Overlap Syndrome. José M. Marin Hospital Universitario Miguel Servet Zaragoza, Spain.

Transcription

1 Overlap Syndrome José M. Marin Hospital Universitario Miguel Servet Zaragoza, Spain.

2 I have nothing to disclose.

3 Agenda Effects of sleep on breathing Sleep in COPD The Overlap Syndrome Treatment of the Overlap Syndrome

4 Agenda Effects of sleep on breathing Sleep in COPD The Overlap Syndrome Treatment of the Overlap Syndrome

5 States of Being Wake REM Sleep NREM Sleep

6 Effects of sleep on breathing Physiologic Variable Heart rate Respiratory rate Blood pressure Skeletal muscle tone Brain 02 consumption Ventilatory response Temperature Sexual changes NREM Regular Regular Regular Preserved Reduced Normal Normal Rare REM Irregular Irregular Variable Absent Increased Reduced Poikilothermic Frequent

7 Respiratory Response to Sa02 During Normal Sleep Awake VenDlaDon (L/min) Oxygen SaturaDon (%) 3/4 2 REM

8 Respiratory Response to CO 2 During Normal Sleep Douglas NJ Clin Chest Med 1985 VenDlaDon (L/min) End- Ddal PCO(mmHg) Awake Stage 3/4 Stage 2 REM VenElatory response to CO 2 is depressed during NREM sleep Slope of response line is depressed further in REM sleep Set point for response to CO 2 increases during NREM sleep and further in REM sleep - Requires a higher PaCO 2 to semulate respiraeon

9 Agenda Effects of sleep on breathing Sleep in COPD The Overlap Syndrome Treatment of the Overlap Syndrome

10 Effects of Sleep on Patients with COPD PaEents with COPD are most profoundly hypoxemic at night (McNicholas WT, Chest 2000). sleep sleep

11 Effects of Sleep on Patients with COPD Awake Pa0 2 predicts nocturnal desaturaeon beuer than exercise Sa0 2 or wake PaC0 2 (Mulloy E, Chest 1996)

12 Effects of Sleep on Patients with COPD COPD paeents are more likely to die at night Nocturnal Deaths in COPD, McNicholas BMJ Patient Numbers Neoplasms Stroke COPD

13 Copenhagen City Heart Study + Copenhagen General PopulaHon Study: COPD

14 FEV1 not related to SEI Kwon JS et al J COPD 2009;6:

15 COPD and Poor Sleep: A Two Way Street How does sleep impact COPD? Reduced chemosensievity Reduced pulmonary funceon Impaired muscle performance How does COPD impact sleep? Symptoms cause sleep disturbance Hypoxemia and hypercarpia disturb sleep

16 Agenda Effects of sleep on breathing Sleep in COPD The Overlap Syndrome Treatment of the Overlap Syndrome

17 Flenly DC. Clin Chest Med 1985;6:51-61

18 COPD The diagnostic The classification Stage Criteria* I: Mild FEV 1 /FVC <0.70, FEV 1 80% predicted II: Moderate III: Severe IV: Very Severe FEV 1 /FVC <0.70, 50% FEV 1 <80% predicted FEV 1 /FVC <0.70, 30% FEV 1 <50% predicted FEV 1 <30% predicted or FEV 1 <50% predicted plus chronic respiratory failure Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Carverley P et al. "Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: GOLD Executive Summary". Am. J. Respir. Crit. Care Med. 2007; 176:532

19 OSA The diagnostic The classification Stage Criteria* I: Mild AHI 5 to 15 II: Moderate AHI 15 to 30 III: Severe AHI > 30 *

20 Overall prevalence of COPD, OSA and overlap syndrome. COPD > 10% Overlap Syndrome > 2% OSA > 20%

21 Typical pauern during sleep of a paeent with OSA and overlap syndrome OSA alone Sleep onset Overlap In a patient with both snoring and COPD, the O2Sat baseline is reduced during sleep but the saw-tooth pattern is suggestive of obstructive sleep apnea.

22 Pathways involved in producing nocturnal hypoxemia and hypercapnia in overlap syndrome. COPD OSA Respiratory mechanics - Chest wall muscle tone - Accessory muscle weakness - Short diaphragm length - Lung hyperinflaeon Control of breathing - Central output - Airway muscular tone - CO 2 venelator responses - Chemical drives response Upper airway resistance - Smoking - Neck obesity - Neck fluid accumulaeon - Mucosa inflammaeon V/Q mismatch HypovenDlaDon Hypoxemia Hypercapnia

23 InteracDons between COPD and OSA. AggravaDng factors for OSA Age Smoking Weight gain Fluid reteneon CorEcosteroids COPD Overlap syndrome ProtecDve factors again OSA Smoking cessaeon Weight loss Sleep postures Bronchodilators

24 costs in overlap Shaya FT et al Sleep Breath 2009;13:

25 Health related quality of life in overlap Mermigkis C et al Int J Clin Pract 2007;61(2):

26 How is the Overlap Syndrome Different than COPD or OSA? PaEents with the Overlap Syndrome have increased risk of complicaeons compared to those with COPD or OSA alone (Gan WQ Thorax, 2004; JM Marin AJRCCM 2010; Greenberg- Dotan S, Sleep Breath 2013) Respiratory failure Pulmonary hypertension HypovenElaEon More severe hypoxemia Diabetes Obesity Death

27 Accelerated cardiovascular disease in Overlap Smoking Obesity Overlap OSA COPD Hypoxia Oxidative stress TNF-α, IL8, IL-6, PCR Endothelial dysfunction Atherosclerosis Cardiovascular disease

28 Right Ventricular Remodeling in COPD and Overlap syndrome B. Sharma et al; COPD ; 10(1): 4 10.

29 Agenda Effects of sleep on breathing Sleep in COPD The Overlap Syndrome Treatment of the Overlap Syndrome

30 Effect of nocturnal nasal oxygen on Sa0 2, systemic and pulmonary artery pressures. (Clement ID Respir Physiol 1992.)

31 Obesity hypoventilation syndrome on supplemental oxygen and TcPCO2) has climbed from approximately 60 mm Hg (top tracing) to just below 90 mm Hg. Therefore, use of supplemental oxygen in padents with OLS and significant daydme hypercapnia may worsen nocturnal hypercapnia. n supplemental oxygen TcPCO2 climbed from 60 mm Hg (top tracing) to just below 90 m Hg. Therefore, use of supplemental oxygen in patients with COPD and daytime ypercapnia may worsen nocturnal hypercapnia.

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33 Leg movement Respiratory effort Flow Pulse O 2 saturaton Position CPAP 7 cmh2o CPAP 9 cmh2o

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35 Nine- year non randomized prospeceve cohort study Overlap Syndrome: CPAP users - n= 288 Overlap Syndrome : CPAP non users - n= 213 total = 711 COPD - only: n= 210

36 Marin JM, 2010

37 Survival curves of COPD patients with COPD-only and Overlap patients Overlap without CPAP showed higher mortality (RR:1.79) and exacerbation with hospitalization compared to COPD-only CPAP users showed no increase risk of death nor exacerbation compared to COPD-only (adjusted for age, sex, BMI, co-morbidities, COPD severity, IAH and diurnal hypersomnolence) Marin JM, AJRCCM 2010

38 Conclusions of the study - CPAP treatment reduces mortality and also hospitalization in patients with Overlap Syndrome - There are worst mortality and hospitalization in patients with Overlap Syndrome not treated with CPAP than in patients with COPD-only Marin JM, AJRCCM 2010

39 A. Malhorta et al: J Clin Sleep Med 2013;9(8):

40 NIV. RCTs are Rare and Small (Bhett SP Int J COPD 2013) 30 COPD paeents (FEV 1 < 50% pred and PaCO 2 < 52mmHg) randomized. (OSA was excluded) AcEve treatment: Bilevel 15/5 cm H 2 0 vs usual care Outcomes: Dyspnea (by TDI) was more improved in the NPPV arm at 6 wks and 3 mos, but not 6 mos. QoL slightly improved in one domain in NPPV arm Pa0 2 increased (+ 2.1 mmhg) in treatment arm, but decreased (- 7.2 mmhg) in control arm. No difference in PaC0 2, 6- minute walk, FEV 1, number of exacerbaeons, or sleep quality (PSQI)

41 OSA is a reversible co-morbidity! Baseline data BMI= 43.6 Kg/m2 PaO2 = 48 mmhg PaCO2 = 68 mmhg FEV1= 34% pred. AHI= 90/h 5 hosp/ last 12 mo Several co-morbidities 1 year treatment BiPAP + LTOT + global treatment Courtesy of Dr. Machado from Brasil

42 Overlap Syndrome Treatment 1- Weight loss - Clearly will benefit patients with OSA and obesity - However, in COPD: weight loss is usually associated with increased mortality 2- Oxygen Therapy - Supplemental oxygen is the mainstay of treatment for those with daytime and nocturnal hypoxemia - LTOT decreases mortality if used > 18 h/day - To much oxygen can be dangerous!!!! Poulain M, 2006 GOLD, NOTT, MRC,1981

43 Martin RJ, 1999 McNicholas WT, 2004 Ryan S, Sampol G, 1996 JMMarin, 2011 Overlap Syndrome Treatment-2 3- Bronchodilators and Corticosteroids - Taken together, previous studies suggest that pharmacological treatment of COPD in Overlap Syndrome will ameliorate nocturnal oxygen desaturation 4- Continuous Positive Airway Pressure (CPAP) - CPAP remains the accepted standard treatment for OSA and for Overlap Syndrome - CPAP plus LTOT can be necessary in some patients - BiPAP vs CPAP

44 Take home massages Sleep disturbances are common in COPD parecularly insomnia and episodic hypoxaemia. Nocturnal oxygen desaturaeon largely reflects the physiological impact of sleep on venelaeon. Sleep apnea is not especially common in COPD and sleep studies are not rouenely indicated. Management of sleep- related disturbances should focus on opemising management of the underlying COPD and correceng hypoxemia. NIV during sleep can be beneficial in selected cases, parecularly during acute exacerbaeons.