dr.

Wistiani, SpA

Epidemiology
Most common disorders encountered in infants and children : 10% to 24% of population Children and adolescent more commonly affected Boys > in childhood, equal during adulthood

Nelson. Essentials of Pediatrics. 2006 Gentile DA, Shapiro GG, Skoner DP. Pediatric Allergy

 Allergic rhinitis is characterized by nasal inflammation

Mast cell activation Release of chemical mediators Influx of inflammatory cells (eg, eosinophils)1

Allergic Rhinitis Is Associated With Inflammation

IgE-mediated nasal response to allergens results in

Inflammation leads to congestion1 Congestion adversely impacts quality of life1,2

Sleep disruption snoring, sleep apnea Daytime fatigue

1. Craig et al. J Allergy Clin Immunol. 1998;101:633. 2. Young et al. Arch Intern Med. 2001;161:1514.

Mast Cells Are the Primary Immune Effector Cells in Allergic Rhinitis

Mast cells are the major source of mediators

Histamine Cytokines Prostaglandins/leukotrienes

Kovarova and Rivera. Curr Med Chem. 2004;11:2083.

ARIA Guidelines: Classification of Allergic Rhinitis

Intermittent <4 days per week Or <4 weeks Persistent 4 days per week And >4 weeks

Mild Normal sleep and No impairment of daily activities, sport, leisure Normal work and school No troublesome symptoms

Moderate-Severe 1 or more items Abnormal sleep Impairment of daily activities, sport, leisure Abnormal work and school Troublesome symptoms

ARIA = Allergic Rhinitis and its Impact on Asthma.

Bousquet et al. J Allergy Clin Immunol. 2001;108 (5 suppl):S147. Bousquet et al. Allergy. 2002;57:841.

 Asthma

Allergic Rhinitis: Common Comorbid Conditions

25%-35% of patients with AR also have asthma >85% of patients with asthma have AR

Conjunctivitis
Prevalence ~50%

Rhinosinusitis and Nasal Polyposis

Prevalence of chronic rhinosinusitis >75%

Otitis Media Eczema

Bousquet et al. J Allergy Clin Immund. 2001;108:S147.

Allergens...

Nasal Inflammation: An Underlying Mechanism in Allergic Rhinitis

Early-Phase Response Mast Cell Allergen
Histamine Proteases

Late-Phase Response Cellular Infiltration/Inflammation

Eosinophil

Basophil
Chemotactic factors

Mast cell
Other Inflam. mediators

Monocyte

Lymphocyte

Other Inflammatory Mediators

Nasal Mucosa in Patients with PAR

Pearlman. J Allergy Clin Immunol. 1999;104:S132. Bascom et al. Am Rev Respir Dis. 1988;138:406. Bascom et al. J Allergy Clin Immunol. 1988;81:580. Quraishi et al. J Am Osteopath Assoc. 2004;104(suppl 5):S7. Minshall et al. Otolaryngol Head Neck Surg. 1998;118:648.

Mast Cells Mediate Allergic Reactions

IgE + FceRI

MC
Histamine

Allergic reaction

Graphics courtesy of Prof. M. Maurer.

Mast Cells Mediate Allergic and Inflammatory Reactions

IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, TNFa, MIPs, IFNg, GM-CSF, TGFb, bFGF, VPF/VEGF, PGD2, LTB4, LTC4, PAF, Serotonin, Heparin, Chondroitinsulfate, Chymase, Tryptase, Cathepsin G
Activation

Extravasation

MC

Vasodilation

Recruitment

Graphics courtesy of Prof. M. Maurer.

Molecules released by Mast cells on activation

Symptoms of Allergic Rhinitis

Sneezing Anterior rhinorrhea Nasal itch Posterior rhinorrhea Congestion

Patients may not present with all symptoms Majority of patients experience worst symptoms in the morning

Eyes....

Nose, itchy....

Nose...

Factors Contributing to the Severity of Morning Symptoms in AR

AR is influenced by circadian rhythms1 Increased indoor and outdoor allergen exposure
Pollen concentrations are usually highest in morning2

High levels of histamine and inflammatory mediators

1. Storms. J Allergy Clin Immunol. 2004;114(suppl):S146. 2. American Academy of Allergy, Asthma, & Immunology. At: http://www.aaaai.org/media/resources/pollen_qa.stm

Circadian Variation in Allergic Rhinitis Symptoms

AR symptoms vary during the day, but are most severe during the morning hours
Sneezing
10 12 12

Stuffy Nose

Runny Nose
12

Itchy Nose

Arbitrary units

8 10 10 6 5

12 18 Clock hours

12 18 Clock hours

12 18 Clock hours

12 18 Clock hours

Female (n=435)

Male (n=330)

Peak-to-trough differences were statistically significant (P<0.008) There were no differences between male and female subjects
Reinberg et al. J Allergy Clin Immunol. 1988;81:51.

Definition, Causes, and Prevalence of Nasal Congestion

A term used to denote swollen mucosa caused by dilatation of the capacitance vessels and exudation of serum/plasma because of increase in capillary permeability1 Most commonly caused by allergic rhinitis (seasonal/perennial)2 Other causes2: nasal polyps, upper respiratory infection, rhinosinusitis, miscellaneous More than half of allergy patients suffer from nasal congestion at its worst at bedtime and early morning3 Particularly troublesome during the night, adversely affecting sleep3-5 Nasal congestion and mucus production predominate in most patients with perennial allergic rhinitis6

1. 2. 3. 4. 5. 6.

Jessen and Malon. Allergy. 1997;52(suppl):3. Corey et al. Ear Nose Throat J. 2000;79:690. Data on file, Schering Corporation, Kenilworth, NJ. Craig et al. J Allergy Clin Immunol. 1998;101:633. Young et al. Arch Intern Med. 2001;161:1514. Skoner. J Allergy Clin Immunol. 2001;108(suppl):S2.

Inflammation in Upper Respiratory Diseases Leads to Congestion

Inflammation1-4
Allergic Rhinitis Nasal Polyposis Rhinosinusitis

Congestion*4

*Image of congested nasal passage courtesy of Professor J.-M. Klossek.

1. Minshall et al. Otolaryngol Head Neck Surg. 1998;118:648. 2. Bachert et al. J Allergy Clin Immunol. 1997;99:837. 3. Bachert et al. Allergy. 1998;53:2. 4. Van Drunen et al. Allergy. 2005;60(suppl 80):5.

Congestion and Inflammation: Adverse Clinical Impact in Upper Respiratory Disease

Allergic rhinitis

Nasal polyps
Congestion Inflammation

Asthma with AR

Sleep disturbance, including sleepdisordered breathing

Common cold

Rhinosinusitis (acute and chronic)

Congestion and Inflammation are Hallmarks of Allergic Rhinitis

All 50 patients with seasonal allergic rhinitis had either severe (n=26) or moderate (n=24) nasal congestion
Moderate Severe Congestion Congestion 8 (7.5-9) 11 (10-11) P Value <0.0001

TSS

Nasal flow (mL/s) Eosinophils IL-5 (pg/mL)

56586
7.462.60 5.151.13

40771
13.32.70 7.681.24

<0.0001
<0.0001 <0.0001

TSS = total symptom score; IL = interleukin.

Ciprandi et al. Otolaryngol Head Neck Surg. 2005;133:429.

Inflammation Reduces Nasal Airflow in Allergic Rhinitis

800 700
r = -0.85 p<0.001

Nasal flow (ml/s)

600
500 400 300

200
100 0 0 5 10 15 20

Eosinophils
Ciprandi et al. Int Arch Allergy Immunol. 2004;134:34.

Nasal Congestion: Impact on Patients

Nasal Congestion
Bothersome, difficult symptom Impairs sleep: 1. Sleep-disordered breathing 2. Daytime fatigue/somnolence

Impairs work/school performance

Impacts health: 1. Hypertension 2. Heart disease (CAD, CHF) 3. Stroke

Data on file, Schering Corporation, Kenilworth, NJ. Roper Public Affairs Group of NOP World. Impact of nasal congestion among allergic rhinitis sufferers. May-June 2004. Forbes Consulting Group. Understanding the Dynamics Surrounding Allergy Suffering and Treatment. September 2005. Stuck et al. J Allergy Clin Immunol. 2004;113:663. Vuurman et al. Ann Allergy. 1993;71:121.

Impact of Nasal Congestion in Allergic Rhinitis: Survey Design and Respondent Characteristics
Eligible respondents who were diagnosed as having allergic rhinitis by physicians completed a demographic (9 questions) and symptom/treatment (43 questions) survey Respondents scored symptom severity on a scale of 1 (not severe at all) to 10 (extremely severe) for nasal congestion and other symptoms 85% (2002/2355) of respondents with allergic rhinitis reported nasal congestion
Severe (score 9-10): 40% Moderate (score 7-8): 35% Mild (score 1-6): 25%

Data on file, Schering Corporation, Kenilworth, NJ. Roper Public Affairs Group of NOP World. Impact of nasal congestion among allergic rhinitis sufferers. May-June 2004.

Impact of Nasal Congestion in Respondents with Allergic Rhinitis: Survey

Results
Patient Survey Results (n=2002)
80 70 60 50 40 30 20 10 0
Most likely to result in Most bothersome physician visit symptom Affected at work/ school
Children Adults

69 54 58 48 61

59

Data on file, Schering Corporation, Kenilworth, NJ. Roper Public Affairs Group of NOP World. Impact of nasal congestion among allergic rhinitis sufferers. May-June 2004.

Simons FER. Learning impairment and allergic rhinitis. Allerg Asthma Proc 1996; 17:185-189.
sneezing nasal itch rhinorrhea nasal congestion

sleep loss
daytime fatigue

learning problems during school hours

Nasal Congestion is the Symptom Most Respondents Want to Prevent: Survey Results
Children

70 60 50 40 30 20 10 0

63 50

Adults

19

17 8 11

Nasal Congestion

Runny nose

Sneezing

Data on file, Schering Corporation, Kenilworth, NJ. Roper Public Affairs Group of NOP World. Impact of nasal congestion among allergic rhinitis sufferers. May-June 2004.

Nasal Congestion Impacts Respondents Sleep:

Survey Results
60 50 40 30 21 20 10 0
Awakes patients Makes it difficult to fall asleep Prevents patients from falling asleep
Children

49

51

Adults

49

48

26

Data on file, Schering Corporation, Kenilworth, NJ. Roper Public Affairs Group of NOP World. Impact of nasal congestion among allergic rhinitis sufferers. May-June 2004.

Nasal Congestion Leads to Obstructive Sleep Apneas*

1.0

Increase in obstructive sleep apnea frequency

0.8 0.6 0.4 0.2 0 0 10 20 30 40 50 60 70

Increase in nasal resistance (%)

*5 men with seasonal allergic rhinitis.
McNicholas et al. Am Rev Respir Dis. 1982;126:625.

 Common inflammatory process links upper and lower airways1

Asthma and allergic rhinitis commonly co-exist2,3 In concomitant disease, experts recommend evaluation and treatment of one condition to aid management of the other4 Asthma management guidelines from ARIA,4 the NIH,5 AAFP,6 and AAAAI7 encourage treatment of AR (and other URDs) to help control asthma

The One Airway Concept

Common inflammatory process links upper and lower airways1
Asthma and allergic rhinitis commonly co-exist2,3 In concomitant disease, experts recommend evaluation and treatment of one condition to aid management of the other4 Asthma management guidelines from ARIA,4 the NIH,5 AAFP,6 and AAAAI7 encourage treatment of AR (and other URDs) to help control asthma
Bachert C, et al. Immunol Allergy Clin N Am. 2004;24:19-43. Nayak AS. Allergy Asthma Proc. 2003;24:395-402. 3. Halpern MT, et al. J Asthma. 2004;41:117-126. Bousquet J, et al. Allergic Rhinitis and its Impact on Asthma (ARIA). Allergy. 2002;57:841-855. NIH. Guidelines for the Diagnosis and Management of Asthma.1997. NIH publication 97-4051. 6. AAFP. Asthma & Allergy Resource Guide. 2004:18. 7. AAAAI. The Allergy Report. 2000;2:33,54. 2. 1.

4. 5.

Conclusion
Allergic rhinitis symptoms vary during day but are most severe during morning hours Allergic rhinitis is characterized by nasal inflammation which leads to congestion Congestion impacts quality of life patient Impaired Sleep (disruption, snoring, sleep apnea, daytime fatigue) Bothersome (difficult symptoms) Impairs work/school performance Impacts health (hypertension, stroke, heart disease) Congestion in Allergic Rhinitis Is a Major Reason for Physician Visits Nasal congestion is the symptom most respondents want to prevent

Figure 12-3

Figure 12-5 part 1 of 2

Figure 12-5 part 2 of 2