allergies and asthma paul keith md msc frcpc mcmaster university president, canadian society of...
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Allergies and Asthma
Paul Keith MD MSc FRCPC
McMaster UniversityPresident, Canadian Society of Allergy and Clinical Immunology
DISCLOSURE INFORMATION
I have the following financial relationship to disclose:
Consultant for: CSL Behring, GSK, Merck, Novartis, Takeda, Viropharma
Grant/Research support from: CSL Behring, GSK, Merck, Shire
Honoraria from: CSL Behring, GSK, Merck, Takeda
Name: Dr. Paul Keith
CSACI Mission:
“…is the advancement of the knowledge and practice of allergy, clinical immunology, and asthma for optimal patient care.
The Society is also dedicated to improving the quality of life of people with allergies through research, advocacy, and continuing professional development and public education."
TRUE or FALSE?
1. Intranasal steroids are first line for the treatment of rhinitis when moderate congestion is present
2. Exposure to hand sanitizer is associate with increased rate of allergen sensitization
3. Allergy specific IgE levels go up as you Vitamin D levels go down
Father's desperate screams spur CPR rescue
THE HAMILTON SPECTATOR Aug 27, 2010 Jordan Hertz, a 12-year-old asthmatic
boy from east Hamilton, "He has severe asthma, and during the
day he said, 'Dad, I can't breathe,'" said Hertz. "That's a sign for me to rush him to the hospital."
While racing to Hamilton General, Jordan began saying, "I can't breathe, I can't breathe." His father called 911 on his cellphone and went to pull over. Before he could stop and give his son a puff from a rescue inhaler, Jordan lost consciousness.
The patient was 'vital signs absent' upon arrival
Inverse Relation between the Incidence of Prototypical Infectious Diseases (Panel A) and the Incidence of Immune Disorders (Panel B) from 1950 to 2000.
Bach J. N Engl J Med 2002;347:911-920.
Age-adjusted Australian hospital admission rates for anaphylaxis
1993-2005
*Rate per million population
Mullens RJ. Med J Aust 2007; 186 (12): 618-621.
The atopic march
Baatenburg de Jong A et al. Pediatr Allergy Immunol 2009;20:735
Food
Inhalant
Age in yrs
miliaseptumturrbinate
Asthma
Before
10 Minutes After Allergen Challenge
Laitinen et al. J Allergy Clin Immunol. 1992;90:32-42.
Eosinophilic Esophagitis
Allergy skin prick testing
IgE-dependent Release of Inflammatory Mediators
Immediate ReleaseGranule contents:Histamine, TNF-, Proteases, Heparin
Over MinutesLipid mediators: ProstaglandinsLeukotrienes
Over HoursCytokine production:Specifically TNF-a, IL-4, IL-13
IgE
FcRI
FcRIbinding site
Cell recruitment
Sneezing Nasal congestionItchy, runny noseWatery eyes
WheezingBronchoconstriction
Priming:Increased
responsiveness to repeated
allergen exposure
IgE Ab
Mast cell
Release of histamine and
other mediators
Early-phase reaction
Sneezing, rhinorrhoea, congestion, eye
symptoms
Antigen
Eosinophils
Late-phase reaction
Cellular Infiltration
Allergic inflammation and priming
Naclerio R, manuscript in development.
Mould
• sampled 46 rooms in 4 urban elementary schools (northeastern United States) and from 38 student bedrooms
Sheehan WJ et al Ann Allergy Asthma Immunol 2009 Feb;102(2):125-30
Epidemiology of allergic rhinitis in adults
Bauchau V, Durham SR. Eur Respir J 2004;24:758–64.
0
10
20
30
Belgium France Germany Italy Spain UK
% g
ener
al p
op
ula
tio
n
Prevalence of allergic rhinitis (AR) in European adults during 2001
Do you have nasal congestion or nasal symptoms?
• 44% of eligible respondents reported either nasal congestion or nasal symptoms.
• 20 % had been diagnosed with AR by a physician
n=3,671
Allergies in Canada Survey: Symptom control in worst month ( n=1001)
Allergies in Canada Survey: symptoms during worst month (n=1001)
35
29
23
21
22
16
7
8
6
11
5
32
30
30
27
19
18
17
15
14
10
7
17
15
17
13
12
14
18
13
14
7
11
0 20 40 60 80 100
stuffed nose
sneezing
runny nose
watering eyes
itchy nose
post-nasal drip
headache
sleep loss
facial pain
loss of smell
ear symptoms
daily few days/week few days/month
Concomitant treatment in 6829 Canadians with SAR at baseline
Keith PK et al. Clin Ther 2007
30 352520151050% of patients
INS
Oral nonsedating antihistamine
Ophthalmic drugs
Immunotherapy
Oral sedating antihistamineTopical nasal decongestant
Oral nasal decongestant
Intranasal antihistamine
Oral corticosteroid
Cromolyn
Intranasal anticholinergic
INS, intranasal corticosteroid; SAR, seasonal allergic rhinitis
Visits for allergic rhinitis are infrequent
44% >1yearor never
12%13% 13%
16%
29%
15%
Past month Past 3 months Past 6 months Past 12 months Greater than 1 year ago Never
DISCUSSED ALLERGY WITH PHYSICIAN
Q11: When was the last time you discussed your allergies and/or allergy medication(s) with your physician?
Most patient’s symptoms are not at least mostly controlled
9%
16%
34%
37%
4%
Not at all A little Somewhat Mostly Fully
SYMPTOMS CONTROLLED
Q3: How well do you consider your allergy symptoms controlled?
Most patient’s symptoms are not at least mostly controlled
9%
16%
34%
37%
4%
Not at all A little Somewhat Mostly Fully
SYMPTOMS CONTROLLED
Q3: How well do you consider your allergy symptoms controlled?
59% not controlled
Impact of allergic rhinitis on patients’ daily life
1. Scadding G et al. EAACI 2007, Abstract 1408. 2. Reilly MC et al. Clin Drug Invest 1996;11:278–88. 3. Tanner LA et al. Am J Manag Care 1999;5(Suppl 4):S235–S247. 4. Blanc PD et al. J Clin Epidemiol 2001;54:610–18. 5. Juniper EF et al. J Allergy Clin Immunol 1994;93:413–23. 6. Marshall PS, Colon EA. Ann Allergy 1993;71:251–8.
SLEEP AND TIREDNESS• 46% of patients feel tired1
• 77% of patients have trouble falling asleep1
WORK AND SCHOOL PRODUCTIVITY
• ≤90% effectiveness at work4
• 93% impaired classroom performance3,5
EMBARRASSMENT• Adolescents embarrassed to
use inhalers6
Impact ofallergicrhinitis
DAILY ACTIVITIESIMPAIRED2,3
LEARNING AND COGNITIVEFUNCTIONS DISTURBED6
True or false?
l Asthma is more common in the population than allergic rhinitis
• Up to 40% of patients
with allergic rhinitis also
have asthma
• Up to 94% of patients
with allergic asthma also
have allergic rhinitis
AR-Asthma relationship
Allergic rhinitisalone
AR+
asthmaAsthma alone
True or false?
l Asthma is more common in the population than allergic rhinitis
FALSE
Risk of developing asthma over time
Shaaban R et al Lancet 2008; 372: 1049–57
First Line Therapies for Patients with Allergic Rhinitis and Asthma
Leukotriene receptor antagonists
Topical Corticosteroids
(nasal and pulmonary)
Adapted from Corren J AAAAI 2006
Anthistamines
INS vs LTRA vs LTRA+AH vs placebo started prior to season
Pullerits T et al. JACI 2002;109:949-55
FPANS= intranasal steroid, ML= LTRA, LT= antihistamine
Pullerits T et al. JACI 2002;109:949-55
Copyright ©1998 BMJ Publishing Group Ltd.
Weiner, J. M et al. BMJ 1998;317:1624-1629
Intranasal steroids vs oral antihistamines
Treatment of Allergic Rhinitis
Class IMild /
intermittent
Class IIModerate/intermittent
Moderate-severe / intermittent
Severe/ intermittent
Mild / persistent
Class III
Moderate / persistent
Class IVModerate – severe /
persistent
Severe/persistent
Surgery
Immunotherapy
Oral steroids
LTRAs
Intranasal corticosteroids
Oral H1 antihistamines
Allergen / irritant avoidanceSmall et al. J Otolaryngol. 2007
Strength of evidence for treatment of rhinitisARIA update 2007
intervention SAR PAR Persistent adult child adult child rhinitis
oral anti-H1 A A A A A
intranasal CS A A A A A**
intranasal chromone A A A A
anti-leukotriene A A A A**
Anti-IgE mab A A A A A**
Subcutaneous IT A A A A A**
Allergen avoidance D D A* B*
* Not effective in general population
** extrapolated from studies in PAR/SAR
Mea
n c
han
ge
in p
atie
nt-
rep
ort
ed n
asal
co
ng
esti
on
sc
ore
fro
m b
asel
ine
(%)
Days
1-15 16-30 31-45 46-60 61-75 76-90
Mandl et al. Ann Allergy Asthma Immunol. 1997;79:370.
Moderate to severe perennial allergic
Mean % Reduction in Patient-Rated Congestion* From Baseline
EndpointBaseline
† †
†
†
†
†
†
†
†
†
†
†
†
†
†
Mometasone
Growth in children with perennial allergic rhinitis taking nasal mometasone furoate
Mometasone 100 µg/day
Placebo
Month*p=0.02 (6.9 cm vs 6.3 cm)
Schenkel et al. Pediatrics 2000;105:E22
Mean change in height from baseline (mm)
*
Nasal Biopsies
Long-term treatment with mometasone:No evidence of nasal atrophy
Minshall et al. Otolaryngol Head Neck Surg. 1998;118:648.
Before mometasone treatment: After 12 Months of mometasone 200 µg/day treatment:
Disruption of epithelium
Eosinophil infiltration
Epithelium intact
No eosinophil infiltration
Pharmacologic management of mucosal congestion
Allergic Rhinitis Nasal Polyps
Acute Rhinosinusitis
Mucosal Congestion2 sprays OD 2 sprays BID
2-4 sprays BID
First and Second Line Therapies for Patients with Allergic Rhinitis and Asthma
Leukotriene receptor antagonist
Topical Corticosteroids
(nasal and pulmonary)
Anthistamines
Anti-IgE Immunotherapy
Immunotherapy(high dose Ag)
Th1
IFNg
IgG
Tr
IL-10 TGF-b
IgG4 IgA
APC
Natural exposure (low dose Ag) + IgE
Th2
B cell
Eosinophil
IgE
IL-4
IL-5
Allergy(-)
(-)
Robinson DS, Larche ML and Durham SR. J Clin Invest 2004; 114: 1389-97
SLIT = sublingual immuntherapy
SLIT for asthma, rhinitis, and conjunctivitis symptoms adults and
children
Calamita Z et al. Allergy 2006;61:1162
165
119
65
51
28
0
20
40
60
80
100
120
140
160
180
Respiratoryinfections
Hypertension Disorders oflipid
metabolism
Diabetesmellitus
Depressivedisorder
Source: Verispan PDDA 2004
Num
ber o
f com
mon
offi
ce
visi
ts (m
illio
ns)
Respiratory infections are the # 1 reason for physician office visits
1.9 Million patient visits (96.6% treated with drugs)
MAT Dec 2008 IMS CDTI
1.4 Million patient visits (80.1% treated with drugs)
Therapeutic Profile
Acute Sinusitis Chronic Sinusitis
NIS MT4%
Other21%
NIS Adjunct
18%
Antibiotics54%
Nasal Steroids
23%
Other17%
Antibiotics60%
Untreated3%
Macrolide-resistant Pneumococci: Canadian Bacterial Surveillance Network, 1988-
2008
0
5
10
15
20
25
Per
cent
age
of I
sola
tes
Res
ista
nt t
oE
ryth
rom
ycin
1988
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
Canadian Bacterial Surveillance Network, Feb 2009
Rates of Penicillin and Amoxicillin Resistance Canada: 1988-2008
0
1
2
3
4
5
6
7
8% Penicillin Resistance% Amoxicillin Resistance
Canadian Bacterial Surveillance Network, March 2008
Figure 2 Kaplan Meier curves presenting the probability of asthma hospitalization in 30,675 children from the DNBC, who were exposed to maternal use of antibiotic for nonrespiratory infection during pregnancy (N=162) versus children who were not exposed to maternal antibiotic use during pregnancy (N = 1036).
Use of Antibiotics during Pregnancy Increases the Risk of Asthma in Early Childhood
Graff L et al. The Journal of Pediatrics 2012; Nov 6. pii: S0022-3476(12)01141-9
Figure 3 Asthma hospitalization in children from the DNBC presented in a dose-response curve per number of antibiotic prescriptions for nonrespiratory infection the mother received during pregnancy. The risk of asthma increased significantly with increasing number of prescriptions analyzed as a continuous variable, adjusted P value =.01. Number of prescriptions in each category: 27 244 (88.8%) mothers had no prescriptions in pregnancy, 2608 (8.5%) had 1 prescription, 569 (1.9%) had 2 prescriptions, 160 (0.5%) had 3 prescriptions, and 99 (0.3%) mothers had ≥4 prescriptions. Upright bars represent the HR estimates and 95% CI.
Use of Antibiotics during Pregnancy Increases the Risk of Asthma in Early Childhood
Graff L et al. The Journal of Pediatrics 2012; Nov 6. pii: S0022-3476(12)01141-9
Fig 1 Predicted probability of sensitization with 95% CIs by urinary triclosan levels. A, Aeroallergen sensitization for all subjects. B, Food sensitization for male and female subjects .
Savage JH et al. JACI 130;2012;453
Urinary levels of triclosan and parabens are associated with aeroallergen and food sensitization
Primary Efficacy Endpoint: Mean Change in Daily Mean Symptom Score
-5.5
-5
-4.5
-4
-3.5
-3
-2.5
-2
-1.5
-1
-0.5
0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 EP
Mea
n C
han
ge
in D
aily
MS
S
DAYS
placebo
FF 110mcg QD
FF 110mcg BID
Keith PK et al. Prim Care Resp J 2012
Role of vitamin D?
67Camargo CA JACI 2007;120:131-6
Role of vitamin D?
Risk of recurrent wheeze
68Camargo CA et al Am J Clin Nutr 2007;85:788 –95
Vitamin D and s-IgE levels vs season
69Hollams EM et al. ERJ Express. May 12, 2011
Risk of atopy – positive relationship only in males 6-14 yo
70Hollams EM et al. ERJ Express. May 12, 2011
Vitamin D supplementation in children 5 to 18 years old may prevent asthma exacerbations
71Majak P et al JACI 2011 May;127(5):1294-6.
ACE inhibitor angioedema
ACE inhibitor use in Canada
Total volume of prescriptions dispensed from Canadian pharmacies for 1 year ending October 2010 (+ compared to year ending October 2009
Total Scripts Change1. Atorvastatin 15,768,000
+2.7%2. Levothyroxine 14,964,000
+5.1%3. Metformin 10,637,000
+8.4%4. Ramipril 9,349,000 -
1.6%47. Perindopril 2,690,000
+17.3%
( IMS Brogan, Canadian Compuscript)
TRUE or FALSE?
1. Intranasal steroids are first line for the treatment of rhinitis when moderate congestion is present TRUE
2. Exposure to hand sanitizer is associate with increased rate of allergen sensitization TRUE
3. Allergy specific IgE levels go up as you Vitamin D levels go down TRUE
Allergies and Asthma
Paul Keith MD MSc FRCPC
McMaster UniversityPresident, Canadian Society of Allergy and Clinical Immunology