co-morbitities of asthma - allergic rhinitis ... rhinosinusitis-pawankar.pdfcomplications of acute...
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Co-morbitities of Asthma -Allergic Rhinitis,
Rhinosinusitis, OME, OSA
Co-morbitities of Asthma -Allergic Rhinitis,
Rhinosinusitis, OME, OSA
Ruby Pawankar, MD, Ph.D
Nippon Medical School,
Tokyo, Japan
rpawankar @gmail.com
Ruby Pawankar, MD, Ph.D
Nippon Medical School,
Tokyo, Japan
rpawankar @gmail.com
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IntroductionIntroduction� Asthma and allergic rhinitis (AR) are global health
problems that causes major illness and disability worldwide.
� WHO estimates 300 million worldwide have asthma and 400 million people worldwide have AR
� Impairment of quality of life is seen in both adults and children with asthma and AR and asthma.
� Patients have several co-morbidities -sleep disorders, emotional problems, impairment in activities and social functioning.
� The economic impact direct and indirect costs are substantial.
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Co-morbidities of AsthmaCo-morbidities of Asthma
Modified from Spector SL. JACI. 1997;99:S773-S780.
Sinusitis
OME
OSAS
AR
Comorbidities
• Allergic Rhinitis• Sinusitis• Otitis media with effusion• Sleep disorders
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Asthma and ARAsthma and AR
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Allergic Rhinitis Is a Risk Factor for Asthma
Allergic Rhinitis Is a Risk Factor for Asthma
23-year follow-up of college freshmen undergoing allergy testing; data based on 738 individuals (69% male) with average age of 40 years. Adapted from Settipane RJ et al Allergy Proc 1994;15:21-25.
12
10
8
6
4
2
0
% of patients
whodeveloped
asthma
10.5
Allergic rhinitisat baseline
(n=162)
3.6
No allergic rhinitisat baseline
(n=528)
p<0.002
Allergic rhinitis increased the risk of asthma ~ 3-fold
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* Only 50% of study children skin tested.Wright et al. Pediatrics. 1994; 94:895.
Prevalence of Rhinitis in ChildrenPrevalence of Rhinitis in Children
� Physician diagnosed allergic rhinitis in children
- By 6 years of age 42%
• Began in first year 77%
• Began after first year 57%
• Prick skin test positive * 20%� Development of asthma by 6 years
– When rhinitis began in first year 23% (p<.005)
– When rhinitis began after first year 13%
When rhinitis began in the 1st year of life, the de velopment of asthma was twice as high as when it started after t he 1st year
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Prevalence of Asthma in Adults and Children With AR
Diagnosed with asthma
Asthma symptoms in past 12 months
Res
pond
ents
, %
32
39
21
28
0
10
20
30
40
50
60
Adults with AR (N = 2,500) Children with AR (N = 500 )
More children than adults with AR have been diagnos ed with asthma or had asthma symptoms in the past 12 months
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Adapted from Casale TB, et al. Clin Rev Allergy Immunol 2001 and
Kay AB N Engl J Med 2001
Early-phaseresponse
Late-phaseresponseT cells Inflammatory
mediators
Allergen
Cytokines
Preformed MediatorsCysteinyl leukotrienes
ProstaglandinsPlatelet-activating factor
Eosinophils
Membrane-bound IgE
Mastcell
Common Inflammatory Cells and Mediators
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Bronchial biopsies in patients with SAR
0
10
20
30
40
50
60
Cel
ls/m
m2
con
nec
tive
tis
sue
out inpollen season
EG1+
CD45RO+
CD8+
CD4+
Chakir et al, Allergy Clin Immunol 2000
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nose bronchi
0
20
40
60
80Asthmatics
untreated
CS-dependent
nose bronchi
0
20
40
60
80Controls
Eos
inop
hils
(/m
m2)
Eosinophilic inflammation in submucosa
Chanez et al, Am J Respir Crit Care Med 1999
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Bronchial Allergen Challenge ProducedNasal Inflammation
Bronchial Allergen Challenge ProducedNasal Inflammation
Eos
inop
hils
(10
6C
ells
/mm
2 ) 600
500
400
300
200
100
0
Blood(N = 16)
Bronchial Subepithelium
(N = 16)
T0
11
T0 = before challenge; T24 = 24-hr postchallenge.* P <.05 vs control (T0);
†P <.01 vs allergic patients (T0).Braunstahl et al. Am J Respir Crit Care Med. 2000;161:2051-2057.
Nasal Lamina Propria(N = 16)
Eos
inop
hils
(N
o. C
ells
/mm
2 )
Eos
inop
hils
(N
o. C
ells
/mm
2 )
T24
Allergic Patients Control Patients
1600
1200
800
400
0
100
80
60
40
20
0
T0 UnchallengedLeft Lung
T0 T24Allergen-ChallengedRight Middle
Lobe
T24
†
†* *
*
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22% 41%
48% 33%
44% 38%
51% 35%
0% 20% 40% 60% 80% 100%
Impact of AR on Asthma in Child’s Quality of Life
Impact of AR on Asthma in Child’s Quality of Life
Participation in leisure & sports . . .
Concentration at work/ school
Ability to enjoy social activities
Ability to get a good night’s sleep
A great deal and Quite a lotA great deal and Quite a lot A little bitA little bit
85%85%
82%82%
83%83%
63%63%
Total disrupted:Total disrupted:
Erkka V and Pawankar R, 2007. Br. Pulm Med
The co-existence of AR with asthma grossly worsened the QOL
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Price D, et al. Clin Exp Allergy 2005, in press.(Analysis of health-care resource use in adults 16 to 55 years of age with asthma and allergic rhinitis in a general practice in the UK)
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
% of patients
hospitalizedannually
0.76
Patients with asthma + allergic rhinitis
(n=4611)
0.45
Patientswith asthma(n=22,692)
p<0.006
Increased Risk of Hospitalization for Asthma in AR Patients
Patients with AR and asthma had an increased risk o f hospitalization
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Treating Allergic Rhinitis Decreased Asthma-Related Resource Utilization Treating Allergic Rhinitis Decreased Asthma-Related Resource Utilization
Retrospective cohort study of costs over a period of up to one year incurred by patients 12 to 60 years of age with both allergic rhinitis and asthma.Adapted from Crystal-Peters J et al J Allergy Clin Immunol 2002;109(1):57-62.
0.9
2.5
2.0
1.5
1.0
0.5
0
% ofpatients
Patients untreated forallergic rhinitis (n=1357)
Patients treated forallergic rhinitis (n=3587)
2.3
p<0.01
61% fewer hospitalizations in patients treated for AR
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Asthma, AR and SinusitisAsthma, AR and Sinusitis
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Ulanovski et al. Am J Rhinol. 2008;22:122.
Subjects ≤≤≤≤25 years of age(n=35)
Pat
ient
s w
ith
Acu
te R
hino
sinu
sitis
(%
)
Total population(N=136)
Controls (n=82)AR (n=54)
P=0.09
P<0.001
Acute Rhinosinusitis Is More Commonin Patients With AR
Acute Rhinosinusitis Is More Commonin Patients With AR
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Prevalence of Sinus Mucosal Disease in Patientswith Perennial Allergic Rhinitis
In a study comparing the prevalence of sinusitis in patients with perennial allergic rhinitis (PAR) versus normal controls, Berrettini et al. found a prevalence of 67.5% in 40 patients with PAR versus 33.4% in 30 nonallergic controls.This difference was statistically significant.
Sinusitis - defined by sinus CT scan or rhinoscopy. Thirty-six of the 40 patients with PAR also had positive endoscopic findings.
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Increased Risk and Duration of Respiratory Infections in Children
with AR
Increased Risk and Duration of Respiratory Infections in Children
with AR
Tot
al R
I (nu
mbe
r)
Allergic children(n=46)
RI D
urat
ion
(day
s)
P=0.0001
Non-allergic children(n=71)
Allergic children(n=46)
Non-allergic children(n=71)
P=0.009
Ciprandi et al. Pediatr Allergy Immunol. 2006;17:389-391.
Upper Respiratory Infections in Children 5.1 in asthmatic children vs 3.8 in controls
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Complications of Acute Rhinosinusitis
Complications of Acute Rhinosinusitis
� Orbital cellulitis (ethmoid)� Meningitis� Subdural/epidural empyema
(frontal)� Brain abscess (frontal)� Cavernous sinus thrombosis
(sphenoid)� Osteomyelitis (frontal)� Asthma exacerbation
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Upper Respiratory Infections in Children
Upper Respiratory Infections in Children
� 5.1 in asthmatic children
vs� 3.8 in controls
Minor et al. J. Pediatr. 1974; 85:472-477.
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Chronic SinusitisChronic Sinusitis
� 50% with chronic sinusitis have OME
� 53% have abnormal sinus radiographs
– 27% near total opacification
G. Shapiro. J. Allergy Clin. Immunol. 1988; 81:1025.
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Influx of Eosinophils into the Maxillary Sinuses After Nasal Allergen ChallengeInflux of Eosinophils into the Maxillary Sinuses After Nasal Allergen Challenge
0
100
200
300
400
500
600
700
Pre Dil A1 A2 A3 1 2 3 4 5 6 7 8
Time (hrs)
Tot
al E
osin
ophi
ls
IpsilateralContralateral
*
* *
*
**
*p<0.05 vs DilN=15
*
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RightMaxillary
Sinus
LeftMaxillary
Sinus
Central Nervous System
LeftNostril
RightNostril
Efferent PathwaysAfferent PathwaysAxon Reflexes
Nasal and Sinus Reflexes
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AR and Otitis Media with EffusionAR and Otitis Media with Effusion
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Nasal Allergy and Chronic OME in various Paediatric populationsNasal Allergy and Chronic OME
in various Paediatric populations
OME = Otitis Media with Effusion.Tomonaga et al. Acta Otolaryngol. (Stockh) 1988; 458 (suppl):41.
School Children Allergic Rhinitis Children Chroni c OME Children
50% Allergic Rhinitis21% OME
6% OME
1.9% OME + Allergic Rhinitis
17% Allergic Rhinitis
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Eustachian Tube Obstruction:Ragweed Pollen Season
Eustachian Tube Obstruction:Ragweed Pollen Season
05
10152025303540
Pre-SeasonalPeak-SeasonalPost-Seasonal
Eustachian Tube
Obstruction (%)
15/58
32/96p<.001
9/62
p<.02
Hurst, Venge. Otolaryngol. Head Neck Surg. 1993; 108:711.
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Eosinophils
T-lymphocytes
NonAtopic
CD3+ cells in MEE
Atopic
Same trend for IL-4 and IL-5
Asthma and OME
Nguyen LHP, et al. J Allergy Clin Immunol 2004; 114: 1110.
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Asthma and OME
Similar allergic inflammation in the middle ear and the airways
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Sinusitis, Asthma and OME in house dust mite AR patients
Sinusitis, Asthma and OME in house dust mite AR patients
Pawankar R et al.
0
5
10
15
20
25
30
35
40
SinusitisAsthmaOME
% of total HDM - AR patients
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Chronic allergic respiratory syndrome
Modified from Stokes JR and Casale T. AR, asthma and OSA- the link. In- Allergy Frontiers Epigenetics to Future Perspective. Eds- Pawankar. Holgate Rosenwasser
SinusitisOME
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SummarySummary
� Asthma is rarely found in isolation and needs to be considered in the context of systemic allergic disease associated with numerous comorbid disorders
� Upper airway co-morbidities of asthma include AR, sinusitis, and OME( with consequent disordered sleep/ behavioral effects)
� Treating the underlying inflammation is key to relieving symptoms & reducing consequences / co-morbidities in patients with asthma
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