reduced FEV1 and FEV1/VC ratio
3
Q
what is the lung function with COPD?
A
impairment is fixed ans irreversible
4
Q
what is FEV1?
A
the maximum volume of air exhaled in the first second of a forced expiration, following full inhalation
5
Q
what is the FEV1/ FVC ratio?
A
measure the proportion of a persons total air capacity that an be exhaled in the first second of a forced breath
6
Q
what is COPD the end result of?
A
complex biological and environmental interactions over the lifetime that can damage the lungs and/or affect their normal developing or aging processes
7
Q
what are the main environmental exposures leading to COPD?
A
tobacco smoking
inhaltion of toxic particles and gases from household air pollution but also occupational settings, frequent lung infections as a child
8
Q
what is the rare genetic risk of COPD caused by?
A
mutations in SERPINA1 gene leading to a1-antitrpsin deficiency
9
Q
what is non-smoking COPD more common in?
A
females in younger age, milder respiratory symptoms, lesser rate of decline in lung function, less emphysema, lower neutrophiles and higher eosinophils
10
Q
what does chronic exposure to air pollution do?
A
impairs lung growth in children, accelerates lung function decline in adults and increases risk of COPD exacerbations
11
Q
how long does it take for lungs to grow and mature?
A
20-25 years
12
Q
what are childhood disadvantage factors for COPD?
A
in utero exposure to noxious substances, premature birth, neonatal lung injury, repeat lung infection in early life
13
Q
what immunity is involved in COPD inflammation?
A
innate and adaptive
14
Q
what is the predominant inflammatory response?
A
neutrophillic Th1 inflammatory response with a significant role played by macrophages
15
Q
what is there an increase of in the lungs of patient with COPD?
A
macrophages
increased BAL granulocytes, predominantly neutrophils
16
Q
what does cigarette smoke result in the lungs?
A
direct injury of airway epithelial cells, leads to the release of endogenous intracellular molecules or danger associated molecular patterns
17
Q
what Th1 proinflammatory cytokines are released when cigarette smoke damages the lungs?
A
TNFa
IL-1B
IL-8
interferon (IFN)
TGFB
18
Q
what does macrophages with black particles from smoking cause?
A
continual activation of the inflammatory signalling in the lungs, oxidativ stress also leads to impaired phagocytosis of other pathogens so cant deal with bacterial infections
19
Q
what does release in cytokines result in?
A
recruitment of macrophages, neutrophiles and dendritic cells to the site of inflammation to orchestrate the innate immune response
20
Q
when does oxidative stress occur?
A
when ROS are produced in excess of the antioxidant defence mechanism and result in harmful effects, including damage to lipids, proteins and DNA
21
Q
what are consequences of oxidative stress?
A
increased proliferation of fibroblasts and fibrosis, increased proliferation of mucous secreting cells and smooth muscle cells
22
Q
what is the dysfunction in macrophages in COPD?
A
impaired phagocytosis - reduced ability to clear infection and are much more prone (efferocytosis)
23
Q
what do neutrophiles release in COPD?
A
reactive oxygen species during respiratory burst contributing to oxidative damage of the lugn tissue
24
Q
what is the major consequence of excessive neutrophillic inflammation?
A
increased protease activity from degranulation resulting in enzyme release
25
what do dendritic cells do when foreign substances are inhaled?
signal the entry
links between innate and adaptive systems
26
what does CD8+ T cells release in COPD?
serine proteases, granzyme B which can cause tissue injury and remodelling
27
what does Th2 cytokines mediate in COPD?
promote eosinophil recruitment and activation
mucus hypersecretion
IgE production, which is assoicated with allegic responses
28
what is dysnapis?
disproportionate scalling of the airway dimensions to lung volume or a mismathc of airway tree caliber to lung size
29
what is bronchiatis?
persistant inflammation of the airways, proliferation of mucous glands, loss of cillia which facilitates mucous clearance
30
what is simple mucoid bronchitis?
infection of the main airways, causing them to become irritated and inflammed, temporary
31
what is chronic bronchiatis?
chronic cough and sputum production for at lwast 3 moths per year for two consecutive years, in the absense of other conditions
32
what is the consequences in the small airways and bronchioles in bronchiatis?
goblet cell mataplasia, smooth muscle hypertrophy, fibrosis - increased mucous production and increased expiratory flow resistance
33
what are the clinical manifestations of chronic bronchiatis?
- excessive mucus production
- bronchospasm, dyspneoa and wheezing
- hypoxia or hypercapnia
- productive cough
- increased body weight
34
what is a complication of chronic bronchiatis?
Cor-pulmonale - right sided heart failure
35
what is emphysema?
an abnormal permanent enlargement of air spaces distal to the terminal bronchioles, accomponied by destruction of their walls
36
what does emphysema result in?
- loss of alveolar gas exchange
- remodelling of the small airway compartment and loss of elastic recoil
- reduced oxygen delivery (result in tachponea)
37
what are clinical features of emphysema?
- barrel chest - outward bulging of the chest due to overinflation of the lungs
- dysponea (shortness of breath even at rest)
- fatigue (due to reduced oxygen intake)
- weight loss: increased energy expentiture
38
why are people with COPD more prone to infections?
- excess mucus provides a favourable environment dor bacteria
- impaired mucocillary clearance
- reduced bacteria phagocytosis
- increased incidence of exacerbations
39
what mis the main goals of managment of COPD?
- control symptoms
- preserving lung function
- preventing exacerbations
- reducing mortality
40
what is the effect of smoking of FEV1?
drastic decline, leading to airway limitation to the point of causing disavility and death
41
what is the main symptom that is aimed to treat in COPD?
dysponea due to hyperinflation of lungs during exertion or at rest
42
what airways are limited in COPD?
smaller airways
43
what does air trapping happen in COPD?
mismatch of how much air is breathed in and out
44
what drugs increase FEV1
bronchodilators by altering smooth muscle tone
45
what is the targets of bronchodilators?
- airway smooth muscle cells have high number of B2 adrenoreceptors
- B2 agonist act by binding to these receptors
46
what is the sympathetic affect of smooth muscle in the airway?
no direct sympathetic innervation. passive activation from circulating adrenaline causes smooth muscle relaxation to increase intake of air during fight or flight
47
how does the sympatetic nerves mediation contractions in the lungs?
in response to acetylcholine through activation of muscarinic receptors - inhibtion of this causes dilation
48
what does binding of beta agonist to beta 2 adrenoreceptors activate?
stimulates cAMP which activates protein kinase A, inhibts myosin light kinase chain - preventing the interaction of smooth muscle alpha actin with myosin filaments via cross bridge cycling
49
what are the mechanisms of B2 activation?
- receptors also present n vascular endothelium, cillited cells, circulating inflammatory cells and sub mucosal cells
non bronchodilator effects:
- inhibtion of mast cell release
- reduction of mucus
- enhancement of mucocillary clearance
- reduction of neutrophil recruitment
- inhibition of smooth muscle cell proliferation
50
what is the clinical efficacy of salbutamol in COPD?
- used in acute and chronic COPD
- onset of action is within 3 mins and peak after 2.5 hrs
- duration of action is 4-6 hrs
51
what is the clinical efficacy of LABAs in copd?
- symptomatic despite SABA use
- formeterol effects in 1-3 minutes due to water solubility allowing it to rapidly diffuse into BAR (salmeterols is longer)
- long duration due to lipophillic properties
52
where are M1 receptors expressed?
peribronchial ganglia
53
where are M2 receptors located?
post ganlionic para-sympatetic nerve and act as auto receptors
54
what is optimal inhibition of muscarinic receptors achieved by?
blocking M1 and M3 receptors
55
what is the mechanism of action of Ach binding to M3 receptors?
- activates Gq protein which increases phospholipase C acitivity
- PLC activates hydrolysis og PIP2 which produces IP3 and DAG
- IP3 leads to contraction by increasing the release of Ca2+ from SR
- Release of Ca2+ stimulates muscle contraction
56
what are short acting muscarinic antagonists?
eg. ipratropium
- blocks all muscarinic receptors without sub-type selectivity
- onset of action within minutes, with peak activity within 1-2 hrs
- duration of action of approx 4 hrs
57
what are long acting muscarinic antagonists?
eg. tiotropium
- binds to M1-M3 receptors and 10 times more potent than ipratropium
- dissociates slowly from receptors - longer acting (dissociates fast from M2)
- onset of bronchodilation within 30 minutes with peak activity at 3hrs and lasts over 24hrs
58
what is better in COPD LABAs or LAMAs?
LAMAs - in terms of preventing exacerbations and disease related hospitalisation (LABA still used in some cases)
59
what are methylxantines?
eg. theophylline
- adenosine receptor antagonists - airways bronchodilation by increasing cAMP
60
what is the mechanism of action of theophylline?
inhibiton of PDE4 on inflammatory cells, reduces cytokine and chemokine release
- enhancement of histone deacetylation, decreased inflammatory gene expression
61
what are the cautions with theophylline?
narrow therapeutic window
toxicity: anorexia, abdominal discomfort, anxiety
more severe: arrhythmias and seizures
62
what are phosphodiesterase 4 inhibitors?
- reduce inflammation by inhibiting breaking down cAMP
- roflumislast is a once daily medication with no direct bronchodilator activity
- used in moderate to severe exacerbations in combination with corticosteroid
63
what are adverse effects of PDE-4 inhibitors?
- diarrhoea
- nausea
-reduced appetite
- weight loss
- abdominal pain, sleep disturbance and headache
64
what is the inflmamtion of COPD dominated by?
neutrophillic infiltration with increased numbers of macrophages and CD8 T lymphocytes
65
what is the effect of using iCS in COPD?
neutrophillic infiltration is not as responsive to steorids as seen in asthma so much less effective
66
what is the caution of ICS use in COPD?
increased risk of infection and local side effects
67
what is the effect of combination therapy of ICS + LABA in copd?
- behave synergistically
- repeat binding B2 agonists lead to internalisation which reduces the number of receptors on the surface however ICS increases that exposure
68
how do mucolytic agents work?
eg. carbocisteine
- reduces mucus viscosity by altering glycoproteins composition
- enhances mucocillary clearance
- reduces mucus hypersecretion
- prevents airway obstruction
- free radical scavenging properties can reduce oxidative stress
69
what is the definition of an exacerbation of COPD?
defined by an event characterised by dyspnoea and/or cough and sputum what worsen over <14 days
70
what are COPD excaerbations often associated with?
increased local and systemic inflammation caused by airway infection, pollution or other insults to the lungs
71
what is the management of COPD exacerbations?
- bronchodilators (SABA with or without SAMA for immediate relief)
- antibiotics when patients have clinical signs of bacterial infection eg. increased sputum purulence
- Corticosteroids - shorten recovery time and improve lung function (FEV1)
72
what is not recommend in copd exacerbations?
IV methylxantines due to significant side effects
73
what is the effect of corticosteroids in COPD exacerbation?
- suppress activity of immune cells
- inhibits transcription of peo-inflammatory genes - reduction in chemokines and cytokines
- inhibits phospholipase A2 - decreases prostaglandins and leukotrienes
74
what are coritcoteroids more effective in COPD?
COPD with eosinophilia
75
how long is the treatment of corticosteroids in exacerbation of COPD
< 5 days (longer use associated with increased risk of pneumonia and mortality)
76
what are protease inhibitors useful in?
patients with emphysema caused by alpha 1 anti-trypsin deficiency
77
what are side effects of protease inhibitors?
anaphalaxis and low grade fever (especially in patients with IgA deficinecy)
78
what is an example of biologics in COPD and how do they work?
- dupilumab - blocks shared receptor for IL-4 and IL-13
- fewer exacerbations, better lung function and quality of life
79
when is a cough in COPD worse?
in the morning due to catarrh build up, cillia regenerate at night so in the morning they are able to bring up more sputum
80
is night time wakening is COPD common?
not common
81
what is one pack year smoking?
20 cigarettes a day for one year
82
what happens each time someone with COPD has a severe exacerbation?
loose some lung function you wont get back
83
why do SABAs not have much effect in COPD?
chronic occlusion
84
what FEV1 and FEV1/FVC results in a COPD diagnosis?
Any and <0.7 predicted
85
what does grade 1 on the MRC dysponea scale indicate?
not troubled except on strenuous exercise
86
what is grade 2 of the MRC dyspeonea scale?
short of breath when hurrying on the flat or walking up a slight hill
87
what is grade 3 of the MRC scale?
walks slower that most on the flat, stops after about a mile, or stops after walking 15 minutes at own pace
88
what is grade 4 of the MRC scale?
Stops for breath after walking 100 yards or a few minutes on the level
89
whats grade 5 of the MRC scale?
too breathless to leave the house or when undressing
90
what is the COPD assement tool?
low score<10 indicates better control
91
what vaccincations should be recommended to someone with COPD?
annual flu
covid
pneumococcal
92
what is pulmonary rehab?
an exercise and education programme designed for people with lung disease that experiences breathlessness, it focuses on tailored physical education and information to help better understand their condition
93
what inhaler would you recomment to a patient with one, moderate exacerbation in the last year and daily activity is not limited but history of asthma as a child?
salbutamol
94
when would an ICS be added into COPD treatment?
lots of exacerbations/raised eosinophils but there is a risk of penumonia
95
what shoulds patients carry if on oral corticosteroids?
steroids warning card
96
when is SABA used in COPD?
only in mild copd but all patients will usually have a saba
97
when are LABAs used in COPD?
in combination with ICS or LAMA
98
when are LAMAs used?
FEV1 less than 50%
little effect on lung function but large effect of quality of life
99
what happens if you give too much oxygen to someone with COPD?
O2 becomes the driver to breathing rather than CO2 so if you give too much they might stop breathing as they already have enough O2 in the blood
100
how are mild exacerbations treated in COPD?
SABA
101
how are moderate exacerbations of COPD treated?
SABAs plus A/Bs and/or oral ccs
102
what is the window of preventing a moderate exacerbation becoming a severe exacerbation of COPD?
48hrs
103
what will patients be given to prevent infection causing an exacerbation?
rescue pack of ICS and antibiotics
104
what often happens to viral infections in COPD?
patient almost always picks up bacterial infection after so worth giving antibiotics
105
what % oxygen is given to someone having an exacerbation of COPD?
24-28%
106
what is O2 saturation maintained at in hospital with copd?
88-92%
107
why are nasal canulas not used in COPD?
most people are mouth breathers
108
what is the duration of treatment of prednisolone in exacerbation of COPD?
5-7 days
109
when is tapering of prednisolone required?
if duration > 21 days
110
what are likely pathogens of exacerbations of COPD?
strep pneumonia
haemophillus influenzae
moraxella catarrhalis
111
what is the antibacterial therapy for exacerbation of COPD?
-amoxicillin 500mg every 8hrs
-doxycycine 200mg as a single dose the 100mg each day
-clarithromycin 500mg BD
112
what is the maintainence treatment of COPD after hospital discharge?
LAMA+/- LABA
113
when would a COPD patient be reviewed again after being discharged from hospital?
1-4/52 then again after 12-16/52 post exacerbation
114
what is the criteria of three for infected exacerbation of COPD
one of the three: increased breathlessness, increased purulence, increased volume
115
what is the concern of home oxygen?
dont want patient smoking or anyone else smoking, gas fires, wood burners all increase fire risk
116
what do you do in bronchiectasis to prevent antimicrobial resistance?
Rotate antibiotics
117
what is the problem of nebulising antimicrobials?
can inhale other exipients, can cause irritation, can lead to overgrowth orally, might not get full dose
118
what airways does bronchiectasis, asthma and copd affect
B = smaller airways
C = smaller
A= larger airway
119
what is acidosis and alkalosis?
acidosis - low PH/ raised H+
alkalosis - high pH/ Low H+
120
what is hypercapnia?
raiser blood PaCO2
121
what is hypocapnia?
lowered blood PaCO2
122
what is hypoxia?
low oxygen in tissues/ poorly oxygenated tissues
123
what is hypoxemia?
low blood PaO2
124
how to calculate serum anion gap?
(Na+) + (K+) - ((Cl-) + (HCO3-))
125
what is the reference range for pH of the blood?
7.35-7.45
126
what does values below and above reference range of PaCO2 mean?
below - alkalotic
above - acidic
ref = 4.7-6 kPa
127
what does above and below reference ranges for HCO3- mean
below = acidotic
above= alkalotic
ref range = 22-26mmol/l
128
what is the ref range for anion gap?
10-16
129
what is type 1 resp failure?
where the patient is hypoxemic in the absense of hypercapnia due to reduced efficiency of oxygen transfer form alveoli to blood
130
what is type 2 resp failure?
both hypoxemic and hypercapnic (eg. reduced lung surface area for gaseous exchange as in COPD)
131
what does innapropriate oxygen in type 2 failure cause?
increase of PaO2, reduced respiration and potential CO2 narcosis
132
how do the kisneys compensate in respiratory acidosis?
retaining HCO3-, buffering excess acid
133
what is the mechanism of repiratory acidosis?
damaged alveoli -> reduced gas exchange
CO2 not removed efficiently
CO2+H20 -> carbonic acid -> increases H+ which deceases pH
134
what can hyperventilation lead to?
respiratory alkalosis die to excess CO2 loss, which affects calcium binding
135
what is the affect of incresed calcium binding in respiratory alkalosis?
reduced ionised calcium - causes muscle crampd, tingling, parethsia, tetany
136
what is an examples of metabolic alkalosis?
severe vomiting - loss of gastric acid, dehydration worsens alkalosis by increasing bicarbonate reabsorption
137
at what levels of the MRC scale will someone be eligible for PR?
3-5
138
what would you do if there is no improvement with ICS treatment after 3 months?
stop treatment and go back ro LAMA/LABA
139
what is the percentage of oxygen in air
21%
MP324
flashcards
Decks in class (16)
# Cards
-
Immune system57
-
autoimmune disorders43
-
skin conditions108
-
Asthma116
-
formulation of medicines of respiratory system31
-
COPD139
-
bronchiectasis and interstitial lung disease42
-
Chemistry and ADME30
-
Pulmonary embolism14
-
Pharmacology of coughs44
-
pharmacokinetics of theophylline19
-
Health promotion7
-
Cystic fibrosis39
-
personalised medicine11
-
fungal lung disease27
-
emerging challenges8
