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وجهه الكريموجهه الكريم

Is There any Link Is There any Link between between OSAS& OSAS&

ASTHMAASTHMA??

Dr. Aliaë Abd-Rabou Mohamed-HusseinEuropean Respiratory Society Scientific European Respiratory Society Scientific CommitteeCommittee

Editor in World Journal of RespirologyEditor in World Journal of RespirologyProfessor of Pulmonology, Chest Department

Assiut University Hospitals, Assiut, Egypt

Size of the problems

6-8% of US population 4-6% of US population

CAN ASTHMA…..CAN ASTHMA…..

AFFECT AFFECT SLEEP ???SLEEP ???

Patients with Patients with asthmaasthma appear to appear to have an increased risk for have an increased risk for OSAOSA

Large epidemiologic studies demonstrate that asthma patients

More frequently report snoringsnoring.

OSA symptomsOSA symptoms are highly prevalent in clinic-based populations of well-characterized asthma patients.

Also….patients with Also….patients with asthma asthma has has "Nocturnal""Nocturnal" awakening awakening

Mechanisms of nocturnalnocturnal awakening “asthma”asthma”

Probable:Probable:Circadian features

airway inflammationmelatonin

Possible:Possible:Airways coolingSupine postureAllergic FactorsGastroesophageal refluxSnoring or Sleep Apnea

Sutherland, (2005)

Patients with good controlgood control report less frequent and less severe sleep disturbancesless frequent and less severe sleep disturbancescompared to uncontrolled subjects.

Conversely, Conversely, sleepsleep per se could per se could

…worsen …worsen asthmaasthma

HOW????

Normal subject PEFR 8%

Asthmatic subjects 50%

Catterall et al,(1989) found that Airway resistance in asthmatic patients to be

approximately double that in non-asthmatics at the start of the nocturnal recording period

and the magnitude of the overnightovernight riserise was

much greater in asthmatics.

Aim: To determine whether a high OSA risk is associated to uncontrolled asthma

Sleep Disorders Questionnaire (SA-SDQ)

Asthma Control Questionnaire. (ACQ)

Multivariate Logistic Regression Models of Not-Well-Controlled Asthma on High OSA Risk,High OSA Risk, with Adjustment for Factors Known To Worsen Asthma Control

OSAOSA is a potential contributor to overall asthma controlasthma control and indipendent ot the other known contributors to asthma control

OR 3.4

Eur Respir J 2005; 26: 812–818

The National Asthma Education and Prevention Program Expert Panel Report recommends evaluating for OSA OSA as a potential contributor to poor asthma poor asthma controlcontrol.

In short, OSAOSA and AsthmaAsthma may have a bidirectional relationship in which each can

exacerbate the other .

What are the linksWhat are the links??

Mechanisms linking asthma, and Mechanisms linking asthma, and sleep apneasleep apnea

CORECORE

The coexistence and The coexistence and hypothetical link betweenhypothetical link between

Cough/asthma, Obesity/OSA,

Rhinosinusitis, and Esophageal reflux could be referred to as the

““CORE”CORE” syndrome.

In asthmatic patients’ refractory to therapy, CORE CORE components must be considered in the management..

1st component “COORE”

ObesityObesity

Increased incidence of asthma in overweighed and obese subjects

Beuther DA, Sutherland ER: Overweight, Obesity, and Incident Asthma: A Meta-analysis of Prospective Epidemiologic Studies. AJRCCM 2007;175:661-666.

Beuther DA et al. Pulmonary Perspectives: Obesity and Asthma. Am J Respir Crit Care Med. 2006;174:112-9

Obesity and Asthma(Mediators)

ObesityObesity and OSASOSASThe Posthumous Papers of the Pickwick Club- 1836

Charles Dickens  

JOE

OBESITY IS.……

Strongest risk factor for OSA

Present in > 60% of patients referred for

a diagnostic sleep evaluation

Wisconsin Sleep Cohort Study A one standard deviation difference in BMI was

associated with a 4-fold increase in disease prevalence

OBESITY ISOBESITY IS……. A cause of

1- Increased parapharyngeal fat deposition

neck circumference: > 17” males

> 16” females

With subsequent:

smaller upper airway

increase the collapsibility of the pharyngeal airway

OBESITYOBESITY.……

2. Changes in neural compensatory mechanisms that maintain airway patency:

diminished protective reflexes

ObesityObesity ……… ………

3. ↑ waist circumference

↓functional residual capacity which can lead to loss of caudal traction on the upper airway

low lung volumes are associated with diminished oxygen stores

2nd component “CORRE”

ASTHMAASTHMA

OSASOSAS

Bronchial Asthma

Allergen bronchial challenge

EosinofphilIL-5

BasophilMast cell degranlulation

EosinophilICAM-1VCAM-1

Allergen Challenge

nose-bronchial reflex

Allergen

Post nasal drip

Cytokine

Loss ofFilter ability

Viral ifection

Bone marrow

Stem cell

Allergic Rhinitis...

United Airways Disease

Allergic rhinitisAllergic rhinitis .…

Nasal obstruction contributes to snoring, sleep-disordered breathing in predisposed individuals.

Scharf and Cohen (1997)

3rd component “COREE”

GERDGERD.….…

GERD GERD is a common condition that affects approximately 20–30% of the adult population.

Several studies have reported an increased

prevalence of GERD in patients with OSA.

(Spechler, 1992 )and (Petersen et al, 1995)

GERDGERD..…..…

Acid reflux into the airway

enhances Vagal activity

can trigger asthma asthma in some individuals

as well as with symptoms of

OSASOSAS. Gislason Janson Vermeire et al, )2002(

4th component ….”CCORE”(Cardiac)

Sleep Disorders and CV diseases

OSA is associated with significant cardiovascular morbidities as:

Left ventricular dysfunction, Arrhythmias, Myocardial infarction, and Systemic hypertension.

CardiovascularCardiovascular complications of OSAOSA and how they may relate to asthma asthma??

ComplicationResultant effectAsthma relation

HTNLVH, IHD, LVDPulmonary edemaAsthma worsening

IHDIschemiaAsthma worseningCough worsening

ASCVD, Arrhythmia, HTN

Stroke, cognitive decline

Poor compliance with medication

PHTNDyspneaAsthma mimic

MedicationsBeta–blockersACE-inhibitor

Asthma worseningCough worsening

Adapted from (Kasasbeh et al, 2007)

5th Component ( Inflammation)

A

S

T

H

M

A

OSAS

Multiple Pro-Inflammatory Factors in Allergic Asthma & Rhinitis Affect Sleep and OSAS Symptoms

MediatorEffect on Sleep

Histamine↑ airway, nasal obstruction, rhinorrhea, & pruritus

Balance between wakefulness and sleep, arousal

CysLT↑ Nasal, airway obstruction, rhinorrhea

↑ Slow-wave sleep, ↑ Sleep-disordered breathing

IL-1↑ Airway inflammation

↑ Latency to REM and ↓ REM durationIL-4

IL-10

Bradykinin↑ Nasal, airway obstruction & rhinorrhea

↑ Sleep apnea;

Substance P↑ Latency to REM, arousal; ↑ Nasal obstructionAdapted from Ferguson. Otolaryngol Head Neck Surg. 2004;130:617.

Treatment modalitiesTreatment modalities

Prospective Clinical Studies Reporting the Impact of Treatment With CPAPImpact of Treatment With CPAP on Asthma Outcome in Patients With Concomitant OSAS

Ann Allergy Asthma Immunol. 2008;101:350–357.

• ↑mean airway pressure

• Recruits underventilated alveoli

• ↑ minute ventilation,

• ↓ airways resistance

• Stabilizes upper aireways

• Prevents peripheral airways closure

Beneficial effects of CPAP in patients with asthma and OSAS “LOCAL”

↑ end-expiratory lung volume

↑ expiratory muscle function

↓ respiratory rate and dyspnea

↓ OSAS induce vagal stimulation

↓ OSAS induced increased intrathoracic pressure

Beneficial effects of CPAP in patients with asthma and OSAS

“ SYSTEMIC”

Impact of asthma asthma treatment on sleepsleep

OSASOSAS

OSAS TherapyOSAS Therapy

GERD therapyGERD therapy

GERDGERD

Does the treatment of OSA OSA by CPAP improve GERDGERD?

AuthorNResults

Kerr (1992)6 OSADecreased pH <4 esophageal exposure 6.3–0.1% (p<0.05)

Kerr (1993)6 non-OSADecreased pH <4 esophageal exposure 28–6% (p<0.05)

Ing (2000)

14 OSADecreased pH <4 esophageal exposure 12–4% (p<0.05)

Decreased overall number of reflux events (p<0.05)

8 non-OSADecreased pH <4 esophageal exposure 4–1% (p<0.05)

Decreased overall number of reflux events (p<0.05)

Green (2003)

165 OSA48% reduction in GERD symptom score (p<0.001)

While patients without CPAP had no improvement

Does Treatment of GERD GERD (PPI)(PPI) affect OSAOSA symptoms?

AuthorNMedication (t× time)Results

Ing (2000)6Nizatidine (30 days)50% AI reduction (p<0.05)

No significant reduction in AHISymptom reduction not evaluated

Senior (2001)10Omeprazole (30 days)31% AI reduction (p=0.04)

25% RDI reduction (p=0.06)Symptom reduction not evaluated

Steward (2004)27Pantoprazole (90 days)No significant reduction in AHI

Reduced daytime sleepiness (p=0.002)Reduced GERD symptoms (p=0.0006)

Mohamed-Mohamed-Hussein et al., Hussein et al., 20112011

34Pantoprazole ( 60 days)Significant reduction in RDI, snoring

events, ESS, improved SaO2

Published articles

Gastroeosophygeal Reflux in Patients with Obstructive Sleep Apnea Syndrome: Value of isolated treatment with Proton-Pump inhibitor Aliaë AR Mohamed-Hussein1, M. Kobeisy2, M. Ibrahim3

Chest1, Iinternal Medicine2 and Gastroenterology and Hepatology3 Departments, faculty of Medicine, Assiut University Hospitals, Assiut, Egypt

Taken together..…

Obstructive sleep apnea (OSA)Obstructive sleep apnea (OSA) and asthma asthma can coexist in the same patient for various reasons.

Obesity

Rhinitis,

GERD

Are common risk factors for both asthma and OSA and need to be looked for and treated aggressively.

Management of patients with combined asthma and OSA is often multidisciplinary, requiring multiple approaches including:

behavioral/psychosocial, pharmacological, mechanical (CPAP), and surgical therapies.

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