Latest advances in the management of childhood allergic rhinitis Jason Y K Chan Assistant Professor Department of Otorhinolaryngology, Head & Neck Surgery The Chinese University of Hong Kong
Disclosures None
Objectives Discussion of Hong Kong study on prevalence and risk factors in children and adolescents Discuss the management of primarily allergic rhinitis Discuss the challenges regarding the management of allergic rhinitis
Introduction 8 year old presents with a history of nasal congestion on most days of the year. Worse in winter Sniffing and runny nose. An episode of wheeziness and difficulty breathing a few years ago
Diagnosis Patient Presents with symptoms of Rhinitis History Physical Examination
Allergic Rhinitis
Allergic Rhinitis in Children Allergic diseases are common amongst children Significant impact of allergic rhinitis on the quality of life in Children Sleep quality Cognitive function School performance Common cause of school absence
Allergic Rhinitis and Co-morbid Airway Disease Asthma Otitis Media with Effusion Allergic Rhinitis Upper Respiratory tract infection Nasal polyposis Sinusitis
Allergic rhinitis and Quality of life with SF- 36 survey Marple et al. Otolaryngol Head Neck Surg. 2007. S107-124
Allergic Rhinitis and Quality of Life Marple et al. Otolaryngol Head Neck Surg. 2007. S107-124
Allergic Rhinitis and work productivity/school attendance Marple et al. Otolaryngol Head Neck Surg. 2007. S107-124
Study on Allergic Rhinitis in Children in Hong Kong
Allergic rhinitis data from Children in China Sparse data in China regarding allergic rhinitis in Children Last analysis a prevalence of rhinitis symptoms in the last 12 months was 35.1% noted in Hong Kong in 2001 Based on ISAAC Survey Age group 6 8 year olds
Methods Study design Stratified, clustered cross sectional survey of children aged between 8 17 years old in Hong Kong January to July 2011 13 schools selected
Methods
Methods Chinese version of The International Study of Asthma and Allergies in Childhood (ISAAC) survey was used Univariate analysis with Chi-Square for categorical data Binary logistic regression for multivariate analysis
Results Questionnaires distributed to 7223 children 6421 questionnaires returned 88.9% completion rate Further 28 (0.4%) children excluded as did not complete information regarding rhinitis symptoms in the last 12 months
Results - Prevalence Rhinitis Symptoms in last 12 Months 44% 57% Yes No
Results - Prevalence Doctor Diagnosis of Allergic Rhinitis 24% Yes No 76%
Results - Prevalence Conjunctivitis symptoms in last 12 months 38% 62% Yes No
Results Associated allergic diseases
Results Associated allergic diseases
Results Disease severity AR symptoms duration > 4 days and weeks 32% Yes No 68%
Results Quality of life AR and daily life 52% 12% 1% 3% 2% 33% Not affected Mildly affected Moderately affected Severely affected Missing
Results Quality of Sleep AR and Sleep 45% 13% 1% 4% 3% 38% Not affected Mildly affected Moderately affected Severely affected Missing
Results - Discomfort AR and discomfort 48% 17% 5% 4% 1% 30% Not affected Mildly affected Moderately affected Severely affected Missing
Results AR symptoms by month 100.00% 90.00% 80.00% 70.00% 60.00% 50.00% 40.00% 30.00% 20.00% 10.00% 0.00% AR Symptoms by month Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec
Results AR and AQHI by month 100.00% 90.00% 80.00% 70.00% 60.00% 50.00% 40.00% 30.00% 20.00% 10.00% 0.00% AR and AQHI in HK Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Percent AQHI Mean
Results Rhinitis symptoms univariate Variable Rhinitis Symptoms in the past 12 months OR 95% CI (P-value) Gender (Male/Female) 0.94 0.85 1.03 (0.20) Race (Chinese/Non Chinese) 0.67 0.41 1.12 (0.13) Breastfeeding 1.03 0.93 1.14 (0.59) Smoker at home 1.06 0.95 1.18 (0.29) Ceiling or wall mould 1.44 1.29 1.61 (<0.001) Asthma Diagnosis 2.64 2.08 3.35 (<0.001) Bronchitis Diagnosis 3.44 2.89 4.09 (<0.001) Eczema Diagosis 1.91 1.59 2.28 (<0.001) Food Allergy Diagnosis 1.97 1.61 2.42 (<0.001) Familial allergy 2.33 2.11 2.58(<0.001) Any Pets 1.19 1.05 1.35 (0.008) Obesity 0.92 0.79 1.08 (0.30) Sibling 2 0.81 0.72 0.92 (<0.001)
Results Rhinitis symptoms multivariate analysis Variable Rhinitis Symptoms in the past 12 months OR 95% CI (P-value) Gender (Male/Female) 0.92 0.82 1.02 (0.11) Age group 1.07 0.96 1.20 (0.23) Smoker at home 1.08 0.97 1.21 (0.17) Ceiling or wall mould 1.35 1.20 1.52 (<0.001) Asthma Diagnosis 1.90 1.32 2.73 (<0.001) Bronchitis Diagnosis 2.97 2.42 3.66 (<0.001) Eczema Diagosis 1.45 1.16 1.80 (<0.001) Food Allergy Diagnosis 1.72 1.32 2.23 (<0.001) Familial allergy 2.04 1.83 2.27 (<0.001) Interaction terms Any Pets 1.17 1.02 1.33 (0.03) Siblings 2 0.80 0.71 0.92 (<0.001) Asthma*bronchitis diagnosis 0.45 0.26 0.76 (0.003) Eczema*food allergy diagnosis 0.46 0.28 0.75 (0.002)
Discussion of results Previous prevalence in HK based on ISAAC survey in 2001 of 35.1% and now 57% based on question of rhinitis in the last 12 months Rhinitis is a common symptom Most patients with AR: Have intermittent symptoms Have mod-severe
Discussion of results The One Airway concept is important: 8.34% had a diagnosis of asthma 18.8% had a diagnosis of reactive airway disease 12.0% had a diagnosis of eczema 9.3% had a diagnosis of food allergies Significant association with these factors and allergic rhinitis on multivariate analysis
Discussion of results Family history of allergic disease are important Number of siblings is associated with reduced risk of allergic rhinitis No association with obesity found
Limitations Despite use of the ISAAC survey Different age groups from previous study Survey in Children is notoriously difficult No objective allergy testing performed Cross sectional survey
Conclusions Reason for increasing prevalence is unclear Further studies needed to see if this is attributed to change in outdoor environmental pollutants or indoor pollutants
Allergic Rhinitis Management
Allergic Rhinitis Lakhani N, North M, Ellis AK (2012) Clinical Manifestations of Allergic Rhinitis. J Aller Ther S5:007.doi: 10.4172/2155-6121.S5-007
ARIA Guidelines: Recommendations for Management of Allergic Rhinitis Mild intermittent Moderate severe intermittent Intranasal steroid Local cromone Second-generation nonsedating H 1 antihistamine Intranasal decongestant (<10 days) or oral decongestant Allergen and irritant avoidance Mild persistent Moderate severe persistent ARIA = Allergic Rhinitis and its Impact on Asthma. Bousquet et al. Allergy. 2003;58:192. Bousquet et al. Allergy. 2002;57:841. Immunotherapy
ARIA 2010 Guidelines: Recommendations for Management of Allergic Rhinitis Bousquet et al. ARIA. J Allergy Clin Immunol 2012
Clinical Efficacy of Various Treatments for Allergic Rhinitis: ARIA Guidelines Corticosteroids are the most effective pharmacological treatment for allergic rhinitis Intranasal agents are recommended first-line therapy when nasal congestion is a major symptom of allergic rhinitis Congestion Rhinorrhoea Itching/ Sneezing Duration Intranasal steroids +++ +++ ++/+++ 12-48h Oral antihistamines + ++ +++/++ 12-24h Oral decongestants + - -/- 3-6h Intranasal cromones + + +/+ 2-6h Anticholinergics - ++ -/- 4-12h Antileukotrienes ++ + -/- Not reported Bousquet et al. Allergy. 2003;58:192. Bousquet et al. Allergy. 2002;57:841. Van Cauwenberge et al. Allergy. 2000;55:116.
Systematic review of medications in Seasonal Allergic Rhinitis and Perennial Allergic Rhinitis Benninger et al. Ann Allergy Asthma Immunol. 2010
Antihistamines First Generation Second Generation Nasal Chlorpheniramine Cetirizine Azelastine Diphenhydramine Desloratadine Levocabastine Pheniramine Fexofenadine Olopatadine Promethazine Levocetirizine Loratadine Rupatadine No superiority of non-sedating antihistamines over each other
Intranasal Steroids: Systemic Bioavailability Dexamethasone 1 >80% Beclomethasone 2 Budesonide 3 10% 44%* Fluticasone propionate 4 <2% Fluticasone Furoate 6 <0.5% Mometasone Furoate 5 0.1% 0 20 40 60 80 100 Bioavailability (%) *1% intranasal bioavailability plus 43% systemic bioavailability from swallowed portion of intranasal administration. 1. Brannan et al. J Allergy Clin Immunol. 1996;97(pt 3):198; 2. Beconase PI. At: http://www.rxlist.com; 3. Rhinocort PI. At: http://www.az-air.com/phy_prod/rhinocort_prescribing_information.asp; 4. Flonase PI. At: http://www.flonase.com; 5. NASONEX PI. At: http://www.nasonex.com.
Clinical Considerations for intranasal steroids
Clinical Considerations: Intranasal Steroids
Intranasal Steroids are Considered the most effective drugs for both symptoms and inflammation, but..
Physician Concerns
Survey of compliance with recommendations in Mexico Linnemann et al. World Allergy Organization Journal. 2015 8(18)
Suggests need to re-inforce, educate physicians regarding safety and efficacy of intranasal steroids in allergic rhinitis
Patient Compliance
Dissatisfaction with medication and reasons requesting a change in medication prescription Meltzer et al. J Allergy Clin Immunol. 2009. 124:S43-70
Concern of effectiveness over time Effectiveness of INS over 24 hours Meltzer et al. J Allergy Clin Immunol. 2009. 124:S43-70 Effectiveness of all nasal sprays over time
Compliance based on Overall Nasal Spray Evaluation Questionnaire (ONSEQ) Stokes et al. Otolaryngol Head Neck Surg. 2004:131:225-31
Taking into consideration patient preference as an important factor in treatment compliance Consider trying different suitable intranasal steroids to suit the preferences
OTHER NOVEL DEVELOPMENTS
More Innovative ways of improving compliance with - telemonitoring Pizzuli et al. Clinical & Experimental Allergy. 2014. 44: 1246-54
More Innovative ways of improving compliance with - SMS Wang et al. Int Arch Allergy Immunol. 2014. 163:51-8
Using Mobile Apps MASK Rhinitis MASK Rhinitis (MACVIA-ARIA Sentinel NetworK for Allergic Rhinitis) App Bousqyet et al. Allergy. 2017. DOI: 10.1111/all.13125.
Immunotherapy Subcutaneous immunotherapy: Weekly injection with increasing concentrations of allergen to maintenance dose then monthly injections Maintenance for several years Proven efficacy in controlling allergic rhinitis, asthma and conjunctivitis Effect persists
Immunotherapy Sublingual immunotherapy: No direct comparison with subcutaneous therapy Indirect comparison subcutaneous more effective for symptom relief Less reports of anaphylaxis Less adherence to therapy for recommended duration than with subcutaneous therapy
Combination of Intranasal Fluticasone propionate and Intranasal Azelastine Bousquet et al. Expert Opinion on Pharmacotherapy. 2015. 16: 913-28
Comparison of Intranasal Fluticasone Furoate and Intranasal Levocabastine Murdoch et al. Clinical & Experimental Allergy. 2015. 1346-55
Future Directions
Antihistamines against H3 - receptor Leads to an increase in norepinephrine Might have an advantageous decongestant effect Clinical trials ongoing but limited data Possibility of increased side effects insomnia, headache
Immunotherapy Omalizumab Combination with SCIT had improved safety profile and better efficacy in symptom control Meta- analysis showed symptoms improvement in poorly controlled AR Recombinant allergens and synthetic peptide immunoregulatory epitopes (SPIREs) Cat allergy symptoms significantly improved Evaluating in house dust mite
Other areas of development Defining the appropriate use, timing of and duration of immunotherapy For example the Preventive Allergy Treatment Study Showed preventive effect of immunotherapy for new allergies or asthma in children with allergic rhinitis but not asthma
Thank you! Faculty of Medicine The Chinese University of Hong Kong