World Health Organisation Initiative. Allergic rhinitis and its impact on asthma. (ARIA). Bousquet J, van Cauwenberge P. Geneva: WHO;2000.

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2 Infectious Viral Bacterial Other infective agents Allergic Intermittent Persistent Occupational (allergic/non-allergic) Intermittent Persistent Drug-induced Aspirin Other medications Hormonal Other Causes Non-allergic rhinitis with eosinophilia syndrome Irritants Food Emotional Atrophic Gastro-oesophageal refiux Idiopathic World Health Organisation Initiative. Allergic rhinitis and its impact on asthma. (ARIA). Bousquet J, van Cauwenberge P. Geneva: WHO;2000.

3 Differential diagnosis of rhinitis Polyps Mechanical Factors Deviated septum Adenoidal hypertrophy Foreign bodies Choanal atresia Tumours Benign Malignant Granulomas Wegener's Granulomatosis Sarcoid Infectious Malignant midline destructive granuloma Ciliary defects Cerebrospinal rhinorrhoea World Health Organisation Initiative. Allergic rhinitis and its impact on asthma. (ARIA). Bousquet J, van Cauwenberge P. Geneva: WHO;2000.

4 RHINITIS? ALLERGIC INFECTIVE OTHER?

8 HISTORY SPT Healthcare worker Animal contact Baker Damp housing Small child Latex Relevant Ag Wheat, amylase Moulds Milk, egg etc

9 SKIN PRICK TEST Negative or not in agreement Positive and In agreement With history RAST Positive ALLERGY Negative or not in agreement NASAL CHALLENGE Positive Negative NO ALLERGY

10 HISTORY Occupation Drugs Endocrine Immune deficiency

11 HISTORY Occupation Endocrine Drugs Immune deficiency EXAMINATION Nasal Septum Polyps Pus Granulomas General Asthma/ bronchiectasis Auto- immunity,vasculitis Endocrine

12 TESTS Nitric oxide-low in PCD, CF, Obstruction Airway nose and lung Xrays- Sinus CT, CXR Challenge- aspirin Beta transferrin BLOOD TESTS FBC, Eosinophils, ESR Thyroid Immunoglobulins, subclasses, antibody responses Auto- antibodies, ANCA, ACE Alpha 1 antitrypsin

13 Unilateral Blood stained discharge Pain Rhinorrhoea only MSc Allergy Nasal Disease

14 Further investigation of rhinitis History + ve SPTs ve Further SPTs suggested by history e.g. latex, pet, occupational allergen ve Check for inflammation nasal smear for eosinophils ( nno may be a substitute) + ve + ve ve ALLERGIC RHINITIS + ve Nasal allergen challenge(s) (according to history) or nasal aspirin challenge Non-allergic Non-inflammatory Rhinitis (NINAR) ve? neurogenic ve Oral aspirin challenge + ve Non-allergic Rhinitis with Eosinophilia Syndrome (NARES) ve + ve ASPIRIN / NSAID SENSITIVITY

15 Possible mechanisms of non-allergic rhinitis Cold & Dry Air, Pressure, Dust, Perfume, Virus, Smoke STIMULI Mass cell degranulation (not via IgE) Mediators Epithelium Activated/Damaged Sensory Nerves Activated/Hyperresponsive Autonomic Imbalance (sympathetic/ parasympathetic) SYMPTOMS Vascular congestion, Vascular leakage, Sneeze and itch, Mucus secretion Glandular and vascular hyperresponsiveness NON-ALLERGIC RHINITIS

16 The FDA agreed with: perennial symptoms; negative allergen skin tests or RAST; negative nasal cytology for eosinophils However The FDA stated that inhaled irritants and weather/temperature changes are two distinct sets of triggers inducing different disease entities Therefore For VMR subjects should have symptoms triggered predominantly by weather/temperature changes. It is recognized that these subjects may also have inhaled or strong odors as minor triggers, but these respiratory irritants should not be the major cause of symptoms

17 Allergic Rhinitis (43%) Non-Allergic Rhinitis (23%) Mixed Rhinitis (34%)? Is there really a mixed phenotype 1000 patients from 18 USA rhinitis clinics

18 Do they represent disease models? Do they reveal phenotype differences? Are they good models to analyze sensory neuronal reflexes? Can they be used for proof of pharmacology?

Cold dry air Unilateral challenge induces bilateral secretion, reduced by topical atropine Induces nasal secretion, reduction in nasal patency, release of mast cell mediators Distinguishes NAR group

19 Cold dry air Unilateral challenge induces bilateral secretion, reduced by topical atropine Induces nasal secretion, reduction in nasal patency, release of mast cell mediators Distinguishes NAR group from control groups (?) rhinorrhea, congestion, mast cell activation, neuronal reflexes Hyperosmolar solutions Unilateral challenge induces bilateral secretions & substance P release Enhanced response observed in allergic rhinitics vs control group? Evidence for response in NAR (with chronic fatigue syndrome?): significant tonicity dependent increase in pain intensity and sensation of drip rhinorrhea, mast cell activation, neuronal reflexes

20 Histamine Induces symptoms including sneezing reflex in allergic rhinitics Does not distinguish NAR vs control group, except in group defined as runners Sneezing, secretion, increase in nasal airway resistance Capsaicin Glandular secretion & vascular leakage detected in allergic rhinitics Evidence for response in NAR patients Secretion, vascular leakage Methacholine Secretory response detected in NAR subjects defined as runners

21 NAR patients Identify disease drivers epidemiology, triggers, history, symptoms Assessment of disease SPT, nasendoscopy, CT scan, nasal lavage +-Eosinophilia Exclusion of patients with allergic rhinitis Capsaicin Challenge Cold air/hts challenge Characterise the Pathology Allergen/Irritant challenge? Vascular Dysfunction Inflammatory Cells Influx Epithelial Dysfunction Glandular Overreactivity Neuronal Dysfunction Biopsy / Lavage / scrapings Nasal/systemic biomarkers: genetics/genomics/proteomics Imaging: MRI Response to available drugs

Anti-allergic Effect of Bee Venom in An Allergic Rhinitis

Anti-allergic Effect of Bee Venom in An Allergic Rhinitis Dr: Magdy I. Al-Shourbagi Sharm International Hospital Allergic Rhinitis Rhinitis: Symptomatic disorder of the nose characterized by itching, nasal