the impact of allergic rhinitis on asthma
DESCRIPTION
The impact of allergic rhinitis on asthma. Gert-Jan Braunstahl Pulmonary medicine, EMCR, Rotterdam. ARIA. Objectives: Update knowledge of AR Recognise AR as global health problem Asthma and AR commonly occur together Evidence-based approach to diagnosis and treatment - PowerPoint PPT PresentationTRANSCRIPT
The impact of allergic rhinitis The impact of allergic rhinitis on asthmaon asthma
Gert-Jan BraunstahlGert-Jan BraunstahlPulmonary medicine, EMCR, RotterdamPulmonary medicine, EMCR, Rotterdam
ARIAARIA
Objectives:Objectives: Update knowledge of ARUpdate knowledge of AR Recognise AR as global Recognise AR as global
health problemhealth problem Asthma and AR commonly Asthma and AR commonly
occur togetheroccur together Evidence-based approach Evidence-based approach
to diagnosis and treatmentto diagnosis and treatment Management of allergic Management of allergic
airways diseaseairways disease
Bousquet et al, J Allergy Clin Immunol 2001
Dendritic cell
Th1-cell Th2-cellIFN-
IL-10
IL-1
Th0-cell
VCAM-1 ICAM-1 E-selectin
IL-4 IL-13
B-cell
IgE
Allergen
Mast cell
histamine
LTs PGs PAF
Eotaxin IL-5 RANTES
Eosinophil
MBP ECP
Systemic circulation
Airway inflammationAirway inflammation
Pathogenesis allergic Pathogenesis allergic airway disease airway disease
Genetic factors
Environmental factors
Atopic sensitization
Structural changes
Mucosal inflammation
Phenotype
Association Association rhinitis/sinusitisrhinitis/sinusitis
and asthmaand asthma
0
2
4
6
8
10
R-S- R+S- R-S+ R+S+
OR
1
*
*
* p < 0.001 Guerra, J Allergy Clin Immunol 2002
80-95% of asthmatic patients have 80-95% of asthmatic patients have rhinitis.rhinitis.
76% asthmatic patients reported 76% asthmatic patients reported presence of rhinitis before onset presence of rhinitis before onset asthma.asthma.
Asthma presence associated with Asthma presence associated with duration and severity of rhinitis.duration and severity of rhinitis.
EpidemiologyEpidemiology
Leynaert, J Allergy Clin Immunol 2004
Causal relationshipCausal relationship
rhinitis
asthma
Dis
ease
sev
erit
y
time
Togias, Allergy 1999
QuestionsQuestions
What is the relationship between What is the relationship between allergic rhinitis and asthma?allergic rhinitis and asthma?
Is there any interaction between upper Is there any interaction between upper and lower airwaysand lower airways??
What are the mechanisms that may What are the mechanisms that may play a role in nasobronchial cross-talk?play a role in nasobronchial cross-talk?
QuestionsQuestions
What is the relationship between What is the relationship between allergic rhinitis and asthma?allergic rhinitis and asthma?
Is there any interaction between upper Is there any interaction between upper and lower airwaysand lower airways??
What are the mechanisms that may What are the mechanisms that may play a role in nasobronchial cross-talk?play a role in nasobronchial cross-talk?
Australia
asthma 18%
rhinitis 25%
Canada
asthma 13%
rhinitis 25%
Sweden
asthma 8%
rhinitis 15%
China
asthma 5%
rhinitis 10%
Brasil
asthma 10%
rhinitis 22%Kenya
asthma 8%
rhinitis 13%
ISAAC study, Lancet 1998
Worldwide prevalenceWorldwide prevalence
Prevalence asthma and Prevalence asthma and rhinitis in NLrhinitis in NL
Non-allergic
68
Allergic no symptoms
10
Rhinitis12
Asthma + Rhinitis
8
Asthma
2
Nasal inflammation in Nasal inflammation in asthmaasthma
Gaga M. et al, Clin Exp Allergy 2000
16
AR ANR
HC
EG
2+ c
ells
per
field
12
8
4
0p<0.001
p<0.001
Nasal inflammation and Nasal inflammation and BHRBHR
Nasa
l eosi
nophil
num
ber
20
22
absent
3
low
11
moderate
12
high
10
0 PD20 methacholine
Ciprandi G. et al, Int Arch Allergy Immunol 2004
Lower airway involvement Lower airway involvement in in
atopic patientsatopic patients
5
6
7
8
9
10
m RBM
* *
HC NANR RNA A+Rn=16 n=8 n=18 n=19
Braunstahl GJ. et al, Clin Exp Allergy 2003* = p < 0.05 vs controls
cell/mm2Eosinophils
0
20
40
60
HC NANR RNA A+Rn=16 n=8 n=18 n=19
*
** **
5
6
7
8
9
10
m RBM
* *
HC NANR RNA A+Rn=16 n=8 n=18 n=19
5
6
7
8
9
10
m RBM
* *
5
6
7
8
9
10
m RBM
5
6
7
8
9
10
m RBM
5
6
7
8
9
10
m RBM
* ** ** *
HC NANR RNA A+Rn=16 n=8 n=18 n=19HC NANR RNA A+R
n=16 n=8 n=18 n=19
Braunstahl GJ. et al, Clin Exp Allergy 2003* = p < 0.05 vs controls
cell/mm2Eosinophils
0
20
40
60
HC NANR RNA A+Rn=16 n=8 n=18 n=19
*
** **cell/mm2
Eosinophils
0
20
40
60
0
20
40
60
HC NANR RNA A+Rn=16 n=8 n=18 n=19HC NANR RNA A+R
n=16 n=8 n=18 n=19
*
** **
Bronchial remodeling in Bronchial remodeling in asthma and rhinitisasthma and rhinitis
Chakir et al, Lab Invest 1996Chakir et al, Lab Invest 1996
0
5
10
15
20
25
base
men
t m
embr
ane
thic
knes
s (µ
m)
controls rhinitis asthma
type I collagen
0
5
10
15
20
25
controls rhinitis asthma
type III collagen
0
5
10
15
20
25
controls rhinitis asthma
fibronectin
Nasal and bronchial mucosa Nasal and bronchial mucosa in asthma and rhinitisin asthma and rhinitis
nosenose bronchusbronchus
EpitheliumEpithelium
sheddingshedding 0 to +0 to + ++++++
metaplasia metaplasia 00 00
Basement membrane Basement membrane
pseudo-thickeningpseudo-thickening 0 to + 0 to + ++ to +++++ to +++
collagen depositioncollagen deposition 0 to +0 to + ++ to +++++ to +++
other proteinsother proteins ?? ++ to +++++ to +++
Fibroblasts sub-mucosaFibroblasts sub-mucosa 0 to + ?0 to + ? ++ to +++++ to +++
Collagen in sub-mucosaCollagen in sub-mucosa ?? + to +++ to ++
Courtesy of Jean Bousquet
SummarySummary
Mucosal inflammation is present in the entire airway of patients with allergic rhinitis and/or asthma.
Upper airway inflammation is associated with bronchial hyperresponsiveness
Lower airway remodeling is present in asthmatic, but also in allergic rhinitis patients.
InflammationInflammationInflammation
QuestionsQuestions
What is the relationship between What is the relationship between allergic rhinitis and asthma?allergic rhinitis and asthma?
Is there any interaction between upper Is there any interaction between upper and lower airwaysand lower airways??
What are the mechanisms that may What are the mechanisms that may play a role in nasobronchial cross-talk?play a role in nasobronchial cross-talk?
NP in allergic rhinitis NP in allergic rhinitis influence on lower airwaysinfluence on lower airways
T0
blood sample
bronchus biopsy
nose biopsy
hr
= PNIF, PEF, symptom score
T24
9 9
subjects
T0
blood sample
bronchus biopsy
nose biopsy
T0
blood sample
bronchus biopsy
nose biopsy
hrhr
= PNIF, PEF, symptom score
T24
= PNIF, PEF, symptom score= PNIF, PEF, symptom score
T24
9 9
subjects
9 999 99
subjects
Symptoms (VAS)Symptoms (VAS)
RhinitisControls
0 ½ 2 4 6 8 10 12 24 24½ hr
Nose
mm
NP
Braunstahl GJ et al, JACI, 2001
p = 0.0002 (ANOVA)
0 ½ 2 4 6 8 10 12 24 24½ hr
Lung
mm
NP
p = 0.01
RhinitisControls
0 ½ 2 4 6 8 10 12 24 24½ hr
Nose
mm
NP
Braunstahl GJ et al, JACI, 2001
p = 0.0002 (ANOVA)
RhinitisControlsRhinitisControls
0 ½ 2 4 6 8 10 12 24 24½ hr
Nose
mm
NP
Braunstahl GJ et al, JACI, 2001
p = 0.0002 (ANOVA)
0 ½ 2 4 6 8 10 12 24 24½ hr
Nose
mm
NP
Braunstahl GJ et al, JACI, 2001
p = 0.0002 (ANOVA)
0 ½ 2 4 6 8 10 12 24 24½ hr
Lung
mm
NP
p = 0.01
0 ½ 2 4 6 8 10 12 24 24½ hr
Lung
mm
NP
p = 0.01
Airway functionAirway function
RhinitisControls
PNIF
0 ½ 2 4 6 8 10 12 24 24½ hr
L/min
NP
Braunstahl GJ et al, JACI, 2001
p = 0.0001
0 ½ 2 4 6 8 10 12 24 24½ hr
PEFL/min
NP
p = 0.04
RhinitisControls
PNIF
0 ½ 2 4 6 8 10 12 24 24½ hr
L/min
NP
Braunstahl GJ et al, JACI, 2001
p = 0.0001
0 ½ 2 4 6 8 10 12 24 24½ hr
PEFL/min
NP
p = 0.04
Bronchial inflammation Bronchial inflammation after NPafter NP
T0 T24
*
0
20
40
60
80
VCAM-1% +vessels
control
rhinitis
* = p < 0.05 vs controls and T0
Braunstahl GJ et al, JACI, 2001
T0 T24
*
0
40
80
120
160Cell/mm2
Eosinophils
T0T0 T24
*
T24
**
0
20
40
60
80
VCAM-1% +vessels
0
20
40
60
80
VCAM-1% +vessels
0
20
40
60
80
VCAM-1% +vessels
0
20
40
60
80
VCAM-1% +vessels
control
rhinitis
* = p < 0.05 vs controls and T0
Braunstahl GJ et al, JACI, 2001
T0T0 T24
*
T24
**
0
40
80
120
160Cell/mm2
Eosinophils
0
40
80
120
160Cell/mm2
Eosinophils
0
40
80
120
160
0
40
80
120
160Cell/mm2
Eosinophils
SBP in allergic rhinitisSBP in allergic rhinitis
influence on upper airwaysinfluence on upper airways
8 8
subjects
control
allergic biopsy after (T24)
biopsy before (T0)
+
8 8
subjects
control
allergic
8 888 88
subjects
control
allergic
control
allergic biopsy after (T24)
biopsy before (T0)
++
Nasal inflammation after Nasal inflammation after SBPSBP
MBP Lamina propria
controls
allergic
before
*
after0
20
40
60
80LungCell/mm2
before
*
after0
10
20
30
40
NoseCell/mm2
Braunstahl GJ et al, AJRCCM, 2000
Chymase (C) and Tryptase (T) 400x
Nasal inflammation after Nasal inflammation after SBPSBP
MCTC Lamina propria
MCTMCC
MCTC
before
*
after0
50
100
150
200
Cell/mm2
controls
allergicBraunstahl GJ et al, AJRCCM, 2001
Nose
SummarySummary
The interaction between nose and lung in allergic airways disease is a bi-directional process
QuestionsQuestions
What is the relationship between What is the relationship between allergic rhinitis and asthma?allergic rhinitis and asthma?
Is there any interaction between upper Is there any interaction between upper and lower airwaysand lower airways??
What are the mechanisms that may What are the mechanisms that may play a role in nasobronchial cross-talk?play a role in nasobronchial cross-talk?
Nasal vs. oral ventilationNasal vs. oral ventilation effect of cold air inhalationeffect of cold air inhalation
McLane, J. Appl. Physiol. 2000
B = baseline
R = frigid air
NHV NHV OHVN
R c
m H
2O
/L/s
ec
FEV
1
P value 0.01
0.27
<0.001B R B R B R
FEV
1
0
5
0
4
0
4
Pulmonary aspiration?Pulmonary aspiration? Radio-active markersRadio-active markers
Bardin et al, JACI, 1990
Maxillary sinusnasopharynx
Oesophagusstomach
Rest of GI tract
99mTc1 hr 6 hr 24
hr
Naso-bronchial reflex?Naso-bronchial reflex?effect of intranasal methacholineeffect of intranasal methacholine
base peak
controls
base peak
asthmatics
LARcmH20/L/sec
5
4
3
2
1
0
*
*
Lidocaine: no blockage
base peak
controls
base peak
asthmatics
NARcmH20/L/sec
20
15
10
5
0
* *
* = p < 0.05 vs baseline
Littell et al, Am Rev Respir Dis, 1990Phenylephrine: blockage
Systemic interaction?Systemic interaction?effect of NP on IL-5 plasmaeffect of NP on IL-5 plasma
Beeh et al, Clin Exp Allergy, 2003
IL-5
(pg/m
L)
Allergenpre post
80
*
Placebopre post
60
40
20
0
* p < 0.001
control
allergic
before
*
after0
10
20
30
40
50 IL-5pg/mL
before
*
after0
100
200
300
400eosinophils
cell x 106
Braunstahl GJ et al, AJRCCM, 2001
Systemic interaction?Systemic interaction?effect of SBP on IL-5 and effect of SBP on IL-5 and
eosinophilseosinophils
SummarySummary
Allergen
Aspiration
Neural reflex
Lymph nodes
Circulation
Ingestion
Nose breathing
Mouthbreathing
Allergen
Aspiration
Neural reflex
Lymph nodes
Circulation
Ingestion
Nose breathing
Mouthbreathing
Take home messagesTake home messages
Allergic rhinitis often precedes asthma.Allergic rhinitis often precedes asthma. Allergic rhinitis and asthma Allergic rhinitis and asthma
characterized by global airway characterized by global airway inflammation.inflammation.
There is a bi-directional influence There is a bi-directional influence between upper and lower airways.between upper and lower airways.
The systemic pathway plays an The systemic pathway plays an important role in the interaction important role in the interaction between nose and lungbetween nose and lung