Continuous Positive Airway Pressure Versus Noninvasive Ventilation in Patients With Overlap Syndrome
Continuous Positive Airway Pressure Versus Noninvasive Ventilation in Patients With Overlap Syndrome
The purpose of this study is to determine if Bipap should assume a standard-of-care role in
 the management of overlap syndrome.
Chronic obstructive pulmonary disease (COPD) is a leading cause of disability and death
 worldwide. Acute exacerbations of COPD (AECOPD), in particular, serve as marker of an
 accelerated disease course and thus herald an increased risk of not only repetitive AECOPD
 episodes but also deteriorating pulmonary function and death (2). Obstructive sleep apnea
 (OSA), when it occurs in combination with COPD, is an increasingly recognized contributor to
 AECOPD episodes. OSA consists of repetitive sleep-related partial loss of airway caliber
 arising from increased transmural pressures which favor luminal collapse. OSA is estimated to
 afflict 4 to 9% of the populations, a prevalence which is anticipated to climb hand-in-hand
 with the rising incidence of obesity.

 The combination of the two disorders, which has been arbitrarily labeled as Overlap Syndrome
 (OS), has been linked with greater elevations in arterial carbon dioxide tensions and
 pulmonary vascular resistance and lower arterial oxygen tensions than is seen with either of
 its component disorders in isolation. Elevated pulmonary artery pressures may progress to
 cause cor pulmonale, a process whereby compensatory right ventricle remodeling, hypertrophy,
 and eventually, florid heart failure. In the setting of OSA, the therapeutic gold standard is
 nightly continuous positive airway pressure (CPAP). Essentially, CPAP machines function by
 administering a single continuous positive pressure airflow to the person's airway via an
 appropriately fitted nasal mask. The applied pressure stents open partially occluded airway
 segments during sleep. Though effective in OSA and OS, it is increasingly realized that for
 OS patients there may exist a reduction not only in airway patency but also in ventilatory
 drive when sleeping such that means to augment per breath volumes may attain incremental
 benefits to the use of CPAP alone. Although CPAP is ineffective in COPD, Bipap has shown
 benefit suggesting that patient with OSA and COPD may derive an improvement in health-related
 outcomes by using a ventilation modality which addresses both of the underlying conditions.

 Bipap functions by combining the single flow in CPAP with a second inspiratory pressure
 assist which not only overcomes sleep-related airway resistance but also increases the
 magnitude of each breath resulting in lower diurnal carbon dioxide tensions and pulmonary
 artery pressures. Bipap may harbor a mortality benefit in COPD; but the study results are
 conflicting. It is unclear if Bipap is more effective at treating OSA than usual CPAP.
 However, it is in the setting of OS that Bipap may assume a prominent role through its
 ability to address both disorders; CPAP for the OSA portion and an inspiratory pressure
 assist to ameliorate the COPD piece. Thus far no study has been conducted to address whether
 OS may derive a particular benefit from Bipap or, more specifically, examine whether Bipap
 may diminish the risk of AECOPD, or heart failure-related hospitalizations.
Inclusion Criteria:

 -  Patients aged > 35 years, the diagnosis of both OSA and COPD. OSA must have been
 diagnosed using an American Academy of Sleep Medicine (AASM)-protocol overnight Type I
 polysomnogram assessment with a resultant RDI of >5 events/hour in association with
 OSA-attributable diurnal symptoms.

 -  COPD must be diagnosed using American Thoracic Society (ATS)-protocol pulmonary
 function testing.

 -  Patients must have Global Obstructive Lung Disease (GOLD) stage II COPD FEV1/FVC < 70%
 predicted in conjunction with an FEV1 <80% predicted.

 -  The patient must have a > 10 pack years smoking history and a documented history of at
 least one exacerbation leading to treatment with systemic glucocorticoids or
 antibiotics or hospitalization within the previous year.

 Exclusion Criteria:

 -  Significant diseases other than COPD, i.e. disease or condition which, in the opinion
 of the investigator, may have put the patient at risk because of participation in the
 study or may have influenced either the results of the study or the patients' ability
 to participate in the study

 -  Patients with a diagnosis of asthma

 -  Patients with a life-threatening pulmonary obstruction, or a history of cystic
 fibrosis

 -  Patients with known active tuberculosis

 -  Patients with brittle/unstable diabetes mellitus

 -  Patients with a history of and/or active significant alcohol or drug abuse. See
 exclusion criterion 1

 -  Patients with a history of myocardial infarction within the year prior to Visit 1

 -  Patients with cardiac arrhythmia that required medical or surgical treatment in the 3
 months prior to enrollment

 -  Patients who had taken an investigational drug within 30 days or 6 half-lives
 (whichever is greater) prior to Visit 1

 -  Use of systemic corticosteroid medication at unstable doses (i.e., less than 6 weeks
 on stable dose) or at doses in excess of the equivalent of 10 mg prednisolone per day
 or 20 mg every other day

 -  Pregnant or nursing women or women of childbearing potential not using a medically
 approved means of contraception (i.e., oral contraceptives).

 -  Patients with any respiratory infection or COPD exacerbation in the 4 weeks prior to
 Visit 1 or during the run-in period should have been postponed. In the case of a
 respiratory infection or COPD exacerbation during the run-in period, the run-in period
 could have been extended up to 4 weeks

 -  Patients who, during their CPAP titration study are found to require such excessive
 CPAP pressures as to mandate a Bipap titration

 -  Patients with either Cheyne-stokes respiration noted on PSG assessment or a central
 sleep apnea with an associated central event index > 5 events/hour (using AASM central
 apnea/hypopnea scoring criteria)