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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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REM
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Ventilation (L/min)
Awake
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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
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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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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
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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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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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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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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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sleep history
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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