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Allergies and Asthma Paul Keith MD MSc FRCPC McMaster University President, Canadian Society of Allergy and Clinical Immunology.

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Presentation on theme: "Allergies and Asthma Paul Keith MD MSc FRCPC McMaster University President, Canadian Society of Allergy and Clinical Immunology."— Presentation transcript:

1 Allergies and Asthma Paul Keith MD MSc FRCPC McMaster University President, Canadian Society of Allergy and Clinical Immunology

2 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

3 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."

4 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

5 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

6 Inverse Relation between the Incidence of Prototypical Infectious Diseases (Panel A) and the Incidence of Immune Disorders (Panel B) from 1950 to Bach J. N Engl J Med 2002;347:

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8 Age-adjusted Australian hospital admission rates for anaphylaxis *Rate per million population Mullens RJ. Med J Aust 2007; 186 (12):

9 The atopic march

10 Baatenburg de Jong A et al. Pediatr Allergy Immunol 2009;20:735 Food Inhalant Age in yrs

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12 milia septum turrbinate

13 Asthma Before 10 Minutes After Allergen Challenge Laitinen et al. J Allergy Clin Immunol. 1992;90:32-42.

14 Eosinophilic Esophagitis

15 Allergy skin prick testing

16 IgE-dependent Release of Inflammatory Mediators Immediate Release Granule contents: Histamine, TNF- , Proteases, Heparin Over Minutes Lipid mediators: Prostaglandins Leukotrienes Over Hours Cytokine production: Specifically TNF- , IL-4, IL-13 IgE Fc  RI binding site Cell recruitment Sneezing Nasal congestion Itchy, runny nose Watery eyes Wheezing Bronchoconstriction

17 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.

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24 Mould

25 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

26 Epidemiology of allergic rhinitis in adults Bauchau V, Durham SR. Eur Respir J 2004;24:758– BelgiumFranceGermanyItalySpainUK % general population Prevalence of allergic rhinitis (AR) in European adults during 2001

27 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

28 Allergies in Canada Survey: Symptom control in worst month ( n=1001)

29 Allergies in Canada Survey: symptoms during worst month (n=1001)

30 Concomitant treatment in 6829 Canadians with SAR at baseline Keith PK et al. Clin Ther % of patients INS Oral nonsedating antihistamine Ophthalmic drugs Immunotherapy Oral sedating antihistamine Topical nasal decongestant Oral nasal decongestant Intranasal antihistamine Oral corticosteroid Cromolyn Intranasal anticholinergic INS, intranasal corticosteroid; SAR, seasonal allergic rhinitis

31 Visits for allergic rhinitis are infrequent 44% >1year or never Q11: When was the last time you discussed your allergies and/or allergy medication(s) with your physician?

32 Most patient’s symptoms are not at least mostly controlled Q3: How well do you consider your allergy symptoms controlled?

33 Most patient’s symptoms are not at least mostly controlled Q3: How well do you consider your allergy symptoms controlled? 59% not controlled

34 Impact of allergic rhinitis on patients’ daily life 1. Scadding G et al. EAACI 2007, Abstract Reilly MC et al. Clin Drug Invest 1996;11:278– Tanner LA et al. Am J Manag Care 1999;5(Suppl 4):S235–S Blanc PD et al. J Clin Epidemiol 2001;54:610– Juniper EF et al. J Allergy Clin Immunol 1994;93:413– Marshall PS, Colon EA. Ann Allergy 1993;71:251–8. SLEEP AND TIREDNESS 46% of patients feel tired 1 77% of patients have trouble falling asleep 1 WORK AND SCHOOL PRODUCTIVITY ≤90% effectiveness at work 4 93% impaired classroom performance 3,5 EMBARRASSMENT Adolescents embarrassed to use inhalers 6 Impact of allergic rhinitis DAILY ACTIVITIES IMPAIRED 2,3 LEARNING AND COGNITIVE FUNCTIONS DISTURBED 6

35 True or false? lAsthma is more common in the population than allergic rhinitis

36 Up to 40% of patients with allergic rhinitis also have asthma Up to 40% of patients with allergic rhinitis also have asthma Up to 94% of patients with allergic asthma also have allergic rhinitis Up to 94% of patients with allergic asthma also have allergic rhinitis AR-Asthma relationship Allergic rhinitis alone AR + asthma Asthma alone

37 True or false? lAsthma is more common in the population than allergic rhinitis FALSE

38 Risk of developing asthma over time Shaaban R et al Lancet 2008; 372: 1049–57

39 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

40 Copyright ©1998 BMJ Publishing Group Ltd. Weiner, J. M et al. BMJ 1998;317: Intranasal steroids vs. oral antihistamines

41 INS vs LTRA vs LTRA+AH vs placebo started prior to season Pullerits T et al. JACI 2002;109:949-55

42  FPANS= intranasal steroid, ML= LTRA, LT= antihistamine Pullerits T et al. JACI 2002;109:949-55

43 Copyright ©1998 BMJ Publishing Group Ltd. Weiner, J. M et al. BMJ 1998;317: Intranasal steroids vs oral antihistamines

44 Treatment of Allergic Rhinitis Class I Mild / intermittent Class II Moderate/intermittent Moderate-severe / intermittent Severe/ intermittent Mild / persistent Class III Moderate / persistent Class IV Moderate – severe / persistent Severe/persistent Surgery Immunotherapy Oral steroids LTRAs Intranasal corticosteroids Oral H 1 antihistamines Allergen / irritant avoidance Small et al. J Otolaryngol. 2007

45 Strength of evidence for treatment of rhinitis ARIA update 2007 intervention SAR PARPersistent adultchild adult childrhinitis oral anti-H1 A A A AA intranasal CS A A A AA** intranasal chromone A A A A anti-leukotriene A AAA** Anti-IgE mab A AA AA** Subcutaneous IT A A A AA** Allergen avoidance D D A* B* * Not effective in general population ** extrapolated from studies in PAR/SAR

46 Impact of Bronchial Allergen Challenge on Nasal Inflammation (Patients with AR and No Asthma) Adapted from Braunstahl G et al AJRCCM 2000 Bronchial Tissue (Subepithelial Layer)

47 Impact of Bronchial Allergen Challenge on Nasal Inflammation (Patients with AR and No Asthma) Adapted from Braunstahl G et al AJRCCM 2000 Nasal Tissue (Lamina Propria)

48 Nose and Sinus interaction: median levels of mediators in the maxillary sinus after allergen (solid circles, n=20) and control (open circles, n=11) challenges *p<.05 and +p<.01 versus respective diluent challenges Baroody FM et al. JACI 2008;121:

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50 Denburg, JA, Allergy, 1999 Pollen (Allergen) Lung Bone Marrow (IL-5) Nose Pollen (Allergen) Hemopoietic Signals Blood Vessels Eosinophil Progenitor Allergic Inflammation

51 Mean change in patient- reported nasal congestion score from baseline (%) Days 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

52 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) *

53 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

54 Pharmacologic management of mucosal congestion Allergic Rhinitis Nasal Polyps Acute Rhinosinusitis Mucosal Congestion 2 sprays OD 2 sprays BID 2-4 sprays BID

55 First and Second Line Therapies for Patients with Allergic Rhinitis and Asthma Leukotriene receptor antagonist Topical Corticosteroids (nasal and pulmonary) Anthistamines Anti-IgE Immunotherapy

56 (high dose Ag) Th1 IFN  IgG T r IL-10 TGF-  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:

57 SLIT = sublingual immuntherapy

58 SLIT for asthma, rhinitis, and conjunctivitis symptoms adults and children Calamita Z et al. Allergy 2006;61:1162

59 Source: Verispan PDDA 2004 Number of common office visits (millions) Respiratory infections are the # 1 reason for physician office visits

60 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 Antibiotics 54% Antibiotics 60% Untreated 3%

61 Macrolide-resistant Pneumococci: Canadian Bacterial Surveillance Network, Canadian Bacterial Surveillance Network, Feb 2009

62 Rates of Penicillin and Amoxicillin Resistance Canada: Canadian Bacterial Surveillance Network, March 2008

63 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: S (12)

64 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: (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: S (12)

65 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

66 Primary Efficacy Endpoint: Mean Change in Daily Mean Symptom Score Keith PK et al. Prim Care Resp J 2012

67 Role of vitamin D? 67 Camargo CA JACI 2007;120:131-6

68 Role of vitamin D? Risk of recurrent wheeze 68 Camargo CA et al Am J Clin Nutr 2007;85:788 –95

69 Vitamin D and s-IgE levels vs season 69 Hollams EM et al. ERJ Express. May 12, 2011

70 Risk of atopy – positive relationship only in males 6-14 yo 70 Hollams EM et al. ERJ Express. May 12, 2011

71 Vitamin D supplementation in children 5 to 18 years old may prevent asthma exacerbations 71 Majak P et al JACI 2011 May;127(5):

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73 ACE inhibitor angioedema

74 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 ScriptsChange Atorvastatin15,768, % Levothyroxine14,964, % Metformin10,637, % Ramipril9,349, % 47. Perindopril2,690, % ( IMS Brogan, Canadian Compuscript)

75 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

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77 Allergies and Asthma Paul Keith MD MSc FRCPC McMaster University President, Canadian Society of Allergy and Clinical Immunology


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