David Cremonesini Specialist Paediatrician January

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David Cremonesini Specialist Paediatrician cdavid@ahdubai.com January 1 2015

Emma 15 years old with allergic rhinitis Dropped a grade during mock school exams Stops playing sports 2 months a year Itchy eyes, runny nose, poor sleep Previous eczema Pet dog at home Lots of runny nose over winter On regular piriton + nasal steroid How would you manage her?

What are the triggers? Does she have seasonal asthma? Trial of asthma medication Winter symptoms perennial rhinitis or viral colds? Skin prick tests / sige On a sedating antihistamine change! Is she compliant? Technique? Check prescriptions / technique

7% reported symptoms of AR 89% had asthma 44% were poly-sensitised 39% received treatment Symptoms were aggravated by 59% dust 44% grass/pollens 21% animals Winter peak season in 37%

Mechanism Scadding, GK BSACI guidelines Clinical and Experimental Allergy,2008, 38, 19 42

SYMPTOMS 2 or more for > 1 hour a day: Running Blocking Itching Sneezing AND ask about conjunctivitis

Unilateral symptoms Blood stained discharge Pain Rhinorrhoea only (ΔΔ PCD) ENT referral please!

Severity of allergic rhinitis Mild: none of the following is present Moderate-severe: at least one of the following is present Sleep disturbance Impairment of daily activities, leisure and/or sport Impairment of school or work Troublesome symptoms ARIA Guidelines 1999, 2008

Intermittent allergic rhinitis is unusual < 2yrs AR most prevalent during school age yrs Management same for children and adolescents Think of other allergic conditions Might be a cause for persistent glue ear

PREVALENCE OFALLERGIC RHINITIS AND ASTHMA Allergic Rhinitis Asthma UK Australia Canada Brazil USA South Africa Germany France Argentina Algeria China Russia UK Australia Canada Brazil USA South Africa Germany France Argentina Algeria China Russia 0 5 10 15 20 25 30 35 40 % prevalence 0 5 10 15 20 25 30 35 40 % prevalence Study of worldwide prevalence of atopic diseases in 463,801 children 13 14 years of age. Children self-reported symptoms over 12 months using questionnaires. Adapted from the International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee. Lancet 1998;351:1225-1232.

Asthma prevalence is increased in allergic and non-allergic rhinitis Rhinitis is almost always present in asthma (70-80%) Rhinitis - increased risk of developing asthma Many patients with allergic rhinitis have nonspecific bronchial hyperreactivity (perennial or seasonal) Higher medical costs in those with both (46%)

Reduction of ER visits OR 0.5 1 Reduction of hospitalization 61% 2 Reduction of both 3 1. Adams et al JACI 2002 2. Crystal-Peters JACI 2002 3. Corren JACI 2004

School performance 1834 students sitting national examinations Cases: dropped 1 or more grades in core subject from winter mocks to summer finals Cases (vs. controls)significantly more likely to have AR symptoms (OR 1.4; 95% CI, 1.1-1.8; p= 0.002), taken any allergic rhinitis medication (OR, 1.4; 95% CI, 1.1-1.7; p=0.01) taken sedating antihistamines (OR, 1.7; 95% CI, 1.1-2.8; p=0.03) Walker J Allergy Clin Immunol 2007;120:381-7

Complications of allergic rhinitis may include: Sleep disturbance Daytime tiredness Headaches Poor concentration Recurrent ear infections in children Recurrent sinus infections in adults Asthma which is more difficult to control

Prevalence Co-morbidities Complications Quality of Life Costs

Diagnosis History Examination Allergy tests skin prick or sige TREATMENT

Worst symptoms in order Past history? When? Previous atopy? Where? Family History? What increases them? Social history? Damp house? Associated symptoms? What decreases them? Treatment? School/work, hobbies, food, medication, reactions, smoking Asthma???

Allergic salute Allergic shiner

Atopic children are sensitised to allergens present in their local environment Grass pollen HDM Tree pollen Cat Alternaria Horse Dog 377 children aged 6-18 years Leech 2001

History key any test might just show sensitisation so corroborate history House dust mite Grass pollen May to August Tree Pollen Feb - June Cat Dog Moulds Should diagnose 90% of allergy component

Allergen avoidance Pharmacotherapy Immunotherapy RARELY surgery Education, Education, Education Nature of disease, need for long term treatment, how to use it, possible SEs and avoidance measures www.whiar.org

House dust mite allergy House Dust Mite

House dust mite allergy House Dust Mite Small 0.3mm Feed on human skin scales Ideal habitat: 80% humidity; 25oC Carpets, mattresses, pillows, bedcovers, soft furnishings Allergen: Der p1 gut protein in fecal pellets

HDM is the most common allergen No easy way of removing it There is no vacuum cleaner, dust mite spray or dry cleaning that will completely eliminate it The first room tackle is the bedroom and in particular the bedding Single measures do not usually lead to benefit

Bedding

Mattress protectors reduce house dust mite exposure but may not improve symptoms Mattress encasements reduce mite allergen Ehnert B et al. JACI 1992;90:135-138 Owen S et al. Lancet 1990;336:449 Tovey E et al. Lancet 1993;342:126 but did not reduce symptoms or use of ICS De Vries et al. Br J Gen Pract 2007;57(536):184-190 Used alone are unlikely to prove effective Nurmatov et al. Allergy 2012 67(2):158-165

Bed linen Washing in water > 55oC removes allergen & kills HDM Cooler water removes mite allergen but doesn t kill HDM McDonald LG & Tovey ER JACI 1992;90:599-608 Tumble drying at temperatures > 55oC for > 20 minutes Owen S et al. Lancet 1990;335:396-397 Recommend weekly washing of bed linen on a hot cycle Electric blankets reduce mite growth Mosbech H et al. JACI 1988;81:706-710

Carpets Live mites difficult to remove from carpet Regular vacuum cleaning reduces mite reservoir Vacuuming creates disturbance which increases airborne mite levels but large particles settle quickly Filters / enclosed systems may reduce exposure Wet vacuum cleaning or steam cleaning has no added benefit and may increase HDM numbers Carpet shampooing may be more effective than dry vacuum cleaning de Boer R JACI 1990;86:808-814 Exposure to direct sunlight for several hours kills HDM Tovey E & Woolcock A JACI 1994;93:1072-1074

Reduce humidity - Have a dry and well ventilated house, do not dry clothes on the bedroom radiator Venetian blinds or flat blinds are easier to clean than heavy curtains. Washable curtains or external shutters another option. Expensive dehumidifiers UNPROVEN

Air filters and ionisers are ineffective HEPA air filters fail to reduce HDM levels Antonicelli L et al. Allergy 1991;46:594-600 Ionisers reduce airborne Der p 1 but didn t improve symptoms Warner JA et al. Thorax 1993;48:330-333

Stuffed animals Freezing for 24 hours kills HDM but doesn t reduce allergen Dodin A & Rak H J Med Entemol 1993;30:810-811 Remove wherever possible Keep in a toy box

Practical Dust Mite avoidance 1. 2. 3. 4. 5. 6. 7. 8. 9. Written information BSACI HDM reduction information sheet Remove carpets wooden / lino / laminate floors Vacuum carpets daily - or as often as practical Separate out bunk beds Air bedroom during the day - Open the windows - Remove duvet and hang over banister Wash bedlinen weekly at 60oC Avoid drying clothes over radiators Keep bedrooms clutter free Remove old sofas replace with leather

House dust mite avoidance measures for perennial allergic rhinitis: an updated Cochrane systematic review Nurmatov, Van Schayck, Hurwitz & Sheikh. Allergy 2012; 67:158-65 Trials are small and poor quality Interventions reducing HDM load may reduce rhinitis symptoms Acaricides are the most promising Isolated use of HDM impermeable bedding is unlikely to be effective It s time to rethink mite allergen avoidance Tovey and Marks. JACI 2011; 128:723-727 Need to tailor interventions to an individuals living situation and pattern of disease

So what should we do about the cuddly toys on her bed?...

Pets

Cats and dogs are a major source of allergens in the home. People are not allergic to an animal's hair But to an allergen found in the saliva, dander (dead skin flakes) or urine of an animal with fur Although the amount of allergen released can vary between breeds, there are no hypoallergenic breeds.

American Journal of Rhinology in 2011 Analysed dust samples from 173 homes with one dog 62 dog breeds were studied, 11 of which were hypoallergenic No differences in allergen levels between homes with hypoallergenic dogs and nonhypoallergenic ones

As allergens are stuck to the hair and skin of pets, the allergens become airborne when the pet sheds their hair. The allergens can remain airborne for some time. Cat allergen is especially difficult to remove from houses. Cat allergen can be found in places where cats have never lived. For example, it can be carried around on clothing to schools and offices.

The most effective method of allergen avoidance is removal of the pets from the home. If pets cause only minor problems, keeping pets out of bedrooms and living areas may be a compromise. Even then, it may take years after pet removal before allergen levels are reduced. The effectiveness of washing animals frequently and using HEPA air filters remains uncertain.

Cat removal Allergen levels fall slowly after cat removal Clinical benefit may not be seen for several months Wood RA et al. JACI 1989;83:730-734 Thorough and repeated cleaning is needed after cat removed Levels fall faster if carpets and upholstered furniture also removed Cat allergen may persist in mattresses for years Van der Brempt X et al. JACI 1991;87:595-596

If parents insist on keeping pets: 1. 2. 3. 4. 5. 6. 7. Restrict animal to one area of the house Keep out of bedroom HEPA or electrostatic air filters Especially in the bedroom Remove carpets and reservoirs for allergen collection Especially in bedroom Mattress and pillow covers should be used routinely Tannic acid modest reduction in cat allergen levels but effects short lived when cat is present Cat washing Transient benefit and should be done at least twice a week alongside other methods (Castrate a male / get a female)

Antihistamines help to decrease the release of histamine, possibly decreasing the symptoms of itching, sneezing, or runny nose but they are not as effective in controlling severe nasal blockage and dribble The advantage of antihistamines is their flexibility; you can take them when you have problems, and avoid them when you are well. Some benefit of taking EVERYDAY. Safe to use up to 4x standard dose in children for short periods

Corticosteroid nasal sprays help to decrease the swelling in the nose They have a potent action on inflammation when used regularly (like asthma preventer medication). They work best when used before the symptoms start, but can also be used during a flare-up Intranasal corticosteroid nasal sprays (INCS) These need to be used regularly and with careful attention to the way in which they are used

Aren t steroid sprays bad for me? No but In children who are taking multiple different steroid preparations your allergist should monitor the child s growth

Newer INS: low bioavailability Bioavailability of currently used steroid sprays Bryson HM, Faulds D. Drugs 1992;43:760 75. Daley-Yates PT, Baker RC. Br J Clin Pharmacol 2001;51:103 5. Daley-Yates PT et al. Eur J Clin Pharmacol 2004;60:265 8. Allen A et al. Clin Ther 2007;29:1415 20.

My nasal sprays don t work Are you eating the spray? Commonest reasons for nasal sprays not working are: 1. Patients expecting an instant result and giving up after a few days 2. Not washing their nose with salt water before using the spray 3. Sniffing the spray (eating it and their snot!) 4. Tipping their head back 5. Not starting treatment before the pollen season kicks in

Common errors to avoid when using a nose spray include the following: - forgetting to prime the spray device; - skipping doses - wrong head position (should be tilted forward, not back) - pushing nozzle too hard or too far into the nose; - blowing nose hard after spraying (the medicine is lost) - sniffing hard after spraying (the medicine is deposited in the throat instead of the nose) - using saline sprays or irrigations after using corticosteroid spray, instead of before

Allergen Immunotherapy Immunotherapy is an effective treatment for adults and children with severe allergic rhinitis (AR) that does not respond to conventional pharmacotherapy and allergen avoidance measures It involves giving graded increases of allergens to which the sufferer is sensitive in order to induce allergen tolerance, which may last for years following discontinuation. Immunotherapy is reserved for patients with one or two major problematical allergens and without chronic asthma

Two types SCIT SLIT

Patients insufficiently controlled by antihistamines and moderate dose of topical glucocorticosteroids. Patients who do not want to be on constant or longterm pharmacotherapy. Patients in whom pharmacotherapy induces undesirable side-effects. Patient desire for a cure.

Mild Moderate persistent asthma Well-controlled with ICS / B2 agonists/ltras PGC-Sofia-3 June 14

Adults Children & Adolescents Don't Like Sprays 20% Don't Like Spray 15% Symptoms Not Serious 20% Side Effects 12% No Symptoms Side Effects 10% 9% No Symptoms 11% Doctor Never Prescribed 7% Not Effective enough 6% Not Effective 6% Doctor Never Prescrived 6% Worried About 4% Worried About 5% Other Reasons Difficult to Use 3% 5% Difficult to Use 2% Not Sure 11% Can Not Toletate 1% 0% 10% 20% 30% Percent of Respondents 0% 10% 20% 30% Percent of Respondents Katelaris CH, Lai CKW, Rhee C-S et al. Nasal allergies in the Asian-Pacific population: Results from the Allergies in Asia-Pacific Survey. American Journal of Rhinology & Allergy 2011; 25:S3-S15

Monosensitization Monoallergy Polysensitization Polyallergy Stop Specific Immunotherapy Stop Allergic Rhinitis Allergic Asthma 77

Patients NOT eligible for SLIT Clinical relevance not proven Age <5 yr (Some studies demonstrated a good safety for children age 3-5 years) Malignant diseases Autoimmune diseases Current therapy with ß-blockers Uncontrolled asthma Pregnancy at the start of AIT Chronic mouth diseases Long-term compliance not assured

Patient selection: Moderate/severe AR affecting daily life Confirmed allergy diagnosis Adhering to maximum treatment Tried allergy avoidance Pollen induced rhinitis Animal dander / House Dust Mite allergy NO perennial asthma Advantage over subcut: Noninvasive Home delivery Much safer

2011 SLIT: most common adverse events (children & adults) - 4-2 0 2 4 The majority of reported adverse events were mild to moderate and did not require any treatment. 80

Uncommon /Rare SLIT Undesirable Effects Uncommon Rhino-conjunctivitis, asthma, urticaria Very rare Generalized urticaria, angioedema, oropharyngeal oedema, severe asthma, Anaphylactic shock (10 cases published) No fatalities

2 min under the tongue before swallowing First dose of under the supervision of the doctor : patient education and safety assessment.

Morning!! 5 min Breakfast! Staloral Special recommendations No teeth brushing (5 min before and after SLIT) No eating (5 min before and after SLIT) PGC-Sofia-3 June 14

When should Staloral administration be temporarily stopped? Dental extraction or lost (children), oral surgery or injury inducing bleeding (Stop until recovery) Fever > 38 C (until recovery) Simultaneous viral vaccination (1 day) Asthma exacerbation (until recovery) Acute gastroenteritis (until recovery) Oropharyngeal inflammation (until recovery)

50 % 70-80 % 80 % Stop Months

Start IT 3 6 9 12 16 20 24 28 32 36 4 5 6 7 8 9 10 11 12 100 80 60 40 Symptoms Medication Quality of life 20 0 80 %? Month SIT Stop Years

Acute Exacerbations/Year 39 children with asthma and rhinitis, allergic to house dust mite were treated for 3 years with HDM SLIT Before SLIT After 3 years of SLIT Complete clinical remission of asthma was recorded in 37 (95 %) patients. Similarly, complete clinical remission of allergic rhinitis was recorded in 32 (82 %) patients. No significant side effects were reported.

Di Rienzo V. et al. Clin Exp Allergy 2003; 33: 206-210 Long-lasting effect of sublingual immunotherapy in children with asthma due to house dust mite: a ten-year prospective study SLIT Follow-up after SLIT cessation 55 patients 30 patients 25 patients No SLIT (Pharmacotherapy only) 0 5 years 10 years

Asthmatic Patients 30 NS 0.001 0.001 25 20 15 T0: Baseline T5: After 5 yrs SLIT T10: 5 yrs after SLIT cessation 10 5 0 T0 T5 T10 T0 T5 T10 No SLIT SLIT After SLIT, there was a significant difference vs. baseline for the presence of asthma and the use of asthma medications, whereas no difference was observed in the control group. The mean peak expiratory flow result was significantly higher in the active group than in the control group after 10 years. Di Rienzo V. et al. Clin Exp Allergy 2003; 33: 206-10.

SLIT is effective and long-lasting treatment for pollen and Dust mite allergic rhinitis 3 years daily treatment for dust mite 3 years of 6 months treatment for pollen allergy Mild-to-moderate asthma, well controlled Need to select patient properly It s safe and can be done at home, unlike injections Needs commitment and close follow up initially as SE settle down