Co-morbitities of Asthma - Allergic Rhinitis ... rhinosinusitis-Pawankar.pdf · Co-morbitities of...
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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
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.
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
Asthma and ARAsthma and AR
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
* 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
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
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
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
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
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
†
†* *
*
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
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
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
Asthma, AR and SinusitisAsthma, AR and Sinusitis
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
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.
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
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
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.
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.
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
*
RightMaxillary
Sinus
LeftMaxillary
Sinus
Central Nervous System
LeftNostril
RightNostril
Efferent PathwaysAfferent PathwaysAxon Reflexes
Nasal and Sinus Reflexes
AR and Otitis Media with EffusionAR and Otitis Media with Effusion
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
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.
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.
Asthma and OME
Similar allergic inflammation in the middle ear and the airways
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
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
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