Feb 2014 allergy b clinical and aqhi

Allergy BClinical and AQHI

Gimli Glider Pilot School/FMPEAbbotsford/Mission & Langley/Aldergrove

19 February & 25 February 2014

Typical Presentation of Allergic Rhinoconjunctivitis in Children

Allergic Rhinitis

1. Small P, Frnkiel S, Becker A, et al. Rhinitis: A practical and comprehensive approach to assessment and therapy. Journal of Otolaryngology. 2007;36(Supl 1):S5-S27.

● The previous classification of seasonal or perennial Allergic Rhinitis is being replaced with intermittent and persistent Allergic Rhinitis1

● Intermittent episode = symptoms last <6 weeks

● Persistent episode = symptoms last >6 weeks

S O I R

Sneezing

E

Nasal Obstruction

Nasal Itch (pruritus)

Nasal Rhinorrhea

+ Itchy Watery Eyes

(conjunctivits)

Allergic Rhinitis Diagnosis: 2 or More of ‘S O I R E’ Symptoms for More Than 1 Hour on Most Days

Allergic Shiners

The Patient with Allergies”: Franzese, CB, Burkhalter, NW. “The Patient with Allergies.” Medical Clinics of North America, 2010, 94 (5), pp. 891-902

Allergic Faces

Physical Findings

When to Consider Discussing Allergen Immunotherapy With Parents or Caregivers

When to Consider Allergen Immunotherapy

Immunotherapy by allergen injections for seasonal allergic rhinitis ('hay fever')

Seasonal allergic rhinitis ('hay fever') is a global health problem and its prevalence has increased considerably in the last two decades. Treatment includes allergen avoidance, drugs such as antihistamine tablets and nasal sprays, and immunotherapy (vaccination). For those patients whose symptoms remain uncontrolled despite drug treatment, specific allergen immunotherapy (SIT) is advised.

Calderon MA, Alves B, Jacobson M, Hurwitz B, Sheikh A, Durham S. Immunotherapy by allergen injections for seasonal allergic rhinitis ('hay fever'). Cochrane Summaries. January 21, 2009 http://summaries.cochrane.org/CD001936/immunotherapy-by-allergen-injections-for-seasonal-allergic-rhinitis-hay-fever#sthash.7BSYsB2K.dpuf


Specific allergen immunotherapy is most commonly administered as subcutaneous (under the skin) injections by specialists requiring a building-up period followed by a maintenance period of 3 to 5 years. Immunotherapy may also be delivered by the oral, nasal or sublingual route and these will be studied in separate Cochrane reviews, as will immunotherapy for perennial (all year round) allergic rhinitis. In this review we aimed to evaluate the efficacy and safety of injection immunotherapy, compared with placebo, for reducing symptoms and the need for medication.



We identified randomised, double-blind, placebo controlled trials of specific allergen immunotherapy in patients with seasonal allergic rhinitis due to tree, grass or weed pollens. 51 studies satisfied our inclusion criteria. In total there were 2871 participants (1645 in the treatment groups and 1226 in the placebo), each receiving on average 18 injections. The duration of treatment varied from three days to three years.



• This review has shown that injection immunotherapy in suitably selected patients with hay fever results in significant reductions in symptom scores and medication use. Injection immunotherapy has a known and relatively low risk of severe adverse events. We found no long-term consequences from adverse events and no fatalities.





TABLE 1 | Potential mechanisms of antigen-specific therapy of allergyRudolf Valenta; Nature Reviews Immunology 2, 446-453 (June 2002); http://www.nature.com/nri/journal/v2/n6/fig_tab/nri824_F1.html

Allergy: the unmet need A blueprint for better patient care. A report of the Royal College of Physicians Working Party on the provision of allergy services in the UK. Royal College of Physicians June 2003. http://www.bsaci.org/pdf/allergy_the_unmet_need.pdf

Basic Mechanisms: Immunization Replace IgE with IgG

IgE

IgG4

Basic Mechanisms: Replace IgE with IgG

FIGURE 3 | Proposed action of prophylactic allergy vaccines.Rudolf Valenta; Nature Reviews Immunology 2, 446-453 (June 2002); http://www.nature.com/nri/journal/v2/n6/fig_tab/nri824_F1.html

Sublingual Immunotherapy for the Treatment of Allergic Rhinoconjunctivitis and Asthma

s/l pill Radulovic S, Calderon MA, Wilson D, Durham S. Sublingual immunotherapy for allergic rhinitis (including hay fever). Cochrane Summaries. February 16, 2011. : http://summaries.cochrane.org/CD002893/sublingual-immunotherapy-for-allergic-rhinitis-including-hay-fever#sthash.3xD98siS.dpuf

File:Illustration Phleum pratense0.jpg

http://en.wikipedia.org/wiki/File:Illustration_Phleum_pratense0.jpg

Product Monograph Descriptions/l tablet: 2800 BAU

Standardized Allergenic Extract, Timothy Grass (Phleum pratense) Sublingual Tablet) is an allergy immunotherapy tablet for the treatment of signs and symptoms of grass allergy.

PRODUCT MONOGRAPH: GRASTEK™ Standardized Allergenic Extract, Timothy Grass (Phleum pratense) ; Sublingual Tablet, 2800 BAU; Allergy Immunotherapy table; Submission Control No: 148335 ; Merck Canada Inc. Date of Preparation: December 12, 2013. http://www.merck.ca/assets/en/pdf/products/GRASTEK-PM_E.pdf


The active substance is a natural grass pollen extract which is purified and standardized from Timothy Grass.



It is formulated as an orally disintegrating tablet designed to rapidly dissolve under the tongue.Each sublingual tablet has a strength of 2800 BAU.


A1. Indications and Clinical Use s/l tablet: 2800 BAU

Indicated for reducing the signs and symptoms of moderate to severe seasonal Timothy and related grass pollen induced allergic rhinitis (with or without conjunctivitis) in adults and children 5 years of age and older [ages 5 to 65].


A2. Indications and Clinical Use s/l tablet: 2800 BAU

1. Confirmed by clinically relevant symptoms for at least 2 pollen seasons

2. and a positive skin prick test and/or a positive titre to Phleum pratense specific IgE;

3. and who have responded inadequately, or are intolerant to conventional pharmacotherapy.


B1. Contraindications s/l tablet: 2800 BAU

1. Are hypersensitive to any of the excipients in the formulation or component of the Container.2. Have previously had a severe systemic allergic reaction to Timothy or related grass immunotherapy.



3. Have unstable, severe chronic or severe seasonal asthma (FEV1 < 70% of predicted value after adequate pharmacologic treatment in adults; < 80% in children).


Sublingual Tablet, 2800 BAU Efficacy

• All studies included patients with concomitant asthma, but none included patients with severe or unstable asthma. Autoinjected epinephrine was provided to all patients enrolled in the US studies.

Medscape Medical News: Grastek Recommended by FDA Panel for Timothy Grass Allergy; FDA Allergenic Products Committee Meeting. December 12, 2013http://www.medscape.com/viewarticle/817771

http://www.medscape.com/news




4. Are taking β-blockers, as they can be non-responsive to beta-agonists that may be required to reverse a systemic reaction



5. Have active inflammatory conditions in the oral cavity, e.g., oral lichen planus with ulcerations, severe oral candidiasis, dental extraction


C1. Warnings and Precautions s/l tablet: 2800 BAU

Treatment with 2800 BAU should only be prescribed and initiated by physicians with adequate training and experience in the treatment of respiratory allergic diseases. In case of pediatric treatment, the physicians should have the corresponding training and experience in children.



Systemic allergic reactions, including life-threatening anaphylactic shock and severe local allergic reactions, have been observed in patients receiving 2800 BAU, and may require emergency administration of epinephrine, antihistamines, bronchodilators or systemic corticosteroids.


An Immunotherapy-Shot Alternative for Respiratory Allergies?

Lin and colleagues reviewed the entire literature on this topic, accepting only studies that provided good scientific data. Sixty-three studies that included 5131 persons aged 4-74 years received sublingual tablets of 1 or more allergens or placebo, which were taken on a maintenance basis at daily or weekly intervals over extended periods ranging from 3 months to 5 years. The principal efficacy outcomes were symptom improvement, need for additional (rescue) medication, and quality of life. Adverse events were included for safety.

Local reactions were frequent, but anaphylaxis was not reported and presumably absent. The reviewers cautioned that their conclusions were limited by the great variations among studies in the type of immunotherapy used and its dose, frequency, and duration.

1. Nicholas Gross, MD, PhD. An Immunotherapy-Shot Alternative for Respiratory Allergies?. http://www.medscape.com/viewarticle/8048162. Lin SY, Erekosima N, Kim JM, et al . Sublingual Immunotherapy for the Treatment of Allergic Rhinoconjunctivitis and Asthma: a Systematic Review

JAMA. 2013;309:1278-12883. Nelson HS. Is sublingual immunotherapy ready for use in the United States? JAMA. 2013;309:1297-1298.4. Radulovic S, Calderon MA, Wilson D, Durham S. Sublingual immunotherapy for allergic rhinitis (including hay fever). Cochrane Summaries. February 16,

2011. http://summaries.cochrane.org/CD002893/sublingual-immunotherapy-for-allergic-rhinitis-including-hay-fever Accessed April 30, 2013.

s/l tablet: 2800 BAU Safety Adults

• In pooled analyses of data from children and adolescents, most adverse events occurred within the first 1 to 2 weeks of treatment, and the highest percentage of adverse events occurred on day 1.






The first tablet of 2800 BAU must be taken at the physician’s office under medical supervision and the patient must be monitored for at least 30 minutes.Extra precautions must be taken while treating pediatric patients, including: each administration of GRASTEK™ must be given under direct adult supervision for at least 30 minutes


s/l tablet: 2800 BAU Safety Adults

• The treatment-emergent adverse events that were reported most frequently were:

1. oral pruritus (26.7%, MK-7243; 3.5%, placebo)

2. throat irritation (22.6%, MK-7243; 2.8%, placebo)

3. ear pruritus (12.5%, MK-7243; 1.1%, placebo)

4. mouth edema (11.1%, MK-7243; 0.8%, placebo).





s/l tablet: 2800 BAU Safety Child

• The treatment-emergent adverse events that were reported most frequently were:

1. oral pruritus (24.4%, MK-7243; 2.1%, placebo)

2. throat irritation (21.3%, MK-7243; 2.5%, placebo)

3. tongue pruritus (9.2%, MK-7243; 0.9%, placebo)

4. mouth edema (9.8%, MK-7243; 0.2%, placebo).





Sublingual immunotherapy for allergic rhinitis (including hay fever)

Allergic rhinitis is characterised by red, itchy eyes, a blocked and runny nose, and sneezing. The most common causes of allergic rhinitis are different pollens (grass and tree), house dust mites, mould and animal dander. Allergic rhinitis can be intermittent (such as hay fever) or persistent (all year round).

Radulovic S, Calderon MA, Wilson D, Durham S. Sublingual immunotherapy for allergic rhinitis (including hay fever). Cochrane Summaries. February 16, 2011. : http://summaries.cochrane.org/CD002893/sublingual-immunotherapy-for-allergic-rhinitis-including-hay-fever#sthash.3xD98siS.dpuf


The treatment of allergic rhinitis depends on its severity and duration, and is usually based on the use of antihistamines and nasal corticosteroids. If these drugs cannot control symptoms immunotherapy is recommended.



Immunotherapy involves the administration of gradually increasing doses of the allergen over a period of time to desensitise the patient.It is the only known treatment that modifies the immune response and treats the cause rather than the symptoms.



In reviewing 60 trials we found a significant reduction in symptom and medication scores in patients treated with sublingual immunotherapy compared to placebo. There were no serious adverse reactions reported in the included trials and no patient needed the use of adrenaline. This updated Cochrane Review therefore reinforces the conclusions of the earlier review in confirming the efficacy and safety of sublingual immunotherapy.


Sublingual Immunotherapy for the Treatment of Allergic Rhinoconjunctivitis and Asthma:

Our review found moderate strength in the evidence to support the use of sublingual immunotherapy for allergic rhinitis and asthma. This indicates moderate confidence that the evidence reflects a true efficacy.

There were limitations in the standardization of adverse event reporting, but no life-threatening adverse events were noted.

Lin S.Y.; Sublingual Immunotherapy for the Treatment of Allergic Rhinoconjunctivitis and AsthmaA Systematic ReviewJAMA. 2013;309(12):1278-1288. doi:10.1001/jama.2013.2049.[March 27, 2013, Vol 309, No. 12 ]



There were 13 studies of allergic asthma, of which 9 provided "strong evidence...that sublingual immunotherapy improved symptoms" and decreased the need for supplemental medications.






36 studies of allergic rhinoconjunctivitis provided "moderate evidence" that supported a decrease in symptoms and improvements in disease-specific quality of life.






How long is the patient advised to wait after immunotherapy ?


Time to Onset of Systemic Reactions with Allergen Immunotherapy

Greineder DK. J Allergy Clin Immunol 1996; 98:S330-S334. [Data from Matloff et al. Allergy Proc 1993; 14:347-50.]

Time not recorded10% 2-24 hours

8%60-120 minutesminimum 2%

0-30 minutes72%

30-60 minutes8%

Note: based on this, patients should be advised that they must wait 30 minutes in the clinic after receiving subcutaneous immunotherapy

Immunotherapy for seasonal allergic rhinitisSCIT vs SLIT



Vial #01:1000

Vial #11:100

Vial #21:10

Vial #31:1

Dose mL Dose mL Dose mL Dose mL

1 0.10 6 0.10 11 0.05 17 0.05

2 0.20 7 0.20 12 0.10 18 0.07

3 0.30 8 0.30 13 0.20 19 0.10

4 0.40 9 0.40 14 0.30 20 0.15

5 0.50 10 0.50 15 0.40 21 0.20

16 0.50 22 0.25

***Hollister-Stier Extract***

Note: Record all injections in the treatment record.

Note: This dosage chart is offered as a suggested schedule. However, the degree of sensitivity varies in many individuals. In these cases, the size of the dose and intervals between doses may have to be adjusted and should be regulated by the patient’s tolerance and reaction. Treatment is normally started with the weakest dilution in the set. Beginning with dose #1 as listed in the schedule. Doses should be administered at weekly or twice-weekly (at least two days apart) intervals while working up. The maintenance level is […]

23 0.30

24 0.35

25 0.40

26 0.45

27 0.50

Gradually increase intervals to monthly maintenance. *Please read text to left*

Subcutaneous IT: Sample Dose ChartDr.: Patient: Content:

Lot No.: Expiry Date:

This is a suggested dose chart only. Please read the instructions before commencing desensitization. Observe patients for 30 minutes after each injection.

Check extract dilution and dose: Check the patient for local or systemic reaction(s) to previous injection.

Potential Benefits of SLIT

Timothy Grass Pollen Allergen Extract s/l tablet: 2800 BAU

• The recommended dose is 1 sublingual tablet daily; patients begin treatment 12 weeks before and continue throughout the grass pollen season.

• The first dose is given at the healthcare provider's office; all other doses are taken at home. The tablet dissolves in less than 10 seconds, according to the company briefing.


Sublingual Immunotherapy for the Treatment of Allergic Rhinoconjunctivitis and Asthma

s/l pill Radulovic S, Calderon MA, Wilson D, Durham S. Sublingual immunotherapy for allergic rhinitis (including hay fever). Cochrane Summaries. February 16, 2011. : http://summaries.cochrane.org/CD002893/sublingual-immunotherapy-for-allergic-rhinitis-including-hay-fever#sthash.3xD98siS.dpuf

SCIT vs SLIT

SCIT = subcutaneous immunotherapy SLIT = sublingual immunotherapy

1 2 3 4 5 6 7 8 9 10 +

1 2 3 4 5 6 7 8 9 10 +

http://www.ec.gc.ca/cas-aqhi/default.asp?lang=En&n=9E5D28AD-1

Environment Canada

http://www.bcairquality.ca/readings/index.html

Abelsohn A., Stieb DM; Health effects of outdoor air pollution; Approach to counseling patients using the Air Quality Health Index; Clinical Review; Can Fam Physician 2011;57:881-7

Health effects of outdoor air pollution

Air Quality Health Index (AQHI)


Air Quality Health Index (AQHI)


Typical Presentation of Allergic Rhinoconjunctivitis in Children

Diagnostic Testing

Threefold Approach to Treatment

Health & Medicine

Feb 2014 allergy b clinical and aqhi