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Sleep and Asthma/COPD Pr o

John Harrington, MD Associate Professor of Medicine University of Nebraska Medical Center



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 No COI or disclosures for this lecture

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Learning Objectives

 Understand how sleep and circadian rhythms affect both

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respiratory physiology and pathology

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COPD

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 Identify key clinical features of nocturnal asthma and

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 Learn about the assessment and management of nocturnal

asthma and COPD

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Introduction

 Relationship between sleep and respiratory disorders is

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bidirectional

 Sleep quality is affected by respiratory disorders and by

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 Other factors

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medications and vice versa Sleep deprivation



Circadian rhythms



Comorbid sleep disorders

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Pulmonary Physiology during Sleep

Respiratory System Pr es e

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Behavioral input is lost leaving only metabolic processes (O2 and CO2) to control respiration during sleep

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PaO2 (by 2-12 mmHg) PaCO2 (by 2-8 mmHg) SaO2 (by 2%) Tidal volume Minute ventilation Ventilatory response to hypoxia/hypercapnia UA dilator muscle tone

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3/4

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REM

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Ventilation (L/min)

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Ventilatory Response to Hypoxia

5 100

90 80 Oxygen Saturation (%)

Douglas NJ. Clin Chest Med 1985;6:563 Principles and Practice of Sleep Med 2010

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Ventilatory Response to Hypercapnia Stage 2 REM

30

40 50 End-tidal PCO2 (mmHg)

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10

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Stage 3/4

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Ventilation (L/min)

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20

Douglas NJ Clin Chest Med 1985

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Circadian Variation in Lung Function

Cortisol CBT

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PEF

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FEV1

Hertzel MR et al. Thorax 1980;35:723-738 Spengler C et al. AJRCCM 2000;162;1038-1046

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Respiration During Sleep

Respiratory pattern

N1

Periodic breathing with episodes of hypopneas and hyperpneas

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Regular frequency and amplitude Irregular pattern of respiration Variable RR and TV Periodic breathing may occur during phasic REM sleep

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REM

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Sleep stage

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Asthma



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Asthma

 Airway hyperreactivity to specific and nonspecific stimuli

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 Reversible bronchoconstriction

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 Episodic dyspnea, wheezing or coughing

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Nocturnal Asthma

 Sleep complaints

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 Insomnia

3/4 have nocturnal awakenings ≥ once weekly



2/3 have nocturnal awakenings ≥ three times a week

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 Excessive sleepiness

 Nocturnal hypoxemia

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Nocturnal Asthma

 Causes of poor sleep quality

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 Coughing, dyspnea, wheezing and chest discomfort

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 Majority report having poor sleep quality even in the absence

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of nighttime asthma attacks

Luyster FS. Sleep Breath 2012

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Nocturnal Asthma

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 Nocturnal symptoms indicate sub-optimally treated asthma  Inverse correlation between asthma control and presence and severity of sleep disturbance  Sleep disturbance present in 11-20% with totally controlled asthma Braido F. Asian Pac J Allergy Immunol 2009

 Asthma attacks not specific to any sleep stage

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Nocturnal Asthma

 Mechanisms for nocturnal asthma  Circadian variability in airflow

Lowest levels in the early morning

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 Sleep-related changes in  Autonomic nervous system activity  Increased parasympathetic tone  Decreased sympathetic activity  Lung capacity  Inflammatory mediators  Other disorders – nocturnal GERD or OSA

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Nocturnal GERD

Emilsson et al. Eur Respir J 2013

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Nocturnal Asthma

 Diagnosis of nocturnal asthma

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 Monitoring morning and evening PEF or FEV1 over several

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days to weeks

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 Reduced evening values compared to daytime

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Polysomnography

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Arousals and awakenings

Sleep efficiency; total sleep time

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Avoid precipitants Inhaled corticosteroids Long-acting bronchodilators Leukotriene inhibitors Short-acting beta-agonists for acute control PAP therapy for concurrent asthma and OSA

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     

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Nocturnal Asthma: Therapy

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Asthma and OSA

 Patients with OSA were 3.6 times more likely to have

uncontrolled asthma

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Teodorescu Chest 2010  Nocturnal CPAP in stable mild-to-moderate asthmatics and newly diagnosed OSA  Did not alter airway responsiveness or FEV1  Did improve AHI and asthma quality of life Lafond Eur Respir J 2007  Poorly controlled asthma and symptoms of OSA should undergo evaluation US National Asthma Education and Prevention Expert Panel Report 3

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CPAP Asthma Control Test (ACT) and EuroQol questionnaire

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In this pilot study, CPAP therapy reduced peak flow variability and improved symptom control in nonapneic patients with severe asthma.

CPAP therapy in asthma

Nocturnal continuous positive airway pressure in severe non apneic asthma. A pilot study. D Amato M, Stanziola AA, de Laurentiis G, Radicella D, Russo C, Maniscalco M, D Amato G, Sofia M. Clin Respir J. 2013 Dec 6.

PEF amplitude (P < 0.05) and PEF morning dip (P < 0.001) PEF: peak expiratory flow

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Chronic Obstructive Pulmonary Disease



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Chronic Obstructive Pulmonary Disease  Progressive, not fully reversible, airflow limitation

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particles or gases

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 Due to injury to the small airways and alveoli from noxious

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 Includes chronic bronchitis and emphysema  Dyspnea, chronic cough and chest tightness – common

complaints

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COPD: Nighttime Symptoms

 Prevalence of nighttime symptoms and sleep

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disturbance – not well understood  Frequently unreported  No uniform definition  May exceed 75%

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COPD: Sleep Disturbance

 Insomnia

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 Difficulty falling asleep

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 Sleep-related complaints are common

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 Repetitive awakenings  Early awakening

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 Non-restorative sleep

 Excessive sleepiness

Maggi S et al. J Am Geriatr Soc 1998 Cormick W et al. Thorax 1986 Newman AB et al. J Am Geriatr Soc 1997 Bella V et al. Sleep 2003

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Prevalence of Insomnia Pr es e

Tucson Epidemiologic Study of Chronic Lung Disease

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53% Two symptoms  39% One symptom

28% Asymptomatic

Klink M et al. Chest 1987

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Causes of Sleep Disturbance

Klink M et al. Chest 1984 Dodge R et al. Arch Intern Med 1995

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Causes of Sleep Disturbance

 Frequency of arousals does not appear to be related to the

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degree of nighttime hypoxemia

Mulloy E et al. ARRD 1993 Martin RJ et al. ARRD 1992 Berry RB et al. ARRD 1991

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Insomnia Therapy

Roth Sleep Med 2009

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Insomnia Therapy

Kapella et al. Int J COPD 2011

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Restless Legs Syndrome

 Diagnostic criteria

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 Secondary

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 Primary (idiopathic and often hereditary)

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 Nutritional deficiencies (iron, folate, vitamin B12)  Medical conditions (ESRD, pregnancy, rheumatologic

disorders, or neurologic conditions)

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Restless Legs Syndrome

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Prevalence of RLS-type Symptoms in COPD

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29-36% during stable disease

54% during acute exacerbations

Aras G. COPD 2011

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Prevalence Severity (IRLSS) EDS (ESS)

COPD 36% 20.5

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RLS in COPD

11.8

Controls 11% 18

P < 0.001 P = 0.016

8.6

P = 0.009 Lo Coco D. Sleep Med 2009

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Consequences in COPD

Cavalcante AG. Sleep Med 2012 Aras G. COPD 2011

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Consequences in COPD

Cavalcante et al. Sleep Med 2012

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Less hypoxia

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COPD: Nocturnal O2 Desaturation Worse hypoxia

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Oxygenation During Wakefulness is the Major Predictor of Mean and Lowest Oxygen Saturation During Sleep in COPD

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P < 0.0001 R = 0.75

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Lowest SaO2 Asleep (%)

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60

80

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Mean SaO2 Awake (%) Connaughton JJ et al. Am Rev Respir Dis 1988;138:341-344

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Mechanisms for Nocturnal Hypoxemia

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Diminished Lung Volumes

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VQ Mismatching

Hypoventilation Most Important Factor

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COPD: Overlap Syndrome

 Presence of both COPD and OSA

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 Prevalence of OSA in COPD is similar to general population

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 Lower PaO2

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 Compared to isolated COPD

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 Higher PaCO2

 Higher mean PA pressures

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Overlap Syndrome

 Compared to isolated COPD  Increased risk of death and hospitalization

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More extensive RV remodeling Increased arterial stiffness

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 

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 Higher economic burden  Higher medical service claims and medical costs Sharma B. COPD 2012 Shiina K. Respir Med 2012 Shaya FT. Sleep Breath 2009

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Overlap Syndrome

 Prevalence of OSA in COPD is similar to that in the general

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population, and vice versa

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 Decreased pulmonary function in COPD is not an

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independent risk factor for OSA

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 No correlation between FEV1 % predicted and risk for OSA,

AHI and ODI

Sharma B. Lung 2011

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COPD: Evaluation

 PSG is not routinely indicated in persons with COPD

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 Should be considered if

Clinical suspicion for OSA



Complications from unexplained hypoxemia



Severity of pulmonary hypertension out of proportion to degree of airflow limitation

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 Home sleep apnea testing not recommended

Celli BR et al. Eur Respir J 2004

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Polysomnography

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Sleep latency; sleep stage changes; arousals and awakenings Sleep efficiency; total sleep time; REM sleep Fleetham J. ARRD 1982 McSharry DG. Respirology 2012

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Indications for Overnight Oximetry  Daytime hypercapnia and/or hypoxemia

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 Right heart failure

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 Pulmonary and systemic hypertension

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Actigraphy

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SE, TST and sleep activity correlated with severity of dyspnea

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Low SE Prolonged SOL Short sleep duration Increased mean activity More WASO Budhiraja R. Sleep 2012 Nunes DM. Sleep Breath 2012

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COPD: Therapy Pr es e

 Symptoms

 Breathlessness, wheezing, cough

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 Hypoventilation

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 Hypoxia

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 Respiratory mechanics

 Expiratory flow limitation

 Comorbid sleep disorders

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COPD: Indications for Oxygen Therapy  PaO2  55 mmHg, or SaO2  88%

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 PaO2  59 mmHg, or SaO2  89% plus  Cor pulmonale  Right heart failure, or  Erythrocytosis (Hct > 55%)

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Positive Airway Pressure

Stanchina et al. J Clin Sleep Med 2013 Wang et al. Resp Res 2013

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Home NPPV (BPAP 15/5 cmH2O) improved quality of life in stable COPD patients with nonhypercapnic respiratory failure (PaCO2 < 52 mmHg).

NPPV arm

Quality of life

Improved Transitional Dyspnea Index (TDI)-Task at 6 months (P = 0.03)

Improved Chronic Respiratory Disease Questionnaire (CRQ)-Mastery domain (P = 0.04)

PaO2

Remained stable (P=0.02)

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Dyspnea

Noninvasive positive pressure ventilation in subjects with stable COPD: a randomized trial. Bhatt SP, Peterson MW, Wilson JS, Durairaj L. Int J Chron Obstruct Pulmon Dis. 2013;8:581-9.

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Summary of Key Points  Many patients present with disturbances in duration, timing or

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quality of sleep

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 Evaluation of sleep complaints relies chiefly on a comprehensive

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 Frequent follow-up is recommended to determine response to

therapy as well as development of new sleep complaints