are rhinitis and asthma two manifestations of one disease? stephen r. durham
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Are rhinitis and asthma two manifestations of one disease? Stephen R. Durham Allergy and Clinical Immunology Royal Brompton Hospital and Imperial College London. WAO Cancun Dec 7 th 2011. Relationship between rhinitis and asthma – implications for treatment. - PowerPoint PPT PresentationTRANSCRIPT
Are rhinitis and asthma two manifestations of one disease?
Stephen R. Durham
Allergy and Clinical ImmunologyRoyal Brompton Hospital andImperial College London
WAO Cancun Dec 7th 2011
Relationship between rhinitis and asthma – implications for treatment
Is there a relationship between rhinitis and asthma ?
Is the relationship causal ?
Does treating rhinitis improve asthma?
Jarvis D et al Allergy 2011 Nov 4. [Epub ahead of print]
Asthma in adults and its association with chronic rhinosinusitis: The GA(2)LEN survey in Europe.
52,000 adults (18 -75 yr) 19 centres,12 countries.
Strong association of asthma with CRS (adjusted OR: 3.47; 95% CI: 3.20-3.76).
Association stronger in those with CRS and allergic rhinitis (adjusted OR: 11.85; 95% CI: 10.57-13.17).
Allergic rhinitis is a risk factor for asthmaAllergic rhinitis increased the risk of asthma ~3-fold
23-year follow-up of college freshmen undergoing allergy testing; data based on 738 individuals (69% male) with average age of 40 years.
12
10
8
6
4
2
0% o
f pati
ents
who
dev
elop
ed a
sthm
a
10.5
Allergic rhinitisat baseline
(n=162)
3.6
No allergic rhinitisat baseline
(n=528)
p<0.002
Settipane RJ et al Allergy Proc 1994;15:21-25.
The nose is that part of the lung which is accessible to the finger
Rhinitis / Asthma : Similarities Frequently coexist Respiratory pseudostratified epithelium IgE-dependent mechanisms Th2 T lymphocyte activation Eosinophil rcruitment Mast cell / basophil activation and
transepithelial migration
Rhinitis / Asthma: Differences
Epithelium intact Basement membrane normal No airway smooth muscle Venous sinusoids Submucosal glands prominent Remodelling absent Antihistamines effective 2-agonists ineffective
Epithelium disrupted Basement membrane abnormal Bronchial smooth muscle No venous sinusoids Submucosal glands few Remodelling present Antihistamines ineffective (?) 2-agonists effective
Rhinitis Asthma
Nasal allergen provocation induces adhesion molecule expression and tissue eosinophilia in upper and lower airways.
Braunstahl G-J, Overbeek SE, KleinJan A, Prins J-B, Hoogsteden HC, Fokkens WJ.
J Allergy Clin Immunol 2001;107:469-76.
Study design
AgNasal Ag provocation Nasal Ag provocation
Nasal mucosa Bronchial mucosa
T 24h
T 0h
ICAM-1 VCAM-1 ICAM-1 VCAM-1
0 24
0
20
40
60
80
100
0
20
40
60
80
100
0
20
40
60
80
100
0
20
40
60
80
100
0
20
40
60
80
100
0
20
40
60
80
100
Allergic Rhinitis
Controls (n=9)
0 24 0 24
0 24
0 24
0 24
ICAM-1/CD31 VCAM-1/CD31 ELAM-1/CD31
ICAM-1/CD31 VCAM-1/CD31 ELAM-1/CD31
Per
cent
pos
itive
Per
cent
pos
itive
NoseBronchus
NoseBronchus
*
***
** * p<0.05
Influence of nasal challenge on expression of adhesion molecules on blood vessels in the
nasal ( ) and bronchial ( ) mucosa
Treatment of allergic rhinitis
mildintermittent
mildpersistentmoderate
severeintermittent
moderatesevere
persistent
Allergen and irritant avoidance
Immunotherapy
Intra-nasal steroid (+/- antileukotriene)
Oral or topical antihistamine
http://www.whiar.org/
Does treating hayfever help patients with asthma?
Antihistamines Leukotriene antagonists
Nasal corticosteroids
Allergen immunotherapy
High-dose H1 receptor antagonist treatment in persistent asthma
Simons FER. Clin Exp Allergy 1999; 29: S98–104
Effect of cetirizine in patients with seasonal rhinitis and concomitant asthma
placebocetirizine
1 2 3 4 5 6
1 2 3 4 5 6
2
4
6
8
0
2
4
6
8
0
10
Study week
Study week
Mea
n to
tal
rhin
itis s
core
Mea
n to
tal
asth
ma
scor
e
Grant et al. J Allergy Clin Immmunol 1995; 97: 923–732
Does treating hayfever help patients with asthma?
Antihistamines
Leukotriene antagonists
Nasal corticosteroids
Allergen immunotherapy
Philip G. Curr Med Res Opin. 2004 Oct;20(10):1549-58.
Montelukast: Effect on hayfever in patients with asthma (n=631)
* p < 0.001 compared with placebo
Philip G. Curr Med Res Opin. 2004 Oct;20(10):1549-58.
Montelukast: Effect on hayfever in patients with asthma (n=631)
Philip G. Curr Med Res Opin. 2004 Oct;20(10):1549-58.
Does treating hayfever help patients with asthma?
Antihistamines
Leukotriene antagonists
Nasal corticosteroids Allergen immunotherapy
Welsh PW, Stricker WE, Chu CP, Naessens JM,Reese ME, Reed CE and Marcoux.
Efficacy of beclomethasone nasal solution flunisolide,and cromolyn in relieving symptoms of ragweed allergy. Mayo Clin Proc.1987;62:125-34.
All three treatments superior to placebo (p< 0.001). Glucocorticoids more effective than cromolyn (p<0.001). All 3 intranasal treatments ALSO reduced seasonal asthma.
Study randomised but NOT blinded:
100
80
60
40
20
0
7.11 7.24 8.7 8.21 9.49.187.17 7.31 8.14 8.28 9.111984
Treatment
Mea
n w
eekl
y ha
y fe
ver r
aw sc
ore
NasalcromPlacebo
NasalideBeconase aqueous
Welsh PW. Mayo Clinic Proceedings 1987; 62: 125-34.
Efficacy of beclomethasone nasal solution, flunisolide, and cromolyn in relieving symptoms of ragweed rhinitis
Efficacy of beclomethasone nasal solution, flunisolide, and cromolyn in relieving symptoms of ragweed asthma
15
10
5
0
-5
Asth
ma
scor
e m
ean
wee
kly
diffe
renc
e fr
om b
asel
ine
Treatment
NasalcromPlacebo
NasalideBeconase aqueous
Welsh PW. Mayo Clinic Proceedings 1987; 62: 125-34.
Dahl R. Allergy 2005: 60: 875–881
- DBPC double-dummy study in seasonal rhinitis and asthma- no effect of intranasal steroids on asthma outcomes- no effect of inhaled steroids on nasal outcomes- but ? too mild disease to show an effect
Intranasal and inhaled fluticasone propionate for pollen-induced rhinitis and asthma
Dahl R. Allergy 2005: 60: 875–881
Geometric mean PD20 methacholine measured at baseline () and after 4 weeks treatment () (*** p < 0.001 IHFP ± INFP vs INFP or placebo). INFP, fluticasone proprionate nasal spray; IHFP, inhaled fluticasone propionate.
Does treating hayfever help patients with asthma?
Antihistamines
Leukotriene antagonists
Nasal corticosteroids
Allergen immunotherapy
Allergens of Proven Efficacy in Double-Blind Placebo-Controlled Studies
Birch Cat Mites Grass
Walker SM. J Allergy Clin Immunol 2001; 107: 87-93
% re
duct
ion
from
bas
elin
e (1
998/
1996
)
Subcutaneous immunotherapy for hayfever:effect on symptoms and rescue medication
0
-50
-100
P = .01
P = .007
Immunotherapy group
Placebo group
Symptoms Medication
Walker SM et al JACI 2001; 107: 87-93
50% decrease in nasal Symptoms85% decrease in asthma symptoms
P = .04
Immunotherapy
P = .01 P = ns
Winter SummerSummer
1996 1996 1998
Winter SummerSummer
1996 1996 1998
Placebo
>16.0
16.0
8.0
4.0
2.0
1.0
Met
hach
olin
e PC
20, m
g/m
L
Walker SM. J Allergy Clin Immunol 2001; 107: 87-93
Effect of immunotherapy on airway responsiveness to methacholine
Does treating hayfever help patients with asthma?
Antihistamines
Leukotriene antagonists
Nasal corticosteroids
Allergen immunotherapy
Adams RJ et al. J Allergy Clin Immunol 2002; 109: 636-42.
Retrospective study of 13,844 asthmatics 1031 had emergency dept visit (7.4%) Relative risk-INS 1/yr = 0.7, >3/yr = 0.5 RR anti-histamine = 0.9
Effect of rhinitis treatment on asthmaexacerbations
Adams RJ et al. J Allergy Clin Immunol 2002; 109: 636-42.
Corren J. J Allergy Clin Immunol 2004; 113: 415-9.
Corren J. J Allergy Clin Immunol 2004; 113: 415-9.
Rhinitis therapy and the prevention of hospital care for asthma: A case-control study
Adjusted odds ratios for asthma-related hospital care in relation to intranasal corticosteroid and second generation antihistamine use during 1-year period before the index date
Is there a relationship between rhinitis and asthma ? Yes
Is the relationship causal ? Yes
Does treating rhinitis Maybeimprove asthma?
Relationship between rhinitis and asthma – implications for treatment
Patients with rhinitis should be evaluated for asthma
Patients with asthma should be evaluated for rhinitis
A strategy should combine the treatment of upper and lower airways in terms of efficacy and safety
Recommendations