Resp Authors Flashcards
(281 cards)
1
Q
CF
Fletcher and Peto BMJ 1977
A
Asthma = oscillatory FEV1 but slow, normal decline
Severe asthma = very oscillatory + more rapid decline -> resembles COPD
COPD = More rapid decline in FEV1 than severe asthma, but 80-85% (smokers) may not be susceptible
BUT benefit at stopping smoking at ANY time
2
Q
CF
Asthma = oscillatory FEV1 but slow, normal decline
Severe asthma = very oscillatory + more rapid decline -> resembles COPD
COPD = More rapid decline in FEV1 than severe asthma, but 80-85% (smokers) may not be susceptible
BUT benefit at stopping smoking at ANY time
A
Fletcher and Peto BMJ 1977
3
Q
CF
Elborn et al
A
Ivacaftor study
10% FEV1 increase
50% decrease in sweat chloride
Increased time until 1st exacerbation
4
Q
CF Ivacaftor study 10% FEV1 increase 50% decrease in sweat chloride Increased time until 1st exacerbation
A
Elborn et al
5
Q
CF
Ramsey et al
A
Combined Ivacaftor + Lumacaftor
Lumacaftor alone failed initially (for deltaF508 block in processing):
- No Sig dif in AE, LF, patient reported outcomes
COMBINATION - 5% increase in FEV1
6
Q
CF
Combined Ivacaftor + Lumacaftor
Lumacaftor alone failed initially (for deltaF508 block in processing):
- No Sig dif in AE, LF, patient reported outcomes
COMBINATION - 5% increase in FEV1
A
Ramsey et al
7
Q
CF
Kerem et al
A
Atalauren study
Appeared to have no sig effect
BUT when stratified by ABx use (inhaled) there was protection from a drop in FEV1 (only -0.2% change over 48 weeks)
8
Q
CF
Atalauren study
Appeared to have no sig effect
BUT when stratified by ABx use (inhaled) there was protection from a drop in FEV1 (only -0.2% change over 48 weeks)
A
Kerem et al
9
Q
CF
Accurso et al
A
30% CFTR activity associated with symptom reduction
10
Q
CF
30% CFTR activity associated with symptom reduction
A
Accurso et al
11
Q
Cold and Heat
Seidenburg et al
A
Inc bronchoconstriction with hyperventilation of cold air
Increases osmolality of epithelial lining fluid
12
Q
Cold and Heat
Inc bronchoconstriction with hyperventilation of cold air
Increases osmolality of epithelial lining fluid
A
Seidenburg et al
13
Q
Cold and Heat
PHEWE study
A
1 deg decrease in temp
35% increase in daily number natural deaths
72% inc CV, 30% resp, 25% CerebroVD
14
Q
Cold and Heat
1 deg decrease in temp
35% increase in daily number natural deaths
72% inc CV, 30% resp, 25% CerebroVD
A
PHEWE study
15
Q
Cold and Heat
Donaldson et al
A
Winter death increase recorded since 1990s
Severe winters = increased mortality
Mortality increases by age group (ie 85+ sig worse)
- Also spend more time indoors
16
Q
Cold and Heat
Winter death increase recorded since 1990s
Severe winters = increased mortality
Mortality increases by age group (ie 85+ sig worse)
A
Donaldson et al
17
Q
Cold and Heat
Finrisk study
A
Symptoms: Women > Men (hot and cold)
Symptoms: Cold > Hot
18
Q
Cold and Heat
Symptoms: Women > Men (hot and cold)
Symptoms: Cold > Hot
A
Finrisk study
19
Q
Cold and Heat
S.Singh
A
Anxiety and depression significantly higher in winter
20
Q
Cold and Heat
Anxiety and depression significantly higher in winter
A
S.Singh
21
Q
Cold and Heat
Eccles et al
A
Inhalation of cold air cools nasal respiratory lining -> inhibits muco-cilliary + phagocytic activity of leukocytes
22
Q
Cold and Heat
Inhalation of cold air cools nasal respiratory lining -> inhibits muco-cilliary + phagocytic activity of leukocytes
A
Eccles et al
23
Q
Cold and Heat
EUROSTUDY
A
Inc death with 1deg temp decreased GREATER in WARMER countries because: Decreased clothes / poorer insulation
GREATER increase in deaths with 1 deg INCREASE in cooler countries (inc insulation)
Increasing mortality with decreased temp not SEEN in countries that are always cold - eg russia. More clothes/double doors
Mortality = similar all year when heating is included with house
24
Q
Cold and Heat
Schwartzstein et al
A
Cold air on face - easier to breath palliative lung cancer
25
Cold and Heat
| Cold air on face - easier to breath palliative lung cancer
Schwartzstein et al
26
Cold and Heat
| W,R Keatings
Heat related deaths rapid (no delay)
| GREATER increase in deaths with 1 deg INCREASE in cooler countries (inc insulation)
27
Heat related deaths rapid (no delay)
Cold and Heat
GREATER increase in deaths with 1 deg INCREASE in cooler countries (inc insulation)
W,R Keatings
28
Cold and Heat
| Wedzicha
Infection increases MIs and strokes
29
Cold and Heat
| Infection increases MIs and strokes
Wedzicha
30
Immunotherapy
| Calderon et al [Cochrane]
Meta-analysis of SCIT v SLIT
SCIT = greater efficacy but both good
SLIT = safer
31
Immunotherapy
Meta-analysis of SCIT v SLIT
SCIT = greater efficacy but both good
SLIT = safer
Immunotherapy
| Calderon et al [Cochrane]
32
Immunotherapy
| Durham et al
Showed early on the safety of SCIT - <5% withdrawals
| Another study = followed pts up 2 yrs post Rx -> still seeing positive effects
33
Immunotherapy
Showed early on the safety of SCIT - <5% withdrawals
Another study = followed pts up 2 yrs post Rx -> still seeing positive effects
Durham et al
34
Immunotherapy
| Scadding et al - GRASS trial
Discovered that 2 yr Rx is not sufficient
| - Serum IgE went back up alongside SS + peak nasal flow
35
Immunotherapy
Discovered that 2 yr Rx is not sufficient
- Serum IgE went back up alongside SS + peak nasal flow
Scadding et al - GRASS trial
36
Immunotherapy
| Abramson et al
SCIT for asthma -> no improvement in FEV1 but did improve SS
37
Immunotherapy
| SCIT for asthma -> no improvement in FEV1 but did improve SS
Abramson et al
38
Immunotherapy
| Mosbech et al
Another trial of SCIT for asthma, did decrease ICS dose (HDM SCIT) relative mean dose decrease = 42%
39
Immunotherapy
| Another trial of SCIT for asthma, did decrease ICS dose (HDM SCIT) relative mean dose decrease = 42%
Mosbech et al
40
Immunotherapy
| Mitra study
SLIT decreased asthma exacerbation by 34% (SLIT HDM)
41
Immunotherapy
| SLIT decreased asthma exacerbation by 34% (SLIT HDM)
Mitra study
42
Immunotherapy
| GAP trial
Tried to assess prophylactic SLIT in children with A.R who had no signs asthma. Randomised. SLIT had no effect on onset of asthma
Did decrease asthma symptoms, total IgE, Skin pricks, grass pollen-specific IgE
Local SEs tolerated well
43
CF
| Eric alton + UK CF Gene therapy consortium (PILOT)
Wave 1 product involved using liposome with hCEFI (prev used CMV promotor which failed - expression dwindled by day 14). Deleted all CpG promotors in order to reduce immune response + flu like symptoms.
PILOT STUDY = still had flu like symptoms.
Were giving too much. Reduced symtpoms with reduced dose
44
CF
Wave 1 product involved using liposome with hCEFI (prev used CMV promotor which failed - expression dwindled by day 14). Deleted all CpG promotors in order to reduce immune response + flu like symptoms.
PILOT STUDY = still had flu like symptoms.
Were giving too much. Reduced symtpoms with reduced dose
Eric alton + UK CF Gene therapy consortium (PILOT)
45
CF
| Eric alton + UK CF Gene therapy consortium (WAVE 1 MULTICENTRE TRIAL)
Double blind placebo
50-90% FEV1, 12+ age
```
Results:
NO AE
Saved ~4% dec in FEV1
Treatment effect doubled for FEV1 50-70%
NO effect for milder patients 70-90%
Possibly due to impaction in larger airways
```
46
CF
Double blind placebo
50-90% FEV1, 12+ age
```
Results:
NO AE
Saved ~4% dec in FEV1
Treatment effect doubled for FEV1 50-70%
NO effect for milder patients 70-90%
Possibly due to impaction in larger airways
```
Eric alton + UK CF Gene therapy consortium (WAVE 1 MULTICENTRE TRIAL)
47
CF
| Eric alton + UK CF Gene therapy consortium (WAVE 2)
Combined Sendai (F/HN) (infects all epithelial cells)
Lentivirus (able to integrate DNA into genome)
Appeared to have longer term effects - persisted for 2 yrs. Could be repeatedly administered. Less inflammatory response than prev lipsome
No evidence of tumour formation.
Currently in phase 1
48
CF
Combined Sendai (F/HN) (infects all epithelial cells)
Lentivirus (able to integrate DNA into genome)
Appeared to have longer term effects - persisted for 2 yrs. Could be repeatedly administered. Less inflammatory response than prev lipsome
No evidence of tumour formation.
Currently in phase 1
Eric alton + UK CF Gene therapy consortium (WAVE 2)
49
COPD NEW TREATMENTS
| Kornmann et al
Indacetrol>salmeterol
Increased SS + trough FEV1
170vs60ml
50
COPD NEW TREATMENTS
Indacetrol>salmeterol
Increased SS + trough FEV1
170vs60ml
Kornmann et al
51
COPD NEW TREATMENTS
GLOW 2 Trial
P.Barnes
Discovered glycopyronium works on M3 receptors in lungs (competitive antagonist)
52
COPD NEW TREATMENTS
| Discovered glycopyronium works on M3 receptors in lungs (competitive antagonist)
GLOW 2 Trial
| P.Barnes
53
COPD NEW TREATMENTS
| Van Noord
Showed indacaterol 300micGs = 600 in terms of FEV1 improvement
BUT against everyones belief adding glycopyronium combination FEV1 improvement was DOUBLED
54
COPD NEW TREATMENTS
Showed indacaterol 300micGs = 600 in terms of FEV1 improvement
BUT against everyones belief adding glycopyronium combination FEV1 improvement was DOUBLED
Van Noord
55
COPD NEW TREATMENTS
| Singh D
ICS/LABA/LAMA triple superior to ICS/LABA in sig dif between exacerbations
BUT the difference was modest, they had a large N number
Likely that LABA/LAMA equally effective
56
COPD NEW TREATMENTS
ICS/LABA/LAMA triple superior to ICS/LABA in sig dif between exacerbations
BUT the difference was modest, they had a large N number
Likely that LABA/LAMA equally effective
Singh D
57
COPD NEW TREATMENTS
FLAME STUDY
Wedzicha
LABA/LAMA vs ICA/LABA
LABA/LAMA = 17% reduction
inda/glyco vs FP/SALM
58
COPD NEW TREATMENTS
LABA/LAMA vs ICA/LABA
LABA/LAMA = 17% reduction
inda/glyco vs FP/SALM
FLAME STUDY
| Wedzicha
59
COPD NEW TREATMENTS
| Pascoe et al
Retrospective analysis of LABA vs ICS/LABA
EOSINOPHILLIC COPD does benefit
42% decrease in exacerbations with EOS >6%
32% decrease in exacerbations with EOS >4%
Low Eos = no benefit
60
COPD NEW TREATMENTS
Retrospective analysis of LABA vs ICS/LABA
EOSINOPHILLIC COPD does benefit
42% decrease in exacerbations with EOS >6%
32% decrease in exacerbations with EOS >4%
Low Eos = no benefit
Pascoe et al
61
COPD NEW TREATMENTS
| Magnussen et al
```
CXCR2 antagonist Navarixin
Dec Sputum neutrophils
Increased FEV1
Decreased MMP9 and exacerbations
BUT ANC too low. Below 22% on average. Some = very profound.
```
62
COPD NEW TREATMENTS
Retrospective analysis of LABA vs ICS/LABA
EOSINOPHILLIC COPD does benefit
42% decrease in exacerbations with EOS >6%
32% decrease in exacerbations with EOS >4%
Low Eos = no benefit
Magnussen et al
63
COPD NEW TREATMENTS
Russel et al
Churg et al
Increased MMP9 in COPD
Tried recombinant TIMP1 inhibitor Marmistat
Very expensive
Too many SEs
64
```
COPD NEW TREATMENTS
Increased MMP9 in COPD
Tried recombinant TIMP1 inhibitor Marmistat
Very expensive
Too many SEs
```
Russel et al
| Churg et al
65
COPD NEW TREATMENTS
| Calverley et al
PDE4 Inhibitor
In animal models it was shown to decrease emphysema, fibrosis, MUC expression
Romiflast worked ONLY in severe disease with frequent exacerbations and CMH
BUT only 50ml change in FEV1 - barely noticeable - only significant because of high N number >3000
Had no effect on QOL + symptoms
HUGE amount of SEs: Nausea/Headaches/Diarrhoea
Discovered PDE4(d)=nausea, PDE4(b) anti-inflammatory.
4B selective version STILL too many SEs
66
COPD NEW TREATMENTS
PDE4 Inhibitor
In animal models it was shown to decrease emphysema, fibrosis, MUC expression
Romiflast worked ONLY in severe disease with frequent exacerbations and CMH
BUT only 50ml change in FEV1 - barely noticeable - only significant because of high N number >3000
Had no effect on QOL + symptoms
HUGE amount of SEs: Nausea/Headaches/Diarrhoea
Discovered PDE4(d)=nausea, PDE4(b) anti-inflammatory.
4B selective version STILL too many SEs
Calverley et al
67
COPD NEW TREATMENTS
| Barnes et al (PDE4)
PDE4 inhaled form had no efficacy
| Increased SEs stangely -> sudden onset nausea
68
COPD NEW TREATMENTS
| TORCH study
Seretide has no effect on mortality
69
COPD NEW TREATMENTS
| Seretide has no effect on mortality
TORCH study
70
COPD NEW TREATMENTS
PDE4 inhaled form had no efficacy
Increased SEs stangely -> sudden onset nausea
Barnes et al (PDE4)
71
COPD NEW TREATMENTS
| Lomas et al
Losmapimod = p38 MAPK inhibitor
No effect on neutrophillia / FEV1, IL6/8 MMP9
Freq SEs: skin rashes, loss of efficacy over time
72
COPD NEW TREATMENTS
Losmapimod = p38 MAPK inhibitor
No effect on neutrophillia / FEV1, IL6/8 MMP9
Freq SEs: skin rashes, loss of efficacy over time
Lomas et al
73
COPD NEW TREATMENTS
| Large chinese study
Showed rate of FEV1 decline is slower with T.Bromide Rx
74
Showed rate of FEV1 decline is slower with T.Bromide COPD NEW TREATMENTS
Rx
Large chinese study
75
ASTHMA NEW TREATMENTS
| Cochrane Omalizumab
```
Systematic review concluded omalizumab s/c 2-4 weeks:
Halved asthma emergency visits
Decreased ICS dose
No effect on FEV1
Licenced for severe persistence
S/C > IV, Inhaled doesn't work
```
76
```
ASTHMA NEW TREATMENTS
Systematic review concluded omalizumab s/c 2-4 weeks:
Halved asthma emergency visits
Decreased ICS dose
No effect on FEV1
Licenced for severe persistence
S/C > IV, Inhaled doesn't work
```
Cochrane Omalizumab
77
ASTHMA NEW TREATMENTS
| Leckie et al
Anti IL-5 Meopilzumab
No effect LAR
Did remove blood eosinophillia+ 50% mucosal
78
ASTHMA NEW TREATMENTS
Anti IL-5 Meopilzumab
No effect LAR
Did remove blood eosinophillia+ 50% mucosal
Leckie et al
79
ASTHMA NEW TREATMENTS
| Dream study, Ian Pavord (other studies also confirmed = SIRIUS + MENSA)
Dec exacerbations by 50%
Dec AQLQ
Dec oral ICS 50%
80
ASTHMA NEW TREATMENTS
Dec exacerbations by 50%
Dec AQLQ
Dec oral ICS 50%
Dream study, Ian Pavord (other studies also confirmed = SIRIUS + MENSA)
81
ASTHMA NEW TREATMENTS
| Anti IL5R Benralizumab
Benralizumab undergoing phase 3 currently. Thought to be able to lyse eosinophils in tissue too
82
ASTHMA NEW TREATMENTS
| Benralizumab undergoing phase 3 currently. Thought to be able to lyse eosinophils in tissue too
Anti IL5R Benralizumab
83
ASTHMA NEW TREATMENTS
| Corren et al (mAB)
Ant IL-13 Lebrizikumab
No FEV improvement even when selecting by periostin (a marker of IL13 release)
IL13 thought to be good target: [Main stimulator of IgE, mast cell/fibrobast/macrophage recruitment]
84
ASTHMA NEW TREATMENTS
Ant IL-13 Lebrizikumab
No FEV improvement even when selecting by periostin (a marker of IL13 release)
IL13 thought to be good target: [Main stimulator of IgE, mast cell/fibrobast/macrophage recruitment]
Corren et al (mAB)
85
ASTHMA NEW TREATMENTS
| Wenzel et al
```
Dupilimab
87% reduction in exacerbations
Increased FEV1 marginally
Withdrew Rx in trial
Do not need to select by blood eosinophils!!
```
86
```
ASTHMA NEW TREATMENTS
Dupilimab
87% reduction in exacerbations
Increased FEV1 marginally
Withdrew Rx in trial
Do not need to select by blood eosinophils!!
```
Wenzel et al
87
ASTHMA NEW TREATMENTS
| Gavreaus et al//Corren et al
```
Anti TSLP Tezepelumab
70% reduction in exacerbations
Increase in FEV1
Decrease in FeNO, Blood eosinophils
No need select by eosinophils though
```
88
```
ASTHMA NEW TREATMENTS
Anti TSLP Tezepelumab
70% reduction in exacerbations
Increase in FEV1
Decrease in FeNO, Blood eosinophils
No need select by eosinophils though
```
Gavreaus et al//Corren et al
89
ASTHMA NEW TREATMENTS
| Krug et al
GATA3 DNAzyme not really as good as ICS
90
ASTHMA NEW TREATMENTS
| GATA3 DNAzyme not really as good as ICS
Krug et al `
91
ASTHMA NEW TREATMENTS
| Brusselle et al
Macrolides
| Tried azithromycin - decreased exacerbations by 42% in BLOOD EOSINOPHILLIA ONLY
92
ASTHMA NEW TREATMENTS
Macrolides
Tried azithromycin - decreased exacerbations by 42% in BLOOD EOSINOPHILLIA ONLY
Brusselle et al
93
ASTHMA NEW TREATMENTS
Bousquet
Mercado
Tried Roflumilast
Too severe SEs - N/V/Diarrhoea
10% FEV1 increase though
Tired p38 MAPK inhibitor - only worked in steroid resistant with LOW FEV1.
Too Many SEs
94
ASTHMA NEW TREATMENTS
Tried Roflumilast
Too severe SEs - N/V/Diarrhoea
10% FEV1 increase though
Tired p38 MAPK inhibitor - only worked in steroid resistant with LOW FEV1.
Too Many SEs
Bousquet
| Mercado
95
Non-Invasive Markers
| Kharitonov et al
Found FeNO rised in the LAR sig, also if not adhering to ICS
96
Non-Invasive Markers
| Found FeNO rised in the LAR sig, also if not adhering to ICS
Kharitonov et al
97
Non-Invasive Markers
| Jakatonian et al
Depicted that this correlates with the extent on inflammation
98
Non-Invasive Markers
| Depicted that this correlates with the extent on inflammation
Jakatonian et al
99
Non-Invasive Markers
| Green RH et al
Monitored patients using sputum eosinophils and changed ICS dose accordingly. Recorded 2/3rs less exacerbations.
100
Non-Invasive Markers
| Monitored patients using sputum eosinophils and changed ICS dose accordingly. Recorded 2/3rs less exacerbations.
Green RH et al
101
Non-Invasive Markers
| Paredi et al
Discovered method of measuring bronchial blood flow using c2h2 which is inert and soluble.
Found bronchial blood flow is higher in asthmatics and correlates with FeNO
102
Non-Invasive Markers
Discovered method of measuring bronchial blood flow using c2h2 which is inert and soluble.
Found bronchial blood flow is higher in asthmatics and correlates with FeNO
Paredi et al
103
Invasive Markers
| Donaldson Chest 2005
IL-6 correlates with FEV1 decline in COPD
104
Invasive Markers
| IL-6 correlates with FEV1 decline in COPD
Donaldson Chest 2005
105
Invasive Markers
| Macedo et al 2009
Asthmatics have increased SM [hypertrophy]
106
Invasive Markers
| Asthmatics have increased SM [hypertrophy]
Macedo et al 2009
107
GC MoA
| Farshou et al
FP 250:100 changes cell counts by:
Mast cells 29:80
Eosinophils 53:93
T cells 51:87
108
```
GC MoA
FP 250:100 changes cell counts by:
Mast cells 29:80
Eosinophils 53:93
T cells 51:87
```
Farshou et al
109
GC MoA
| Markwick et al
Oxidative stress induces steroid insensitivity in macrophages
110
GC MoA
| Oxidative stress induces steroid insensitivity in macrophages
Markwick et al
111
GC MoA
| Chalmers et al
Cigarette smoking decreases asthmatic response to FP
112
GC MoA
| Cigarette smoking decreases asthmatic response to FP
Chalmers et al
113
GC MoA
| Usmani et al (2)
Decreased GR expression in asthma ASM
| Decreased GR translocation in COPD
114
GC MoA
Decreased GR expression in asthma ASM
Decreased GR translocation in COPD
Usmani et al
115
GC MoA
| Hakim 2012
Oxidative stress reduces GR nuclear translocation, affecting proteins importin 7 / RAN
116
GC MoA
| Oxidative stress reduces GR nuclear translocation, affecting proteins importin 7 / RAN
Hakim 2012
117
GC MoA
| Ito et al 2005
HDAC2 expression is decreased with increasing severity in COPD.
118
GC MoA
| HDAC2 expression is decreased with increasing severity in COPD.
Ito et al 2005
119
GC MoA
| Su et al [hdac] 2009
HDAC2 activity is decreased in asthmatic children
120
GC MoA
| HDAC2 activity is decreased in asthmatic children
Su et al [hdac] 2009
121
COUGH
| Irwin et al
75% of GORD pts silent
5% GORD associated with cough
PPI Trial recommended
122
COUGH
75% of GORD pts silent
5% GORD associated with cough
PPI Trial recommended
Irwin et al
123
COUGH
Sundar et al
Birring et al
44% cough patients have OSA
| CPAP sig reduces cough
124
COUGH
44% cough patients have OSA
CPAP sig reduces cough
Sundar et al
| Birring et al
125
```
COUGH
Groneburg et al
Birring et al
O'Connel et al
Niimi et al
```
Increased TRPV1 with chronic cough
Increased histamine / LTs / PGE2 with chronic cough
Increased density of nerves
Goblet cell hyperplasia
126
```
COUGH
Increased TRPV1 with chronic cough
Increased histamine / LTs / PGE2 with chronic cough
Increased density of nerves
Goblet cell hyperplasia
```
Groneburg et al
Birring et al
O'Connel et al
Niimi et al
127
COUGH
| Morice et al
Low dose morphine good at reducing cough
128
COUGH
| Low dose morphine good at reducing cough
Morice et al
129
COUGH
| Usmani et al
Theobrominde RCT vs placebo and codeine
Did inhibit capsaicin induced cough (to induce 5 coughs)
No AEs
130
COUGH
Theobrominde RCT vs placebo and codeine
Did inhibit capsaicin induced cough (to induce 5 coughs)
No AEs
Usmani et al
131
COUGH
| Mintz et al
Found gabapentin reduces cough
132
COUGH
| Found gabapentin reduces cough
Mintz et al
133
COUGH
| Banner et al
Steam inhalation with Vick Vaporub does reduce cough incidence
134
COUGH
| Steam inhalation with Vick Vaporub does reduce cough incidence
Banner et al
135
SLEEP
| Stradling et al
PCO2 rises during sleep
| DEC ventilation, minute ventilation, TV
136
SLEEP
PCO2 rises during sleep
DEC ventilation, minute ventilation, TV
Stradling et al
137
SLEEP
| Skatrud et al
Threshold pCO2 >40.9kpa
- dec sensitivity
- removal of voluntary breathing
138
SLEEP
Threshold pCO2 >40.9kpa
- dec sensitivity
- removal of voluntary breathing
Skatrud et al
139
SLEEP
| Thomson + Morrel et al
Removed CO2 whilst patient slept on ventilator
Pt stopped breathing
CO2 Rose -> pt woke up
140
SLEEP
Removed CO2 whilst patient slept on ventilator
Pt stopped breathing
CO2 Rose -> pt woke up
Thomson + Morrel et al
141
```
GC MoA
GC+Bagonists:
Greening
Nelson
Adcock (2)
FACET
FULFIL
```
```
Increase LF in comparison to placebo
Increase GR nuclear translocation
Depositied together
AD - GCS: Dec B adrenoceptor desensitsation, Increase B adrenoceptor expression
FACET = decrease exacerbations
FULFIL = Triple>Double (buuuuuut)
```
142
```
GC MoA
Increase LF in comparison to placebo
Increase GR nuclear translocation
Depositied together
AD - GCS: Dec B adrenoceptor desensitsation, Increase B adrenoceptor expression
FACET = decrease exacerbations
FULFIL = Triple>Double (buuuuuut)
```
```
GC MoA
GC+Bagonists:
Greening
Nelson
Adcock (2)
FACET
FULFIL
```
143
Delivery Devices
Self
Benet
Newman
Rapid onset
Smaller dose
Fewer SEs
144
Delivery Devices
| Morgan et al
pMDIs with spacer as effective as nebuliser in PTs with acute asthma attack
145
Delivery Devices
| pMDIs with spacer as effective as nebuliser in PTs with acute asthma attack
Morgan et al
146
Delivery Devices
Biddiscome et al 1993
Usmani and Biddiscome 2005
Only 10-20% reaches lung MDIs
| >6 oro, 2-6 conducting airways, <2 alveolar
147
Delivery Devices
Only 10-20% reaches lung MDIs
>6 oro, 2-6 conducting airways, <2 alveolar
Biddiscome et al 1993
| Usmani and Biddiscome 2005
148
MITOCHONDRIA
| Hoffman
COPD mitochondria SWOLLEN, cristae depletion, all fused
149
MITOCHONDRIA
| COPD mitochondria SWOLLEN, cristae depletion, all fused
Hoffman
150
MITOCHONDRIA
| Weigman and Michaeloudes (2)
Dec membrane potential, Dec O2 consumption (thus resp), Dec ATP production
Made Ozone mouse - dec membrane potential, increased ROS, increased BAL cells
151
MITOCHONDRIA
Dec membrane potential, Dec O2 consumption (thus resp), Dec ATP production
Made Ozone mouse - dec membrane potential, increased ROS, increased BAL cells
Weigman and Michaeloudes
152
MACROPHAGES
Guillams et al
Hashimoto et al
Alveolar macrophage colonisation in the first few days of birth is dependent on fetal monocytes.
Proliferate in situ
153
MACROPHAGES
Alveolar macrophage colonisation in the first few days of birth is dependent on fetal monocytes.
Proliferate in situ
Guillams et al
| Hashimoto et al
154
MACROPHAGES
| Lavin et al
The lung microenvironment reprogrammes differentiated tissue resident macrophages -> alveolar
155
MACROPHAGES
| The lung microenvironment reprogrammes differentiated tissue resident macrophages -> alveolar
Lavin et al
156
CYTOKINES
| Rennard et al
Navarixin failed
- ANC too low
Did increase FEV1 by 68ml in COPD, 168 in smokers
157
CYTOKINES
Navarixin failed
- ANC too low
Did increase FEV1 by 68ml in COPD, 168 in smokers
Rennard et al
158
CYTOKINES
| Stockley et al
COPD receptor recycling is:
More frequent
Cells move faster + with less direction
159
CYTOKINES
COPD receptor recycling is:
More frequent
Cells move faster + with less direction
Stockley et al
160
INNATE
| Edwards et al (2)
Dec T1 IFN production in asthmatics
Dec Irak4 TLR signalling in asthmatics
IE fail to make T1IFNs in response to TLR signalling
161
INNATE
Dec T1 IFN production in asthmatics
Dec Irak4 TLR signalling in asthmatics
IE fail to make T1IFNs in response to TLR signalling
Edwards et al (2)
162
CMH
| Elbina et al
Controlled long term trials show hypertonic saline IS safe, effective and cheap.
163
CMH
| Controlled long term trials show hypertonic saline IS safe, effective and cheap.
Elbina et al
164
CMH
| Jay A Nadel
Discoverred EGFR intimately involved in sythesis and hyperplasia
Showed EGFR upregulated in asthma/COPD/Smokers
165
PROTEASES
| Donlen et al
MMP 3+9 increased in asthma
166
CMH
Discoverred EGFR intimately involved in sythesis and hyperplasia
Showed EGFR upregulated in asthma/COPD/Smokers
CMH
| Jay A Nadel
167
PROTEASES
| MMP 3+9 increased in asthma
Donlen et al
168
PROTEASES
| Bergin et al
MMP 9 increased in CF
169
PROTEASES
| MMP 9 increased in CF
Bergin et al
170
PROTEASES
| Segura et al
MMP1,2,8,9 elevated in COPD
171
PROTEASES
| Senlor and Antholsen
MME-ve mice had reduced MLI after 6 months CSE
172
PROTEASES
| MME-ve mice had reduced MLI after 6 months CSE
Senlor and Antholsen
173
PROTEASES
| MMP1,2,8,9 elevated in COPD
Segura et al
174
PROTEASES
| Shapiro et al
NE -ve mice dec MLI than +ve
175
PROTEASES
| NE -ve mice dec MLI than +ve
Shapiro et al
176
EICOSANOIDS
| Wenzel et al
Cyst LTs + TXA2 increased sig in asthma
177
EICOSANOIDS
| Cyst LTs + TXA2 increased sig in asthma
Wenzel et al
178
EICOSANOIDS
| Agarwall et al
Increased CystLTs in asthma sputum [NOT SEVERE]
179
EICOSANOIDS
| Increased CystLTs in asthma sputum [NOT SEVERE]
Agarwall et al
180
Delivery Devices
Rapid onset
Lower dose
Reduced SEs
Delivery Devices
Self
Benet
Newman
181
EICOSANOIDS
Seymour
Weller
Wenzel
Inc LTB4 in COPD, asthma
LTB4 Causes proliferation of ASM
Increased in BAL blood urine and sputum of asthmatics
182
EICOSANOIDS
Nayak/Laviolette et al
Lima et al
CystLTR antagonists can protect against degree of LF decline in severe asthmatics
Some polymorphisms respond better
183
EICOSANOIDS
Gavreau et al
Walters
Maher et al
Inhaled PGE2 prevents allergen induced decrease in FEV1, also decreases Eosinophils
BUT causes cough via EP3 receptor (EP1-4)
EP4 receptor bronchoprotective + anti-inflammatory
184
EICOSANOIDS
Inc LTB4 in COPD, asthma
LTB4 Causes proliferation of ASM
Increased in BAL blood urine and sputum of asthmatics
EICOSANOIDS
Seymour
Weller
Wenzel
185
EICOSANOIDS
CystLTR antagonists can protect against degree of LF decline in severe asthmatics
Some polymorphisms respond better
EICOSANOIDS
Nayak/Laviolette et al
Lima et al
186
EICOSANOIDS
Inhaled PGE2 prevents allergen induced decrease in FEV1, also decreases Eosinophils
BUT causes cough via EP3 receptor (EP1-4)
EP4 receptor bronchoprotective + anti-inflammatory
EICOSANOIDS
Gavreau et al
Walters
Maher et al
187
PCD
| Narang et al
FeNO very low in PCD
188
PCD
| FeNO very low in PCD
Narang et al
189
LUNG CANCER
| Churg et al
Compared SABR vs surgery for stage 1
SABR = HR 0.14 = 86% mortality Risk Reduction
- Had to pool data from 2 studies due to failure to accrue
190
LUNG CANCER
Compared SABR vs surgery for stage 1
SABR = HR 0.14 = 86% mortality Risk Reduction
- Had to pool data from 2 studies due to failure to accrue
Churg et al
191
LUNG CANCER
| Lim et al
ctDNA evenly distributed
| Reduced sample heterogeneity
192
LUNG CANCER
ctDNA evenly distributed
Reduced sample heterogeneity
Lim et al
193
ARDS
| ARDSNetwork Trial
Discovered 12ml/kg sig higher mortality that 6ml/kg TV
~9% difference
Idea of the baby lung
194
ARDS
Discovered 12ml/kg sig higher mortality that 6ml/kg TV
~9% difference
Idea of the baby lung
ARDSNetwork Trial
195
Inhaled Pollutants
| 1952 smog
Days black smoke and sulphur rose - increased deaths seen.
Also increased deaths for following 2 months. Old / neonates
Bronchitis
196
Inhaled Pollutants
50% more hospital admissions, 160% more respiratory admissions.
Days black smoke and sulphur rose - increased deaths seen.
Also increased deaths for following 2 months. Old / neonates
Bronchitis
1952 smog
197
Inhaled Pollutants
| 1956 clean air act
People given money to board up fire places
| Only allowed to use high grade coal
198
Inhaled Pollutants
People given money to board up fire places
Only allowed to use high grade coal
1956 clean air act
199
Inhaled Pollutants
| Dockery 1993
6 cities with differing amounts of fine particles
Showed a dose response (mortality+fine particles)
Also showed that there is increased mortality with prolonged low level exposure
Was corrected for smoking
200
Inhaled Pollutants
6 cities with differing amounts of fine particles
Showed a dose response (mortality+fine particles)
Also showed that there is increased mortality with prolonged low level exposure
Was corrected for smoking
Dockery 1993
201
Inhaled Pollutants
| Pope 1995
Repeated the 6-city America study with 151 metropolitan US cities
Adjusted mortality rate still showed a linear correlation with fine particles
202
Inhaled Pollutants
Repeated the 6-city America study with 151 metropolitan US cities
Adjusted mortality rate still showed a linear correlation with fine particles
Pope 1995
203
Inhaled Pollutants
| Lim et al
Adding ambient particulate exposure and indoor pollution exposure makes pollution the greatest contributor to disability adjusted life years
204
Inhaled Pollutants
Adding ambient particulate exposure and indoor pollution exposure makes pollution the greatest contributor to disability adjusted life years
Lim et al
205
Inhaled Pollutants
| Cames and Helmers
Described the trends of diesel vehicles being bought and produced in Japan, America, EU
EU = significantly rose to meet required kyoto accord
- Also made no sense as diesel produced in russia/us whereas we could produce our own gas
206
Inhaled Pollutants
Described the trends of diesel vehicles being bought and produced in Japan, America, EU
EU = significantly rose to meet required kyoto accord
- Also made no sense as diesel produced in russia/us whereas we could produce our own gas
Cames and Helmers
207
Inhaled Pollutants
| IARC 2012
Diesel Type 1 carcinogen
208
Inhaled Pollutants
| Diesel Type 1 carcinogen
IARC 2012
209
Inhaled Pollutants
| IARC 2013
Air pollution = type 1 carcinogen
210
Inhaled Pollutants
| Air pollution = type 1 carcinogen
IARC 2013
211
Inhaled Pollutants
| Mudway et al
Recreated exposures of diesel engine
Individual consented to breathing it in.
Spent time exercising on bike to recreate "stop/start"
Had to be done in sweden to obtain a HEALTHY control ie no NO2 bus exposure.
RESULTS
Increased NFkB activation
Decreased NRF-2 (ant-inflammatory)
Increased IL8/GROa
Increased unburnt carbons, increased NE, increased neutrophils!
NO CHANGE IN SYMPTOMS
212
Inhaled Pollutants
Recreated exposures of diesel engine
Individual consented to breathing it in.
Spent time exercising on bike to recreate "stop/start"
Had to be done in sweden to obtain a HEALTHY control ie no NO2 bus exposure.
RESULTS
Increased NFkB activation
Decreased NRF-2 (ant-inflammatory)
Increased IL8/GROa
Increased unburnt carbons, increased NE, increased neutrophils!
NO CHANGE IN SYMPTOMS
Mudway et al
213
Inhaled Pollutants
Behndig et al
Carleston C et al
Chung et al
AGAINST EVERYONES BELIEF:
Repeated the Bus engine exposure chamber - saw no significant changes in neutrophils, MPO, IL6/8, or eosinophils
Espose Exposed Pts to diesel THEN allergen or saline
Diesel and allergen caused HUGE increase in NE, IL8, TH2 etc etc.
Somehow sensitises to allergen
Walked asthmatics down Ox st vs Hyde Park
Dec FEV1 in ox group sustained for 22hrs
214
Inhaled Pollutants
| Gauderman et al
Children who grow up near main road have nearly 100ml less FEV1 that cannot be regained
215
Inhaled Pollutants
| Children who grow up near main road have nearly 100ml less FEV1 that cannot be regained
Gauderman et al
216
IPF
| Maher et al (IPF)
Acute IPF exacerbation associated with up to 50% increase in mortality in 2 weeks
217
IPF
| Acute IPF exacerbation associated with up to 50% increase in mortality in 2 weeks
Maher et al (IPF)
218
Cellular Therapy
| Yamanaka et al
Discovered a method of generating iPSCs-MSCs
Somatic cell -> reprogrammed to iPSC -> Differentiated to MSC
Reprogramming genes:
Sox2, Oct4, Nanog Lin28
Diffferentiating genes:
bFGF PDGF EGF
219
Cellular Therapy
Discovered a method of generating iPSCs-MSCs
Somatic cell -> reprogrammed to iPSC -> Differentiated to MSC
Reprogramming genes:
Sox2, Oct4, Nanog Lin28
Diffferentiating genes:
bFGF PDGF EGF
Yamanaka et al
220
```
Cellular Therapy
Brazilian Phase 1
Osiris
Netherlands
EBV insertion
```
4 patients GOLD IV - safe but no clinical improvement
62 patients GOLDII/III, dec crp, no FEV1 improvements or AEs
Trialled before LVRS - dec fibrosis seen, 7 patients, NO AE, GOLD IV
Phase 1 prior to EBV insertion
No AEs, Dec CRP
221
Cellular Therapy
4 patients GOLD IV - safe but no clinical improvement
62 patients GOLDII/III, dec crp, no FEV1 improvements or AEs
Trialled before LVRS - dec fibrosis seen, 7 patients, NO AE, GOLD IV
Phase 1 prior to EBV insertion
No AEs, Dec CRP
Brazilian Phase 1
Osiris
Netherlands
EBV insertion
222
Cellular Therapy
| Weigman and Michaeloudes
Dec membrane potential in mouse ozone model
Increased ROS seen
When given mitoQ antioxidant the effects are reversed (ROS)
223
Cellular Therapy
Dec membrane potential in mouse ozone model
Increased ROS seen
When given mitoQ antioxidant the effects are reversed (ROS)
Weigman and Michaeloudes
224
Cellular Therapy
| P Bhavsar
CSE exposure to ASMCs - randomised iPSC-MSCs
Increased ROS and Decreased Membrane Potential in the CONTROL
Administration of MSCs reduced ROS and improved membrane potential. Also alleviated apoptosis AHR and BAL cell count.
Subsequently did staining for collagen and actin -> successfully documented TNTs for the first time
225
Cellular Therapy
CSE exposure to ASMCs - randomised iPSC-MSCs
Increased ROS and Decreased Membrane Potential in the CONTROL
Administration of MSCs reduced ROS and improved membrane potential. Also alleviated apoptosis AHR and BAL cell count.
Subsequently did staining for collagen and actin -> successfully documented TNTs for the first time
P Bhavsar
226
AIT
| M Snobar
Lolium Perenne purified peptides (as opposed to whole protein)
Phase 2a = open prospective dose study
8 visits over 2 weeks with incremental dose increases (n=65) Increased IgG4, IgE
Dec IgE:IgG4 ratio, IgEFAB CPT score
Conjunctival provocation testing
Went on to Placebo controlled trial
Same results
SHORTER RX time - 3 visits over 4 weeks - could be Rx prior to pollen season each year - cheaper too
227
AIT
Lolium Perenne purified peptides (as opposed to whole protein)
Phase 2a = open prospective dose study
8 visits over 2 weeks with incremental dose increases (n=65) Increased IgG4, IgE
Dec IgE:IgG4 ratio, IgEFAB CPT score
Conjunctival provocation testing
Went on to Placebo controlled trial
Same results
SHORTER RX time - 3 visits over 4 weeks - could be Rx prior to pollen season each year - cheaper too
M Snobar
228
Strategies of AIT Rx
| LEAP study - Du Toit
Randomised peanut eating before the age of 5
2 groups = eczema and early allergy(positive skin prick)
and control. BOTH were protective
229
Strategies of AIT Rx
Randomised peanut eating before the age of 5
2 groups = eczema and early allergy(positive skin prick)
and control. BOTH were protective
LEAP study - Du Toit
230
Strategies of AIT Rx
Morgan et al
Sheik et al
Randomised total allergen control (mattress toppers/vacuum filters etc...
Did have decreased wheezy days (34), improved symptoms scores, reduced asthma consultations
$1k per child - sig cheaper than anti-IgE
Systematic review by sheik showed mono-intervention did not work (for HDM)
231
Strategies of AIT Rx
Randomised total allergen control (mattress toppers/vacuum filters etc...
Did have decreased wheezy days (34), improved symptoms scores, reduced asthma consultations
$1k per child - sig cheaper than anti-IgE
Systematic review by sheik showed mono-intervention did not work (for HDM)
Morgan et al
Sheik et al
232
Strategies of AIT Rx
Davidson et al
storms
Increased asthma exacerbations in thunderstorm - increases grass pollen.
Even young atopic non-asthmatics had asthma like exacerbations
233
Strategies of AIT Rx
Increased asthma exacerbations in thunderstorm - increases grass pollen.
Even young atopic non-asthmatics had asthma like exacerbations
Davidson et al
234
Strategies of AIT Rx
Walker et al
grades
Increased chance of dropping a grade at GCSE with hayfever
235
Strategies of AIT Rx
| Increased chance of dropping a grade at GCSE with hayfever
Walker et al
| grades
236
Strategies of AIT Rx
| Corren et al AR
80% of asthmatics have AR
| Study depicted that exacerbation risk/hospitalisation was lower if asthmatics also Rx for AR
237
Asthma exacerbations
| Seb Johnston et al (2)
Showed drops in PEF with RV infection / viral
Increased asthma symptoms
Compared 74 asthmatics yo non atopic partners
Had same FREQ infections, but increased SS in and dec PEF in asthmatics
238
Asthma exacerbations
Showed drops in PEF with RV infection / viral
Increased asthma symptoms
Compared 74 asthmatics yo non atopic partners
Had same FREQ infections, but increased SS in and dec PEF in asthmatics
Asthma exacerbations
| Seb Johnston et al
239
Asthma exacerbations
| NW Johnston september
Increased AEs in 1st 3 weeks september - correlated to going to school
Viruses detected in 62% hospitalised
Hospitalised less likely to use inhalers
240
Asthma exacerbations
Increased AEs in 1st 3 weeks september - correlated to going to school
Viruses detected in 62% hospitalised
Hospitalised less likely to use inhalers
NW Johnston september
241
Asthma exacerbations
| Wark et al IFN
IN RESPONSE TO RV
Asthmatics = dec T1 IFN production from PBMCs, HBECs, DCs
Decreased apoptosis
INCREASED RV replication
Normal pro-inflammatory responses aside from that.
IDEA THAT TH2-IFN antagonise one another.
242
Asthma exacerbations
IN RESPONSE TO RV
Asthmatics = dec T1 IFN production from PBMCs, HBECs, DCs
Decreased apoptosis
INCREASED RV replication
Normal pro-inflammatory responses aside from that.
IDEA THAT TH2-IFN antagonise one another.
Wark et al IFN
243
Asthma exacerbations
| Message et al
Infected asthmatics with RV
| Saw increased SS, Dec PEF, increased BAL eosinophils, lymphocytes, neutrophils, increased NE
244
Asthma exacerbations
Infected asthmatics with RV
Saw increased SS, Dec PEF, increased BAL eosinophils, lymphocytes, neutrophils, increased NE
Message et al
245
Asthma exacerbations
| Psarras et al
Increased VEGF after RV infection
246
Asthma exacerbations
| Increased VEGF after RV infection
Psarras et al
247
Asthma exacerbations
| Kuo et al
Increased collagen production in response to RV infection
248
Asthma exacerbations
| Increased collagen production in response to RV infection
Kuo et al
249
Asthma exacerbations
Murray et al
Green et al
Observational study
Children = 20x more likely to have exacverbation IF sensitised, exposed AND RV infection
Adults: 8x more likely with all 3. 2x more lilely with sensitised + exposed
250
Asthma exacerbations
Observational study
Children = 20x more likely to have exacverbation IF sensitised, exposed AND RV infection
Adults: 8x more likely with all 3. 2x more lilely with sensitised + exposed
Murray et al
| Green et al
251
Asthma exacerbations
| Gill et al
Cross linking of IgE receptors on DCs PREVENTS ABILITY TO PRODUCE IFNs
252
Asthma exacerbations
| Cross linking of IgE receptors on DCs PREVENTS ABILITY TO PRODUCE IFNs
Gill et al
253
Asthma exacerbations
| Teach et al
```
Randomised children to omalizumab
6vs36% exacerbations
Took PBMCs before and after Rx
IFN response measured before and after
Pre therapy = same response
Post therapy omalizumab group had sig more IFN production
```
INTERESTINGLY across both groups, exacerbation was much more likely in individuals with
254
```
Asthma exacerbations
Randomised children to omalizumab
6vs36% exacerbations
Took PBMCs before and after Rx
IFN response measured before and after
Pre therapy = same response
Post therapy omalizumab group had sig more IFN production
```
INTERESTINGLY across both groups, exacerbation was much more likely in individuals with
Teach et al
255
Microbiome
| Hills and Artis
Gut bacteria changes significantly during breast feeding and weaning
256
Microbiome
| Gut bacteria changes significantly during breast feeding and weaning
Hills and Artis
257
Microbiome
| Bisgaard et al 2007
Neonates colonised with M.catarrhalis, H influenza, S pneumoniae in the hypopharyngeal region are at increased risk of recurrent wheeze and asthma in early life
258
Microbiome
Neonates colonised with M.catarrhalis, H influenza, S pneumoniae in the hypopharyngeal region are at increased risk of recurrent wheeze and asthma in early life
Bisgaard et al 2007
259
Microbiome
| Byorkston 2001
Differences in the composition of the gut flora in infants who will and will not develop allergy will emerge before any clinical manifestations of atopy.
Mice lacking microbiome = increased risk allergy
Infants born by C section = increased risk infection, obesity and a/i diseases later on in life.
260
Microbiome
Charlson et al
BUT
Downward et al
Concluded there is continuity of the microbiome from U->LRT
SOME populations unique to LRT - metacommunities
BUT
Did discover differences in communities in each lobe/branch
261
Microbiome
Differences in the composition of the gut flora in infants who will and will not develop allergy will emerge before any clinical manifestations of atopy.
Mice lacking microbiome = increased risk allergy
Infants born by C section = increased risk infection, obesity and a/i diseases later on in life.
Byorkston 2001
262
Microbiome
Concluded there is continuity of the microbiome from U->LRT
SOME populations unique to LRT - metacommunities
BUT
Did discover differences in communities in each lobe/branch
Charlson et al
BUT
Downward et al
263
Microbiome
| Jones et al
Microbial communities very different during asthma exacerbations in CF patients
Administration of ABx does not change compositions of microbiota (esp pseudomonas) by the time exacerbation has resolved.
Increased anaerobes.
264
Microbiome
Microbial communities very different during asthma exacerbations in CF patients
Administration of ABx does not change compositions of microbiota (esp pseudomonas) by the time exacerbation has resolved.
Increased anaerobes.
Jones et al
265
Microbiome
| Staley et al
Great platelet count anomaly - only 5% of microorganisms culturable currently
266
Microbiome
| Great platelet count anomaly - only 5% of microorganisms culturable currently
Staley et al
267
NEO
| Sigurs et al
Increased asthma and wheeze with children who have had RSV bronchiolitis
268
NEO
| Increased asthma and wheeze with children who have had RSV bronchiolitis
Sigurs et al
269
NEO
| Blanken et al
Pralivizumab caused 61% decrease in cumulative wheeze days vs placebo in RSV season
n=215 per group
270
NEO
Pralivizumab caused 61% decrease in cumulative wheeze days vs placebo in RSV season
n=215 per group
Blanken et al
271
NEO
| Prendergast et al
```
DCs = dec T1 IFNs
TH1 = decreased differentiation and IFNy and IL12 production
TH17 = enhanced responses and differentiation (IL1b,6,23)
Treg = increased expression
```
272
NEO
DCs = dec T1 IFNs
TH1 = decreased differentiation and IFNy and IL12 production
TH17 = enhanced responses and differentiation (IL1b,6,23)
Treg = increased expression
Prendergast et al
273
NEO
| Levy et al
Neutrophils, Macrophages and NK cells have reduced responses to TLR1/2/4/6
274
Hygeine Hypothesis
| Haatela et al
Finland Conscript study
| Increased prevalence, discharge and exemption for asthma
275
Finland Conscript study
| Increased prevalence, discharge and exemption for asthma
Haatela et al
276
Greenland 1987-1998
Atopic prevalence originally ~5-10% across each age groups
| 1998 = 20% across each
277
Atopic prevalence originally ~5-10% across each age groups
| 1998 = 20% across each
Greenland 1987-1998
278
Karmans et al
Systematic review concluded sig less AR with 3 sibs vs none
| - Not all asthma allergic therefore link not as strong
279
Systematic review concluded sig less AR with 3 sibs vs none
| - Not all asthma allergic therefore link not as strong
Karmans et al
280
Kramer et al
Age at entry nursery
Cross sectional
6-11 months = no extra risk of hayfever /sensitsation if from SMALL family
24months+ = if from small family ->3.63x increased risk of hayfever. 2.72x risk of sensitisation
281
Age at entry nursery
Cross sectional
6-11 months = no extra risk of hayfever /sensitsation if from SMALL family
24months+ = if from small family ->3.63x increased risk of hayfever. 2.72x risk of sensitisation
Kramer et al
