OVERLAP SYNDROME

BY
DR ANIMESH ARYA
SENIOR CONSULTANT CHEST PHYSICIAN
SRI BALAJI ACTION MEDICAL INSTITUTE
NEW DELHI
Overview

 Review COPD and OSA

 Understanding Overlap Syndrome

 Identifying Patients with Overlap Syndrome

 Effective Treatment for Overlap Syndrome

 Documentation Requirements

 Compliance to therapy
GOLD DEFINITION OF COPD
 COPD is a common, preventable, and treatable
disease that is characterized by persistent respiratory
symptoms and airflow limitation that is due to
airway and/or alveolar abnormalities usually caused by
significant exposure to noxious particles or gases.
 Chronic inflammation causes
◦ structural changes,
◦ small airways narrowing,
◦ destruction of lung parenchyma.

THE CHRONIC AIRFLOW LIMITATION IN COPD and

DISTURBED MUCOCILIARY CLEARANCE WHICH IS
PROGRESSIVE AND PARTIALLY REVERSIBLE AND
ASSOCITAED WITH VARIOUS COMORBIDITIES
COPD DEFINITION- GOLD
GUIDELINE
 “a common preventable and treatable
disease, characterized by persistent
airflow limitation that is usually
progressive and associated with an
enhanced chronic inflammatory response
in the airways and the lung to noxious
particles or gases”
 The definition of COPD and its subtypes
(emphysema, chronic bronchitis, and
chronic obstructive asthma) and the
interrelationships between the closely
related disorders that cause airflow
limitation provide a foundation for
understanding the spectrum of patient
presentations.
CONCEPT OF OVERLAP
 CB,EMPHYSEMA, ASTHMA
 Figure 1

CHEST 2017 152, 1318-1326DOI: (10.1016/j.chest.2017.04.160)

Copyright © 2017 American College of Chest Physicians Terms and Conditions
Overall Changes in Breathing
During Sleep

 Decrease in minute ventilation 0.5-

1.5 L
 Increase in airway resistance
 Decrease in metabolic rate (CO2)
production 10-15%
 Decrease in chemosensitivity 20-50%
 DecreasePaO2 3-10 mmHg
 DecreaseSaO2 2%
 Increase PaCO2 2-8 mmHg
Mohsenin, Semin Resp Crit Care Med 2005;26:109
Effects of COPD on Sleep

 Cough and wheezing interrupt and delay sleep (Klink M

Chest 1987)
 Sleep is more fragmented, with increased arousals
and reduced amounts of deep nREM and REM sleep
(McSharry DG, Respirology 2012)
 Severity of COPD correlates with severity of
subjective sleep complaints (Omachi TI Sleep Med 2012), but
not with objectively measured sleep variables (Hynninen
MJ Sleep Med 2013).
 Pathophysiology of sleep-related respiratory changes in chronic obstructive pulmonary
disease.

Walter T. McNicholas et al. Eur Respir Rev 2013;22:365-375

©2013 by European Respiratory Society

Effects of Sleep on Patients with COPD

 Patients with COPD are most profoundly

hypoxemic at night (McNicholas WT, Chest 2000).
 COPD patients are more likely to die at
night (McNicholas WT Br Med J 1984).
 Oxygen desaturation is greater during
sleep than during exercise in COPD, and
wake Sa02 predicts nocturnal desaturation
better than exercise Sa02 or wake PaC02
(Mulloy E, Chest 1996)
Effects of COPD on Sleep
(McNicholas WT Sleep Breath 2013)

 Daytime sleepiness (by Epworth) and poor quality sleep (by

PSQI) compared to that of matched controls (Zohal A Glo J
Health Sci 2013).

 Increased prevalence of insomnia complaints

 Increased use of hypnotics

 Figure 2

CHEST 2017 152, 1318-1326DOI: (10.1016/j.chest.2017.04.160)

Copyright © 2017 American College of Chest Physicians Terms and Conditions
COPD and Poor Sleep: A Two Way
Street
(Kent BD, Sleep Med 2014)
 How does sleep impact COPD?
• Reduced chemosensitivity
• Reduced pulmonary function
• Impaired muscle performance
• Systemic inflammation
 How does COPD impact sleep?
• Symptoms cause sleep disturbance
• Hypoxemia and hypercarbia disturb sleep
 Obstructive Sleep Apnea
 OSA is one of the most common sleep
disorders
 Characterized by partial or complete
collapse of the upper airway during
sleep

Unobstructed Airway Snoring Obstructed Airway

Pathophysiology
•Muscle relaxation •Anatomical factors
(Sleep)
•Muscle atonia (REM)
•Neuromuscular dis
Pharyngeal Insp. Neg. pressure
dilators
Opened
AW

Closed AW
 Pathophysiology

 tissue laxity and redundant mucosa

 anatomic abnormalities
 decreased muscle tone with REM sleep
 airway collapse
Pathophysiology
 desaturation
 arousal with restoration of airway
 sleep fragmentation leading to
hypersomnolence
Anatomical Factors
EEG
OSAS: PSG screen
ECG

Chin EMG

Airflow

Peripheral Pulse
Volume

BP

Leg Mt.

Oximetry
Javaheri 2007 Sleep Medicine Cl
Pulmonary Hypertension (PAH) and
Sleep Apnea
 OSA recognized by WHO in 1998 as a
secondary cause of PAH
 15 – 70% of OSA patients have PAH
 COR pulmonale may occur in cases of
severe OSA, especially if associated with
high PaCO2
 Several but not all studies show
compliant, effective treatment of OSA
improves PAH
Obstructive and Central OSA and
Heart Failure HFREF HFPEF
 Major public health issue
 High mortality and morbidity
 Frequent hospital admissions and readmissions
 High economic impact
 Obstructive sleep apnea is the most common,
least recognized
co-morbidity -- 70% of HF patients have
OSA/CSA
 Similar symptoms in heart failure and OSA
 CSA associated with higher mortality
 PAP may not improve mortality in HF patients
Coronary Heart Disease and Sleep
Apnea
 CAD estimated to be present in 20– 25% of OSA patients
 Prevalence is 30% in case controlled studies with an
independent association
 Direct causality is not well established
 Major cardiac events are more likely in patients with severe
OSA
 CPAP may significantly reduce c-v events
 AHI severity is an independent predicator of mortality in
patients with CAD
 Screening for both disorders in patients with risk factors for
one is suggested as well as co-management strategies
 Impaired sleep in men and disturbed sleep in women may be
related to moderately higher risk of poor cardiac prognosis
after first AMI
(A. Clark SLEEP2014)
Sleep Disorders and Mortality
 Many prospective long term studies suggest that
untreated patients with OSA have higher risk of
death from all causes, particularly cardiovascular
 There is a relationship between severity of the
OSA and cardiovascular risk
 OSA predicts incident sudden cardiac death and
the risk magnitude is predicted by multiple
parameters characterizing OSA severity,
independent of established risk factors
 Therapy with effective compliant PAP significantly
reduces mortality from c-v disease and auto
accidents
Sleep Apnea and the Association
with Cancer

Peppard PE; Nieto FJ. Here come the sleep apnea-cancer studies. SLEEP
COPD-OSA overlap syndrome
What is Overlap Syndrome?
 Refers todiseases that overlap one another - combined effect of multiple
diseases or conditions are worse than either one alone

 Overlap Syndrome
 Combination of COPDand OSAwhich results in nocturnal
hypoventilation and hypoxemia
 First introduced in 1985 by Professor David Flenley (University of
Edinburgh)
 Additive effect ‘1+1=3’
 More by chance than pathophysiological link
◦ Chance alone suggests that one disorder has 10% chance of the
other
How is the Overlap Syndrome
Different than COPD or OSA?

 Patients with the Overlap Syndrome have increased

risk of complications compared to those with COPD
or OSA alone (Gan WQ Thorax, 2004, Greenberg-Dotan S, Sleep
Breath 2013)
• Respiratory failure
• Pulmonary hypertension
• Hypoventilation
• More severe hypoxemia
• Diabetes
• Obesity
• Death
 Pathophysiological interactions between chronic obstructive pulmonary disease (COPD),
sleep and obstructive sleep apnoea syndrome (OSAS).

Walter T. McNicholas et al. Eur Respir Rev 2013;22:365-375

©2013 by European Respiratory Society

 Figure 4

CHEST 2017 152, 1318-1326DOI: (10.1016/j.chest.2017.04.160)

Copyright © 2017 American College of Chest Physicians Terms and Conditions
IDENTIFYING
PATIENTS WITH
OVERLAP SYNDROME
Signs and Symptoms
OSA COPD
• Snoring, choking or gaspingduring • Increase in sputum
night • Increase in SOB, cough and/or
• Sleepiness during the day wheezing
• Morning headaches • Forgetfulness, confusion
• Memory, learning problems, lack of • Trouble sleeping
concentration • Using more pillows or sleeping in a
• Irritable, depressed, or moodiness chair instead of a bed to avoid
• Nocturia shortness of breat h
• Dry mouth or sore throat on • Increased feeling of fatigue and lackof
awakening energy that ispers istent
• Morning headache s, dizzy spells,
restlessness
Overlap:
• Hypoxemia + hypercapnia
• Increased pulmonary artery pressure
• Older
• Similar BMI
 Arterial oxygen saturation (SaO2) patterns during sleep in obstructive sleep apnoea (OSA)
alone and the overlap syndrome.

Walter T. McNicholas et al. Eur Respir Rev 2013;22:365-375

©2013 by European Respiratory Society

A.Different patterns of oxygen desaturation during sleep in patients with COPD;
(B) overlap syndrome, and
(C) OSA. Ptcco2 = transcutaneous carbon dioxide tension; Sao2 = arterial
oxygen saturation; Spo2 = oxygen saturation measured by pulse oximetry. See
 Figure 5

CHEST 2017 152, 1318-1326DOI: (10.1016/j.chest.2017.04.160)

Copyright © 2017 American College of Chest Physicians Terms and Conditions
Kaplan-Meier survival curves for outcomes among patients with COPD without OSA (COPD
group), patients with COPD and coexisting OSA (overlap group), and patients with overlap
syndrome treated with CPAP since enrollment (overlap with CPAP group).
A, Percentage survival and
(B) percentage of severe COPD exacerbation-free survival curves among the three study
groups. The differences between COPD alone and COPD with OSA treated with CPAP are
statistically significant from patients with COPD and untreated OSA (P < .001).
Screening your COPD patients for OSA
 There are several tools to help screen these patients
during a regularly scheduled appointment.
The American Sleep Apnea Associationendorses three
tests that you can quickly and easily administer and
will help you identify your patients most at risk for
sleep apnea:
 STOPBang questionnaire
 Epworth Sleepiness Scale
 Berlin Questionnaire
 American Thoracic Society/European Respiratory
Society guidelines also suggest that those with
relatively mild COPD and evidence of pulmonary
hypertension should be referred for overnight testing
 Kaplan–Meier survival curves for outcomes among chronic obstructive pulmonary disease
(COPD) patients without obstructive sleep apnoea (OSA) (COPD group), patients with COPD
and coexisting OSA (overlap group), and patients with overlap syndrome treated with...

Walter T. McNicholas et al. Eur Respir Rev 2013;22:365-375

©2013 by European Respiratory Society

TREATMENT
OPTIONS FOR THE
OVERLAP PATIENT
Modalities of treatment of overlap
syndrome
1. Weight loss
2. Oxygen therapy
3. Bronchodilator therapy – manage exacerbations with anitbiotics/steroids

4. CPA P therapy - high humidification to mobilize secretions (+

supplemental02)1
5. Bi-level ventilatory support
6. Volume preset ventilation
1. Most commonly used for individuals where bi-level support has failed to
control sleep hypoventilation, where tracheostomy ventilation isneeded

7. Newer technology might include Nasal High Flow (NHF) with a high
level of humidity
 OxygenTherapy
• Oxygen is a common treatment
• Shown to improve overall mortality if used formore than 18 hours per day,
including during sleep

Data is lacking for improvement with oxygen therapy alone in OSA1

• nocturnal oxygen desaturations are improved, BUT…not
• sleep architecture
• arousals
• blood pressure (which is improved after 2 weeks of CPAPtherapy)
• subjective daytime sleepiness
Alford Study
• 4 lpm 02 administered to 20 men with OverlapSyndrome
• Obstructive events increased in duration (25.7 to 31.4)
• PC02 increased (52.8 to 62.3)
• 02 should not be used alone for treatment

1Effect of
continuous positive airway pressure versus supplemental oxygen on sleep quality in obstructive sleep apnea: a
placebo-CPAP-controlled study.
Loredo JS,Ancoli-Israel S,Kim EJ,Lim WJ, Dimsdale JE,Sleep. 2006 Apr; 29(4):564-71.
Treatment - CPAP
 100% effective if obstruction is excluded
 titrate pressure
 poor compliance - 50-80%
 Compliance may improve with BiPAP and
Auto-CPAP
CPAP Therapy
 CPAPremains the accepted standard treatment for OSAand is also the
accepted standard for overlap syndrome.

 But CPAPalone may not fully correct hypoxemia, so supplemental oxygen

may be required
 By using CPAPthere could potentially be an unloading of the respiratory
muscles which could lead to:
• decrease hypoventilation, oxygen consumption, or carbon dioxide
production by the respiratory muscles.
 These muscles may be rested by CPAPuse, since it prevents the increase in
upper- airway resistance that occurs during sleep.
 Alternatively, CPAPmay offset intrinsic PEEPin severeCOPD.
OSA showing closed upper airways

Snoring: showing partially close upper

airways

CPAP: showing the opening of the upper

airway
Effects of CPAP
Patients with overlap syndrome
who use CPAP therapy have
experienced
 Improved survival and decreased
hospitalizations9
 Decreased risk of mortality14
 Increased survival estimates15
 Improved blood gases and mean
pulmonary arterial pressure16
 Improved PaCO2, PaO2 and FEV1 17
CPAP Reduces Death Rates
Marin JM Am Rev Respir Crit Care Med 2010
CPAP Reduces Exacerbation Rates
(
Marin JM Am Rev Respir Crit Care Med 2010)
 Machado et al, Brazil 2010
 Evaluated the impact of OSAStreatment with CPAPon the
survival of hypoxemic COPDpatients between January 1996 and
July 2006.
 CPAPtherapy was associated with a higher survival in patients with
moderate-to- severe OSASand hypoxemic COPD.
 Of 603 hypoxemic COPDpatients receiving LTOT, 95 were
diagnosed with moderate-to-severe OSAS.

95 Patients Treatment Control

CPAPadherence 61 (64%) 34
5 year survival 71% 26%
Toraldo et al, Spain 2010
 Supports early treatment with nasal CPAPin overlap patients.
 Included patients with both severe OSAand mild-to-moderate COPD

 After 3 months of CPAPtherapy:

◦ arterial blood gases and mean pulmonary artery pressure (MPAP)
improved and stabilized
◦ patients reported improvements in daytime sleepiness utilizing
Epworth Sleepiness Score (ESS),

 The improvement in these parameters remained stable over 12 months'

follow- up.
Non-Invasive Ventilation
• Can improve gas exchange during wakefulness
• Can improve sleep quality (Meecham Jones DJ Am J Respir
Crit Care Med 1995)
• Can be withdrawn for up to 2 weeks without
deterioration in daytime ABGs (Masa Jimenez JF Chest 1995)
• Can reduce need for intubation and mechanical
ventilation in COPD exacerbations (Brochard L NEJM
1995)
• May improve dyspnea and QoL (Bhatt SP Int Jour COPD)
• Is associated with improved mortality in retrospective
trials, but not RCTs.
• Controversy exists about whether to use high-
intensity (rate) or high pressure settings.
 • A subset of patients with stable COPDwho may benefit from NIPPVincludes
• those with daytime hypercapnia and super-imposednocturnal
hypoventilation 1

• Bi-level
• The effects of b-level PAPhave not been specificallyevaluated2
• Difference between IPAP and EPAPmaintaining alveolar ventilation and
reducing PaC02

Benefits vs. Quality of Life?

1 Nick Hill Noninvasive ventilation for chronic obstructive pulmonary disease. Respir Care 2004; 49:72–87
NIV therapy can theoretically rest
overloaded respiratory muscles, prevent
nocturnal hypoventilation, and reset
central respiratory drive in patients with
hypercapnia.19
 NIV devices also include several
synchronization features that can prolong
expiratory time, which helps to prevent
air trapping and may greatly improve
patient comfort and compliance.
 COPD-OSA Overlap Syndrome

THWalter T. McNicholas, MD, FCCP

THANK YOUCHEST
Volume 152, Issue 6, Pages 1318-1326 (December 2017)
DOI: 10.1016/j.chest.2017.04.160

THANK YOU

Copyright © 2017 American College of Chest Physicians Terms and Conditions