Role of Allergy in Severe Asthma
Harold Kim MD, FRCPC Kitchener, ON
Overview Allergy in asthma Environmental control in asthma Specific allergy treatment in asthma
Key Components of the Allergic Asthma Cascade Allergen TLR4
Mucus EpC
GM CSF TSLP IL-25 IL-33
IL-13 CD4*
Th2
APC MHC II:TCR
IL-4
B cell
IL-5
Eosinophilia
Fcﾔ然I
Mast cell Histamines, eicosanoids, cytokines Chemokines, enzymes, growth factors
Allergic Asthma Adapted from Murdoch JR, et al: Mutat Res 2010;690(1-2):24-39.
Important Allergens in Asthma/AR Pollens(cross reacting, geography) Moulds(as many as possible) Cat, Dog, and other animals House dust mite Cockroach Latex Occupational
Allergic Rhinitis and Asthma: Possible Interactive Mechanisms Aspiration of inflammatory secretions from the upper airway into the lower airway
Nasobronchial reflex
Shift from nasal to mouth breathing
Systemic mediation of nasal and lower-airway inflammation
Adapted from Togias A. Allergy 1999; 54:94-105
Treatment of allergic rhinitis with INS in patients with Mild asthma:effect on lower airway responsiveness (n=21 RCT cross-over)
JACI 93;91:97
JACI 2002;109:636
“Three main features must be considered in the diagnosis of asthma: symptoms, variable airflow obstruction and airway inflammation. Airway inflammation is not yet readily tested in routine clinical practice and will not be considered further here. However, skin testing may be an adjunct to diagnosis ….”
Canadian Asthma Guidelines
Skin testing
Most rapid, sensitive and cost-effective testing method in allergic disease
JACI 2005;116:744
Relations of BHR to allergy skin test reactivity,lung function,respiratory symptoms and the diagnoses in 13-year-old New Zealand children JACI 95;95:548
720 caucasion children from Dunedin, New Zealand Skin tested to 11 common allergens MC performed Compared results of skin tests to MC results 11 skin tests performed Mite,cat,dog,Aspergillus fumigatus identified as important
Relations of BHR to allergy skin test reactivity,lung function,respiratory symptoms and the diagnoses in 13-year-old New Zealand children JACI 95;95:548
ST total(mm) for DM,cat,dog,asper
Lancet 2006;368:763
Skin testing in Asthma/Allergy Support the diagnosis Identify specific allergens for avoidance Identify pet allergy before recommending pet removal Prognosis especially in children Identify specific allergens for immunotherapy *Performed by specialist trained in methods and inpretation of the test results
Hollister-Stier Prick Lancetter
1 cm
Overview Allergy in asthma Environmental control in asthma Specific allergy treatment in asthma
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125 household allergen reduction and 122 sham randomized intervention reduced all measured allergens Cat, dog, dust mites Intervention group slight decrease in medication No other measures different
Environment Indoor Allergens Outdoor Allergens Indoor Pollutants Outdoor Pollutants Occupational Exposures Food and Food Additives(Sulfites) Drugs (beta blockers,NSAIDs) Emotional Stress
Environment Allergens Dust mite Pets Cockroach Moulds
Smoke
Dermatophagoides Farinae
Levels Dust Mite Antigen 100
10 Der p I ug/g dust 1
0.1 Living Room
Bedroom
Mattress
NEJM 1990 323:503
Eliminating Dust Mite
Mean Percentage Mites Killed at Water Temperatures Ranging from 15 - 55 Degrees Celsius JACI 1992 90:599
Airborne Particles - Mites
Settling of Mite After Changing Bedding Based on Particle Size
JACI 1985 76:224
Avoidance dust mites Barrier Furnishings Temperature (heat and cold) Humidity Chemicals
Asthmatics and Dust Mite Free Bedrooms
% Days
Pediatrics 1983 71:418
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Children 5-18 years old admitted to hospital asthma No knowledge sensitization or exposure 13 active and 10 placebo Encase mattress, box springs, pillows, hot water wash, no carpet 3% tannic acid Placebo covers, cold water wash, water spray Active group improved PEFR, but no difference FEV1, MC
Pet Allergens
“Acquiring a dog may be the only opportunity a human ever has to choose a relative� Mordecai Siegal
- Labradoodle, poodle, Spanish waterdon, airedale terrier - Vs. Labrador and others
Airborne Particles - Cat
Settling of Cat Particles After Changing Bedding Cat Slept On.
JACI 1985 76:224
Cat Removal and Time to Clearance of Allergen Wood JACI 1989;83:730-34
Airborne Fel d 1 Produced by the Cat Entering a Room Unrestrained, wrapped in Plastic or after Washing DeBlay Am Rev Resp Dis 1991;143:1334
A Novel Method of Decreasing Cat Allergen
Holiday
Pumpkin
Allergy 2000;55:570
Air Filtration units in Homes with Cats
CEA 2003;33:765
Cockroach particularly urban 36% asthmatic children in US 50% were exposed in studies Studies on extermination early
THE ROLE OF COCKROACH ALLERGY AND EXPOSURE TO COCKROACH ALLERGEN IN CAUSING MORBIDITY AMONG INNER-CITY CHILDREN WITH ASTHMA (n=476)
NEJM 1997:336:1356
Severe Asthma and Mould
Jan Feb Mar Apr May June July Aug Sep Oct Nov Dec Alternaria Season Timing of Episodes of Respiratory Arrest in Young Patients with Asthma. Each Circle Corresponds to One Episode.
NEJM 1991 324:359
Clues to Indoor Mould Allergy Symptoms are perennial Worse indoors Can smell or see moulds
Mould Elimination Adequately filter outdoor air Eliminate dampness and leaks Remove damaged materials Clean with dilute bleach Respiratory protection while disturbing fungal growth
Smoking Impairs the Therapeutic Response to Oral Steroids
N=14
N=10
N=26
AJRCCM 2003;168:1308
Effects of Smoking Cessation in Asthma
AJRCCM 2006;174:127
AJRCCM 2006;174:127
Home-based Environmental Intervention in Urban Childhood Asthma
NEJM Sept 9, 2004
Overview Allergy in asthma Environmental control in asthma Specific allergy treatment in asthma
Xolair Indication Canada “Xolair has been approved…treatment of adults and adolescents with moderate-to-severe persistent asthma who have a positive skin test or in vitro reactivity to a perennial allergen and whose symptoms are inadequately controlled with ICS.”
ASA Allergy 55 yo female Severe persisting asthma 9 years on budesonide/formoterol, mometasone, montelukast Nasal polyps 15 years Advil caused severe asthma requiring intubation ASA caused severe asthma Should we give her ASA?
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RCT 31 pts with DF AR +/- asthma 70 mcg, 1 mcg DF vs placebo over 12-18 months No severe reactions High dose group improve BHR threshold to allergen challenge
JAMA April 2016
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834 adults with asthma poorly controlled on ICS or combo DM allergic rhinitis FEV1 > 70% 6 SQ, 12 SQ vs Placebo Efficacy assessed last 6 months of trial when ICS halved and then withdrawn Primary outcome time to first exacerbation
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51 HDM sensitive pts with mild to moderate asthma randomized SCIT, SLIT, SCIT+SCIT, medication 1,4,12,18 month assessments In SCIT and SCIT+SLIT groups, decreased asthma attacks, ICS VAS better only in the SCIT+SLIT group SCIT, SLIT groups Increased TH1 cytokines Novel approach to treatment
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Multicenter RCT Omalizumab or placebo followed by SCIT to cat,dog,DM 4 week 18 injection cluster regimen To assess efficacy and safety 248 randomized pts Omalizumab pts fewer systemic reactions and more likely to reach the final dose of IT
Close Asthmatics are typically allergic Avoidance measures might help Specific allergy treatment might be helpful in asthma Must be cautious with immunotherapy and asthma