Is CPAP helpful in severe Asthma?

Is CPAP helpful in severe Asthma? P RAP UN KI TTIVORAVITKUL, M.D. PULMONARY AND CRITICAL CARE DIVISION DEPARTMENT OF MEDICINE, PHRAMONGKUTKLAO HOSPITAL

Outlines o Obstructive sleep apnea syndrome (OSAS) and Asthma overlap? o Potential effects of pathophysiologic o Asthma effect on OSA o OSA effect on Asthma o Role of CPAP treatment o What s mechanism? o Improve asthma?

Asthma Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation. It is defined by the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness and cough that vary over time and in intensity, together with variable expiratory airflow limitation. J Allergy Clin Immunol 2002;109:S492.

OSAS o Characterized by repetitive episodes of complete (apnea) or partial (hypopnea) upper airway obstruction occurring during sleep o Result in reductions in blood oxygen saturation and arousals from sleep

Pathogenesis of OSAS Awake: Small airway + neuromuscular compensation Loss of neuromuscular compensation + Decreased pharyngeal muscle activity Airway collapses Apnea Sleep onset Intermittent Hypoxia Increased vagal tone Inflammation (local& systemic) Hyperventilate: correct hypoxia&hypercapnia Airway opens Pharyngeal muscle activity restored Arousal from sleep Hypoxia& Hypercapnia Increased ventilatory effort

OSAS and Asthma Overlap? Study/year Study design/sample (n) Measurement Result Alharbi et al 2009 Cross-sectional/OSA referral population (606) OSA: AHI >5/hour on PSG Asthma: self-report of physician-diagnosed asthma 35% prevalence of asthma, body mass index (BMI) was a significant predictor (OR 2.1; CI 1.7,2.4) Teodorescu et al 2009 Cross-sectional/asthma referral population (244) OSA: SA-SDQ Asthma: symptoms (NAEPP classification) Predictors of high OSA risk in asthma were female gender (OR 2.1; CI 1.1,4.0), asthma severity (OR 1.6; CI 1.2,2.0), GERD (OR 2.7; CI 1.5,4.8), use of ICS (OR 4.0; CI 1.5,10.5) Auckley et al 2008 Cross-sectional/asthma clinic population (177) vs general medicine clinic population (GMC; 328) OSA: Berlin sleep questionnaire Asthma: pulmonologist diagnosed, severity assessed by spirometry GMC: participants with history of OSA and asthma excluded High OSA risk was more prevalent in asthma vs GMC population (39.5% vs 27.2%, p =0.004) B.Prasad et al. Sleep Medicine Reveiws 18(2014); 165-171

OSAS and Asthma Overlap? Study/year Study design/sample (n) Measurement Result Bhattacharya et al 2012 Cross-sectional/adult OSA related office visits to otorhinolaryngologist (4.1±1.2 million visits) OSA and Asthma: ICD-9 codes Increased risk for asthma (OR 2.7; CI 1.6,4.6) in OSA Teodorescu et al 2012 Cross-sectional/adult asthma referral population (752) OSA: SA-SDQ Asthma: frequency of daytime and nighttime symptoms (NAEEP classification) Increased OSA risk with persistent daytime (OR 1.9; CI 1.3,2.9) and nighttime (OR 1.9; CI 1.3,2.9) symptoms of asthma Williams et al 2011 Cross-sectional/women before and during pregnancy (1335) OSA: habitual snoring Asthma: self-report of physician-diagnosed asthma Increased OSA risk in asthmatics both before (OR 2.1; CI 1.1,4.1) and during (OR 1.79; CI 1.1,3) pregnancy Teodorescu et al 2010 Cross-sectional/adult asthma referral population (472) OSA: SA-SDQ Asthma control questionnaire (ACQ) Asthmatics at high risk for OSA had increased risk for poorly-controlled asthma (OR 2.9; CI 1.5,5.3) B.Prasad et al. Sleep Medicine Reveiws 18(2014); 165-171

Chicken or the Egg? Asthma & OSA: Who is First?

Population-based prospective epidemiologic study (the Wisconsin Sleep Cohort Study) beginning in 1988. Asthma is associated with the development of OSA? To examine the prospective relationship of asthma with incident OSA Random sample of Wisconsin state employees to attend overnight polysomnography studies at 4- year intervals Asthma and covariate information were assessed during polysomnography studies through March 2013 Eligible participants were identified as free of OSA by 2 baseline PSG The final sample consisted of 547 participants who contributed a total of 1105 sets of 4-year intervals: 211 participants (39%) with 1 set, 173 participants (32%) with 2 sets, 105 participants (19%) with 3 sets, 57 participants (10%) with 4 sets, and 1 participant with 5 sets Teodorescu et al, JAMA. 2015;313(2):156-164.

22 of 81 participants (27%;95%CI, 17%-37%]) with asthma experienced incident OSA over their first observed 4-year follow-up interval compared with 75 of 466 participants (16%;95%CI, 13%-19%]) without asthma Teodorescu et al, JAMA. 2015;313(2):156-164.

Using all 4-year intervals, 45 cases of incident OSA during 167 4-year intervals (27%[95%CI,20%-34%]) and participants without asthma experienced 160 cases of incident OSA during 938 4-year intervals (17%[95%CI, 15%-19%]) Adjusted relative risk (RR) was 1.39 (95%CI, 1.06-1.82), controlling for sex, age, baseline and change in body mass index, and other factors. Teodorescu et al, JAMA. 2015;313(2):156-164.

Asthma was also associated with new-onset OSA with habitual sleepiness (RR, 2.72 [95%CI, 1.26-5.89], P =.045) Asthma duration was related to both incident OSA (RR, 1.07 per 5-year increment in asthma duration [95%CI, 1.02-1.13], P =.01) and incident OSA with habitual sleepiness (RR, 1.18 [95%CI, 1.07-1.31], P =.02). Teodorescu et al, JAMA. 2015;313(2):156-164.

OSAS and Severity of Asthma Study/year Study design/sample (n) Measurement Result Teodorescu et al 2009 Cross-sectional/asthma referral population (244) OSA: SA-SDQ Asthma: symptoms (NAEPP classification) Predictors of high OSA risk in asthma were female gender (OR 2.1; CI 1.1,4.0), asthma severity (OR 1.6; CI 1.2,2.0), GERD (OR 2.7; CI 1.5,4.8), use of ICS (OR 4.0; CI 1.5,10.5) Julian et al 2009 Severe vs Moderate Asthma vs Control (26 vs 26 vs 26) OSA: full PSG (AHI 15 /hr) Asthma: symptoms (American Thoracic Society criteria) 23 of 26 (88%) patients with severe asthma, 15 of 26 (58%) patients with moderate asthma, and 8 of 26 (31%) controls without asthma (x2: P <.001) Byun et al 2013 Cross-sectional/pulmonary and sleep clinic (167) OSA: ApneaLink (flow signal) Asthma: symptoms (American Thoracic Society criteria) Age, male gender, and moderate to severe asthma showed positive correlations with OSA on univariate and multivariate analyses Teodorescu et al 2015 Severe vs non-severe Asthma vs control (94 vs 161 vs 146) OSA: SA-SDQ Asthma severity: frequency of daytime and nighttime symptoms (NAEEP classification) Significant association of SA-SDQ with sputum PMN%

What is the link between Asthma and OSAS? Asthma Increased nasal resistance Rhinitis Polyposis GERD Obesity Systemic & airway inflammation Possible links Genetic factor Female Gender Cardiovascular disease OSAS B.Prasad et al. Sleep Medicine Reveiws 18(2014); 165-171

Pathophysiologic between Asthma and OSAS? Asthma Bidirectional interaction OSAS

Asthma effect on OSAS Increase Airway resistance Asthma OSAS

Asthma effect on OSAS Asthma Corticosteroid effect Nasal disease OSAS Yigla M et al. Journal of asthma. 2003;40(8):865-71.

OSAS effect on Asthma Asthma Local and Systemic inflammation Chronic intermittent Hypoxia & VEGF Leptin GERD Cardiac dysfunction Nerve reflex Vagal tone Sleep Fragmentation OSAS

OSAS effect on Asthma Asthma Local and Systemic inflammation Chronic intermittent Hypoxia o & VEGF Leptin o GERD Vibration o Cardiac dysfunction trauma from OSA Nerve reflex Vagal tone Sleep Fragmentation OSAS Boyd JH et al. Chest 2004; 126:13-18.

OSAS effect on Asthma Asthma Local and Systemic inflammation Chronic intermittent Hypoxia & VEGF Leptin GERD Chronic low-grade Cardiac dysfunction systemic inflammation α Nerve reflex Vagal tone Sleep Fragmentation OSAS Hatipoglu U, et al. Chest. 2004;126(1):1-2.

Asthma OSAS effect on Asthma Local and Systemic inflammation Chronic intermittent Hypoxia & VEGF Leptin Hypoxia from apnea or hypopnea o GERD Cardiac dysfunction Nerve reflex Vagal tone Sleep Fragmentation OSAS Alkhalil M, et al. Obstructive sleep apnea syndrome and asthma: what are the links? JCSM 2009;5(1):71-8.

Asthma OSAS effect on Asthma o Local and Systemic inflammation Chronic intermittent Hypoxia & VEGF Leptin GERD Cardiac dysfunction α Nerve reflex Vagal tone Sleep Fragmentation OSAS Dixon et al., Proc Am Thorac Soc 7: 325 335, 2010.

OSAS effect on Asthma Asthma Local and Systemic inflammation Chronic intermittent Hypoxia & VEGF Leptin GERD Cardiac dysfunction Nerve reflex Vagal tone Sleep Fragmentation OSAS

OSAS effect on Asthma Asthma Local and Systemic inflammation Chronic intermittent Hypoxia & VEGF Leptin GERD Cardiac dysfunction Nerve reflex Vagal tone Sleep Fragmentation OSAS

OSAS effect on Asthma Asthma Local and Systemic inflammation Chronic intermittent Hypoxia & VEGF Leptin GERD Cardiac dysfunction Nerve reflex Vagal tone Sleep Fragmentation OSAS

OSAS effect on Asthma Asthma Local and Systemic inflammation Chronic intermittent Hypoxia & VEGF Leptin GERD Cardiac dysfunction Nerve reflex Vagal tone Sleep Fragmentation OSAS

Inspiration Expiration

Continuous Positive Airway Pressure(CPAP) Effects Decreased venous return Increased upper airway patency Decreased afterload End-expiratory lung volume Increased CO Increased O2 Antonescu-Turcu A, Parthasarathy S. Respir Care. 2010 Sep;55(9):1216-29

Local and Systemic Antiinflammatory Effects Bronchodilatory Effect Decrease Airway Hyperresponsiveness Restore Sleep pattern Promote Wt. loss Suppress Leptin secretion Improve cardiac function Suppress Acid Reflux Alkhalil M, et al. Ann Allergy Asthma Immunol 2008; 101: 350-357.

Take home message OSAS and Asthma are highly prevalent respiratory disorders that frequently overlap in patients High index of suspicion is warranted for overlap of OSAS and asthma Obesity, Rhinitis, GERD and poor responsive to therapy CPAP are recommended as treatment of OSA can improve their asthma symptoms