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Common Pitfalls in Allergy. Prof. Kiat Ruxrungtham, M.D. Head, Division of Allergy and Clinical Immunology Department of Medicine Faculty of Medicine Chulalongkorn University. Epidemiology of Allergic Diseases in Thai Children. AllergyChula. Epidemiology of Allergic Rhinitis in Thai Adults.
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Common Pitfalls in Allergy Prof. Kiat Ruxrungtham, M.D. Head, Division of Allergy and Clinical ImmunologyDepartment of MedicineFaculty of MedicineChulalongkorn University
Epidemiology of Allergic Diseasesin Thai Children AllergyChula
Epidemiology of Allergic Rhinitisin Thai Adults AllergyChula
Allergic Rhinitis:The General Perception • Common disease • Easy to Diagnose • Easy to treat “This is partially true”
Common Pitfalls inManaging Allergic Rhinitis • Underdiagnosis • Undertreatment
PAR versus SAR Characteristic Seasonal Perennial Secretion +++ (watery) + /++ Seromucous, Post nasal drip Sneezing +++ + /++ Obstruction + /+++++ predominant Anosmia 0 /+ +/ ++ Eye symptoms +++ 0/+ Asthma 0/++ ++ Sinusitis + ++ Van Cauwenberge P et al Allergy 2000 AllergyChula
Clinical Patterns of PAR • Classic Type: Runner/Sneezer <10% • Blocker Type 30 % • Combined Type 50 % • Under diagnosed Type: ~20 % Chronic cough Post-nasal drip, throat clearing symptoms Chronic headache Shortness of breath or mouth breathing Vertigo, Epistaxis Problems in sleep, sleepiness during the day Snoring Hyperventilation syndrome AllergyChula
Nasal Blockage Allergy Chula 1999
Symptoms of Unrecognized Chronic Nasal Blockage Chronic Cough Postnasal drip, +/- BHR Paranasal sinsuses obstruction Chronic Headache Postnasal drip Throat clearing S/S Unregnized Nasal Blockage Severe obstruction Mouth breathing Dry mouth, stomatitis Aggravating asthma Difficulty in Breathing Vertigo ET dysfucntion Snoring or problem in sleeping AllergyChula
FUNCTION Airway: upper airway Olfaction Filtration Mucociliary transport Airconditioning Control of middlle ear pressure DYSFUNCTION Blockage, mouth breathing Anosmia Cough, infection Cough, infection Headache, Sinusitis Eustachian tube dysfunction, vertigo Functions of the Nose AllergyChula
The link : Noses, Eyes, Ears, and Sinuses
Common Pitfalls in Diagnosis of RhinitisCommonlyUnrecognised Symptoms • Chronic cough(including nocturnal cough) • The most common cause is rhinitis, not bronchitis • Mechanisms: post-nasal drip (PNDS), rhinitis with BHR • Shortness of Breath(requires mouth breathing) • “Inadequate air”, relieve by mouthing breathing, some may have “carpo-pedal spasm” due to hyperventilation ~ can be miss-Dx as anxeity neurosis. Mechanism: Severe nasal obstruction • Chronic headache(frontal, periorbital, paranasal) • Rhinitis +/- sinusitis is also a common cause of headache • Mechanisms: severe nasal congestion, sinus congestion, sinusitis • Vertigo/dizziness(Eustachian tube dysfunction) • Post-nasal drip Throat clearing, hoarseness of voice AllergyChula
Infra-orbital Edema and Discoloration Allergic Shiner Ocular pruritus Increased lacrimation
Mouth Breathing • Will lead to • Dry mouth • Stomatitis • Dental malocclusion Indicating Severe Nasal Obstruction
Phenomenon After Allergen Exposure:Immediate, Late Phase Allergic Reactions and Hyperreactivity Nasal Symptoms Nasal Hyperresponsiveness Late phase Immediate phase Antigen minutes 1 2 3 4 5 6 7 8 9 10 -hrs//------days Time after Allergen Challenge
Treatment of allergic rhinitis (ARIA) Allergic rhinitis and its impact on asthma >4 days /wk >4 wk/yr <4 days /wk <4 wk /yr Impaired QOL Moderate severe persistent Mild persistent Moderate severe intermittent Mild intermittent Intra-nasal steroid local cromone Antihistamines : oral or local non-sedative H1-blocker Intra-nasal decongestant (<10 days) or oral decongestant Allergen and irritant avoidance immunotherapy
Treatment of Allergic Rhinitis in Adults Van Cauwenberge P et al Allergy 2000
Sites of Action of Corticosteroids Scadding GK. Allergy 2000 Corrigan CJ. 1999 Epithelium ICAM-1 PGE2, PGF2a endothelin, NO Fibroblast GM-CSF, G-CSF IL-6, RANTES, Eotaxin, etc SCF Mo, DC TNFa, IL-1 Mast cell T cell Th2 IL-2 IL-3 Myeloid precursor B Cell IL-5 IL-4 Th2 IL-3, 5 IL-5 Endothelium Basophil VCAM-1 permeability LTC4, histamine Eosinophil AllergyChula
Meta-analysis of Intranasal Steroids Favors Steroid AllergyChula
Pitfalls in prescribing of the 1st, 2nd and 3rd generation antihistamines
Impact of Sedating Antihistamines on Safety and Productivity Kay GG, Quig ME. Allergy Asthma Proc 2001 • Sedating antihistamines remains commonly use • Patients taking these agents frequently don’t feel sleepy, but their brain function impaired • Frequently found to be a causal factor in: • Work-related injuries • fatal traffic accidents • aviation fatalities
Antihistamines in Elderly • Drawsiness, fatigue and may increase risk falling or accident • The first-generation H1 antagonist should be avoided in patient with glaucoma • The first-generation H1 antagonist should also be avoided in patient with prostrate hypertrophy • Be aware of cardiotoxic risk; terfenadine, astemizole should be used with caution AllergyChula
Common Cold: Antihistamines ? • Only 1st generation but not the 2nd generation antihistamines is effective on treating clinical symptoms and signs of “COMMON COLD” • Confirmed both in the natural or experimental “COLDs” Muether PS Clin Infect Dis 2001 Nov; 33:1483-8 AllergyChula
Clinical Uses of H1 Antagonists Generation of Antihistamines Clinical First Second and Third Allergic Rhinitis ++ ++ (better compliance) Urticaria ++ ++ (better compliance) Atopic dermatitis ++/+++ ++ (better compliance) Asthma - -/++(Meta-analysis= NS)URI/NAR ++ - Itching dermatosis ++/+++ ++ Anti-motion sickness ++ - Antiemetic ++ - Appetite stimulation ++ -(+ for astemizole) Insomnia ++ - AllergyChula
PAR and Rhinosinusitis Concordance of Allergy and Sinusitis 25-70 % Rachelefsky GS et al JACI 1978 Shapiro GG Ped Infect Dis J 1985
The Respiratory Tract • Upper Respiratory Tract • Structures - Nose —> trachea • - Sinuses, eustachian tubes • - Ciliated mucosal lining • Functions • - Conditioning the air • - Defense • Filtration • Inflammatory reaction • Immune reaction • - Smell • - Voice The Link • Lower Respiratory Tract • Structures • - Trachea —> alveoli • Functions • - Inhalation-exhalation • - Gas exchange • - Acid-base balance
How to Avoid • Underdiagnosis of AR • Be aware of non-nasal symptoms or the underrecognized symptoms • Undertreatment of AR • Chronic moderate/severe cases required nasal steroid therapy not antihistamines PAR is easy to diagnose and easy to treat, if we really know about it
ASTHMA Common Pitfalls
Asthma: Risk Factors 5q: IL4, CD14, B2ADR 6p: DRB1, TNF 11q: FCERB1, CC16 16p: IL4RA Environmental Genetic ~19 genes Aeroallergens Pollutants Triggers ~5 % in Adults 13 % in Children Clinical Asthma Thailand AllergyChula
Asthma 2002 Airway Inflammation Smooth Muscle Dysfunction Airway Remodeling
Normal Asthma Barnes PJ 1999
Early and Late Phase Allergic Reactions (EPAR and LPAR) FEV1 BHR mins 1 2 3 4 5 6 7 8 9 10 -hrs//------days Time after Allergen Challenge Antigen AllergyChula
Pitfalls in Asthma Diagnosis • Over diagnosis • Shortness of breath is not always caused by asthma • diagnose COPD as asthma • Under diagnosis • mild asthma • nocturnal asthma
Classification of Severity CLASSIFY SEVERITY Clinical Features Before Treatment Nocturnal Symptoms FEV1 or PEF Symptoms Continuous Limited physical activity STEP 4 Severe Persistent < 60% predicted Variability > 30% Frequent 60 - 80% predicted Variability > 30% STEP 3 Moderate Persistent Daily Attacks affect activity > 1 time week > 80% predicted Variability 20 - 30% > 2 times a month STEP 2 Mild Persistent > 1 time a week but < 1 time a day < 1 time a week Asymptomatic and normal PEF between attacks STEP 1 Intermittent > 80% predicted Variability < 20% > 2 times a month The presence of one feature of severity is sufficient to place patient in that category.
Part 4: Long-term Asthma Management : GINA 2002 Stepwise Approach to Asthma Therapy - Adults Outcome: BestPossible Results Outcome: Asthma Control • Controller: • Daily inhaled corticosteroid • Daily long –acting inhaled β2-agonist • plus (if needed) • When asthma is controlled, reduce therapy • Monitor • Controller: • Daily inhaled corticosteroid • Daily long-acting inhaled β2-agonist • Controller: • Daily inhaled corticosteroid Controller: None -Theophylline-SR -Leukotriene -Long-acting inhaled β2- agonist -Oral corticosteroid Reliever: Rapid-acting inhaled β2-agonist prn STEP 2: Mild Persistent STEP 3: Moderate Persistent STEP 4: Severe Persistent STEP 1: Intermittent STEP Down Alternative controller and reliever medications may be considered (see text).
The Guidelines : not well implemented 48 yo female, with chronic persistent asthma for 3 years • Recently, she has asthmatic attack everyday including at night for 6 months. • She has been seeking treatment from at least 2 hospitals. The main prescriptions included slow-released theophylline and inhaled b-2 agonist as needed. • The severity of her asthma became more and so severe that she had to miss several working days a week. • She was eventually forced to leave the job.
A Case Study (2) • Baseline PEFR=150 and 180 L/min, pre and post b-2 agonist, respectively. • After 2 weeks of a short course prednisolone followed by inhaled corticosteroids plus inhaled long-acting b-2 agonist PEFR = 360 L/min. • Her QOL has returned to normal. • Unfortunately, however, she has lost her job. AllergyChula
Asthma: A Highly Variable Disease Infection AR Avoidance Sinusitis Allergens Treatment Airway Inflammation Adherence Pollutants AHR Variable Asthmatic Symptoms Genetics Smooth Muscle Dysfunction Airway Remodeling Reversible Airway Obstruction • Intermittent • Persistent • Mild • Moderate • Severe • Irreversibility Drugs Psychological ASA/NSAIDS Cold air Excercise Treating Asthma: Individualized and Dynamics Approach
Peak Flow Meter Male : >500 L/min Female : >400 L/min
Case Study 1: PM, age 44(cont’d) Variation of Clinical symptoms and PEF LABA/ICS LABA/ICS Lost FU Sinusitis Sinusitis Sinusitis
Case Study 2: VN, Male age 60 Known of Asthma for 30 years, non-smoker Variation of Clinical symptoms and PEF LABA/ICS LABA/ICS Non-adherence worsening AR Lost FU Lost FU
Case Study 3: PK, male age 35 Known of Mild Persistent Asthma and AR since 17 y-o Variation of Clinical symptoms and PEF Treated Asthma ICS Started Treating AR only
Pitfalls in Asthma managementUndertreatment with inhaled corticosteroids even in developed countries
Comparable Asthma Severity in the Study Populations AIRE AIA Moderate Moderate Intermittent Intermittent Severity classified by NIH Symptom Severity Index AllergyChula
AIRE : Anti-inflammatory uses N=2803 in 7 European Countries AllergyChula
American: AIA Study Patients and Inhaled CorticosteroidsMedicines Used to Treat Asthma by NIH Severity Index:Inhaled Corticosteroids vs Quick-Relief Medications Base: All patients (unweighted N=2509). AllergyChula
Asian-Pacifc: AIRIAP 2001 Prevention treatment vs. Quick Relief Bronchodilators AllergyChula
Comparison of AIRE, AIA and AIRIAP AIRE : N=2803 in 7 European Countries AIA : N= 2509 in USA AIRIAP: N=3206 in 8 Asian-Pacific countries 1-2 in 10 1 in 10 3 in 10 AllergyChula