Treatment of Sleep Associate disturbance in Allergy Diseases

Timothy J. CraigProfessor of Medicine and Pediatrics

Distinguished EducatorPenn State University

Presentation Overview

• Allergic Rhinitis and Sleep Disturbance• Mechanisms of Sleep Disturbance in Allergic

Rhinitis• Impact of AR-associated Sleep Disturbances• Effects of Allergic Rhinitis Therapies on Sleep

and Quality of Life

conflicts of interest with this presentation

• Merck- speaker, researcher, consultant• Astra-Zeneca- speaker• Teva- speaker• GSK- researcher

Allergic Rhinitis Adversely Impacts Sleep in Adults and Children/Adolescents

96 93

79

0

20

40

60

80

100

120

40

36

32

28

0

10

20

30

40

50 N=476 Adults/Adolescents/Children with AR

Patie

nts

with

Mod

erat

e or

Sev

ere

Impa

ct (%

)

Sleep DailyActivities

School/WorkPerformance

Lifestyle

O’Connor and Punekar. J Allergy Clin Immunol. 2006;117:S322. Abstract 1244.Scadding and Punekar. EAACI Abstract Book. 2006;211. Abstract 741.

N=221 Adolescents/Children with AR

Patie

nts

with

Impa

ct (%

)

School/WorkPerformance

NormalActivities

Sleep

Allergic Rhinitis Symptoms are Associated with Sleep Complaints

Leger et al. Arch Intern Med. 2006;166:1744.

17.2

27.125.4

19.6

12.8

20.518.3

23.3

40.3

63.2

46.8

28.7

42.841.6

0

10

20

30

40

50

60

70 Controls (n=502)

AR Patients (n=591)

Subj

ects

with

com

plai

nt (%

)

Difficulty FallingAsleep

NocturnalAwakening

EarlyAwakening

NonrestorativeSleep

Feeling ofLack of Sleep

Snoring ESS score>10

Prevalence of Sleep Complaints in Patients with Allergic Rhinitis and Controls

*P<0.001 vs controls.

* *

*

*

*

*

*

Allergic Rhinitis (AR) Symptoms are Associated with Sleep Disorders

Leger et al. Arch Intern Med. 2006;166:1744.

Prevalence of Sleep Disorders in Patients with Allergic Rhinitis and Controls

*P≤0.003 vs controls.

24.3

0.5

10.4

16

32.6

3.8

23.2

35.8

0

5

10

15

20

25

30

35

40 Controls (n=502)

AR Patients (n=591)

Subj

ects

with

dis

orde

r (%

)

Insomnia SevereInsomnia

Sleep ApneaSyndrome

Hypersomnia

*

*

*

*

7.6 fold increase of OSA in AR

Allergic Patients Experience More Apnea/Hypopnea than Non-allergic Controls

P<0.001

0

0.2

0.4

0.6

0.8

1.0

Allergic rhinitis group Control group

AH

I

Before allergy season

During allergy season

Stuck et al. J Allergy Clin Immunol. 2004;113:663.

Allergic patients had more apnea/hypopnea episodes than non-allergic controls

AHI=apnea/hypopnea index, determined as the total number of apnea and hypopneaepisodes (assessed by polysomnography) divided by hours of sleep.

Patients with rhinitis had 10 times moremicroarousals (average of 50) than controls (n=14)

Lavie et al. Acta Otolaryngol. 1981;92;529.

Allergic Rhinitis is Associated with Increased Microarousals

Lavie et al. Acta Otolaryngol. 1981;92;529.

Microarousals Correlate with Impaired Breathing

Microarousals in Allergic Rhinitis Correlate with Impaired Breathing

Similarities between the twoObese man with severe OAS • Increase in IL-1• Increase in TNF• Increase in Il-6• Increase in T-helper 2

cytokines• Decrease in T-helper 1

cytokines

A young girl snoring and with rhinitis

• Increase in IL-1• Increase in TNF• Increase in Il-6• Increase in T-helper 2

cytokines• Decrease in T-helper 1

cytokines

What is the Mechanism of Sleep Disturbance in Allergic Rhinitis?

1. Inflammatory components of the allergic response

2. Symptoms of allergic rhinitis3. Nasal congestion4. All three

Answer

Impact of Poor Sleep

•Delayed onset•Sleep fragmentation

• Arousals/microarousals•Sleep Disordered

Breathing• Snoring• Obstructive Sleep Apnea

Impaired Social Functioning:• daytime fatigue/somnolence• Impaired performance• Impaired learning• Emotional/behavioral impact

Associated Diseases:•Hypertension•Cardiovascular disease•Stroke•Diabetes•Psychological disorders

Treatment Options

Treatment Options:Snoring Children

The approach to the child with concerns for having OSA

The affect of OSA and benefits of T+A on asthma

The affect of OSA and benefits of T+A on poorly controlled asthma

Kheirandish-Gozal. Pediatrics 2008

Sleep apnea in children treated with topical budesonide nasal spray

Leukotrienes in tonsil tissue in children with sleep apnea (SA) and those with recurrent infection (RI)

LTC-4 LTB-4

Adenoid reduction with 16 weeks of montelukast therapy

Montelukast affect on sleep in children with sleep apnea compared with those receiving no therapy

Treatment Options for Rhinitis Associated With Sleep disordered Breathing

Treatment Considerations in Allergic Rhinitis: ARIA Guidelines

Congestion RhinorrheaItching/

SneezingSleep

Intranasal steroids

Oral antihistamines

Intranasal antihistamines

Oral decongestants

Intranasal decongestants

Intranasal cromones

Anticholinergics

Antileukotrienes

Bousquet et al. Allergy. 2003;58:192. Bousquet et al. Allergy. 2002;57:841. Van Cauwenberge et al. Allergy. 2000;55:116.

Treatment Considerations in Allergic Rhinitis: ARIA Guidelines

Congestion RhinorrheaItching/

SneezingSleep

Intranasal steroids +++ +++ ++/+++ ++++

Oral antihistamines

Intranasal antihistamines

Oral decongestants

Intranasal decongestants

Intranasal cromones

Anticholinergics

Antileukotrienes

Bousquet et al. Allergy. 2003;58:192. Bousquet et al. Allergy. 2002;57:841. Van Cauwenberge et al. Allergy. 2000;55:116.

Treatment Considerations in Allergic Rhinitis: ARIA Guidelines

Congestion RhinorrheaItching/

SneezingSleep

Intranasal steroids +++ +++ ++/+++ ++++

Oral antihistamines + ++ +++/++ +

Intranasal antihistamines

Oral decongestants

Intranasal decongestants

Intranasal cromones

Anticholinergics

Antileukotrienes

Bousquet et al. Allergy. 2003;58:192. Bousquet et al. Allergy. 2002;57:841. Van Cauwenberge et al. Allergy. 2000;55:116.

Treatment Considerations in Allergic Rhinitis: ARIA Guidelines

Congestion RhinorrheaItching/

SneezingSleep

Intranasal steroids +++ +++ ++/+++ ++++

Oral antihistamines + ++ +++/++ +

Intranasal antihistamines + ++ ++/++ tiredness

Oral decongestants

Intranasal decongestants

Intranasal cromones

Anticholinergics

Antileukotrienes

Bousquet et al. Allergy. 2003;58:192. Bousquet et al. Allergy. 2002;57:841. Van Cauwenberge et al. Allergy. 2000;55:116.

Oral decongestants compared to placebo and benefit on sleep and rhinitis

Oral decongestants compared to placebo and benefit on sleep and rhinitis

Treatment Considerations in Allergic Rhinitis: ARIA Guidelines

Congestion RhinorrheaItching/

SneezingSleep

Intranasal steroids +++ +++ ++/+++ ++++

Oral antihistamines + ++ +++/++ +

Intranasal antihistamines + ++ ++/++ tried

Oral decongestants ++ - -/- 0

Intranasal decongestants

Intranasal cromones

Anticholinergics

Antileukotrienes

Bousquet et al. Allergy. 2003;58:192. Bousquet et al. Allergy. 2002;57:841. Van Cauwenberge et al. Allergy. 2000;55:116.

Treatment Considerations in Allergic Rhinitis: ARIA Guidelines

Congestion RhinorrheaItching/

SneezingSleep

Intranasal steroids +++ +++ ++/+++ ++++

Oral antihistamines + ++ +++/++ +

Intranasal antihistamines + ++ ++/++ tried

Oral decongestants ++ - -/- 0

Intranasal decongestants ++++ - - +

Intranasal cromones

Anticholinergics

Antileukotrienes

Bousquet et al. Allergy. 2003;58:192. Bousquet et al. Allergy. 2002;57:841. Van Cauwenberge et al. Allergy. 2000;55:116.

Treatment Considerations in Allergic Rhinitis: ARIA Guidelines

Congestion RhinorrheaItching/

SneezingSleep

Intranasal steroids +++ +++ ++/+++ ++++

Oral antihistamines + ++ +++/++ +

Intranasal antihistamines + ++ ++/++ tried

Oral decongestants ++ - -/- 0

Intranasal decongestants ++++ - - +

Intranasal cromones + + +/+ -

Anticholinergics

Antileukotrienes

Bousquet et al. Allergy. 2003;58:192. Bousquet et al. Allergy. 2002;57:841. Van Cauwenberge et al. Allergy. 2000;55:116.

Treatment Considerations in Allergic Rhinitis: ARIA Guidelines

Congestion RhinorrheaItching/

SneezingSleep

Intranasal steroids +++ +++ ++/+++ ++++

Oral antihistamines + ++ +++/++ +

Intranasal antihistamines + ++ ++/++ tried

Oral decongestants ++ - -/- 0

Intranasal decongestants ++++ - - +

Intranasal cromones + + +/+ -

Anticholinergics - ++ -/- -

Antileukotrienes

Bousquet et al. Allergy. 2003;58:192. Bousquet et al. Allergy. 2002;57:841. Van Cauwenberge et al. Allergy. 2000;55:116.

Treatment Considerations in Allergic Rhinitis: ARIA Guidelines

Congestion RhinorrheaItching/

SneezingSleep

Intranasal steroids +++ +++ ++/+++ ++++

Oral antihistamines + ++ +++/++ +

Intranasal antihistamines + ++ ++/++ tried

Oral decongestants ++ - -/- 0

Intranasal decongestants ++++ - - +

Intranasal cromones + + +/+ -

Anticholinergics - ++ -/- -

Antileukotrienes ++ + -/- ++

Bousquet et al. Allergy. 2003;58:192. Bousquet et al. Allergy. 2002;57:841. Van Cauwenberge et al. Allergy. 2000;55:116.

Effect of Therapies for Allergic Rhinitis on Sleep and Quality of Life: Summary

• Intranasal steroids provide significant relief of congestion and ocular symptoms and improve sleep in patients with allergic rhinitis

• Non-sedating antihistamines and leukotriene receptor antagonists provide modest improvements in congestion, ocular, and nighttime symptoms

• Decongestants effectively reduce congestion, but have minimal affect on sleep-disordered breathing

Adverse Impact of Allergic Rhinitis on the Patient Quality of Life-Focus on Sleep: Conclusions

• Allergic rhinitis is associated with impaired sleep• Sleep impairment in allergic rhinitis can be caused by

– Inflammatory mediators– Nasal symptoms, primarily congestion and rhinorrhea– Ocular symptoms

• Impaired sleep adversely affects performance, productivity and social functioning, and increases the risk of associated diseases

• Intranasal steroids effectively target inflammation and relieve symptoms to provide improved sleep

Thank you

• Stephanie Teets• Stan Golden• Josh Berlin• Sujani Kukumanu• Katherine Hughs• Casey Glass

• Joel Torretti• Faina Gurevich• Wenxin Wei• Jeff McCann• Chris Hanks• Carah Santos• Niti Sardana

Questions

Have a great day.