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سبحان من ال تطيب الدنيا اال بذكره ... وال االخرة اال بعفوه... وال الجنة اال برؤية وجهه الكريم Is There any Link between OSAS& ASTHMA? Dr. Aliaë Abd-Rabou Mohamed-Hussein European Respiratory Society Scientific Committee Editor in World Journal of Respirology Professor 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….. AFFECT SLEEP ??? Patients with asthma appear to have an increased risk for OSA Large epidemiologic studies demonstrate that asthma patients More frequently report snoring. OSA symptoms are highly prevalent in clinic-based populations of well-characterized asthma patients. Also….patients with asthma has "Nocturnal" awakening Mechanisms of nocturnal awakening “asthma” Probable: Circadian features airway inflammation melatonin Possible: Airways cooling Supine posture Allergic Factors Gastroesophageal reflux Snoring or Sleep Apnea Sutherland, (2005) Patients with good control report less frequent and less severe sleep disturbances compared to uncontrolled subjects. Conversely, sleep per se could …worsen asthma 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 overnight rise 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, with Adjustment for Factors Known To Worsen Asthma Control OSA is a potential contributor to overall asthma 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 as a potential contributor to poor asthma control. In short, OSA and Asthma may have a bidirectional relationship in which each can exacerbate the other. What are the links? Mechanisms linking asthma, and sleep apnea CORE The coexistence and hypothetical link between Cough/asthma, Obesity/OSA, Rhinosinusitis, and Esophageal reflux could be referred to as the “CORE” syndrome. In asthmatic patients’ refractory to therapy, CORE components must be considered in the management.. 1st component “CORE” Obesity 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. Obesity and Asthma (Mediators) Beuther DA et al. Pulmonary Perspectives: Obesity and Asthma. Am J Respir Crit Care Med. 2006;174:112-9 Obesity and OSAS JOE The Posthumous Papers of the Pickwick Club- 1836 Charles Dickens 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 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 OBESITY……. 2. Changes in neural compensatory mechanisms that maintain airway patency: diminished protective reflexes Obesity……… 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 “CORE” ASTHMA OSAS United Airways Disease Allergic Rhinitis... Eosinofphil IL-5 Basophil Mast cell degranlulation Allergen Challenge Loss of Filter ability Allergen Post nasal drip nose-bronchial reflex Stem cell Cytokine Bone marrow Viral ifection Eosinophil ICAM-1 VCAM-1 Allergen bronchial challenge Bronchial Asthma Allergic rhinitis…. Nasal obstruction contributes to snoring, sleep-disordered breathing in predisposed individuals. Scharf and Cohen (1997) rd 3 component “CORE” 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) GERD….. Acid reflux into the airway enhances Vagal activity can trigger asthma in some individuals as well as with symptoms of OSAS. Gislason Janson Vermeire et al, (2002) th 4 component ….”CORE” (Cardiac) Sleep Disorders and CV diseases OSA is associated with significant cardiovascular morbidities as: Left ventricular dysfunction, Arrhythmias, Myocardial infarction, and Systemic hypertension. Cardiovascular complications of OSA and how they may relate to asthma ?? Complication Resultant effect Asthma relation HTN LVH, IHD, LVD Pulmonary edema Asthma worsening IHD Ischemia Asthma worsening Cough worsening ASCVD, HTN Arrhythmia, Stroke, decline cognitive Poor compliance medication PHTN Dyspnea Asthma mimic Medications Beta–blockers ACE-inhibitor Asthma worsening Cough worsening with Adapted from (Kasasbeh et al, 2007) 5th Component ( Inflammation) A S T H M A O S A S Multiple Pro-Inflammatory Factors in Allergic Asthma & Rhinitis Affect Sleep and OSAS Symptoms Mediator Effect 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 IL-4 ↑ Airway inflammation ↑ Latency to REM and ↓ REM duration IL-10 Bradykinin Substance P ↑ Nasal, airway obstruction & rhinorrhea ↑ Sleep apnea; ↑ Latency to REM, arousal; ↑ Nasal obstruction Adapted from Ferguson. Otolaryngol Head Neck Surg. 2004;130:617. Treatment modalities Prospective Clinical Studies Reporting the Impact of Treatment With CPAP on Asthma Outcome in Patients With Concomitant OSAS Ann Allergy Asthma Immunol. 2008;101:350–357. Beneficial effects of CPAP in patients with asthma and OSAS “LOCAL” • ↑mean airway pressure ↑ end-expiratory lung volume • Recruits underventilated alveoli ↑ expiratory muscle function • ↑ minute ventilation, ↓ respiratory rate and dyspnea • ↓ airways resistance ↓ OSAS induce vagal stimulation • Stabilizes upper aireways ↓ OSAS induced increased intrathoracic • Prevents peripheral airways closure pressure Beneficial effects of CPAP in patients with asthma and OSAS “ SYSTEMIC” Impact of asthma treatment on sleep GERD therapy OSAS Therapy GERD OSAS Does the treatment of OSA by CPAP improve GERD? Author N Results Kerr (1992) 6 OSA Decreased pH <4 esophageal exposure 6.3–0.1% (p<0.05) Kerr (1993) 6 non-OSA Decreased pH <4 esophageal exposure 28–6% (p<0.05) 14 OSA Decreased pH <4 esophageal exposure 12–4% (p<0.05) Decreased overall number of reflux events (p<0.05) 8 non-OSA Decreased pH <4 esophageal exposure 4–1% (p<0.05) Decreased overall number of reflux events (p<0.05) 165 OSA 48% reduction in GERD symptom score (p<0.001) While patients without CPAP had no improvement Ing (2000) Green (2003) Does Treatment of GERD (PPI) affect OSA symptoms? Author Ing (2000) Senior (2001) Steward (2004) MohamedHussein et al., 2011 N 6 10 27 34 Medication (t× time) Results Nizatidine (30 days) 50% AI reduction (p<0.05) No significant reduction in AHI Symptom reduction not evaluated Omeprazole (30 days) 31% AI reduction (p=0.04) 25% RDI reduction (p=0.06) Symptom reduction not evaluated Pantoprazole (90 days) No significant reduction in AHI Reduced daytime sleepiness (p=0.002) Reduced GERD symptoms (p=0.0006) Pantoprazole ( 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) and 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. ... اشهد ان ال اله اال انت...سبحانك اللهم و بحمدك استغفرك و اتوب اليك Thank you for staying awake! Or, you may now wake up and ask questions!